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Biomedical subjects

C E Griffiths

Publications and source records attributed to C E Griffiths.

At least 55 records · Page 3Linked to original sources
PubMed2000

The spectrum of skin disorders in abdominal stoma patients.

BACKGROUND: Skin integrity is essential for the normal usage of a stoma appliance. However, there is little published on the prevalence, nature or management of stoma-related skin disorders. Objectives To document stoma-related skin disorders in a large cohort of patients. METHODS: We sent a postal questionnaire to all surviving patients who had had abdominal stoma surgery at Hope Hospital, Salford, U.K. in the 10 years from 1 January 1989. Those reporting skin disease were invited to attend a clinic run by a dermatologist and a stoma-care specialist nurse. All lesions were categorized and swabs taken for microbiological examination. RESULTS: Of 525 surviving patients, 325 (62%) replied to the questionnaire. Of these, 73% reported a skin problem that had affected normal stoma bag use. Dermatoses included irritant reactions, particularly from leakage of urine or faeces (42%); pre-existing skin diseases, principally psoriasis, seborrhoeic dermatitis and eczema (20%); infections (6%); allergic contact dermatitis (0.7%) and pyoderma gangrenosum (0.6% annual incidence). A further 15% of patients with skin problems had persistent or recurrent dermatitis not explained by allergy, frank infection or faecal irritation. This responded to short-term treatment with topical corticosteroids. Further investigation is under way into its pathogenesis. CONCLUSIONS: Skin disorders are common in stoma patients, and various patterns can be recognized and effectively treated.

Abdomen↗
PubMed2000

The use of folic acid supplementation in psoriasis patients receiving methotrexate: a survey in the United Kingdom.

There is little literature on the use of folic acid supplementation in psoriasis patients being treated with methotrexate. Under the auspices of the British Association of Dermatologists we surveyed, using a questionnaire, the use of folic acid supplementation with methotrexate therapy for psoriasis by dermatologists in the UK. Six-hundred and fifteen questionnaires were sent and 153 responses were received (25%). One-hundred and fourteen of the responders (75%) used folic acid supplementation with methotrexate in psoriasis patients. Thirty (26%) of these used folic acid supplementation in all patients taking methotrexate and 84 (74%) used folic acid only under certain circumstances, the most common of which was an elevated erythrocyte mean corpuscular volume. Forty-six per cent of respondents believed that folic acid supplementation reduced nausea and 60% believed that folic acid did not interfere with the efficacy of methotrexate. A wide variety of dosing regimens were used for folic acid supplementation. In the absence of guidelines and controlled trials, there is great variation in the indication for use, dosing regimens used and beliefs regarding methotrexate supplementation for psoriasis. Randomized controlled trials are necessary to address these questions.

Dermatologic Agents↗
PubMed2000

Langerhans cell migration.

Epidermal Langerhans cells (LC) play pivotal roles in the induction of cutaneous immune responses. Encounter with antigen in the skin, or other stimuli, cause the mobilization of LC and their migration, via afferent lymphatics, to draining lymph nodes where they localize within the paracortex. During their movement from the skin LC acquire the characteristics of immunostimulatory dendritic cells (DC) such that the antigen-bearing cells which accumulate in lymph nodes are able to provoke specific T-lymphocyte responses. Epidermal cytokines initiate and regulate LC migration (and maturation), of particular importance being interleukin-1beta and tumour necrosis factor-alpha. Collectively, these cytokines, together with relevant chemokine receptor-ligand interactions, effect the liberation of LC from the epidermis and their directed movement to, and localization within, peripheral lymph nodes. Described here are the phenotypic changes induced during the activation of LC and the mechanisms through which their migration is regulated.

Antigen-Presenting Cells↗
PubMed2000

Topical sucralfate in the management of peristomal skin disease: an open study.

Dermatoses affecting the skin around stoma sites are common and difficult to treat. We have investigated the effectiveness of topical sucralfate in the management of peristomal dermatoses in adults using an open study design. Apart from forming a physical barrier to further irritation, sucralfate binds to basic fibroblast growth factor preventing its degradation and thereby promotes healing. In eight out of nine patients with faecal or urine erosions, daily, topical sucralfate treatment was associated with healing within 4 weeks. There was limited or no response to treatment in a further nine patients with traumatic ulcers, excoriated dermatitis or pyoderma gangrenosum. Topical sucralfate represents a safe, inexpensive and effective therapeutic intervention, particularly for those patients with high output or short stomas where repeated stoma leakage may be unavoidable.

Abdomen↗
PubMed2000

Therapeutic strategies for psoriasis.

Psoriasis is a chronic, inflammatory, hyperproliferative skin disease that affects approximately 1-2% of the general population in the U.K. and U.S.A. It is rarely life-threatening, but causes considerable patient morbidity. The disease waxes and wanes, with substantial variability both between and within individual patients. There is no cure for psoriasis; therefore, the aim of treatment is to minimize the extent and severity of the disease to the point at which it no longer disrupts substantially the patient's quality of life. We review the current treatment options, which include topical therapies, phototherapy and systemic agents. Lack of efficacy, adverse effects and aesthetic problems limit the use of many topical therapies. Likewise, the risk of toxicity is a major problem with currently available phototherapies and systemic treatments. Advances in understanding the aetiology and pathogenesis of psoriasis allude to the possibility of innovative, targeted therapies in the future.

Administration, Oral↗
PubMed2000

Peristomal dermatoses: a novel indication for topical steroid lotions.

BACKGROUND: Dermatoses that interfere with the normal use of a stoma appliance are common. When preventable causes, such as infection or allergy, are not identified, barrier preparations or topical steroids have been used. However, topical medicaments formulated in a cream or ointment base will cause stoma bags to detach, resulting in leaks. OBJECTIVE: Our purpose was to investigate the efficacy and suitability of corticosteroids in aqueous/alcohol lotions in the management of peristomal dermatoses. METHODS: A clinic run by a dermatologist and 2 stoma nurses was created. Patients with a variety of noninfective, inflammatory dermatoses were treated with topical corticosteroid lotions up to a maximum of 4 weeks, with occasional use thereafter in some cases. RESULTS: Topical, aqueous/alcohol, corticosteroid lotions have been used in 60 patients and have proved particularly useful for the treatment of irritant dermatitis, pyoderma gangrenosum, psoriasis, and constitutional eczema. After the initial treatment course, occasional applications, approximately every 2 weeks, may be necessary to control the skin disorder. This low frequency of application minimizes the risk of side effects so that we have not identified local or systemic side effects in any of the patients treated so far. CONCLUSION: Topical corticosteroids formulated in aqueous alcohol lotion are effective and acceptable treatments for peristomal dermatoses. If used appropriately, the risk of side effects is low.

Administration, Topical↗
PubMed2000

Cost-effectiveness analysis of topical calcipotriol versus short-contact dithranol. In the treatment of mild to moderate plaque psoriasis.

OBJECTIVE: To examine the relative cost effectiveness of topical calcipotriol and short-contact dithranol in the treatment of mild to moderate plaque psoriasis. DESIGN AND SETTING: This was a modelling study from the perspective of the UK National Health Service as payer. METHODS: The interventions were compared using 2 decision-analytic models: one using a short term horizon (12 weeks) and the other using a longer term horizon (up to 1 year). Clinical success of treatment and relapse rates were obtained from the results of randomised controlled trials. MAIN OUTCOME MEASURES AND RESULTS: The outcome measure used was the degree of improvement in psoriasis as judged by the patient. In the short term comparison, calcipotriol was the most effective treatment (60.8% success), but it was also the most expensive (96.03 Pounds; 2000 values). The incremental cost per success was 577.50 Pounds using a 12-week course of calcipotriol compared with short-contact dithranol. Over the long term horizon, first-line treatment with calcipotriol still had the highest expected cost per successful treatment (164.91 Pounds), but the incremental cost using this strategy was 38.66 Pounds compared with short-contact dithranol. In terms of cost per successful day's treatment (i.e. the cost for a day in which the patient reported a marked improvement or cleared lesions), the cost of each additional successful day's treatment was 19.93 Pounds when using calcipotriol as first-line treatment rather than short-contact dithranol. CONCLUSION: The combination of differences in drug acquisition costs and relapse rates can lead to large differences in the comparative cost effectiveness of topical treatments for plaque psoriasis. From the perspective of the prescriber, the results of this analysis suggest that selecting short-contact dithranol as first-line treatment was the most cost-effective strategy.

Administration, Topical↗
PubMed2000

Parastomal pyoderma gangrenosum: clinical features and management.

BACKGROUND: The importance of pyoderma gangrenosum (PG) as a cause of ulceration around abdominal stomas is not well recognized. OBJECTIVE: Our purpose was to describe the incidence, clinical and histologic features, disease associations, and possible risk factors for parastomal PG. METHODS: A clinic, run by a dermatologist and two stoma nurses, was created. Five hundred patients approached by postal questionnaire were invited to attend if they had skin problems. In addition, local surgical, dermatologic, and nursing services were invited to refer patients with parastomal skin problems. Cases of parastomal PG were identified, investigated, and treated. RESULTS: The annual incidence of parastomal PG in the questionnaire-based cohort of patients was 0.6% (3 patients). An additional 23 patients with the condition were seen. No consistent hematologic, biochemical, immunologic, microbiological or histologic abnormalities were identified. Local skin damage did not appear to be an important trigger for parastomal PG. The condition is recurrent in one third of cases. Topical tacrolimus (0.3% in carmellose sodium paste) has been effective in 4 patients. CONCLUSION: Parastomal PG is far more common than previous reports would suggest, and it may be associated with diseases other than inflammatory bowel disease.

Abdomen↗
PubMed1999

Clinical measures of disease severity and outcome in psoriasis: a critical appraisal of their quality.

In clinical trials, a wide range of outcome measures has been used to evaluate the severity of psoriasis and its response to treatment. Despite their widespread use, many measures have received little attention with regards to their reliability and validity. Selecting an appropriately developed measurement tool is therefore of critical importance. We conducted a literature survey to examine the status of clinical outcome measures used in psoriasis research. The measures most commonly used were individual sign scores, e.g. for erythema, plaque thickness or scaling, and pooled indices, e.g. the Psoriasis Area and Severity Index. None of these, however, systematically fulfilled all the requirements of a validated instrument for disease assessment. Ideally, a core set of reliable and validated outcome measures for use in all psoriasis clinical trials is needed. Objective instrumental methods should minimise observer variation, but unless a simple non-invasive method can be developed, the uptake of such technology will probably be limited by cost and lack of practicality. Moreover, the translation of instrumental readings into clinically relevant measures is always a major problem, and for none of the methods has there been a robust mapping of instrumental readings on to a clinically meaningful scale. Further research is needed to determine the most appropriate and sensitive parameters to use as surrogate measures for capturing the distress which psoriatic patients feel but which is not measured with sufficient sensitivity or precision with current quality of life or distress questionnaires.

Outcome Assessment, Health Care↗
PubMed1999

Tumour necrosis factor-alpha induces Langerhans cell migration in humans.

The role of tumour necrosis factor (TNF)-alpha in the mobilization and migration of human epidermal Langerhans cells (LC) has been investigated. Intradermal injection of normal human volunteers with homologous recombinant TNF-alpha was found to cause a dose-dependent reduction in the frequency of LC within epidermal sheets 2 h later. Equivalent results were obtained when epidermal LC were identified on the basis of either CD1a or HLA-DR expression. At the dose of TNF-alpha used routinely (500 U), treatment resulted in an average reduction in LC density of approximately 24%. Treatment with TNF-alpha was associated with a perivascular polymorphonuclear infiltration at 2 h, but the epidermis appeared normal with neither fibrinoid necrosis nor vasculitis, and LC morphology was not affected significantly. These results demonstrate that TNF-alpha provides an important signal for LC migration in humans and is likely therefore to play a crucial part in the induction of cutaneous immune responses.

Adult↗
PubMed1999

Combination treatment with methotrexate and cyclosporin for severe recalcitrant psoriasis.

An increasingly important approach to the management of patients with severe psoriasis is the concurrent use of two systemic treatments. Previous guidelines have advised against the use of methotrexate and cyclosporin in combination. We report the successful use of a combination of methotrexate and cyclosporin in the treatment of 19 patients with severe, recalcitrant psoriasis, 15 of whom had psoriatic arthropathy. Most patients had previously received two or more systemic treatments. Before combination treatment was started nine of the patients were taking methotrexate and 10 were taking cyclosporin at the maximum tolerated doses. The duration of combination treatment was bimodally distributed, with seven patients having short-term treatment (mean +/- SD duration 18. 9 +/- 15.7 weeks) and 12 patients having long-term treatment (mean +/- SD duration 193.2 +/- 160.6 weeks). Those patients who received short-term treatment did not develop any evidence of toxicity from either agent. Of those patients on long-term treatment, three developed mild impairment of renal function that returned to normal following a reduction in dose of cyclosporin, and three had impairment of renal function (following long-term cyclosporin monotherapy) that improved, but did not normalize, following a reduction in dose of cyclosporin. In each case, combination treatment for psoriasis resulted in good control of both skin and joint problems using lower doses of each agent than would have been used for monotherapy. We conclude that the combination of methotrexate and cyclosporin is an effective treatment for this group of patients.

Adult↗
PubMed1999

Intermittent short courses of cyclosporin (Neoral(R)) for psoriasis unresponsive to topical therapy: a 1-year multicentre, randomized study. The PISCES Study Group.

We performed a 1-year study to determine whether intermittent short courses of the microemulsion formulation of cyclosporin (Neoral) could effectively control plaque psoriasis and whether tapering or abrupt cessation of cyclosporin therapy would influence time to relapse. Four hundred patients with plaque psoriasis were included in this open, multicentre, randomized study. All patients commenced cyclosporin at a dose of 2.5 mg/kg daily. Cyclosporin dosage could be increased to a maximum of 5 mg/kg daily. Treatment was continued until clearance of psoriasis or for a maximum of 12 weeks. Patients were then randomly assigned either to stop cyclosporin abruptly or to have the dose reduced by 1 mg/kg daily each week until cessation. On relapse, patients were given another course of cyclosporin. Patients were followed for at least 1 year, during which they could receive as many treatment courses as necessary. The number of patients who required one, two, three and four treatment courses was 400, 259, 117 and 26, respectively. The median time to relapse after the end of the first treatment period was 109 days in the group of patients randomized to stop cyclosporin abruptly and 113 days in patients randomized to taper off cyclosporin (P = 0.038). More than 30% of patients had not relapsed 6 months after having stopped treatment. After each treatment course, the Kaplan-Meier probability of achieving 75% or more reduction in disease area by day 84 of treatment was 83%, 76%, 73% and 66%, respectively. Mean serum creatinine concentration and blood pressure did not show any clinically significant changes over time. Our results show that intermittent short-course therapy with Neoral, when used in conjunction with topical therapy, is well tolerated and provides effective control of plaque psoriasis for 1 year. Tapering off cyclosporin on treatment cessation induces a slight delay in psoriasis relapse.

Adolescent↗
PubMed1999

Levels of endothelial cell stimulating angiogenesis factor and vascular endothelial growth factor are elevated in psoriasis.

Neovascularization appears to play an early and important part in the evolution of psoriatic plaques. We studied the distribution and production of two known angiogenesis factors, endothelial cell stimulating angiogenesis factor (ESAF) and vascular endothelial growth factor (VEGF), in the skin of patients with chronic plaque psoriasis and normal control subjects. Our results showed that tissue levels of ESAF and VEGF were significantly elevated in involved as compared with normal control skin (P = 0.006 and P < 0. 0001, respectively). Tissue levels of ESAF and VEGF were also raised in involved skin as compared with uninvolved skin in patients with psoriasis (P = 0.001 and P < 0.0001, respectively). Tissue levels of ESAF and VEGF in plaques of psoriasis correlated closely with the clinical severity of psoriasis (r = 0.6 and r = 0.9, respectively). Serum levels of ESAF and VEGF were significantly raised in patients with psoriasis as compared with control subjects (P = 0.001 and P = 0.02, respectively). In vitro culture studies revealed that ESAF is produced by both keratinocytes and fibroblasts in approximately equal quantities in normal skin, whereas VEGF is secreted predominately by keratinocytes. A similar pattern is seen in both involved and uninvolved skin of patients with psoriasis. However, there is increased secretion of both factors in keratinocytes and fibroblasts from involved and uninvolved skin as compared with normal control skin (P < 0.001). The increased levels and secretion in plaques of psoriasis of two molecules, ESAF and VEGF, known to promote new blood vessel formation, suggest a pathogenetic role for them in this disease.

Adult↗
PubMed1999

Dowling Oration delivered at the Royal College of Physicians, London, Friday 5 June 1998. Retinoids: renaissance and reformation.

There is confusion as to the cutaneous signs of ageing. For the most part the features of photoageing, namely actinic lentigines and wrinkling, are misinterpreted as features of ageing. Wrinkling is associated with a loss of collagens from the papillary dermis resulting from imperfect remodelling of the dermal extracellular matrix following sun exposure. Retinoids are either derivatives of vitamin A or synthetic ligands of nuclear retinoid receptors. Retinoid receptors, notably retinoic acid receptor gamma and retinoid X receptor alpha are present in human skin. Topically applied all-trans retinoic acid can repair and probably prevent photoageing of the skin by modulation of collagen synthesis in the dermis. There is emerging evidence that intrinsic ageing of the skin is also amenable to reversal by topical retinoids.

Aging↗
PubMed1999

Chronic granulomatous disease and acute neutrophilic dermatosis.

Chronic granulomatous disease is an inherited disorder characterized by defective oxidative killing by neutrophils and other phagocytes. This results in susceptibility to persistent and life-threatening infections. We describe a 25-year-old man with chronic granulomatous disease who presented with an acute, febrile neutrophilic dermatosis. This indicates that normal neutrophil intracellular killing mechanisms are not essential in the pathogenesis of neutrophilic dermatoses.

Adult↗