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Biomedical subjects

R J Hay

Publications and source records attributed to R J Hay.

At least 73 records · Page 4Linked to original sources
PubMed1997

Tinea capitis in south-western Ethiopia: a study of risk factors for infection and carriage.

BACKGROUND: Tinea capitis is a common dermatophyte infection which constitutes an important public health problem among children worldwide. The endemic nature of scalp ringworm in Africa is perpetuated mainly by the lack of knowledge about the prevalence and carrier status, and the absence of control measures. METHODS: Two hundred and nineteen schoolchildren from urban and rural communities of the Illubabor district, south-western Ethiopia, were examined, and scalp samples were taken. Children were classified according to clinical signs and mycologic findings. RESULTS: Physical examination revealed that 29% of the children had clinical lesions compatible with tinea capitis. Dermatophytes were isolated from 33% of the children's scalp samples; of these, 16% had clinical lesions and 17% were identified as carriers. Trichophyton violaceum was responsible for 97% of infections. CONCLUSIONS: Tinea capitis was the second most prevalent cutaneous finding in these children, with a higher prevalence in the urban community; the predictive value of the clinical diagnosis was low and a high proportion of children were identified as carriers in these communities. No relationship between household overcrowding and scalp infection was found.

Adolescent↗
PubMed1997

Development of a novel antigen detection test for histoplasmosis.

Histoplasmosis is an important systemic fungal infection, particularly among immunocompromised individuals living or travelling in areas of endemicity, who, without antifungal therapy, may develop a progressive disseminated fatal infection. For such patients, the detection of antibody responses by immunodiffusion or complement fixation test is of limited use. In contrast, the detection of Histoplasma capsulatum circulating antigens may provide a more practical approach to the rapid diagnosis of the disease. Accordingly, an inhibition enzyme-linked immunosorbent assay (ELISA) for the detection of a 69- to 70-kDa H. capsulatum-specific determinant and incorporating a species-specific murine monoclonal antibody was developed. With sera from patients with different forms of the disease (n = 35), the overall sensitivity of the test was found to be 71.4%, while the specificity was found to be 98% with normal human sera from areas of endemicity (n = 44) and 85.4% with sera from patients with other chronic fungal or bacterial infections (n = 48). This novel, highly specific ELISA provides a significant addition to the existing diagnostic tests for the detection of histoplasmosis.

Adolescent↗
PubMed1997

Use of monoclonal antibodies in diagnosis of paracoccidioidomycosis: new strategies for detection of circulating antigens.

The precise diagnosis of paracoccidioidomycosis, in most cases, is established by direct methods and indirect immunological tests. The latter method is reliant on the identification of the host's humoral responses, which are usually impaired or absent in patients with severe juvenile forms of the disease and in immunocompromised patients. Determining disease activity or assessing treatment responses by measuring antibody levels is difficult, since antibody titer may remain elevated or persist at stationary levels, even in the presence of clinical improvement. Consequently, there is a need for alternative tests aimed at the identification of circulating antigens. A modification of the standard hybridoma production method was used to raise a panel of murine monoclonal antibodies (MAbs) against the yeast form of Paracoccidioides brasiliensis. Of these, MAb PIB, directed against an 87-kDa determinant, was used to develop an inhibition ELISA (inh-ELISA) capable of detecting as little as 5.8 ng of circulating antigen per ml of serum. Sera from 46 patients with paracoccidioidomycosis or other mycoses and sera from healthy individuals were evaluated by the inh-ELISA; overall sensitivity was 80.4% (37 of 46 paracoccidioidomycosis patients tested positive), and specificity compared with that of normal controls from areas of endemicity was 81.4%. The inh-ELISA detected circulating antigen in 100% of patients with the acute form of paracoccidioidomycosis and in 83.3 and 60% of patients with the chronic multifocal and unifocal forms of paracoccidioidomycosis according to the patients' clinical presentation. These results indicate that the inh-ELISA with MAb PIB is effective in the detection of circulating antigen and that this test may be useful for monitoring responses to treatment and establishing disease prognoses.

Antibodies, Fungal↗
PubMed1997

Chronic mucocutaneous candidosis associated with hypothyroidism: a distinct syndrome?

Chronic mucocutaneous candidosis (CMC) is a rare, complex disorder characterized by chronic and recurrent candida infections of the skin, nails and oropharynx. In over 50% of cases there is an associated endocrine disease, the complex being described as the candida endocrinopathy syndrome. Inheritance of familial endocrine associated cases has been thought to follow an autosomal recessive pattern. In addition, autosomal recessive and autosomal dominant forms of CMC not associated with endocrinopathy have been described. We report a new syndrome in which there is vertical transmission of CMC within families associated with primary hypothyroidism. This suggests that the candida endocrinopathy syndrome can be subdivided into at least two types, one associated with hypoparathyroidism and/or hypoadrenalism which is inherited as an autosomal recessive trait, the other associated with hypothyroidism which is an autosomal dominant disease. We emphasize the importance of early and regular monitoring thyroid function in individuals with CMC and a need to provide appropriate genetic counselling to affected members.

Adult↗
PubMed1997

Dermatology quality of life scales--a measure of the impact of skin diseases.

Patient-generated dermatology quality of life scales (DQOLS) were developed to assess the impact of skin conditions on patients' psychosocial state and everyday activities. The items were derived from the self-reported impacts of their skin condition by 50 dermatology out-patients. The resulting 17 psychosocial items and 12 activities items were assigned five-point scales and self-completed by 118 out-patients. Factor analyses grouped the items into four psychosocial subscales (embarrassment, despair, irritableness, distress) and four activities subscales (everyday, summer, social, sexual). Tests of the psychometric properties indicated that the internal consistency of responses was high, with Cronbach's alpha coefficients of 0.92 for the 17 psychosocial items and 0.83 for the 12 activity items. Assessment of reliability based on 41 psoriasis patients attending phototherapy treatment identified good short-term test-retest reliability, with intraclass correlation coefficients of 0.84 for both the psychosocial and activities scales. Construct validity was confirmed by the ability of the scales to identify clinically expected differences and their greater sensitivity to the impacts of skin problems compared with a widely used generic health status measure. The DQOLS thus form a robust measure of patient-perceived impacts. They were quickly self-completed and provide information that complements traditional clinical indicators. These scales should assist in informing treatment decisions by identifying impacts of different skin conditions and variations in responses among social and cultural groups, as well as guiding priorities for services within the specialty.

Acne Vulgaris↗
PubMed1997

The impact of onychomycosis on quality of life.

Onychomycosis is a common disease, which is estimated to affect approximately 3% of the UK population. It is often viewed as being relatively trivial in nature; however, there has been little research to evaluate how this condition affects patients' physical and psychological well-being. The aim of this study was to assess the possible effect of onychomycosis on different aspects of patients' quality of life.

Adult↗
PubMed1996

Fungal infections: a survey of laboratory services for diagnosis and treatment.

A questionnaire on the services provided and the methods used for the diagnosis of fungal infections and for the support of antifungal chemotherapy was sent to members of the British Society for Medical Mycology (BSMM) and the British Society for Antimicrobial Chemotherapy (BSAC). Ninety-five responses from general microbiology laboratories in the United Kingdom were analysed, and we compared services provided by laboratories that serve a transplant unit with those offered by other laboratories. We estimate that about 150 cases of cryptococcosis, 500 to 600 of candidaemia, and 300 to 400 of invasive aspergillosis are identified by laboratories in the United Kingdom (UK) each year. The clinical laboratories are aware of the importance of fungal infection, but rely heavily on reference services. In some laboratories, however, the degree of investigation of specimens and the procedures in use are inadequate for diagnosing systemic mycoses and determining the susceptibility of isolates to antifungal agents. The balance between reference and local services requires attention and external quality assurance needs to be applied effectively. In addition, effective methods for the diagnosis of systemic mycoses, and reliable and practicable methods for determining the susceptibility of isolates to antifungal agents, are needed urgently.

Antifungal Agents↗
PubMed1996

Cell line banks and their role in cancer research.

The utility of centralized cell banks in providing reference cultures for cancer research is reviewed. Procedures applied at The American Type Culture Collection in development, maintenance and expansion of such a resource are discussed for example, with emphasis on human tumor cell lines. The various categories of cell-line holdings are explained, and status with regard both to the numbers of lines available and distribution experienced are documented. The locations of other national cell repositories plus contact data are provided.

Adolescent↗
PubMed1996

Purification and characterisation of a novel 34,000-Mr cell-associated proteinase from the dermatophyte Trichophyton rubrum.

A novel cell-associated proteinase was purified to homogeneity from cytoplasmic antigen preparations of Trichophyton rubrum by sequential isoelectric focusing and gel filtration chromatography. The enzyme exhibited relative molecular masses of 34,000-Mr (non-reduced sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE)), 15,000-Mr (reduced SDS-PAGE) and 37,000-Mr (substrate SDS-PAGE). It had a pH optimum of 7.5 and a pI of 4.5. The proteinase exhibited broad substrate specificity and it was strongly inhibited by the serine proteinase inhibitors phenylmethylsulfonyl fluoride and chymostatin. The N-terminal amino acid sequence of the 34,000-Mr proteinase shared 50% homology with the deduced amino acid sequence of a Coccidioides immitis wall-associated chymotrypsin-type serine proteinase. This is the first cell-associated proteinase to be purified and characterised from T. rubrum and it would appear to be related to the chymotrypsin-type serine proteinases, a class of enzymes that have rarely been isolated from fungi. The function of the proteinase remains speculative although it may play a role in the development and subsequent proliferation of the fungus in vivo.

Amino Acid Sequence↗
PubMed1996

Yeast infections.

Yeasts are unicellular fungi that reproduce by the process of budding in which daughter cells are produced from parents by outpouching of the cell membrane and wall, migration of cytoplasm into the new structure thus formed, and then separation from the parent cell. Yeasts that are pathogenic in humans range in size from 2 to 12 microns in diameter; most, therefore, can be engulfed by phagocytic cells. These pathogens include many of the best known of pathogenic fungi, such as the Candida species, Cryptococcus neoformans, and the lipophilic yeasts of the genus Malassezia.

Antifungal Agents↗
PubMed1996

Tinea capitis in south-east London--a new pattern of infection with public health implications.

Recent observations on tinea capitis cases in London suggest that there has been a change in the pattern of infection with a recent and significant rise in the incidence of infections due to anthropophilic fungi. The purpose of this study was to investigate the prevalence and identity of tinea capitis in schools in south-east London and factors which might affect the spread of infection. This was achieved by carrying out a survey of all children, with parental consent for scalp examination, in 14 nursery, infant or junior schools in Lambeth. In addition, the accuracy of clinical diagnosis was compared with mycological findings. There were 1057 children from 4 to 14 years of age in the study. The infection rate in different schools ranged from 0 to 12% with a mean of 2.5%. A further 4.9% of children were scalp carriers of dermatophytes (range in classes 0-47%). A striking feature was that all infections were caused by anthropophilic fungi, mainly Trichophyton tonsurans or Microsporum rivalieri, and there was a correlation between the presence of two or more carriers within a class and the infection in the other children. There was a poor correlation between ability of trained observers to predict infection on clinical grounds and mycological results. This investigation shows variable but significant levels of scalp ringworm in schools and that the dominant organisms are anthropophilic. It provides support for the observation that there has been a shift in the pattern of tinea capitis in London and, possibly, other U.K. centres, with a trend towards more infections transmissible among children, with T, tonsurans being the commonest organism. The implications for control, which involve screening in schools, where appropriate, and guidance to general practitioners on treatment, are discussed.

Carrier State↗
PubMed1996

Update on the management of onychomycosis: highlights of the Third Annual International Summit on Cutaneous Antifungal Therapy.

Onychomycosis is an increasingly common fungal infection of the nail, which has traditionally been difficult to diagnose and treat and has physical and psychological consequences for the patient. Onychomycosis can be caused by dermatophytes, nondermatophytic filamentous fungi, and yeasts. The relative percentages of cases due to these etiologic agents vary with geographic location; however, in the United States, dermatophytes are the most common pathogens. Toenails are affected four times as often as fingernails. Microscopy and culture are the diagnostic "gold standards" for onychomycosis, although biopsy of the nail may be required to obtain a definitive diagnosis when conditions that mimic onychomycosis, such as psoriasis, are suspected. The treatment of onychomycosis includes a combination of topical therapy, surgical or chemical nail avulsion, and systemic therapy. The new generation of systemic agents (itraconazole, fluconazole, and terbinafine) is associated with a higher cure rate and shorter courses of treatment than are the older systemic antifungal drugs (i.e., griseofulvin and ketoconazole); these characteristics have sparked new interest in onychomycosis. Of these newer antifungals, itraconazole and terbinafine are the only agents currently approved by the U.S. Food and Drug Administration for the treatment of onychomycosis.

Administration, Oral↗
PubMed1996

Purification and partial characterization of the Cu,Zn superoxide dismutase from the dermatophyte Trichophyton mentagrophytes var. interdigitale.

Cell homogenization, isoelectric focusing and gel filtration FPLC have been used to purify a superoxide dismutase (SOD) from the dermatophyte Trichophyton mentagrophytes var. interdigitale (T. interdigitale). N-terminal amino acid sequencing identified this enzyme as a Cu,ZnSOD, with a pH of 5.1, a reduced molecular mass of 18 kDa, and a non-reduced molecular mass of 59 kDa. SOD activity was detectable in culture filtrates, as early as the mid-log phase of growth. The known Cu,Zn inhibitor potassium cyanide caused some inhibition of the purified enzyme, whereas the inhibitors sodium azide, guanidinium hydrochloride, EDTA and chloroform/ethanol had no discernible effect. The T. interdigitale SOD was pH insensitive in the range 7.0-10.5 and remained active after prolonged incubation at 50 degrees C. The purification and characterization of this enzyme represents the first step in determining whether SOD plays any part in protecting T. interdigitale from free radicals generated by the oxidative burst of immune effector cells.

Amino Acid Sequence↗
PubMed1996

Imported mucocutaneous leishmaniasis.

We report a case of mucocutaneous leishmaniasis in a otherwise fit Caucasian man who had traveled in an endemic area. Initial tissue microscopy failed to identify the causative organism, which was only determined by subsequent culture as Leishmania braziliensis. This case illustrates the variability in the presence of Leishman-Donovan (LD) bodies in histopathological studies and emphasizes the need for culture in suspected cases of leishmaniasis, particularly given the ability of certain Leishmania species such as L. braziliensis to cause recalcitrant and destructive infections of the nose and mouth.

Adult↗
PubMed1996

The Cu,Zn superoxide dismutases of Aspergillus flavus, Aspergillus niger, Aspergillus nidulans, and Aspergillus terreus: purification and biochemical comparison with the Aspergillus fumigatus Cu,Zn superoxide dismutase.

Cu,Zn superoxide dismutases (SODs) have been purified to homogeneity from Aspergillus flavus and A. niger, which are significant causative agents of aspergillosis, and from A. nidulans and A. terreus, which are much rarer causative agents of disease, using a combination of isoelectric focusing and gel filtration fast protein liquid chromatography. The purified enzymes have been compared with the previously described SOD from the most important pathogen in the genus, A. fumigatus (M. D. Holdom, R. J. Hay, and A. J. Hamilton, Free Radical Res. 22:519-531, 1995). The N-terminal amino acid sequences of the four newly purified enzymes were almost identical and demonstrated homology to known Cu,Zn SODs from a range of organisms including that from the previously described SOD from A. fumigatus. SOD activity was detectable in the culture filtrates of all species, and intracellular Cu,Zn SOD activity as a proportion of total protein was highest in early-log-phase cultures. The specific activities of the purified enzymes were similar, and all four of the newly described enzymes were inhibited by potassium cyanide and diethyldithiocarbamate, known Cu,Zn SOD inhibitors. Sodium azide and o-phenanthroline demonstrated inhibition at concentrations from 5 to 30 mM, and EDTA also exhibited a varying degree of inhibition of SOD activity. However, there were differences in the nonreduced molecular masses, the reduced molecular masses, and the isoelectric points of the four newly described SODs and the A. fumigatus enzyme; these varied from 55 to 123 kDa, 17.5 to 19.5 kDa, and 5.0 to 5.9, respectively. Of particular note was the observation that the A. fumigatus enzyme was thermostable compared with the SODs from the other species; in addition, the A.fiumigatus enzyme retained all of its activity at 37 degrees C relative to 20 degrees C, whereas the SODs of A. nidulans and A. terreus lost significant activity at the higher temperature. Aspergillus Cu,Zn SOD plays a hypothetical role in the avoidance of oxidative killing mechanisms, and our data suggest that the thermotolerant A. fumigatus Cu,Zn SOD would be more effective in such a protective system than, for example, the equivalent enzyme from the more rarely pathogenic A. nidulans.

Amino Acid Sequence↗