Biomedical subjects

J N Galgiani

Publications and source records attributed to J N Galgiani.

At least 109 records · Page 6Linked to original sources

PubMed1987

Coccidioidomycosis in the acquired immunodeficiency syndrome.

Of 27 patients with the acquired immunodeficiency syndrome (AIDS) in Tucson, Arizona, 7 had concurrent coccidioidomycosis. Early manifestations of infection in 6 patients included diffuse nodular pulmonary infiltrates and Coccidioides immitis in many extrathoracic sites. By comparison, a retrospective review of the cases of 300 patients hospitalized with coccidioidal infection identified only 13 patients without AIDS who had the same extent of infection, and only 3 of these patients had no immunosuppressing conditions. Antibodies for coccidioidal antigens at serum dilutions as high as 1:2048 were detected in 5 of the 7 patients with AIDS. Six had temporary responses to amphotericin B treatment, taken both alone and combined with ketoconazole, but all died within 14 months of their diagnosis of coccidioidomycosis. Because annual rates of coccidioidal infection in the Tucson area are 4% or less, the rate of 27% that we calculated, based on 7 patients having the infection during 26 years of risk for AIDS, suggests frequent reactivation of the infection or enhanced susceptibility to endemic exposure in persons with AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed1986

Susceptibility of Candida albicans to flucytosine when tested in different formulations of yeast nitrogen base broth.

The influence of various formulations of yeast nitrogen base broth and temperature on the flucytosine sensitivity of Candida albicans was examined. Each of 15 isolates was tested concurrently in yeast nitrogen base from two different suppliers, with or without supplemental dextrose and L-asparagine, and with incubation at either 30 degrees C or 37 degrees C. Observed differences were related to media source, media supplementation, and temperature of incubation. For all three variables, higher endpoint results were associated with greater rates of yeast growth as reflected by turbidity after 24 hr of incubation. Despite these differences, their magnitudes were sufficiently small so that variations in yeast nitrogen base formulation appear not to be an important source of imprecision in susceptibility testing of yeasts.

Candida albicans↗

PubMed1986

Inhibition of different phases of Coccidioides immitis by human neutrophils or hydrogen peroxide.

As arthroconidia of Coccidioides immitis transform into spherules, the fungal particles progressively become more resistant to the inhibitory effects of human polymorphonuclear leukocytes (PMNLs) as measured by PMNL inhibition of fungal incorporation of N-acetylglucosamine. Similar changes were noted when leucine incorporation was measured. When H2O2, at a concentration of 2.0 mM, was substituted for PMNLs, an equivalent inhibition of arthroconidia was produced and, as with PMNL effects, was lost with spherule maturation. The results from these studies indicate that C. immitis may evade natural inhibition by PMNLs by transformation into the spherule phase.

Acetylglucosamine↗

PubMed1986

Humoral antibody responses to specific antigens of Coccidioides immitis.

To identify antigens important to the diagnosis or pathogenesis of coccidioidomycosis, we analyzed three coccidioidal extracts by immunoblotting techniques with sera from patients infected with Coccidioides immitis and from immunized rabbits. When denatured fungal extracts were used, sera from at least 9 of 10 patients reacted with antigens of 100, 60, and 45 kilodaltons (kDa). By agar diffusion, the 100-kDa antigen appeared to be identical to the conventional tube precipitin antigen. Five of the six sera from patients with pulmonary syndromes reacted with another antigen of 70 kDa, but sera from patients with disseminated disease did not react with this antigen. Both the 100-kDa and the 70-kDa antigens were present in the 70-130-kDa region of the nondenatured fungal extracts. Our results suggest that the 100-kDa antigen may be useful in future diagnostic tests and that the 70-kDa antigen may identify patients whose infection is confined to the chest.

Antibodies, Fungal↗

PubMed1986

Phaeohyphomycosis caused by the fungal genera Bipolaris and Exserohilum. A report of 9 cases and review of the literature.

We have reported 7 new cases of Bipolaris infection and 2 of Exserohilum infection, which demonstrate the capability of these 2 genera to cause invasive as well as "allergic" disease. As noted previously, it is likely that all of the cases of "Helminthosporium" and Drechslera infections reported in the literature were caused by Bipolaris or Exserohilum. Infections due to these 2 genera are probably more common than previously recognized. They should be included in the differential diagnosis of central nervous system and disseminated fungal disease, sinusitis, keratitis, peritonitis associated with continuous ambulatory peritoneal dialysis, and allergic bronchopulmonary disease. These various entities have distinct histopathologic characteristics. With disseminated disease in the immunocompromised patient, the most frequent findings are acute inflammation with prominent vascular invasion, thrombosis, and infarction. In contrast, granulomatous inflammation and leukocytoclastic vasculitis are seen in meningoencephalitis caused by these fungi. The histologic features of allergic bronchopulmonary disease and sinusitis are similar. A chronic inflammatory infiltrate of lymphocytes, plasma cells and eosinophils within edematous granulation tissue is found in addition to squamous metaplasia and thickening of the basement membrane. Infections caused by Bipolaris/Exserohilum and Aspergillus show many clinical and pathologic similarities despite the lack of taxonomic relationship between these fungi. Both cause disseminated disease in immunocompromised patients that is characterized by tissue necrosis and vascular invasion. Both cause central nervous system disease, osteomyelitis, and sinusitis and are associated with allergic bronchopulmonary disease. Sinusitis, the most common form of disease caused by Bipolaris and Exserohilum, occurs in otherwise healthy patients with nasal polyposis and allergic rhinitis. Although pathologic evidence of bone invasion may not be found, there frequently is radiographic evidence of invasive disease. Most patients who are treated initially with surgical debridement and amphotericin B have apparently been cured. However, longer follow-up will be necessary in these patients. Amphotericin B appears to be the treatment of choice for invasive infections caused by Bipolaris/Exserohilum species. Ketoconazole and other imidazole derivatives may also be effective in certain of the disease entities caused by these black moulds; however, their role has yet to be defined.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1986

Activity of fluconazole (UK 49,858) and ketoconazole against Candida albicans in vitro and in vivo.

Fluconazole (UK 49,858), a new orally administered bis-triazole, was compared with ketoconazole for activity in synthetic broth dilution susceptibility tests against Candida albicans and also in treatment of experimental systemic candidal infections in rats. In vitro studies indicated that fluconazole activity is less sensitive to acidic medium than is that of ketoconazole. At physiologic pH, fluconazole was approximately 16-fold less active than ketoconazole against 35 representative isolates of C. albicans. Two additional isolates (K-1 and K-3) recovered from patients who had failed ketoconazole therapy were 32- to 64-fold more resistant than the median of each drug for other isolates. In animal studies, fluconazole was very effective in prolonging survival of rats infected with a representative candidal strain. With an inoculum sufficient to kill 29 of 38 sham-treated animals, only 1 of 18 animals treated with 0.5 mg of fluconazole per kg per day died compared with 13 of 20 animals treated with 10.0 mg of ketoconazole per kg per day. However, when similar fluconazole treatment was administered to rats infected with the more resistant strain, K-1, no prolongation of survival was found. Thus, in vivo and in vitro results between strains correlated well for fluconazole. However, in comparing results between drugs, ketoconazole was 16-fold more active in vitro and fluconazole was 20-fold more active in vivo. This discrepancy may be due to drug distribution, modes of drug metabolism, or other pharmacologic differences between the two agents.

Animals↗

PubMed1986

Results of a survey of antifungal susceptibility tests in the United States and interlaboratory comparison of broth dilution testing of flucytosine and amphotericin B.

In a survey of 350 laboratories, 41 of 210 respondents indicated that they performed antifungal susceptibility tests. Two-thirds performed 20 or fewer tests per year, and most used a broth dilution method to test amphotericin B and flucytosine activity against Candida albicans. The broth dilution procedure of S. Shadomy and A. Espinel-Ingroff (p. 647-653, in E.H. Lennette, ed., Manual of Clinical Microbiology, 3rd ed., 1980) was the method most frequently cited, and therefore this method was used to test the susceptibility of five isolates of C. albicans and one of Saccharomyces cerevisiae to amphotericin B and flucytosine in seven research laboratories. Agreement among replicates performed on the same day by each laboratory was excellent for both drugs, all values being within 1 twofold drug dilution. Precision from week to week for each laboratory was also good, with 95 and 92% of values being within 1 drug dilution for amphotericin B and flucytosine, respectively. Interlaboratory precision, however, was poor. For amphotericin B, values varied 8- to 32-fold, and for flucytosine, they varied 32- to greater than 512-fold. We conclude that antifungal susceptibility testing is currently being performed in small volumes by numerous laboratories in the United States and that results from one laboratory may not agree with results from another. Improved standardization of fungal susceptibility tests is necessary before their results can be generally applied to clinical situations.

Amphotericin B↗

PubMed1986

Development of dermal hypersensitivity to coccidioidal antigens associated with repeated skin testing.

Four antigens prepared from Coccidioides immitis were found to evoke no dermal reactions in 1,245 volunteers on first testing, but 2 months later, upon retesting, 18.6% of the subjects reacted to 1 or more of the antigens. In no subject did other findings indicate an intercurrent coccidioidal infection. Conversion of a skin test to reactive significantly (p less than 0.018) increased with subject age. No association was found with either years of residence within areas endemic for C. immitis or occupational exposure, associations that would be expected if conversion was due to latent hypersensitivity from a prior coccidioidal infection. Possible explanations for our findings include either boosting of immunity to a noncoccidioidal stimulus or primary sensitization from the skin testing itself. Until this phenomena is understood more fully, physicians should be reluctant to accept interval conversion of coccidioidal skin tests as a means of diagnosing recent coccidioidal infection.

Adolescent↗

PubMed1986

Coccidioides immitis infections in bones and joints.

Coccidioides immitis infections of bones and joints pose difficult problems in diagnosis and treatment. To evaluate further the diagnosis and treatment of this disease, a retrospective review was conducted of 24 patients with 44 separate skeletal lesions of C. immitis infection, as determined by positive culture. Patients treated with combined medical and surgical treatment are more likely to have a successful outcome than those treated with medical therapy alone (p less than 0.005). Although immunosuppression did not appear to prevent a satisfactory response to therapy, patients with a high complement fixation titer (greater than or equal to 1:128) were more likely to fail to respond to medical therapy alone (p less than 0.01).

Adult↗

PubMed1985

Studies of the effects of spherulin from Coccidioides immitis on human polymorphonuclear leukocytes.

The effects of spherule lysate (spherulin) on human polymorphonuclear leukocyte (PMN) function was examined. PMN adherence to glass and capping was increased by spherulin, findings which may account for spherulin's interference with complement-mediated migration through cellulose ester filters. In contrast, PMN attachment to yeast, killing of bacteria, and effects on spherules were virtually unaffected by spherulin, suggesting that it does not directly inhibit PMN antimicrobial function.

Antigens, Fungal↗

PubMed1985

Coccidioidomycosis at a university health service.

At a single university health service within an endemic area, 172 cases of coccidioidomycosis were retrospectively identified by fungal cultures, serologic studies, or intercurrent skin test conversions. The average annual incidence of symptomatic infection was 0.43% for susceptible students. Peak case rates occurred in November and June (11 cases/10,000 clinic visits) and were 1.5 to 6 times greater than in other months. Although mononucleosis was diagnosed approximately twice as frequently as coccidioidomycosis, coccidioidal infections required 74% more visits per patient and over 3 times longer clinical supervision than did mononucleosis. Although only 2 patients disseminated, diagnosis and management of patients with coccidioidomycosis constituted more than 2% of our clinic's visits, for an estimated annual cost of more than $34,000. Because our patient population is young and otherwise healthy, our estimates of the impact of primary coccidioidal infection may underestimate that on civilian public health as a whole.

Adult↗

PubMed1984

Human polymorphonuclear-leukocyte inhibition of incorporation of chitin precursors into mycelia of Coccidioides immitis.

Human polymorphonuclear leukocytes (PMNLs), when added to arthroconidial suspensions of Coccidioides immitis, markedly inhibit fungal incorporation of the cell-wall precursor N-acetylglucosamine. This effect does not require serum but is facilitated by a heat-labile serum component(s), probably by promoting PMNL attachment to the arthroconidia. Inhibition is entirely reversible within 24 hr. In parallel with this finding, PMNLs exhibited virtually no killing of arthroconidia and (as determined by electron microscopy) did not produce damage to the fungal ultrastructure. PMNLs from a patient with chronic granulomatous disease suppressed fungal incorporation of N-acetyl-glucosamine by only 0%-22% under various conditions, as compared with 54%-85% suppression by PMNLs from normal donors. Our studies demonstrate that PMNLs can influence the metabolism of C immitis and raise the possibility that their presence in coccidioidal histopathology may be an important immediate host defense in limiting progression early after infection.

Acetylglucosamine↗

PubMed1984

Ornithyl amphotericin methyl ester treatment of experimental candidiasis in rats.

After intravenous Candida albicans infection, rats received orinthyl amphotericin methyl ester, amphotericin B, or diluent intravenously. At doses of 0.1 and 0.5 mg/kg, the drugs were equally effective in preventing deaths. However, at doses of 2.0 mg/kg, mortality after treatment with amphotericin B was greater than that after placebo, whereas orinthyl amphotericin methyl ester was fully protective.

Amphotericin B↗

PubMed1984

Analysis of pH and buffer effects on flucytosine activity in broth dilution susceptibility testing of Candida albicans in two synthetic media.

We examined the influences of different pH levels and three different buffers on flucytosine activity against 12 isolates of Candida albicans in two synthetic media, yeast nitrogen base (YNB) and synthetic amino acid medium-fungal (SAAMF), using broth dilution techniques and measuring the endpoints of visual MICs and turbidimetric 50% inhibitory concentrations. The two media were originally prepared as follows: YNB, unbuffered, pH 5.6; SAAMF, buffered with morpholinepropanesulfonic acid-Tris, pH 7.4; the resultant geometric mean MIC and 50% inhibitory concentration of 5-FC were 78- and 32-fold higher, respectively, in SAAMF. Raising the pH of YNB or lowering the pH of SAAMF had virtually no effect on these differences in MIC and 50% inhibitory concentration in the two media. In contrast, virtually all of the discrepancy appeared to be due to morpholinepropanesulfonic acid-Tris, which exerted concentration-dependent inhibition of flucytosine activity not evident when N-2-hydroxyethylpiperazine-N'-ethanesulfonic acid or phosphate buffer systems were substituted. In other turbidimetric studies, growth was slowed more than 50% in YNB as the pH was raised to 7.4, regardless of which buffer was used. Based on our studies, we recommend modifying the composition of SAAMF by substituting a nonantagonistic buffer if any buffer is to be used with SAAMF in the testing of flucytosine. With this modification, SAAMF warrants further study as a generally applicable medium for fungal-susceptibility testing.

Buffers↗

PubMed1984

Pseudallescheria boydii infections treated with ketoconazole. Clinical evaluations of seven patients and in vitro susceptibility results.

Seven patients infected with Pseudallescheria boydii were treated with oral ketoconazole, 200 to 600 mg/day for one to 13 months. Five patients had pulmonary infections; two had skeletal infections. Improvement of pretreatment abnormalities occurred in five patients, one of whom had concurrent arthrodesis of his infected knee. The other two patients were subsequently healed by surgical resection of their pulmonary lesions. Ketoconazole appeared less active than miconazole against 22 clinical isolates of P boydii when tested by two in vitro methods. We conclude that ketoconazole is effective treatment for some patients infected with P boydii, although this may not be predicted by current in vitro susceptibility tests. Further experience is needed to establish the optimal use of ketoconazole with respect to its dosage, duration of administration and concurrent surgical resection.

Aged↗

PubMed1984

Antigenemia in primary coccidioidomycosis.

Clinical findings in patients with primary infection due to Coccidioides immitis have suggested that fungal antigenemia may occur. To study this possibility, we devised an inhibition enzyme-linked immunosorbent assay (ELISA) to measure antigenic activity compared to the activity of antigens derived from spherules. Twenty-one of 27 sera from 19 infected patients showed antigenic activity above that found in sera from uninfected persons. Activity was highest early in the course of illness. In other studies, anti-spherulin antibody activity was measured by ELISA, which demonstrated an association of antigen activity with IgM, but not IgG or IgA. One possible explanation for this phenomenon is that IgM antibody and antigen are present as circulating immune complexes.

Adolescent↗

PubMed1984

High-dose ketoconazole therapy and adrenal and testicular function in humans.

Ketoconazole, an oral antifungal, when given in conventional doses, transiently blocks testosterone synthesis and adrenal response to corticotropin. Higher therapeutic doses (ie, 800 to 1,200 mg/day), even once daily, caused more prolonged blockade. In some men, the serum testosterone concentrations were always subnormal. Bound and free testosterone values were equally diminished. Oligospermia and azospermia after prolonged therapy were noted. Impotence and decreased libido were found. Gynecomastia appeared more common than with lower doses. Depressed response to corticotropin was pronounced. Urine cortisol excretion was depressed. The blockade appeared related to the serum ketoconazole concentration. Instances of normal hormone levels or responsiveness were associated with low ketoconazole concentrations. The hormonal effects were generally unrelated to duration of therapy, although there may have been partial reversal with continued therapy. These effects appeared reversible with discontinuation of therapy. Patients receiving ketoconazole should be considered potentially unable to mount an adrenal stress response and may require testosterone supplementation.

Adrenal Glands↗

PubMed1983

Ketoconazole therapy for fungal urinary tract infections.

Ketoconazole was used in 11 patients to treat 12 episodes of fungal urinary infections: 6 in the upper urinary tract and 6 presumed to be in the lower urinary tract. Five patients had catheters in place. Of the 12 infections 8 were caused by Candida species, 1 by mixed Candida tropicalis and Torulopsis glabrata, and 3 by Torulopsis glabrata. Ketoconazole was administered orally at doses of 200 to 800 mg. per day for courses ranging from 5 days to more than 2 years. Five episodes of Candida urinary tract infection resolved in association with ketoconazole therapy, while only 1 of the Torulopsis glabrata infections improved. Our findings suggest that ketoconazole may be of some benefit in yeast urinary tract infections. However, the role of ketoconazole in relation to other antifungal drugs is not yet clear.

Adult↗