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Biomedical subjects

G M Cox

Publications and source records attributed to G M Cox.

36 records · Page 2Linked to original sources

Molecular methods for epidemiological and diagnostic studies of fungal infections.

Over the past two decades there has been a remarkable increase in the incidence of invasive fungal infections. Molecular methods, such as karyotyping, restriction analysis and polymerase chain reaction (PCR), have now been applied to improve our current understanding of the epidemiology of these fungal infections. For example, investigations on nosocomial outbreaks of fungal infections have been greatly facilitated by molecular methods. In addition, the ability to diagnose and identify deep-seated mycoses may be enhanced by the use of molecular techniques. In the near future it is possible that PCR-based methods will supplement, or perhaps even replace, traditional methods for detection of Candida albicans blood stream infections, invasive aspergillosis and Pneumocystis carinii pneumonia. This review examines the progress of molecular biology into the clinical arena of fungal epidemiology, laboratory identification and diagnosis.

DNA, Fungal↗

Oropharyngeal yeast flora and fluconazole resistance in HIV-infected patients receiving long-term continuous versus intermittent fluconazole therapy.

OBJECTIVE: To examine the impact of continuous versus intermittent fluconazole therapy on fungal colonization and fluconazole resistance in the oropharynx of HIV-infected patients. DESIGN: Case-control study. SETTING: Duke University Adult Infectious Diseases Clinic, a tertiary referral center in North Carolina which provides care for 700 HIV-infected persons. PATIENTS: Nineteen HIV-infected patients on daily continuous fluconazole for a minimum of 6 months and eleven HIV-infected patients on intermittent fluconazole for a minimum of 6 months were matched by sex and CD4 cell count to HIV-infected patients who had not received fluconazole in the preceding 6 months. MAIN OUTCOME MEASURES: Fungal isolation and fluconazole susceptibility testing were performed on oral saline rinses from each patient. RESULTS: The patients taking continuous fluconazole were more likely than matched controls to have had sterile mouth rinses (14 out of 19 versus five out of 19; P < 0.001), and the yeasts that were isolated were more likely than matched controls to be non-Candida albicans species and to have minimum inhibitory concentrations (MIC) to fluconazole > or = 16 micrograms/ml. None of these isolates were associated with symptoms. In contrast, none of the patients in the intermittent fluconazole group had sterile cultures. When this group was compared to controls, they were more likely to have had non-C. albicans species, and the C. albicans isolates obtained had higher MIC to fluconazole. CONCLUSIONS: Long-term continuous therapy with fluconazole may prevent the appearance of Candida in the oral cavity. This finding may reduce recurrence rates and might favorably impact on the clinical appearance of mucosal candidiasis with resistant C. albicans.

Adult↗

In vitro and in vivo efficacies of the azole SCH56592 against Cryptococcus neoformans.

Multiple isolates of Cryptococcus neoformans were tested to compare the in vitro activity of a new triazole, SCH56592, with those of amphotericin B, fluconazole, and itraconazole, MICs of each drug were determined, and minimum fungicidal concentrations of SCH56592 and amphotericin B were measured. MICs of SCH56592 were lower than those of amphotericin B and fluconazole but not those of itraconazole. Minimum fungicidal concentrations of SCH56592 were lower than those of amphotericin B. SCH56592 in the presence of human serum produces an in vitro fungicidal effect for Cryptococcus neoformans. The data indicate that SCH56592 might exert fungicidal as well as inhibitory properties in vivo. On the basis of these results, SCH56592 was evaluated with a rabbit model of experimental cryptococcal meningitis; SCH56592 treatment was compared with treatment with fluconazole. Despite no detectable drug concentrations in the cerebrospinal fluid, the activity of SCH56592 against C. neoformans infection was equivalent to that of fluconazole. SCH56592 has potent in vitro activity against C. neoformans and compares favorably to treatment with fluconazole for a central nervous system infection. SCH56592 should be studied for use in humans with cryptococcal infections.

Amphotericin B↗

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↗

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↗

The epidemiology of myasthenia gravis in central and western Virginia.

We conducted a study of the epidemiology of myasthenia gravis (MG) in four locations in central and western Virginia from 1970 through 1984. The population surveyed was 555,851 in 1984. A total of 73 new cases of MG occurred during the survey period, producing an overall average annual incidence rate of 9.1 per million. The point prevalence rate in 1980 was 13.4 per 100,000, and in 1984 it was 14.2. Approximately 15% of the population was black, and we found that incidence and prevalence rates for the black population were higher than the corresponding white population. When the population was subdivided into <50 and 50+ age groups, the incidence and prevalence were significantly higher in the older group. The rates we report here are higher than rates reported from any other locality. The reasons for the higher rates include optimal case identification, survey of a population with a higher incidence, and increasing aging of the population.

Adult↗

Genetic susceptibility to naevi--a twin study.

The risk of malignant melanoma to an individual is strongly related to their total number of benign melanocytic naevi. To investigate the possibility that numbers of naevi may have an inherited basis, naevi were examined in 23 monozygotic and 22 dizygotic twin pairs. A strong correlation in total numbers of naevi 3 mm or more in diameter was observed between MZ twins (intraclass correlation 0.83), but there was no significant correlation between DZ twins (correlation -0.24). There was no increased concordance in presence of naevi 5 mm or more over that expected by chance, for MZ or DZ twins. The results suggest a strong inherited basis for total naevus count and hence melanoma risk, perhaps involving a number of interacting genes.

Adult↗

A study of oral pain experience in sickle cell patients.

This study was designed to measure the degree of association between dental pain and its frequency during sickle cell crisis. Randomized study and control groups, each consisting of outpatient clinic patients, were selected. Each subject was interviewed via a questionnaire designed to record information describing immediate and past experiences of dental pain and its characteristics. The results were analyzed statistically. This investigation showed that there is an increase of dental pain, in the apparent absence of specific pathosis, in sickle cell patients during crisis. It was found that 36% of these patients had experienced some significant transitory pain in the oral-maxillofacial complex either alone or as part of the crisis syndrome.

Anemia, Sickle Cell↗

The actin gene from Cryptococcus neoformans: structure and phylogenetic analysis.

Using heterologous probing of a genomic library, we have cloned and sequenced the actin gene from the pathogenic yeast Cryptococcus neoformans. The actin gene is 1371 bp in length, and exists as a single copy, as is the case for all fungi studied to date. The locations of the introns in the C. neoformans actin gene are unique among all other known actin genes, and the deduced coding sequence results in a 375 amino acid chain with very high homology to other actins. A phylogenetic tree comprising 31 actin-coding sequences from a wide variety of organisms shows that the C. neoformans actin gene is grouped on a distinct branch together with all other known fungal actin sequences. The availability of the C. neoformans actin gene will aid future phylogenetic and molecular studies of this important human pathogen.

Actins↗

Syringe exchanges: a public health response to problem drug use.

This paper presents the findings of the first ever Irish follow-up study to establish the effectiveness of syringe exchanges as a harm reduction strategy in the context of public health. The study was conducted in collaboration with 370 injecting drug users who attended the Merchant's Quay Project's Health Promotion Unit between May 1st 1997 and October 31st 1998. Data was collected from respondents by means of a structured interview at first visit and three-months after initial contact. Evidence from the study demonstrates that syringe exchanges play an important contributing role in significantly reducing the numbers reporting both the use of heroin as a primary drug (n=41; McNemar x2=10.1;p<0.01), and its frequency of use (n=70; McNemar x2=4.13;p<0.05) at follow-up. Moreover, there were significant reductions in the reported borrowing (n=60; McNemar x2=10.1;p<0.01) and lending (n=42: McNemar x2=7.9;p<0.01) of used injecting equipment. There was however no significant change in the reported sharing of injecting paraphernalia or in levels of reported condom use. The results of this study illustrate that low threshold services such as the Health Promotion Unit have the ability to attract injecting drug users not in contact with other drug treatment services. Furthermore, this type of service has been shown to be effective in maintaining contact with injecting drug users and promoting safer drug use among attendees. Even though the distribution of sterile injecting equipment reduces the situational sharing, this is hampered by the limited availability of sterile injecting equipment in Dublin. There is a need to continue to develop strategies to prevent HIV and hepatitis C transmission. One such approach would be to develop effective outreach as a means of reaching greater numbers of drug users earlier in their injecting histories. Other areas for future HIV and HCV prevention include discouraging the transition from smoking to injecting, and among those who inject, encouraging further reductions in sharing, sustaining risk reduction over time, and encouraging the adoption of safer sexual behaviour.

HIV Infections↗

Dominant selection system for use in Cryptococcus neoformans.

Present transformation systems for Cryptococcus neoformans depend on complementation of auxotrophic mutants. We have developed a dominant selection system for transformation of wild-type strains of cryptococci in which resistance to the antibiotic hygromycin B is used as the selectable marker. A heterologous fusion gene construct was created by attaching the putative promoter sequence and start site from a cryptococcal actin gene to a truncated hygromycin B phosphotransferase gene from E. coli. Biolistic transformation with this construct resulted in cryptococci resistant to hygromycin B, and transformation efficiencies approached approximately 500 transformants per microgram DNA. The construct was found to exist in transformants as both extrachromosomal and integrative forms. The transformants with integrated constructs were stable both in vitro and in vivo, and constructs were recoverable from most transformed cells using a plasmid rescue technique. This is the first dominant selection system for use in C. neoformans, and it should prove useful for molecular studies with this important pathogenic yeast.

Actins↗