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A J McDonagh

Publications and source records attributed to A J McDonagh.

At least 19 recordsLinked to original sources
PubMed2001

Association analysis of IL1A and IL1B variants in alopecia areata.

Alopecia areata is an inflammatory hair loss disease with a major genetic component. The disease is characterized by focal inflammatory lesions with perifollicular T-cell infiltrates, reflecting the role of local cytokine production in the development of patchy hair loss. IL-1 alpha and IL-1 beta are important inhibitors of hair growth in vitro. Their effect is opposed by the interleukin-1 receptor antagonist, IL-1ra. Genes of the IL-1 cluster are candidate genes in the pathogenesis of alopecia areata. To investigate the role of the IL-1 system in alopecia areata we examined three biallelic polymorphisms within the IL-1 gene cluster (IL1A+4845, IL1B+3954 and IL1B-511) in 165 patients and a large number of matched controls (n=1150). There was no significant association of IL1B-511 or IL1B+3954 genotypes with the overall dataset, or with disease severity or age at onset, in contrast with a previous report. The results suggested the possibility of an association with IL1A+4845 in the overall dataset [OR 1.39 (95% CI 1.00, 1.93)] although this was not statistically significant. This was due mainly to the contribution from mild cases of alopecia areata [OR 1.48 (0.96, 2.29)], suggesting that IL-1 alpha may have a particular role in the pathogenesis of this subgroup.

Adult↗
PubMed2000

Structure and polymorphism of the human gene for the interferon-induced p78 protein (MX1): evidence of association with alopecia areata in the Down syndrome region.

Alopecia areata (AA) is a chronic inflammatory disease characterised by patchy hair loss with T cell infiltration of hair follicles. AA occurs in approximately 0.1% of the general population, but this is increased to 9% in Down syndrome (DS). DS is associated with an additional copy (full or partial) of chromosome 21, and the DS region may potentially include genes involved in the pathogenesis of AA. MX1 is the gene encoding the interferon-induced p78 protein (MxA). MxA protein confers resistance to influenza viruses, and we have previously shown that MxA protein is strongly expressed in lesional anagen hair bulbs from patients with AA but not in normal follicles. We therefore studied the possible involvement of MX1 in the pathogenesis of AA. To establish markers in the MX1 region which could be screened by PCR-based methods, we defined the human MX1 exon/intron organisation and screened the exons and the introns by conformation-sensitive gel electrophoresis. We found that the MX1 gene contains 17 exons extending over 33 kb. The size and sequence of the region from exon 6 to exon 16 are highly conserved between human and mouse. Screening of 4747 bp within the MX1 gene revealed four single nucleotide polymorphisms in intron 6. These polymorphisms are concentrated within 147 bp and show strong linkage disequilibrium. In a case-control association study for the MX1 (+9959) polymorphism in 165 AA patients and 510 controls we found a significant association of this marker with AA (odds ratio 1.79, 95% CI 1.21-2.66, chi2 = 8.464, P = 0.0036). The risk of disease was greater for patchy AA (mild disease) and with early age at onset (odds ratio 2.34, 95% CI 1.24-4.43, P = 0.0072), providing new evidence of genetic heterogeneity in AA. Our demonstration of genetic association between the MX1 gene and disease supports the hypothesis that this is a new candidate gene in AA.

Alopecia Areata↗
PubMed2000

Rupert Hallam and the development of dermatology in Sheffield.

(Arthur) Rupert Hallam worked as a dermatologist in Sheffield from 1911 to 1944. Early in his career, he also specialized in diagnostic radiology and established this speciality in Sheffield. Hallam performed investigative work on the aetiology of papular urticaria and erythema multiforme, the prognosis of psoriasis, and the aetiology of chilblains. He was an original member of the British Association of Dermatologists from 1920 becoming president in 1935. He also helped to found the North of England Dermatological Society. He was an innovator in both clinical and administrative matters and was the first British dermatologist to develop a full-time training post in the specialty.

Dermatology↗
PubMed1996

The pathogenesis of alopecia areata.

Knowledge of the disease mechanisms in alopecia areata is discussed in the light of progress in hair biology, immunology, and genetics. A disease model is presented incorporating polygenic determination of disease severity and susceptibility with largely unknown trigger factors responsible for initiating clinical disease expression. Experimental systems including animal models for alopecia areata offer new opportunities for investigation of alopecia areata and developing novel therapies.

Alopecia↗
PubMed1995

Fractal and integer-dimensional geometric analysis of pigmented skin lesions.

Accurate in vivo diagnosis of pigmented skin lesions is required to identify and excise malignant melanomas but to avoid unnecessary excision of benign lesions; the published rates of clinical diagnostic accuracy are about 65%. This study investigates whether fractal geometric analysis of pigmented skin lesions can improve the rate of diagnostic accuracy. Forty-two pigmented skin lesions (15 malignant melanomas, 21 melanocytic naevi, and 6 basal cell papillomas) on patients attending a dermatology clinic were photographed, excised, and sent for histopathological examination. The fractal dimension of the boundary of the lesions was measured using a box-counting method implemented on a microcomputer-based image analysis system. Euclidean geometric parameters were also measured. The fractal dimension of all the lesions was greater than the topological dimension (one), indicating that there is a fractal element to their structure. Using all measured parameters together, multivariate linear discriminant analysis produced a confusion matrix in which 45% of the lesions were assigned to the correct diagnostic group with a kappa statistic of 0.33. There was no significant difference between the fractal dimension of melanocytic naevi and that of malignant melanomas (p = 0.18). Although pigmented skin lesions have a fractal element to their structure, the fractal dimension of their boundaries is not a useful morphometric discriminant between the diagnostic groups of malignant melanomas and benign melanocytic naevi.

Algorithms↗
PubMed1994

The aetiology and pathogenesis of alopecia areata.

In common with a number of inflammatory autoimmune diseases, genetic factors including HLA class II associations have been identified in alopecia areata. No consensus has been reached on the identity of a specific disease target within the hair follicle in alopecia areata. Suggested candidate cell types include the dermal papilla cells, the keratinocytes of the matrix and presumptive cortex and the hair bulb melanocytes, but these need not be mutually exclusive. The pathogenesis is known to involve disturbance of immune function but there is no proof that an autoimmune mechanism is fundamental. We propose a pathogenetic model incorporating polygenic determination of disease susceptibility and severity with additional, possibly environmental, factors as triggers for disease expression.

Alopecia Areata↗
PubMed1994

Severity of alopecia areata is associated with a polymorphism in the interleukin-1 receptor antagonist gene.

One of the most potent pro-inflammatory mediators is the early-acting cytokine interleukin-1. Its actions are regulated by a structurally related anti-inflammatory cytokine known as the interleukin-1 receptor antagonist. We have previously characterized a DNA polymorphism in this gene (IL-1rn) and have found associations between allele 2 and several chronic inflammatory diseases. In the present study, we tested the frequency of allele 2 of the IL-1rn gene in 90 patients with alopecia areata compared with 261 healthy controls. There was a significant association between allele 2 of the polymorphism and the severity of alopecia areata. The frequency of allele 2 increased from 24.1% in the control population to 25.9% in patchy alopecia areata, 36.1% in alopecia totalis, and 47.2% in alopecia universalis (p = 0.005). This severity association is similar to that found in other epithelial-related diseases, including inflammatory bowel disease, lichen sclerosus, and systemic lupus erythematosus.

Alleles↗
PubMed1994

An audit of the value of patch testing: the patient's perspective.

Evaluation of the benefits of patch testing has been difficult. We have attempted to establish patients' views on patch testing and to assess the effectiveness of advice given in the clinic. Postal questionnaires were sent to 135 patients. A total of 105 replies were received (77.8% response rate). 42 patients (40.4%) reported improvement in their skin condition after testing. Of the 43 patients with a final diagnosis of allergic contact dermatitis (ACD), 31 (72%) believed that patch testing had helped. About 1/2 of these were able to avoid the allergens concerned and had made changes in their lifestyle. This contrasts with the group of patients with final diagnoses other than ACD, in whom only 20 of 62 (32%) recorded patch testing as helpful. Similar numbers in both groups had improved sufficiently to be discharged from the clinic. 91 of the patients were entirely correct in their knowledge of the patch test results. 39 felt that the results had not been explained in sufficient detail. This study shows that patch testing is beneficial, especially for those with ACD. Patients' knowledge of the results was good but education could be improved.

Adolescent↗
PubMed1993

Phytophotodermatitis mimicking child abuse.

A 13-month-old girl presented with red finger marks on both shoulders thought initially to be secondary to child abuse. The appearance of the marks was not typical of bruising of the stated age and there were no social concerns or other medical features of child abuse. Direct questioning revealed that the mother had been gardening on a sunny day and had picked the child up prior to the appearance of the marks. The marks are thought to represent a phytophotodermatitis. Many paediatric skin conditions can mimic child abuse. Recognition of this further possibility will prevent avoidable errors of diagnosis.

Child Abuse↗
PubMed1993

Chloracne--study of an outbreak with new clinical observations.

A recent outbreak of chloracne in 17 workers is reported at a plant manufacturing dichloroaniline derivatives. Comedones developed 6-12 weeks after accidental exposure to the chloracnegenic contaminants and were present in every case. Cutaneous xerosis and a folliculitis, previously only rarely described as manifestations of chloracne, were noted in half the patients. The pathogenesis of these lesions is uncertain but may involve a disorder of keratinization.

Acne Vulgaris↗