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Biomedical subjects

C E Griffiths

Publications and source records attributed to C E Griffiths.

At least 73 records · Page 4Linked to original sources
PubMed1999

Figurate erythema with bullous pemphigoid: a true paraneoplastic phenomenon?

There has been controversy about the possible link between bullous pemphigoid and underlying malignancy. We report a case of bullous pemphigoid with marked figurate erythema which arose shortly before the clinical presentation of colonic carcinoma and cleared completely 1 week after its resection. We review the literature and conclude that patients who present with clinically atypical bullous pemphigoid may warrant investigation for underlying neoplasia.

Colonic Neoplasms↗
PubMed1999

Fibrillin-rich microfibrils are reduced in photoaged skin. Distribution at the dermal-epidermal junction.

Chronic sun exposure results in photoaged skin with deep coarse wrinkles and loss of elasticity. We have examined the distribution and abundance of fibrillin-rich microfibrils, key structural components of the elastic fiber network, in photoaged and photoprotected skin. Punch biopsies taken from photoaged forearm and from photoprotected hip and upper inner arm of 16 subjects with a clinical range of photoaging were examined for fibrillin-1 and fibrillin-2 expression and microfibril distribution. In situ hybridization revealed decreased fibrillin-1 mRNA but unchanged fibrillin-2 mRNA levels in severely photoaged forearm biopsies relative to photoprotected dermal sites. An immunohistochemical approach demonstrated that microfibrils at the dermal-epidermal junction were significantly reduced in moderate to severely photoaged forearm skin. Confocal microscopy revealed that the papillary dermal microfibrillar network was truncated and depleted in photoaged skin. These studies highlight that the fibrillin-rich microfibrillar network associated with the upper dermis undergoes extensive remodeling following solar irradiation. These changes may contribute to the clinical features of photoaging, such as wrinkle formation and loss of elasticity.

Adult↗
PubMed1999

Drug treatment of photoaged skin.

Although the prevention of skin aging is a holy grail of the cosmetic and pharmaceutical industries, this venture may be misplaced. The predominant clinical and biochemical features of aged skin are mostly attributable to photoaging rather than chronology. For instance chronic sun exposure is the major determinant of age spots (actinic lentigines) and wrinkles. Surgical approaches to the treatment of photoaging include face-lift, dermabrasion, chemical peeling, collagen and botulinum toxin injections, and laser re-surfacing. These approaches all have benefit and improve the clinical features of facial photoaging. Drug or pharmaceutical prevention and treatment of photoaged skin is still in its infancy. The main pharmaceutical approach to prevention of photoaging lies in the assiduous use of sunscreens. Recent evidence points to the importance of ultraviolet A (UVA) radiation as well as ultraviolet B (UVB) radiation in the aetiology of photoaging and thus the need for sunscreens that block both UVB and UVA. Drug treatment of photoaged skin can be categorised as antioxidants, alpha-hydroxy acids and topical retinoids. Of these 3 approaches only topical retinoids, particularly tretinoin (all-trans retinoic acid), have a well documented ability to repair photoaged skin at the clinical, histological and molecular level. Furthermore, the use of topical retinoids may actually prevent photoaging. The current interest in pharmaceutical modulation of the photoaging process has attracted considerable research into the mechanisms of photoaging and cutaneous aging. It is likely that treatment for, or prevention of, the chronological aging process may result from such research.

Aged↗
PubMed1999

Patients with psoriasis and their compliance with medication.

BACKGROUND: Poor compliance with treatment advice in chronic conditions, such as psoriasis, represents a major challenge to health care professionals. Previous research suggests that the rate of noncompliance in chronic conditions may be as high as 40%. OBJECTIVE: This study was designed to examine self-reported compliance in patients with psoriasis. METHODS: We undertook an anonymous postal survey sent to consecutive patients with psoriasis attending a tertiary psoriasis specialty clinic. RESULTS: Thirty-nine percent of participants reported that they did not comply with the treatment regimen recommended. The noncompliant group had a higher self-rated severity of psoriasis (t = -2.16, P =. 03), were younger (t = 3.28, P =.001), and had a younger age at onset (t = 2.35, P =.02) than those who were compliant. The noncompliant group reported that psoriasis had a greater impact on daily life (t = -2.23, P =.028), but general well-being was not significantly different from those who complied (t =.47, P = not significant). CONCLUSION: Patients who reported intentional noncompliance with treatment advice were more likely to believe that both psoriasis and its treatment interfered with their quality of life but not overall well-being. The impact of treatment on daily life highlights the importance of joint decision making in planning treatment.

Adolescent↗
PubMed1998

GMDP and psoriasis.

Explore the source record for details and available documents.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1998

What patients with psoriasis believe about their condition.

BACKGROUND: Patients' beliefs about their disease have been shown to be of fundamental importance in adjustment to their condition. OBJECTIVE: We investigated patients' beliefs about their psoriasis and examined the relationship between these beliefs and clinical severity, symptom report, and other clinical and demographic variables. METHODS: A total of 162 patients with psoriasis (84 male, 78 female) completed the illness perception questionnaire that provides a standardized assessment of beliefs about causes, consequences, chronicity or recurrence, controllability, and symptoms of the condition. RESULTS: The most commonly reported agents of causation were stress (60.1%) and genetic factors (55.5%)--the latter group being significantly more likely to have a family history of psoriasis (P=.0001). Forty-six percent of patients believed that their behavior could improve or worsen their psoriasis, whereas 32% believed that treatment would be curative. Desquamation and pruritus were experienced "frequently" or "all the time" by 80% and 76% of patients respectively. Overall clinical severity was not associated with any of the beliefs held by patients or with symptom report. CONCLUSION: The beliefs held and symptoms experienced by patients with psoriasis are not governed by overall clinical severity of the disease.

Adolescent↗
PubMed1998

Calcipotriene-induced improvement in psoriasis is associated with reduced interleukin-8 and increased interleukin-10 levels within lesions.

Calcipotriene is a synthetic analogue of 1,25-dihydroxyvitamin D3 established to be effective topically in the treatment of psoriasis. We investigated the early cellular and immunological events induced by calcipotriene in psoriasis. Thirty patients with moderate plaque-type psoriasis were randomly assigned to receive twice daily applications of either calcipotriene ointment 0.005% or matching vehicle for 6 weeks. Skin biopsies (6 mm) were performed from designated plaques at baseline and days 3 and 7. On these days and at weeks 2, 4 and 6, complete clinical evaluations were made in a double-blind fashion. Consistent with previous studies, significant clinical improvement (P < 0.05) in psoriasis was observed in patients receiving calcipotriene vs. those receiving vehicle by day 7 for scale and erythema, and by day 14 for thickness. No significant improvement, however, was seen on day 3. None of the immunohistological markers (CD1a, CD4, CD8, ICAM-1, VCAM-1, E-selectin, HLA-DR) semiquantitatively assessed in psoriatic plaques was significantly changed by calcipotriene treatment for 7 days. In the calcipotriene-treated group, interleukin (IL)-10 levels (pg/microgram of protein) increased by 57% from baseline (0.030 +/- 0.006; mean +/- SEM) to day 3 (0.047 +/- 0.011) (P = 0.05 vs. baseline; n = 10) and remained elevated at day 7 (0.046 +/- 0.012). IL-8 levels (pg/microgram of protein), however, declined by 70% from baseline (0.13 +/- 0.06) to day 3 (0.04 +/- 0.01), and remained low at day 7 (0.03 +/- 0.02) (P < 0.05 vs. baseline; n = 10). Both IL-8 and IL-10 were unaffected by vehicle treatment. Calcipotriene-induced clinical improvement of psoriasis is preceded by an increase in IL-10 and a concomitant decrease in IL-8 levels. The changes in the level of these two cytokines provide further evidence for immunological changes as a significant part of the mechanism of action of calcipotriene in psoriasis.

Adolescent↗
PubMed1998

Fibrillin microfibrils are reduced in skin exhibiting striae distensae.

Striae distensae (striae: stretch marks) are a common disfiguring condition associated with continuous and progressive stretching of the skin--as occurs during pregnancy. The pathogenesis of striae is unknown but probably relates to changes in those structures that provide skin with its tensile strength and elasticity. Such structures are components of the extracellular matrix, including fibrillin, elastin and collagens. Using a variety of histological techniques, we assessed the distribution of these extracellular matrix components in skin affected by striae. Pregnant women were assessed for the presence of striae, and punch biopsies were obtained from lesional striae and adjacent normal skin. Biopsies were processed for electron microscopy, light microscopy and immunohistochemistry. For histological examination, 7 microns frozen sections were stained so as to identify the elastic fibre network and glycosaminoglycans. Biopsies were also examined with a panel of polyclonal antibodies against collagens I and III, and fibrillin and elastin. Ultrastructural analysis revealed alterations in the appearance of skin affected by striae compared with that of normal skin in that the dermal matrix of striae was looser and more floccular. Light microscopy revealed an increase in glycosaminoglycan content in striae. Furthermore, the number of vertical fibrillin fibres subjacent to the dermal-epidermal junction (DEJ) and elastin fibres in the papillary dermis was significantly reduced in striae compared with normal skin. The orientation of elastin and fibrillin fibres in the deep dermis showed realignment in that the fibres ran parallel to the DEJ. However, no significant alterations were observed in any other extracellular matrix components. This study identifies a reorganization and diminution of the elastic fibre network of skin affected by striae. Continuous strain on the dermal extracellular matrix, as occurs during pregnancy, may remodel the elastic fibre network in susceptible individuals and manifest clinically as striae distensae.

Actin Cytoskeleton↗
PubMed1998

Comparison of teleconsultations and face-to-face consultations: preliminary results of a United Kingdom multicentre teledermatology study.

The objective of this multicentre study was to undertake a systematic comparison of face-to-face consultations and teleconsultations performed using low-cost videoconferencing equipment. One hundred and twenty-six patients were enrolled by their general practitioners across three sites. Each patient underwent a teleconsultation with a distant dermatologist followed by a traditional face-to-face consultation with a dermatologist. The main outcome measures were diagnostic concordance rates, management plans and patient and doctor satisfaction. One hundred and fifty-five diagnoses were identified by the face-to-face consultations from the sample of 126 patients. Identical diagnoses were recorded from both types of consultation in 59% of cases. Teledermatology consultations missed a secondary diagnosis in 6% of cases and were unable to make a useful diagnosis in 11% of cases. Wrong diagnoses were made by the teledermatologist in 4% of cases. Dermatologists were able to make a definitive diagnosis by face-to-face consultations in significantly more cases than by teleconsultations (P = 0.001). Where both types of consultation resulted in a single diagnosis there was a high level of agreement (kappa = 0.96, lower 95% confidence limit 0.91-1.00). Overall follow-up rates from both types of consultation were almost identical. Fifty per cent of patients seen could have been managed using a single videoconferenced teleconsultation without any requirement for further specialist intervention. Patients reported high levels of satisfaction with the teleconsultations. General practitioners reported that 75% of the teleconsultations were of educational benefit. This study illustrates the potential of telemedicine to diagnose and manage dermatology cases referred from primary care. Once the problem of image quality has been addressed, further studies will be required to investigate the cost-effectiveness of a teledermatology service and the potential consequences for the provision of dermatological services in the U.K.

Attitude of Health Personnel↗
PubMed1998

All-trans retinoic acid compromises desmosome expression in human epidermis.

An undesirable side-effect of retinoid treatment is skin fragility. As desmosomes are important in maintaining the cohesion of epidermal keratinocytes, we investigated whether all-trans-retinoic acid (RA) compromises desmosome expression in human epidermis, thereby predisposing skin to fragility. Solutions containing 0.025% RA, 5% sodium dodecyl sulphate (SDS) as an irritant control, or vehicle alone were applied to three sites on the buttocks of normal volunteers (n = 9). Treated sites were occluded for 4 days, and biopsies taken under local anaesthesia. Cryostat sections were stained with a panel of antibodies to desmosomal proteins and visualized by immunofluorescence microscopy. Stained sections were randomized and assessed for intensity of staining. The epidermal thickness of each treated site was quantified by image analysis. Western blots of epidermal desmocollins were quantified by densitometry. RA and SDS treatments significantly, but equivalently, increased epidermal thickness compared with vehicle. Immunohistochemically, both RA and SDS were shown to reduce epidermal staining for desmoplakin, desmoglein 1, plakophilin 1 and desmocollin 3 equally compared with vehicle-treated skin (P < 0.001). RA produced a greater reduction in desmocollin 1 staining compared with SDS (P < 0.001). Similar reductions in desmocollins were found by Western blot analysis. Reduced desmocollin expression may indicate compromised desmosomal adhesion, leading to the skin fragility that results from retinoid treatment.

Adult↗
PubMed1998

Adapalene 0.1% gel and adapalene 0.1% cream stimulate retinoic acid receptor mediated gene transcription without significant irritative effects in the skin of healthy human volunteers.

A randomized, investigator masked, intra individual comparative study was conducted in 30 healthy volunteers to compare the cutaneous effects of adapalene 0.1% gel and adapalene 0.1% cream with their respective vehicles, using tretinoin 0.05% cream (n = 21) or tretinoin 0.1% cream (n = 9) and a tretinoin cream vehicle (n = 30) as controls. The products were applied to hip/buttock skin for 4 days under occlusive conditions. Cytosolic retinoic acid binding protein-II (CRABP-II) mRNA levels were measured using the RT-PCR technique in punch biopsies taken from 10 subjects. Epidermal thickness was assessed using image analysis of haematoxylin and eosin stained sections from another 11 subjects. Erythema was assessed in all subjects both by a visual scoring system and by chromameter. Adapalene 0.1% gel and adapalene 0.1% cream produced similar significant increases in CRABP-II mRNA levels compared to their vehicles (P < 0.01). The two tretinoin formulations also resulted in similar significant increases in CRABP-II compared to the cream vehicle (P < 0.001). However, only the two tretinoin formulations resulted in an increase in epidermal thickness and only the tretinoin 0.1% cream resulted in significant erythema. Adapalene 0.1% gel and adapalene 0.1% cream induce RAR-mediated gene expression to a similar degree in this model, without the irritant effects of tretinoin.

Adapalene↗
PubMed1998

Quality of life measures in psoriasis: a critical appraisal of their quality.

In recent years, the importance of patient-generated evaluations in assessing the impact of healthcare has been recognized. A plethora of quality of life (QoL) instruments have been developed to measure the burden of psoriasis and its treatment on the patient. We review the QoL measures and provide a critical appraisal of their quality. There is considerable variation in how the instruments have been constructed, the categories and items included, and the methods by which their reliability and validity have been examined. In order to guide investigators in their choice of instrument, further head-to-head comparisons of measures should be undertaken. When QoL measures are compared, a Pearson or rank-order correlation coefficient is not sufficient to indicate agreement. Methods that examine agreement, rather than association, are available and should be used. In the future, we will need to demonstrate whether these measurement tools are ready for widespread implementation in clinical trials or routine patient follow-up.

Data Collection↗
PubMed1998

Differential expression of peroxisome proliferator-activated receptor subtypes during the differentiation of human keratinocytes.

The expression of mRNA encoding peroxisome proliferator-activated receptor (PPAR) subtypes in human keratinocytes was determined by semiquantitative reverse transcriptase-polymerase chain reaction. When normal human keratinocytes were induced to differentiate by shifting the culture medium to high Ca2+ concentration, the expression of PPAR-alpha and -gamma mRNA was increased, whereas that of PPAR-delta remained unchanged. At the protein level, the expression of PPAR in cultured human keratinocytes was demonstrated by a DNA mobility shift assay and the functionality of the receptor subtypes was assessed by transactivation experiments. In epidermis reconstructed in vitro, the level of PPAR-alpha and -gamma mRNA was also associated with keratinocyte differentiation. In lesional compared with nonlesional psoriatic epidermis, the expression of PPAR-alpha and -gamma mRNA was reduced, indicating that these two subtypes are tightly linked to the epidermal differentiation process.

Cell Differentiation↗
PubMed1998

Novel therapeutic approaches to psoriasis.

Psoriasis is common, chronic and currently incurable. First-line therapies consist of topical preparations, the most recent of which include vitamin D3 and retinoid analogues. New approaches to phototherapy include narrow band ultraviolet B and photodynamic therapy. Considerable research is currently focused on immunomodulatory approaches to this disease.

Cholecalciferol↗
PubMed1998

Retinoids and vitamin D analogues: action on nuclear transcription.

Receptors for retinoids and vitamin D belong to the superfamily of ligand-dependent nuclear transcription factors. Development of topical and systemic retinoids and topical vitamin D3 analogues is revolutionizing dermatological therapy, particularly the management of acne, psoriasis, ichythyoses, photoageing and skin cancer.

Humans↗