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Biomedical subjects

T A Chave

Publications and source records attributed to T A Chave.

At least 19 recordsLinked to original sources

Toxic epidermal necrolysis: current evidence, practical management and future directions.

Toxic epidermal necrolysis (TEN) is a rare disorder characterized by extensive epidermal death. Almost all cases appear to be caused by an idiosyncratic drug reaction. Proposed pathogenic mechanisms are conflicting, and the evidence for the benefits of individual treatments is inadequate, and in some cases contradictory. The mortality rate remains high. We review the literature pertaining to the pathogenesis of TEN and drug reactions in general. The rationale for therapeutic interventions, together with reported evidence of efficacy, are considered. We present a composite model of TEN, based on previous work and suggested pathogeneses of TEN, mechanisms of drug reactions and reported cytotoxic lymphocyte (CTL) cytolytic pathways. In this system, TEN, like some other cutaneous drug eruptions, is an HLA class I-restricted, specific drug sensitivity, resulting in clonal expansion of CD8+ CTLs. Cytotoxicity is mediated by CTL granzyme and possibly death receptor (DR) ligand (DR-L), probably Fas ligand (FasL). Particular to TEN, there is then an amplification sequence involving further DR-L expression. FasL is likely to be particularly important but tumour necrosis factor (TNF) may well contribute, via the TNF receptor 1 (TNF-R1) death pathway. Alternatively, we suggest the possibility of upregulation of an antiapoptotic TNF-R1-nuclear factor kappaB pathway, which would proscribe treatments which downregulate this pathway. None of the published data on individual treatment efficacies is sufficiently strong to suggest a definitive single treatment. Currently a multifaceted regimen appears indicated, targeting various likely intermediary mechanisms, including elimination of residual drug, immunosuppression, inhibition of DR pathways, general antiapoptotic strategies, and aggressive supportive care. Particular attention has been directed at avoiding potential conflicts between different treatments and avoiding agents that theoretically might have a net proapoptotic rather than antiapoptotic effect. Nursing on a specialized unit is of paramount importance.

Adrenal Cortex Hormones↗

Comparison of diagnostic accuracy for cutaneous malignant melanoma between general dermatology, plastic surgery and pigmented lesion clinics.

BACKGROUND: Since the 1980s there have been dedicated pigmented lesion clinics (PLCs) in the U.K. Important considerations when comparing the efficacy of the PLC with other referral clinics include diagnostic accuracy. OBJECTIVES: To compare the false-negative rate of clinical diagnosis (FNR) in the PLC with that in the other clinics of primary referral of malignant melanoma (MM) in the same geographical area. We have previously shown that certain clinical features are risk factors for diagnostic failure of MM. A further aim of this study was to correct for any differences in frequency of these factors in the melanoma populations between clinics and to estimate the false-positive diagnostic rate (FPR) in the PLC. METHODS: To compare the FNR between clinics, the case notes of all patients presenting with histologically proven cutaneous MM in Leicestershire between 1987 and 1997 were examined retrospectively. A false-negative diagnosis was defined as documentation of another diagnosis and/or evidence in the case notes that the diagnosis was not considered to be MM. The FNR was estimated as the number of false-negative clinical diagnoses/number of true-positive histological diagnoses. To estimate the diagnostic FPR, which was defined as the number of false-positive clinical diagnoses of MM/total number of positive clinical diagnoses, in the PLC, the outcome of 500 consecutive patients attending the PLC was surveyed. RESULTS: The case notes of 731 patients were available, of whom approximately two-thirds initially attended the PLC, one-fifth the General Dermatology clinics (D) and the remainder were divided approximately equally (one-twentieth each) between Plastic Surgery clinics (P), other clinics (O) and the surgery of the general practitioner (GP). The last was regarded as the primary referral clinic if the lesion were excised there prior to any referral. The FNR was lowest for the PLC, at 10%, compared with 29% (D), 19% (P), 55% (O) and 54% (GP) (P < 0.0001). Lesions with risk factors for diagnostic failure were under-represented in the PLC (P < 0.0001), the mean frequencies of the risk factors being 20% (PLC), 25% (D), 22% (P), 31% (O) and 30% (GP). Differences were not large but still could partially explain the lower FNR of the PLC. However, when the FNR was estimated for lesions exhibiting each of these risk factors, the PLC was found to have the lowest rate in every case (PLC vs. all clinics combined, P = 0.04 to P < 0.0001). The mean FNR for the risk factors combined was 18% (PLC), 45% (D), 50% (P), 68% (O) and 71% (GP). Also on logistic multivariable analysis of the PLC vs. all the other clinics on FNR and the above factors, the higher FNR of the other clinics retained significance (odds ratio 5.9, P < 0.0001). In the 500 patients surveyed separately in the PLC, the MM pick-up rate on biopsy was 32% and the diagnostic FPR was 41%. CONCLUSIONS: The FNR of MM was lower in the PLC than in the other clinics, while the pick-up rate for MM on biopsy and the FPR were acceptably low.

Aged↗

Red tattoo reactions.

Considering the ever increasing popularity of tattoos, significant reactions remain unusual. Red pigments are the commonest cause of delayed tattoo reactions. Histology typically shows extensive lichenoid basal damage, well away from the dermal pigment. We report two cases of lichenoid reactions to red tattoo pigment and review the literature on the subject.

Coloring Agents↗

Recalcitrant necrobiotic xanthogranuloma responding to pulsed high-dose oral dexamethasone plus maintenance therapy with oral prednisolone.

A patient with the rare condition necrobiotic xanthogranuloma was treated from 1992 to 1999 with multiple therapies, none of which was effective. Her disease was progressive, causing significant disability. In September 1999 a trial of high-dose pulsed oral dexamethasone with maintenance corticosteroids led to a substantial improvement in her condition.

Aged↗

Thalidomide usage in Wales: the need to follow guidelines.

BACKGROUND: Thalidomide is a potentially useful drug for several dermatological disorders. OBJECTIVES: To assess prescribing and monitoring practices for this drug in Wales. METHODS: A questionnaire was completed by 17 of 19 consultant dermatologists concerning thalidomide usage in Wales (population 2.93 million). RESULTS: Eleven of the 17 respondents had used thalidomide in 40 patients. Only two consultants gave information leaflets and only five obtained written consent. Four obtained baseline nerve conduction studies and nine obtained these during therapy. Of seven women of child-bearing age currently taking thalidomide, none had had baseline pregnancy tests. CONCLUSIONS: We describe variability in prescribing practices for thalidomide. Published guidelines are reviewed and suggestions made concerning consent forms, pregnancy testing, nerve conduction studies and patient information.

Dermatologic Agents↗