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Saturday 19 May 1973. 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. Saccharomyces cerevisiae is a ubiquitous, ascomycetous yeast, and vaginitis caused by this organism has been reported only very rarely. Because drugs with different mechanisms of action produced this effect, this suggests that it is the result of factors mediated by the cells. Click the button below to download Dr David Stevenss resume as a PDF. When serum was absorbed with HK B. dermatitidis or live B. dermatitidis, absorbed serum failed to significantly inhibit TNF-alpha production by RAW cells plus B. dermatitidis, and immunoblotting showed that absorbed serum was depleted of MBL-C. My role at the University of Birmingham includes - alongside teaching and research - helping other academics to engage with wider audiences, beyond the university campus. During the past several decades, there has been a steady increase in the frequency of opportunistic invasive fungal infections (IFIs) in immunocompromised patients. Using. Overall, itraconazole was more efficacious on an mg/kg basis; at high doses they were similarly effective. View details for DOI 10.3109/10408410903213393, View details for Web of Science ID 000275267300002. The decision to taper corticosteroids should be made on an individual basis, depending on the clinical course (BIII). Clemons, J.H. The present era, which is characterized largely by the modifications of azole drugs, began with ketoconazole and brought agents which can be given orally and have increasing potency, decreasing toxicity and a broader spectrum of activity. DEX suppression of cytokine production by BAM+LPS was modestly but significantly antagonized by GM-CSF. View details for Web of Science ID 000286214200026. Walsh, T. J., Raad, I., Patterson, T. F., Chandrasekar, P., Donowitz, G. R., Graybill, R., Greene, R. E., Hachem, R., Hadley, S., Herbrecht, R., Langston, A., Louie, A., Ribaud, P., Segal, B. H., Stevens, D. A., van Burik, J. H., White, C. S., Corcoran, G., Gogate, J., Krishna, G., Pedicone, L., Hardalo, C., Perfect, J. R. Experimental animal models of coccidioidomycosis. CNS aspergillosis is the most frequent and devastating manifestation of dissemination and mortality is high.Cyclophosphamide-suppressed CD-1 mice were infected intracerebrally with conidia of Aspergillus fumigatus and treated for 10 days with suboptimal doses of Abelcet (4 mg/kg) plus micafungin (1 mg/kg), caspofungin (1 mg/kg), itraconazole (100 mg/kg) or voriconazole (40 mg/kg) and compared with monotherapy. [2], Originally training as a chemist, Stevens subsequently trained at the Middlesex Hospital, London, qualifying as a surgeon. View details for DOI 10.1016/j.cyto.2006.08.004, View details for Web of Science ID 000243154800001. View details for DOI 10.3109/13693780903117473, View details for Web of Science ID 000274739900002. Conversely, GM-CSF decreased I kappaB levels. 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.Comparative sequence analyses of the calmodulin locus revealed the presence of the recently recognized species A. alabamensis (n = 4) in this collection. We report here studies which show that escape from growth inhibition is related to the enzymatic transformation of progesterone to polar metabolites. 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. Predictability of European marine climate over seasons to decades, Ocean Dynamics as Drivers of Seasonal to Decadal European Atmospheric Variability. The AUC for these enzymes was also similar in the two groups. Little is known about the effect of surfactant-associated proteins in bronchoalveolar lavage fluid (BALF) on the interaction of BAM and Blastomyces dermatitidis. 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. Here we describe a model of orogastrointestinal candidiasis. Subculture of a minority of tubes above the minimum fungicidal concentration yielded a few viable cells, suggesting random distribution, in some strains, of a few cells with propensity to grow in the presence of drug. GM-CSF given 24 h before DEX resulted in blocking of DEX suppression of BAM conidiacidal activity. Montoya, J. G., Chaparro, S. V., Celis, D., Cortes, J. The rate of adverse events was similar in the two groups. View details for DOI 10.1128/IAI.01185-07, View details for Web of Science ID 000253563500016, View details for Web of Science ID 000252221200001. Strokes due to transmural vasculitis associated with coccidioidal meningitis result in significant morbidity and mortality. Levels of matrix metalloproteinase-9 within cerebrospinal fluid in a rabbit model of coccidioidal meningitis and vasculitis. Major fungal diseases that are discussed include invasive disease due to Candida species, Aspergillus species and other molds, Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis. 01). We treated a patient who had acquired aspergillosis some 80 days after allogeneic bone marrow transplantation, with oral itraconazole, 600 mg daily. 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. Stevens, D. A., Kim, K. K., Johnson, N., Lee, J., Hamilton, J. R. Experimental Evidence That Granulocyte Transfusions Are Efficacious in Treatment of Neutropenic Hosts with Pulmonary Aspergillosis. In seven of the eight reported cases, blood cultures were positive for the organism. The mortality of clinical Aspergillus infections necessitates consideration of the utility of a vaccine. After initial deterioration, clinical and radiographic resolution occurred during 3 months of therapy despite severe graft-vs.-host and cytomegalovirus disease. Effect of 3M-003, an imidazoquinoline, on phagocyte candidacidal activity directly and via induction of peripheral blood mononuclear cell cytokines. View details for DOI 10.1128/CMR.00062-10, View details for Web of Science ID 000289346500004. View details for DOI 10.1080/13693780500051497, View details for Web of Science ID 000230896300029. We devised a pulmonary infection model in neutropenic BALB/c mice, used an antibacterial regimen to prevent confounding sepsis, and optimized PMN induction, purifications, and dose. Twenty-seven percent experienced possible symptomatic side effects, which resulted in 2 patients discontinuing therapy, and 42% had asymptomatic laboratory abnormalities, none of which were progressive. "I like to think I have been an archaeologist about one-half of one-tenth of a millennium," he says with a customary dry wit. IL-6 production in vivo in response to fungal-serum complexes could affect pathogenesis by opposing the host defense modulation by proinflammatory cytokines or by modulating the destructive effects of inflammation on host tissues. View details for DOI 10.1128/AAC.01538-08, View details for Web of Science ID 000265528700019, View details for PubMedCentralID PMC2681538. View details for DOI 10.1111/j.1574-695X.2010.00664.x, View details for Web of Science ID 000277321600009. I teach using a variety of techniques from traditional chalk and talk to computer based lectures. Genetic susceptibility to vaginal candidiasis. Successful immunizations have been demonstrated in turkeys and mice. The pharmacokinetics of a conventional and an intermittently administered high-dose regimen liposomal amphotericin B are linear. [1] He took up his own archaeological digs and eventually found Palaeolithic implements in the Reading drift gravels and excavated sites at Gas Works Lane and at Cemetery Junction in Reading. Many fungi have been shown to use hormonal (pheromonal) fungal molecules for intercellular communication, and there are increasing numbers of examples of interactions between mammalian hormones and fungi, including the specific binding of mammalian hormones by fungal proteins, and suggestions of mammalian hormonal modulation of fungal behavior. Studies of comparative virulence, host response, and pathogenesis are also possible using this model. Dissemination to livers occurred and was 100% on days 5 to 15; fewer animals had kidney infection. In recent years, understanding the role of messenger molecules (cytokines), in coordinating and augmenting cellular immunity has been ascendant. Many of the latter patients are in the intensive care unit. 529 followers . View details for DOI 10.1196/annals.1406.039, View details for Web of Science ID 000250750700039, Cryptococcus neoformans (Cn) var. In sequence treatment experiments, initial treatment of BAM with GM-CSF protected against subsequent treatment with DEX. View details for Web of Science ID A1987L150800003, View details for Web of Science ID A1977DC47300023, View details for Web of Science ID A1977DK44100032, View details for Web of Science ID A1974R882300002, Rhoda Benham Medal, Medical Mycology Society of the Americas (1999), Outstanding Achievement in Medicine Award, Santa Clara County Medical Association (2003), Lucille Georg Medal, International Society for Human and Animal Mycology (2006), Charles E. Smith Memorial Award, Coccidioidomycosis Study Group (2006), Department: Medicine - Med/Infectious Diseases, California Institute for Medical Research, Susceptibility of Candida albicans from Cystic Fibrosis Patients. Endobronchial and intracavitary instillation of antifungals or oral itraconazole may be useful for this condition. This feasibility study suggests that a short intermittent high-dose course of 10/5/5 mg LAB kg(-1) on days 1, 3 and 6 may be as safe and effective as a standard 14 day course of 3 mg kg(-1) per day, with drug-acquisition cost savings and reduced drug exposure. Oral therapy with cyclodextrin (control) or itraconazole or fluconazole at 10, 25, or 50 mg/kg of body weight twice daily (BID) was given for 12 days, from day 3 of infection. Cellular DNA, isolated after the lysis of protoplasts, was amplified by PCR using ITS1 and ITS4 primers, purified by liquid chromatography, and digested with restriction endonucleases. Denning, D. W., Stepan, D. E., Blume, K. G., Stevens, D. A. ULCERATIVE TRACHEOBRONCHITIS AFTER LUNG TRANSPLANTATION - A NEW FORM OF INVASIVE ASPERGILLOSIS. Itraconazole is a broad-spectrum oral triazole whose greatest advantages over the imidazoles are in its activity against aspergillosis and cryptococcosis, though it is also efficacious against the endemic deep mycoses. A model was used to compare the efficacies of itraconazole and fluconazole. 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. Concentrations of ITZ and its active metabolite, hydroxyitraconazole (OH-ITZ), in plasma and tissue samples were measured using high-performance liquid chromatography. In vitro studies and some animal studies almost always indicate an absence of antagonism when caspofungin is combined with azole or polyene antifungal agents. Perfect, J. R., Cox, G. M., Lee, J. Y., Kauffman, C. A., de Repentigny, L., Chapman, S. W., Morrison, V. A., Pappas, P., Hiemenz, J. W., Stevens, D. A. > present (Member of the Visitors Board of Oxford University Museum of Natural History) and [????] And finally what do you see when you look in the mirror? View details for Web of Science ID 000269145100014. The markers were then used to simultaneously map a multidrug-resistance locus and four other loci with high resolution (11 to 64 kilobases). Caspofungin at 0.1 micorg/ml and 0.05 microg/ml or Monos alone against germlings caused significant inhibition. Stevens, D. A., Clemons, K. V., Levine, H. B., Pappagianis, D., Baron, E. J., Hamilton, J. R., Deresinski, S. C., Johnson, N. Genomic DNA microarray comparison of gene expression patterns in Paracoccidioides brasiliensis mycelia and yeasts in vitro. Lipid formulations of amphotericin are indicated for the patient who has impaired renal function or who develops nephrotoxicity while receiving deoxycholate amphotericin (AII). Invited essay in The SAA Archaeological Record 11(4). Stevens then became . She completed a PhD in Egyptian Archaeology at Monash Uni versity in Australia in 2003, with a study of the archaeology of private religion at Amarna . Outbred mice are immunosuppressed using weekly doses of 5-fluorouracil to induce neutropenia and damage the mucosal epithelial layer, and are also maintained on a broad-spectrum antibiotic regimen to reduce secondary bacterial infection. Combinations of AmBi plus CAS or MICA prolonged survival, but were not better than monotherapy. Human phagocytes of various lineages work cooperatively in vitro with antifungal drugs to inhibit or kill fungal pathogens, and this activity is augmented by several recombinant cytokines. Four responses were complete and seven were partial; these included five patients with pulmonary sites and six patients with disseminated sites. On the other hand, desired effects of DEX could be maintained in other compartments. Random mating among PS1 isolates, which were distributed across North America, was only detected after partitioning isolates into six geographic regions. Sampling 24 h after the last treatment showed that AmBisome at 3 but not at 10 mg/kg, as well as Abelcet, caspofungin, and voriconazole, reduced brain CFU. Mannan is a candidate for a cross-protective conjugate fungal vaccine. Here we investigated the possibility that GM-CSF could antagonize DEX down-regulation of interleukin (IL)-1alpha and tumour necrosis factor (TNF)-alpha production by stimulated BAM. Infection with Trichosporon beigelii is an uncommon cause of endocarditis. For weeks after treatment, in vitro IFN-gamma treatment enabled PM Blastomyces killing. Dr Stevens is without doubt one of the worlds most accomplished facilitators. In the second study, Abelcet alone significantly prolonged survival and reduced cfu in the organs versus the controls. On a more functional note, Im now much more interested in the environments our children grow up in, and early education. University of Wales, Cardiff, Glamorgan, Wales, United Kingdom. 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. Donald asks the courts to let him tweet. These data show that GM-CSF in vivo blocks the in vivo immunosuppressive effects of DEX on BAM killing of conidia and suggest a potential use of GM-CSF in patients at risk for aspergillosis due to immunosuppressive DEX treatment. Toxicity was reversible, and principal side effects were nausea and vomiting (50%), gynecomastia (21%), decreased libido (13%), alopecia (8%), elevated liver function tests (5%), pruritus (5%), and rash (4%). Sixty-two C. dubliniensis strains were collected from the authors of previously published studies. William David Thomas. Murine models of infection are used most often for these studies and provide numerous advantages, including availability of immunological reagents, many strains with defined genetics, and ease of handling and cost considerations. There is an important need for generation of consensus definitions of outcomes of IFD that will form a standard for evaluating treatment success and failure in clinical trials. Also known as: Kimberly David Stevens, David Kstevens Or, Kimberly Stevens. Frequency of paradoxical effect with caspofungin in Candida albicans, Comparative Efficacies of Lipid-Complexed Amphotericin B and Liposomal Amphotericin B against Coccidioidal Meningitis in Rabbits. (ODYSEA), Decadal variability of the extratropical response to the Madden-Julian Oscillation, North Atlantic Oscillation response to the MaddenJulian Oscillation in a coupled climate model, Reversal of ocean gyres near ice shelves in the Amundsen Sea caused by the interaction of sea ice and wind, Seasonal extrema of sea surface temperature in CMIP6 models. Its value depends entirely on how it is used, and only an artist can use it. Experimental vaccines in mouse models have demonstrated a promising avenue of approach for the prevention of aspergillosis, as well as infections caused by other fungal pathogens, such as Coccidioides, the etiological agent of valley fever (coccidioidomycosis). The distributions among ethnic groups were not different, however they differed (p = 0.002) from global populations. Candida albicans is a common microbe, colonizer and potential pathogen found in respiratory cultures of cystic fibrosis (CF) patients. In this book, David Stevens explains how the principles of Participatory Business Planning may be applied to any business or public body, of any size and how they can turn adversity into prosperity and efficiency. 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. View details for Web of Science ID 000075665900020. The collection was assembled so that approximately half of the isolates were resistant to azole drugs. nov.) in the environment, most closely related to H. magadiensis. In basilar arteries of infected animals versus controls, mRNAs encoding for IL-6, iNOS, IFN-gamma, IL-2, MCP-1, IL-1beta, IL-10, TNF-alpha, CCR-1, MMP-9, TGF-beta, as well as MMP-9 protein in CSF, were found to be significantly up-regulated. All regimens tested prolonged survival (P < 0.05 to 0.0001). View details for DOI 10.1128/AAC.47.4.1452-1455.2003, View details for Web of Science ID 000181842000049. Self 1 episode, 2002 Ron Curley . Almost all models are murine, with 1 rabbit model; and 2 avian models (in collaboration with Veterinary School, Univ. The innovative approach to business planning described in this book is the result of not only many years research, but of the experience of running over 300 participatory sessions in a whole range of enterprises, in every State in Australia as well as other countries throughout the world. Amphotericin B are linear to decades, Ocean Dynamics as Drivers of Seasonal to European... To livers occurred and was 100 % on days 5 to 15 ; fewer had! Children grow up in, and pathogenesis are also possible using this model acquired aspergillosis some 80 days allogeneic! Messenger molecules ( cytokines ), in plasma and tissue samples were measured using high-performance chromatography. 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