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J R Perfect

Publications and source records attributed to J R Perfect.

At least 91 records · Page 5Linked to original sources
PubMed1996

Fatal, disseminated Acremonium strictum infection in a neutropenic host.

Disseminated Acremonium strictum infection in a neutropenic patient is reported. Positive fecal cultures preceded positive cutaneous and blood cultures by 18 and 21 days, respectively, which suggests gastrointestinal colonization and invasion as initiating events. Microscopic examination of cutaneous biopsy and pulmonary specimens revealed hyphae, phialides, and phialoconidia in vivo. These adventitious forms also can occur in infections due to other phialidic fungi such as Fusarium and Paecilomyces species and can be misdiagnosed as Candida species. Budding cells also can occur in vivo for species of Fusarium, Paecilomyces, and apparently Acremonium, further adding to the potential for misdiagnosis. The occurrence of adventitious forms in infections caused by species of Acremonium, Fusarium, Paecilomyces, Scedosporium, and Blastoschizomyces is suggested as a mechanism for dissemination of infection and as an explanation of the relatively higher frequency of positive blood cultures in these cases.

Acremonium↗
PubMed1995

Cutaneous infection caused by Curvularia pallescens: a case report and review of the spectrum of disease.

A 75-year-old woman being treated with prednisone and methotrexate had a 5.5 x 2.2 cm ulcer on the leg. A biopsy specimen revealed suppurative, granulomatous dermal inflammation with necrotic areas of septate, branching hyphae containing brown pigment. Cultures grew Curvularia pallescens. Oral ketoconazole therapy was started and the lesion was excised. The site healed after multiple excisions and grafts, and ketoconazole therapy was stopped after 7 months. This is the first reported case of invasive cutaneous infection by C. pallescens.

Aged↗
PubMed1995

Cryptococcosis in the era of AIDS--100 years after the discovery of Cryptococcus neoformans.

Although Cryptococcus neoformans and cryptococcosis have existed for several millennia, a century has passed since the discovery of this encapsulated yeast and its devastating disease. With the advent of the AIDS pandemic, cryptococcal meningitis has emerged as a leading cause of infectious morbidity and mortality and a frequently life-threatening opportunistic mycosis among patients with AIDS. Both basic and clinical research have accelerated in the 1990s, and this review attempts to highlight some of these advances. The discussion covers recent findings, current concepts, controversies, and unresolved issues related to the ecology and genetics of C. neoformans; the surface structure of the yeast; and the mechanisms of host defense. Regarding cell-mediated immunity, CD4+ T cells are crucial for successful resistance, but CD8+ T cells may also participate significantly in the cytokine-mediated activation of anticryptococcal effector cells. In addition to cell-mediated immunity, monoclonal antibodies to the major capsular polysaccharide, the glucuronoxylomannan, offer some protection in murine models of cryptococcosis. Clinical concepts are presented that relate to the distinctive features of cryptococcosis in patients with AIDS and the diagnosis, treatment, and prevention of cryptococcosis in AIDS patients.

AIDS-Related Opportunistic Infections↗
PubMed1994

Targeted gene replacement demonstrates that myristoyl-CoA: protein N-myristoyltransferase is essential for viability of Cryptococcus neoformans.

Cryptococcus neoformans is a major cause of systemic fungal infection in immunocompromised patients. Myristoyl-CoA:protein N-myristoyltransferase (Nmt) catalyzes the transfer of myristate (C14:0) from myristoyl-CoA to the N-terminal glycine of a subset of cellular proteins produced during vegetative growth of C. neoformans. A Gly487-->Asp mutation was introduced into C. neoformans NMT by targeted gene replacement. The resulting strains are temperature-sensitive myristic acid auxotrophs. They are killed at 37 degrees C when placed in medium lacking myristate and, in an immunosuppressed animal model of cryptococcal meningitis, are completely eliminated from the subarachnoid space within 12 days of initial infection. C. neoformans and human Nmts exhibit differences in their peptide substrate specificities. These differences can be exploited to develop a new class of fungicidal drugs.

Acyltransferases↗
PubMed1994

Amphotericin B lipid complex in the treatment of experimental cryptococcal meningitis and disseminated candidosis.

In the quest for safer and more effective antifungal agents, amphotericin B (AMB) has been placed in a variety of lipid preparations. In this study, we examined the efficacy of amphotericin B lipid complex (ABLC) on experimental cryptococcal meningitis and disseminated candidosis. This formulation is relatively safe compared to the parent compound, and therefore doses ten times greater than the commercial amphotericin B deoxycholate can be given to rabbits. Although at equal doses the ABLC preparation is less potent than AMB, a higher dose of ABLC was rapidly fungicidal in the contexts of both a central nervous system infection with Cryptococcus neoformans during immune suppression, and a heart and kidney infection with Candida albicans. Rapid sterilization of tissue should be a goal of antifungal drug therapy, particularly in the immune compromised host. From these studies, this AMB lipid formulation has the ability to produce rapid fungicidal activity in vivo, but it requires higher doses than AMB deoxycholate. Clinical trials in humans must examine carefully the therapeutic-toxic ratio in dose-escalation protocols to determine the optimal dosage strategy for this agent.

Amphotericin B↗
PubMed1994

First report of involvement of Nodulisporium species in human disease.

Allergic fungal sinusitis is a common disease that results from a hypersensitivity reaction mounted by the host against fungi living in the paranasal sinuses. We have recently treated a patient with allergic fungal sinusitis due to a Nodulisporium species. This is the first description of a Nodulisporium species involved in human disease. The genus Nodulisporium contains both dematiaceous and nondematiaceous members. These fungi occur worldwide in nature, often as accompanying conidial anamorphs of certain wood decay ascomycetes. Clinical mycology laboratories may encounter this new agent of phaeohyphomycosis.

Adult↗
PubMed1993

Uncommon invasive fungal pathogens in the acquired immunodeficiency syndrome.

This communication lists fungi reported to cause invasive infection in patients with AIDS. It excludes the well known and common fungi that infect these patients such as Candida, Cryptococcus, Histoplasma, Coccidioides and Aspergillus. It is likely that these less common fungal pathogens will be seen more frequently in the enlarging AIDS population as it is continuously exposed to many of these potentially opportunistic fungi.

AIDS-Related Opportunistic Infections↗
PubMed1993

Cryptococcal ventricular-peritoneal shunt infection: clinical and epidemiological evaluation of two closely associated cases.

OBJECTIVE: To determine the cause of meningitis associated with Cryptococcus neoformans in two patients with recent ventricular-peritoneal (VP) shunt placement. DESIGN: A retrospective review of materials, records, and concurrent cases of VP shunt procedures. Isolates of C neoformans from each patient were submitted for analysis by colony morphology, biochemical testing, and karyotyping by pulsed-field electrophoresis. SETTING: Two 400-bed community hospitals. PATIENTS: Two immunocompetent patients presented with symptoms of progressive hydrocephalus in August 1991. Each received a VP shunt on the same day by the same surgeon using materials from a common vendor and hospital. RESULTS: Both patients presented within six to eight weeks with symptoms of fever, headache, rash, and cultures of cerebrospinal fluid (CSF) that yielded C neoformans. Each patient recovered after therapy with amphotericin B and flucytosine followed by several months of fluconazole, although one required replacement of the VP shunt for cure. Review of each patient's history and CSF characteristics at the time of shunt placement suggested reactivation of a preexisting infection. Isolates of C neoformans from each patient were submitted for analysis by colony morphology, biochemical testing, and karyotyping by pulsed-field electrophoresis. Each isolate was found to be unique by chromosomal karyotyping. CONCLUSIONS: Our data and previous reports suggest that cryptococcal VP shunt infections appear to be a complication of shunts placed in previously infected persons rather than nosocomial transmission of cryptococcus during placement.

Adult↗
PubMed1993

Correlation of in vitro fluconazole resistance of Candida isolates in relation to therapy and symptoms of individuals seropositive for human immunodeficiency virus type 1.

Yeast strains isolated from the oropharynx of 87 consecutive patients infected with human immunodeficiency virus type 1 were examined for in vitro susceptibility to fluconazole. Candida albicans was isolated from 73 patients. Fifty-one patients had received antifungal therapy in the month preceding the yeast infection. Thirty-two patients had symptomatic oropharyngeal candidiasis. The MICs were correlated with azole use and with clinical symptoms and signs. Although there is overlap between groups, in vitro testing identified a large group of patients for whose yeast isolates the fluconazole MICs were high and who remained symptomatic while receiving azole therapy. This study supports the ability of in vitro testing to predict the clinical outcome of mucosal fungal infections. The study also demonstrates that azole resistance of oropharyngeal yeasts is a common problem in patients infected with human immunodeficiency virus type 1 and that this azole resistance has clinical relevance.

Adult↗
PubMed1993

Uptake of itraconazole by alveolar macrophages.

Itraconazole is a broad-spectrum potent triazole antifungal agent. Its efficacy in treatment cannot always be explained by body fluid drug levels. In this study, itraconazole was shown to accumulate into host cells. Its intracellular accumulation in cells is greater than that of the antibacterial agent clindamycin, which is known for intracellular localization, and the uptake process does not appear to be active. This ability to reach high concentrations intracellularly may be an important property for the in vivo efficacy of itraconazole.

Animals↗
PubMed1993

The gene encoding phosphoribosylaminoimidazole carboxylase (ADE2) is essential for growth of Cryptococcus neoformans in cerebrospinal fluid.

A cryptococcal meningitis model in corticosteroid-treated rabbits was used to assess the requirement for the phosphoribosylaminoimidazole gene (ADE2) for virulence of Cryptococcus neoformans. A wild-type strain (H99), an ade2 auxotroph of H99 (M001), and a randomly selected prototrophic transformant of M001 (M001.1c) which had received the cloned ADE2 cDNA copy were inoculated intrathecally into immunosuppressed rabbits. While M001 was avirulent in the central nervous system model, virulence was completely restored to wild-type pathogenicity in the prototrophic transformant. This study identifies the pathogenic importance of an endogenous adenine pathway in this yeast and confirms that purine biosynthesis is a potential target for antifungal therapy. It also demonstrates that the virulence of C. neoformans can be molecularly changed and detected within a clinically relevant animal model.

Animals↗
PubMed1993

Gene transfer in Cryptococcus neoformans by use of biolistic delivery of DNA.

A transformation scheme for Cryptococcus neoformans to yield high-frequency, integrative events was developed. Adenine auxotrophs from a clinical isolate of C. neoformans serotype A were complemented by the cryptococcal phosphoribosylaminoimidazole carboxylase gene (ade2) with a biolistic DNA delivery system. Comparison of two DNA delivery systems (electroporation versus a biolistic system) showed notable differences. The biolistic system did not require linear vectors and transformed each auxotrophic strain at similar frequencies. Examination of randomly selected transformants by biolistics showed that 15 to 40% were stable, depending on the recipient auxotroph, with integrative events identified in all stable transformants by DNA analysis. Although the ade2 cDNA copy transformed at a low frequency, DNA analysis found homologous recombination in each of these transformants. DNA analysis of stable transformants receiving genomic ade2 revealed ectopic integration in a majority of cases, but approximately a quarter of the transformants showed homologous recombination with vector integration or gene replacement. This system has the potential for targeted gene disruption, and its efficiency will also allow for screening of DNA libraries within C. neoformans. Further molecular strategies to study the pathobiology of this pathogenic yeast are now possible with this transformation system.

Blotting, Southern↗
PubMed1993

Karyotyping of Cryptococcus neoformans as an epidemiological tool.

Karyotyping of Cryptococcus neoformans var. neoformans can be used as an epidemiological tool for C. neoformans infections. In this study of over 40 isolates from both clinical and environmental sources, 90% had a unique chromosome banding by pulsed-field electrophoresis. There was no conserved pattern associated with body site of infection, geographical location of the isolate, or human immunodeficiency virus status. Karyotypes of individual isolates remained stable during both in vitro passage and in vivo infections. Karyotype was used to exclude the possibility of nosocomial spread of C. neoformans in one clinical situation and supported relapse in two other cases. Because of its variable sizes between isolates, karyotyping of C. neoformans is a convenient method for molecular identification of different strains.

AIDS-Related Opportunistic Infections↗
PubMed1992

Cloning the Cryptococcus neoformans TRP1 gene by complementation in Saccharomyces cerevisiae.

We have cloned the phosphoribosyl anthranilate isomerase (PRAI)-encoding gene (TRP1) of Cryptococcus neoformans by genetic complementation in Saccharomyces cerevisiae. Sequence analysis of this gene revealed it to be 939 bp in length, and without known promoter or termination sequences. Unlike some of the filamentous fungi, where PRAI enzymatic activity is controlled by a trifunctional gene product, the C. neoformans PRAI appears to be unifunctional. PRAI of C. neoformans exhibits 39% amino acid (aa) sequence identity compared to the S. cerevisiae counterpart. The TRP1 gene of C. neoformans maps to different size chromosomes in strains with different serotypes. The cloning of this gene for vector constructions, and the demonstration that S. cerevisiae can be used as a surrogate for C. neoformans gene expression, should help with the molecular studies of this significant fungal pathogen in our increasing immunocompromised population.

Aldose-Ketose Isomerases↗
PubMed1992

A nationwide survey of clinical laboratory methodologies for fungal infections.

Many hospitalized patients are at risk for fungal infections. In order to characterize present clinical laboratory experience and facilities for diagnosis and management of fungal infections, a nationwide survey of laboratory diagnostic methodologies was conducted. Data from calendar year 1988 were collected from 71 institutions (52 university teaching hospitals and 19 community hospitals) enrolled in the Drug Surveillance Network. Surveyed hospitals received 75,828 specimens for fungal culture in 1988, representing 18,705 positive cultures from 7373 patients. About 1.3% of patients admitted to teaching or community hospitals had positive fungal cultures, the most common isolates being Candida species. Yeast identification was most commonly performed by the germ tube test and carbohydrate assimilation testing. Dimorphic fungi were identified to the species level at 67% of hospitals. Cryptococcal antigen testing was available at all hospitals, and Candida serology testing was done at 55 institutions. A small number of hospitals performed antifungal drug concentration determinations for amphotericin B (n = 9), ketoconazole (n = 7) and flucytosine (n = 12). Fungal susceptibility testing was available at 77% of hospitals, either within the institution or at an external laboratory. Laboratory testing for diagnosis and management of fungal infections represents a major laboratory investment. Proficiency in this area, along with expert clinical advice, will be needed to advance therapy of patients complicated with fungal infections during the next decade.

Fungi↗
PubMed1992

Prophylactic intravenous amphotericin B in neutropenic autologous bone marrow transplant recipients.

This study assessed the efficacy, toxicity, and pharmacology of low-dose amphotericin B given prophylactically to patients (serum concentrations of 0.2-0.4 microgram/ml) undergoing bone marrow transplantation. Yeast isolates from patients' oropharyngeal areas had MICs of 0.1-0.2 microgram/ml, and none were amphotericin B resistant. The effect of low-dose amphotericin B on reducing the numbers of yeast colonizing the oropharyngeal area was significant (P less than .01). The average delay in switching to high-dose prophylactic amphotericin B was only 1 day; the decision to do so because of a perceived fungal infection occurred more frequently for the placebo group (P = .06). Fewer patients from the low-dose amphotericin B group (8.8%) than from the placebo group (14.3%) had fungi isolated from normally sterile body sites (P = .35). Infusion-related side effects but not systemic toxicities were significantly greater (P less than .001) in the amphotericin B group. The 6-week survival was greater in those receiving amphotericin B (P less than .03), but the improved survival could not be attributed to the prevention of fungal infections.

Adult↗