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Biomedical subjects

R J Hay

Publications and source records attributed to R J Hay.

At least 289 records · Page 16Linked to original sources
PubMedDate not supplied

In vitro studies of antibiotic sensitivities of Streptomyces somaliensis--a cause of human actinomycetoma.

Ten Streptomyces somaliensis strains isolated from mycetoma patients were tested in vitro against 13 antibacterial agents. Rifampicin was the most effective antibiotic in terms of low minimum inhibitory concentration (MIC) followed by erythromycin, tobramycin, fusidic acid and streptomycin sulphate. The S. somaliensis strains were all resistant to trimethoprim, even though the combination of sulphamethoxazole and trimethoprim is commonly used as treatment.

Actinomycetales Infections↗
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Preparation of murine monoclonal antibodies against the yeast phase of the dimorphic fungus Sporothrix schenckii.

Three murine monoclonal antibodies (Mabs) were raised against a cytoplasmic antigen of the yeast phase of the pathogenic fungus Sporothrix schenckii using a modification of standard hybridoma technology incorporating the immunosuppressive drug cyclophosphamide. When tested for species-specificity within the pathogenic dimorphic fungi one of these Mabs (S5) showed little cross-reactivity by enzyme-linked immunosorbent assay and Western blot, though there was some recognition of Paracoccidioides brasiliensis antigen. This Mab recognized a 70-75 kDa molecule on reduced Western blots of S. schenckii antigen. The other two Mabs (S12 and S15) showed cross-reactivity with all dimorphic fungal antigens tested, though they appeared to recognize a molecule of similar molecular weight. This is the first report of any attempt to raise species-specific Mabs against this important causative agent of dermatological disease.

Animals↗
PubMedDate not supplied

Preparation of monoclonal antibodies that differentiate between Histoplasma capsulatum variant capsulatum and H. capsulatum variant duboisii.

The immunosuppressive drug cyclophosphamide was used to facilitate the production of monoclonal antibodies (Mabs) which differentiated between the yeast phase of the two variants of the dimorphic fungus Histoplasma capsulatum by both enzyme-linked immunosorbent assay and Western blot. Two Mabs are described, identifying epitopes on a 70-75 kDa molecule, which are specific to H. capsulatum var. capsulatum and which do not identify epitopes of H. capsulatum var. duboisii. These Mabs have potential use in the epidemiology and serodiagnosis of histoplasmosis in areas where both classical and African forms of the disease occur.

Animals↗
PubMedDate not supplied

Murine monoclonal antibodies recognizing a non-capsular antigen that distinguishes between Cryptococcus neoformans var. neoformans and C. neoformans var. gattii.

A panel of 4 monoclonal antibodies (mabs) of the IgG1 subclass have been made against a cytoplasmic antigen of Cryptococcus neoformans. Mab 4E2 recognized isolates of C. neoformans var. gatti by enzyme-linked immunosorbent assay (ELISA), whilst the other antibodies did not recognize these antigens. By Western blot 4E2 recognized determinants at 110-125, 65-70, 45-50 and 36-38 kDa. Mabs 9E6, 7C7 and 5D9 recognized bands at 36-38 and approximately 30 kDa. All 4 mabs (4E2, 9E6, 7C7 and 5D9) recognized both non-encapsulated and encapsulated isolates of C. neoformans var. neoformans by ELISA, and in addition showed reactivity to only the cytoplasm and cell membrane of yeasts by immunofluorescence. Mab 7C7 recognized antigens of the closely related fungus Trichosporon beigelii by ELISA but did not recognize any other fungal antigens. The other 3 mabs showed no recognition of T. beigelii or any other fungal pathogens tested.

Animals↗
PubMedDate not supplied

Post-operative responses of paranasal Aspergillus granuloma to itraconazole.

Paranasal Aspergillus granuloma is an invasive infection, seen mainly in tropical countries, involving the paranasal sinuses, orbit and brain. Previously surgical excision has been followed by a high relapse rate, 80% in some series, and mortality. This study involved the use of post-operative therapy with oral itraconazole in doses of 200-300 mg daily. Twenty-two patients were treated for a mean period of 19.7 weeks. Of 19 patients for whom follow-up data were available, 12 (62%) were rated as being in complete remission in a mean period of 17.2 months after the end of therapy. Only one patient developed progressive disease during itraconazole therapy. No serious adverse effect was seen. Use of itraconazole shows promise as a means of preventing relapse after surgery in this progressive infection.

Adolescent↗
PubMedDate not supplied

Isolation and partial characterization of a Paracoccidioides brasiliensis 58 kDa extracellular glycoprotein which is recognized by human immune sera.

A novel 58 kDa antigenic determinant of the fungus Paracoccidioides brasiliensis was identified by enzyme-linked immunosorbent assay using a panel of species-specific murine monoclonal antibodies (MAbs). Western immunoblot analysis, deglycosylation studies and isoelectric focusing indicated that this 58 kDa antigen is a glycoprotein, with a pI of approximately 5.2. The molecule was purified from P. brasiliensis culture filtrate and yeast cytoplasmic antigens by membrane ultrafiltration, liquid isoelectric focusing and gel filtration; N-terminal amino acid sequence data revealed no substantial homology with known proteins. The presence of the antigen in the cytoplasm of both yeast and mycelial forms of the fungus was demonstrated when these MAbs were used as markers in immunofluorescence, immunoperoxidase and immunoalkaline phosphatase techniques to label P. brasiliensis in cryostat sections. These MAbs also recognized the cytoplasm of P. brasiliensis yeast forms in paraffin-embedded pathological specimens from human cases. A preparation of the 58 kDa component from yeast cytoplasmic antigen was reacted by Western immunoblotting with 26 different serum samples from paracoccidioidomycosis patients, and 81% of them recognized it.

Adult↗
PubMedDate not supplied

Exposure to Cryptococcus neoformans var. gattii--a seroepidemiological study.

An enzyme-linked immunosorbent assay was developed to study prevalence of immunoglobulin G (IgG) antibody to non-capsular Cryptococcus neoformans var. gattii antigen in a population of healthy Papua New Guinea (PNG) controls and patients. Patients with acute C. neoformans var. gattii meningitis had elevated levels of IgG which declined significantly following treatment (P = 0.034). Levels in the sera of convalescent patients were significantly higher than those in PNG controls (P < 0.001), which in turn were significantly higher than in a UK control group (P < 0.001). Clear differences were observed amongst the PNG controls. Adults had significantly higher levels than children (P = 0.002) and men had significantly higher levels than women (P = 0.047). No difference was observed between levels in patient-related and unrelated controls. IgG responses in PNG controls mirror the prevalence of disease in this population. It is postulated that exposure to C. neoformans var. gattii is less common in children and women due to some as yet unidentified behavioural difference and that exposure occurs away from the home environment.

Adolescent↗
PubMedDate not supplied

Overview of studies of fluconazole in oropharyngeal candidiasis.

Studies with fluconazole in oropharyngeal candidiasis have focused primarily on three groups of infections: chronic atrophic candidiasis, oropharyngeal infections associated with either neutropenia or AIDS, and chronic mucocutaneous candidiasis. In two studies of chronic atrophic candidiasis associated with dentures, 82 patients received 7 or 14 days of therapy with fluconazole (50 mg daily). Clinical and mycologic cure rates ranged from 69% to 100%, with the best results occurring with 14 days of therapy in combination with the cleansing of dentures. Thirteen patients with oroesophageal candidiasis associated with chronic mucocutaneous candidiasis were treated with 50 or 200 mg of fluconazole daily, and clinical and mycologic remissions were achieved in a mean period of 10 days. So far 95 patients have been treated with fluconazole for oropharyngeal candidiasis associated with malignancy, therapeutic immunosuppression, AIDS, or AIDS-related complex. Infection was cured by clinical criteria in 84% of those studied. While the majority of patients with clinical cure had significant reductions in the number of yeast colonies, only 48% had negative oral cultures at the end of therapy with courses of 50 mg of fluconazole daily for 5 days to 8 weeks.

Candidiasis↗
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Treatment of chronic mucocutaneous candidosis with ketoconazole: a study of 12 cases.

Twelve patients with chronic mucocutaneous candidosis were treated orally with ketoconazole (doses, 200-400 mg daily) for a mean period of six months. Seven of the patients had one of the following abnormalities: congenital endocrinopathy syndrome, an autosomal recessive or autosomal dominant defect in which candidosis is not associated with endocrinopathy, or the malabsorption syndrome. All patients had fungal infections of the mouth, and 11 had onychomycosis. Two patients were also infected with dermatophytes. At the end of treatment, 10 patients were cured of oral infection, and 11 with nail infections showed significant improvement. Marked improvement of hand and foot infections was also recorded. Patients infected with dermatophyte fungi had the poorest responses to therapy. The mean (+/- SD) MIC for isolates of Candida albicans from eight patients was 0.95 (+/- 0.78) microgram/ml. Clinical and biochemical monitoring showed no toxicity, and no resistant fungi emerged during treatment. Results of this initial study of ketoconazole for treatment of severe and recalcitrant superficial infections indicate the need for further assessment of this drug, which appears to offer a simple, nontoxic, and effective treatment of fungal infections.

Adolescent↗
PubMedDate not supplied

Treatment of chronic dermatophytosis and chronic oral candidosis with itraconazole.

Itraconazole was evaluated in patients with forms of superficial fungal infection that were previously unresponsive to treatment. Two groups of patients were treated, those with chronic dermatophytosis caused by Trichophyton rubrum affecting the body (10) or palm (five) and those with chronic oral candidosis (eight). All of the patients with dermatophytosis achieved complete remission in a mean period of 9.1 weeks, with three subsequent relapses. Seven patients with oral candidosis had originally presented with chronic mucocutaneous candidosis; recurrent or persistent oral candidosis had developed after initially successful treatment with ketoconazole. All of the patients with chronic oral candidal infections responded to itraconazole after a mean treatment period of 5.4 weeks, with two subsequent relapses. These results indicate that itraconazole is effective in treating these recalcitrant superficial mycoses and should be assessed in a larger unselected group of patients and compared with alternative drugs.

Adolescent↗
PubMedDate not supplied

The clinical and epidemiologic features of tropical ulcer (tropical phagedenic ulcer).

A comparative survey of patients with tropical ulcer has been carried out in Zambia, Gambia, Southern India and Papua New Guinea. The clinical features, socioeconomic background and nutritional correlates have been compared in 170 patients. In 96% of cases the condition occurred on the foot or lower leg. In only 10 instances did the ulcer last for over six months. There was one patient with a squamous cell carcinoma arising in situ from the ulcer margin. No significant differences in clinical features were seen in the countries surveyed. In all areas apart from southern India most cases were seen in the rural population and in children or teenagers. There was no correlation between the development of an ulcer and nutritional status found in this survey. Evidence is presented that there is an association between tropical ulcer and exposure to mud or slow moving fresh water.

Adolescent↗
PubMedDate not supplied

The antigenic composition and protein profiles of eumycetoma agents.

The protein profiles of different eumycetoma agents were compared by SDS gel electrophoresis. Dendrograms confirmed the homogeneity of isolates of Pseudallescheria boydii but amongst Madurella species, particularly isolates identified as M. grisea, there were substantial differences in protein composition. However using Western blotting reference isolates of the different species showed distinct antigen patterns in response to immune rabbit sera. In particular there was little evidence of cross reactivity between M. mycetomatis and M. grisea. However this specificity was not apparent when human sera from patients with different eumycetoma infections were compared in an ELISA system using the same antigens. It is possible that the formation of a mycetoma grain may limit a patient's exposure to antigens which confer specificity, an explanation which may also account for the variability in antibody responses seen.

Antigens, Fungal↗
PubMedDate not supplied

Partial purification and characterization of a 235,000M(r) extracellular proteinase from Trichophyton rubrum.

An extracellular proteinase has been partially purified from culture filtrates of Trichophyton rubrum by ultrafiltration, isoelectric focusing and gel filtration chromatography. The enzyme has a non-reduced molecular weight of 235,000 by substrate SDS-PAGE. It has a pH optimum of 8.5 using azocasein and azoalbumin as substrates and a pI of 3.6-3.8. The metalloproteinase inhibitors EDTA and 1,10-phenanthroline, together with the chymotrypsin inhibitor chymostatin, strongly inhibited its activity. The serine proteinase inhibitors phenylmethanesulphonyl fluoride and diisopropylfluorophosphate showed weak inhibitory activity. The proteinase exhibited broad substrate activity against azocoll, azoalbumin, azocasein, laminin and fibronectin. It exhibited weak activity against elastin and keratin. Observations on the occurrence of this proteinase together with previously described lower molecular weight proteinases suggests that the former is the first to appear in minimal medium cultures. Freeze/thaw cycling of the partially purified 235,000 M(r) proteinase was found to generate low molecular weight proteinases, particularly at 53,000, 27,000 and 25,000 M(r), indicating that the latter may originate from the larger molecule.

Culture Media↗
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The prevalence of skin disease among school children in rural Ethiopia--a preliminary assessment of dermatologic needs.

It is always assumed that the prevalence of skin diseases in developing countries is very high, and that infestations and skin infections are highly endemic in poor rural communities; however, very few epidemiologic reports verify these assumptions. As part of a continuing study of dermatologic needs in southwestern Ethiopia, and to estimate the prevalence of treatable skin disease in children, a school survey was undertaken in Shebe. In October 1992, 112 children were examined by a team of dermatologists and their conditions were recorded. Twenty-two children (19.6%) were considered healthy and 90 (80.4%) had one or more skin diseases. A total of 140 conditions were identified and considered treatable in 98% of children. Infestations were the most prevalent skin pathology, 81.2%, followed by fungal infections, 13.4%.

Adolescent↗