Disseminated cryptococcal infection despite treatment for cryptococcal meningitis.
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Adult↗
Biomedical subjects
R J Hay
Publications and source records attributed to R J Hay.
Purification, N-terminal amino acid sequence and partial characterization of a Cu,Zn superoxide dismutase from the pathogenic fungus Aspergillus fumigatus.
A superoxide dismutase (SOD) has been purified to homogeneity from the fungal pathogen Aspergillus fumigatus using a combination of cell homogenization, isoelectric focusing and gel filtration FPLC. The N-terminal amino acid sequence of the purified enzyme demonstrated substantial homology to known Cu,Zn superoxide dismutases for a range of organisms, including Neurospora crassa and Saccharomyces cerevisiae. The enzyme subunit has a pI of 5.9, a relative molecular mass of 19 kDa and a spectral absorbance maximum of 550nm. The non reduced enzyme has a relative molecular mass of 95 kDa. The enzyme remained active after prolonged incubation at 70 degrees C and was pH insensitive in the range 7-11. Potassium cyanide and diethyldithiocarbamate, known Cu,Zn SOD inhibitors, caused inhibition of the purified enzyme at working concentrations of 0.25 mM, whilst sodium azide and o-phenanthroline demonstrated inhibition at higher concentrations (10-30 mM). SOD activity was also detectable in culture filtrate of A. fumigatus. This enzyme may have a potential role as a virulence factor in the avoidance of neutrophil and phagocyte oxidative burst killing mechanisms.
Amino Acid Sequence↗
Wastage of family income on skin disease in Mexico.
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Absenteeism↗
Childhood eczema: disease of the advantaged?
OBJECTIVE: To determine whether the increased prevalence of childhood eczema in advantaged socioeconomic groups is due to increased parental reporting. DESIGN: Comparison of parental reports of eczema with visible eczema recorded by medical officers during a detailed physical examination. SETTING: National birth cohort study. SUBJECTS: 8279 children from England, Wales, and Scotland born during 3-9 March 1958 and followed up at the ages of 7, 11, and 16. MAIN OUTCOME MEASURES: Prevalence of eczema according to parental report compared with medical officer's examination at the ages of 7, 11, and 16. RESULTS: Prevalence of both reported and examined eczema increased with rising social class at the ages of 7, 11, and 16 years. The point prevalence of examined eczema at age 7 was 4.8%, 3.6%, 3.6%, 2.4%, 2.2%, and 2.4% in social classes I, II, III non-manual, III manual, IV, and V respectively (chi 2 value for linear trend 12.6, P < 0.001). This trend persisted after adjustment for potential confounders such as region and family size and was not present for examined psoriasis or acne. CONCLUSIONS: Eczema is more prevalent among British schoolchildren in social classes I and II than those in lower classes. Exposures associated with social class are probably at least as important as genetic factors in the expression of childhood eczema.
Adolescent↗
Environmental sampling for aspergilli during building construction on a hospital site.
During the course of extensive building activity at Guy's Hospital, London, air sampling was carried out weekly, for one year, to monitor the frequency of spores of Aspergillus spp. in both the hospital grounds and a number of defined ward areas. Nasal swabs were taken from patients on a selected ward to assess the nasal carriage of Aspergillus. The weather conditions were monitored at the time of sampling. The predominant species was Aspergillus fumigatus which occurred at a low frequency throughout the year, with little evidence of seasonal variation bar a peak in March. Few differences were found between internal and external spore counts. Localized building activity in a ward area and a laboratory area did not result in higher internal levels. Six percent of the nasal swabs were positive for A. fumigatus, though none of these patients became infected.
Air Microbiology↗
Liposomal amphotericin B, AmBisome.
The unilamellar liposomal formulation of amphotericin B, AmBisome, is composed of hydrogenated soy phosphatidylcholine, distearoyl phosphatidylglycerol and cholesterol. Early studies of its efficacy in an open design showed that remissions could be induced in candidosis and aspergillosis and that doses of up to 5 mg/kg could be used. Adverse events were infrequent, with the main abnormality seen being hypokalaemia in about 18% of patients. Subsequent developments have extended this work. AmBisome has been used in two open studies of patients with invasive aspergillosis; in one of these remission was achieved in 77% of 17 patients with confirmed infection who had failed to respond to conventional amphotericin B. In AIDS patients with cryptococcosis AmBisome given for 6 weeks at 3 mg/kg daily produced mycological remission of meningitis in 67%. Other infections treated with the drug include zygomycete (mucormycosis) and Fusarium infections. AmBisome has also been used as preventative therapy in bone marrow transplant recipients and was found to reduce fungal colonisation rates. There were fewer systemic fungal infections in the treated versus placebo groups although this did not achieve statistical significance. Lack of renal and liver toxicity or anaemia has been confirmed in subsequent studies. In addition febrile reactions to the AmBisome are rare. The drug has also been used effectively in children, including infants, with systemic fungal infections. In visceral leishmaniasis patients, including HIV positive individuals, remissions have been obtained using drug regimens of 1-2 mg/kg of 2.1 days and 3 mg/kg for 10 days.
Amphotericin B↗
Antifungal therapy of yeast infections.
Candida infections of the skin and mucous membranes are common in both healthy and immunocompromised patients. Management with topical azole or polyene therapy is generally straightforward except in immunocompromised patients with oropharyngeal infections and in Candida onychomycosis. Oral candidosis in patients with AIDS generally requires oral therapy with fluconazole, itraconazole, or ketoconazole. Continuous suppressive therapy carries the risk of the development of clinical tolerance or secondary drug resistance. In nail disease, oral antifungal therapy is appropriate except in paronychia, for which topical azole antifungals appear to be equally effective. In any case it is important to determine whether Candida isolated from nail material is a true nail pathogen or merely colonizing the nail plate. Distal erosion of the nail plate, the presence of underlying host abnormalities such as Raynaud's disease, and hyphae in the nail plate are clues that organism is invading the nail plate.
Acquired Immunodeficiency Syndrome↗
Antifungal drugs on the horizon.
In the past 10 years there has been a major expansion in the development of antifungal drugs, but there are still weaknesses in the range and scope of current antifungal chemotherapy. New developments have included the modification of existing drug molecules to eliminate toxicity and improve activity, for instance, the development of the lipid formulations of the polyene antifungal agent amphotericin B. Three different amphotericin B derivatives, a unilamellar liposome (AmBisome), a colloidal dispersion (ABCD--Amphocil), and a lipid complex (ABLC) are undergoing evaluation. New triazoles with broad-spectrum antifungal activity, such as saperconazole, are also being assessed. The development of groups of drugs with novel modes of action such as cell wall biosynthesis inhibitors has been slower, although a number of molecules with activity against key enzymes, including chitin or glucan synthase, have been found. The morpholine antifungal amorolfine, a sterol biosynthesis inhibitor, has been developed for the topical treatment of fungal nail infections. The assessment of these drugs is a major challenge because it will be necessary to show that they have some advantage over existing compounds in efficacy, speed of action, or lack of toxicity.
Acquired Immunodeficiency Syndrome↗
Epidemiology of fungal skin and nail disease: roundtable discussion held at Dermatology 2000, Vienna, 17 May 1993.
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Canada↗
The U.K. Working Party's Diagnostic Criteria for Atopic Dermatitis. I. Derivation of a minimum set of discriminators for atopic dermatitis.
A working party of 13 dermatologists, two family practitioners and a paediatrician was assembled, with the aim of developing a minimum list of reliable discriminators for atopic dermatitis. Each physician was asked to select 10 consecutive new cases of unequivocal mild to moderate atopic dermatitis and 10 controls with other inflammatory dermatoses. Each subject was examined by two independent observers, who were blind to the clinical diagnosis and study aim, with regard to 31 clinically useful diagnostic features for atopic dermatitis. Two hundred and twenty-four patients were studied (120 cases and 102 controls). Using the key physician's clinical diagnosis as a gold standard, the sensitivity and specificity of each of the 31 diagnostic criteria were tested. Using multiple logistic regression techniques, a minimum set of diagnostic criteria for atopic dermatitis was derived. These were: history of flexural involvement, history of a dry skin, onset under the age of 2, personal history of asthma, history of a pruritic skin condition, and visible flexural dermatitis. Adjustment for age, sex, region, social class and ethnic group did not alter the choice of final criteria. The discriminatory value of these criteria was also satisfactory when tested against a further sample of 150 patients drawn from the community, who did not have skin disease.
Adolescent↗
The U.K. Working Party's Diagnostic Criteria for Atopic Dermatitis. II. Observer variation of clinical diagnosis and signs of atopic dermatitis.
The level of agreement between 14 physicians as to what constitutes a case of atopic dermatitis was tested on 15 selected patients with a range of diagnoses. Between-observer agreement was good, with a mean pair agreement index (P0) of 0.94, and a chance corrected index (kappa) of 0.78. Between-observer agreement in the recording of 18 separate physical signs of atopic dermatitis was then tested by asking the 14 physicians to note the presence or absence of each sign in a different group of patients to those seen in the first part of the exercise. Substantial between-observer agreement (kappa > 0.61) was only present for truncal dermatitis. Most signs showed only fair to moderate agreement (kappa 0.21-0.60), and some signs, such as keratosis pilaris, xerosis, orbital pigmentation, fine hair, and extensor dermatitis, showed poor agreement (kappa 0.01-0.20). The findings were similar when the responses of two independent observers from the national study outlined in Paper I were compared for each sign. Within-observer variation for the recording of physical signs was substantially better than between-observer variation. Physicians interested in atopic dermatitis agree reasonably well on what constitutes a typical case of atopic dermatitis. Between-observer variation with regard to some physical signs of atopic dermatitis is of a magnitude which argues against their continued use in clinical and epidemiological studies.
Dermatitis, Atopic↗
The U.K. Working Party's Diagnostic Criteria for Atopic Dermatitis. III. Independent hospital validation.
In order to qualify as a case of atopic dermatitis, we propose that an individual must have an itchy skin condition plus three or more of the following: history of flexural involvement, a history of asthma/hay fever, a history of a generalized dry skin, onset of rash under the age of 2 years, or visible flexural dermatitis. When tested in an independent sample of 200 consecutive dermatology outpatients of all ages, this arrangement of the diagnostic criteria achieved 69% sensitivity and 96% specificity when validated against physician's diagnosis. Based on the findings of this first exercise, minor modifications in the wording of the criteria were undertaken, and these were tested on a sample of 114 consecutive children attending out-patient paediatric dermatology clinics. Overall discrimination improved, with a sensitivity of 85% and specificity of 96%. The simplified criteria are easy to use, take under 2 min per patient to ascertain, and do not require subjects to undress. These two independent validation studies suggest that the newly proposed criteria for atopic dermatitis perform reasonably well in hospital out-patient patients. Further validation in community settings and in developing countries is needed.
Adolescent↗
Confluent and reticulate papillomatosis of Gougerot and Carteaud clearing with minocycline.
Confluent and reticulate papillomatosis is a rare disorder producing sharply circumscribed hyperpigmented ichthyosiform scaling lesions in a seborrhoeic distribution. Its exact aetiology is unknown and its response to therapy is poor. This case is unusual in responding to minocycline having failed with the more conventional approaches.
Adolescent↗
Liposomal amphotericin B in hepatic candidosis.
A 4 year old girl treated with a standard chemotherapy protocol for acute lymphoblastic leukaemia developed hepatic candidosis during the consolidation phase. This relapsed after a prolonged course of amphotericin B and flucytosine. An eight week course of liposomal amphotericin produced a marked clinical improvement which was sustained for one year. A subsequent relapse was associated with transformation to myelodysplastic leukaemia.
Amphotericin B↗
Dermatophilus congolensis human infection.
Four cases of human dermatophilosis observed in Rio de Janeiro, Brazil, are reported. Data that suggest nail infection by Dermatophilus congolensis are presented. The clinical spectrum of the disease ranged from an asymptomatic infection to a pustular eruption. Our findings suggest that epidermal Langerhans cells play a role in the pathogenesis of the infection.
Actinomycetales Infections↗
Necrobiotic xanthogranuloma without periorbital lesions.
Cutaneous necrobiotic xanthogranuloma is rare and closely resembles widespread necrobiosis lipoidica. It is important to recognize this skin disorder because of its strong association with paraproteinemia and, in some cases, with a hematologic malignancy. We describe two patients with necrobiotic xanthogranuloma who are unusual in that they had no periorbital involvement, a feature previously believed to be diagnostic of this condition.
Aged↗