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D A Stevens

Publications and source records attributed to D A Stevens.

At least 127 records · Page 7Linked to original sources
PubMed1997

Effect of granulocyte colony-stimulating factor on the candidacidal activity of polymorphonuclear neutrophils and their collaboration with fluconazole.

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 of PMN was found to be significantly increased when they were pretreated with GCSF. Fluconazole (1 microg/ml) was found to be highly fungistatic (90%) for Candida albicans Sh27 and collaborated with PMN for significantly increased killing. Collaborative killing by PMN significantly increased when they were treated with GCSF before and after fungal exposure. The enhancing activities of GCSF required optimization of the GCSF dose and were thus inoculum and strain dependent.

Antifungal Agents↗
PubMed1997

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 microg/ml. The efficacies of various treatment durations (3, 5, or 10 days) and doses (200, 400, or 1,000 mg/kg of body weight) of nikkomycin Z given twice daily were compared with those of itraconazole at 200 mg/kg given twice daily and amphotericin B at 6.25 mg/kg in a murine model of pulmonary blastomycosis. All treatments prolonged survival compared with untreated controls (P < 0.05 to 0.01); 100% survival was achieved with 5 or 10 days of any nikkomycin Z dose or with amphotericin B. Amphotericin B and nikkomycin Z, but not itraconazole, reduced infection compared with controls. Amphotericin B and the 10-day regimens of all nikkomycin Z doses were equivalent and superior to itraconazole or nikkomycin Z for < or = 5 days at any dose (P < 0.05 to 0.01). Increased duration and/or dosage improved the efficacy of nikkomycin Z, with 10 days of each dose curing 50 to 90% of the animals. Only a 1,000-mg/kg/day dose of nikkomycin Z was curative when treatment lasted less than 10 days. In contrast, itraconazole cured no mice, while amphotericin B cured all mice. Based on the total amount of drug given, amphotericin B was estimated to be 32 times as active as nikkomycin Z and nikkomycin Z was estimated to be 3 times as active as itraconazole. Overall, nikkomycin Z given orally was well tolerated, had good activity against blastomycosis, and could result in biological cure, thus producing results equivalent to those of parenteral amphotericin B.

Aminoglycosides↗
PubMed1997

Comparative analysis of genetic variability among Candida albicans isolates from different geographic locales by three genotypic methods.

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 between isolates might be associated with geographic locations. The genotypes of 86 unrelated isolates of C. albicans (from the United States and Europe) and 26 isolates from Singapore were examined by three DNA typing methods. Computer-assisted methods were used to analyze the gel patterns for all isolates. A dendrogram based on the overall similarity of the patterns obtained by restriction endonuclease analysis (REA) with EcoRI clustered the U.S. and European isolates into two major groups (groups A and B). The Singaporean isolates demonstrated unique REA profiles, with nine isolates having both or neither of the REA-characteristic 3.7- and 4.2-kb bands present in groups A and B. By REA profiles, the Singaporean isolates were related to each other with similarity values (S(AB)s) of > 0.80, but only one isolate mixed with the U.S. and European isolates at this S(AB) (an arbitrary threshold for genetic similarity). Randomly amplified polymorphic DNA (RAPD) analysis generated DNA profiles that clustered the C. albicans isolates into approximately the same number of distinct typing groups as REA. However, isolates identical to each other by REA were generally different from each other by RAPD analysis. In a composite dendrogram prepared from the results obtained by RAPD analysis, the isolates from the United States and Europe clustered in major groups with S(AB)s of > 0.85, while Singaporean isolates connected to these clusters at S(AB)s of > or = 0.75. Pulsed-field gel electrophoresis was less discriminatory, discerning about one-third as many distinct subtypes as REA or RAPD analysis; the Singaporean isolates were distributed randomly with the U.S. and European isolates. These results suggest that a high degree of genetic diversity exists between C. albicans isolates from Southeast Asia and those from the United States and Europe.

Candida albicans↗
PubMed1997

Application of DNA typing methods and genetic analysis to epidemiology and taxonomy of Saccharomyces isolates.

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 fragment length polymorphism (RFLP) patterns and genetic analysis were done. The cellular DNA of each of 49 clinical and 11 nonclinical isolates of Saccharomyces was digested with the endonuclease EcoRI, and the resultant fragments were separated by electrophoresis. Sixty isolates were grouped on the basis of the presence (group B) or absence (group A) of a 3-kb band. Group A contained 43 isolates (35 clinical and 8 nonclinical isolates) in 31 discernible subgroups, and group B had 17 isolates (14 clinical and 3 nonclinical isolates) in 10 subgroups. Interestingly, six of eight known vaginal isolates were group B, with four of those six being identical. Virulence of isolates was associated with membership in group A (P = 0.03). Comparison of known members of sibling species within the genus Saccharomyces, which cannot be distinguished by standard biochemical tests, showed that S. paradoxus, S. bayanus, and S. cerevisiae could be differentiated by RFLP analysis. Genetic analysis of the isolates forming viable spores showed that most group A isolates were diploid and members of the species S. cerevisiae. Those group A and B isolates unable to form viable spores may be diploid hybrids between Saccharomyces species. The group B isolates that formed viable spores were tetraploid and may also be interspecific hybrids. Overall, clinical isolates of Saccharomyces were very heterogeneous and exhibited little clonality. RFLP pattern analysis could be a useful method of demonstrating transmission in patients with infection or between environmental sources and patients.

DNA, Fungal↗
PubMed1997

Virulent isolates and mutants of Blastomyces in mice: a legacy for studies of pathogenesis.

This article provides information on the history of Blastomyces dermatitidis isolates and spontaneous mutants, the relationship with maintenance of cultures, and their virulence as quantified in murine models. Virulent isolates have been obtained from soil or from patients. Regardless of origin, mutants attenuated in virulence have sometimes arisen from storage as frozen yeast, frozen mycelia, or refrigerated yeast or serial passage in vitro at 35 degrees to 37 degrees C. Once virulence is lost, reversion to the virulent phenotype (even after serial passage in animals) has not been seen. These data, methods, and isolates provide a basis for future studies of virulence factors.

Animals↗
PubMed1997

Animal models of blastomycosis.

Mice offer many advantages as a model system for the study of experimental blastomycosis. The murine model has allowed quantitative assessments of disease initiation and progression. These methods of assessment have enabled studies of histopathology, and of the effect of age, host genetic background, fungal isolate virulence, and different routes of challenge on the outcome of infection. The model has been a particularly fertile soil for researching dissection of the immune response to fungal infections and the study of new agents (particularly polyenes and azoles) for the treatment of the mycoses.

Animals↗
PubMed1996

Is it ever safe to stop azole therapy for Coccidioides immitis meningitis?

OBJECTIVE: To determine 1) whether patients with coccidioidal meningitis who had achieved remission with oral azole therapy were cured and 2) when oral azole therapy could be discontinued in these patients. DESIGN: Data were gathered on patients with coccidioidal meningitis who had successfully responded to azole therapy in previous clinical trials. SETTING: Referral centers, including university, county, and veterans' hospitals and clinics. PATIENTS: 18 patients in whom azole therapy for meningitis had been discontinued, usually because of a presumption of cure. MAIN OUTCOME MEASURES: Clinical and cerebrospinal fluid relapse. RESULTS: 14 of 18 patients (78% [95% CI, 52% to 94%]) had relapse with disseminated disease after discontinuation of therapy, for a total of 1 nonmeningeal and 15 meningeal relapses to date. Relapse occurred both soon and late (range, 0.5 to 30 months) after therapy was discontinued. The characteristics of patients who did not have relapse, including the particular azole used, the duration of therapy, the reason therapy was discontinued, and the cerebrospinal fluid indices before discontinuation, were similar to the characteristics of patients who had relapse. Relapse had serious consequences in some patients; 3 patients died. CONCLUSION: Our data suggest 1) that disease is only suppressed in patients with meningitis who achieve remission while receiving azole therapy and 2) that discontinuing azole therapy is unsafe. The alternative is lifelong treatment with azoles; this appears to be acceptable, because toxicity is uncommon with triazole therapy, even long-term triazole therapy.

Administration, Oral↗
PubMed1996

Synergy of human neutrophils with fluconazole in killing Candida species.

The killing of Candida species by human neutrophils in a long-term 24-h assay and possible synergy with fluconazole (FCZ) for killing was investigated. The test medium (TM) consisted of RPMI-1640, penicillin and streptomycin (P/S), and 10% fresh autologous serum. TM alone was highly fungistatic for Candida species compared to TM without serum. When neutrophils were cocultured in TM with Candida species for 24 h the inoculum colony-forming units (CFU) were always significantly reduced (killing) by 58 to 99%. FCZ was tested over a range of 1-500 micrograms/ml, and though almost always fungistatic itself, it synergized with neutrophils for significantly increased killing of C. albicans (isolate Sh27) (P < 0.01) and C. albicans (isolate 94-20) (P < 0.05). Killing of non-albicans Candida species was so efficient in the absence of FCZ that demonstration of synergy with FCZ was difficult.

Antifungal Agents↗
PubMed1996

Study of the role of iron in the anticryptococcal activity of human serum and fluconazole.

Anticryptococcal activity of human serum and apotransferrin in RPMI 1640 was studied in vitro. The effects of varying concentrations of FeCl3 on this activity was investigated. Possible synergy of serum and apotransferrin with fluconazole was also measured. The fungistatic activity of human serum, whether lyophilized, stored at 4 degrees C, fresh frozen or purchased from commercial sources vs. Cryptococcus neoformans was comparable. There was no significant loss of fungistatic activity after freezing and thawing the serum up to 10 times. The fungistatic activity of human serum was similar when tested in different tissue culture media with the exception of Medium 199. The addition of apotransferrin (2.0 or 0.2 mg/ml) to RPMI 1640 had an inhibitory effect on cryptococcal growth. This effect was reversed by 20 microM, of FeCl3 at both apotransferrin concentrations. By contrast, addition of FeCl3 to human serum and RPMI 1640 did not reverse inhibition of growth. Fluconazole synergized with the human serum preparations described, but not with pooled commercial serum, for fungicidal activity. Synergistic activity of fluconazole and human serum was not affected by the addition of FeCl3. Apotransferrin did not show any synergistic fungicidal activity with fluconazole.

Antifungal Agents↗
PubMed1996

Semantic-free scaling of odor quality.

The validity of the odor quality reports given by naive human subjects is often questionable. On the one hand, social conventions can influence the labeling of odorants, especially those that have putrid or uncommon odor qualities, and on the other, semantic differences exist for odor descriptors among individuals. We are interested in the individual differences in the quality reports elicited by two nominally putrid odorants, androstenone (AND) and pemenone (PEM). Here we sought to establish empirical support for the individual differences previously obtained in studies of their odor quality, using a nonverbal, semantic-free method of classification. Undergraduate volunteers sniffed a moderate concentration (390 microM) of PEM, rated its intensity, and provided a verbal odor descriptor. The subjects were then classified as PEM osmic (n = 42) if the quality report was putrid (rancid, urinous, sweaty), allosmic (n = 23), if the quality was nonputrid, and anosmic (n = 39) if no odor was detected. The subjects then sorted 15 odorants matched for intensity, five selected from each of three nominal odor quality types, into as many odor groups as they wished, as long as each group contained all of the compounds with similar odors. The number of times each odorant was paired with another was used as data for an independent multidimensional scaling with ALSCAL, for each class of subject. Three-dimensional solutions showed that this nonverbal, semantic-free scaling method produced odor classifications consistent with those found when each class of subject reported odor qualities from a defined list of quality descriptors. Cluster analysis of the MDS coordinates revealed that these solutions also retained the individual odor quality differences thought to be characteristic of osmic, allosmic and anosmic subjects.

Adult↗
PubMed1996

Pemenone and androstenone do not cross-adapt reciprocally.

Explorations of the qualitative and quantitative differences between the odors of pemenone (PEM), androstenone (AND) and isovaleric acid (IVA) show that they share a number of common perceptual characteristics. Among these are similarities in their odor quality and relative intensity ratings. PEM is also an efficient cross-adaptor and modulator of a subject's AND sensitivity. Here we evaluate the reciprocal efficacy of AND adaptation to alter the perceived intensity and quality of PEM, IVA and AND. Twenty-three people, including both those osmic and allosmic (n = 11) for the putrid odor quality of PEM, were tested. Following training in odor quality and intensity rating techniques, subjects sampled a selected substance for 2 min to obtain adaptation and then reported quality and intensity ratings for the three test stimuli. There was significant self-adaptation by PEM and IVA in all subjects, but self-adaptation by AND was only observed in the PEM-osmic subjects. AND did not cross-adapt PEM or IVA to any significant extent. Collectively, these results contrast with our earlier study in which PEM was an efficient cross-adaptor of AND. Here, AND was no more efficient than the control as an adapting substance for PEM, despite significant self-adaptation of PEM by itself. This lack of reciprocity in the effectiveness of PEM and AND as cross-adapters is not related to differences in odor intensity, as the PEM and AND concentrations were adjusted for each subject to elicit comparable intensity reports. These results support the notion that PEM, AND and IVA share certain perceptual characteristics, but interact differentially with three or more sets of perceptual channels that are now thought to result in a putrid odor quality.

Adaptation, Physiological↗
PubMed1996

Central nervous system abscesses due to Coccidioides species.

Meningitis occurs in one-third to one-half of patients with disseminated coccidioidomycosis, but mass lesions have rarely been described; these lesions are usually found at autopsy. We report six cases of disseminated coccidioidomycosis with central nervous system (CNS) abscesses. Four patients had cerebellar involvement, and two had spinal cord involvement. Four patients were diabetic, and two subsequently died. Review of the literature on CNS coccidioidomycosis indicated that parenchymal brain involvement occurs in 1%-33% of cases, and < 40 cases with mass lesions have been reported since 1905. Almost all patients were male and had other active disseminated foci of coccidioidomycosis. In approximately one-third of all cases, meningitis was absent. Brain lesions may be superficial or deep and multiple or single. In the absence of meningitis, serology of cerebrospinal fluid is negative. Hematogenous origin appears to be more common than direct extension from the meninges. Spinal cord involvement is rare. Diabetes was present in several cases, thus suggesting a vascular predisposition. We hope our experience will increase awareness of this entity, which appears to be more common than previously appreciated, and will facilitate diagnosis.

Abscess↗
PubMed1996

Treatment of Mycobacterium avium complex infection: do the results of in vitro susceptibility tests predict therapeutic outcome in humans?

The ability of various in vitro methods of antibiotic susceptibility testing to predict therapeutic outcome in patients infected with Mycobacterium avium complex (MAC) was evaluated. Pretreatment bloodstream MAC isolates from 38 patients with AIDS, previously treated in a randomized fashion with either ethambutol, rifampin, or clofazimine, were tested by three conventional methods using broth or agar, as well as by cocultivation with macrophages. The results obtained with each method were compared with the quantitatively determined bacteriologic response to the administration of the single agent in humans. None of the conventional in vitro susceptibility methods was predictive of therapeutic outcome, while the results of cocultivation with macrophages were of moderate predictive value. The positive predictive value of a response in humans based on a response in macrophages (defined by > or = to 1.0 log reduction in baseline colony counts after 5 days of treatment) was 74%. The negative predictive value was 82%.

AIDS-Related Opportunistic Infections↗
PubMed1996

Treatment of Myocardium avium complex infection: does the beige mouse model predict therapeutic outcome in humans?

To determine the predictive value of a standard murine model in the treatment of disseminated Myocardium avium complex (MAC) infection, beige mice were infected with MAC strains isolated from human immunodeficiency virus-infected patients and treated with the same antibiotic (ethambutol, clofazimine, or rifampin) that had been administered to the subject from whom that strain had been recovered. While ethambutol had the greatest bacteriologic efficacy in humans (mean decrease +/-SD, 1.0+/-0.5 log 10 cfu/mL of blood), clofazimine had the greatest bacteriostatic efficacy in mice (mean decrease +/- SD, 2.8 +/- 0.7 log(10) cfu/g of tissue). A linear correlation was not observed between bacteriostatic activity in mouse liver or spleen and the degree of bacteriologic response in humans (P > or = to .1). Odds ratios for a response in humans based on a bacteriologic response in mice were not significant for each agent (P > or = to .1, all cases).

AIDS-Related Opportunistic Infections↗
PubMed1996

Role of extended culture time on synergy of fluconazole and human monocyte-derived macrophages in clearing Candida albicans.

Possible enhanced candidacidal synergy of fluconazole and human monocyte-derived macrophages by extended culture time was studied. Synergistic candidacidal activity increased from 1 day to 3 days and was maximal at 6 days. Enhanced synergistic candidacidal activity at 144 h was observed over a 10-fold challenge dose range. Enhanced synergy with culture time was seen with fluconazole-susceptible and -resistant isolates of Candida albicans. These findings emphasize the importance of dosage and an adequate period of therapy.

Antifungal Agents↗
PubMed1996

D-mannitol in cerebrospinal fluid of patients with AIDS and cryptococcal meningitis.

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 experimental meningitis in rabbits. Mannitol present in the cerebrospinal fluid (CSF) of CM patients could exacerbate raised intracranial pressure and contribute to neurological damage. To link CSF mannitol to cryptococcal infection, levels of mannitol in the CSF of AIDS patients with CM were measured by gas-liquid chromatography. Mannitol was detected in 19 of 21 samples (range, 1.5 to 26.2 mg/liter), but there was no quantitative correlation between the mannitol concentration and the cryptococcal antigen titer.

AIDS-Related Opportunistic Infections↗
PubMed1996

Interactions of glucocorticoids and beta 2-agonists.

Beta 2-adrenoreceptor agonists and glucocorticosteroids are the two most effective treatments for asthma and are often used in combination. Glucocorticoids mediate their anti-inflammatory effects through the action of activated glucocorticoid receptors (GRs). Many of the effects of GRs on the synthesis of cytokines and other inflammatory mediators are due to a direct interaction with other deoxyribonucleic acid (DNA)-binding proteins belonging to the basic leucine zipper (bZIP) group of transcription factors, such as activator protein-1 (AP-1) and nuclear factor-kappa B (NF-kappa B). Beta 2-agonists are potent bronchodilators at low doses and at high doses can activate gene transcription via a bZIP protein, cyclic adenosine monophosphate (cAMP) response element binding protein (CREB). Activated GRs and CREB can interact with each other within the nucleus to modulate both DNA-binding and gene transcription in either a positive or inhibitory manner, depending on cell type. In lung cells, high doses of beta 2-agonists reduce the ability of GR to bind DNA, a process which is mediated by CREB activation. Inhibition of GR DNA-binding by CREB raises the possibility that high-dose beta 2-agonists could have functional antiglucocorticoid activity and may be a basis for the reported increase in asthma morbidity and mortality in industrialized countries, which have increasing per capita beta 2-agonist use.

Adrenergic beta-2 Receptor Agonists↗