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Biomedical subjects

C E M Griffiths

Publications and source records attributed to C E M Griffiths.

65 records · Page 4Linked to original sources
PubMed2002

Randomized comparison of the type 4 phosphodiesterase inhibitor cipamfylline cream, cream vehicle and hydrocortisone 17-butyrate cream for the treatment of atopic dermatitis.

BACKGROUND: Therapeutic options to treat atopic dermatitis are limited. Leukocytes from atopic patients have an abnormally high activity of cyclic adenosine monophosphate (AMP)-phosphodiesterase (PDE), which can be normalized in vitro by PDE inhibitors. Cipamfylline is a new potent and selective inhibitor of PDE-4. OBJECTIVES: To compare the efficacy and safety of up to 14 days' topical treatment with cipamfylline (0.15%) cream with vehicle and with hydrocortisone 17-butyrate (0.1%) cream. PATIENTS AND METHODS: International, multicentre, prospective, randomized double-blind, left-right studies of cipamfylline vs. vehicle and cipamfylline vs. hydrocortisone 17-butyrate in adult patients with stable symmetrical atopic dermatitis on the arms. RESULTS: Both cipamfylline and hydrocortisone 17-butyrate reduced the Total Severity Score significantly (P < 0.001). The reduction with cipamfylline was significantly greater than that with vehicle (difference vehicle-cipamfylline 1.67 95% confidence interval (CI) 1.06, 2.28; P < 0.001) and was significantly less than with hydrocortisone 17-butyrate (difference hydrocortisone-cipamfylline -2.10 95% CI -2.93, -1.27; P < 0.001). Investigator and patient assessments of the overall treatment response showed a similar picture. CONCLUSIONS: Cipamfylline cream is significantly more effective than vehicle, but significantly less effective than hydrocortisone 17-butyrate cream in the treatment of atopic dermatitis.

Administration, Topical↗
PubMed2002

Recent advances in cutaneous angiogenesis.

An understanding of the molecular basis of angiogenesis is key to the appreciation of many of the advances made in the field of neovascularization over the past two decades. The sequence of events involved in angiogenesis includes: (i) increased vascular permeability and leakage; (ii) degradation of basement membrane; (iii) endothelial cell proliferation and migration through the surrounding extracellular matrix; and (iv) maturation and stabilization of the newly formed vessel bed. This review provides an update on the molecular basis of such pathways in the skin, with particular emphasis on the endothelial cell-specific vascular endothelial growth factor and angiopoietins as modulators of angiogenesis that can be targeted in therapy of cutaneous disease.

Angiogenesis Inducing Agents↗
PubMed2002

Downregulation and altered spatial pattern of caveolin-1 in chronic plaque psoriasis.

BACKGROUND: Caveolin-1 is a key structural and functional protein for plasmalemmal invaginations termed caveolae. Caveolin-1 is known to modulate multiple signal-transducing pathways involved in cell differentiation and proliferation. Psoriasis is viewed as a multifactorial pathology characterized by keratinocyte hyperproliferation and abnormal cell maturation. We hypothesized that loss of caveolin-1 within epidermal keratinocytes may contribute to the development and/or progression of the psoriatic phenotype. OBJECTIVES: To examine the expression and spatial distribution of caveolin-1 in skin biopsies from normal subjects and in patients with psoriasis. METHODS: Using immunohistochemical methods caveolin-1 protein expression was assayed in two independent patient groups. Firstly, a retrospective analysis was conducted on archival skin samples obtained from nine normal subjects and from involved tissue of 12 patients with psoriasis. Following this, a prospectively designed study was conducted in 10 further patients with active psoriasis and involving caveolin-1 staining of biopsy tissue from the uninvolved, advancing edge and lesional skin tissue from within the same subject. RESULTS: In normal skin or uninvolved skin from psoriasis patients intense caveolin-1 staining was present throughout full-thickness epidermis. In 20 of the 22 patient cases (combined retrospective and prospective samples) caveolin-1 protein was significantly reduced and consistently showed very weak or absent staining within the hyperproliferative basal cell layers of the psoriatic plaque (P < 0.002 for retrospective archival study and P < 0.01 for prospectively designed study). Comparisons between caveolin-1 staining in uninvolved tissue and at the advancing edge of a migrating plaque were more equivocal (P > 0.05). CONCLUSIONS: The findings of this study are consistent with a downregulation of caveolin-1 that may serve as an aetiological factor in the development and/or progression of psoriasis. Further mechanistic investigations are required with the potential that caveolin-1 protein may be a novel target for therapy of psoriasis.

Adolescent↗
PubMed2002

Patients' strategies for coping with psoriasis.

There is a paucity of research on the types of strategies that patients with psoriasis use to cope with the impact of their condition. By contrast there are a number of studies assessing coping by patients with nondermatological disease. The purpose of the present study was to examine strategies for coping in patients with psoriasis and investigate whether they differ as compared with normal controls and patients with other major medical diseases. Two hundred and fifty patients with a definite dermatologist-confirmed diagnosis of psoriasis participated in this cross-sectional study. Patients were assessed by psoriasis area severity index and all patients completed the COPE questionnaire and psoriasis disability index. Sixty healthy, control participants completed the COPE questionnaire for comparison purposes. Mean COPE scores from patients with psoriasis were also compared with published COPE scores from other medical diseases. The coping strategies most frequently used by patients with psoriasis were acceptance, planning, active coping and positive reinterpretation. The least frequently used were alcohol and nonprescription drugs, religion, and denial of their condition. Despite reporting greater disability, patients with severe psoriasis did not significantly differ from those with mild/moderate disease in their use of particular forms of coping strategies. Patients with psoriasis as a whole tended to use significantly less active coping strategies, planning, positive reinterpretation and humour when compared with normal controls. There was marked similarity in the frequency of use of particular coping strategies between patients with psoriasis and patients with other medical conditions. Similar types of coping strategies are utilized by patients regardless of whether their illness is visible (psoriasis) invisible (chronic fatigue syndrome, atrial fibrillation), has significant physical impairment (spinal cord injury), or is life-threatening (cancer, and myocardial infarction). It appears that illness brings with it a generic form of coping that may require shaping to fit the individual demands of diseases such as psoriasis.

Adaptation, Psychological↗
PubMed2002

Cytokine blocking agents in dermatology.

Cytokines are intercellular messengers that have an important role in the development and maintenance of cutaneous inflammation. The primacy of cytokines in eliciting cutaneous immune responses makes them a highly attractive target for new biological response modifiers. Targeting of cytokines is still in its infancy for therapy of skin disease. However, blocking tumour necrosis factor alpha by infliximab or etanercept has shown particular promise, especially in the management of psoriasis. Anecdotally, this approach is also effective for a variety of dermatological conditions including pyoderma gangrenosum and Behçet's syndrome. We review the current and prospective roles of cytokine blocking agents in the treatment of skin disease.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

CO2 laser vaporization for disfiguring lupus pernio.

Presented in this paper are two cases of longstanding gross and disfiguring lupus pernio of the nose successfully treated by CO2 laser resurfacing Both patients were resistant to previous medical therapy and have had an excellent postoperative cosmetic result.

Adult↗
PubMed2002

Lactoferrin: influences on Langerhans cells, epidermal cytokines, and cutaneous inflammation.

It has been suggested previously that, in addition to other biological roles, lactoferrin (LF) may display antiinflammatory properties secondary to the regulation of cytokine expression. To explore this concept further, we have here examined in human volunteers the influence of recombinant homologous LF on the migration of epidermal Langerhans cells (LC), a process that is known to be dependent upon the local availability of certain proinflammatory cytokines including tumor necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta). In common with previous studies in mice, it was found that topical administration of LF prior to exposure at the same site to the contact sensitizer diphenylcyclopropenone resulted in a significant reduction of allergen-induced LC migration from the epidermis (measured as a function of the frequency of CD1a+ or HLA-DR+ LC found in epidermal sheets prepared from punch biopsies of the treated skin sites). However, under the same conditions of exposure, LF was unable to influence migration of LC induced by the intradermal administration of TNF-alpha data consistent with the hypothesis that one action of LF in the skin is to regulate the local production of this cytokine. Further support for this hypothesis was derived from experiments conducted with IL-1beta. This cytokine is also able to induce the mobilization of LC following intradermal injection, although in this case, migration is known to be dependent upon the de novo production of TNF-alpha. We observed that prior exposure to LF resulted in a substantial inhibition of IL-1beta-induced LC migration, data again consistent with the regulation of TNF-alpha production by LF. Collectively, these results support the view that LF is able to influence cutaneous immune and inflammatory processes secondary to regulation of the production of TNF-alpha and possibly other cytokines.

Administration, Topical↗
PubMedDate not supplied

An investigation of the effect of prolonged glove wearing on the hand skin health of dental healthcare workers.

OBJECTIVES: Glove wearing during patient treatment has been central to dental surgery infection control for over 15 years. However, little is known about the cutaneous effects of glove wearing on the hands of dental healthcare workers (DHCWs). The objective of this project was to assess the hand skin health of DHCWs before and after wearing gloves of two types and to compare this with a control group of non-DHCWs. METHODS: Following a mailing to all dentists in the West of Scotland, 50 DHCWs who wore gloves during dental treatment procedures for a minimum of 8h daily for at least 4 days per week were invited to participate in the project. The control group comprised 25 subjects who did not routinely use surgical or examination gloves. Hands were assessed by clinical examination and by transepidermal water loss at baseline, 1 month and 3 months. RESULTS: Of the 50 DHCWs, 26 wore a non-powdered latex glove (Microtouch Powder-free: Johnson and Johnson, Arligton, TX, US), and 24 wore a nitrile glove (Hartalega SDN BHD, Malaysia) from the time of the baseline examination until the 3-month examination. No differences were observed in hand skin health between the control group and the DHCWs at baseline, nor between those wearing the latex or nitrile gloves during the 3 month period of the study. CONCLUSION: It is concluded that the hand skin health of the DHCWs examined were no different from those of a control group of non-DHCWs, and that the wearing of the two types of gloves used in the 3 month study had no significant effect.

Analysis of Variance↗
PubMedDate not supplied

Psoriasis and psoriatic arthritis: immunological aspects and therapeutic guidelines.

Psoriasis is an inflammatory skin disease that affects 1-3% of the European population. Chronic plaque psoriasis, the commonest form of the condition - affecting the majority of patients - usually manifests as red, heavily scaled plaques on elbows, knees, scalp and lower back, but any skin surface may be affected. Psoriasis is associated with an inflammatory sero-negative arthritis, namely "psoriatic arthritis", in approximately 15%of patients with psoriasis and occurs more commonly in people with inflammatory bowel disease such as patients with Crohn's disease. Several studies have demonstrated the role of genetic predisposition, innate and adaptive immunity in the pathogenesis of psoriasis. There is considerable evidence that innate immunity and specifically a dysregulation of the innate immune response is central to the development of psoriasis. The role of TNFalpha is particularly intriguing. The evidence includes further observations that a variety of anti-TNF approaches such as monoclonal antibodies and fusion proteins of soluble TNF receptors are effective therapies both in psoriasis and psoriatic arthritis. In this review, in addition to pathogenetic aspects, some preliminary guidelines for the use of anti-TNFalpha therapy in patients with psoriasis and psoriatic arthritis will be discussed.

Arthritis, Psoriatic↗