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Biomedical subjects

J M Cobb

Publications and source records attributed to J M Cobb.

13 recordsLinked to original sources
PubMed1981

Ultrastructure of Coccidioides immitis after exposure to the imidazole antifungals miconazole and ketoconazole.

Scanning and transmission electron microscopy was performed on the various phases of Coccidioides immitis, exposed for different periods of time to the imidazole antifungals miconazole and ketoconazole. The development of spherules into endospores, which takes place in cultures under normal growth conditions, was suppressed in the drug treated cultures. Typical ultrastructural changes were localized at the cell periphery and in the vacuolar system. The drugs did induce changes in mature, resting endospore cultures and in cultures incubated statically at room temperature. Aerobically growing endospores were not susceptible to either drug. The transformation of arthroconidia into mycelium was fully prevented after treatment. Mycelial cells were most susceptible to the antifungals for necrosis was induced in a substantial part of the hyphae after exposure for 24 h.

Coccidioides↗
PubMed1978

Oral therapy for experimental coccidioidomycosis with R41 400 (ketoconazole), a new imidazole.

Oral treatment of mice with R41 400, ketoconazole, after intranasal challange with arthrospores of Coccidioides immitis prevented death at doses of 40 mg per kg of body weight per day. Doses of 160 mg per kg of body weight per day during 50 to 100 days eradicated the fungus from the lungs, liver, spleen and kidneys of approximately one half of the infected animals. Resistance to the drug was not induced during prolonged treatment. Hydropic changes in the liver occurred in animals receiving doses of 160 mg per kg of body weight per day by the fiftieth day of treatment, but did not occur at lower doses.

Administration, Oral↗
PubMed1978

Therapeutic properties of oral ambruticin (W7783) in experimental pulmonary coccidioidomycosis of mice.

Oral administration of ambruticin (W7783) (by gavage) was lifesaving in mice infected intranasally with arthrospores of Coccidioides immitis. Doses of 25 and 50 mg/kg of body weight, given twice daily by different schedules for from 17 to 60 days, eradicated the fungus from 71 to 100% of the infected mice. Lower doses (5 or 10 mg/kg once or twice daily by an intermittent 50-day regimen) prevented death in all instances but produced many fewer biologic cures. The animals tolerated all these doses well but were adversely affected by doses of 200 mg/kg given daily. Resistance to the drug was not induced by prolonged treatment. Dose-related fungicidal and fungistatic properties in vitro correlated with doses that were life-sustaining or curative (or both) in vivo.

Administration, Oral↗
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↗
PubMedDate not supplied

Ketoconazole in early and late murine coccidioidomycosis.

Ketoconazole (35 mg/kg) was administered orally to mice twice daily, beginning at different intervals after intranasal infection with arthrospores of Coccidioides immitis. When treatment was begun on the fourth day after infection, before extensive extrapulmonary dissemination of the infection had occurred, all animals survived, and extension of the disease from lungs to liver, spleen, and kidneys was prevented. Mortality was 90% in untreated control animals. In most of the drug-treated animals, lung lesions were not rendered free of fungus after 21 days of treatment. When treatment was begun on the 12th day of infection, after extrapulmonary dissemination had occurred, the drug was life-preserving. However, lesions of the peritoneal organs of 30%--60% of the surviving animals and pulmonary lesions of 90% of these animals harbored viable fungi after 82 days of treatment. Mortality was lower when treatment was given from the 35th through the 120th day after infection to survivors of a challenge dose that was lethal to 28% of the animals within 30 days. These data indicate that the antifungal activity of the drug observed in vitro also operates in vivo. Mycologic cure was optimal when infections were treated early. It became difficult to eradicate the fungus once it became entrenched in lesions of the peritoneal organs or lungs.

Animals↗
PubMedDate not supplied

Psychosocial stress and susceptibility to upper respiratory tract illness in an adult population sample.

OBJECTIVE: To assess the influence of life event stress and hassles, and the moderating effects of psychological coping style, social support, and family environment, on susceptibility to upper respiratory tract infectious illness. METHOD: One hundred seven adults aged 18 to 65 years took part in a 15-week study. Measures of life event stress were obtained for the 12 months preceding the study and for the study period itself, and social support, information seeking and avoidant coping styles, and family environment were assessed. Hassles and perceived stress were measured weekly, whereas dysphoric mood and changes in personal health practices (smoking, alcohol consumption, exercise, and sleep patterns) were assessed at three weekly intervals. Episodes of upper respiratory tract infectious illness were verified by clinical examination. RESULTS: During the study period, 29 individuals experienced at least one clinically verified episode of upper respiratory tract illness. There were no differences in cigarette smoking, sleep habits, or exercise between those who did and did not become ill but alcohol consumption was lower among those who experienced verified episodes. Risk of infectious illness was greater in those who experienced high life event stress both before and during the study period, but the impact of life events was buffered by an avoidant coping style. Strict family organization was associated with illness risk. The three weeks preceding illness onset were characterised by high levels of perceived stress, but also by a decrease in the number of hassles reported. CONCLUSIONS: Results suggest that under naturalistic conditions, the influence of stressful experience on risk of infectious illness is moderated by psychosocial resources. Variations in personal health practices do not seem to be responsible.

Adaptation, Psychological↗