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Biomedical subjects

J N Galgiani

Publications and source records attributed to J N Galgiani.

At least 127 records · Page 7Linked to original sources
PubMed1983

Ketoconazole inhibition of testicular secretion of testosterone and displacement of steroid hormones from serum transport proteins.

In vivo perfusion of canine testes with ketoconazole inhibited the stimulation of testosterone production by human chorionic gonadotropin in a dose-dependent manner. Ketoconazole also selectively displaced steroids from serum-binding globulins. Dihydrotestosterone and estradiol binding to sex hormone-binding globulin were inhibited by ketoconazole. Cortisol binding to corticosteroid-binding globulin was unaffected. The concentrations of ketoconazole that inhibited human chorionic gonadotropin stimulation of testicular androgen production and displaced sex steroids from sex hormone-binding globulin were in the range of blood levels found in patients on higher therapeutic dosage regimens. Suppression of testicular testosterone synthesis and displacement of estrogens from sex hormone-binding globulin may decrease the androgen/estrogen ratio of the blood and contribute to the development of gynecomastia that has been reported in some ketoconazole-treated patients.

Animals↗
PubMed1983

Comparison of immunodiffusion techniques with standard complement fixation assay for quantitation of coccidioidal antibodies.

Quantitative immunodiffusion (QID) and complement fixation (CF) methods were compared for their agreement in detecting coccidioidal antibodies. For these studies, we assayed 719 sera from 181 patients with coccidioidomycosis. Over 60% of the specimens had CF results of 1:2 to 1:256. A total of 43 patients had five or more specimens obtained over periods of between 1 and 8 years. The QID method, as originally performed, agreed within a twofold dilution of the CF titer in 191 of 267 sera (71.5%). Modification of QID by repeated filling of the antigen and serum wells improved agreement to 84.7% (383 of 452 sera). The degree of CF titer change in patients over time periods was more closely matched by the modified than by the original QID method. Discrepancies between the CF and QID methods appeared not to be due to a subpopulation of patients. QID measurement of coccidioidal antibodies may be a useful substitute for the CF assay in certain clinical laboratories.

Antibodies, Fungal↗
PubMed1983

Ketoconazole in the treatment of coccidioidomycosis.

Ketoconazole is the newest antifungal agent evaluated for efficacy in the treatment of coccidioidomycosis and the only one used by oral administration. The inhibition of Coccidioides immitis observed by in vitro susceptibility testing has been corroborated in murine studies in which ketoconazole therapy has led to survival in otherwise lethally infected animals. In man, absorption of ketoconazole from the gastrointestinal tract is generally favourable. However, there is considerable variation between patients in achieved serum concentrations, the causes of which may be multiple and as yet are incompletely understood. All completed studies of ketoconazole treatment of human coccidioidomycosis have been non-comparative in design. Entry criteria have selected patients that would have been treated otherwise with another antifungal agent. Dosages were usually 200 or 400 mg/day and treatment was continued for many months. Soft tissue infections improved more frequently and after less ketoconazole than did pulmonary or skeletal infections. No effect on coccidioidal meningitis has been found at these dosages. In skeletal infections, symptoms, physical findings and coccidioidal antibody levels commonly improved, but radiographs of skeletal lesions frequently did not change. Repeat culture of treated lesions, even those that had improved, often continued to grow C. immitis. Relapses after stopping ketoconazole have occurred in a significant number of patients. Untoward effects were usually manageable without discontinuing therapy. Ketoconazole appears to be of use in the treatment of progressive forms of coccidioidomycosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1982

Ketoconazole treatment of nonprimary coccidioidomycosis. Evaluation of 60 patients during three years of study.

Sixty patients with coccidioidomycosis were treated with ketoconazole rather than with another antifungal agent, and their responses were evaluated in relation to the predominant site of involvement. For the three main groups, improvement occurred in 12 of 19 patients with chronic pulmonary infections, in 20 of 23 with soft tissue lesions and in six of 11 with skeletal involvement. Infections in soft tissues improved most rapidly (average of 34 days) and often with 200 mg per day, whereas pulmonary and skeletal infections improved more slowly (63 and 165 days, respectively), usually requiring 400 mg per day. Of 12 patients with response in whom therapy has been discontinued, seven have had relapses. Recurrence was apparent usually within the first month and after six months or less of treatment. Patients in remission had received ketoconazole for six to 17 months. Untoward drug effects included abdominal complaints (23 percent) and gynecomastia (8 percent). Therapy was discontinued in only three patients for side effects. Our findings support the use of ketoconazole in the treatment of certain forms of chronic coccidioidal infections.

Bone Diseases↗
PubMed1982

Leukocyte effects on the dimorphism of Coccidioides immitis.

To assess the influences of leukocytes on the dimorphism of Coccidioides immitis, mycelial elements (arthroconidia) or spherules were incubated with polymorphonuclear leukocytes (PMNLs) or mononuclear leukocytes. In the presence of human leukocytes, arthroconidia became separated spherules as determined by electron microscopy but grew as mycelia when viable leukocytes were absent. Plasma was not required for this effect. In a new assay, PMNLs, lymphocytes, or monocytes from human blood as well as rabbit alveolar macrophages inhibited spherules from forming germ tubes. In flat-bottomed glassware, maximal inhibition occurred with PMNL:spherule ratios above 15:1, whereas in conical-bottomed glassware a ratio of 3:1 was maximally suppressive with PMNLs as well as mononuclear leukocytes. Cytochalasin B and colchicine blocked the effect of PMNLs but not that of other blood leukocytes on spherules. These studies indicate that leukocytes influence coccidioidal dimorphism toward the spherule phase. This effect may be important in host defenses against C. immitis.

Coccidioides↗
PubMed1982

Disposition of ketoconazole, an oral antifungal, in humans.

The pharmacology of ketoconazole was studied in patients with fungal infections. After administration of 50-, 100-, and 200-mg doses of ketoconazole, there was a linear increase in the area under the curve of serum concentrations; this was not apparent when higher doses of ketoconazole were given. An increase in the area under the curve occurred in patients receiving 200 mg daily who were restudied after 1 to 12 months of therapy. However, normalized area under the curve appeared to decrease after higher doses were administered chronically. The half life ranged from 2.0 to 3.3 h. Peak serum concentrations up to 50 micrograms/ml were detected in this study, and potentially therapeutic concentrations were detectable up to 26 h after high doses. Ketoconazole penetrated the saliva and inflamed joint fluid and meninges, although variably, and could be demonstrated in some other tissue compartments. In the presence of renal failure, ketoconazole disposition was not altered, whereas in the presence of hepatic insufficiency, an alteration in disposition was suggested. The interactions of ketoconazole and other drugs were studied. Of note, antacids did not significantly affect ketoconazole pharmacokinetics (nor did meals), and ketoconazole and warfarin did not appear to affect the pharmacokinetics of the other.

Administration, Oral↗
PubMed1982

The incidence and implications of coccidioidouria.

To estimate the frequency and significance of isolating Coccidioides immitis from urine specimens, we reviewed the records of 75 patients with various forms of coccidioidomycosis of whom 29 had urine cultures for fungi. The 7 patients (24%) who had coccidioidouria appeared similar as a group to those whose cultured urine did not yield C. immitis. Over half of the patients had no other evidence of extrathoracic spread, and in 2 patients with coccidioidouria, illness resolved without treatment. Usually only a few colonies of the fungus were isolated from 200-ml specimens. Thus, our use of a concentrating technique and repeated sampling may account for the high incidence of coccidioidouria in this study. Isolating C. immitis from the urine may be helpful for diagnosis and should lead to further evaluation of the urinary tract for destructive parenchymal lesions. However, as an isolated finding, coccidioidouria does not always indicate the need for therapy.

Adolescent↗
PubMed1982

Coccidioidomycosis in renal replacement therapy.

The potential risk of coccidioidomycosis has led to concern about the advisability of maintaining renal transplantation programs in endemic areas. We reviewed the charts of 721 patients undergoing dialysis and 260 renal transplant recipients in Arizona to determine the incidence, risk factors, and clinical course of coccidioidomycosis in these immunosuppressed populations. Symptomatic infection occurred in six (0.83%) patients undergoing dialysis and 18 (6.9%) transplant recipients. Male sex and blood type B predisposed to dissemination. Urine cultures for fungus were important diagnosis aids. Four of six patients with infection limited to the thorax and five of 18 patients with dissemination remained alive after seven months to 7 1/2 years. Although the rate of dissemination (75%) and mortality (63%) from coccidioidomycosis were high, the incidence of infection was low and does not preclude renal transplantation in Arizona. Those who have received transplants elsewhere should be advised not to move or to visit areas endemic for coccidioidomycosis.

ABO Blood-Group System↗
PubMed1981

Prevalence of chorioretinal scars associated with coccidioidomycosis.

A retrospective study was conducted to determine the prevalence and spectrum of chorioretinal involvement among individuals with previously documented systemic coccidioidomycosis. Fifty-four subjects were given a modified ocular examination, and their medical records were abstracted for clinical classification of the disease and its correlation with ocular findings. Five of 54 subjects with documented past infection with Coccidioides immitis had characteristic inactive peripheral chorioretinal scars. No relationship between the presence of scars and the extent of disease was evident; typical scars were found in patients who had experienced mild respiratory tract infection as well as in more extensively disseminated disease. We conclude that dissemination of C immitis to the eye can occur during benign pulmonary coccidioidomycosis as well as with more severe systemic disease, and the prevalence of chorioretinal lesions is more common than isolated case reports would indicate.

Adolescent↗
PubMed1981

Simultaneous tuberculosis and coccidioidomycosis in end stage renal disease.

During a ten year period, tuberculosis and coccidioidomycosis occurred in less than one and three percent respectively of 380 patients who had received dialysis and renal transplants in Southern Arizona. In two patients, who were immunosuppressed by diabetes, renal failure, and inanition, these infections were concurrent and diagnosis was delayed. Because the occurrence of both illnesses in two patients is unlikely by chance alone and because both infections were present when symptoms developed, potentiation of one infection by the other may have occurred.

Coccidioides↗
PubMed1981

Gynecomastia with ketoconazole.

Three of forty men developed bilateral gynecomastia upon ketoconazole treatment. Symptoms abated despite continued therapy. This appears to be a direct drug effect on breast tissue.

Adult↗
PubMed1980

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↗
PubMed1980

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↗
PubMed1979

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↗