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Biomedical subjects

C E Griffiths

Publications and source records attributed to C E Griffiths.

At least 91 records · Page 5Linked to original sources

Assessing illness-related stress in psoriasis: the psychometric properties of the Psoriasis Life Stress Inventory.

The purpose of the present study was to undertake a clinical and psychometric reappraisal of the Psoriasis Life Stress Inventory (PLSI). Total PLSI score was inversely related to age of onset of psoriasis, but bore no significant relationship to duration or to clinical severity. Similarly, patients' stress score did not differ with regards to the nature of their current treatment, to their beliefs as to what was responsible for exacerbation or improvement of their condition, or to the patients' gender. Factor analysis extracted two factors which suggested that the psychosocial impact of psoriasis results from stress associated with: (i) engaging in anticipatory/avoidance coping behavior that is effected to limit the sociocognitive intrusiveness of psoriasis; and (ii) stress resulting from patients' beliefs or actual experiences of being evaluated by others solely on the basis of their skin. The internal reliability of the scale can be improved by the deletion of three items. Revision of the PLSI is recommended to render it psychometrically and clinically acceptable for use in the UK.

Adaptation, Psychological↗

Progress in psoriasis. Psoriasis: from gene to clinic. London, UK, 5-7 December 1996.

In a meeting dedicated to a single common complex disease such as psoriasis, it is not surprising that many unanswered questions were raised. However, the meeting highlighted the impressive progress being made in psoriasis research at both the investigative and the therapeutic levels. A follow-up meeting is to take place in 1999, when further characterization of susceptibility gene loci should be available, together with data concerning the selective nature of disease-causing T cells and the antigens that trigger the disease. Identification of these critical factors should allow development of highly specific therapeutic agents, some of which are beginning to find their way into clinical development.

Cell Differentiation↗

Clinical features of photodamaged human skin are associated with a reduction in collagen VII.

Chronically sun-exposed or photodamaged human skin is characterized by a number of clinical features, including wrinkles. However, little is known about the molecular mechanisms that underlie these features. We investigated the hypothesis that the mechanism of wrinkle formation may involve loss of anchoring fibrils, composed mainly of collagen VII, which are important in maintaining dermal-epidermal junction integrity. Ten volunteers with moderate to severe photodamage of dorsal forearm skin were recruited to the study. Using immunohistochemistry, transmission electron microscopy and in situ hybridization, we compared collagen VII protein and mRNA content of photodamaged forearm skin with that of sun-protected hip and upper inner arm skin from the same subjects. Numbers of anchoring fibrils per linear microns of basement membrane (mean +/- SEM) were significantly lower in photodamaged skin (1.79 +/- 0.10) as compared with sun-protected hip (2.28 +/- 0.11) and upper inner arm skin (2.21 +/- 0.10) (P < 0.01), and similarly keratinocyte expression of collagen VII mRNA, quantitated as number of positively stained keratinocytes per high power field, was significantly reduced in photodamaged skin (6.3 +/- 2.5) as compared with sun-protected hip (20.0 +/- 5.6) and upper inner arm skin (17.7 +/- 4.9) (P < 0.001). Semiquantitative assessment of immunohistochemical staining for collagen VII showed a non-significant reduction in photodamaged skin as compared with sun-protected skin. We propose that reduced content of collagen VII in photodamaged skin contributes to wrinkle formation by weakening the bond between the dermis and epidermis.

Aged↗

Quality of life in patients with psoriasis: the contribution of clinical variables and psoriasis-specific stress.

The purpose of this study was: (i) to examine the impact of the clinical severity, anatomical location and treatment of psoriasis on patients' quality of life, and (ii) to investigate the effects of perceptions of psoriasis-related stress on patients' physical and mental health and on areas of disability in everyday life. All patients (n = 204) attending a psoriasis specialty clinic were invited to complete a multidimensional quality of life assessment comprising the Psoriasis Disability Index (PDI), the SF-36 Health Survey and the Psoriasis Life Stress Inventory (PLSI). Results (n = 150) indicated that overall clinical severity of psoriasis as assessed by the Psoriasis Area and Severity Index, and duration of psoriasis, were unrelated to impairment in any areas of quality of life. Anatomical location (social visibility) of psoriasis was associated with self-report of poor physical health (P = 0.01), and there was a modest association with patients' mental health (P = 0.04); however, anatomical location of psoriasis was not significantly associated with self-reported disability in everyday life, or stress scores. Patients who were classified as more reactive to the stress associated with psoriasis (78% of the sample) were functioning less well in terms of their mental health (P = 0.001) and also experienced significantly more disability in all areas of everyday life (P = 0.001). Differences in method of treatment for psoriasis did not significantly affect scores on the psoriasis-specific (PDI; PLSI) or generic (SF-36) quality of life measures. A multiple regression analysis demonstrated that stress resulting from anticipating other people's reactions to their psoriasis contributed more to the variance in patients' disability in everyday life than any other medical or health status variable. The results support the importance of assessing the effects of stress in patients' adjustment to their condition and may indicate a role for adjunctive psychological stress management training for a significant number of patients with psoriasis.

Activities of Daily Living↗

A comparison of wire brush and diamond fraise superficial dermabrasion for photoaged skin. A clinical, immunohistologic, and biochemical study.

BACKGROUND: Superficial dermabrasion has a proven beneficial effect on photoaged skin, but little is known about the differences between the two major modalities used in dermabrasion, the diamond fraise (DF) and the wire brush (WB). OBJECTIVE: We compared the clinical, immunohistologic, and biochemical changes after superficial dermabrasion with DF and WB. METHODS: Eight photoaged patients (mean age, 68 years; range, 49 to 80 years) underwent facial dermabrasion to the level of the papillary dermis. Clinical assessments were performed at baseline and at 3 and 12 weeks after dermabrasion. Biopsy specimens were taken from both dermabraded halves at the same time points and assessed by routine histologic and immunohistologic examinations, western blot analysis, and radioimmunoassay. Scoring of intracellular and extracellular transforming growth factor-beta 1 was based on a semiquantitative ordinal scale (0 = no staining to 4 = maximum staining) in half-unit increments. The score for each specimen represents the average of values obtained from four high-power fields. RESULTS: Both methods of dermabrasion resulted in significant resolution of actinic keratoses, lentigines, and wrinkling. No statistical significance was noted between the two methods in regard to clinical efficacy. Significantly fewer milia occurred after DF than after WB. Solar elastosis decreased with both the WB and DF. Immunohistologic examination demonstrated a highly significant increase in papillary dermal fibroblast staining for amino terminal procollagen I (type I pN-collagen) at 3 weeks for both DF and WB compared to baseline. Staining at 12 weeks had decreased from the peak noted at week 3, but was still significantly increased from baseline. Western blotting of type I pN-collagen demonstrated a 5.4-fold (p = 0.01) increase from baseline at 3 weeks and a 4.9-fold (p = 0.002) increase at 12 weeks after dermabrasion with the WB. Similarly, the DF produced a 4.9-fold (p = 0.006) increase at 3 weeks and a 5.1-fold (p = 0.008) increase at 12 weeks after dermabrasion. Western blotting of amino terminal procollagen III (type III pN-collagen) showed a 6.1-fold (p = 0.07) increase from baseline at 3 weeks and a 3.9-fold (p = 0.04) increase at 12 weeks after dermabrasion with the DF. The WB showed a 3.8-fold (p = 0.07) increase from baseline at 3 weeks and a 5.1-fold (p = 0.05) increase at 12 weeks. Transforming growth factor-beta 1 demonstrated a significant increase in extracellular staining with DF (3.3 +/- 0.2) and WB (3.7 +/- 0.2) from baseline (1.2 +/- 0.2, p < 0.001) at 3 weeks. CONCLUSION: Superficial dermabrasion with DF and WP appears to be similarly efficacious in the treatment of photoaged skin. Significant increases in type I pN-collagen, type III pN-collagen, and TGF-beta 1 occurred in the papillary dermis after both types of dermabrasion. These results suggest that increased fibroblast activity and consequent collagen I and III synthesis underlie the clinical improvement.

Aged↗

Elevated levels of circulating intercellular adhesion molecule-3 (cICAM-3) in Psoriasis.

Intercellular adhesion molecule (ICAM)-3 is important in regulating leukocyte function and T-lymphocyte-antigen presenting cell interactions. Soluble, circulating forms of ICAM-3 and ICAM-1 (cICAM-3, cICAM-1) exist in serum, and levels are elevated in a variety of autoimmune diseases. Two types of soluble circulating tumour necrosis factor receptor (cTNF-R1, cTNF-R2) are found in the sera of healthy people. cTNF-R1 binds TNF-alpha and is important in regulating TNF-alpha-mediated inflammation. Psoriasis is a T-lymphocyte-mediated disease, characterized by cutaneous expression of ICAM-1, ICAM-3 and TNF-alpha. As it is unknown whether cICAM-3 is increased in sera of patients with psoriasis, we measured serum levels of cICAM-3 and compared them to levels of cICAM-1, cTNF-R1 and clinical severity of psoriasis. Sera was taken from 112 healthy controls and 32 patients with psoriasis. Clinical severity of psoriasis was assessed using the psoriasis area severity index (PASI). cICAM-1, cICAM-3 and cTNF-R1 in serum were quantitated using a dual antibody, solid phase ELISA, Levels of cICAM-3, cICAM-1 and cTNF-R1 were significantly increased in sera of patients with psoriasis as compared with controls, and these elevated levels correlated with clinical severity of psoriasis as assessed by the PASI. Also, there were good correlations between serum levels of cICAM-3, cICAM-1 and cTNF-R1 in psoriasis. These results demonstrate, for the first time, that circulating levels of cICAM-3 are increased in psoriasis and that these levels correlate both with disease severity and with elevated levels of cICAM-1 and cTNF-R1. The exact physiologic roles of circulating, soluble adhesion molecules and cTNF-R1 are unknown, but it is hypothesised that elevation of their circulating levels, as observed in psoriasis, may play a role in modulating the inflammatory reactions occurring in this disease.

Adolescent↗

Topical tretinoin (retinoic acid) improves early stretch marks.

BACKGROUND AND DESIGN: Stretch marks are disfiguring lesions usually caused by excessive stretching of skin. We investigated the response of early, clinically active stretch marks to topical 0.1% tretinoin (retinoic acid) cream. In a double-blind, randomized, vehicle-controlled study, 22 patients applied either 0.1% tretinoin (n = 10) or vehicle (n = 12) daily for 6 months to the affected areas. Patients were evaluated by physical examination monthly and by analysis of biopsy specimens of stretch marks obtained before and at the end of therapy in comparison with untreated normal skin. RESULTS: After 2 months, patients treated with tretinoin had significant improvements in severity scores of stretch marks compared with patients who received vehicle (P < .05). After 6 months, eight (80%) of the 10 tretinoin-treated patients had definite or marked improvement compared with one (8%) of the 12 vehicle-treated patients (P = .002). Targeted stretch marks in patients treated with tretinoin had a decrease in mean length and width of 14% and 8%, respectively, compared with an increase of 10% (P < .001) and 24% (P = .008), respectively, in patients who received vehicle. There were no significant differences in various measures of quality and quantity of dermal collagen and elastic fibers in stretch marks when tretinoin and vehicle treatments were compared. CONCLUSIONS: Topical application of tretinoin significantly improves the clinical appearance of early, active stretch marks. The processes that are responsible for the clinical improvement remain unknown.

Administration, Cutaneous↗

Topical retinoic acid changes the epidermal cell surface glycosylation pattern towards that of a mucosal epithelium.

Topical all-trans retinoic acid (RA) produces a number of epidermal changes which are indistinguishable from those observed following treatment with a local irritant, namely sodium lauryl sulphate (SLS). This observation has led to criticism that the efficacy of RA in disorders such as photoageing, is merely a result of irritancy. In stratified epithelia, the cellular differentiation process is characterized by a stepwise synthesis of cell surface carbohydrates, and each type of stratified epithelium has its own specific pattern of carbohydrate expression. Glycosyltransferases, which are responsible for carbohydrate synthesis, are influenced by retinoids. Thus, we investigated whether epidermal cell surface glycosylation is altered in skin treated with topical RA, and contrasted it with changes induced by topical SLS. Skin biopsies were obtained from seven normal volunteers who had been treated, on three separate areas of buttock skin, with single applications of 0.1% RA, 2% SLS, or vehicle creams, followed by 4-day occlusion. Biopsies were assessed immunohistologically using highly specific monoclonal antibodies to cell surface carbohydrates (types 1, 2 and 3 chain structures), previously demonstrated in the epidermis and in oral mucosal epithelium. Although type 1 chain structures were not demonstrated in any of the samples, the distribution of type 2 and 3 chain structures in RA-treated epidermis was altered towards that seen in a mucosal epithelium. T antigen, a mucin-type cell surface carbohydrate structure normally expressed throughout the epidermis, was only observed in the granular layer of RA-treated epidermis--a feature of mucosal epithelia. Ley, normally only seen in non-keratinized buccal epithelium, was strongly expressed in RA-treated epidermis. In contrast, the glycosylation pattern of the SLS-treated epidermis was not significantly different from that observed after vehicle treatment. Thus, RA treatment converts normal stratified epithelium towards the phenotype of mucosal epithelium with a decrease in T antigen and a concomitant increase in Ley. These changes are not observed following treatment with SLS and identify an important difference between RA effects and irritancy.

Adult↗

Concurrent application of tretinoin (retinoic acid) partially protects against corticosteroid-induced epidermal atrophy.

Cutaneous atrophy arising from prolonged use of potent topical corticosteroids has long been a concern. Thus, it would be advantageous to find an agent which protects against atrophy produced by corticosteroids but at the same time does not impair their anti-inflammatory effects. Recent work shows that topical all-trans retinoic acid (tretinoin) prevents skin atrophy in mice treated with topical corticosteroids, but such studies have not been performed in humans. We performed an 8-week clinical, histological and biochemical study to test the ability of tretinoin to enhance efficacy and inhibit atrophogenicity of topical corticosteroids, when used in the treatment of psoriasis. In each of 20 psoriasis patients, one plaque, and its perilesional skin, was treated once daily with betamethasone dipropionate and tretinoin 0.1%, and one plaque, and its perilesional skin, treated with once daily betamethasone dipropionate and tretinoin vehicle. There was no difference in the speed or degree of improvement in plaques treated with either the topical corticosteroid/tretinoin combination or with corticosteroid alone. Light microscopy revealed a 19% reduction in epidermal thickness, in corticosteroid-treated perilesional skin, as compared with a slight (1%) increase in corticosteroid/tretinoin-treated perilesional areas (P = 0.067). Western blot analysis showed a 55% reduction in procollagen I aminopropeptide in perilesional skin treated corticosteroid alone, as compared with a 45% reduction in corticosteroid/tretinoin-treated perilesional skin. These data indicate that the addition of tretinoin does not impair the efficacy of a topical corticosteroid, in the treatment of psoriasis, and partially ameliorates epidermal atrophy produced by the topical corticosteroid.

Administration, Topical↗

Prolonged occlusion in the treatment of psoriasis: a clinical and immunohistologic study.

BACKGROUND: An occlusive dressing that is both cosmetically acceptable and long term is needed for psoriasis treatment. The mechanisms that underlie the efficacy of occlusion in psoriasis are unknown. OBJECTIVE: We performed a clinical and immunohistologic study in patients with psoriasis of the effects of occlusion, topical corticosteroid alone, and occlusion plus corticosteroid, with a new prolonged dressing as the occlusive therapy. METHODS: Nineteen patients completed a 3-week study of efficacy of prolonged occlusion dressing, fluocinonide ointment, or a combination of the two. An immunohistologic study was performed in 10 patients with psoriasis treated for 1 week with prolonged occlusion. RESULTS: The combination of fluocinonide ointment and occlusion produced significantly more improvement than either treatment alone (p < 0.01). There was no significant difference between the efficacy of prolonged occlusion or fluocinonide ointment. On 4-week follow-up plaques treated with occlusion alone or combined fluocinonide and occlusion were still significantly improved (p = 0.05 and p < 0.001, respectively). None of the immunohistologic and proliferation markers assessed in psoriatic plaques was significantly affected by occlusion as compared with untreated plaques. CONCLUSION: Prolonged occlusion is an effective therapy for psoriasis either as monotherapy or in combination with a high-potency topical corticosteroid. However, the mechanism of action of prolonged occlusion alone in the improvement of psoriasis is unknown.

Administration, Cutaneous↗

A clinical and histologic mycosis fungoides simulant occurring as a T-cell infiltrate coexisting with B-cell leukemia cutis.

One year after the onset of chronic lymphocytic leukemia, an elderly man had scaly cutaneous plaques on the thighs that clinically and histologically resembled the mycosis fungoides type of cutaneous T-cell lymphoma. Two years later the patient had indurated, red dermal nodules on the face that clinically and histologically were characteristic of cutaneous chronic lymphocytic leukemia. Immunophenotyping results from a facial nodule confirmed the presence of a B-cell infiltrate (CD20+). Immunophenotyping of a lesion on the right thigh showed that half the cells were composed of a CD2+, CD45RO+ (UCHL-1+) upper dermal and focally epidermotropic population of T cells consistent with mycosis fungoides; however, these T cells coexisted with an equal number of CD20+ B cells arranged in distinct clusters. DNA from the thigh lesion exhibited a B-cell immunoglobulin gene rearrangement, but the T-cell receptor gene rearrangements were germline. In this case, the evidence favors a mycosis fungoides simulant occurring as a reactive T-cell infiltrate to an underlying B-cell chronic lymphocytic leukemia.

Aged↗