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Biomedical subjects

R J Holt

Publications and source records attributed to R J Holt.

At least 55 records · Page 3Linked to original sources
PubMed1976

Topical pharmacology of imidazole antifungals.

Four imidazole derivatives have now undergone extensive open and comparative trials as topical agents in dermatomycoses and vaginal candidosis. They are chlormidazole (Chemie Grünenthal), clotrimazole (Bayer), miconazole (Janssen) and econazole (Janssen, Cilag-Chemie); all also have some antibacterial activity. Many other imidazoles have been marketed, usually as antiprotozoal or anthelminthic agents, and some of these have some antimycotic activity as well as other miscellaneous therapeutic properties. The mode of action of imidazole antimycotic agents is discussed; after prolonged topical application to animals and human subjects, systemic absorption is negligible. All four agents which are available as cream, powder, lotion or vaginal tablets have many sucessful studies to their credit, often with clinical and mycological cure rates of over 80% in a variety of dermatomycoses and in vaginal candidosis. The relative value of these topical agents is discussed, and it is suggested that in severe and extensive dermatomycoses consideration should be given to the systemic use of miconazole in support of topical therapy.

Administration, Topical↗
PubMed1976

Childhood actinomycosis. Report of 3 recent cases.

Three cases of childhood actinomycosis are reported, 2 with the commonest presentation of cervicofacial abscess and the third with a rarely reported superficial chest wall abscess. The importance of prompt bacteriological diagnosis and adequate treatment with surgical drainage and chemotherapy is stressed. Though in adults males are affected more frequently than females, the sexes are probably equally affected in childhood.

Actinomyces↗
PubMed1975

Laboratory tests of antifungal drugs.

The procedures evolved in the author's laboratory over the past 20 years for the microbiological assessment of antifungal drugs are described; methods are detailed for the estimation of the sensitivity of pathogenic fungi to therapeutic agents and for the assay of those agents in body fluids. The preparation and maintenance of stock reference solutions of the drugs, the culture media used, and the incubation temperature and time are discussed. Sensitivity tests by paper disc and by liquid titration for minimal inhibitory and cidal concentrations estimated are described, and the importance of standardized initial inocula is emphasized. Two groups of assay procedures are given, the liquid dilution and the agar diffusion methods, and suitable indicator organisms for both methods are named. The paper concludes with a discussion on the problem of differential assays when two antimycotic agents are in simultaneous clinical use.

Agar↗
PubMed1973

The antimycotic activity of 5-fluorocytosine.

5-Fluorocytosine (5 FC) showed marked in vitro activity against nearly all the clinical isolates of Candida and Cryptococcus examined; the required minimal inhibitory concentration was usually below 2 mug/ml and the minimal cidal concentration below 10 mug/ml. The drug had limited activity towards Aspergillus species and dermatophytes. Strains of Candida and other fungi with greatly enhanced resistance were fairly readily obtained by successive cultures on increasingly high concentrations of 5-fluorocytosine.Serum, urine, and faecal assays of 5 FC were made by a microbiological method on specimens from eight children who received between 100 and 25 mg/kg/day of the drug over several weeks for candidosis of the urinary tract usually associated with congenital anatomical abnormalities. Seven of these cases were successfully treated but in the other the Candida became highly resistant and treatment was discontinued. Serum drug levels ranged up to 30 mug/ml; urine levels were frequently between 200 and 500 mug/ml. No 5 FC was detected in faecal samples. Sensitivity tests and assays were also made on samples from subjects receiving 5 FC in other hospitals; five had systemic C. albicans infection, the sixth had cryptococcal meningitis. In the latter case levels up to 34 mug/ml were recorded in the cerebrospinal fluid after oral administration, and an investigation was made into the possibility of competitive antagonism by intrathecal cytosine arabinoside given for Hodgkin's disease. The emergence in two other cases of strains of Candida highly resistant to 5 FC is discussed, and it is suggested that careful laboratory monitoring of cases receiving 5 FC must continue throughout therapy and afterwards.

Adult↗
PubMed1972

Laboratory assessment of the antimycotic drug clotrimazole.

Laboratory studies on clotrimazole showed that it had marked activity in vitro against all the Candida spp. and Cryptococcus spp. tested, against almost all strains of dermatophytes, and against Aspergillus spp and other fungal genera responsible for systemic mycoses; it had limited activity towards Gram-positive bacteria. The majority of Candida strains required MICs below 1 mug/ml and MCCs below 2 mug/ml.Serum, urine, and faecal assays of clotrimazole were made by microbiological methods on five children who received 100 mg/kg/day clotrimazole for several weeks. In-vitro sensitivity tests and biological fluid drug assays are also reported on specimens from 18 patients in other hospitals receiving clotrimazole for severe candidosis; several were renal transplant cases. Similar investigations are reported on specimens from 18 patients with pulmonary aspergilloses. The significance of low levels of the drug in body fluids, even after prolonged therapy, is discussed, and it is suggested that clotrimazole may be the first of a long series of imidazole derivatives with varying pharmacological and therapeutic properties.

Antifungal Agents↗