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D W Warnock

Publications and source records attributed to D W Warnock.

At least 109 records · Page 6Linked to original sources
PubMed1988

Vaginal candidosis: relation between yeast counts and symptoms and clinical signs in non-pregnant women.

Of 277 non-pregnant women, 67 (24%) harboured Candida albicans in the genital tract. Of 56 women yielding C albicans who had no other infection diagnosed, 14 were symptomless and 10 had no clinical signs of vulval redness, vaginitis, or discharge. Symptoms and signs tended to be more severe in women with higher yeast counts. Of 22 women with moderate or severe symptoms (pruritus with or without discharge) and signs, 15 had yeast counts of more than 10(3) colony forming units (cfu)/ml, whereas six of nine women with no symptoms or signs had counts of fewer than 10(3) cfu/ml.

Candida albicans↗
PubMed1988

Intermittent local prophylaxis against recurrent vaginal candidosis.

Women with recurrent vaginal candidosis were treated until the infection cleared and were then given one clotrimazole 500 mg vaginal tablet a month or an identical placebo as prophylaxis. Of 21 women who received placebo, 16 developed symptoms or signs within three months, compared with nine of 17 women given active treatment. Women who relapsed were treated and then given active prophylaxis once a month. Of 30 women given such treatment, 13 relapsed within three months. Women who relapsed were treated and then given two clotrimazole 500 mg vaginal tablets a month. Of 17 women given prophylaxis twice a month, four developed symptoms or signs within three months, but 10 remained clear for 12 months. No appreciable difference was seen in the incidence of mycological recurrence between the different regimens; within three months over half the women in all treatment groups had become recolonised.

Adolescent↗
PubMed1988

Clinical pharmacokinetics of ketoconazole.

Ketoconazole, a synthetic imidazole antifungal, is effective for superficial fungal infections, genital candidosis and chronic mucocutaneous candidosis, and has been used in immunocompromised patients and advanced prostatic carcinoma. Absorption of ketoconazole is variable after oral administration, with large variability in peak serum concentrations. Antacids reduce, and food or dilute hydrochloric acid increase, absorption. Renal failure and bone marrow transplantation are associated with reduced absorption. Ketoconazole is not absorbed systemically after topical administration, and minimally absorbed from the vagina. Distribution of ketoconazole varies according to the tissue sampled, the underlying disease and the dose and duration of treatment. Ketoconazole does not cross the intact blood-brain barrier, and crosses to only a limited extent in fungal meningitis. Urinary concentrations of ketoconazole are usually low, but vaginal and vaginal tissue concentrations correlate with those in serum. Seminal fluid concentrations are inadequate for treatment of epididymitis. Ketoconazole is 83.7% plasma protein (mainly albumin) bound, and 15.3% is erythrocyte bound, resulting in only 1% of free drug. Animal studies indicate strong binding to the cytochrome P-450 mono-oxygenase complex. Extensive metabolism to inactive metabolites occurs, the products being mainly excreted in the faeces. Saturable hepatic first-pass metabolism is probable. The half-life of ketoconazole is dose-dependent, increases during long term treatment, suggesting auto-inhibition of metabolism. The kinetics after oral administration fit a 2-compartment model. Drug interactions of theoretical, if not practical, significance include warfarin, chlordiazepoxide, methylprednisolone, cyclosporin and drugs known to induce microsomal enzymes. In each case, some dosage adjustment for ketoconazole, or the interacting drug, may be required.

Administration, Intravaginal↗
PubMed1987

Evaluation of a new slide latex agglutination test for diagnosis of vaginal candidosis.

A new commercial slide latex particle agglutination test for rapid (2 min) diagnosis of vaginal candidosis was evaluated and compared with conventional methods. Of the 263 women studied, 63 (23.9%) had yeasts in the vagina. Clinical signs of vulvitis or vaginitis were seen in 23 women (8.8%) and 40 (15.2%) were harbouring yeasts without clinical signs. Yeast counts were generally higher in women with clinical signs of vaginal candidosis than in those without. The test was positive in 15 of the 23 women (65.2%) with clinical signs, the incidence of a positive test increasing in direct proportion to the amount of yeasts isolated. The test's sensitivity, specificity and predictive values were comparable to those of microscopy and culture. Being both rapid and simple to perform, this new test offers a useful alternative to conventional methods for the diagnosis of vaginal candidosis.

Antigens, Fungal↗
PubMed1986

Ketoconazole pharmacokinetics during chronic dosing in adults with haematological malignancy.

Ketoconazole pharmacokinetics were determined in nine adults with haematological malignancy after one week on a 200 mg daily dose and later after one week on a 400 mg daily dose. The area under the serum concentration time curve (AUC) reached 12.3 +/- 7.7 mg/l.h (mean +/- S.D.) on the 200 mg dose and increased to 23.0 +/- 18.2 mg/l.h on the 400 mg dose (p less than 0.05). The half-life of ketoconazole was 3.1 +/- 1.9 h on the 200 mg dose and 3.5 +/- 1.7 h on the 400 mg dose. Peak concentrations were 3.2 +/- 1.8 mg/l and 4.6 +/- 3.2 mg/l on the 200 mg and 400 mg doses, respectively. Trough ketoconazole concentrations were undetectable 24 h after either dose. There was no correlation between the leucocyte count and any pharmacokinetic parameter for ketoconazole. Variation in AUC was 20-fold on the 200 mg daily dose and 8-fold on the 400 mg per day regimen. Measurement of serum levels during ketoconazole treatment appears necessary in view of the unpredictable concentrations achieved. Once-a-day dosage regimens of ketoconazole in immunocompromised patients may be inappropriate. Future clinical trials should adopt a two or three times a day dosing regimen, as this may confer a pharmacokinetic and therapeutic advantage.

Adult↗
PubMed1986

New developments in the diagnosis of opportunistic fungal infection.

This review considers recent developments in the diagnosis of aspergillosis, candidosis and cryptococcosis and discusses the prospects for routine application of a number of novel methods. The introduction of lysis-centrifugation and radiometric methods for blood culture has improved the diagnosis of deep candidosis, but the value of these methods for the diagnosis of aspergillosis has not yet been determined. Recent developments in serological diagnosis have included the evaluation of newly discovered antigens of Candida albicans in an attempt to distinguish colonization from significant infection. Antigen detection, an established method for the diagnosis of cryptococcosis, has also been evaluated and appears promising for the diagnosis of aspergillosis and candidosis. Another promising approach has been the use of gas-liquid chromatography to detect fungal metabolites in serum and other host fluids.

Antigens, Fungal↗
PubMed1986

In-vitro effect of itraconazole, ketoconazole and amphotericin B on the phagocytic and candidacidal function of human neutrophils.

Neither itraconazole nor ketoconazole had significant effects on the phagocytosis or killing of Candida albicans blastospores by human neutrophil polymorphonuclear (PMN) leucocytes, whether following simultaneous addition of drug with the blastospores, prior treatment of the PMN cells with drug, or prior treatment of the blastospores with drug. Following simultaneous addition, amphotericin B caused significant impairment of phagocytosis in tests with PMN cells from one of two donors, but had no effect on subsequent killing of ingested blastospores. Prior treatment of PMN cells or blastospores with amphotericin B had no effect on phagocytosis or killing. In tests in which blastospores of an azole-sensitive and an azole-resistant strain of C. albicans were added to PMN cells, fewer than 25% of ingested blastospores of either strain had initiated germ tube formation after 6 h. Addition of ketoconazole had no effect on the proportion of ingested blastospores of either strain which germinated. Ketoconazole had no effect on germ tube elongation of ingested blastospores of the azole-resistant strain, but caused marked inhibition of germ tube elongation of ingested blastospores of the azole-sensitive strain. After 24 h, the azole-resistant strain had produced abundant mycelium and few phagocytic cells remained intact. With the azole-sensitive strain, PMN cells were still evident at 24 h, with ingested germ-tube-forming blastospores, most of which were dead.

Amphotericin B↗
PubMed1986

High performance liquid chromatographic determination of ketoconazole in human serum.

A reversed-phase high-performance liquid chromatographic (HPLC) method with terconazole as internal standard is described for the rapid analysis of ketoconazole in human serum. Except for diazepam no other drug interfered with the analysis. The lowest reproducible limit of the method was 0.05 mg/l. The coefficient of variation of the procedure was less than or equal to 7.5% over a range of ketoconazole concentrations from 1.0 to 10.0 mg/l and less than or equal to 16.75% over a range from 0.05 to 0.5 mg/l. Comparison with a microbiological method showed good correlation.

Biological Assay↗
PubMed1986

Azole resistance in Candida albicans.

An isolate of Candida albicans from a patient with chronic mucocutaneous candidosis who relapsed during ketoconazole treatment was compared with a number of other azole-sensitive and azole-resistant isolates by tests in vitro and in three animal models of vaginal or disseminated infection. In-vitro tests indicated that the isolate was cross-resistant to all imidazole and triazole antifungals tested. In the animal models, treatment with miconazole, ketoconazole, itraconazole or fluconazole failed to influence the infection.

Adult↗
PubMed1985

Candidosis of the genital tract in non-pregnant women.

Of 300 non-pregnant women seen in an STD clinic, 94 (31.3%) harboured C. albicans or C. glabrata in the genital tract; 84 of these women (89.4%) had at least one moderate or marked symptom or clinical sign. Of the 94 women with Candida, 50 had another genital infection; 38% of these 50 women had at least one moderate or marked symptom or clinical sign, compared with 75% of the 44 women with no other infection. This difference is significant. Of the 146 women taking oral contraceptives, 51 (34.9%) had Candida, compared with 43 (27.9%) of the 154 women who were not. The incidence of trichomoniasis, anaerobic vaginitis and non-specific genital infection was lower among women with Candida than among the others.

Candidiasis, Vulvovaginal↗
PubMed1985

Resistogram typing of Candida albicans isolates from oral and cutaneous sites in irradiated patients.

Thirteen resistogram strains of Candida albicans were found among isolates obtained from the mouth and cutaneous sites of irradiation of 27 patients receiving treatment for oral and laryngeal cancer. In all cases the yeast was recovered from the mouth before treatment, but not from the skin site until after treatment had begun. Of the 27 patients, 25 harboured one or more strains with identical resistograms in both sites.

Adult↗
PubMed1984

Prevalence of oral colonization with Candida albicans and anti-C. albicans IgA in the saliva of normal children and children with acute lymphoblastic leukaemia.

The prevalence of oral colonization with C. albicans was studied in 40 children with acute lymphoblastic leukaemia (ALL) and 40 matched normal children. Colonization was more common in the ALL group (25% colonized) than the normal group (7.5% colonized). Total saliva IgA levels were lower in the ALL group, but low levels did not correlate with oral colonization. The three normal children with oral colonization all had anti-C. albicans IgA in their saliva, as had seven of the ten colonized ALL patients.

Adolescent↗
PubMed1984

Antigen and antibody attachment in ELISA for Aspergillus fumigatus IgG antibodies.

Four commercial antigen extracts of Aspergillus fumigatus were evaluated for use in a rapid enzyme-linked immunosorbent assay (ELISA) for anti-A. fumigatus IgG. Initial binding of both somatic and culture filtrate preparations to a polyvinyl chloride solid phase was concentration dependent and increased with incubation time. Antigen binding to the solid phase was reproducible. Binding of A. fumigatus precipitin-positive serum to bound antigen was rapid. All four A. fumigatus antigens demonstrated similar dose-response curves when tested against pooled sera containing a high titre of A. fumigatus antibodies. Detectable activity in precipitin test-negative sera decreased rapidly with dilution. All the antigen preparations were found to be suitable for ELISA procedures and permit the rapid determination of IgG antibodies to A. fumigatus.

Alkaline Phosphatase↗