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Biomedical subjects

A D Pearse

Publications and source records attributed to A D Pearse.

At least 19 recordsLinked to original sources
PubMed2006

Modulation of ultraviolet (UV) transmission by emollients: relevance to narrowband UVB phototherapy and psoralen plus UVA photochemotherapy.

BACKGROUND: Patients with psoriasis undergoing or about to undergo ultraviolet (UV) phototherapy and photochemotherapy often have thick scale on their plaques which can prevent the penetration of UV radiation. Emollients are used to moisturize the skin and to prevent or reduce some of the milder side-effects ('dryness', itching) sometimes experienced during UV therapy. However, emollients can alter the UV transmission of skin and thus may alter the clinical effects of phototherapy and photochemotherapy. OBJECTIVES: We tested 30 of the topical emollients in the British National Formulary (BNF) using a standard in vitro technique used to test sunscreens. We also surveyed U.K. phototherapy units to establish routine practice for emollient use in phototherapy and photochemotherapy. METHODS: We used a standard in vitro technique to measure the monochromatic protection factors (MPFs) of 30 non-bath emollients from the BNF. An application rate of 2 mg cm-2 was used. For the assessment of effects during narrowband UVB (TL-01) phototherapy, the mean of the protection factors at 310 and 315 nm was calculated; for psoralen plus UVA photochemotherapy the mean UVA protection factor was used. A questionnaire survey was used to assess routine practice concerning emollient use prior to phototherapies in phototherapy units throughout the U.K. RESULTS: In the UVA range, 17 of the 30 emollients gave protection factors of 1.2 or above. In the UVB range, 23 of 30 had an MPF of 1.2 or above. Yellow soft paraffin had the highest protection factor in the UVB range. Of 78 centres surveyed, 57 returned completed questionnaires (73%). Seventeen of 57 (30%) centres routinely used emollients immediately prior to administering phototherapy treatments. The remaining 40 of 57 (70%) did not. Forty-five (79%) responding centres recommended the use of emollients after phototherapy. CONCLUSIONS: This study has revealed considerable variability in the practice of emollient use before phototherapy treatments. Although the majority of centres included in this study did not routinely use emollients, almost one third did. Our in vitro measurement of 30 emollients revealed marked variation in UV transmission, with many emollients blocking sufficient UV to affect the response to therapy.

Drug Utilization↗
PubMed2005

Photosensitive Smith-Lemli-Opitz syndrome is not caused by a single gene mutation: analysis of the gene encoding 7-dehydrocholesterol reductase in five U.K. families.

BACKGROUND: Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive malformation syndrome characterized by a disorder in cholesterol metabolism. SLOS is caused by mutations in the DHCR7 gene which encodes 7-dehydrocholesterol reductase, an enzyme that catalyses the final step in cholesterol biosynthesis. We have previously established the clinical and photobiological features of the photosensitivity that is frequently a feature of SLOS. OBJECTIVES: In this study, we have performed mutational analysis of the DHCR7 gene in individuals from five families with SLOS. In each family, one member was affected by severe photosensitivity as a manifestation of SLOS. METHODS: Fifteen samples (including family controls) were screened using polymerase chain reaction amplification and direct automated sequencing. RESULTS: Six different DHCR7 mutations were identified of which five were single point mutations that caused missense amino acid substitutions (P51H, T93M, L99P, E448K and R450L). The other was a splice site mutation (G-->C in splice acceptor site) affecting the intron 8-exon 9 splice junction (IVS8-1 G-->C). This splice site mutation and four of the five missense mutations have been previously published as causal in SLOS but the P51H is a novel mutation which has not previously been reported. CONCLUSIONS: This is the first study in which DHCR7 gene mutational analysis has been performed on SLOS subjects with severe photosensitivity and indicates that no single mutation is responsible for the photosensitivity which characterizes this disorder.

Adolescent↗
PubMed2002

Guidelines for topical photodynamic therapy: report of a workshop of the British Photodermatology Group.

Topical photodynamic therapy (PDT) is effective in the treatment of certain non-melanoma skin cancers and is under evaluation in other dermatoses. Its development has been enhanced by a low rate of adverse events and good cosmesis. 5-Aminolaevulinic acid (ALA) is the main agent used, converted within cells into the photosensitizer protoporphyrin IX, with surface illumination then triggering the photodynamic reaction. Despite the relative simplicity of the technique, accurate dosimetry in PDT is complicated by multiple variables in drug formulation, delivery and duration of application, in addition to light-specific parameters. Several non-coherent and coherent light sources are effective in PDT. Optimal disease-specific irradiance, wavelength and total dose characteristics have yet to be established, and are compounded by difficulties comparing light sources. The carcinogenic risk of ALA-PDT appears to be low. Current evidence indicates topical PDT to be effective in actinic keratoses on the face and scalp, Bowen's disease and superficial basal cell carcinomas (BCCs). PDT may prove advantageous where size, site or number of lesions limits the efficacy and/or acceptability of conventional therapies. Topical ALA-PDT alone is a relatively poor option for both nodular BCCs and squamous cell carcinomas. Experience of the modality in other skin diseases remains limited; areas where there is potential benefit include viral warts, acne, psoriasis and cutaneous T-cell lymphoma. A recent British Photodermatology Group workshop considered published evidence on topical PDT in order to establish guidelines to promote the efficacy and safety of this increasingly practised treatment modality.

Aminolevulinic Acid↗
PubMed2001

Bowen's disease, solar keratoses and superficial basal cell carcinomas treated by photodynamic therapy using a large-field incoherent light source.

BACKGROUND: Photodynamic therapy (PDT) has not yet been demonstrated to be superior to conventional treatment in the treatment of superficial skin cancers and premalignant skin conditions. A limitation for PDT is the absence to date of a light source suitable for the treatment of larger lesions or 'field changes' where several lesions are present on one anatomical site. OBJECTIVES: To investigate the safety and efficacy of a large field light source, the Waldmann PDT 1200, in the treatment of Bowen's disease (BD), superficial basal cell carcinomas (BCCs) and solar keratoses (SKs). METHODS: After application of 5-aminolaevulinic acid for 4-6 h, each lesion was irradiated with 105 J cm-2 of incoherent red light centred on 640 nm. Eighty-eight patients with 239 lesions were recruited. RESULTS: Within two treatments, 88% of BD lesions, 95% of BCCs and 99% of SKs showed complete clinical clearance. At 12 months the complete response rates were 69% for BD, 82% for BCC and 72% for SK. CONCLUSIONS: This study confirms that PDT is a useful treatment and that selected superficial BCCs and SKs respond well to PDT. The PDT 1200 light source proved capable of treating multiple lesions amounting to a 'field change' and also lesions up to 10 cm in diameter within an acceptable treatment time. Thus far, PDT has failed to become established as a routine treatment for small premalignant and malignant skin lesions as it has not proved superior to simple cheaper conventional therapies such as cryotherapy, curettage and cautery, topical chemotherapy with 5-fluorouracil, or surgery. However, PDT has become established as a treatment for selected cases in some centres. This study suggests a role for PDT in the treatment of large premalignancies, superficial BCCs and field change where existing treatments may be problematic.

Adult↗
PubMed1999

Cigarette smoking-associated elastotic changes in the skin.

BACKGROUND: Clinical features of the skin in persons who smoke include increased wrinkling, gauntness, and discoloration that has been termed smoker's face. The histologic changes in the sun-exposed skin of these patients have not been previously elucidated. OBJECTIVE: The purpose of this study was to assess the amount of elastosis in the sun-exposed skin of smokers and nonsmokers. METHODS: We evaluated the skin from the forehead and cheeks of 17 smokers and 14 nonsmokers for the presence of elastosis. With the use of a computer-generated analysis of tissue sections at 4 different levels, the amount of elastotic material was expressed as an average percent of the field staining for elastic tissue. Patients were also evaluated for the presence of other malignancies, arsenic and radiation exposure, and previous skin cancers. RESULTS: There was a significantly greater amount of elastosis (P < .05) in the skin of patients who smoked compared with those patients who did not. No significant differences were found between the 2 groups with regard to the other parameters evaluated. CONCLUSION: Cigarette smoking is associated with an increase in elastosis, which may contribute to the clinical features of "smoker's face."

Elastic Tissue↗
PubMed1999

Characterization of photosensitivity in the Smith-Lemli-Opitz syndrome: a new congenital photosensitivity syndrome.

Photosensitivity has recently been reported as a feature of the Smith-Lemli-Opitz syndrome (SLO). The aim of this study was to establish the photobiological features of this disorder and to examine the hypothesis that the photosensitivity is caused by the high levels of 7-dehydrocholesterol found in SLO. All known cases of SLO in the U.K. were reviewed and clinical details of photosensitivity were recorded in detail. The action spectrum of the photosensitive eruption was defined by monochromator light testing. Thirteen of the 23 subjects (57%) had severe photosensitivity, and in 10 there was no photosensitivity. No correlation was identified between levels of 7-dehydrocholesterol and severity of photosensitivity, suggesting that the photosensitivity in SLO is not caused by a direct phototoxic effect mediated by 7-dehydrocholesterol. A novel pattern of photosensitivity was observed, with onset of a sunburn-like erythema on sun-exposed skin within minutes of sun exposure, which persisted in most cases for up to 24-48 h before fading. Monochromator light testing in three subjects showed an ultraviolet (UV) A-mediated photosensitivity eruption with greatest photosensitivity at 350 nm. Photosensitivity is a common and prominent feature of SLO and appears to be UVA-mediated. Elucidation of its biochemical basis may provide insight into normal cutaneous protective mechanisms against UVA-induced photodamage, and also sun sensitivity in general.

Adolescent↗
PubMed1998

Photosensitivity associated with the Smith-Lemli-Opitz syndrome.

A case of severe photosensitivity in a girl with the Smith-Lemli-Opitz syndrome is reported. Children with this recessively inherited metabolic disorder of cholesterol metabolism present with a variety of congenital abnormalities of the nervous system and internal organs in association with varying degrees of mental retardation. Photosensitivity is a feature which has previously only briefly been mentioned in the literature in association with this syndrome. However, more recently, it has become apparent that photosensitivity is not uncommon among children with the Smith-Lemli-Opitz syndrome, although the nature of the photosensitivity in these patients has remained undefined. Our patient has suffered from sunlight intolerance since early infancy, with redness and pruritus of sun-exposed skin developing within minutes of sun exposure. Monochromator ultraviolet (UV) radiation and visible light testing revealed an immediate and persistent reaction to low-dose UVA at 350 nm, and an abnormal erythemal response to visible light at 400 nm.

Child, Preschool↗
PubMed1995

The effects of chronic sunscreen use on the histologic changes of dermatoheliosis.

BACKGROUND: Sunscreen application to the skin of hairless mice is effective in reversing the histologic changes associated with photoaging (solar elastosis, epidermal thickening, collagen depletion, glycosaminoglycan deposition). These reparative processes have not been studied in human beings. OBJECTIVE: The aim of this study was to evaluate histologically the effects of daily application of a UVA/UVB sunscreen versus placebo. METHODS: We examined 46 patients who were given either sunscreen or vehicle and asked to apply it daily for 24 months. Punch biopsy specimens were obtained from preauricular skin at 0, 12, and 24 months. Each specimen was examined for epidermal thickening and organization and dermal inflammatory infiltrate by light microscopy. Computer-generated analysis of tissue sections was used to evaluate solar elastosis. RESULTS: A significant difference in solar elastosis was found between the treatment groups; however, the other features remained largely unchanged. CONCLUSION: The dermal changes of photoaging may be affected differently than epidermal changes when UV radiation exposure is diminished. UVA and UVB may contribute diversely to these cutaneous changes. Computer-generated evaluation of dermatoheliosis may be more accurate than visual inspection.

Adult↗
PubMed1994

Expression of c-fos proto-oncogene mRNA in non-melanoma skin cancer.

c-fos is a member of the proto-oncogene family and is implicated in the modulation of cell proliferation and differentiation. Previous studies have shown that the c-fos gene expression is regulated in a tissue specific manner. In order to clarify the role of the c-fos gene in human epidermis, we have investigated c-fos mRNA expression in both normal skin and non-melanoma skin cancer. In normal skin the intensity of the c-fos mRNA expression in spinous cells was found to be stronger than that observed in basal cells. In lesions of solar keratosis and Bowen's disease the spinous cells also showed stronger c-fos mRNA expression than in basal cells. In two of four cases of Bowen's disease some upper spinous cells showed very strong mRNA expression of the c-fos gene. In squamous cell carcinomas studied there was considerable variation in the intensity of c-fos mRNA expression. Our findings indicate that the degree of c-fos mRNA expression is related to the degree of dysplasia present. In all cases of basal cell carcinoma examined the c-fos mRNA expression was markedly decreased. These results suggest that c-fos expression may be involved in the differentiation of human keratinocytes in vivo rather than in the neoplastic process itself.

3T3 Cells↗
PubMed1993

The acute effects of ultraviolet-B radiation on c-myc and c-Ha ras expression in normal human epidermis.

It is well known that ultraviolet radiation (UVR) causes DNA damage due to the formation of photoproducts which result in the inhibition of DNA synthesis. It has been reported that DNA damage by physical agents such as UVR and chemical carcinogens induces alteration of certain gene expressions. Recently the transient induction of c-myc and c-Ha ras proto-oncogene expressions has been observed in a human keratinocyte cell line in vitro. The present study was designed to investigate whether the induction of these proto-oncogenes occurs in normal human epidermis after UVR in vivo and to relate these findings to DNA synthesis. C-myc and c-Ha ras transcripts were detected throughout human epidermis before and after UVR. C-myc expression increased significantly 5 h after two times the minimal erythema dose (2 x MED) of UVR, while DNA synthesis of the irradiated skin had recovered from the UVR-induced inhibition. The intensity of c-Ha ras expression remained unchanged at both 5 and 24 h after UVR. These results suggest that the c-myc gene plays an important role in the recovery of keratinocytes from acute damage following UVR.

Adult↗
PubMed1992

Derivation of a dysplasia index for epidermal neoplasia.

Measurements have been performed on histological sections of normal, paralesional and affected skin of patients with solar keratoses in an attempt at quantification of the degree of dysplasia. Features of dysplasia, including the epidermal thickness, the nuclear fraction and nuclear size distribution and shape, have been individually derived and incorporated into a formula designed to reflect the degree of dysplastic change within the epidermis. Application of this 'index of dysplasia' has been shown to differentiate lesional epidermis from that of the surrounding and normal non-sun-exposed skin. In addition, this index correlated well with independent dermatopathologists' assessments of the degree of dysplasia.

Cell Nucleus↗
PubMed1988

Clinical response and tissue effects of etretinate treatment of patients with solar keratoses and basal cell carcinoma.

Patients with basal cell carcinoma and solar keratoses were treated with etretinate. Substantial and prolonged clinical improvement was seen. All patients with solar keratoses showed a decrease in the mean area and number of lesions and eight patients demonstrated complete healing clinically. Two patients experienced recurrence at 9 months after completion of treatment. Histometric and cell kinetic measurements on the epidermis of skin samples from these patients were performed. They revealed epidermal thickening and increased deoxyribonucleic acid (DNA) synthesis both in lesions and in clinically uninvolved skin following treatment. Assessments were also made of enzyme activities in lesions and uninvolved skin with the use of established quantitative cytochemical techniques. Significant reduction in levels of succinic dehydrogenase activity following etretinate treatment was detected in solar keratoses and in basal cell carcinomas. This was also the case for uninvolved skin of patients with solar keratoses. Glucose-6-phosphate dehydrogenase (G6PD) activity was significantly reduced following etretinate treatment in solar keratoses and in basal cell carcinomas, but uninvolved skin did not exhibit significant changes. These changes are in contrast to those previously reported in normal subjects, where the activity increased, but are similar to those observed in patients with ichthyotic disorders. The alterations in the cytochemical profile following administration of etretinate in the lesions of patients reported here are consistent with the view that the drug promotes a more normal pattern of epidermal differentiation. We favor the view that etretinate's antineoplastic action is exerted by preferentially allowing differentiation of normal epidermal cells and inhibiting dysplastic cells.

Aged↗
PubMed1987

Epidermal changes in human skin following irradiation with either UVB or UVA.

We have demonstrated previously that following UVB irradiation to normal volunteers there is an increase in epidermal and stratum corneum thickness and an increase in the thymidine autoradiographic labeling index. These changes are coupled with alterations in epidermal glucose-6-phosphate dehydrogenase and succinic dehydrogenase activities, despite the absence of erythema clinically. The use of a sunscreen did not completely prevent these changes. In this study, we have examined the effects of repeated irradiation of human skin with either UVB or UVA alone in order to compare the changes produced in the epidermis and to ascertain whether UVA irradiation could cause these. Irradiation with either UVB or UVA alone was found to increase the mean epidermal thickness, the mean stratum corneum thickness, and mean keratinocyte height significantly. Glucose-6-phosphate dehydrogenase activity was significantly increased throughout the epidermis, and succinic dehydrogenase activity was significantly decreased. The autoradiographic labeling index was significantly increased following UVB irradiation but not following UVA irradiation. These results demonstrate that UVA alone can have a direct effect on epidermal morphology and metabolism, suggesting that protection of skin from UV radiation should include adequate protection from UVA.

Adult↗
PubMed1986

Techniques for assessing the activity of topically applied retinoids.

The retinoid drugs have profound effects on many aspects of skin biology. The exact activity profile depends on the particular analog and its route of administration. The topical retinoids used at present have marked therapeutic effects on epidermal cell production and desquamation. All-trans-retinoic acid (tretinoin) also acts on dermal connective tissue and microvasculature in a way that is less well established but may also be of therapeutic benefit. We investigated both tretinoin and motretinide in normal subjects and in patients with ichthyosis. The quantitative dansyl chloride test has been particularly useful in monitoring the desquamatory action of these topically applied retinoids. Both compounds resulted in enhanced rates of epidermopoiesis and desquamation. Marked changes in the cytochemical profile of the epidermis were also detected, changes that differed somewhat from the alterations induced by the systemic administration of etretinate. Changes in dermal structure and vascularization were monitored by A-scan ultrasound and laser Doppler flowmetry. However, only minor changes were recorded, probably because of the comparatively short application time. These newer techniques for investigating skin structure and function offer considerable opportunities for delineating the action of retinoids.

Administration, Topical↗
PubMed1986

The effects of an aromatic retinoid (etretinate) on epidermal cell production and metabolism in normal and ichthyotic patients.

Normal subjects and ichthyotic patients were biopsied before and after etretinate (Tigason) therapy. Histometric and cell kinetic measurements showed minimal changes following treatment. The metabolic activity across the epidermis was measured by a novel approach using the Quantimet 720 image analyser, and was significantly increased in the normal subjects as demonstrated by glucose-6-phosphate dehydrogenase (G6PDH), succinic dehydrogenase (SDH) and non-specific esterase (NSE) activities. In the ichthyotics studied the levels of G6PDH and SDH activity were significantly lowered following etretinate therapy, to levels similar to those demonstrated in normal subjects. In contrast, the activity of NSE was increased in the ichthyotics after etretinate therapy. It is suggested that the effect of retinoids is to 'normalize' the process of epidermal differentiation when it is abnormal.

Adult↗
PubMed1985

Effect of zinc pyrithione on mitotic activity in normal human skin.

Two concentrations (0.02% and 0.002%) of zinc pyrithione (ZPT) in water and a water control were applied to normal forearms - both on normal skin (six subjects) and also where the skin had been stripped to the 'glistening layer' (six subjects) with adhesive tape. Measurements of labelling index (LI), mean epidermal thickness (MET), mean stratum-corneum thickness (MSCT), total epidermal thickness (TET) and basal/granular cell ratio (B/G) showed no significant differences between the three treatments on normal skin or the parameters studied in stripped skin. It is concluded that ZPT has no effect on epidermal renewal in normal skin in vivo.

Adult↗