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Biomedical subjects

D A Stevens

Publications and source records attributed to D A Stevens.

At least 397 records · Page 22Linked to original sources
PubMed1978

Coccidioides immitis endospores: phagocytosis by human cells.

Phagocytosis of killed endospores by glass adherent peripheral human mononuclear cells was studied. Phagocytosis continued through 30 minutes of incubation. No difference in rates of ingestion could be detected when cells from coccidioidin-reactive and nonreactive subjects were compared although both groups ingested endospores more avidly than latex particles.

Cells, Cultured↗
PubMed1978

Turbidimetric studies of growth inhibition of yeasts with three drugs: inquiry into inoculum-dependent susceptibility testing, time of onset of drug effect, and implications for current and newer methods.

Susceptibility testing with the broth-dilution visual end-point method is inoculum dependent with miconazole and 5-fluorocystosine, but not with amphotericin B. Turbidimetric measurements of yeast growth in the presence of antifungal drugs were therefore performed. With miconazole and 5-fluorocytosine, over the range of concentrations studied, growth occurred until a plateau phase was reached. With drug present prior to log phase growth, a delayed onset of effect was noted which was proportional to the generation time of the organism. With amphotericin B, in contrast, there was sharp transition with increasing drug concentration from no inhibition to complete arrest of growth, and no relation of onset of effect to generation time. These findings provide a possible explanation of inoculum dependence; i.e., at higher inocula, partially inhibited but growing yeasts become visible at higher drug concentrations. Supporting evidence derives from observations with different starting inocula, varying time of reading end points, and other methods of studying growth inhibition. The delay in miconazole and 5-fluorocytosine effect described suggests that rapid methods of susceptibility testing should be utilized with cultures already in log phase.

Amphotericin B↗
PubMed1978

Chemotaxigenic activity of extracts from the mycelial and spherule phases of Coccidioides immitis for human polymorphonuclear leukocytes.

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 peripheral blood of uninfected subjects. Soluble substances prepared from the mycelial (saprophytic) and spherule (tissue) phases exhibited, in the presence of serum, dose-dependent chemotactic activity. The dose-response correlations were different. The spherule-derived preparation showed decreased activity at the high concentrations, a diminution not observed with equivalent concentrations of the mycelial filtrate. Chemotactic activity was not observed with either substance in the absence of serum or if heat-inactivated serum was substituted. Because the response of human polymorphonuclear leukocytes to these fungal substances appears complement mediated, a selective cellular defect in this function which antedates exposure to C. immitis seems unlikely.

Chemotaxis, Leukocyte↗
PubMed1978

Complement fixation antibody test for human nocardiosis.

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 secreted into liquid growth medium by cultures of N. asteroides. Apparent false positives reactions were found in three of three patients with leprosy and two of five patients with tuberculosis--results similar to some previously reported methods. N. asteroides and mycobacteria share antigens. Only the false positives with tuberculosis are considered a diagnostic problem. No reactions were obtained with sera from 26 patients with other infections and 41 unifected individuals. Whereas previous nocardia serodiagnostic methods have a sensitivity of approximately 50%, our overall sensitivity (81%) compares favorably and included 9 of 11 positive tests in immunocompromised nocardiosis patients (a source of false negative reactions with previous methods).

Adult↗
PubMed1978

Mouse model of pulmonary blastomycosis: utility, simplicity, and quantitative parameters.

A murine model of pulmonary mycotic disease using Blastomyces dermatitidis is defined quantitatively. Intranasal inoculation with yeasts avoids delays in growing microconidia and can be performed with routine precautions without sophisticated biohazard facilities. The particles rapidly reach the bronchioles and alveoli, producing a progressive focal pneumonia, studied histologically. In vitro growth conditions are defined to titer inocula reproducibly with visual methods. Median survival can be titrated with the challenge inocula. Although initial postchallenge lung cultures are not always positive, replication eventually proceeds, at a rate defined for various challenge sizes, to a ceiling of 10(7) to 10(8) colony-forming units per g of tissue incompatible with life. Lung weight correlates closely with colony-forming units per g above a threshold. Lethality correlates with initial body weight and with age. During the course of infection, weight is an accurate predictor of mortality. Extrapulmonary dissemination occurs as a premortem event in protracted infections. A wide variation in fungal strain virulence is documented. Quantification of these features of the model makes it useful for study of host response or therapeutic intervention, because efficacy can be related to stage of disease and parasitic burden.

Animals↗
PubMed1978

Paracoccidioidomycosis (South American blastomycosis): treatment with miconazole.

Six patients with multisystem paracoccidioidomycosis proven by serology and culture or smear were treated with relatively brief courses of intravenous miconazole. Two had relapsed following prior therapy; 6 had active pulmonary, 4 laryngeal, 2 oropharyngeal, 2 lymphoid, and 1 abdominal disease. Paracoccidioides brasiliensis was highly susceptible to miconazole in vitro; minimal inhibitory concentration was less than or equal to 0.001 microgram/ml. Clinical examination showed a prompt and objective response in all patients, confirmed by smear or culture and X-rays; in 4/6 serological response was shown. Side effects were minor. Two patients relapsed 3--5 mo after therapy; another had a rise in antibody 6 mo after therapy and was given maintenance oral sulfa. One remains in remission 7 mo after treatment; two given oral sulfa after response to miconazole remain in remission 4--6 mo after treatment. Paracoccidioidomycosis responds well to miconazole, but longer courses may be needed to prevent relapse.

Adolescent↗
PubMed1978

Cell-mediated immunity, Epstein-Barr virus and nasopharyngeal carcinoma.

Cellular immunity is apparently important in host defenses against cancer. A growing body of information on CMI to EBV is here reviewed, providing a strong basis for studies of such reactivity in NPC. Present work suggests that CMI responses to virus- and tumour-associated antigens may have implications for etiology, diagnosis and treatment.

Animals↗
PubMed1978

Otomycosis due to coccidioidomycosis.

The course and treatment of two patients with otomycosis due to Coccidioides immitis, believed to be the first such cases reported, are described. Both infections appeared due to reactivation of hematogenously disseminated foci. Local and systemic chemotherapy plus surgery resulted in remission, and host immune response also appears to be an important factor. One patient, with systemic lupus erythematosus, required more extensive surgery, more chemotherapy, and reduction in steroid dose to arrest the disease. A combined surgical and chemotherapeutic approach appears necessary when otomycosis is due to invasive fungi such as C immitis.

Adult↗
PubMed1978

Cellular immunity in infectious mononucleosis: I. Spontaneous and phytohaemagglutinin-induced blast transformation in infectious mononucleosis, with special reference to depressed cellular reactivity and stimulation-blocking serum factors.

Lymphocytes of patients with infectious mononucleosis (IM), EBV sero-positive subjects, patients with viral infections other than EBV, and EBV sero-negative subjects were tested for phytohaemagglutinin (PHA)-induced and spontaneous transformation in vitro. Lymphocytes of EBV sero-positive healthy subjects, tested in autologous serum, have higher spontaneous transformation than those of EBV sero-negative subjects. IM patients, in the acute phase of illness, have depressed spontaneous lymphocyte transformation, independent of serum factors. Serum factors are present in acute IM that depress spontaneous transformation further, and to a lesser extent depress reactivity to PHA. By the time the IM patients had recovered, greater than 9 weeks after onset of illness, the defects observed had disappeared.

Antibodies, Viral↗
PubMed1978

Cellular immunity in infectious mononucleosis. II. Specific reactivity to Epstein-Barr Virus antigens and correlation with clinical and hematologic parameters.

Infectious mononucleosis (IM) patients, Epstein-Barr virus (EBV)-seropositive and seronegative healthy donors, and patients with other viral infections were tested for lymphocyte blastogenesis (LB) with phytohemagglutinin and six EBV (virus concentrate, culture supernatant, and soluble [S] antigen) or control antigens. Fluorescent antibodies to EBV viral capsid antigen of IgG, IgM, IgA specificities, to nuclear antigen (EBNA), and heterophile antibodies were also assayed. These were correlated with clinical parameters (fever, pharyngitis, adenopathy, hepatitis, splenomegaly, atypical lymphocytes, and total mononuclear cell counts). EBV viral and S antigen-induced LB was significantly greater in seropositive donors. IM patients had antigenspecific LB below that of seropositive donors initially and low responses for the acute phase of illness when clinical symptoms were present and antibody titers were maximal. Specific LB rose to a peak at 3.5 to 9 weeks when the patients had recovered, most laboratory findings had returned to normal, and antibodies had declined. At peak, specific LB in IM patients exceeded that of seropositive donors, but later declined. These results demonstrate specific cell-mediated immunity (CMI) to EBV, and indicate that this develops slowly in IM and contrasts with the evolution of the clinical events and humoral immunity. This correlation supports the hypothesis that CMI is the mechanism of terminating lymphoproliferation in IM.

Antibodies, Viral↗
PubMed1977

Spherulin skin testing and histoplasmal and coccidioidal serology: lack of effect.

This study demonstrated that the administration of a spherulin skin test to subjects whose skin-test reactions were either positive or negative, at the dose used (Usual Test Strength), did not elicit an antibody response to antigens of Coccidioides immitis or Histoplasma capsulatum, as determined by standard serologic methods. Of 32 subjects, one developed a seroconversion by the latex agglutination test. The data suggested that spherulin can be used clinically as a diagnostic reagent without affecting the serologic reactions, which are of both prognostic and diagnostic value.

Antibodies, Fungal↗
PubMed1977

Fungal endocarditis: need for guidelines in evaluating therapy. Experience with two patients previously reported.

Successful treatment of fungal endocarditis is being described with increasing frequency. Two patients, previously reported as free of disease by two different groups of investigators, subsequently died in our institutions with evidence of continued disease. Both patients had been receiving antifungal chemotherapy at the time their case histories were reported. The lack of clinical signs and symptoms in fungal endocarditis, the suppression of manifestations of infection by chemotherapy, and the uncertain reliability of laboratory aids led us to suggest guidelines in reporting results of therapuetic regimens. These include avoidance of terms implying cure in patients who are concurrently maintained on chemotherapy, indication of attempts to evaluate fungemia, and minimum follow-up of 1-2 years' duration. The potential utility of serologic studies is illustrated by the course of one of these patients.

Adult↗
PubMed1977

Treatment of fungal meningitis with miconazole.

Twelve patients with fungal meningitis (ten cases were due to Coccidioides immitis, two were from Cryptococcus neoformans) were treated with brief courses of intravenous (IV) miconazole. Eleven patients, including patients with severe, chronic disease, had been treated unsuccessfully with amphotericin B. Four patients also received miconazole injected directly into the CSF. The drug was well tolerated by any route, with mild reversible side effects. After IV administration the miconazole concentration in the CSF rarely exceeded the minimal inhibitory concentration (MIC) of the infecting organism. Intra-CSF administration of 20 mg generally produced levels above the MIC for 24 hours. Five of ten patients with coccidiodial meningitis responded clinically. Of these five, four received only IV miconazole; three relapsed after therapy was stopped. Miconazole appears promising as a treatment of fungal meningitis, but trials of longer duration might prevent relapse.

Adolescent↗