Biomedical subjects

P J Dykes

Publications and source records attributed to P J Dykes.

At least 19 recordsLinked to original sources

PubMed2005

The role of menthol in skin penetration from topical formulations of ibuprofen 5% in vivo.

In vivo plasma profiles from formulations containing 5% ibuprofen were compared after a single topical application in a randomised, double-blind, cross-over trial. Ibuleve gel (Dermal Laboratories, UK) contained only ibuprofen whilst Deep Relief gel (Mentholatum, UK) also contained 3% menthol. In contrast to results obtained when these products were compared under in vitro conditions, there was no statistically significant difference in vivo between delivery of ibuprofen. Estimated relative bioavailability fraction (Deep Relief gel/Ibuleve gel) from log-transformed AUC((0-24h)) was 0.99 (95% CI: 0.94-1.04), estimated C(max )ratio was 0.96 (95% CI: 0.91-1.00) and estimated t(max) ratio was 1.01 (95% CI: 0.81-1.20). Menthol produces local vasodilation, which reduces skin barrier function, and these data demonstrate that it is inappropriate to extrapolate from in vitro data where formulation components produce biologically-mediated enhancement of permeation which cannot be modelled ex vivo. In clinical use, these products deliver comparable amounts of ibuprofen, but only Deep Reliefgel provides the secondary immediate benefit of the direct analgesic action of menthol.

Administration, Cutaneous↗

PubMed2003

The Children's Dermatology Life Quality Index: validation of the cartoon version.

BACKGROUND: In 1995 the Children's Dermatology Life Quality Index (CDLQI) was developed as a tool to allow quality of life assessment of children with skin conditions. This initial questionnaire was in a written format. OBJECTIVES: Using the same validated questions, a full-colour cartoon version has been developed. The aim of this study was to validate this against the initial written questionnaire in a three-part study. METHODS: The first part of the study piloted the use of both versions in an outpatient setting. One hundred and one children completed both versions of the CDLQI in a random order. A further 66 children completed the cartoon CDLQI in outpatients, and subsequently completed the cartoon version on the same day at home, which was returned by post. The scores were compared. In the second part, in more controlled conditions to eliminate parental and investigator bias, 107 children with current dermatological problems were administered both versions of the CDLQI in a random order. The scores were analysed, and time to complete each version, and the child and parental preferences, were recorded. The third part assessed compliance by asking 546 children recently reviewed in dermatology clinics to return a single completed postal CDLQI. Half of the children were given the text, and half the cartoon version. RESULTS: The median age of participating children was 11 years. There was no significant difference in scores between the two versions in both parts 1 and 2, but the cartoon version was completed faster (median 90 s) than the written version (median 120 s) (P < 0.0001). Both children and their parents significantly preferred the cartoon version and found it easier to use. Forty-six per cent of the postal CDLQI questionnaires were returned; there was no difference in compliance between the two versions. CONCLUSIONS: The cartoon CDLQI is equivalent to the previously validated written CDLQI version, but is faster and easier for children to use, and is preferred by both children and parents.

Adolescent↗

PubMed2003

The link between the peel force of adhesive dressings and subjective discomfort in volunteer subjects.

OBJECTIVE: The study compared the level of discomfort experienced by healthy volunteers on the removal of a range of adhesive wounds. METHOD: This was an open, within subject comparative study of six adhesive dressings in 24 volunteers. The test site was the lower back. Allocation of test materials to the test sites was randomised. The peel force of removal was recorded after 24 hours of application using a device that removed the dressing at a constant speed and angle to the skin surface. The discomfort experienced at each removal was assessed by the subjects themselves using an electronic visual analogue scale. RESULTS: Overall, Mepilex Border was given a significantly lower discomfort score (p < or = 0.01) by the subjects than the other dressings. There were no clear differences between the five other products tested. Tielle and Allevyn Adhesive had significantly higher (p < or = 0.05) peel force than the other products. Mepilex Border caused less discomfort on removal than Duoderm Extra Thin, Biatain and Versiva, even though the peel force was similar. Tielle and Allevyn had higher peel force, but the levels of discomfort were not significantly higher for these products. CONCLUSION: It may be that the level of discomfort experienced by subjects on removal of an adhesive dressing is not entirely dependent on the peel force and that other aspects of the interaction of the skin surface and adhesive play a role.

Adhesives↗

PubMed2001

The Infants' Dermatitis Quality of Life Index.

BACKGROUND: The impact on quality of life (QOL) caused by atopic dermatitis (AD) has been quantified in children and adults using established QOL measures. However, these are not suitable for use in infants under the age of 4 years, when AD usually develops. OBJECTIVES: To validate a new parent-generated QOL questionnaire, the Infants' Dermatitis QOL Index (IDQOL), which measures the impact of AD on the infant, and to provide further validation of the Family Dermatitis Index (FDI), which measures the impact of a child's dermatitis on the family. METHODS: Parents of 102 predominately caucasian infants under 4 years with AD (34 postal and 68 outpatients) were asked to complete the IDQOL and the FDI on two separate occasions to test for repeat validity. The Infants' Behavioural Check List (BCL) was also given to the study group and to parents of 22 normal control infants. Post-treatment IDQOL and FDI questionnaires were obtained from 25 of the study group. RESULTS: The return rate for initial questionnaires was 87.3% (61 boys, 28 girls) and for retest 70.6%. The mean score for IDQOL was 7.89 and for FDI 8.87. Spearman rank correlation between the IDQOL and FDI was high (r = 0.87). Correlations of IDQOL and FDI with clinical severity assessment by parents were lower (r = 0.58 for IDQOL and r = 0.5 for FDI). Test-retest data for IDQOL and FDI confirmed repeatability, there being negligible differences between the pairs using the method of Bland and Altman. The three highest scoring questions for IDQOL referred to itching and scratching, mood change and sleep disturbance. For the FDI they were parental sleep disturbance, tiredness and exhaustion, and emotional distress. Post-treatment questionnaires from 25 patients indicated sensitivity to clinical change with both IDQOL and FDI. Parameters of behaviour measured using the BCL in 82 study infants and 22 controls showed greater problems with frequent night-time wakening (43% vs. 4.5%) and miserable mood changes (24.4% vs. 9%) in the study infants. CONCLUSIONS: Initial validation of the IDQOL and further validation of the FDI show good test-retest repeatability and apparent sensitivity to change with treatment. The effect on health-related QOL as measured by these methods is poorly correlated with clinical severity, confirming that QOL measures should be used in conjunction with clinical measures for global assessments of disease impact. This work requires further validation but suggests that QOL measures may be useful as outcome measures in clinical practice and research. Their simple construction allows quick and easy use, which is particularly valuable in large-scale and postal studies.

Child, Preschool↗

PubMed2001

Effects of adhesive dressings on the stratum corneum of the skin.

Two human models were developed to quantify the stratum corneum removed by different adhesive dressings and to measure the peel force of dressing removal and relate this to stratum corneum removal. The first was an open study designed to compare the effects of applying Mepiform Safetac, Tielle and Duoderm Extra Thin to the skin of 12 normal volunteers aged 19-53 years. Treatments were applied once (one 24-hour application) or three times (three x 24-hour applications) to forearm skin which had been prestained with methylene blue. After dressing removal the dye left on the skin was sampled using the skin surface biopsy method and measured spectrophotometrically. The results show that, after one and three applications, the Mepiform Safetac sites had a higher level of dye than those on which the other dressings had been applied (p < 0.05, after three applications). Based on the assumption that the more dye is left on the skin, the less damage is caused, this suggests that Mepiform Safetac is less damaging to the skin surface than the other products tested. In the second study the peel force needed to remove adhesive dressings from prestained skin was measured and related to the amount of stratum corneum removed. Mepilex Border Safetac, Duoderm Extra Thin, Allevyn Adhesive, Biatain Adhesive and Tielle Hydropolymer Dressing were compared in 20 normal volunteers aged 23-64 years. Three consecutive 24-hour applications of each product were made, with measurements of peel force at 24, 48 and 72 hours. The amount of dye remaining on the skin at 72 hours was assessed by the surface biopsy method. Statistically significant differences between products were observed in terms of both peak force and steady state force of removal. Differences in the level of damage to the superficial stratum corneum were also detected. However, low levels of peel force were not always associated with low damage and, therefore, other factors must contribute to stratum corneum removal in this model.

Adhesives↗

PubMed2000

Impaired quality of life of adults with skin disease in primary care.

BACKGROUND: Although 75% of skin problems are managed exclusively in primary care, most information on the impact of skin disease on quality of life is hospital based. OBJECTIVES: To examine the ease of use of the Dermatology Life Quality Index (DLQI) in primary care and to measure the handicap levels found, analysed by skin disease, sex and age. METHODS: The handicap levels identified were compared with those published for patients with the same conditions attending hospital clinics. Some conditions that rarely present in secondary care were also studied. RESULT: S The overall mean +/- SD DLQI score was 7.37 +/- 5.71 (women 7.8 +/- 5.8, n = 196; men 6.8 +/- 5.6, n = 145). The scores for separate diseases were similar in ranking and only slightly lower than those in hospital-based studies. The possibility of bias towards surveying an unrepresentative sample of patients is discussed. There was no correlation between age and DLQI score. CONCLUSIONS: The DLQI proved easy to use in general practice. The impact of skin diseases on the quality of life of patients seen in primary care is comparable with that of patients seen in secondary care. This information could be used to inform the planning of services for these patients.

Adult↗

PubMed1997

Keratinocyte growth stimulation by granulocyte-macrophage colony-stimulating factor (GM-CSF).

Human granulocyte-macrophage colony stimulating factor (GM-CSF) is a 22 kD glycoprotein derived from activated T cells, endothelial cells, fibroblasts and macrophages. It stimulates the proliferation and differentiation of haematopoietic cells and certain nonhaematopoietic cells. This study investigated the effect of GM-CSF on cultured human keratinocytes and determined whether these cells express GM-CSF receptors. Measurement of keratinocyte growth by image analysis showed that GM-CSF mildly stimulated the growth of keratinocytes. With 4 ng/ml GM-CSF the growth of primary keratinocytes and subcultured keratinocytes was only stimulated up to 25% and 18% of the control cell level, respectively. Human keratinocytes were incubated with GM-CSF at 4 ng/ml for 4 days to induce receptor expression. These cells showed only a weak positive reaction on affinity labelling using digoxigenated GM-CSF. We conclude that keratinocyte growth may be stimulated by GM-CSF but that the presence of GM-CSF receptors on these cells is equivocal.

Cell Division↗

PubMed1996

Handicap in Darier's disease and Hailey-Hailey disease.

One hundred and thirty-seven patients with Darier's disease and 66 patients with Hailey-Hailey disease completed the Dermatology Life Quality Index (DLQI). The average DLQI score for Darier's disease was 5.89 (19.6% of the maximum score), median = 4, quartiles: 1.9. The average DLQI score for Hailey-Hailey disease was 6.06 (20.2% of the maximum score), median = 5, quartiles: 2.9. The DLQI score did not correlate with the physician's assessment of clinical severity in both diseases, thus emphasizing the importance of remembering the potential for handicap even in patients with disease that seems to be mild. The domains of the questionnaire with the highest mean scores in both diseases were for questions relating to symptoms and feelings. Domains relating to personal relationships and work obtained low mean scores even in severe disease. It is encouraging that most patients with Darier's disease and Hailey-Hailey disease maintain good relationships at work and home and seem to be able to adapt to their skin disease.

Adolescent↗

PubMed1996

The kinetics of skin thinning induced by topical fluticasone propionate 0.05% cream in volunteer subjects.

Fluticasone propionate (FP) 0.05% (CutivateTM) cream is a novel corticosteroid used for the treatment of corticosteroid-responsive dermatoses. To date there are no published data concerning its effect on cutaneous atrophy. This randomized, double-blind study of 40 volunteer subjects was performed to investigate the kinetics of skin thinning induced by topical 0.05% FP cream vs. placebo after once-daily application for 2-8 weeks. The results of this study showed no significant effect on the skin thickness of subjects after 8 weeks' treatment with 0.05% FP cream compared with placebo.

Administration, Cutaneous↗

PubMed1996

Clinical manifestations in 100 Japanese bullous pemphigoid cases in relation to autoantigen profiles.

The relationship between clinical findings and antigen profiles in 100 bullous pemphigoid (BP) patients has been investigated. The patients were divided into four groups based upon the results of immunoblot analysis, namely patients whose sera detected the 230-kDa BP antigen (BP230) and the 180-kDa BP antigen (BP180), those recognizing either BP230 or BP180 alone, and those recognizing neither antigen. Analysis by the chi-squared test showed predominant occurrence of oral (P < 0.05) and facial lesions (P < 0.005) in patients whose sera detected BP180, and these patients also tended to have more extensive lesions (P < 0.005). Patients that were positive for BP180 alone needed treatment with higher doses of steroids than the patients positive for BP230 alone (P < 0.05). Furthermore, all five recalcitrant cases, which did not respond well to steroid treatment, were shown to possess autoantibodies against BP180 in their sera. Patients with antibodies to BP230 had a tendency to have a high titre of anti-BMZ antibodies (P < 0.005). These results suggest that anti-BP180 antibodies may be more related to the disease severity than anti-BP230 antibodies. Bullous pemphigoid (BP) is an autoimmune blistering disorder characterized clinically by tense blister formation and immunologically by the presence of tissue-bound and circulating antibasement membrane zone (BMZ) autoantibodies. A number of immunoblot analyses have indicated that two major antigenic proteins of epidermal extracts, the 230-kDa BP antigen (BP230 or BPAG1) and the 180-kDa BP antigen (BP180, BPAG2 or type XVII collagen), are detected by sera from patients with BP in various patterns. Some BP sera recognize both antigen proteins, while others detect only BP230 or BP180 or none. Recently, cDNAs for these antigens have been isolated, and the characteristics for these molecules have been investigated in more detail. The exact relationship between these two proteins is still unclear; however, more recent studies showed that BP180 has an extracellular domain and polyclonal rabbit antibodies raised against an extracellular non-collagenous domain of the murine BP180 antigen were pathogenic in a passive transfer model. Several investigators have suggested a relationship between clinical findings and laboratory data in BP. Arbesman et al. compared the extent and duration of the disease with age, serum levels of IgE, IgA and IgG and titre of anti-BMZ antibodies. The results indicated that serum level of IgE and IgA correlated significantly to the extent of the disease and that titre of anti-BMZ antibodies correlated significantly (only in males) to the duration. There has been only one report which has analysed the relationship between pemphigoid antigens and clinical findings or laboratory data; no correlation was found. In a previous study, the reactivities of BP sera by immunoblotting using human epidermal extracts and two recombinant polypeptides produced from a mouse cDNA clone BPM1 were examined. The results of immunoblotting using epidermal extracts revealed that the two major BP antigens, BP230 and BP180, were detected by 74% and 51% of BP sera, respectively. Comparison of the clinical data with BP antigens gave the impression that the cases whose sera reacted only with BP180 were clinically more severe and less respondent to steroid treatment than the cases which detected BP230 alone on immunoblots. In the study reported here we have examined further the relationship between clinical and immunoblot data by applying a statistical analysis to the results previously obtained.

Adult↗

PubMed1995

The growth of ichthyotic epidermal cells in a 3-dimensional reconstruction of human skin, the skin equivalent.

We have studied the differentiation of ichthyotic epidermis in vitro using the skin equivalent model. The morphology of these ichthyotic cultures has been investigated using histopathological and histometric techniques including epidermal and stratum corneum thickness measurements. The skin equivalents have also been investigated for the presence of markers of differentiation using immunolocalization techniques. These markers include the 65.5 and 67 kDa keratins, desmoplakin, involucrin, laminin and filaggrin. It has been shown that the ichthyotic epidermis develops a fully differentiated epidermis and stratum corneum, equivalent to those seen in normal skin equivalents.

Cell Differentiation↗

PubMed1995

A stepwise procedure for evaluating irritant materials in normal volunteer subjects.

1. The cutaneous response to a known irritant has been assessed in human volunteer subjects using both clinical scoring and two non-invasive instrumental methods; erythema measurement using an erythema meter and capillary blood flow using a laser Doppler device. 2. Aqueous solutions (0.5% and 1%) of sodium hydroxide were applied to back skin for 3, 15 and 60 min with assessments immediately after removal and at 1, 24 and 48 hours. 3. Increased erythema was seen with increasing duration of exposure and an increase was also seen at 1 h, 24 h and 48 h after removal of the patch. The results obtained with the erythema meter paralleled the clinical erythema scores. However, the laser Doppler device showed the greatest changes immediately after removal of the patch with subsequent readings showing a gradual decrease. 4. Statistical analysis of the data has been carried out to determine the accuracy and precision of the assessment procedures and to determine the minimum test panel size for detecting irritant reactions. 5. Comparison between back and forearm skin indicated a greater sensitivity to sodium hydroxide on the back. 6. The results of this study define an ethical approach to testing irritant materials in human subjects and provide the basis for the development of a classification system for cutaneous irritants.

Adolescent↗

PubMed1992

An evaluation of the irritancy potential of povidone iodine solutions: comparison of subjective and objective assessment techniques.

A double-blind study has been carried out in 12 normal volunteer subjects in order to determine the relative irritancy of povidone-iodine solutions. Aqueous solutions of 10% povidone-iodine (PI), standardized 10% povidone-iodine (SPI) and reformulated standardized 10% povidone-iodine (RSPI) were applied to the backs and occluded using aluminium chambers. At 1, 2, 3, 4, 5, 6, and 8 hours, chambers were removed and the degree of cutaneous irritancy assessed. As well as subjective assessment of erythema, objective measurement of skin colour was performed using an erythema meter. In addition, laser Doppler blood-flow measurements have been carried out. The results show a rapid increase in cutaneous irritancy as evidenced by an increase in visual scores of erythema, increased erythema meter readings and increased cutaneous blood-flow. The increase was greatest for SPI treated sites for all three methods. Statistically these differences were significant at P < 0.05. Thus in this controlled study it has been possible to discriminate between the similar formulations in terms of their cutaneous irritancy.

Adult↗

PubMed1991

The effect of dermatophyte species and density of infection on the pathology of ringworm.

In this study we have measured the mean hyphal length as a function of the density of infection in skin surface biopsies from patients suffering from infection with different species of dermatophyte. The tissue response in the epidermis and dermis of these patients was evaluated for the degree of eczematization (epidermal thickening, spongiosis and dermal infiltrate) in periodic acid Schiff stained histological sections, employing visual analogue scales. There was no correlation between mean hyphal density and the degree of eczematization.

Adult↗

PubMed1991

Heat shock proteins in cultured human keratinocytes and fibroblasts.

Heat shock induces in cells the synthesis of specific proteins called heat-shock proteins. We have compared the induction of these proteins in human keratinocytes, skin fibroblasts, and a human epithelial tumor cell line following exposure to weak and strong inducing agents (heat, cadmium sulphate, and sodium arsenite). The induction of heat shock proteins was measured in cells by one-dimensional gel electrophoresis of [35S] methionine-labeled proteins and by immunofluorescence using a specific HSP72 monoclonal antibody. Both HSP90 and HSP116 were constitutively expressed in these cell types. Exposure of these cells to weak inducing agents such as heat or cadmium sulphate resulted in the synthesis of HSP72 and HSP90, whereas HSP28 and HSP116 synthesis was detected in keratinocytes and fibroblasts following exposure to the strong inducing agent sodium arsenite. In addition, sodium arsenite induced the synthesis of HSP46 in human keratinocytes. Immunofluorescence demonstrated a rapid and reversible accumulation of the 72-kD heat shock protein within the nucleolus of heat-stressed human keratinocytes and fibroblasts.

Arsenic↗

PubMed1991

Phenytoin has little effect on in-vitro models of wound healing.

It has been reported that phenytoin induces gingival and connective tissue hyperplasia and may be of use in wound healing. In this study the effect of phenytoin on human epidermal keratinocytes and skin fibroblasts has been investigated in vitro. Cell cultures were exposed to increasing concentrations of phenytoin from 10(-9) to 10(-4) M in the presence of 1 and 10% serum supplemented medium. In addition the effect of phenytoin on epidermal cell migration (epiboly) has been investigated using organ culture of human skin. No stimulation of cell growth was observed, and only a mild toxicity affecting keratinocytes was seen at the highest concentrations. Similarly, no effect on epidermal cell migration in vitro was observed. The lack of a direct effect in vitro suggests that any in-vivo effect was not the result of interaction between phenytoin and keratinocytes or fibroblasts but possibly due to indirect modulation via other cell types, such as inflammatory or lymphoreticular cells.

Adult↗

PubMed1991

The effect of area of application on the intensity of response to a cutaneous irritant.

The intensity of the cutaneous response was assessed after application of a standard irritant to increasing areas of normal forearm skin. Twenty subjects were tested to determine the minimal irritant dose (MID) to dilutions of aqueous sodium dodecyl sulphate. Each subject was then treated under occlusion for a period of 24 h with different areas of filter paper (9, 25, 100, 225 and 400 mm2) soaked with the concentration required to give the individual's MID. At 25 and 48 h the degree of erythema was assessed using a 0-4 arbitrary scale, a 10-cm visual analogue scale (VAS) and an erythema meter. Cutaneous blood flow was measured with a laser-Doppler device and cutaneous oedema measured by pulsed A-scan ultrasound. The results at 25 and 48 h were almost identical. Both forms of visual assessment (arbitrary scale and VAS) showed an increase in perceived erythema with increasing area and this was confirmed by the erythema meter. Further area-related changes were noted with both cutaneous blood flow and ultrasound measurements.

Administration, Cutaneous↗

PubMed1991

Efficacy of topical dimetindene in experimentally induced pruritus and weal and flare reactions.

Double-blind, placebo-controlled studies were performed to assess the effect of 0.1% dimetindene gel on the itch threshold to intracutaneous histamine and on the weal and flare reaction after intracutaneous injection of histamine in normal volunteer subjects. Treatment of the forearm skin in 20 volunteers resulted in an increase in itch threshold with dimetindene gel compared to placebo. Treatment of the forearm skin with dimetindene gel in 32 volunteers had no significant effect on weal thickness in subjects treated for 10, 30 or 60 min, but there was a significant reduction in weal thickness in those subjects treated for 120 min. Topical dimetindene may be of value in treating conditions mediated through histamine release.

Administration, Topical↗