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Biomedical subjects

Christopher E M Griffiths

Publications and source records attributed to Christopher E M Griffiths.

43 records · Page 3Linked to original sources

Psychological stress, distress and disability in patients with psoriasis: consensus and variation in the contribution of illness perceptions, coping and alexithymia.

OBJECTIVES: The purpose of this study was to examine the relative contribution of medical variables, illness perceptions, coping and alexithymia to the variance in stress, distress and disability in patients with psoriasis. DESIGN: Cross-sectional study. METHOD: A group of 225 patients with psoriasis completed the Hospital Anxiety and Depression Scale (HADS), The Penn State Worry Questionnaire (PSWQ), the COPE, the Illness Perception Questionnaire (IPQ), Toronto Alexithymia Scale (TAS-20), and two measures specific to psoriasis, the Psoriasis Disability Index (PDI), and the Psoriasis Life Stress Inventory (PLSI). The severity of patients' psoriasis was clinically assessed by dermatologists on the Psoriasis Area and Severity Index (PASI). RESULTS: In general, demographic variables, clinical history and extent of disease were consistently the least useful variables in terms of explaining variance in stress, distress or disability. Their utility was limited to accounting for small but significant variations in disability, but even in this case, they accounted for just over half as much variance as illness perceptions. Illness perceptions were uniformly the most important variables in terms of the variance accounted for in outcome. Coping varied widely in its explanatory power; its effects were negligible in both disability (PDI) and everyday stress (PLSI), and it was moderately important in accounting for additional variance in depression and anxiety. However, coping was important in explaining the variance in pathological worrying. Alexithymia accounted for significant additional variance chiefly for anxiety and to a lesser extent for depression, worrying and psoriasis-related life stress. CONCLUSION: The observed importance of cognitive factors in stress, distress and disability invite us to consider the utility of multivariate models of outcome in psoriasis.

Adaptation, Psychological↗

Infliximab induction and maintenance therapy for moderate-to-severe psoriasis: a phase III, multicentre, double-blind trial.

BACKGROUND: Tumour necrosis factor alpha (TNFalpha) is thought to play a part in the pathogenesis of psoriasis. We assessed the efficacy and safety of continuous treatment with infliximab, a monoclonal antibody that binds to and neutralises the activity of TNFalpha, in patients with psoriasis. METHODS: In this phase III, multicentre, double-blind trial, 378 patients with moderate-to-severe plaque psoriasis were allocated in a 4:1 ratio to receive infusions of either infliximab 5 mg/kg or placebo at weeks 0, 2, and 6, then every 8 weeks to week 46. At week 24, placebo-treated patients crossed over to infliximab treatment. Skin and nail signs of psoriasis were assessed using the psoriasis area and severity index (PASI) and nail psoriasis severity index (NAPSI), respectively. The primary endpoint, analysed on an intention-to-treat-basis, was the proportion of patients achieving at least a 75% improvement in PASI from baseline to week 10. FINDINGS: At week 10, 80% (242/301) of patients treated with infliximab achieved at least a 75% improvement from their baseline PASI (PASI 75) and 57% (172/301) achieved at least a 90% improvement (PASI 90), compared with 3% and 1% in the placebo group, respectively (p<0.0001). At week 24, PASI 75 (82% for infliximab vs 4% for placebo) and PASI 90 (58%vs 1%) were maintained (p<0.0001). At week 50, 61% achieved PASI 75 and 45% achieved PASI 90 in the infliximab group. Infliximab was generally well tolerated in most patients. INTERPRETATION: Infliximab is effective in both an induction and maintenance regimen for the treatment of moderate-to-severe psoriasis, with a high percentage of patients achieving sustained PASI 75 and PASI 90 improvement through 1 year.

Adult↗

Epidermal Langerhans cell migration and sensitisation to chemical allergens.

Epidermal Langerhans cells (LC) form part of the wider family of dendritic cells (DC; professional antigen-processing and antigen-presenting cells). LC are considered to serve in the skin as sentinels of the adaptive immune system, surveying the local environment and transporting foreign antigen for presentation to responsive T lymphocytes in regional lymph nodes. As such, LC play pivotal roles in the initiation of cutaneous immune responses, including immune responses to chemical allergens encountered at skin surfaces. Here we explore two aspects of LC function in the context of sensitisation to chemical allergens. The first is consideration of the cytokine and chemokine signals that regulate and counter-regulate the mobilisation and migration of LC from the epidermis to skin-draining lymph nodes following topical sensitisation. The second is examination of the ways in which LC may influence the polarity of induced T lymphocytes, and thereby the quality of immune responses.

Allergens↗

The use of retinoids in the treatment of photoaging.

Photoaging describes the clinical and histologic consequences of chronic sun exposure, the key features of which--wrinkles and mottled hyperpigmentation--are frequently and erroneously attributed to the aging process. Although a number of surgical procedures can improve the clinical appearance of photoaged skin, the only medical therapy with proved benefit derived from randomized clinical trial evidence is the use of topical retinoids, particularly tretinoin, isotretinoin, and tazarotene. Retinoids are capable not only of repairing photoaged skin at both the clinical and biochemical levels but their use may prevent photoaging. There is in addition emerging evidence that topical retinoids could be beneficial in the treatment of intrinsically aged skin.

Administration, Topical↗

The macrolide immunosuppressants in dermatology: mechanisms of action.

Macrolides are xenobiotics, produced by soil fungi, which have immunosuppressant properties. They will probably revolutionise the treatment of inflammatory dermatoses. This article outlines the context and putative mechanisms of action of this novel class of drugs. Cyclosporin, and the structurally distinct macrolides tacrolimus and pimecrolimus (an ascomycin derivative), modulate immune-cell function by inhibiting calcineurin-dependent dephosphorylation-activation of specific nuclear factors, thus preventing transcription of pro-inflammatory cytokines. The macrolide rapamycin (sirolimus) acts by abrogating Target of Rapamycin, a key signalling protein that controls activation of a number of proteins which direct progression of the cell cycle in response to pro-inflammatory cytokines. Tacrolimus and pimecrolimus are small enough molecules to penetrate skin and are available in topical formulations. "Skin-specific" pimecrolimus seems not to cause systemic immunosuppression when given orally. Neither topical tacrolimus nor pimecrolimus are capable of producing skin atrophy. Sirolimus has anti-angiogenic properties that may be beneficial to the treatment of psoriasis and perhaps skin cancer.

Calcineurin↗