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Biomedical subjects

D A Stevens

Publications and source records attributed to D A Stevens.

At least 163 records · Page 9Linked to original sources
PubMed1995

Detection of bovine viral diarrhoea virus antigen and RNA in oviduct and granulosa cells of persistently infected cattle.

Large-scale in vitro bovine embryo production systems commonly use genital tracts obtained from an abattoir as a source of both cumulus-oocyte complexes and co-culture feeder cells. Tissues derived from this source may be contaminated with non-cytopathogenic bovine viral diarrhoea virus (BVDV) since, in several countries surveyed, approximately 1% of animals tested are persistently infected with this pathogen. Therefore, the use of such material in in vitro fertilization systems presents a potential risk for the transmission of BVDV to bovine embryos and via embryo transfer. This potential was investigated by obtaining oviduct epithelial cells and granulosa cells, which are commonly used as feeder cells, from cattle persistently infected with BVDV and examining them for the presence of BVD viral antigen (p80 non-structural protein and gp53 envelope glycoprotein) by indirect immunofluorescent histochemistry, and also viral RNA (encoding the p80 region) by in situ hybridization. In addition, titres of virus present in oviduct, ovary and blood were assayed by immunodetection on calf testis cell cultures. Luminal epithelial cells from the oviduct and primary cultures of granulosa cells and oviduct epithelial cells from such cattle were shown to contain both viral antigen and RNA. The susceptibility of both cell types to BVDV infection was further established by inoculating primary cell cultures of cells derived from cattle not infected with BVDV with a cloned isolate of non-cytopathogenic BVDV (Pe515). RNA encoding BVDV and the antigen were detected 12 h after inoculation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Therapy for opportunistic fungal infections: past, present and future.

The field of antifungal chemotherapy is presently rapidly moving. It began in 1903, with the successful use of potassium iodide (KI). Then there was little progress for 50 years, when in 1951, nystatin was introduced, the first useful polyene. Four years later amphotericin B followed, which is still the historical standard against which new systemic antifungals are compared. Except for the development of flucytosine, there was little progress until the early 1970s and the development of the azole drugs. The present era, which is characterized largely by the modifications of azole drugs, began with ketoconazole and brought agents which can be given orally and have increasing potency, decreasing toxicity and a broader spectrum of activity. Recent studies have examined ways to ameliorate the well-known toxicities of amphotericin B. A new approach has been to complex the drug with lipids or entrap it in liposomes. Itraconazole is a broad-spectrum oral triazole whose greatest advantages over the imidazoles are in its activity against aspergillosis and cryptococcosis, though it is also efficacious against the endemic deep mycoses. Fluconazole is a broad-spectrum triazole. It has been shown to be efficacious in various forms of superficial candidosis, including esophageal disease. We have shown in a randomized, double-blind, placebo-controlled study that maintenance therapy can completely prevent thrush in AIDS patients with recurrent thrush and possibly prevent all deep and superficial mycoses. Other studies have shown efficacy in cryptococcal meningitis in AIDS comparable to conventional therapy and with far less toxicity, and also in prevention of relapse of cryptococcal disease. Early diagnosis of fungal infections in cancer patients is problematic.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗
PubMed1994

Sequential administration of recombinant human interleukin-3 and granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for malignant lymphoma: a phase I/II multicenter study.

Preclinical studies of recombinant human interleukin-3 (rhIL-3) and granulocyte-macrophage colony-stimulating factor (rhGM-CSF) have shown enhancement of multilineage hematopoiesis when administered sequentially. This study was designed to evaluate the safety, tolerability, and biologic effects of sequential administration of rhIL-3 and rhGM-CSF after marrow ablative cytotoxic therapy and autologous bone marrow transplantation (ABMT) for patients with malignant lymphoma. Thirty-seven patients (20 patients with non-Hodgkin's lymphoma and 17 patients with Hodgkin's disease) received one of four different treatment regimens before ABMT. Patients were entered in one of four study groups to receive rhIL-3 (2.5 or 5.0 micrograms/kg/day) administered by subcutaneous injection for either 5 or 10 days starting 4 hours after the marrow infusion. Twenty-four hours after the last dose of rhIL-3, rhGM-CSF (250 micrograms/m2/d as a 2-hour intravenous infusion) administration was initiated. rhGM-CSF was administered daily until the absolute neutrophil count (ANC) was > or = 1,500/microL for 3 consecutive days or until day 27 posttransplant. The most frequent adverse events in the trial included nausea, fever, diarrhea, mucositis, vomiting, rash, edema, chills, abdominal pain, and tachycardia. Three patients were removed from the study because of chest, skeletal, and abdominal pain felt to be probably related to study drug. Four patients died during the study period because of complications unrelated to either rhIL-3 or rhGM-CSF. The median time to recovery of neutrophils (ANC > or = 500/microL) and platelets (platelet count > or = 20,000/microL) was 14 and 15 days, respectively. There were fewer days of platelet transfusions than seen in historical control groups using rhGM-CSF, rhG-CSF, or rhIL-3 alone. In addition, there were fewer days of red blood cell transfusions compared with historical controls using no cytokines or rhGM-CSF. These data indicate that the sequential administration of rhIL-3 and rhGM-CSF after ABMT is safe and generally well-tolerated and results in rapid recovery of multilineage hematopoiesis.

Adult↗
PubMed1994

Anticryptococcal activity of macrophages: role of mouse strain, C5, contact, phagocytosis, and L-arginine.

The antifungal activity of nonactivated resident murine peritoneal macrophages for Cryptococcus neoformans was studied. Macrophages from five of six mouse strains tested had significant (40 to 80%) fungistatic activity, depending on the inoculum size, in a 24-hr coculture system. Macrophages from two outbred (SW and ICR) and three inbred (BALB/c, C57Bl/6, and DBA/2J) strains were fungistatic. Only macrophages from outbred CD-1 mice lacked fungistatic activity. Heat-inactivated and C5-deficient sera did not support phagocytosis or fungistasis by resident BALB/c or DBA/2 macrophages. Fungistasis correlated with contact, complement, and phagocytosis. Macrophages were studied in a Lab-Tek chamber slide system where noningested cells were washed away. Fungistasis in this system was similar to that found with a microtest plate coculture method where a smaller inoculum was cultured continuously with macrophages. After ingestion of yeast cells, CD-1 macrophages could be activated for fungistasis (70%) with interferon-gamma plus lipopolysaccharide. Activated BALB/c macrophages had increased fungistasis but were not fungicidal. NG-Monomethyl-L-arginine (200 microM), which inhibited the fungistatic activity of activated CD-1 macrophages, did not inhibit inherent fungistatic activity of BALB/c macrophages. The fungistatic mechanism of BALB/c macrophages resembled that reported for resident human macrophages.

Animals↗
PubMed1994

Effect of macrophage colony-stimulating factor (M-CSF) on macrophage morphology, phagocytosis, and intracellular multiplication of Histoplasma capsulatum.

M-CSF induced dramatic morphological changes in resident peritoneal macrophages (R-PM) in a time and dose dependent manner. Macrophages increased 2-3-fold in size and developed a dendritic morphology. Compared to macrophages cultured in medium alone M-CSF-treated macrophages were less phagocytic (67 versus 82%) for serum opsonized yeast cells of Histoplasma capsulatum. However, in M-CSF macrophages the intracellular multiplication of ingested yeast cells were significantly inhibited compared to growth in control macrophages. The fungistatic activity of M-CSF macrophages persisted for at least 48 h after infection.

Animals↗
PubMed1994

Overview of amphotericin B colloidal dispersion (amphocil).

Amphotericin B colloidal dispersion (ABCD) is an equimolar mixture of amphotericin B and cholesteryl sulphate with desirable preparation and stability characteristics. It allows the intravenous delivery of amphotericin B in doses up to 7 mg/kg daily. Peak serum concentrations of amphotericin B, given as ABCD, are lower, AUC0-infinity similar and half-life longer than deoxycholate amphotericin B. In vitro activity may be altered with respect to the deoxycholate preparation, some isolates being more resistant and others more susceptible. Preclinical toxicology with ABCD revealed a safety factor of five to 19-fold compared with deoxycholate amphotericin B. Animal models of coccidioidomycosis, disseminated cryptococcosis, candidiasis and invasive aspergillosis indicated a better therapeutic ratio, especially in cryptococcosis. Phase I/II studies in humans demonstrate efficacy against coccidioidomycosis, candidiasis and aspergillosis at doses from 1-7 mg/kg/day in at least 100 patients. Renal toxicity was acceptable but infusion-related side effects and anaemia were common. Side effects appear to decrease on therapy. Comparative studies with deoxycholate amphotericin B are needed.

Amphotericin B↗
PubMed1994

Management of systemic manifestations of fungal disease in patients with AIDS.

In patients with AIDS with cryptococcosis, prompt diagnosis is essential. Poor results with conventional therapy (amphotericin-5FC) have led to exploration of the azoles. Both fluconazole and itraconazole have given good short-term results with less toxicity. However, cure is achieved far less often than in other compromised hosts. Fluconazole is also useful to prevent relapse after successful initial amphotericin therapy, particularly from genitourinary foci. In both histoplasmosis and aspergillosis, itraconazole has produced impressive therapeutic results, and in histoplasmosis, secondary prophylaxis as well. In coccidioidomycosis results thus far have not been better than conventional amphotericin therapy, especially in initial treatment.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Treatment of coccidioidomycosis with SCH 39304.

A new oral triazole antifungal, SCH 39304, was administered to 54 patients with progressive infections due to Coccidioides immitis from six collaborating centers. Patients were grouped according to site of infection including chronic pulmonary (25), bone/joint (17) and skin/soft tissue (12). The median age was 40 years; 83% were male, 52% white, 13% HIV-infected and 35% had failed previous therapy. The majority of patients were treated with either 100 mg or 200 mg day-1. One patient on renal dialysis received 300 mg day-1. Baseline abnormalities were reassessed for evidence of efficacy every 4 months and expressed in a standardized scoring system. Cumulative overall response rates at 4, 8 and 12 months were 7%, 36% and 66% respectively. Twelve month response rates by disease were 77% (pulmonary), 62% (skin/soft tissue) and 31% (bone/joint). Fifteen patients failed therapy although seven of these were still on treatment when the study was discontinued. Two failed due to toxicity. Possible symptoms or signs of toxicity occurred in 24 (44%) patients and were generally mild. SCH 39304 is an effective and well tolerated therapy for progressive forms of coccidioidomycosis.

Administration, Oral↗
PubMed1994

Utility of the triazole D0870 in the treatment of experimental systemic coccidioidomycosis.

The new triazole, D0870, was tested for therapeutic efficacy in the treatment of experimental systemic murine coccidioidomycosis. D0870 at 1 or 10 mg kg-1 daily, or 10 or 100 mg kg-1 every other day, and fluconazole at 100 mg kg-1 daily prolonged survival (P < 0.01), but were equivalent to each other. D0870 at 10 mg kg-1 daily or 100 mg kg-1 every other day cured 20 or 30% of mice of residual infection, respectively, and were superior to 100 mg kg-1 of fluconazole daily (P < 0.001). D0870 is approximately 10-fold more active than fluconazole. It is a promising treatment for coccidioidomycosis, which warrants further testing.

Animals↗
PubMed1994

Efficacy of oral amphotericin B in AIDS patients with thrush clinically resistant to fluconazole.

Reports of thrush clinically refractory to azoles in AIDS patients are increasing with the more widespread use of these agents. We studied our own oral preparation of amphotericin B in the treatment of two AIDS patients who developed oral thrush due to Candida glabrata after prolonged fluconazole use. Improvement occurred in both in less than 1 week, with eventual clearing and absence of side effects. Oral amphotericin B may have advantages over alternatives for this increasing problem.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Individual differences in the perceived intensity and quality of specific odors following self- and cross-adaptation.

Adaptation techniques have traditionally been employed in sensory physiology and psychology to characterize afferent pathways and to dissect the quantitative and, to a lesser degree, the qualitative aspects of perception. We continue to explore the individual differences in olfactory capabilities among subjects initially classified by their ability to detect and identify the diastereoisomeric ketone, cis-4-(4'-t-butylcyclohexyl)-4-methyl-2-pentanone (pemenone) which shares with 5 alpha-androst-16-en-3-one (androstenone) a pronounced urine-sweaty odor. Our previous studies of these and other compounds for which specific anosmias were said to exist revealed significant relationships between intensity scores and a corresponding clustering of the odor quality descriptors used to characterize these materials by subjects judged to be specifically anosmic for the urinous note. Here, we attempt to dissect the web of interactions which give rise to individual differences in perceived odor quality by evaluating the effects of self- and cross-adaptation on the intensity and quality reports elicited by pemenone, androstenone and four other odors in 18 human subjects including both pemenone-osmic and non-osmic (n = 6) individuals. Intensity and quality ratings for the six compounds were obtained before and after an adaptation sequence in which subjects sniffed a test odorant, pemenone or the diluent. For each odorant, intensity ratings under the different adapting conditions were compared by ANOVA. Self-adaptation was universal but cross-adaptation by pemenone was only found in the intensity ratings of androstenone. The intensity ratings of isovaleric acid, which shares the urinous note with pemenone and androstenone, were unaffected by pemenone adaptation. Most of the subjects judged to be osmic still reported a urinous odor quality for androstenone and isovaleric acid following pemenone adaptation. Except for shifts to the no-odor category, adaptation did not significantly alter the odor quality reports of osmic or non-osmic individuals. This suggests that the odor quality reports engendered by these substances are multidimensional and that compounds which share the same odor quality label may interact with different perceptual channels.

Adaptation, Physiological↗
PubMed1994

Genetic characterization of pathogenic Saccharomyces cerevisiae isolates.

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. cerevisiae and, for this reason, stringent genetic tests have been used to confirm their identity as S. cerevisiae. Most of these clinical isolates are able to grow at 42 degrees, a temperature that completely inhibits the growth of most other S. cerevisiae strains. This property can be considered a virulence trait and may help explain the presence of these isolates in human hosts. The ability to grow at 42 degrees is shown to be polygenic with primarily additive effects between loci. S. cerevisiae will be a useful model for the evolution and genetic analysis of fungal virulence and the study of polygenic traits.

Crosses, Genetic↗
PubMed1994

Comparative pathogenesis of clinical and nonclinical isolates of Saccharomyces cerevisiae.

Although considered nonpathogenic, Saccharomyces cerevisiae is being encountered more frequently in the clinical setting. To assess pathogenic potential, 13 clinical isolates, 10 nonclinical isolates, and 5 constructed strains of S. cerevisiae were analyzed. All were S. cerevisiae by biochemical profiles, sporulation, or genetic evidence. Intravenous inoculation of yeasts into CD-1 mice showed that some clinical isolates proliferated in the brain (5-fold) but nonclinical isolates were cleared (1000-fold) by day 7 after infection. Comparison of burdens with those of YJM128 (clinical) and Y55 (laboratory strain) revealed three virulence groupings: virulent, those greater than or equal to YJM128 (5 clinical and 2 genetic constructs); intermediate virulent, those less than YJM128 and greater than Y55 (5 clinical, 3 genetic constructs, and 4 nonclinical); and avirulent, those less than or equal to Y55 (1 clinical and 6 nonclinical). Genetic crosses indicated that virulence was a dominant trait. Growth of various isolates at 37 degrees C and 39 degrees C indicated that temperature is associated with but not solely responsible for differences in virulence. These data demonstrate that some clinical isolates of S. cerevisiae can proliferate and resist clearance in vivo and support the potential of S. cerevisiae as a cause of clinical disease.

Animals↗