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BACKGROUND: Polymorphic light eruption and erythropoietic protoporphyria (EPP) have been demonstrated to have a moderate and large impact on the quality of life (QoL) of patients, respectively. However, there is little information available about the impact of other photodermatoses on QoL. OBJECTIVES: To assess and compare the impact of all forms of photodermatoses on patients' QoL using the standard 1-week Dermatology Life Quality Index (DLQI) questionnaire and a modified questionnaire to assess the impact over the previous year. METHODS: All patients with photodermatoses seen between 2001 and 2005 at five U.K. photobiology centres were contacted by post on the same day during a forecasted sunny week across the U.K. and asked to complete DLQI questionnaires. RESULTS: A total of 1877 patients were contacted. Seven hundred and ninety-seven (42%) patients replied, with a range from 30% to 48% for the five individual centres. Nearly two-thirds of patients with actinic prurigo (AP) and more than one-third of patients with photoaggravated dermatoses (PAD), chronic actinic dermatitis, EPP and solar urticaria had a DLQI of > 10, confirming a very large effect of the disorders on QoL. Of the cutaneous porphyrias, both variegate porphyria (median DLQI 3) and porphyria cutanea tarda (median DLQI 1.5) had a much lower impact on QoL than EPP. CONCLUSION: This is the first large-scale study to attempt to measure the impact of a range of photodermatoses on QoL. Photodermatoses have a major impact on QoL. This impact is highest in AP and PAD.
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Trastornos por Fotosensibilidad/psicología , Calidad de Vida , Estudios Transversales , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Cooperación del Paciente/psicología , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
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.
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Emolientes/química , Psoriasis/terapia , Protectores Solares/química , Terapia Ultravioleta/métodos , Utilización de Medicamentos/estadística & datos numéricos , Emolientes/administración & dosificación , Encuestas de Atención de la Salud , Humanos , Terapia PUVA/métodos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Psoriasis/tratamiento farmacológico , Dispersión de Radiación , Protectores Solares/administración & dosificación , Reino UnidoRESUMEN
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.
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Mutación , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/genética , Trastornos por Fotosensibilidad/genética , Síndrome de Smith-Lemli-Opitz/genética , Adolescente , Adulto , Secuencia de Bases , Niño , Análisis Mutacional de ADN/métodos , Femenino , Humanos , Masculino , Datos de Secuencia Molecular , Trastornos por Fotosensibilidad/enzimología , Mutación Puntual , Síndrome de Smith-Lemli-Opitz/enzimología , Reino UnidoRESUMEN
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.
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Ácido Aminolevulínico/uso terapéutico , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico , Enfermedad de Bowen/tratamiento farmacológico , Carcinoma Basocelular/tratamiento farmacológico , Costos de la Atención en Salud , Humanos , Queratosis/tratamiento farmacológico , Luz , Fotoquimioterapia/efectos adversos , Fotoquimioterapia/economía , Lesiones Precancerosas/tratamiento farmacológico , Radiometría/métodos , Enfermedades de la Piel/tratamiento farmacológicoAsunto(s)
Hiperlipidemias/tratamiento farmacológico , Hipolipemiantes/efectos adversos , Trastornos por Fotosensibilidad/diagnóstico , Simvastatina/efectos adversos , Enfermedad Crónica , Diagnóstico Diferencial , Humanos , Masculino , Persona de Mediana Edad , Cuello , Trastornos por Fotosensibilidad/inducido químicamente , Trastornos por Fotosensibilidad/patologíaRESUMEN
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.
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Fotoquimioterapia/instrumentación , Lesiones Precancerosas/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad de Bowen/tratamiento farmacológico , Carcinoma Basocelular/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Humanos , Queratosis/tratamiento farmacológico , Iluminación , Masculino , Persona de Mediana Edad , Fotoquimioterapia/efectos adversos , Fotoquimioterapia/métodos , Traumatismos por Radiación/tratamiento farmacológico , Recurrencia , Luz Solar/efectos adversos , Resultado del TratamientoRESUMEN
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.
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Trastornos por Fotosensibilidad/congénito , Piel/efectos de la radiación , Síndrome de Smith-Lemli-Opitz , Rayos Ultravioleta/efectos adversos , Adolescente , Adulto , Niño , Preescolar , Deshidrocolesteroles/sangre , Femenino , Humanos , Lactante , Masculino , Trastornos por Fotosensibilidad/prevención & control , Ropa de Protección , Síndrome de Smith-Lemli-Opitz/sangre , Protectores Solares/uso terapéuticoRESUMEN
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."
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Tejido Elástico/patología , Piel/patología , Fumar/efectos adversos , Elasticidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Piel/efectos de la radiación , Fenómenos Fisiológicos de la Piel , Luz Solar/efectos adversosAsunto(s)
Rayos Infrarrojos , Piel/efectos de la radiación , Adulto , Femenino , Humanos , Masculino , Piel/patologíaRESUMEN
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.
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Trastornos por Fotosensibilidad/diagnóstico , Síndrome de Smith-Lemli-Opitz/diagnóstico , Preescolar , Eritema/etiología , Femenino , Humanos , Trastornos por Fotosensibilidad/patología , Luz Solar/efectos adversosRESUMEN
BACKGROUND/AIMS: One clinical sign of photodamage is a sallow discolouration of the skin, and solar elastotic degenerative change in the upper dermis may cause this change. We have attempted to quantify these phenomena and relate them to each other and to age. METHODS: Twenty-seven healthy volunteers (age 18 to 61 years) were recruited. We examined the back of the hand of photodamaged individuals and the inner upper arm to demonstrate changes due to ageing. Each site was assessed for cutaneous blood flux using a laser Doppler fluxmeter (PF4000, Perimed UK), and for melanin pigmentation using a Melanin Index meter (Dermotronics Ltd, Cardiff, UK). Skin colour was measured using a diode array spectrophotometer (MCPD-1000, Photal, Japan), which computes CIE coordinates L*, a*, b*. Biopsies from each site were obtained from 13 of the subjects and were processed and stained with Gomori's aldehyde fuchsin. The percentage area of elastic staining material in the dermis was measured using image analysis. Sections were measured in four bands of 200 micron depth, and four fields were measured per band. RESULTS: Neither melanin content nor skin blood flux correlated with age for either skin site. Percentage area of elastosis correlated with age on the exposed site from the uppermost 600 microns of the dermis, (<200 micron depth, r=0.74, P<0.01, 200
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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.
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Quemadura Solar/patología , Protectores Solares/uso terapéutico , Adulto , Anciano , Análisis de Varianza , Biopsia con Aguja , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Placebos , Piel/efectos de los fármacos , Piel/patología , Envejecimiento de la Piel/efectos de los fármacos , Quemadura Solar/prevención & control , Factores de TiempoRESUMEN
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.
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Carcinoma Basocelular/metabolismo , Carcinoma de Células Escamosas/metabolismo , Proteínas Proto-Oncogénicas c-fos , ARN Mensajero/metabolismo , Neoplasias Cutáneas/metabolismo , Células 3T3 , Anciano , Animales , Sangre , Enfermedad de Bowen/metabolismo , Carcinoma Basocelular/patología , Carcinoma de Células Escamosas/patología , Humanos , Hibridación in Situ , Queratosis/etiología , Queratosis/metabolismo , Ratones , Persona de Mediana Edad , Proto-Oncogenes Mas , Valores de Referencia , Piel/metabolismo , Neoplasias Cutáneas/patología , Luz Solar/efectos adversosRESUMEN
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.
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Epidermis/fisiología , Expresión Génica/efectos de la radiación , Genes myc/efectos de la radiación , Genes ras/efectos de la radiación , Rayos Ultravioleta , Adulto , ADN/biosíntesis , Femenino , Humanos , Hibridación in Situ , Masculino , Persona de Mediana Edad , Proto-Oncogenes Mas , Valores de Referencia , Piel/metabolismo , Piel/efectos de la radiaciónRESUMEN
Synopsis In this study we have described the construction of a dedicated, inexpensive and portable instrument designed to evaluate sunscreens throughout the UVB and UVA range (290-400 nm). Both Transpore(TM) and an alternative substrate of readily obtainable human stratum corneum have been used as substrates on to which to spread the test products. The transmission of UVR through the substrate of stratum corneum was greater than through Transpore(TM) tape. Both substrates demonstrated a good correlation with in vivo or expected SPF results. However, in 10 out of the 11 sunscreens studied, the comparison of the two substrates demonstrated that the predicted SPF using Transpore(TM) tape was consistently higher than that using human stratum corneum. One sunscreen tested was alcohol based and as such was not suitable to test on Transpore(TM) tape. Predictions of SPF from products with SPF values less than 20 were not significantly different between substrates. However, product SPF values of greater than 20 demonstrated that Transpore(TM) tape overestimated the 'true'SPF. It is postulated that use of human stratum corneum in in vitro SPF testing systems more closely resembles that of human skin in vivo than does Transpore(TM) tape with regard to spreading and absorption of the potential sunscreen product. Résumé Cette étude décrit la construction d'un appareil portable bon marché servant àévaluer des écrans solaires sur les rayons UVA et UVB entre 290 et 400 nm. Le Transpore(TM) et le substrat alternatif d'un stratum corneum ont été utilisés comme substrats sur lesquels on a appliqué les produits tests. La transmission des rayons UVR à travers le substrat du stratum corneum était plus importante qu'à travers le Transpores(TM). Chaque substrat a montré une bonne corrélation avec les réultats des facteurs de protection solaire prévus ou in-vivo. Cependant sur 10 des 11 écrans solaires étudiés, la comparaison des deux substrats a montré que les résultats prévus de facteurs de protection solaires obtenus avec le ruban Transpore(TM)étaient considérablement plus élevés qu'avec le stratum corneum. Un des écrans solaires testé contenait de l'alcool et ne pouvait être testé sur le ruban Transpore(TM). Les prévisions de SPF avec des produits dont les valeurs SPF étaient inférieures à 20 n'ont pas montré de différences notables entre les substrats. Cependant les valeurs SPF supérieures à 20 ont montré que le Transpore(TM) surestimait le SPF réel. Il semble que l'utilisation de stratum corneum humain pour des tests de SPF in vitro corresponde mieux au comportement de la peau humaine in vivo que le Transpore pour l'application et l'absorption d'un écran solaire potentiel.
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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.
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Neoplasias Cutáneas/patología , Piel/patología , Núcleo Celular/ultraestructura , Citodiagnóstico , Epidermis/patología , Humanos , Cariometría , Queratosis/etiología , Queratosis/patología , Piel/efectos de la radiación , Piel/ultraestructura , Luz Solar/efectos adversosRESUMEN
Synopsis In this study a compact, hand-held, solid state erythema meter using light emitting diodes is described. This device has been constructed and used to compare with visual assessments of ultraviolet radiation in human subjects. A statistically significant correlation was obtained between erythema index and visual assessment in 24 ultraviolet irradiated subjects. Furthermore, the effects of three aftersun treatments have also been assessed objectively using the meter and subjectively using visual assessments. The ultraviolet-irradiated areas were less red following treatment than the irradiated and untreated areas. The results obtained by the meter were similar to and statistically significant with those obtained by visual assessment. It is concluded that widespread use of an erythema meter such as that described would greatly improve all cutaneous erythema assessments.
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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.
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Carcinoma Basocelular/tratamiento farmacológico , Etretinato/uso terapéutico , Queratosis/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Carcinoma Basocelular/metabolismo , Carcinoma Basocelular/patología , Ensayos Clínicos como Asunto , ADN/biosíntesis , Epidermis/efectos de los fármacos , Epidermis/metabolismo , Epidermis/patología , Femenino , Glucosafosfato Deshidrogenasa/metabolismo , Humanos , Queratosis/etiología , Queratosis/patología , Masculino , Persona de Mediana Edad , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Succinato Deshidrogenasa/metabolismo , Luz Solar/efectos adversosRESUMEN
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.
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Epidermis/efectos de la radiación , Adulto , Replicación del ADN/efectos de los fármacos , Relación Dosis-Respuesta en la Radiación , Epidermis/metabolismo , Epidermis/ultraestructura , Femenino , Glucosafosfato Deshidrogenasa/análisis , Humanos , Persona de Mediana Edad , Succinato Deshidrogenasa/análisis , Protectores Solares/farmacología , Rayos UltravioletaRESUMEN
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.