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Biomedical subjects

E G Evans

Publications and source records attributed to E G Evans.

At least 19 recordsLinked to original sources
PubMed1992

Short term treatment of dermatophyte onychomycosis with terbinafine.

OBJECTIVE: To evaluate the effect of short term treatment with terbinafine on dermatophytosis. DESIGN: Multicentre, randomised, double blind placebo controlled trial of 250 mg/day terbinafine for 12 weeks in dermatophyte onychomycosis. SETTING: Eight dermatology centres in the United Kingdom. PATIENTS: 112 patients (mean age 44, range 19-78), 99 with mycologically proved toenail infections and 13 with fingernail infections, of whom eight were subsequently excluded and 19 failed to complete the study. INTERVENTION: Terbinafine 250 mg daily or placebo for 12 weeks. Follow up for 36 weeks after stopping treatment. MAIN OUTCOME MEASURES: Mycological cure (negative results on microscopy and culture) and clinical cure at the end of follow up, adverse events, and biochemical and haematological variables at monthly intervals during treatment. RESULTS: After follow up 82% (37/45) (95% confidence interval 68% to 92%) mycological cure and 69% clinical cure were recorded for evaluable patients treated with terbinafine for toenail infection and 71% (5/7) (30% to 96%) mycological cure and clinical cure for those treated for fingernail infection. The corresponding values for those treated with placebo were 12% (3% to 31%) mycological cure and no clinical cure for toenail infections and 33% (1% to 91%) mycological cure and no clinical cure for fingernail infections. On an intention to treat basis for toenail infections the figures were 73% (38/52) (58% to 85%) mycological cure for terbinafine compared with 6% (0% to 30%) for placebo (p less than 0.007). Two withdrawals were related to adverse events with terbinafine, and there were no significant abnormal laboratory test results. CONCLUSION: 12 weeks' terbinafine is effective and safe treatment for nail dermatophytosis.

Adult↗
PubMed1992

Nomenclature of fungal diseases: a report and recommendations from a Sub-Committee of the International Society for Human and Animal Mycology (ISHAM).

The ISHAM Mycoses Nomenclature Committee has considered the present status of fungal disease names. It suggests that the traditional approach to mycoses nomenclature in which the name of a causative taxon is suffixed with '-asis', '-iasis', '-osis' or '-mycosis' leads to names that are frequently unstable with respect to subsequent taxonomic and clinico-epidemiological changes. It is therefore recommended that individual mycoses should be named as often as possible in the form 'pathology A due to/caused by fungus X' or '[adjectival] fungus X pathology A' in preference to construction of names based solely on fungal taxa. A list of recommended mycosis names retained for their long tradition or intrinsic convenience is provided, together with a combined index and list of rejected names.

Animals↗
PubMed1992

A prospective study of life stress, social support, and adaptation in early adolescence.

This study employed a 2-year longitudinal design to examine the relation of stressful life events and social supports to psychological distress and school performance among 166 early adolescents (mean age = 13.5 years). A prospective approach was utilized to control for initial levels of adjustment when examining the relation of Time 1 stress and support variables to Time 2 psychological distress and school performance. Both stress and support variables made significant contributions to the prediction of subsequent psychological distress. Stresses, but not supports, made a significant contribution to the prediction of subsequent school performance. Evidence for reciprocal and interactive linkages was also found, including effects of psychological distress and school performance on subsequent stresses and supports, and greater adaptive impact of school-based supportive resources under conditions of heightened risk outside of school. Implications for ecological and transactional models of development relating to the targeting and efficacy of preventive efforts are discussed.

Adaptation, Psychological↗
PubMed1992

Candida strains from neonates in a special care baby unit.

Carriage and acquisition of Candida spp and Candida albicans biotypes were studied among 163 neonates and 90 staff in a neonatal intensive care and surgical unit during a 17 week period. Twenty one neonates carried yeasts in the mouth, rectum or groin when first sampled, and a further 25 were positive later. C albicans accounted for 94.7% of 431 yeast isolates from neonates but only 67.4% of 43 isolates from staff. The first isolated C albicans biotype persisted in 13 babies monitored longitudinally. Simultaneous colonisation with two Candida spp was found in 2/46 neonates and 5/33 staff. The prevalence of candida was significantly higher among babies of gestational age less than 28 weeks (65%) than those of higher gestational age (26%). Oral and/or crural candida infection was observed in 14 of the babies but none developed deep seated candidosis. Routine antifungal prophylaxis did not affect the frequency of yeasts among the neonates.

Adult↗
PubMed1992

Primary cutaneous zygomycosis due to Absidia corymbifera in a patient with AIDS.

A case of primary cutaneous zygomycosis due to Absidia corymbifera in a patient with AIDS is described. The lesions, which were located on the forehead, jaw and chest, were intradermal, extending into the subcutaneous fat and did not appear to be associated with any trauma. No deep-seated infection was evident suggesting that the superficial lesions were exogenous in origin. The possible aetiology of this infection is discussed.

AIDS-Related Opportunistic Infections↗
PubMed1992

A new, sensitive polynucleotide probe for distinguishing Candida albicans strains and its use with a computer assisted archiving and pattern comparison system.

The repetitive DNA sequence poly[d(GT).d(CA)],(polyGT) can be used to generate DNA fingerprints that distinguish different yeast genera. In this study we demonstrate that the probe can also be used to distinguish individual strains of clinical isolates of Candida albicans. Isolates were fingerprinted by probing Southern blots of restriction enzyme-cleaved DNA samples with radioactively labelled polyGT. The discrimination between strains was clearer than can be achieved by direct visualization of ethidium bromide stained gels and was comparable to that achieved with previous DNA probes. However, the advantage of this probe is that it is not limited to Candida species since polyGT sequences appear to be ubiquitous in eukaryotes. Fingerprints were also generated from Southern blots using a commercial (AMBIS) radioanalytical imaging computer system. A proprietary software package (MICRO PM) was effective in discriminating between the C. albicans strains. These preliminary results indicate the potential value of this probe for discrimination between Candida isolates in epidemiological studies of candidosis.

Blotting, Southern↗
PubMed1991

Mannan estimation as a measure of the growth of Candida albicans.

Determination of Candida albicans mannan levels by an enzyme-linked immunosorbent assay was compared with dry weight measurement and viable counting as a means to estimate growth of the fungus in broth cultures. Levels of extracted mannan showed good correlation with fungal biomass (dry weight) (r = 0.984) and, although biomass and mannan levels correlated with viable counts, the correlation was not as strong (r = 0.954-0.959). The technique offered an accurate alternative to viable counts in the brain and kidney when mannan estimation was used to follow the distribution of C. albicans in an experimental model of systemic candidosis in mice. Mannan levels were less useful in following the course of the infection in the liver and spleen where accumulation of free and serum-bound mannan was a problem. Mannan estimation would therefore seem to offer an accurate alternative to viable counts for determining the quantity of Candida both in vitro and in certain infected organs of experimental animals, where measurement of fungal biomass is not feasible and viable counts can be grossly inaccurate.

Animals↗
PubMed1991

Candida cell wall mannan in the vagina and its association with the signs and symptoms of vaginal candidosis.

Measurement of Candida cell wall polysaccharide (mannan) with an enzyme-linked immunosorbent assay (ELISA) was evaluated as an alternative to viable counting for the enumeration of yeast cell numbers in the human vagina. A statistically significant association was found between mannan levels and the number of colony forming units in vaginal washings collected from 40 women infected with Candida albicans (r = 0.81), indicating the accuracy of mannan levels in reflecting yeast cell load in vulvo-vaginal candidosis. Subsequent comparisons revealed a significant association between mannan levels and clinical signs in the vagina, so reflecting the importance of vulvitis and vaginitis as clinical markers for determining the severity of infection. No association was found between yeast load and the clinical symptoms, indicating the high degree of patient subjectivity. Estimation of mannan levels could be developed and used for the rapid laboratory investigation of chronic vulvo-vaginal candidosis.

Candida albicans↗
PubMed1991

Successful 2-week treatment with terbinafine (Lamisil) for moccasin tinea pedis and tinea manuum.

A new orally active antifungal agent, terbinafine, was used in the treatment of tinea pedis ('dry type' or moccasin type) and tinea manuum. Fifty-three adults over the age of 16 years with fungal infections of the feet and/or hands were treated with either oral terbinafine, 250 mg, or placebo, once daily for 2 weeks. The diagnosis of fungal infection was confirmed by examination of skin scrapings by microscopy and culture. Of these, 28 patients were evaluable for efficacy. At 8 weeks, 12 out of 14 (86%) patients who received terbinafine were mycologically negative (microscopy and culture) compared to one out of 14 (7%) patients on placebo (P less than 0.001, Fishers exact test, one-sided). At the end of the study 71% of patients in the terbinafine group were judged to have received effective therapy compared to 0% in the placebo group (P less than 0.001). Terbinafine was well tolerated, and more side-effects were seen in the placebo group.

Adult↗
PubMed1990

Interaction of azole antifungal antibiotics with cytochrome P-450-dependent 14 alpha-sterol demethylase purified from Candida albicans.

The interaction of azole antifungal antibiotics with purified Candida albicans cytochrome P-450-dependent 14 alpha-sterol demethylase (P-450DM) was measured spectrophotometrically and by inhibition of enzyme activity. Ketoconazole and ICI 153066 (a triazole derivative) formed low-spin complexes with the ferric cytochrome and induced type II difference spectra. These spectra are indicative of an interaction between the azole moiety and the sixth co-ordination position of P-450DM haem. Both azoles inhibited the binding of CO to the sodium dithionite-reduced ferrous cytochrome, and inhibited reconstituted P-450DM activity by binding to the cytochrome with a one-to-one stoichiometry. Similarly, total inhibition of enzyme activity occurred when equimolar amounts of clotrimazole, miconazole or fluconazole were added to reconstituted P-450DM. These results correlated with the inhibition of P-450DM in broken cell preparations, confirming that all five azoles are potent inhibitors of ergosterol biosynthesis in C. albicans.

Antifungal Agents↗
PubMed1990

Cystic fibrosis and allergic bronchopulmonary aspergillosis.

We have prospectively screened our patients with cystic fibrosis for allergic bronchopulmonary aspergillosis. Over a three year period eight patients were identified, an incidence of 5.8%. Patients were clinically well at the time of diagnosis (Shwachman scores 70-90, Chrispin-Norman chest x ray scores 2-15) and they responded rapidly to treatment with oral prednisolone. There has been little deterioration in their respiratory function and nutrition over the study period. We conclude that allergic bronchopulmonary aspergillosis is not uncommon in patients with cystic fibrosis. It is a potential cause of lung damage and prospective screening could lead to earlier detection and treatment.

Aspergillosis, Allergic Bronchopulmonary↗
PubMed1990

Diagnostic laboratory techniques in vaginal candidosis.

The laboratory diagnosis of vulvovaginal candidosis is complicated by the fact that the Candida spp., mainly C. albicans, are found as commensals in the normal vagina. Therefore, the demonstration of Candida in material from the vagina by microscopy (KOH mounts or Gram smears) and/or culture on Sabouraud's agar does not necessarily confirm infection. For this reason, attention is frequently paid to the quantity of yeast isolated in culture and to the morphological form of the organism (yeast/mycelium) seen in the clinical material. However, there is controversy as to whether either of these two criteria, which may be influenced by sampling methods, sample type, sample age, etc, are reliable indicators of Candida infection and correlate with the signs and symptoms attributed to this condition. A more accurate measure of the quantity of Candida present in the vagina may be obtained by measurement of yeast antigen levels in material such as vaginal washings. Correlation of antigen levels with signs and symptoms of infection is required, as is an appraisal of the role of these antigens in the pathogenesis of vulvovaginal candidosis. A new and more rapid method for diagnosis of vulvovaginal candidosis, based on the detection of Candida antigens with a slide latex agglutination test, has been recently introduced.

Antigens, Fungal↗
PubMed1989

Purification and properties of cytochrome P-450-dependent 14 alpha-sterol demethylase from Candida albicans.

The purification of cytochrome P-450-dependent 14 alpha-sterol demethylase (P-450DM) from the important opportunistic fungal pathogen, Candida albicans, is described. Optimal purification (875-fold) was achieved by extracting the cytochrome from microsomes with sodium cholate followed by hydroxyapatite, octyl-Sepharose and CM-Sepharose chromatographies, giving a cytochrome preparation of 17.5 nmol/mg of protein. By the use of SDS/polyacrylamide-gel electrophoresis the cytochrome was judged to be highly purified on the basis of Coomassie Brilliant Blue staining of protein. The Mr of P-450DM was estimated to be 51,000. The absorption spectrum of oxidized P-450DM was characteristic of a low-spin cytochrome, and its reduced CO complex had a Soret absorption peak at 447 nm. When reconstituted in a model membrane system of dilauroylphosphatidylcholine with NADPH and O2, P-450DM catalysed the complete 14 alpha-demethylation of lanosterol, which was inhibited by CO. The cytochrome appeared to have a high degree of substrate specificity; it was unable to oxidize a number of xenobiotic compounds in the reconstituted assay.

Candida albicans↗
PubMed1989

Cytochrome P-450-dependent 14 alpha-demethylation of lanosterol in Candida albicans.

A novel assay for cytochrome P-450-dependent 14 alpha-sterol demethylase of the important opportunistic fungal pathogen, Candida albicans, is described. The enzyme was assayed in microsomal preparations (microsomes) by measuring the incorporation of [14C]lanosterol into (4,14)-desmethylated sterols. The efficacy of different cell-breakage methods was compared; desmethylated-sterol biosynthesis was maximal when cells were broken with a Braun disintegrator. The solubilization of [14C]lanosterol with detergent in the assay system was essential for enzyme activity, which was enhanced considerably when microsomes were gassed with O2. Under these conditions, there was a reciprocal relationship between the amount of radioactivity incorporated into desmethylated sterols and that lost from lanosterol. The major radiolabelled desmethylated sterol was ergosterol. The enzyme had an apparent Km of 52.73 +/- 2.80 microM and an apparent Vmax of 0.84 +/- 0.14 nmol/min per mg of protein (n = 3). Enzyme activity was decreased greatly when microsomes were treated with CO or the triazole antifungal ICI 153066.

Candida albicans↗
PubMed1989

Treatment of dermatophyte infection of the finger- and toe-nails with terbinafine (SF 86-327, Lamisil), an orally active fungicidal agent.

We report on the use of a new orally active fungicidal agent, terbinafine (SF 86-327, Lamisil) in the treatment of patients with dermatophyte onychomycosis. Twenty patients with toe-nail, and 10 with finger-nail infection received 250 mg of terbinafine daily: finger-nail infections were treated for 6 months and toe-nail infections for 12 months. All 24 patients who completed the course of therapy achieved mycological cure, as did two subjects who dropped out of the trial. All but two patients had clinically normal nails at the end of the study period. The mean time for mycological cure was 12.5 weeks for finger-nail infection, and 24 weeks for toe-nail infections. The time for a clinical cure with normal nails was 20.5 weeks for finger-nail infection, and 44 weeks for toe-nail infection. An exacerbation of pre-existing dyspepsia occurred in three of the six patients who did not complete the trial but there were no other significant adverse reactions.

Administration, Oral↗