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Biomedical subjects

J McLelland

Publications and source records attributed to J McLelland.

At least 19 recordsLinked to original sources
PubMed2000

A comparison of molecular and enzyme-based assays for the detection of thiopurine methyltransferase mutations.

S-Methylation by thiopurine methyltransferase (TPMT) is an important route of metabolism for the thiopurine drugs. About one in 300 individuals are homozygous for a TPMT mutation associated with very low enzyme activity and severe myelosuppression if treated with standard doses of drug. To validate the use of molecular genetic techniques for the detection of TPMT deficiency, we have determined red blood cell TPMT activity in 240 adult blood donors and 55 normal children. Genotype was determined by restriction fragment length analysis of polymerase chain reaction products in a cohort of 79 of the blood donors and five cases of azathioprine-induced myelosupression, and this confirmed a close relationship between genotype and phenotype. In 17 of the 24 cases in which mutations were found, DNA was also available from remission bone marrow. In one of these cases, DNA from the remission marrow sample indicated the presence of a non-mutated allele that had not been seen in the blast DNA sample obtained at presentation. These results indicate that polymerase chain reaction-based assays give reliable and robust results for the detection of TPMT deficiency, but that caution should be exercised in relying exclusively on DNA obtained from lymphoblasts in childhood leukaemia.

Adolescent↗
PubMed1996

Metastatic Crohn's disease of the umbilicus.

We report a case of metastatic Crohn's disease of the umbilicus which responded to topical corticosteroid treatment. Crohn's disease is a granulomatous disease of the bowel which may affect other organs. The skin is commonly involved, and the cutaneous manifestations may be non-specific, e.g. pyoderma gangrenosum or erythema nodosum, or specific with epithelioid granulomas and multinucleated giant cells in the skin. Specific skin lesions may be contiguous with the bowel at sites including the perineum, mouth and adjacent to fistulae, or separated from it by normal skin from the bowel, a rare condition which has been termed 'metastatic' Crohn's disease.

Aged↗
PubMed1996

Patch testing with a combination of unrelated allergens: a new strategy.

A simplified method of patch testing was designed, in which several totally unrelated allergens were combined in each patch. The method was evaluated by double blind comparison of responses to 17 standard allergens applied individually as 17 conventional patch tests, and as two different sets of five patches each containing combinations of three of four allergens per patch, in 137 patients under investigation for contact allergic dermatitis. There were 89 positive responses to conventional patch testing with separate allergens and 94 and 86 positives to the two different combinations of the same allergens. Concordance of positive reactions to the two combinations was 80% and there were no irritant reactions. Conventional testing detected 70 and 74% of reactions to combination patches 1 and 2 and combination patches 1 and 2 detected 80 and 79% of the reactions to conventional testing. The combinations detected clinically relevant sensitivities not found by conventional testing. Thus, combination patch testing appears to give consistent and reliable results; its use would reduce the number of patches and increase the diagnostic yield for the specialist and permit preliminary screening by the general practitioner.

Adult↗
PubMed1993

Quantification of contact allergic inflammation: a comparison of existing methods with a scanning laser Doppler velocimeter.

Responses to a range of doses of common contact dermatitis-producing allergens were measured using a novel scanning laser Doppler velocimeter and three commonly used conventional measurement techniques. The techniques were compared in terms of sensitivity, measurement error, range of the linear portion of the dose-response curve and ease of use. The detection thresholds of the objective methods did not differ significantly and did not detect responses at concentrations less than those required to produce a visible response. Of the objective methods the range of linearity was greatest when reactions were measured using change in skin fold thickness, erythema or area of inflammation. Measurement error was greatest with measurements made using the conventional laser Doppler velocimeter. Present instrumental methods are no more sensitive than visual assessment in the reading of patch test reactions. The conventional laser Doppler velocimeter was least suited for measurement of allergic contact hypersensitivity reactions as readings are time-consuming, show detectable changes over a more limited range of allergen concentration, and have a larger measurement error than the other methods. There is no single best method for measuring allergic contact hypersensitivity reactions. Useful data over a wide range of allergen concentrations can best be obtained by measurement of skin fold thickness, erythema or area of reaction using the scanning laser Doppler velocimeter. The scanning laser Doppler velocimeter has the added advantages of being able to measure area of reaction without contact with the skin surface and to measure reactions at all skin sites.

Dermatitis, Allergic Contact↗
PubMed1992

Topical ketoconazole does not potentiate oral cyclosporin A in allergic contact dermatitis.

Cyclosporin A is an effective drug but its use is limited by its side effects. Since oral ketoconazole inhibits the metabolism of oral cyclosporin, we set out to find out whether topical ketoconazole would enhance the effect in the skin of oral cyclosporin. Five patients with contact allergic dermatitis (CAD) were given a 6-day course of cyclosporin (1 mg/kg/day) and applied 2% ketoconazole cream to an area on one arm and the inert base to the other. Serial dilutions of the relevant allergen were applied to the arms at 3 days for 48 hours, and the responses were measured objectively a day later. There was no significant difference between responses at the two sites, indicating that topical ketoconazole does not enable the dose of oral cyclosporin to be reduced in CAD.

Administration, Cutaneous↗
PubMed1991

Oral cyclosporin inhibits the expression of contact hypersensitivity in man.

The expression of delayed contact hypersensitivity was studied in 6 patients with chronic contact dermatitis treated with cyclosporin A (CsA) 5 mg/Kg/day. Quantitative patch test challenge was used to establish individual dose-response curves and threshold concentration to certain allergens in the European Standard Battery. In all 6 patients, responses were reduced over the whole range of allergen concentrations, and in the 5 in whom the threshold for expression of contact hypersensitivity could be determined, the threshold was raised by CsA therapy. In addition, the clinical manifestations of allergic contact dermatitis underwent complete resolution within 2-3 weeks of CsA therapy. It was concluded that CsA inhibits expression of delayed contact hypersensitivity reactions in human skin.

Administration, Oral↗
PubMed1991

Measurement of cutaneous inflammatory reactions using a scanning laser-Doppler velocimeter.

The performance of a new scanning laser-Doppler velocimeter (LDV), which can rapidly measure blood flux over a large area of skin without contact with the skin surface, was compared with that of a conventional laser-Doppler instrument. The vascular response was measured to a range of doses of UVB, and dilutions of contact allergens and sodium lauryl sulphate. The detection threshold of the scanning LDV was equal to, or lower than, that of the conventional instrument. For allergic contact hypersensitivity reactions (ACH), the coefficient of variation was significantly less using the scanning LDV. The scanning LDV allowed accurate measurement of the change in area that occurs with increasing intensity of inflammatory reaction. For ACH reactions the area of inflammation continued to increase at dilutions where blood flux had reached a plateau. The flare area was found to increase linearly with log dose of histamine with no change in blood flux.

Dermatitis↗