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Biomedical subjects

D A Stevens

Publications and source records attributed to D A Stevens.

At least 415 records · Page 23Linked to original sources
PubMed1976

Visceral fungal infections due to Petriellidium boydii (allescheria boydii). In vitro drug sensitivity studies.

Four patients with visceral infections due to the fungus Petriellidium boydii, who were recently hospitalized in our institutions, are described. Three of the patients were compromised hosts; in the fourth patient, infection occurred after trauma. All had received prior steroid and antibiotic therapy. Studies of patients with mycetoma or secondary infection of a pulmonary cavity due to this organism and of patients with visceral infections are reviewed. Because of histologic similarities to Aspergillus species, infections due to P. boydii may have been misdiagnosed in the past if the infecting fungus was not isolated in culture. The fungus has been shown to be resistant in vitro to currently available antifungal agents. Resistance to amphotericin and 5-fluorocytosine is demonstrated in our studies. There are few reports of successful chemotherapy of any manifestation of this infection, and no such reports of visceral disease. We demonstrate in vitro sensitivity of isolates in our cases and in others to micronazole, a new antimicrobial agent; this drug may be indicated for treatment of disease due to P. boydii.

Adult↗
PubMed1976

Miconazole in coccidiodomycosis. II. Therapeutic and pharmacologic studies in man.

Fourteen patients with chronic coccidioidomycosis, many of whom had complicating concurrent diseases and/or had failed to respond to amphotericin therapy, were treated with intravenous miconazole, a synthetic imidazole drug previously shown to be effective in experimental murine coccidioidomycosis. Up to 3.6 g/day was given for up to three months. 7inimal inhibitory concentrations of mycelial and endospore phases of all clinical isolates of C. immitis were less than 2.0 mug/ml. Peak concentrations in the blood of up to 7.5 mug/ml (by assay against C. immitis in vitro) were achieved. Doses above 9 mg/kg or 350 mg/m2 were more efficacious in producing blood levels over 1 mug/ml. Serum protein binding, determined by several methods, was approximately 90 per cent. The disappearance of bioactive drug from blood after infusion has a rapid initial phase (t1/2 approximately 30 minutes) and a final plateau (t1/2 approximately 20 hours). Eight patients had objective evidence of response, three had slight or equivocal responses, two could not be evaluated, and one was a treatment failure. Side effects were generally uncommon, minor and transient except for phlebitis. Infusion into central venous catheters appears to circumvent this problem. Miconazole is a potentially useful drug in the treatment of coccidioidomycosis.

Adult↗
PubMed1976

Reversible thrombocytosis and anemia due to miconazole therapy.

Miconazole was administered intravenously in six consecutive patients with, active coccidioidal infection. Such treatment was associated with progressive anemia and thrombocytosis. The hematological abnormalities appeared to be dose related and potentially reversible. Bone marrow studies demonstrated erythroid hypoplasia and increased or active platelet production in three subjects. No hemorrhagic or thrombotic episodes were identified. It is suggested that careful hematological monitoring be performed in subjects undergoing systemic miconazole therapy.

Adolescent↗
PubMed1976

Antimicrobial susceptibility testing of yeasts: a turbidimetric technique independent of inoculum size.

The current development of potent antifungal drugs necessitates reliable methods of in vitro susceptibility testing of clinical isolates. Other laboratories have noted with some antimicrobials that conventional tube dilution visual end points for determining minimal inhibitory concentrations (MIC) vary markedly with the inoculum. With seven isolates (four species) we compared the conventional method with one developed with a spectrophotometer. Yeasts were diluted to inocula of 10(2) to 10(5) cells/ml and incubated at 37 degrees C with 5-fluorocytosine or miconazole or without drug in a synthetic defined medium. At frequent intervals MICs were determined by the lowest drug concentration without visible turbidity. Concurrently, the percent transmission of each tube was measured and an inhibitory concentration (IC((1/2))) was calculated from the turbidimetric measurements. MICs of both drugs for all strains varied with the inoculum. Intrastrain differences averaged 128-fold for miconazole and greater than 8-fold with 5-fluorocytosine. This variability in MIC occurred when readings were made after 12 to 48 h of incubation. In contrast, IC((1/2)) values of all isolates varied less than two-fold with the same range of inocula. Most isolates showed this independence when measured at 48 h. Fast-growing yeasts showed greater IC((1/2)) variability unless the turbidimetric measurements were taken earlier while the drug-free growth was still in a rapid growth phase. This method is reproducible, inoculum independent, rapid, free from subjectivity and observer variability, and suitable for adaptation to a clinical setting.

Methods↗
PubMed1975

Cellular events in zoster vesicles: relation to clinical course and immune parameters.

The cellular responses in zoster vesicles was studied chronologically in 30 patients, some of whom were compromised hosts with disseminated disease. Cell counts were low initially but rose abuptly later. Polymorphonuclear leukocytes predominated at all times in the vesicular fluid and in the cells adherent to the vesicle base. The abrupt rise in the number of cells generally coincided with an abrupt rise in the titer of vesicular interferon; both increases preceded resolution of local infection and cessation of cutaneous dissemination in disseminated disease, but the sequence of the increases was variable. The peak interferon titer correlated with cessation of dissemination better than did peak cell counts, and the timing of the local events contrasted with appearance of complement-fixing antibody, which commonly occurred after the resolution of disease. Possible interpretations are that a few sensitized lymphocytes may initiate the defensive response, produce interferon, and/or produce chemotactic factors that augment the polymorphonuclear response. The appearance of polymorphonuclear cells may be a nonspecific inflammatory response, or these cells or the deeper mononuclear infiltrate seen in biopsies may contribute to the rise in local interferon.

Antibodies, Viral↗
PubMed1975

Miconazole in coccidioidomycosis. I. Assays of activity in mice and in vitro.

Administration of miconazole to mice infected with Coccidioides immitis prevented death in all cases; the infecting doses killed 60%-100% of the untreated animals. The drug's anticoccidioidal influence was also demonstrated by its capacity to limit fungal proliferation in the lungs. The endospore phase of C. immitis, which predominates in lesions, was more susceptible to miconazole than were the saprophytic arthrospore and mycelial phases. The drug was lethal to endospores in vitro in the presence or absence of human plasma, but plasma decelerated the rate of killing. A sensitive quantitative assay (using endospores) for the drug in plasma was developed, and the inefficacy of determining the sensitivity of strains with mycelia was demonstrated.

Animals↗
PubMed1975

Spherulin and coccidioidin: cross-reactions in dermal sensitivity to histoplasmin and paracoccidioidin.

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 autolysates of the mycelial phase (saprophytic) of the fungus. A more sensitive reagent, spherulin, was developed in 1969 from the spherule phase (parasitic) of the organism. Use of spherulin showed that coccidioidin failed to detect approximately 30% of individuals specifically sensitive to C. immitis. However the potential of spherulin to detect cross-sensitivity induced by Histoplasma capsulatum was unknown. This information was considered to be germane because of the capacity of coccidioidin to detect a histoplasmal experience. Accordingly, both reagents as well as paracoccidioidin were compared simultaneously in 365 Columbian soldiers from areas endemic for histoplasmosis but not for coccidioidomycosis. At standard strength both preparations detected nonspecific responses in 0.8% to 3% of the histoplasmin negative and positive subgroups, respectively. At 10-times standard strength both preparations cross-detected histoplasmin sensitivity comparably; 5.1% to 7.1% of histoplasmin-positive subjects reacted with the coccidioidal antigens. No pattern of cross-reactivity was observed between paracoccidioidin sensitivity and sensitivity to the coccidioidal antigens.

Adolescent↗
PubMed1975

Coccidioidomycosis in compromised hosts. Experience at Stanford University Hospital.

To determine the frequency and clinical characteristics of infection with Coccidioides immitis in immunosuppressed patients at Stanford University Hospital, clinical records of 14 years were examined. Thirteen cases met the diagnostic criteria. Half had Hodgkin's disease. In six the infection was disseminated; five of the six died early in the course of their infectious illness, frequently without diagnosis. Conclusions include: 1. The occurrence of coccidioidomycosis in immunosuppressed patients seen at institutions in or adjacent to the endemic area is not as rare as the literature suggests. 2. Dissemination is frequently explosive and the radiographic appearance of pulmonary involvement may appear late. Widespread pulmonary dissemination may occur within 24 hours after a negative x-ray. 3. Although the skin test loses its diagnostic value, the serology remains valid. Thus immunosuppressed patients with febrile illnesses (with or without radiographically evident pulmonary involvement) who have a history of travel to an endemic area should have serological examinations. 4. Lymphocytopenia correlates with risk of dissemination of coccidioidomycosis. 5. The administration of immunsuppressive chemotherapy correlates with such risk while radiotherapy and the malignant or non-malignant nature of the disease do not.

Acute Kidney Injury↗
PubMed1975

Randomized trial of transfer factor treatment of human warts.

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 child then had a spontaneous regression at multiple warty areas. A similar relationship was seen in four otherwise healthy patients in a pilot study. A randomized double-blind study of thirty patients failed to confirm a causal relationship between the transfer factor therapy (equivalent to 2-1 X 10(8) leucocytes) and wart regressions. The need for randomized trials of transfer factor therapy for diseases with a variable natural history is emphasized.

Adolescent↗