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Biomedical subjects

H B Levine

Publications and source records attributed to H B Levine.

At least 37 records · Page 2Linked to original sources
PubMed1982

Pharmacokinetics of ketoconazole in patients with neoplastic diseases.

Twenty-seven patients with advanced malignancies were given 200 mg of ketoconazole orally every 6 or 12 h. Blood samples were collected during these intervals and after the last dose to determine plasma concentrations and half-lives. The mean plasma concentrations measured after the initial dose were 1.7 +/- 1.1 microgram/ml at 2 h, 0.9 +/- 0.2 microgram/ml at 6 h, and 0.7 +/- 0.4 microgram/ml at 8 h. Plasma concentrations rose significantly in patients on the every-6-h schedule. Concentrations were more variable in patients on the every-12-h schedule, and changes in mean plasma concentrations after 7 and 14 days were not significant. Half-lives ranged from 1.3 to 11.6 h in individual patients. The mean half-life for all patients studied was 3.7 +/- 0.6 h on day 1. The calculated area under the curve was 12.0 +/- 4.7 micrograms-h/ml on day 1; it increased after 7 and 14 days of administration (every-6-h schedule), suggesting plasma binding or wide drug distribution or both. Saturation of storage compartments is also suggested. Less than 1% of the administered dose was recoverable as active drug from the urine over 6 h.

Adolescent↗
PubMed1982

Stimulation and suppression of cell-mediated immunity by endosporulation antigens of Coccidioides immitis.

The culture filtrate of Coccidioides immitis induced to replicate in its parasitic phase in vitro, termed endosporulation antigens (EA), was assayed for ability to stimulate human lymphocyte blastogenesis in vitro. Stimulation of lymphocytes from skin test-positive healthy subjects by EA was comparable to stimulation by spherulin at optimal dilutions, but EA are 500 times more potent when compared on the basis of weight. Both preparations slightly stimulated lymphocytes from skin test-negative subjects. Heating or dialysis of EA enhanced the effect on skin test-positive subjects, but concentration depressed it. Concentrated EA also depressed nonspecific stimulation caused by phytohemagglutinin. Dialysis of concentrated EA reduced the ability to depress responses. EA from an avirulent strain of C. immitis were as stimulatory as EA from a virulent strain, but concentrating the former did not produce as much depression as concentrating the latter did. A survey of subjects with an optimal dose of EA in lymphocyte transformation showed that EA could separate skin test-positive from -negative subjects as well as spherulin could. The survey also showed that a delta cpm (the difference of incorporated counts of tritiated thymidine per minute in the presence or absence of the reagent) of 10,000 is useful for this separation. These results also indicate the presence of suppressive substances in EA which are only partially dialyzable and which were significantly more prominent in a preparation from the virulent strain.

Animals↗
PubMed1982

Toward a psychoanalytic understanding of children of survivors of the Holocaust.

The psychoanalytic study of children of survivors of the Holocaust provides the opportunity to contribute to a more effective approach to this population while simultaneously investigating the impact of psychic trauma on personality development. Transgenerational transmission of trauma and the potential developmental consequences of parental affective unavailability and narcissistic overinvestment are examined, with particular emphasis on separation-individuation, superego formation, the management of aggression, and the development of the ego's capacity to maintain an appreciation of the "make-believe" quality of primitive fantasy.

Adjustment Disorders↗
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↗
PubMed1980

Suppression of cryptococcosis and histoplasmosis by ketoconazole in athymic nude mice.

Congenitally athymic nude (nu/nu) mice are more susceptible to disseminated cryptococcosis and histoplasmosis than their heterozygous (nu/ + ) thymus-bearing litter-mates. The therapeutic efficacy of ketoconazole, an orally absorbable antifungal agent, was evaluated in nu/nu and nu/ + mice infected intraperitoneally with Cryptococcus neoformans and Histoplasma capsulatum. Two- to five-week courses of ketoconazole significantly prolonged the survival of nu/nu mice infected with either fungus in dose-dependent fashion, but death eventually followed discontinuance of therapy. More significant protection was seen in nu/ + mice infected with C. neoformans, and markedly lower fungal counts in organs, with some negative cultures, were seen in ketoconazole-treated nu/ + mice infected with H. capsulatum. These studies indicate that ketoconazole is effective against both fungi, although results of treatment are much better in the immunologically intact nu/ + host.

Animals↗
PubMed1980

Ketoconazole treatment of chronic mucocutaneous candidiasis.

Five patients received ketoconazole treatment of chronic mucocutaneous candidiasis. One also had disseminated histoplasmosis and cryptococcosis. Ketoconazole was well absorbed after an oral dose of 200 mg and produced detectable antifungal blood levels for more than eight hours after each dose. Thrush cleared in less than two weeks in all patients. Cutaneous lesions cleared slowly during several months of treatment. A patient with polymycotic infection had a rapid clearing of candidiasis, but her histoplasmosis did not respond to three weeks of treatment. Adverse drug effects were minimal. Ketoconazole is a promising new agent for treatment of chronic mucocutaneous candidiasis.

Adolescent↗
PubMed1979

Immunization of mice against coccidioidomycosis with a subcellular vaccine.

In vitro-cultivated spherules of Coccidioides immitis were disrupted in a Braun homogenizer. The resultant wall fragments were separated from cell sap and endospores by centrifugation. Extraction of the walls with phosphate-buffered saline yielded a subcellular fraction that was immunogenic in mice. This fraction, which contained polysaccharide and protein, gave substantial protection against intranasal challenge with a usually lethal dose (1,000) of arthrospores, provided that it was administered with adjuvant.

Adjuvants, Immunologic↗
PubMed1979

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↗
PubMed1979

Histoplasmin-CYL, a yeast phase reagent in skin test studies with humans.

A yeast phase histoplasmin, designated CYL, was studied in 156 humans living in areas of the United States endemic for histoplasmosis, coccidioidomycosis, or both fungal entities. Comparisons were made with Food and Drug Administration reference mycelial histoplasmin. Among persons without concurrent spherulin sensitivity, reactor rates and sizes were the same with both reagents. Some persons with spherulin sensitivity reacted only to the mycelial reagent. Histoplasmin-CYL skin tests did not induce significant changes in complement-fixing antibody in histoplasmin-reactive subjects.

Antibodies, Fungal↗
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

Treatment of experimental murine cryptococcosis: a comparison of miconazole and amphotericin B.

Miconazole was compared with amphotericin B in the treatment of murine cryptococcosis. Both subcutaneous and intraperitoneal administration of miconazole produced serum levels higher than the minimum inhibitory concentration for the challenge strain. However, maximal tolerable doses of miconazole gave no increase in survival. When combined with amphotericin B, miconazole demonstrated neither additive nor antagonistic effects on survival. Spleen and brain counts of cryptococci were not lowered by miconazole; also, miconazole did not alter the effect of amphotericin B on reducing tissue counts. In vitro studies confirmed that the strain of Cryptococcus neoformans was quite susceptible to both miconazole and amphotericin B. However, miconazole had a delayed onset of antifungal activity. This was apparent even at miconazole levels 20 times greater than the minimum inhibitory concentration. Also, the antifungal activity of miconazole was markedly inhibited by serum. Delayed antifungal activity and serum inhibition may limit the in vivo effectiveness of miconazole in murine cryptococcosis.

Amphotericin B↗
PubMed1978

Delayed hypersensitivity responses of experimental animals to histoplasmin from the yeast and mycelial phases of Histoplasma capsulatum.

Controlled yeast lysate (CYL) and controlled mycelial lysate (CML) histoplasmins were produced from Histoplasma capsulatum grown in a nutritionally lean, chemically defined medium. The lysates were assayed for skin-test activity in guinea pigs sensitized by infection with the homologous organism. In some studies, nonliving vaccine preparations were employed also. Inter-lot biological variation was minimal, and 20 lots of the CYL reagent elicited strong dermal reactions with high specificity. Further, CYL reagents were nonreactive in guinea pigs infected with Coccidioides immitis, whereas the commercial Food and Drug Administration preparations cross-reacted to some degree. The CML histoplasmins were generally less reactive than the CYL preparations and exhibited somewhat more inter-lot variation in sensitivity and specificity. No correlation between potency and protein:polysaccharide ratios were observed with either reagent. An intradermal test with the CYL reagent did not induce significant changes in the complement-fixing titer of sensitized guinea pigs. Such changes in sensitized animals were elicited by a skin test with commercial histoplasmin.

Animals↗
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↗
PubMed1978

Successful treatment of cryptococcal meningitis with intraventricular miconazole.

A patient with cryptococcal meningitis retractory to amphotericin B was treated primarily with intraventricular miconazole. All parameters of disease improved, and the patient was dischared after four months of therapy. In selected persons with cryptococcosis, it may be possible to successfully utilize intraventricular miconazole in the absence of concurrent intravenous medication.

Amphotericin B↗
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↗