Immunomodulation with Synthetic Molecules: Mechanisms of Actions and Effects on Macrophages. (2002)
Stevens,D. A., Brummer,E., Morrison,C. J.
Immunoenhancing drugs are under study both for their general effects on host immunity and their effects on immune interactions with microbial infections. These studies focused preferentially on...
Brummer,E., Sugar,A. M., Stevens,D. A.
The interaction of elicited murine polymorphonuclear neutrophils (PMN) and the thermally dimorphic fungal pathogen Blastomyces dermatitidis in vitro was studied. The PMN elicited intraperitoneally...
Search for correlation effects in linear chains of trapped ions (2000)
Donald, C. J. S., Lucas, D. M., Barton, P. A., McDonnell, M. J., Stacey, J. P., Stevens, D. A., ...
We report a precise search for correlation effects in linear chains of 2 and 3 trapped Ca+ ions. Unexplained correlations in photon emission times within a linear chain of trapped ions have been...
Precision Measurement of the Lifetime of the 3d D_{5/2} state in 40Ca+ (2000)
Barton, P. A., Donald, C. J. S., Lucas, D. M., Stevens, D. A., Steane, A. M., Stacey, D. N.
We report a measurement of the lifetime of the 3d 2D_{5/2} metastable level in 40Ca+, using quantum jumps of a single cold calcium ion in a linear Paul trap. The 4s S_{1/2} - 3d D_{5/2} transition is...
Stevens, D.A, London Univ. (GB).
Thesis (Ph.D.)
Bioassays for itraconazole blood levels: an interlaboratory collaborative study (1999)
Odds, F. C., Dupont, B., Rinaldi, M. G., Stevens, D. A., Warnock, D. W., Woestenborghs, R.
Duplicate bioassays for itraconazole and hydroxy-itraconazole were run with 30 serum samples in five laboratories, each using a different method. Both itraconazole and hydroxy- itraconazole were used...
Immunomodulation with Synthetic Molecules: Mechanisms of Actions and Effects on Macrophages. (1998)
Immunoenhancing drugs were studied both for their general effects on host immunity and their effects on immune interactions with microbial infections. These studies focused preferentially on defined...
User Manual for Tactical Language Identification Software. (1998)
This report has been issued by Dr. P. Nowell for Rome Laboratory under contract CSMI6694. The report is split into two parts which mirror the major components of the tactical language identification...
Bos, R.P., Noordhoek, J., Stevens, D.A., ...
An evaluation of recently developed antibiotics (1983)
Fernandes, C. J., Stevens, D. A., Murray, S. I., Ackerman, V. P.
A number of newer antibiotics, broad-spectrum penicillins and cephalosporins, have been evaluated against Gram-negative rods. The organisms were selected for multi-resistance and transferable...
LEVINE, H. B., RESTREPO-M, ANGELA, EYCK, D. R. TEN, STEVENS, D. A.
Until recently coccidioidin has been the only antigenic preparation available for detecting delayed dermal sensitivity induced by an experience with Coccidioides immitis. It is prepared from...
Efficacy of Ravuconazole in Treatment of Systemic Murine Histoplasmosis
Clemons, K. V., Martinez, M., Calderon, L., Stevens, D. A.
Ravuconazole (RCZ) was evaluated for efficacy in comparison to fluconazole (FCZ) and itraconazole (ITZ) in murine models of disseminated histoplasmosis. All regimens tested prolonged survival (P <...
Efficacy of the triazole D0870 in a murine model of systemic histoplasmosis.
The efficacy of D0870 was studied in a murine model of systemic histoplasmosis and was compared with that of fluconazole. All regimens of D0870 (1 or 10 mg/kg of body weight given daily or 1, 10, or...
Activities of the triazole SCH 51048 against Coccidioides immitis in vitro and in vivo.
Clemons, K V, Homola, M E, Stevens, D A
The activity of the novel triazole SCH 51048 was tested against Coccidioides immitis. SCH 51048 inhibited C. immitis in vitro; MICs for 13 isolates ranged from < or = 0.39 to 0.78 micrograms/ml, and...
Nassar, F, Brummer, E, Stevens, D A
The inhibitory effect of human serum on the multiplication of Cryptococcus neoformans and the interaction with fluconazole were studied. Compared with cryptococcal multiplication in RPMI 1640 medium...
UR-9746 and UR-9751 are novel azole derivatives each containing a morpholine ring. They were examined for both in vitro and in vivo activities against Coccidioides immitis. In vitro, UR-9746 and...
Itraconazole resistance in Aspergillus fumigatus.
Denning, D W, Venkateswarlu, K, Oakley, K L, Anderson, M J, Manning, N J, Stevens, D A, ...
Invasive aspergillosis is an increasingly frequent opportunistic infection in immunocompromised patients. Only two agents, amphotericin B and itraconazole, are licensed for therapy. Itraconazole acts...
Activity of the triazole SCH 56592 against disseminated murine coccidioidomycosis.
Lutz, J E, Clemons, K V, Aristizabal, B H, Stevens, D A
SCH 56592 (SCH) is a new triazole antifungal with a broad spectrum of activity. In vitro susceptibility testing against five strains of Coccidioides immitis revealed MICs from 0.39 to 3.13 microg/ml...
Natarajan, U, Brummer, E, Stevens, D A
The effect of granulocyte colony-stimulating factor (GCSF) treatment of polymorphonuclear neutrophils (PMN) in vitro was studied with respect to their candidacidal activity. The candidacidal activity...
Efficacy of nikkomycin Z against experimental pulmonary blastomycosis.
Nikkomycin Z is a chitin synthetase inhibitor. In vitro, nikkomycin Z had good activity against Blastomyces dermatitidis, with an MIC of 0.78 microg/ml and a minimal fungicidal concentration of 3.1...
Comparative effects of cilofungin and amphotericin B on experimental murine candidiasis.
The effectiveness of cilofungin (LY121019, referred to hereafter as LY), a lipopeptide, was studied in a murine candidiasis model. CD-1 mice (5 weeks old) were injected intravenously with 3 x 10(5)...
Efficacy of SCH39304 and fluconazole in a murine model of disseminated coccidioidomycosis.
Clemons, K V, Hanson, L H, Perlman, A M, Stevens, D A
The efficacies of SCH39304 (SCH) and fluconazole (FLU) were tested in a murine model of coccidioidomycosis. CD-1 mice were infected with Coccidioides immitis and dosed with SCH at 2, 10, 25, or 50...
Arathoon, E G, Hamilton, J R, Hench, C E, Stevens, D A
Methicillin-resistant Staphylococcus aureus (MRSA) is an important nosocomial infection problem. Colonization appears to be more common than invasive disease is. Eradication of colonization or the...
Pharmacokinetics of fluconazole in cerebrospinal fluid and serum in human coccidioidal meningitis.
Tucker, R M, Williams, P L, Arathoon, E G, Levine, B E, Hartstein, A I, Hanson, L H, ...
The pharmacokinetics of fluconazole, a new oral azole, were evaluated in cerebrospinal fluid and sera of eight patients with coccidioidal meningitis. At a dose of 50 mg/day, peak concentrations of...
Tucker, R M, Hanson, L H, Brummer, E, Stevens, D A
ICI 195,739, a novel orally active triazole, proved 50 times as potent as ketoconazole, produced a clinical cure, and completely eradicated residual infection in a murine model of pulmonary...
Cilofungin (LY121019) is a new lipopeptide antifungal drug. We tested this drug against 141 pathogenic fungal isolates. All fungal species were tested by broth dilution at 35 degrees C. Malassezia...
Pathogenicity of Saccharomyces cerevisiae in complement factor five-deficient mice.
Byron, J K, Clemons, K V, McCusker, J H, Davis, R W, Stevens, D A
We have previously determined the relative virulence of isolates of Saccharomyces cerevisiae on the basis of differences in proliferation and resistance to clearance in CD-1 mice. These infections...
Pharmacology and toxicity of high-dose ketoconazole.
Sugar, A M, Alsip, S G, Galgiani, J N, Graybill, J R, Dismukes, W E, Cloud, G A, ...
One hundred sixty patients were entered in two multicenter protocols to receive 400 to 2,000 mg of ketoconazole once daily for nonmeningeal or meningeal coccidiodomycosis. For 24 h after...
Lefler, E, Brummer, E, Perlman, A M, Stevens, D A
We studied the efficacy of new experimental antifungal drugs, which represent molecular modifications of present active agents, in a murine model of blastomycosis. Ketoconazole, previously the best...
Disposition of ketoconazole, an oral antifungal, in humans.
Brass, C, Galgiani, J N, Blaschke, T F, Defelice, R, O'Reilly, R A, Stevens, D A
The pharmacology of ketoconazole was studied in patients with fungal infections. After administration of 50-, 100-, and 200-mg doses of ketoconazole, there was a linear increase in the area under the...
Synergistic interaction of trimethoprim and sulfamethoxazole on Paracoccidioides brasiliensis.
The in vitro interaction of trimethoprim and sulfamethoxazole on clinical isolates of Paracoccidioides brasiliensis was studied. With complete inhibition and a visual endpoint used as the criteria,...
Stiller, R L, Bennett, J E, Scholer, H J, Wall, M, Polak, A, Stevens, D A
Candida albicans isolates from 402 patients with no prior history of treatment with 5-fluorocytosine were collected at five medical centers from different areas of the United States. Isolates could...
Inhibition and killing of Candida albicans in vitro by five imidazoles in clinical use.
Five imidazoles (clotrimazole, econazole, ketoconazole, miconazole, and tioconazole) in clinical use were compared for their ability to inhibit and kill Candida albicans. Eleven isolates were...
Grosso, D S, Boyden, T W, Pamenter, R W, Johnson, D G, Stevens, D A, Galgiani, J N
In vivo perfusion of canine testes with ketoconazole inhibited the stimulation of testosterone production by human chorionic gonadotropin in a dose-dependent manner. Ketoconazole also selectively...
Cano, L E, Gomez, B, Brummer, E, Restrepo, A, Stevens, D A
Conidia of P. brasiliensis ingested by murine macrophages at 37 degrees C showed enhanced transformation to yeast cells and further intracellular growth compared with conidia in culture medium alone....
Activities of the triazole D0870 in vitro and against murine blastomycosis.
Clemons, K V, Hanson, L H, Stevens, D A
The novel triazole D0870 was tested for in vitro activity, as well as in vivo in a murine model of pulmonary blastomycosis. In vitro, D0870 had inhibitory and fungicidal activity against Blastomyces...
Effect of cyclodextrin on the pharmacology of antifungal oral azoles.
Hostetler, J S, Hanson, L H, Stevens, D A
Concentrations of oral azoles in serum were compared in a single-dose pharmacologic study in mice. When hydroxypropyl-beta-cyclodextrin was used as a carrier and compared with a standard carrier,...
Complexing amphotericin B (AmB) with lipids or entrapping it in liposomes may increase its efficacy by reducing toxicity and affecting distribution. However, depending on the lipids involved,...
Hostetler, J S, Heykants, J, Clemons, K V, Woestenborghs, R, Hanson, L H, Stevens, D A
Pharmacologic studies of itraconazole (IZ), a triazole antifungal, indicated unexplained differences between bioassay and chromatographic determinations and large variations in steady-state blood...
Deresinski, S C, Clemons, K V, Kemper, C A, Roesch, K, Walton, B, Stevens, D A
A cluster of isolates of Candida parapsilosis recovered from clinical specimens was demonstrated, by both classical and molecular epidemiological techniques, to have resulted from contamination in...
D-mannitol in cerebrospinal fluid of patients with AIDS and cryptococcal meningitis.
Megson, G M, Stevens, D A, Hamilton, J R, Denning, D W
Cryptococcal meningitis (CM) is associated with raised intracranial pressure which is linked with serious neurological sequelae. Cryptococcus neoformans produces D-mannitol in vitro and in...
Clemons, K V, Feroze, F, Holmberg, K, Stevens, D A
The objective of the present study was to conduct a comparative genotypic analysis of Candida albicans isolates from the United States, Europe, and Southeast Asia to determine whether differences...
Clemons, K V, Park, P, McCusker, J H, McCullough, M J, Davis, R W, Stevens, D A
We have previously described differences in phenotype and virulence among clinical and nonclinical isolates of Saccharomyces. To further characterize these isolates, a comparison of restriction...
SCH 39304 in the treatment of acute or established murine pulmonary blastomycosis.
Brummer, E, Hanson, L H, Stevens, D A
SCH 39304 was tested for treatment of acute or established murine pulmonary blastomycosis and was compared with ketoconazole and fluconazole in a model of acute infection. Only SCH 39304 at 25 or 50...
Rex, J H, Hanson, L H, Amantea, M A, Stevens, D A, Bennett, J E
An improved bioassay for fluconazole was developed. This assay is sensitive in the clinically relevant range (2 to 40 micrograms/ml) and analyzes plasma, serum, and cerebrospinal fluid specimens;...
Cilofungin, amphotericin B, and a combination of the two drugs were compared in a model of aspergillosis in immunocompetent mice in three experiments. Cilofungin was equivalent to amphotericin B in...
Synergy between cilofungin and amphotericin B in a murine model of candidiasis.
Hanson, L H, Perlman, A M, Clemons, K V, Stevens, D A
The efficacies of cilofungin and amphotericin B separately and together in mice with disseminated candidiasis were studied. Male CD-1 mice (age, 5 weeks) were infected intravenously with 3 X 10(5)...
The efficacy of a novel sterol-complexed preparation of amphotericin B, amphotericin B colloidal dispersion, was compared with that of deoxycholate-complexed amphotericin B in an acute murine model...
Amphotericin B as a lipid complex and as a deoxycholate suspension (Fungizone) was tested against murine blastomycosis. All doses of each form prolonged survival (P less than 0.05 to 0.001)....
Hostetler, J S, Clemons, K V, Hanson, L H, Stevens, D A
The efficacy and safety of amphotericin B colloidal dispersion (ABCD) were compared with those of amphotericin B deoxycholate suspension (ABDS) (Fungizone) in a murine model of disseminated...
Cano, L E, Brummer, E, Stevens, D A, Restrepo, A
Conidia ingested by resident macrophages had an enhanced percentage of transformation to yeast cells compared with those in culture medium without macrophages. The yeast cells subsequently grew...
Seven Blastomyces dermatitidis isolates varying in virulence for mice were compared for susceptibility to polymorphonuclear neutrophil (PMN) killing and the ability to induce superoxide anion (O2-)...
Brummer, E, Sun, S H, Harrison, J L, Perlman, A M, Philpott, D E, Stevens, D A
Transmission electron microscopy was used to study ultrastructures in Paracoccidioides brasiliensis yeast cells after ingestion by nonactivated or cytokine-activated murine peritoneal macrophages....
Inhibition by estrogens of conidium-to-yeast conversion in the fungus Paracoccidioides brasiliensis.
Salazar, M E, Restrepo, A, Stevens, D A
Conidia produced by Paracoccidioides brasiliensis are inhibited by mammalian estrogens in their in vitro conversion into yeast-form cells. This was demonstrated with four different isolates. In these...
Castaneda, E, Brummer, E, Pappagianis, D, Stevens, D A
Humoral and cellular immune responses were measured during the progression of chronic pulmonary and disseminated paracoccidioidomycosis in mice. The chronic disease was established by pulmonary...
The mechanism(s) by which lymphokine-activated peritoneal macrophages kill Blastomyces dermatitidis was studied. Resident peritoneal macrophages from BALB/cByJ mice, when treated overnight with lymph...
Morrison, C J, Brummer, E, Stevens, D A
The effect of in vivo administration of murine recombinant gamma interferon (IFN) on the fungicidal activity of murine peripheral blood polymorphonuclear neutrophils (PB-PMNs) was studied. Mice were...
Progesterone binding and inhibition of growth in Trichophyton mentagrophytes.
Schär, G, Stover, E P, Clemons, K V, Feldman, D, Stevens, D A
Specific binding of [3H]progesterone to cytosol of Trichophyton mentagrophytes was demonstrated. Scatchard analysis of [3H]progesterone binding showed a single class of binding sites with a...
Estradiol-binding proteins from mycelial and yeast-form cultures of Paracoccidioides brasiliensis.
Stover, E P, Schär, G, Clemons, K V, Stevens, D A, Feldman, D
Paracoccidioides brasiliensis, the etiologic agent of paracoccidioidomycosis, causes disease much more frequently in men than it does in women, suggesting that the hormonal milieu of the host might...
Brummer, E, Morrison, C J, Stevens, D A
Recombinant murine gamma-interferon (IFN) and supernatants from concanavalin A (ConA)-stimulated spleen cells were tested for their ability to activate resident peritoneal macrophages (M phi) for...
Restrepo, A, Salazar, M E, Cano, L E, Stover, E P, Feldman, D, Stevens, D A
Evidence that disease due to the thermally dimorphic fungus Paracoccidioides brasiliensis occurs post-puberty predominantly in males led us to hypothesize that hormonal factors critically affect its...
Brummer, E, Sugar, A M, Stevens, D A
Polymorphonuclear neutrophils (PMN) induced locally in immune mice by intraperitoneal injection of antigen exhibit enhanced fungicidal activity compared with PMN elicited with thioglycolate. The...
An in vitro model of in vivo immunological activation of murine polymorphonuclear neutrophils (PMN) was developed. Culture supernatants of spleen cells from Blastomyces dermatitidis-immunized mice...
Susceptibility of Blastomyces dermatitidis strains to products of oxidative metabolism.
Sugar, A M, Chahal, R S, Brummer, E, Stevens, D A
Three strains of Blastomyces dermatitidis which differ in their virulence for mice were exposed in their yeast form to various components of the peroxidase-hydrogen peroxide-halide system....
Application of DNA typing methods to epidemiology and taxonomy of Candida species.
Methods are described for extraction of DNA from the yeast form of Candida spp., followed by digestion and electrophoresis of DNA fragments. The resulting gel patterns (greater than 100 bands) were...
Clemons, K V, Schär, G, Stover, E P, Feldman, D, Stevens, D A
We reported previously that Trichophyton mentagrophytes contains a cytoplasmic macromolecule which specifically binds progesterone. Progesterone is also an effective inhibitor of growth of the...
Denning, D W, Stevens, D A, Hamilton, J R
Growth of Cryptococcus neoformans from the sputum of patients with acquired immunodeficiency syndrome may be obscured by oral contamination with Candida albicans on conventional media. We...
Epidemiologic study by DNA typing of a Candida albicans outbreak in heroin addicts.
Clemons, K V, Shankland, G S, Richardson, M D, Stevens, D A
The epidemiology of an outbreak of Candida endophthalmitis in heroin addicts was studied by DNA typing. Although one biotype was prevalent, the 13 isolates of Candida albicans from seven of the...
Hamilton, J R, Noble, A, Denning, D W, Stevens, D A
Cryptococcal antigen titers in 97 serum and 42 cerebrospinal fluid (CSF) specimens from 37 AIDS patients with culture-proven cryptococcal infection were determined with the Meridian kit (Meridian...
Analysis of Candida albicans phenotypes from different geographical and anatomical sources.
Odds, F C, Abbott, A B, Stiller, R L, Scholer, H J, Polak, A, Stevens, D A
Strain phenotypes of 330 Candida albicans isolates from five areas in the United States were determined on the basis of nine biochemical tests. Statistical analysis of the distribution of phenotypes...
Restrepo, A, Cano, L E, De Bedout, C, Brummer, E, Stevens, D A
The viability of Paracoccidioides brasiliensis yeast-form cells was determined by colony-forming units, direct fluorescent staining, and production of germ tubes in slide culture. The first procedure...
Nikoskelainen, J, Neel, E U, Stevens, D A
Immunoglobulin A (IgA) antibodies to Epstein-Barr virus viral capsid antigen were assayed serially in 19 patients with infectious mononucleosis and in 38 controls. Seventy-four percent of infectious...
Complement fixation antibody test for human nocardiosis.
Shainhouse, J Z, Pier, A C, Stevens, D A
Complement-fixing antibody was detected in 13 of 16 patients with histological and/or culture evidence of infection with Nocardia species. The antigen used was a filtrate of soluble substances...
A Candida albicans dispersed, repeated gene family and its epidemiologic applications.
Candida albicans causes a wide variety of infections but can readily be isolated from the skin and mucosa of healthy individuals. To enable high-resolution epidemiologic studies on this common...
Synergy of itraconazole with macrophages in killing Blastomyces dermatitidis.
Brummer, E, Bhagavathula, P R, Hanson, L H, Stevens, D A
We examined in vitro interaction between the azole antifungal agents itraconazole and ketoconazole and macrophages and their activities against Blastomyces dermatitidis. Fungistatic and fungicidal...
Clemons, K V, Brummer, E, Stevens, D A
Cell-mediated immune responses appear to be critical in the outcome of cryptococcosis. Interleukin-12 (IL-12) was studied for its potential use as a therapeutic agent because of its stimulation of...
Brummer, E, Nassar, F, Stevens, D A
The anticryptococcal activity of murine bronchoalveolar macrophages (BAM) and their synergy with fluconazole (FCZ) was studied. BAM cultured with tissue culture medium for 48 to 72 h were fungicidal...
Nassar, F, Brummer, E, Stevens, D A
Macrophage colony-stimulating factor (M-CSF) given subcutaneously at a dose of 2.5 mg/kg of body weight (4.75 x 10(6) U/kg) to CD-1 male mice 8 to 12 weeks old was found to enhance significantly the...
McCusker, J H, Clemons, K V, Stevens, D A, Davis, R W
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. Clemons, J.H. McCusker, R. W. Davis,...
Brummer, E, Hanson, L H, Restrepo, A, Stevens, D A
The effect of coculturing yeast-form Paracoccidioides brasiliensis with murine cells was studied. Coculture of resident peritoneal or pulmonary macrophages with P. brasiliensis for 72 h dramatically...
Specificity of immunoglobulin E in coccidioidomycosis and correlation with disease involvement.
Cox, R A, Baker, B S, Stevens, D A
Serum immunoglobulin E (IgE) antibodies were quantitated in 26 patients with active pulmonary coccidioidomycosis, 59 patients with active disseminated disease, 12 patients in clinical remission, and...
Morozumi, P A, Brummer, E, Stevens, D A
A model of pulmonary blastomycosis in the mouse, in which the portal of entry is the same as natural human infection, was used to study resistance to challenge after subcutaneous infection. One week...
Brummer, E, Sugar, A M, Stevens, D A
With a new short-term assay, where the reduction of CFUs in the inoculum could be measured, we investigated the killing of the dimorphic fungal pathogen Blastomyces dermatitidis in its yeast phase by...
Susceptibility differences of inbred strains of mice to blastomycosis.
Morozumi, P A, Halpern, J W, Stevens, D A
The susceptibility of inbred strains of mice to pulmonary blastomycosis was studied to derive information relevant to host resistance and genetic background. Initial studies with eight strains with...
Morozumi, P A, Brummer, E, Stevens, D A
The inbred mouse strains C3H/HeJ and DBA/1J have been shown to represent the extremes of susceptibility and resistance, respectively, to pulmonary blastomycosis. This pattern was completely reversed...
Brass, C, Levine, H B, Stevens, D A
The culture filtrate of Coccidioides immitis induced to replicate in its parasitic phase in vitro, termed endosporulation antigens (EA), was assayed for ability to stimulate human lymphocyte...
The purpose of this study was to determine the effects of human monocytes, macrophages, and polymorphonuclear neutrophils (PMN) on the fungal pathogen Blastomyces dermatitidis in vitro. Peripheral...
Marked resistance of 9-week-old mice as compared to that of 5-week-old mice was demonstrated after pulmonary challenge with three strains of Blastomyces dermatitidis of various virulences....
Brummer, E, Morozumi, P A, Philpott, D E, Stevens, D A
Strains of Blastomyces dermatitidis which are virulent (V), attenuated (A), or avirulent (AV) in mice have been identified. Virulence of V has been reported to be associated with its ability to...
Galgiani, J N, Isenberg, R A, Stevens, D A
In order to further characterize human host defenses against Coccidioides immitis, extracts of this fungus were tested in vitro for their ability to attract polymorphonuclear leukocytes derived from...
Loose, D S, Stover, E P, Restrepo, A, Stevens, D A, Feldman, D
Paracoccidioidomycosis, a disease caused by Paracoccidioides brasiliensis, which is endemic to Latin America, is much more common in men than women, suggesting a role for hormonal factors. We...
Complement activation by Coccidioides immitis: in vitro and clinical studies.
Galgiani, J N, Yam, P, Petz, L D, Williams, P L, Stevens, D A
Mycelial- or spherule-phase derivatives of Coccidioides immitis caused a decrease in vitro of total hemolytic complement in serum from a nonsensitized person. Activation involved both classic and...
Genetic Characterization of Pathogenic Saccharomyces Cerevisiae Isolates
McCusker, J. H., Clemons, K. V., Stevens, D. A., Davis, R. W.
Saccharomyces cerevisiae isolates from human patients have been genetically analyzed. Some of the characteristics of these isolates are very different from laboratory and industrial strains of S....
Efficacy of Ravuconazole in Treatment of Systemic Murine Histoplasmosis
Clemons, K. V., Martinez, M., Calderon, L., Stevens, D. A.
Ravuconazole (RCZ) was evaluated for efficacy in comparison to fluconazole (FCZ) and itraconazole (ITZ) in murine models of disseminated histoplasmosis. All regimens tested prolonged survival (P <...
Efficacy of the triazole D0870 in a murine model of systemic histoplasmosis.
The efficacy of D0870 was studied in a murine model of systemic histoplasmosis and was compared with that of fluconazole. All regimens of D0870 (1 or 10 mg/kg of body weight given daily or 1, 10, or...
Activities of the triazole SCH 51048 against Coccidioides immitis in vitro and in vivo.
Clemons, K V, Homola, M E, Stevens, D A
The activity of the novel triazole SCH 51048 was tested against Coccidioides immitis. SCH 51048 inhibited C. immitis in vitro; MICs for 13 isolates ranged from < or = 0.39 to 0.78 micrograms/ml, and...
Nassar, F, Brummer, E, Stevens, D A
The inhibitory effect of human serum on the multiplication of Cryptococcus neoformans and the interaction with fluconazole were studied. Compared with cryptococcal multiplication in RPMI 1640 medium...
UR-9746 and UR-9751 are novel azole derivatives each containing a morpholine ring. They were examined for both in vitro and in vivo activities against Coccidioides immitis. In vitro, UR-9746 and...
Itraconazole resistance in Aspergillus fumigatus.
Denning, D W, Venkateswarlu, K, Oakley, K L, Anderson, M J, Manning, N J, Stevens, D A, ...
Invasive aspergillosis is an increasingly frequent opportunistic infection in immunocompromised patients. Only two agents, amphotericin B and itraconazole, are licensed for therapy. Itraconazole acts...
Activity of the triazole SCH 56592 against disseminated murine coccidioidomycosis.
Lutz, J E, Clemons, K V, Aristizabal, B H, Stevens, D A
SCH 56592 (SCH) is a new triazole antifungal with a broad spectrum of activity. In vitro susceptibility testing against five strains of Coccidioides immitis revealed MICs from 0.39 to 3.13 microg/ml...
Natarajan, U, Brummer, E, Stevens, D A
The effect of granulocyte colony-stimulating factor (GCSF) treatment of polymorphonuclear neutrophils (PMN) in vitro was studied with respect to their candidacidal activity. The candidacidal activity...
Efficacy of nikkomycin Z against experimental pulmonary blastomycosis.
Nikkomycin Z is a chitin synthetase inhibitor. In vitro, nikkomycin Z had good activity against Blastomyces dermatitidis, with an MIC of 0.78 microg/ml and a minimal fungicidal concentration of 3.1...
Comparative effects of cilofungin and amphotericin B on experimental murine candidiasis.
The effectiveness of cilofungin (LY121019, referred to hereafter as LY), a lipopeptide, was studied in a murine candidiasis model. CD-1 mice (5 weeks old) were injected intravenously with 3 x 10(5)...
Efficacy of SCH39304 and fluconazole in a murine model of disseminated coccidioidomycosis.
Clemons, K V, Hanson, L H, Perlman, A M, Stevens, D A
The efficacies of SCH39304 (SCH) and fluconazole (FLU) were tested in a murine model of coccidioidomycosis. CD-1 mice were infected with Coccidioides immitis and dosed with SCH at 2, 10, 25, or 50...
Arathoon, E G, Hamilton, J R, Hench, C E, Stevens, D A
Methicillin-resistant Staphylococcus aureus (MRSA) is an important nosocomial infection problem. Colonization appears to be more common than invasive disease is. Eradication of colonization or the...
Pharmacokinetics of fluconazole in cerebrospinal fluid and serum in human coccidioidal meningitis.
Tucker, R M, Williams, P L, Arathoon, E G, Levine, B E, Hartstein, A I, Hanson, L H, ...
The pharmacokinetics of fluconazole, a new oral azole, were evaluated in cerebrospinal fluid and sera of eight patients with coccidioidal meningitis. At a dose of 50 mg/day, peak concentrations of...
Tucker, R M, Hanson, L H, Brummer, E, Stevens, D A
ICI 195,739, a novel orally active triazole, proved 50 times as potent as ketoconazole, produced a clinical cure, and completely eradicated residual infection in a murine model of pulmonary...
Cilofungin (LY121019) is a new lipopeptide antifungal drug. We tested this drug against 141 pathogenic fungal isolates. All fungal species were tested by broth dilution at 35 degrees C. Malassezia...
Pathogenicity of Saccharomyces cerevisiae in complement factor five-deficient mice.
Byron, J K, Clemons, K V, McCusker, J H, Davis, R W, Stevens, D A
We have previously determined the relative virulence of isolates of Saccharomyces cerevisiae on the basis of differences in proliferation and resistance to clearance in CD-1 mice. These infections...
Pharmacology and toxicity of high-dose ketoconazole.
Sugar, A M, Alsip, S G, Galgiani, J N, Graybill, J R, Dismukes, W E, Cloud, G A, ...
One hundred sixty patients were entered in two multicenter protocols to receive 400 to 2,000 mg of ketoconazole once daily for nonmeningeal or meningeal coccidiodomycosis. For 24 h after...
Lefler, E, Brummer, E, Perlman, A M, Stevens, D A
We studied the efficacy of new experimental antifungal drugs, which represent molecular modifications of present active agents, in a murine model of blastomycosis. Ketoconazole, previously the best...
Disposition of ketoconazole, an oral antifungal, in humans.
Brass, C, Galgiani, J N, Blaschke, T F, Defelice, R, O'Reilly, R A, Stevens, D A
The pharmacology of ketoconazole was studied in patients with fungal infections. After administration of 50-, 100-, and 200-mg doses of ketoconazole, there was a linear increase in the area under the...
Synergistic interaction of trimethoprim and sulfamethoxazole on Paracoccidioides brasiliensis.
The in vitro interaction of trimethoprim and sulfamethoxazole on clinical isolates of Paracoccidioides brasiliensis was studied. With complete inhibition and a visual endpoint used as the criteria,...
Stiller, R L, Bennett, J E, Scholer, H J, Wall, M, Polak, A, Stevens, D A
Candida albicans isolates from 402 patients with no prior history of treatment with 5-fluorocytosine were collected at five medical centers from different areas of the United States. Isolates could...
Inhibition and killing of Candida albicans in vitro by five imidazoles in clinical use.
Five imidazoles (clotrimazole, econazole, ketoconazole, miconazole, and tioconazole) in clinical use were compared for their ability to inhibit and kill Candida albicans. Eleven isolates were...
Grosso, D S, Boyden, T W, Pamenter, R W, Johnson, D G, Stevens, D A, Galgiani, J N
In vivo perfusion of canine testes with ketoconazole inhibited the stimulation of testosterone production by human chorionic gonadotropin in a dose-dependent manner. Ketoconazole also selectively...
Cano, L E, Gomez, B, Brummer, E, Restrepo, A, Stevens, D A
Conidia of P. brasiliensis ingested by murine macrophages at 37 degrees C showed enhanced transformation to yeast cells and further intracellular growth compared with conidia in culture medium alone....
Activities of the triazole D0870 in vitro and against murine blastomycosis.
Clemons, K V, Hanson, L H, Stevens, D A
The novel triazole D0870 was tested for in vitro activity, as well as in vivo in a murine model of pulmonary blastomycosis. In vitro, D0870 had inhibitory and fungicidal activity against Blastomyces...
Effect of cyclodextrin on the pharmacology of antifungal oral azoles.
Hostetler, J S, Hanson, L H, Stevens, D A
Concentrations of oral azoles in serum were compared in a single-dose pharmacologic study in mice. When hydroxypropyl-beta-cyclodextrin was used as a carrier and compared with a standard carrier,...
Complexing amphotericin B (AmB) with lipids or entrapping it in liposomes may increase its efficacy by reducing toxicity and affecting distribution. However, depending on the lipids involved,...
Hostetler, J S, Heykants, J, Clemons, K V, Woestenborghs, R, Hanson, L H, Stevens, D A
Pharmacologic studies of itraconazole (IZ), a triazole antifungal, indicated unexplained differences between bioassay and chromatographic determinations and large variations in steady-state blood...
Deresinski, S C, Clemons, K V, Kemper, C A, Roesch, K, Walton, B, Stevens, D A
A cluster of isolates of Candida parapsilosis recovered from clinical specimens was demonstrated, by both classical and molecular epidemiological techniques, to have resulted from contamination in...
D-mannitol in cerebrospinal fluid of patients with AIDS and cryptococcal meningitis.
Megson, G M, Stevens, D A, Hamilton, J R, Denning, D W
Cryptococcal meningitis (CM) is associated with raised intracranial pressure which is linked with serious neurological sequelae. Cryptococcus neoformans produces D-mannitol in vitro and in...
Clemons, K V, Feroze, F, Holmberg, K, Stevens, D A
The objective of the present study was to conduct a comparative genotypic analysis of Candida albicans isolates from the United States, Europe, and Southeast Asia to determine whether differences...
Clemons, K V, Park, P, McCusker, J H, McCullough, M J, Davis, R W, Stevens, D A
We have previously described differences in phenotype and virulence among clinical and nonclinical isolates of Saccharomyces. To further characterize these isolates, a comparison of restriction...
SCH 39304 in the treatment of acute or established murine pulmonary blastomycosis.
Brummer, E, Hanson, L H, Stevens, D A
SCH 39304 was tested for treatment of acute or established murine pulmonary blastomycosis and was compared with ketoconazole and fluconazole in a model of acute infection. Only SCH 39304 at 25 or 50...
Rex, J H, Hanson, L H, Amantea, M A, Stevens, D A, Bennett, J E
An improved bioassay for fluconazole was developed. This assay is sensitive in the clinically relevant range (2 to 40 micrograms/ml) and analyzes plasma, serum, and cerebrospinal fluid specimens;...
Cilofungin, amphotericin B, and a combination of the two drugs were compared in a model of aspergillosis in immunocompetent mice in three experiments. Cilofungin was equivalent to amphotericin B in...
Synergy between cilofungin and amphotericin B in a murine model of candidiasis.
Hanson, L H, Perlman, A M, Clemons, K V, Stevens, D A
The efficacies of cilofungin and amphotericin B separately and together in mice with disseminated candidiasis were studied. Male CD-1 mice (age, 5 weeks) were infected intravenously with 3 X 10(5)...
The efficacy of a novel sterol-complexed preparation of amphotericin B, amphotericin B colloidal dispersion, was compared with that of deoxycholate-complexed amphotericin B in an acute murine model...
Amphotericin B as a lipid complex and as a deoxycholate suspension (Fungizone) was tested against murine blastomycosis. All doses of each form prolonged survival (P less than 0.05 to 0.001)....
Hostetler, J S, Clemons, K V, Hanson, L H, Stevens, D A
The efficacy and safety of amphotericin B colloidal dispersion (ABCD) were compared with those of amphotericin B deoxycholate suspension (ABDS) (Fungizone) in a murine model of disseminated...
Cano, L E, Brummer, E, Stevens, D A, Restrepo, A
Conidia ingested by resident macrophages had an enhanced percentage of transformation to yeast cells compared with those in culture medium without macrophages. The yeast cells subsequently grew...
Seven Blastomyces dermatitidis isolates varying in virulence for mice were compared for susceptibility to polymorphonuclear neutrophil (PMN) killing and the ability to induce superoxide anion (O2-)...
Brummer, E, Sun, S H, Harrison, J L, Perlman, A M, Philpott, D E, Stevens, D A
Transmission electron microscopy was used to study ultrastructures in Paracoccidioides brasiliensis yeast cells after ingestion by nonactivated or cytokine-activated murine peritoneal macrophages....
Inhibition by estrogens of conidium-to-yeast conversion in the fungus Paracoccidioides brasiliensis.
Salazar, M E, Restrepo, A, Stevens, D A
Conidia produced by Paracoccidioides brasiliensis are inhibited by mammalian estrogens in their in vitro conversion into yeast-form cells. This was demonstrated with four different isolates. In these...
Castaneda, E, Brummer, E, Pappagianis, D, Stevens, D A
Humoral and cellular immune responses were measured during the progression of chronic pulmonary and disseminated paracoccidioidomycosis in mice. The chronic disease was established by pulmonary...
The mechanism(s) by which lymphokine-activated peritoneal macrophages kill Blastomyces dermatitidis was studied. Resident peritoneal macrophages from BALB/cByJ mice, when treated overnight with lymph...
Morrison, C J, Brummer, E, Stevens, D A
The effect of in vivo administration of murine recombinant gamma interferon (IFN) on the fungicidal activity of murine peripheral blood polymorphonuclear neutrophils (PB-PMNs) was studied. Mice were...
Progesterone binding and inhibition of growth in Trichophyton mentagrophytes.
Schär, G, Stover, E P, Clemons, K V, Feldman, D, Stevens, D A
Specific binding of [3H]progesterone to cytosol of Trichophyton mentagrophytes was demonstrated. Scatchard analysis of [3H]progesterone binding showed a single class of binding sites with a...
Estradiol-binding proteins from mycelial and yeast-form cultures of Paracoccidioides brasiliensis.
Stover, E P, Schär, G, Clemons, K V, Stevens, D A, Feldman, D
Paracoccidioides brasiliensis, the etiologic agent of paracoccidioidomycosis, causes disease much more frequently in men than it does in women, suggesting that the hormonal milieu of the host might...
Brummer, E, Morrison, C J, Stevens, D A
Recombinant murine gamma-interferon (IFN) and supernatants from concanavalin A (ConA)-stimulated spleen cells were tested for their ability to activate resident peritoneal macrophages (M phi) for...
Restrepo, A, Salazar, M E, Cano, L E, Stover, E P, Feldman, D, Stevens, D A
Evidence that disease due to the thermally dimorphic fungus Paracoccidioides brasiliensis occurs post-puberty predominantly in males led us to hypothesize that hormonal factors critically affect its...
Brummer, E, Sugar, A M, Stevens, D A
Polymorphonuclear neutrophils (PMN) induced locally in immune mice by intraperitoneal injection of antigen exhibit enhanced fungicidal activity compared with PMN elicited with thioglycolate. The...
An in vitro model of in vivo immunological activation of murine polymorphonuclear neutrophils (PMN) was developed. Culture supernatants of spleen cells from Blastomyces dermatitidis-immunized mice...
Susceptibility of Blastomyces dermatitidis strains to products of oxidative metabolism.
Sugar, A M, Chahal, R S, Brummer, E, Stevens, D A
Three strains of Blastomyces dermatitidis which differ in their virulence for mice were exposed in their yeast form to various components of the peroxidase-hydrogen peroxide-halide system....
Application of DNA typing methods to epidemiology and taxonomy of Candida species.
Methods are described for extraction of DNA from the yeast form of Candida spp., followed by digestion and electrophoresis of DNA fragments. The resulting gel patterns (greater than 100 bands) were...
Clemons, K V, Schär, G, Stover, E P, Feldman, D, Stevens, D A
We reported previously that Trichophyton mentagrophytes contains a cytoplasmic macromolecule which specifically binds progesterone. Progesterone is also an effective inhibitor of growth of the...
Denning, D W, Stevens, D A, Hamilton, J R
Growth of Cryptococcus neoformans from the sputum of patients with acquired immunodeficiency syndrome may be obscured by oral contamination with Candida albicans on conventional media. We...
Epidemiologic study by DNA typing of a Candida albicans outbreak in heroin addicts.
Clemons, K V, Shankland, G S, Richardson, M D, Stevens, D A
The epidemiology of an outbreak of Candida endophthalmitis in heroin addicts was studied by DNA typing. Although one biotype was prevalent, the 13 isolates of Candida albicans from seven of the...
Hamilton, J R, Noble, A, Denning, D W, Stevens, D A
Cryptococcal antigen titers in 97 serum and 42 cerebrospinal fluid (CSF) specimens from 37 AIDS patients with culture-proven cryptococcal infection were determined with the Meridian kit (Meridian...
Analysis of Candida albicans phenotypes from different geographical and anatomical sources.
Odds, F C, Abbott, A B, Stiller, R L, Scholer, H J, Polak, A, Stevens, D A
Strain phenotypes of 330 Candida albicans isolates from five areas in the United States were determined on the basis of nine biochemical tests. Statistical analysis of the distribution of phenotypes...
Restrepo, A, Cano, L E, De Bedout, C, Brummer, E, Stevens, D A
The viability of Paracoccidioides brasiliensis yeast-form cells was determined by colony-forming units, direct fluorescent staining, and production of germ tubes in slide culture. The first procedure...
Nikoskelainen, J, Neel, E U, Stevens, D A
Immunoglobulin A (IgA) antibodies to Epstein-Barr virus viral capsid antigen were assayed serially in 19 patients with infectious mononucleosis and in 38 controls. Seventy-four percent of infectious...
Complement fixation antibody test for human nocardiosis.
Shainhouse, J Z, Pier, A C, Stevens, D A
Complement-fixing antibody was detected in 13 of 16 patients with histological and/or culture evidence of infection with Nocardia species. The antigen used was a filtrate of soluble substances...
A Candida albicans dispersed, repeated gene family and its epidemiologic applications.
Candida albicans causes a wide variety of infections but can readily be isolated from the skin and mucosa of healthy individuals. To enable high-resolution epidemiologic studies on this common...
Synergy of itraconazole with macrophages in killing Blastomyces dermatitidis.
Brummer, E, Bhagavathula, P R, Hanson, L H, Stevens, D A
We examined in vitro interaction between the azole antifungal agents itraconazole and ketoconazole and macrophages and their activities against Blastomyces dermatitidis. Fungistatic and fungicidal...
Clemons, K V, Brummer, E, Stevens, D A
Cell-mediated immune responses appear to be critical in the outcome of cryptococcosis. Interleukin-12 (IL-12) was studied for its potential use as a therapeutic agent because of its stimulation of...
Brummer, E, Nassar, F, Stevens, D A
The anticryptococcal activity of murine bronchoalveolar macrophages (BAM) and their synergy with fluconazole (FCZ) was studied. BAM cultured with tissue culture medium for 48 to 72 h were fungicidal...
Nassar, F, Brummer, E, Stevens, D A
Macrophage colony-stimulating factor (M-CSF) given subcutaneously at a dose of 2.5 mg/kg of body weight (4.75 x 10(6) U/kg) to CD-1 male mice 8 to 12 weeks old was found to enhance significantly the...
McCusker, J H, Clemons, K V, Stevens, D A, Davis, R W
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. Clemons, J.H. McCusker, R. W. Davis,...
Brummer, E, Hanson, L H, Restrepo, A, Stevens, D A
The effect of coculturing yeast-form Paracoccidioides brasiliensis with murine cells was studied. Coculture of resident peritoneal or pulmonary macrophages with P. brasiliensis for 72 h dramatically...
Specificity of immunoglobulin E in coccidioidomycosis and correlation with disease involvement.
Cox, R A, Baker, B S, Stevens, D A
Serum immunoglobulin E (IgE) antibodies were quantitated in 26 patients with active pulmonary coccidioidomycosis, 59 patients with active disseminated disease, 12 patients in clinical remission, and...
Morozumi, P A, Brummer, E, Stevens, D A
A model of pulmonary blastomycosis in the mouse, in which the portal of entry is the same as natural human infection, was used to study resistance to challenge after subcutaneous infection. One week...
Brummer, E, Sugar, A M, Stevens, D A
With a new short-term assay, where the reduction of CFUs in the inoculum could be measured, we investigated the killing of the dimorphic fungal pathogen Blastomyces dermatitidis in its yeast phase by...
Susceptibility differences of inbred strains of mice to blastomycosis.
Morozumi, P A, Halpern, J W, Stevens, D A
The susceptibility of inbred strains of mice to pulmonary blastomycosis was studied to derive information relevant to host resistance and genetic background. Initial studies with eight strains with...
Morozumi, P A, Brummer, E, Stevens, D A
The inbred mouse strains C3H/HeJ and DBA/1J have been shown to represent the extremes of susceptibility and resistance, respectively, to pulmonary blastomycosis. This pattern was completely reversed...
Brass, C, Levine, H B, Stevens, D A
The culture filtrate of Coccidioides immitis induced to replicate in its parasitic phase in vitro, termed endosporulation antigens (EA), was assayed for ability to stimulate human lymphocyte...
The purpose of this study was to determine the effects of human monocytes, macrophages, and polymorphonuclear neutrophils (PMN) on the fungal pathogen Blastomyces dermatitidis in vitro. Peripheral...
Marked resistance of 9-week-old mice as compared to that of 5-week-old mice was demonstrated after pulmonary challenge with three strains of Blastomyces dermatitidis of various virulences....
Brummer, E, Morozumi, P A, Philpott, D E, Stevens, D A
Strains of Blastomyces dermatitidis which are virulent (V), attenuated (A), or avirulent (AV) in mice have been identified. Virulence of V has been reported to be associated with its ability to...
Galgiani, J N, Isenberg, R A, Stevens, D A
In order to further characterize human host defenses against Coccidioides immitis, extracts of this fungus were tested in vitro for their ability to attract polymorphonuclear leukocytes derived from...
Loose, D S, Stover, E P, Restrepo, A, Stevens, D A, Feldman, D
Paracoccidioidomycosis, a disease caused by Paracoccidioides brasiliensis, which is endemic to Latin America, is much more common in men than women, suggesting a role for hormonal factors. We...
Complement activation by Coccidioides immitis: in vitro and clinical studies.
Galgiani, J N, Yam, P, Petz, L D, Williams, P L, Stevens, D A
Mycelial- or spherule-phase derivatives of Coccidioides immitis caused a decrease in vitro of total hemolytic complement in serum from a nonsensitized person. Activation involved both classic and...
Genetic Characterization of Pathogenic Saccharomyces Cerevisiae Isolates
McCusker, J. H., Clemons, K. V., Stevens, D. A., Davis, R. W.
Saccharomyces cerevisiae isolates from human patients have been genetically analyzed. Some of the characteristics of these isolates are very different from laboratory and industrial strains of S....
Hostetler, J S, Brummer, E, Coffman, R L, Stevens, D A
Paracoccidioidomycosis is characterized by depressed cellular but enhanced humoral immune responses, which suggests a Th2 type of response to infection. We investigated possible therapeutic roles for...
The purpose of this study was to determine the effect of murine polymorphonuclear neutrophils (PMN) on the multiplication of the fungal pathogen Blastomyces dermatitidis in vitro and in vivo. With a...
Randomized trial of transfer factor treatment of human warts.
Stevens, D A, Ferrington, R A, Merigan, T C, Marinkovich, V A
Dialysed transfer factor, prepared from the leucocytes of a donor whose warts had undergone recent spontaneous regression, was used in the treatment of a child with the Wiskott--Aldrich syndrome. The...
Activation of pulmonary macrophages for fungicidal activity by gamma-interferon or lymphokines.
The ability of murine recombinant gamma interferon (IFN) or lymphokines to enhance the fungicidal activity of murine pulmonary macrophages (PuM) was studied in in vitro. PuM monolayers were incubated...
Brummer, E, McEwen, J G, Stevens, D A
A characteristic of inflammation is the influx of polymorphonuclear neutrophils (PMN) from peripheral blood to the inflammatory reaction. We report on metabolic alterations and alterations in...
The first line of defence against natural infection by Histoplasma capsulatum (Hc) consists of bronchoalveolar macrophages (BAM) and an early inflammatory response in the lungs. Little is known about...
Zucker, K E, Kamberi, P, Sobel, R A, Cloud, G, Meli, D N, Clemons, K V, ...
Strokes due to transmural vasculitis associated with coccidioidal meningitis result in significant morbidity and mortality. The immunological and inflammatory processes responsible are poorly...
Clemons, K V, Grunig, G, Sobel, R A, Mirels, L F, Rennick, D M, Stevens, D A
IL-10 is associated with a Th2 response, down-regulation of a Th1 response and macrophage activation. We assessed the role of IL-10 during systemic infection with Aspergillus fumigatus. Systemic...
Khatami, S, Brummer, E, Stevens, D A
GM-CSF is a potent stimulator of haematopoietic cells as well as some functions of granulocytes and macrophages. GM-CSF has many clinical uses; however, little is known about the effects of GM-CSF...
Ketoconazole, an oral antifungal: laboratory and clinical assessment of imidazole drugs.
Borelli, D., Bran, J. L., Fuentes, J., Legendre, R., Leiderman, E., Levine, H. B., ...
Miconazole, a parenterally administered imidazole antifungal agent has been shown to produce responses in systemic fungal infections in man. Ketoconazole, an analogue, can be given by mouth. It is...