Although clinical isolates of the organism are generally reported to be susceptible to amphotericin B, isolates can vary in their sensitivities to antifungal agents in vitro depending on the methodology used, and clinical response to therapy with antifungal agents in a regimen that includes amphotericin B is generally poor. An enzyme-linked immunosorbent assay was used to measure tumor necrosis factor alpha (TNF-alpha) in culture supernatants. Vaz, C., Sampaio, P., Clemons, K. V., Huang, Y., Stevens, D. A., Pais, C. Saccharomyces as a vaccine against systemic aspergillosis: 'the friend of man' a friend again? but in my situation, it depends entirely on my husband being the primary carer when Im away working. On 16-19 January 2008, the Third Advances Against Aspergillosis Meeting took place in Miami Beach, FL, USA. The exception was sites associated with or downstream of bicarbonate influx, 12/54 of which were positive. Animal models testing monotherapy versus combination antifungal therapy: lessons learned and future directions, Development of an orogastrointestinal mucosal model of candidiasis with dissemination to visceral organs. David Redhouse. Segal, B. H., Herbrecht, R., Stevens, D. A., Ostrosky-Zeichner, L., Sobel, J., Viscoli, C., Walsh, T. J., Maertens, J., Patterson, T. F., Perfect, J. R., Dupont, B., Wingard, J. R., Calandra, T., Kauffman, C. A., Graybill, J. R., Baden, L. R., Pappas, P. G., Bennett, J. E., Kontoyiannis, D. P., Cordonnier, C., Viviani, M. A., Bille, J., Almyroudis, N. G., Wheat, L. J., Graninger, W., Bow, E. J., Holland, S. M., Kullberg, B., Dismukes, W. E., de Pauw, B. E. A possible mechanism for synergy between antifungal therapy and immune defenses, Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. View details for DOI 10.1196/annals.1406.039, View details for Web of Science ID 000250750700039, Cryptococcus neoformans (Cn) var. Methods, results: BALB/c bronchoalveolar and peritoneal macrophages (PM) were shown deficient in IL-12 production in response to IFN-gamma+LPS. > present (Patron of the Natural Sciences Collections Association) and [????] View details for DOI 10.1186/1471-2180-11-203, View details for Web of Science ID 000296005300001, View details for PubMedCentralID PMC3197500. The anthropologist David Graeber . In seven of the eight reported cases, blood cultures were positive for the organism. > present (Member of the Advisory Board of the Cheltenham Festival of Science) and [????] The incidence of invasive aspergillosis is markedly increasing, and mortality remains dismal. Non-culture methods include antibody- and antigen-based assays, metabolite detection and molecular identification. US based Meghan and Harry.. FameChain has their amazing trees. In 1999 I co-led the ALBATROSScruise around the Scotia Sea. View details for Web of Science ID 000175084400015. Clemons, K. V., Steinbach, W. J., Denning, D. W., Stevens, D. A. Efficacy of posaconazole in a murine model of central nervous system aspergillosis. Safety, tolerance, and efficacy of posaconazole therapy in patients with nonmeningeal disseminated or chronic pulmonary coccidioidomycosis. Additional clinical trial data that expand our knowledge of the usefulness of caspofungin for these and other mycoses, including its administration in combination with other antifungal agents, is anticipated. My career ambitions havent changed much, in that my main ambition is to work hard at whatever I apply myself to. Dr David Stevens is an organisational and corporate psychologist. When lungs of surviving mice were cultured, the 0.1 microg regimen resulted in fewer (P<0.02) cfu. The therapy of coccidioidomycosis has been an early target, both experimentally and clinically, for study of new members of the azole class of drugs, because of the recognition that coccidioidomycosis is one of the most difficult mycoses to treat, and because our research group and our collaborators have been eager to pioneer new therapies for this problem pathogen. [2], At the time of his death, Stevens was a member of the Royal College of Physicians London, and the British Archaeological Association. Two of these were determined to be 1-dehydroprogesterone and 11 alpha-hydroxyprogesterone. [1], Stevens' success in the field of medicine, and his philanthropy, has been well recorded in John Isherwoods' Dr Joseph Stevens of St Mary Bourne (2015). (Finished 1997), View Alice Roberts's Family Tree and History, Ancestry and Genealogy. Low-dose ABLC was less effective than LAmB at reducing brain fungal burdens in both models. The 3 newest drugs include posaconazole, micafungin, and anidulafungin, whose pharmacology, toxicology, and indications are presented. I continue to work on questions of religion and its place within modern democratic societies, as well as other questions on social justice and ethics, as well as within the field of the philosophy of eduction. The prevalence of C. parapsilosis RFLP type VII-1 apparently has risen in the USA and current isolates show some variation in distribution of types in some non-USA localities. Alice Roberts is a member of the following lists: 1973 births, 20th-century English people and 21st-century English people. Factors associated with a poor prognosis have been defined and therapy is difficult because of the lack of a blood supply. From my own experience, breastfeeding (and I know I was lucky my babies took to breastfeeding immediately, and I loved it; I had some difficulties, but nothing that Lansinoh and nipple shields couldnt help me overcome), breastfeeding was a joyful, lovely experience part of caring for a baby that I wouldnt want to have missed out on, and really important for bonding. PCR primer sets flanking the microsatellite repeats were designed and tested with 20 independent isolates. 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. Treatment of B. dermatitidis with anti-1,3-beta-glucan antibody inhibited TNF-alpha production by PM. 2nd year: Hydrodynamics. A systemic model of candidiasis was studied in CD-1 mice by intravenous inoculation of different isolates of C. albicans. Fluconazole appears well tolerated and safe in these doses and durations. 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. Transfusions given every other day did not improve protection. Some populations that are at risk for aspergillosis might be likely candidates for receiving the first vaccinations against aspergillosis, or vaccination of a stem cell donor might be considered in some circumstances. See > present (Patron of the Natural Sciences Collections Association) and [????] View details for DOI 10.1196/annals.1406.029, View details for Web of Science ID 000250750700017. View details for Web of Science ID 000167613000005 The immune events that take place in the central nervous system (CNS) during cryptococcal infection are incompletely understood. of Chemistry, and Div. Particularly, questions of socioeconomic distribution, Rawlsian justice as fairness, equality of opportunity and education, environmental justice. Control BAM responded to increasing numbers of conidia of Aspergillus fumigatus with increasing production of IL-1 and TNF. The addition of mouse serum [corrected] resulted in marked depression of TNF and enhancement of IL-6. 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. Survival and cfu in brain, spinal cord and CSF were determined and histology studied. We tested the efficacy of Abelcet and caspofungin, alone and in combination for treatment of this disease.Male CD-1 mice were immunosuppressed with 200 mg/kg cyclophosphamide 2 days prior to infection and every 5 days thereafter. We investigated BALF enhancement or inhibition of TNF-alpha production by BAM stimulated by B. dermatitidis. Itraconazole appears useful as a corticosteroid sparing agent (BII). > present (Honorary Fellow of the British Science Association and the Royal Society of Biology) and [????] Mice were given 150 mg/kg cyclophosphamide every 4 days and a gentamicin-vancomycin-clindamycin-imipenem regimen daily beginning 4 days before intranasal challenge with 5 10(5) Aspergillus conidia. She worked as Senior Teaching Fellow at the University of Bristol Centre for Comparative and Clinical Anatomy, where her main roles were teaching clinical anatomy, embryology, and physical anthropology, as well as researching osteoarchaeology and paleopathology. Heat-killed Saccharomyces cerevisiae (HKY) used as a vaccine protects mice against systemic aspergillosis and coccidioidomycosis. The AAC workshop identified savings of HK$1.4 billion in three days for a project in Hong Kong; 80 million for another in England in one day; more than Aus$70 million in two days for an airport in Australia. The efficacy of MICA was difficult to assess because of an apparent toxicity at 10 mg kg(-1). Brains from surviving mice had CFU of Aspergillus fumigatus. View details for Web of Science ID 000186262900003, Among patients undergoing heart transplantation, Aspergillus is the opportunistic pathogen with the highest attributable mortality. 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). View details for Web of Science ID 000167156500009. Coccidioidomycosis can be difficult to treat with available therapies, particularly in patients with progressive or disseminated disease. Surgical treatment is definitive but many patients are ineligible. These data indicate that AmBi may offer an improvement in the treatment of coccidioidal meningitis. The purpose of this project was to maintain these programs by clarifying the policies regarding animals, specifically dogs, in the healthcare setting. Studies on combination therapy will prove useful to the clinician in evaluating courses of treatment, especially where clinical-trial data are not available or probable in the future. Help us build our profile of Alice Roberts and David Stevens! A pathogenic role for M. pachydermatis recovered from sources other than blood or catheters was not established. Invasive aspergillosis. Increased levels of transcripts corresponding to IL-1 alpha, tumor necrosis factor alpha (TNF-alpha), and iNOS were detected as early as day 1 postinfection, with TNF-alpha rising by approximately 30-fold and iNOS increasing by approximately 5-fold by day 7. A reproducible murine model was established by lumbar intrathecal injection of Coccidioides immitis arthroconidia. This is an eminently readable book which is full of sound practical advice. The antifungal activity of voriconazole (VCZ) was tested against Cryptococcus neoformans (Cn) with and without the addition of polymorphonuclear neutrophils (PMN), monocytes or monocyte-derived macrophages (MDM) in vitro. 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. Her zodiac sign is Taurus. The growing genus Halomonas includes bacteria favoring or tolerating high-saline/halide and high-pH environments. The efficacy of combination therapy was assessed, with mice given either no treatment, MICA at 1 mg/kg/dose, 0.8 mg kg(-1) of intravenous amphotericin B (AMB), 100 mg kg(-1) of oral itraconazole (ICZ), or 100 mg/kg/dose of twice-daily subcutaneous nikkomycin Z (NIK). Cooperative enhancement of inhibition by a second drug could eradicate the effect. We used EcoRI digestion of cellular DNA to generate RFLP; RAPD analysis on genomic DNA. Iodide in the Ocean:Distribution and Impact on Iodine Flux and Ozone Loss. Choi, J. H., Brummer, E., Kang, Y. J., Jones, P. P., Stevens, D. A. > present (Member of the Advisory Board of the Cheltenham Festival of Science), [????] View details for Web of Science ID 000180636800013. View details for DOI 10.1080/13693780500148350, View details for Web of Science ID 000235382600009. The cytokine production, assayed by antibody array and also quantitation in supernatants, was depressed (particularly TNF) by the addition of mouse serum to these cultures, with the exception of IL-6. Finally, the anti-inflammatory cytokine IL-10 was minimally produced by BAM + conidia or LPS, but IL-10 was produced by PM + conidia or LPS. Two of the most common point mutations in ERG11 associated with resistance, D116E and E266D, were tested by restriction fragment length polymorphism analysis of the isolates from this collection. The young spleen cells also produced more NO, which we demonstrated reduced Con A-induced proliferation. BALFs were standardized in protein concentration. Therefore, it was important to determine if there was any association between putative virulence traits and virulence that might help explain the variation in virulence phenotypes. As a demonstration of the utility of the model to test antifungal activity, daily treatment with 10 or 50 mg/kg itraconazole significantly reduced dissemination to the liver and kidneys and reduced tongue CFU compared to controls. These results suggest MBL may play a deleterious role in systemic aspergillosis. With anti-1,3-beta-glucan antibody, we showed by IFA assay that B. dermatitidis contained 1,3-beta-glucan. Resistance of CD-1 mice to pulmonary blastomycosis correlates with enhanced fungicidal activity of BAM, PM, PMN, and IFN-gamma production by Con A stimulated spleen cells, compared to BALB/c mice. Developing a vaccine against aspergillosis, Hormones and the Resistance of Women to Paracoccidioidomycosis. And thank you to everyone who made motherhood month such a success! The importance of C5 was confirmed by studies using B10.D2/oSnJ (C5-) mice and their congenic C5+ counterparts. Thus, whereas BALF constituents commonly mediate antimicrobial activity, B. dermatitidis may utilize BALF constituents, such as SP-D, to blunt the host defensive reaction; this effect could reduce inflammation and tissue destruction but could also promote disease. Most patients were treated successfully with a combination of antifungal therapy and surgery. Little is known, however, about the most appropriate dosage and schedule of administration. Because aspergillosis is an important pulmonary disease in birds, avian models have been used successfully to study preventative vaccines. The larger repertoire of cytokine production in the macrophages that had been cultured longer (20 h+20 h) in serum may be related to maturation of cell receptors. Recovery of CFU from the kidneys showed that dosages of CAS at 0.1 mg/kg and above were efficacious in the reduction of C. albicans, but were not curative. The order of decreasing resistance was CD-1 > or = CD10 > or = CD10 x CD3F1 > CD10 x B6F1 > CD3 > C57BL/6 and correlated with estrogen responsiveness in endocrine disruptor assays. Infection with Trichosporon beigelii is an uncommon cause of endocarditis. Social justice. What I See talks motherhood with Professor Alice Roberts. These results suggest that the mechanism of inhibition of the innate proinflammatory immune response of PM to B. dermatitidis is mediated by serum MBL binding to B. dermatitidis at 1,3-beta-glucan sites or sterically masking 1,3-beta-glucan sites, thus preventing 1,3-beta-glucan stimulation of PM for TNF-alpha production. To test an effect mediated by leukocytes, BALB/c peripheral blood mononuclear cells (PBMC) were stimulated in vitro with 3M-003 to generate cytokine-containing supernatants. Macrophages could be cultured in the presence or absence of serum during the initial 20 h adherence and establishment period, enabling study of the effect of serum factors. In general, posaconazole therapy was well tolerated, with 12 of 20 patients reporting adverse events that were possibly or probably related to treatment. However, only two or fewer given a regimen of ABLC or AmBi were cured of infection in both tissues. The molecular epidemiology of Candida dubliniensis has been studied using large complex DNA probes for Southern analysis and has revealed the existence of distinct genotypes within this species. Here, we emphasize prevention and an approach to a laboratory accident that minimizes the risk of exposure to laboratory staff and staff in adjacent areas. To improve present results with antifungal drugs, modulation of the host immune response is being explored. View details for DOI 10.1080/13693780500220498, View details for Web of Science ID 000235382600007. 1 technical staff2 student. Several homologous proteins with highly conserved sequences were identified and quantified in A. fumigatus and C. posadasii. We have previously proposed that 17beta-estradiol may be responsible in part for the decreased frequency of clinical paracoccidioidomycosis in females via a blocking of the initial morphological transformation necessary to initiate infection. At the lowest inoculum used, deaths of KO mice were delayed, but survival was not significantly different than WT (P>0.05). Liu, M., Clemons, K. V., Johansen, M. E., Martinez, M., Chen, V., Stevens, D. A. The motivation is to understand the role of the ocean in the climate system. The relative binding affinity that progesterone and its metabolites display for PBP correlates with the relative growth inhibitory potency of these compounds. 0115 95 14859 david.stevens@nottingham.ac.uk Biography I have been at Nottingham since 2000, having previously held positions at Brunel University and Brown University. At 50 mg/kg, itraconazole and fluconazole were equivalent in clearing the fungi from the brain and kidney, but itraconazole was superior to fluconazole in clearing the fungi from the spinal cord and lungs (P < 0.05). Work is still important to me, but I dont feel that it defines me in the way I certainly did before. Who let the dogs out? The laboratory is, in addition, a clinical reference laboratory for fungal and actinomycete susceptibility testing, and body fluid antifungal drug concentration determinations, for hospitals. From 1998 until 2005, Stevens worked as a Senior Vice President of Single Family Lending at Freddie Mac, where his responsibilities included product development, credit risk and contract negotiations for all single family businesses. Understanding how the marketplace of religious ideas works. A total of 3714 biallelic markers, spaced about every 3.5 kilobases, were identified by analyzing the patterns obtained when total genomic DNA from two different strains of yeast was hybridized to high-density oligonucleotide arrays. Although GM-CSF did not enhance IL-1 or TNF production by BAM+conidia, GM-CSF significantly antagonized DEX suppression of IL-1 cytokine production. Although groups of rabbits treated with AmBi regimens did not have significantly fewer animals with meningitis than the control group (P > 0.05), ABLC and AmBi were not significantly different. Isolates from Jews (51), Arabs (35) and Druze (25) were genotyped. Reproducibility was demonstrated by submission of subcultures of 4 isolates each, in triplicate, interspersed with unique numbers among a group of 30 isolates for blind testing. If, in the second 20 h period, a fungus (heat-killed Blastomyces, HK-Bd) was introduced, a more complex pattern of cytokine (particularly TNF) and chemokine production ensued. DEX suppression of cytokine production by BAM+LPS was modestly but significantly antagonized by GM-CSF. > present (Member of the Longitude Prize Committee), [????] Other combinations showed lower cfu, but no significant enhancement over either drug alone. Therapy is predominantly directed at preventing life-threatening hemoptysis. 1,3-beta-Glucan stimulated TNF-alpha production by PM, and this was inhibited by mouse serum. 0 Reviews. Ascioglu, S., Rex, J. H., de Pauw, B., BENNETT, J. E., Bille, J., Crokaert, F., Denning, D. W., Donnelly, J. P., Edwards, J. E., Erjavec, Z., Fiere, D., Lortholary, O., Maertens, J., Meis, J. F., Patterson, T. F., Ritter, J., Selleslag, D., Shah, P. M., Stevens, D. A., Walsh, T. J. Intrathecal amphotericin in the management of coccidioidal meningitis. View details for DOI 10.1016/j.diagmicrobio.2011.05.014, View details for Web of Science ID 000295425700011. One isolate, 95-68, showed paradoxical growth in vivo with significantly higher CFU recovered from mice given CAS at 20 mg/kg than those given CAS at 5 mg/kg, but the effect was not reproducible in a subsequent experiment. A review of published cases, in addition to a recently treated patient, is presented that describes the clinical features and outcomes of triazole therapy for vertebral aspergillosis in immunocompetent patients.Using the Medline database, cases of vertebral aspergillosis in immunocompetent patients treated with triazole were reviewed. All drug regimens prolonged survival (P < or = 0.0008) and reduced cfu (P < or = 0.0001-0.003) recovered from the brains and kidneys compared with untreated. D-optimal design provided maximally informative sampling times for future pharmacokinetic studies. However, rhMBL in combination with itraconazole was not better than itraconazole alone. A safety and feasibility study comparing an intermittent high dose with a daily standard dose of liposomal amphotericin B for persistent neutropenic fever. I am an archaeologist, specialising in ancient Egypt, with research interests that include urbanism in the ancient world, lived religion, cultural interaction and the archaeology of cult. In vitro and in vivo studies suggest that the female hormone (17-estradiol, E(2)) regulates or inhibits M-or-C-to-Y transition. Among the nine infant colonizing isolates, there were four different RFLP subtypes; four of the isolates were subtype VII-1. Lower concentrations of serum also potentiated drug activity. These guidelines are directed to 3 principal entities: invasive aspergillosis, involving several organ systems (particularly pulmonary disease); pulmonary aspergilloma; and allergic bronchopulmonary aspergillosis. For archaeology, being a science, is neither good nor bad, but a fact simply. neoformans infection is usually associated with immunocompromised hosts, whereas Cryptococcusgattii more frequently causes disease in immunocompetent hosts. The available data suggest that clinical symptoms alone are inadequate to make such decisions, since significant lung damage may occur in asymptomatic patients. All regimens tested prolonged survival (P < 0.05 to 0.0001). 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. Once detected, each remained at a relatively constant level through 28 days of infection. A strain demonstrating paradoxical growth was grown in the presence and absence of caspofungin, and the cell wall content was analyzed. Tell, L. A., Clemons, K. V., Kline, Y., Woods, L., Kass, P. H., Martinez, M., Stevens, D. A. The general availability of genetically defined strains, immunological reagents, ease of handling, and costs all contribute to the use of mice as the primary laboratory animal species for models of this disease. ITZ-B suspension was prepared by dispersing the complex of the drug with hydroxypropyl-beta-cyclodextrin in water. If you made any changes in Pure these will be visible here soon. In candidosis, the number of sites of colonization correlates with invasion. No toxicity was noted. View details for Web of Science ID A1997XT59500011. Fay Stevens is an archaeologist (UCL) and award-winning lecturer and researcher. These findings reinforce prior studies that have implicated HCW hands as the source of nosocomial, including neonatal, fungemia. Mortality from invasive pulmonary aspergillosis approaches 80% with few useful therapeutic options available. Risk factors for and symptoms in infants with M. pachydermatis fungemia appeared to be similar to those described for Malassezia furfur sepsis. Furthermore, interspecific hybrids resulting from the mating of sibling species of Saccharomyces were shown to share the ITS-PCR ribotyping patterns of both parental species. These unique observations are consistent with an estrogen-fungus receptor-mediated effect on pathogenesis. Exceptions included skin, subcutaneous fat, and muscle adjacent to the injection site. Resistance to azole antifungals continues to be a significant problem in the common fungal pathogen Candida albicans. Avian aspergillosis is commonly treated with itraconazole (ITZ). CLINICAL AND MICROBIOLOGICAL FEATURES OF INFECTION WITH MALASSEZIA-PACHYDERMATIS IN HIGH-RISK INFANTS. lists They were dating for 5 years after getting together in 1995 and were married in 2000. The availability of genetically defined strains of mice, immunological reagents, cost and ease of handling are factors. Cortisone acetate gave results similar to dexamethasone, but cortisone acetate suppression of BAM responses lasted 7 days, > or = 4 days longer than dexamethasone suppression. Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses study group and European Organization for Research and Treatment of Cancer consensus criteria. This approach is now being pursued in systematic clinical trials. 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