Psoriasis: Ormerod AD

Smith CH, Anstey AV, Barker JN, Burden AD, Chalmers RJ, Chandler D, Finlay AY, Griffiths CE, Grifitths CE, Jackson K, McHugh NJ, McKenna KE, Reynolds NJ, Ormerod AD, Anonymous00078. · St John's Institute of Dermatology, GKT School of Medicine, St Thomas' Hospital, London SE1 7EH, UK. · Br J Dermatol. · Pubmed #16120132 No free full text.

This publication has no abstract.

Ormerod AD. · No affiliation provided · Br J Dermatol. · Pubmed #18275521 No free full text.

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Cals-Grierson MM, Ormerod AD. · L' Oréal Recherche, Clichy, France. · Nitric Oxide. · Pubmed #15275864 No free full text.

Abstract: Endogenously produced nitric oxide (NO) has a remarkably diverse range of biological functions, including a role in neurotransmission, smooth muscle relaxation, and the response to immunogens. Over the last 10 years, it has become clear that this extraordinary molecular messenger also plays a vital role in the skin, orchestrating normal regulatory processes and underlying some of the pathophysiological ones. We thought it pertinent to review the current literature concerning the possible function of NO in normal skin, its clinical and pathological significance, and the potential for therapeutic advances. The keratinocytes, which make up the bulk of the epidermis, constitutively express the neuronal isoform of NO synthase (NOS1), whereas the fibroblasts in the dermis and other cell types in the skin express the endothelial isoform (NOS3). Under certain conditions, virtually all skin cells appear to be capable of expressing the inducible NOS isoform (NOS2). The expression of NOS2 is also strongly implicated in psoriasis and other inflammatory skin conditions. Constitutive, low level NO production in the skin seems to play a role in the maintenance of barrier function and in determining blood flow rate in the microvasculature. Higher levels of NOS activity, stimulated by ultraviolet (UV) light or skin wounding, initiate other more complex reactions that require the orchestration of various cell types in a variety of spatially and temporally coordinated sets of responses. The NO liberated following UV irradiation plays a significant role in initiating melanogenesis, erythema, and immunosuppression. New evidence suggests that it may also be involved in protecting the keratinocytes against UV-induced apoptosis. The enhanced NOS activity in skin wounding (reviewed recently in this journal [Nitric oxide 7 (2002) 1]) appears to be important in guiding the infiltrating white blood cells and initiating the inflammation. In response to both insults, UV irradiation and skin wounding, the activation of constitutive NOS proceeds and overlaps with the expression of NOS2. Thus, at a macro-level, at least three different rates of NO production can occur in the skin, which seem to play an important part in organizing the skin's unique adaptability and function.

Ormerod AD, Mrowietz U. · Aberdeen Royal Infirmary, Foresterhill, Aberdeen AB15 8SG, UK. · Br J Dermatol. · Pubmed #15099356 No free full text.

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Ormerod AD. · Aberdeen University and University Hospitals, Department of Dermatology, Aberdeen Royal Infirmary, Aberdeen, AB25 2ZN, UK. · Curr Opin Investig Drugs. · Pubmed #12833658 No free full text.

Abstract: Alefacept is a lymphocyte function-associated antigen-3/IgG1 fusion protein that inhibits T-cells by antagonizing CD2, which has been developed and launched by Biogen for the potential treatment of psoriasis. In February 2003, Biogen launched alefacept in the US for use in adults with moderate-to-severe chronic plaque psoriasis, and by March 2003, the company was preparing for psoriasis trials to commence in Japan by the end of December 2003.

Ormerod AD. · Department of Dermatology, Aberdeen Royal Infirmary, Foresterhill, Aberdeen AB25 2ZN, UK. · Br J Dermatol. · Pubmed #11736890 No free full text.

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Ormerod AD, Shah SA, Copeland P, Omar G, Winfield A. · Department of Dermatology, Aberdeen Royal Infirmary, Aberdeen AB25 2ZN, UK. · Br J Dermatol. · Pubmed #15840110 No free full text.

Abstract: BACKGROUND: Systemically administered sirolimus has demonstrated efficacy in psoriasis in a multicentre European study. OBJECTIVES: To determine the efficacy and safety of topically applied sirolimus in treating psoriasis. METHODS: In vitro studies were followed by a pilot study designed to determine if sirolimus penetrates human skin, and by a randomized, double-blind, left-right comparative, dose-ranging study consisting of treatment with 2.2% sirolimus for 6 weeks and 8% sirolimus for an additional 6 weeks in 24 patients with stable, chronic plaque psoriasis. The primary outcome measure was clinical score. Secondary measures were ultrasound plaque thickness, plaque erythema, and computerized image analysis of immunohistochemical stains for immunocytes and proliferating cells. Pharmacokinetics and blood chemistry monitoring for safety were also performed. RESULTS: A significant reduction in the clinical score (P = 0.03) (mean score 9.1 following sirolimus vs. 11.2 in control) was achieved with topical sirolimus. Measurements of plaque thickness and erythema did not show significant improvement with treatment. Computerized image analysis of biopsies showed a significant reduction in CD4+ cells (P = 0.0054) and proliferating cells (stained by Ki-67) in the epidermis (P = 0.0153) with sirolimus treatment compared with control. CONCLUSIONS: Topically applied sirolimus penetrates normal skin and may have some antipsoriatic and immunosuppressive activity.

Ormerod AD, Copeland P, Shah SA. · Department of Dermatology, Aberdeen Royal Infirmary, Foresterhill, Aberdeen, AB25 2ZN, U.K. · Br J Dermatol. · Pubmed #10809860 No free full text.

Abstract: A double blind left, right comparative study was carried out in 17 psoriatic subjects to examine the influence of a topically applied inhibitor of nitric oxide (NO) synthesis on the pathogenic events of psoriasis. The inhibitor NG-monomethyl-L-arginine (L-NMMA) in aqueous cream BP was applied to one plaque while aqueous cream BP alone served as control. Compared with the control, the L-NMMA-treated side showed significant (77%) inhibition of NO production and a reduction in blood flow, confirming its bioavailability. L-NMMA significantly reduced staining for endothelial cells and intercellular adhesion molecule 1, while CD1a-positive Langerhans cells and CD8-positive suppressor cytotoxic T cells increased. CD4-positive lymphocytes and epidermal proliferation, as indicated by Ki-67 staining, were unaffected by this degree of inhibition of NO synthesis, and correspondingly significant clinical improvement was not found.

Eedy DJ, Griffiths CE, Chalmers RJ, Ormerod AD, Smith CH, Barker JN, Potter J, Ingham J, Lowe D, Burge S. · Department of Dermatology, Southern Health and Social Care Trust, 68 Lurgan Road, Portadown BT9 6NY, UK. · Br J Dermatol. · Pubmed #19120330 No free full text.

Abstract: BACKGROUND: Medical professionals require data about the structure and delivery of dermatological services in primary and secondary care in order to identify and tackle variations in standards and monitor the impact of healthcare reforms. The British Association of Dermatologists (BAD) commissioned an audit of the provision of care for patients with psoriasis. OBJECTIVES: To assess the staffing and facilities in dermatology units in the U.K. with a focus on the provision of care for patients with psoriasis. METHODS: Data were collected from 100 dermatology units in the U.K. for 1 year using a questionnaire and a web-based collection system. RESULTS: Key results are as follows. Eighteen per cent (18/98) of units had fewer than 2.0 whole-time equivalent consultants and 20% had no specialist dermatology nurse. Only 23% of units collected diagnostic data on outpatients, and half were unable to supply details about the number of attendances for psoriasis. Seventy-seven units reported admitting patients to dedicated dermatology beds, general medical beds, or both; three-quarters of units had access to dedicated adult dermatology beds. Pharmacy services were not always available for dermatology patients. Only 21 units (21%) had dedicated clinics for patients with psoriasis and 56% of units lacked a clinical psychology service willing to accept adult dermatology patients; 59% (55/93) lacked psychological services for children. Fifty-five per cent had no systemic drug monitoring clinic. Phototherapy was run by dermatology nurses in 93% (88/95) of the units and by physiotherapists in 11% (10/94). Biologics for psoriasis were prescribed in 75% (73/97) of units and in 88% (64/73) of these the BAD guidelines for the use of biologics were known to be followed. Of the seventy-three units prescribing biologic therapies, 64% had a nurse trained in the assessment and administration of biologics, 71% had facilities for outpatient infusions (e.g. for infliximab) and 39% were restricted in prescribing biologic agents because of financial constraints. A quality-of-life score was either inadequately or never recorded in outpatient records in 81% of units, increasing to 88% for inpatient records. The Psoriasis Area and Severity Index score was inadequately or never recorded in 79% of outpatient records and 82% of inpatient records. CONCLUSIONS: Units varied in their capacity to meet BAD guidelines and standards. Among the most significant deficiencies identified were a shortage of specialist dermatology nurses, treatment delivery by untrained nurses and financial constraints on the prescription of biologics for psoriasis. Gaps in data collection and record keeping jeopardize efforts to improve standards of care.

Smith CH, Ormerod AD. · No affiliation provided · Arch Dermatol. · Pubmed #18087022 No free full text.

This publication has no abstract.