A systemic model of candidiasis was studied in CD-1 mice by intravenous inoculation of different isolates of C. albicans. Alice Roberts and David Stevens have been mar See This concept has been applied to a wide range of businesses and projects, from small to large, all with outstanding success. Experimental Central Nervous System Aspergillosis Therapy: Efficacy, Drug Levels and Localization, Immunohistopathology, and Toxicity. BAM plus B. dermatitidis (BAM-B. Endothelial cell activation (ICAM-1 and P-selectin in cerebral capillaries) occurred during infection. View details for DOI 10.3109/10408410903213393, View details for Web of Science ID 000275267300002. MMP-9 may contribute to inflammation and vasculitis in this animal model. In this model, intravenous ABLC and AmBi were similarly highly effective, with few clinical signs of infection, 100% survival, and significantly reduced fungal burdens among treated animals. Patients received posaconazole (400 mg/day) in capsule formulation for up to 6 months. Invasive aspergillosis. A high intermittent dose regimen (group A: 10 mg kg(-1) on day 1, 5 mg kg(-1) on days 3 and 6) was compared with standard dosing (group B: 3 mg kg(-1) per day for 14 days) of liposomal amphotericin B (LAB) for empirical treatment of persistent febrile neutropenia. Jeffries, Chief Executive, W.S. Bayesian estimates for clearance and volume increased in a linear manner with weight, but only the former was statistically significant (P = 0.039). Thanks Alice. As more genomes are sequenced, the identification and characterization of the causes of heritable variation within a species will be increasingly important. Amphotericin B tissue and serum concentrations did not correlate with efficacy. Therapy is predominantly directed at preventing life-threatening hemoptysis. Infection with Trichosporon beigelii is an uncommon cause of endocarditis. Candida albicans given in the drinking water resulted in oral infection by day 3 that significantly increased from days 10 to 15 and mucosal infection with 4 to 7 log(10) Candida CFU in the esophagus, stomach, small intestine, and cecum. My main research interest is large scale ocean modelling. His zodiac sign is Cancer. #ScienceGrrl Speed Mentoring: Who championed you? Her work has a clear pedagogy of embedded research and practice with postgraduate teacher training . The protective moiety(ies) appeared to reside in the cell wall and was resistant to 100 C, but not to protease or formalin. We review here data from animal models as an indicator of future potential.The primary data are from murine studies and we will briefly review chemotherapeutic combination studies, some showing benefit over monotherapy and some showing no benefit over monotherapy. Two cohorts were studied. Res Publica: A journal of social and political philosophy. 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. View details for Web of Science ID 000166958800032. There were no differences in distribution of types comparing babies versus adults, or bloodstream isolates versus colonizing or environmental isolates. It describes a range of group problem solving methodologies and illustrates vividly how they can aid modern business. Select the best result to find their address, phone number, relatives, and public records. Saccharomyces cerevisiae isolates have been shown previously to exhibit a high degree of variation in their ability to proliferate and persist in CD-1 mice (K.V. grubii and Cryptococcus gattii in normal and immunodeficient mice. dermatitidis) TNF-alpha production was inhibited > or = 47% by BALF or SP-A-/- BALF (at 290 or 580 microg of protein/ml, P < 0.05 to 0.01); in contrast, SP-D-/- BALF did not significantly inhibit TNF-alpha production. C. metapsilosis appears rarely. The objective of the present work was the identification of new microsatellite loci able to distinguish among C. parapsilosis isolates. View details for DOI 10.1080/13693780500051919, View details for Web of Science ID 000230896300018. Montoya, J. G., Chaparro, S. V., Celis, D., Cortes, J. Paracoccidioidomycosis, one of the most important endemic and systemic mycoses in Latin America, presents several clinical pictures. During a three-year period, M. pachydermatis was also recovered from fungal cultures of an additional 30 patients, 85% of whom were infants. Invasive aspergillosis is a major cause of mortality in immunocompromised patients and therapeutic options are often limited, thus a vaccine would be desirable. Aspergillus species are responsible for most cases of fatal mold infections in immunocompromised patients, particularly in those receiving hematopoietic stem cell transplants. When VCZ was combined with monocytes or monocytes were treated with GM-CSF, inhibition was significantly increased, to similar levels. David Stevens. Albany. Weger, S. D., Ganji, A., Clemons, K. V., Byron, J. K., Minn, Y., Stevens, D. A. Homozygosity at the Candida albicans MTL locus associated with azole resistance. The AUC for these enzymes was also similar in the two groups. View details for DOI 10.1016/j.cyto.2006.08.004, View details for Web of Science ID 000243154800001. Thus, this study identified inflammatory mediators associated with CNS vasculitis and meningitis due to C. immitis infection. Fungal burdens in brains and kidneys were reduced after > 0.3 mg of mannan-BSA (all P < 0.05). Definitive diagnosis of pulmonary fungal infections has also been substantially assisted by the development of newer diagnostic methods and techniques, including the use of antigen detection, polymerase chain reaction, serologies, computed tomography and positron emission tomography scans, bronchoscopy, mediastinoscopy, and video-assisted thorascopic biopsy. This showed GM-CSF reverses the immunosuppressive effect of DEX by enhancing the degradation of IkappaB and promoting the translocation of NF-kappaB to the nucleus. Developmental studies showed that suppression of mice with 5-fluorouracil beginning 3 days prior to infection and given every 7 days thereafter necessitated antibacterial treatment but resulted in a reproducible model. It began in 1903, with the successful use of potassium iodide (KI). The cumulative percent toxicity requiring discontinuation of drug was 6, 17, 23, and 56% at 400-, 800-, 1,200-, and 1,600-mg doses. Further study by 16S rRNA gene sequencing and DNA-DNA hybridization revealed the cultures represented 3 novel species: 1 (H. stevensii sp. Little is known about the effects of serum factors or MBL on the interaction of Blastomyces dermatitidis, a pulmonary fungal pathogen, with macrophages or on tumor necrosis factor alpha (TNF-alpha) production. We treated a patient who had acquired aspergillosis some 80 days after allogeneic bone marrow transplantation, with oral itraconazole, 600 mg daily. Allergic bronchopulmonary aspergillosis (APBA). CD-1 mice received HKY subcutaneously or by oral gavage with or without adjuvants once weekly beginning 3 or 4 weeks prior to infection; oral live Saccharomyces was also studied. View details for DOI 10.1016/j.diagmicrobio.2004.10.006, View details for Web of Science ID 000228091200003. The archaeologist, professor and author of 22 books, Starbuck unearthed artifacts at forts and battlefields in New York and Shaker villages in New Hampshire. Clemons, K. V., Schwartz, J. View details for Web of Science ID 000174578300002. Atkins, PLC, (U.K.). The overall mortality rate was 20%.This report extends the information on invasive aspergillosis in immunocompetent patients and supports the conclusion that triazole therapy should be considered for this serious infection. PhD student in Archaeology Dr Anna Stevens. A standard set of definitions strengthens the consistency and reproducibility of such studies.After the introduction of the original 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 definitions, advances in diagnostic technology and the recognition of areas in need of improvement led to a revision of this document. Company. View details for Web of Science ID 000085846900002. Archaeology of Parchman Place, Coahoma County, Mississippi 2006 M.A., Anthropology, University of Mississippi, University . > present (Patron of Twycross Zoo) and 2018 > present (member of the BHF Council) and 1988 > 1988 (winner: of the BBC1 Blue Peter Young Artists competition). Interestingly, six of eight known vaginal isolates were group B, with four of those six being identical. For 24 h after administration of all doses, mean concentrations in serum exceeded MICs for Coccidioides immitis (trough concentrations, greater than 1 microgram/ml). View details for DOI 10.1097/MD.0b013e3181aede29, View details for Web of Science ID 000268079000008. Four years later amphotericin B followed, which is still the historical standard against which new systemic antifungals are compared. Capilla, J., Clemons, K. V., Liu, M., Levine, H. B., Stevens, D. A. Cryptococcosis as a complication of the immunocompromised host has dramatically increased in frequency since the start of the AIDS epidemic. The only exception to this was the inability to distinguish between Saccharomyces bayanus and S. pastorianus (S. carlsbergensis). Intravenous therapy should be used initially in rapidly progressing disease (BIII). Both methods showed AMB efficacy in the kidneys, and qPCR demonstrated CAS efficacy at all doses. These data indicate that AmBi may offer an improvement in the treatment of coccidioidal meningitis. Only two of six patients who were treated with antifungal agents survived endocarditis caused by T. beigelii and were apparently cured; one of these patients was also managed surgically with valve replacement. No mice died after infection with 10(6) CFU of Y55 or YJM128. The increasing incidence of invasive fungal infections is the result of many factors, including an increasing number of patients with severe immunosuppression. Our results show that the fos-1 deletion strain has significantly reduced virulence as compared with the parental wild-type strain. In these studies we assessed the utility of recombinant human MBL (rhMBL) as a therapeutic against experimental C. albicans vaginitis. Caspofungin was co-cultured for 24h with either human monocytes (Monos), monocyte-derived macrophages (MDM), or polymorphonuclear neutrophils (PMN) against germlings of A. fumigatus and antifungal activity assessed using the XTT metabolic assay. . 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 . Band profiles were used to distinguish and group isolates. Itraconazole appears useful as a corticosteroid sparing agent (BII). View details for PubMedID 12975755. Treatment of invasive aspergillosis with posaconazole in patients who are refractory to or intolerant of conventional therapy: An externally controlled trial. [4][1], Whilst appointed as Medical Officer, Stevens reported that disease was being spread by polluted water and poor hygiene and informed support for significant health legislations including the 1866 Sanitary Act which had been hastened by the cholera epidemic. Here, we report on the construction of a genomic DNA microarray, covering approximately 25 % of the genome of the organism, and its utilization in identifying genes and gene expression patterns during growth in vitro. 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. In fungi, two-component histidine kinases have various functions including regulation of osmosensitivity, and of cell-wall assembly. To study the interaction of antifungal drugs in topical therapy.Local therapy of Candida vaginitis with drugs alone and in combination was examined in a murine model. Proof of a person's disability or proof of the service animal's health or training cannot be required. After infection spleen cells from IL-12 treated mice produced 4-fold more IFN-gamma and 3-fold less IL-10 in response to Blastomyces. View the profiles of professionals named "David Stevens" on LinkedIn. Surgical treatment is definitive but many patients are ineligible. Location. The median time of onset from transplantation for invasive pulmonary aspergillosis (IPA) was 46 days, but the median time to first positive culture result was 104 days among patients with Aspergillus colonization but no invasive disease. Three levels of probability are proposed: "proven," "probable," and "possible." Lethargy, ataxia, or paralysis preceded death. But I was very lucky when I made Digging for Britain to work with a very supportive production company (360 Production). The median duration of treatment was 173 days. The aim of the present investigation was to assess the epidemiological relatedness of a group of vaginal and commercial S. cerevisiae isolates by a previously reported genetic typing method, which divided the isolates into two broad groups with numerous subtypes. Two other local hospitals' dialysis centers, and our own inpatient dialysis facility, were cultured at sites that yielded Halomonas from our RCC, and Halomonas was not isolated. 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. Improvement was noted with amphotericin B or itraconazole followed by voriconazole but not with itraconazole followed by amphotericin B. Marked CFU reduction by AmBisome at 3 mg/kg occurred in association with relatively more intense inflammation. We reported previously that Trichophyton mentagrophytes contains a cytoplasmic macromolecule which specifically binds progesterone. Macrophages were unstimulated or stimulated with A. fumigatus conidia and simultaneously treated with DEX, GM-CSF or DEX + GM-CSF for 2 4 hours. > [????] Flow cytometry of lymphocytes from HKY-vaccinated showed 52% of CD3(+) or 56% of CD8(+) cells exhibited cell division after stimulation with HKY, compared to non-stimulated controls (26 or 23%, respectively) or HKY-stimulated cells from PBS-vaccinated (31 or 34%). Dose-finding studies in CD-1 mice showed that infection with 5 x 106 conidia/mouse consistently caused 100% mortality by day 5-8; no mice died before day 3. The category of proven invasive fungal disease can apply to any patient, regardless of whether the patient is immunocompromised, whereas the probable and possible categories are proposed for immunocompromised patients only.These revised definitions of invasive fungal disease are intended to advance clinical and epidemiological research and may serve as a useful model for defining other infections in high-risk patients. Epidemiological studies of Candida parapsilosis have been performed by molecular methods. Invasive aspergillosis is an important cause of morbidity and mortality in immunocompromised patients. This emphasizes the potential importance of a positive culture for Aspergillus in the critically ill, the need for awareness about possible aspergillosis in patients lacking the classical risk factors, and readiness to proceed with appropriate diagnostic maneuvers. Immunosuppressed mice were infected intracerebrally with Aspergillus fumigatus and treated with an amphotericin B preparation, an echinocandin, or voriconazole (VCZ) given alone or in combination. In Vitro Activity of Amphotericin B Against Aspergillus terreus Isolates from Different Countries and Regions. While other current diagnostic tests perform moderately well, many lack timeliness, efficacy, and are negatively affected by treatments common to critically ill patients. Infected animals were treated with CAS at various dosages (0.01 to 20 mg/kg) and CFU remaining in the kidneys determined. Fundamental Bioscience Professor of Cell Biology, School of Biochemistry Dynamic Cell Biology https://orcid.org/0000-0001-5297-3240 Email David.Stephens @ bristol.ac. Three of the fifteen patients in group B and none in group A developed invasive fungal infections (IFIs). Guinea pig models have primarily been used in therapy studies of invasive pulmonary aspergillosis (IPA). In the initial study, groups of mice were given saline, or 1, 3 or 10 mg kg(-1) of MICA b.i.d., s.c. All saline controls, and 90% of untreated mice succumbed to infection. van Asbeck, E., Clemons, K. V., Martinez, M., Tong, A., Stevens, D. A. Greater numbers of chronic inflammatory foci did not correlate with higher CFU. The largest therapeutic experience is with amphotericin B deoxycholate, which should be given at maximum tolerated doses (e.g., 1-1.5 mg/kg/d) and should be continued, despite modest increases in serum creatinine levels (BIII). Rises in creatinine were mild (clinical toxicity criteria 1) in all patients with elevations. Further PCR analysis demonstrated that loss of the MTLa1 and MTLalpha1 genes corresponded to loss of all of the loci-specific genes, resulting in homozygosity at the MTL locus. View details for DOI 10.1080/13693780802213340, View details for Web of Science ID 000265362300018. The immunological basis for differences in resistance to pulmonary blastomycosis between young (3 to 4-week-old) and adult (7 to 8-week-old) CD-1 mice is unknown. 3rd year: Numerical Solution of Partial Differential Equations, Dynamical Oceanography, Dynamical Meteorology. 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). Measurement of a hyphal organism, like Aspergillus, presents difficulties in that it is problematic to define what constitutes a cell. > present (Science columnist for The Observer newspaper) and 2018 > present (president of Humanists UK) and 2011 > present (patron of Humanists UK) and 2012 > present (Chair of the Birmingham universitys Public Engagement with Science Committee) and [????] View details for Web of Science ID 000172586800004. > present (Patron of the Natural Sciences Collections Association), [????] Histologic examination of samples of brain tissue showed focal abscesses containing Aspergillus hyphae. Imai, J. K., Singh, G., Clemons, K. V., Stevens, D. A. Paradoxical effect of caspofungin: Reduced activity against Candida albicans at high drug concentrations, Genetic susceptibility of mice to Candida albicans vaginitis correlates with host estrogen sensitivity. The definitions are intended for use in the context of clinical and/or epidemiological research, not for clinical decision making. Intraparenchymal abscesses with inflammatory cells in their peripheries were found beginning on day 10. View details for DOI 10.1016/j.ajic.2005.06.005, View details for Web of Science ID 000238967600010. Since Abelcet displayed dose-responsive efficacy, it is possible higher doses could produce superior results, yet not show toxicity. David Stevens . I was deeply involved in theFine Resolution Antarctic Model (FRAM)project and theOcean Circulation and Climate Advanced Modelling (OCCAM)project. Mice were treated with liposomal-amphotericin B (AmBi; AmBisome), lipid-complexed amphotericin B (ABLC; Abelcet), voriconazole (VCZ), micafungin (MICA), caspofungin (CAS) or deoxycholate amphotericin B (AMBd) given alone or in combination. Sixty isolates were grouped on the basis of the presence (group B) or absence (group A) of a 3-kb band. 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. Clemons, K. V., Schar, G., Stover, E. P., Feldman, D., Stevens, D. A. The immunological basis for a >10-fold resistance of outbred CD-1 mice compared to inbred BALB/c mice to pulmonary blastomycosis was investigated. with 10(7) cfu of either the parental grand or a spontaneously derived petite from one of four isolates previously classified with differing degrees of virulence: YJM128, YJM309, YJM145 and Y55. 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