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Biomedical subjects

D A Stevens

Publications and source records attributed to D A Stevens.

At least 379 records · Page 21Linked to original sources

Strain differences in resistance to infection reversed by route of challenge: studies in blastomycosis.

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 when challenge was performed by the intraperitoneal route, whether a virulent or an attenuated strain of Blastomyces dermatitidis was utilized. By a third route (subcutaneous), the differences were insignificant. Inhibition of replication of blastomyces in vitro by macrophages from both strains, before or after activation by subcutaneous infection, was similar.

Animals↗

In vitro assays of cellular immunity in progressive coccidioidomycosis: evaluation of suppression with parasitic-phase antigen.

Patients with progressive coccidioidomycosis commonly have depressed cell-mediated immune responses to coccidioidal antigens. We studied in vitro lymphocyte transformation in response to spherulin, as extract of the parasitic phase of Coccidioides immitis, and the nonspecific mitogen phytohemagglutinin in patients with progressive disseminated coccidioidomycosis who were anergic to spherulin and in healthy skin test-positive and skin test-negative control subjects. Lymphocyte responses to phytohemagglutinin were indistinguishable for all three groups. When assayed in pooled blood group AB serum, lymphocyte responses to spherulin were identical for patients and skin test-positive control subjects; however, the patients' responses to spherulin were depressed in autologous serum. Prolonged incubation of cells in vitro did not restore the hyporesponsiveness. Serial studies of the patients revealed a trend toward restoration of the lymphocyte response during therapy. Preliminary experiments suggest that, although there were no intrinsic cell defects in these patients with coccidioidomycosis, there may be specificity of patient cells to be suppressed by serum. A prospective study of the incidence of depression of lymphocyte responsiveness in autologous serum revealed that this occurs in a minority of patients with negative spherulin skin tests, is rare in patients with positive skin tests, and appears to be associated with clinical deterioration.

Adult↗

Ketoconazole in paracoccidioidomycosis: efficacy of prolonged oral therapy.

Ketoconazole, a new oral imidazole derivative, was employed for the treatment of five patients with paracoccidioidomycosis. The response was excellent, with objective clinical improvement and healing of both mucocutaneous and pulmonary lesions. Mycological and serological tests, as well as delayed hypersensitivity, were assessed and found to correlate with clinical improvement. Therapy was conducted for 12 months with a dose of 200 mg day in 2 patients; in the remainder the dose was reduced (100 mg day) after the first 6 months and maintained as such for an equal period. No side-effects or toxicity were noted despite prolonged treatment. The advantages of the new therapeutic approach are discussed.

Administration, Oral↗

Therapy of endogenous fungal endophthalmitis: miconazole or amphotericin B for coccidioidal and candidal infection.

Three patients with endogenous fungal endophthalmitis were treated intravenously with miconazole. Two patients had disseminated coccidioidomycosis, and one patient had disseminated candidiasis. Intraocular mycotic infections developed in one patient undergoing therapy, and progressed in two others also undergoing therapy. All three patients' ocular infections improved after therapy was switched to intravenous amphotericin B administration. Previous experience with miconazole and amphotericin B therapy for fungal endophthalmitis is reviewed. Whereas several failures have been noted with amphotericin B and success with miconazole, our experience suggests systemic administration of amphotericin B may be superior to systemic administration of miconazole for intraocular mycoses, although further clinical data are urgently needed.

Adult↗

Infection of rhesus monkeys and chimpanzees with Epstein-Barr virus.

Seventy-two nonhuman primates were entered into a long-term study to evaluate the pathogenicity of Epstein-Barr virus (EBV). Infectious virus was inoculated into 42 rhesus monkeys, 4 chimpanzees and 1 cynomolgus monkey. Immunostimulation or immunosuppression was attempted in 34 of these animals to enhance the oncogenic potential of the virus. Eleven inoculated animals were followed for more than 3 years and two were observed for 8 years. No tumors were observed in any of the animals; however, serological evaluation of the 47 inoculated primates and 25 matched controls indicated that at least 14 rhesus monkeys and the cynomolgus monkey were successfully infected with EBV. The potential use of rhesus monkeys as a model for EBV-induced disease in humans is discussed.

Animals↗

Endogenous coccidioidal endophthalmitis.

Coccidioidomycosis is generally a self-limited respiratory illness. The literature indicates ocular involvement is rare, usually confined to the anterior segment and adnexa. Ten consecutive patients with chronic pulmonary and disseminated disease referred for chemotherapy represent the first prospective study of ocular involvement. Four demonstrated presumed coccidioidal dissemination to the posterior segment without significant vitreous or anterior segment involvement. Juxtapapillary choroiditis was seen in three, including one who demonstrated retinal infiltrates, telangiectatic capillary change, and macular edema on fluorescein angiography. Another developed a coccidioidal lid granuloma. Correlation between intraocular involvement and systemic outcome was poor. Systemic amphotericin B appeared more effective than miconazole in treating intraocular disease in two patients. Intraocular involvement in progressive coccidioidomycosis appears more common than previously reported. Serial eye examinations should be performed on patients with chronic pulmonary or disseminated coccidioidomycosis.

Adult↗

Complement activation by Coccidioides immitis: in vitro and clinical studies.

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 alternative pathways as shown by deprssion of hemolytic C4 and by generation of products of activation of components C3, C4, and factor B. In addition, functional complement activity or immunoreactive levels of complement components or both were measured in 23 patients with self-limited or disseminated coccidioidomycosis. Low total hemolytic complement was found in nine, usually during the early phase of primary illness, and was transient. Hemolytic C4 was low, and the effect of inulin to decrease complement levels was blunted, suggested both classic and alternative pathways may be deficient. However, associated depression of immunoreactive levels of components assayed (C3, C4, C5, factor B, and properdin) was not consistently found. This disparity raises the possibility of enhanced in vitro inactivation analogous to activation by immune complexes.

Coccidioides↗

Zoster immune globulin prophylaxis of disseminated zoster in compromised hosts. A randomized trial.

Herpes zoster can be a severe, and sometimes fatal, virus infection in its disseminated form in immunocompromised hosts. Previous studies have suggested that delay in appearance of antibody to varicella-zoster virus occurs as one defect in such patients. In this study, pooled gamma-globulin (normal serum globulin [NSG]) and zoster immune globulin ([ZIG] prepared from convalescent zoster patients) were compared for their ability to prevent dissemination of early localized zoster in immunocompromised hosts. Either agent was given intramuscularly in randomized double-blind fashion within nine days of onset of zoster in 97 patients. Despite greater than 100-fold differences in titer of anti-varicella-zoster virus antibody, ZIG did not appear superior to NSG in prophylaxis of dissemination or diminishing postherpetic pain in zoster in immunocompromised hosts. Zoster immune globulins should be reserved for prophylaxis and modification of varicella, where its beneficial effect has been demonstrated.

Antibodies, Viral↗

Amphotericin B-induced myelopathy.

Two patients with coccidioidal meningitis experienced transient neurologic deficits shortly after receiving intrathecal injections of amphotericin B. Continuation of treatment eventually led to a severe flaccid paraparesis with a thoracic sensory level in one patient, and a partial Brown-Séquard's syndrome in the other. Myelography was normal in both, with no evidence of arachnoiditis. Autopsy findings in the first patient showed a focal area of necrosis in the left half of the spinal cord consistent with the patient's clinical findings during life. The distribution of the lesion corresponded to the area supplied by a central sulcal artery. Amphotericin B may exert a direct toxic effect on the spinal cord or its vascular supply when given intrathecally.

Amphotericin B↗

Kluyveromyces fragilis as an opportunistic fungal pathogen in man.

An immunosuppressed cardiac transplant patient with pulmonary infection due to the yeast Kluyveromyces fragilis is described. Isolation of this fungus from human sources is rarely reported, and previous reports of human infection are unavailable in the modern literature. The organism is poorly pathogenic even in immunocompromised hosts. In vitro susceptibility studies with several strains presented here indicate inhibition by 5-fluorocytosine and miconazole, and borderline susceptibility to amphotericin B. The patient was treated with amphotericin B, and recovered without sequelae.

Amphotericin B↗

Deep infections from Petriellidium boydii treated with miconazole.

Infections due to the fungus Petriellidium boydii, particularly deep infections, are being reported with increased frequency. The organism generally is resistant to antifungal agents. Three patients were treated with miconazole, a new drug demonstrated to be active in vitro against the fungus. Miconazole alone was effective in treating two patients. The third patient showed an excellent therapeutic result with concomitant surgery. This experience confirms the in vitro results and suggests the utility of this drug in petriellidiosis.

Adult↗

Association of ABO blood group and outcome of coccidioidal infection.

Dissemination of fungal infection due to Coccidioides immitis has been previously shown to be related to hereditary factors. Two associations reported to date are race (e.g., Filipino and black ancestry) and HLA histocompatibility type (HLA-19). In the present study of 105 patients a significant association of blood group B and dissemination is demonstrated. C. immitis is known to possess antigens with blood group A activity. Previous epidemiologic studies have also shown HLA-A9 and blood group B are both more common in persons of black and Filipino ancestry. Further studies are needed to define whether these are independent variables, and may define subgroups at particularly high risk following coccidioidal infection.

ABO Blood-Group System↗

Variability of agar dilution-replicator method of yeast susceptibility testing.

The agar dilution method of in vitro susceptibility testing of fungi was analyzed with a Steers-type inoculum replicator, ten strains, and three drugs. The replicator reproducibly delivered the same inoculum to each series of plates. The minimal inhibitory concentrations of ketoconazole (an imidazole) and 5-fluorocytosine, but not that of the polyene nystatin, were dependent on the initial inoculum size. With the former two drugs, but not with the latter, minimal inhibitory concentrations were highly variable depending on the time of reading. Results with agar and broth dilution methods were divergent, and the differences in minimal inhibitory concentrations were variable in serial comparisons by the two methods. If the agar dilution minimal inhibitory concentrations were determined at first appearance of control growth, a commonly used end point, small variations in the time of reading (as could occur by variation in observer perception of when initial growth appears) induced large variations in the minimal inhibitory concentrations of 5-fluorocytosine and ketoconazole, particularly with rapidly growing strains. Results at 35 and 30 degrees C were similar. The differences in results with the three drugs suggest different mechanisms of action. The variability quantitated with the agar dilution method could result in variability in results between laboratories and even observers in the same laboratory.

Agar↗

Epstein-Barr virus-specific serum immunoglobulin A as an acute-phase antibody in infectious mononucleosis.

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 mononucleosis patients demonstrated IgA antibody, whereas this was found in 13% of controls. This antibody appeared early in infectious mononucleosis and was virtually gone 10 weeks after onset. Comparison of IgA antibody kinetics was made with IgG and IgM antibodies to viral capsid antigen, heterophile antibody, and antibody to Epstein-Barr virus early antigen and nuclear antigen. Failure to demonstrate IgA antibody was associated with severe illness, prolonged illness, delay in IgG and anti-Epstein-Barr virus nuclear antigen antibody, and low or absent heterophile and anti-early antigen antibody. Assay of IgA antibody to viral capsid antigen is a potentially useful adjunct in the serodiagnosis of infectious mononucleosis or recent Epstein-Barr virus infection, as are the other antibodies tested, but in this study IgM viral capsid antigen antibody was the only acute-phase antibody present in all patients.

Acute Disease↗

Ketoconazole, an oral antifungal: laboratory and clinical assessment of imidazole drugs.

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 inhibitory in vitro at low concentrations to most fungi. Blood levels after oral administration to animals and man greatly exceed these inhibitory concentrations for several hours. The efficacy of this drug has been demonstrated in animal models. Initial clinical evaluation has produced responses to therapy with 200-400 mg/day in 13 of 16 evaluable patients with systemic and superficial fungal infections, involving 10 fungal pathogens. No toxicity has been noted to date in these human studies. Ketoconazole is a promising agent needing further extensive evaluation.

Adolescent↗