Growth rate of cultured human fibroblasts increased by glucocorticoids.

Selected glucocorticoids have been demonstrated to increase the growth rate of human skin fibroblasts in culture, over a physiologically significant concentration range. At the same concentrations and identical conditions, the glucocorticoid compounds tested inhibited the growth rate of mouse L-929 cells. We have discussed currently acceptable theories of glucocorticoid mechanism of action that permit this dichotomous effect, the main point being that inhibition can no longer be regarded as the only response of fibroblasts to glucocorticoids. Conclusions drawn from observations of cell cultures affected by addition of glucocorticoids must have considered the source of the cells, as response may vary with source and biologic state of the cells in culture.

Psoriatic plaques exhibit red autofluorescence that is due to protoporphyrin IX.

In evaluating the autofluorescence properties of normal and diseased skin we discovered that psoriatic plaques can emit a distinct red fluorescence when illuminated with UVA or blue light. Using a macrospectrofluorometer equipped with a 442 nm excitation laser, a sharp in vivo fluorescence emission peak around 635 nm could be demonstrated within the plaques of 34 of 75 (45%) patients with psoriasis. This peak was absent from normal appearing skin of psoriatic patients and also from the skin of 66 patients with other dermatologic diseases. A microspectrofluorometer coupled with the same excitation laser was used to obtain emission spectra of separated epidermal sheets and dermis from plaques demonstrating macroscopic red autofluorescence. An emission peak around 635 nm was observed in all three patients thus studied, but only on spectra obtained from the epidermis. Additional spectra of vertical microscopic sections of intact psoriatic skin from five other patients revealed that the peak originated from the stratum corneum. Emission spectra from other microlocations including the mid-epidermis and dermis of psoriatic and normal skin, as well as the stratum corneum of normal skin, failed to demonstrate a 635 nm peak. The excitation and emission fluorescence spectra of acid extracts of psoriatic scale from five patients were all similar to those of protoporphyrin IX in acid solution. High performance liquid chromatography identified the presence of protoporphyrin IX in the acid extracts from psoriatic scale of the same patients. We conclude that native psoriatic plaques can exhibit red autofluorescence that is due to elevated levels of protoporphyrin IX within scales.

Chemical exposures, medical history, and risk of squamous and basal cell carcinoma of the skin.

The role of non-sunlight-related risk factors for squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) of the skin was investigated in a population-based, case-control study conducted among males in Alberta, Canada. In total, 180 SCC and 226 BCC cases and 406 randomly selected male controls, frequency matched by 5-year age groups to the cases, were interviewed by trained personnel using a standardized etiological questionnaire. Data were analyzed using conditional logistic regression techniques. After adjustment for age, skin and hair color, mother's ethnic origin, and sunlight exposure, elevated risks for SCC were seen in subjects exposed to insecticides [odds ratio (OR), highest tertile, 2.8; 95% confidence interval (CI), 1.4-5.6], herbicides (OR, highest tertile, 3.9; 95% CI, 2.2-6.9), and fungicides and seed treatments (OR, highest tertile, 2.4; 95% CI, 1.4-4.0), as well petroleum products, grease, and several other exposures. Elevated risks of BCC were seen in subjects exposed to fiberglass dust (OR, 2.0; 95% CI, 1.0-3.9) and dry cleaning agents (OR, 4.6 95% CI, 1.1-19.7). Prior nondiagnostic X-ray treatment for skin conditions increased risk of both cancers. Although solar UV radiation is known to be the major environmental exposure causing nonmelanocytic skin cancer, results of this study suggest that nonsolar factors may also be important.

An open study to assess the efficacy and safety of topical 3% diclofenac in a 2.5% hyaluronic acid gel for the treatment of actinic keratoses.

BACKGROUND: Actinic keratoses are potential precursors of invasive squamous cell carcinoma; therefore, treatment is often recommended. Current topical treatments may cause considerable discomfort, pain, or skin irritation. This study was established to explore the role, if any, of topical 3% diclofenac in 2.5% hyaluronic acid gel in the management of actinic keratoses. OBSERVATIONS: An open-label study was conducted of topical 3% diclofenac in 2.5% hyaluronic acid gel applied to 1 or more actinic keratoses. Patients were instructed to apply 1.0 g of the gel twice daily for as many as 180 days. Treatment was stopped earlier than 180 days if lesions were assessed as cleared. Twenty-nine adults were treated for periods of 33 to 176 days (median, 62 days). Of the 29 subjects, 27 were reevaluated 30 days after drug therapy discontinuation. Of the 27 patients, 22 (81%) had a complete response and another 4 (15%) showed marked clinical improvement. The preparation was generally well tolerated, although in 7 patients (24%) an irritant-type contact dermatitis developed, which was confined to the treatment site. CONCLUSION: Topical 3% diclofenac in 2.5% hyaluronic acid gel may be a clinically useful topical agent for the treatment of actinic keratoses.

Sunlight exposure, pigmentary factors, and risk of nonmelanocytic skin cancer. I. Basal cell carcinoma.

BACKGROUND AND DESIGN: Basal cell carcinoma (BCC) of the skin is the most common neoplasm in white populations, and solar radiation is generally accepted to be the dominant environmental risk factor for this disease. However, little information is available on the nature of the relationship between BCC and sunlight. The purpose of this study was to evaluate the nature of the relationship between sunlight exposure, pigmentary factors, and BCC of the skin. A population-based case-control study of 226 male patients with BCC diagnosed from January 1, 1983, through December 31, 1984, and 406 randomly selected male control subjects was conducted in Alberta, Canada. The study was conducted using a standardized questionnaire, administered in person by trained interviewers. Data were analyzed using conditional logistic regression methods. RESULTS: After controlling for other host and pigmentary factors, the risk of BCC was increased in subjects with light skin color and those who freckled in childhood. A history of severe sunburn in childhood also increased risk. Subjects of southern European ethnic origin were at significantly lower risk of BCC. Surprisingly, no association was seen between mean annual cumulative summer sunlight exposure and risk of BCC. A significantly increased risk of BCC was seen in subjects with increased recreational sunlight exposure in adolescence and childhood (age, 0 to 19 years), although an inverse relationship was seen with lifetime recreation exposure. The relationship with childhood sun exposure was most pronounced among sun-sensitive subjects whose skin tended to burn rather than tan in the sun. CONCLUSIONS: The lack of association between cumulative sun exposure and BCC contradicts conventional wisdom about the cause of this tumor, and the increased risk with sun exposure at age 0 to 19 years suggests that childhood and adolescence may be critical periods for establishing adult risk for BCC.

Sunlight exposure, pigmentation factors, and risk of nonmelanocytic skin cancer. II. Squamous cell carcinoma.

INTRODUCTION AND DESIGN: Squamous cell carcinoma of the skin (SCC), a common cancer in white populations, is related to sunshine exposure; however, relatively little information is available on how timing and character of exposure affect the relationship. The purpose of this study was to investigate the nature of the relationship of SCC to individual solar UV exposure after control for phenotype and pigmentary factors. All newly diagnosed cases of SCC were in men aged 25 through 79 years, ascertained in the province of Alberta from January 1, 1983, through December 31, 1984, who were approached for participation; 80% completed a standardized etiologic interview that was conducted in their homes by a trained interviewer. Control subjects were chosen at random from the Alberta Health Care Insurance Plan subscribers list, matched only by sex (male) and age (within a 5-year age group). The response rate among controls was 71%. RESULTS: Subjects with pale skin and red hair had an elevated risk of SCC. Subjects whose mother was of southern European ancestry had a reduced risk of SCC. After accounting for pigmentary factors, no association was seen between risk of SCC and cumulative lifetime sun exposure. However, a strong trend toward increasing risk was seen with increasing chronic occupational sun exposure in the 10 years prior to diagnosis. CONCLUSION: The results suggest that recent sun exposure (in the 10 years prior to diagnosis) may be important in accounting for individual risk of SCC.

Anatomic distribution of acquired melanocytic nevi in white children. A comparison with melanoma: the Vancouver Mole Study.

The presence of acquired benign nevi is a risk factor for cutaneous melanoma, yet relatively little is known about the etiology of nevi. We have conducted a study of the prevalence of melanocytic nevi among 1146 white Vancouver (Canada) schoolchildren aged 6 to 18 years. Numbers of nevi per square meter of body surface area increase with age in children of both sexes. Male adolescents have more nevi than female adolescents on the head and neck as well as on the trunk, while prevalence in females is higher on the upper and lower limbs. This distribution parallels that of cutaneous melanoma in British Columbia adults. Nevi are more common in children on intermittently exposed body sites than on constantly or minimally sun-exposed sites. This suggests that exposure to strong intermittent sunlight in childhood (a risk factor for cutaneous melanoma) may also be important in the etiology of acquired benign nevi.

Suntan, sunburn, and pigmentation factors and the frequency of acquired melanocytic nevi in children. Similarities to melanoma: the Vancouver Mole Study.

The association between prevalence of benign melanocytic nevi and a number of skin cancer risk factors was examined among 913 white Vancouver (Canada) school children aged 6 to 18 years. Subjects with light skin, with a propensity to burn rather than tan in the sun, and with numerous or severe sunburns in the previous 5 years had significantly higher nevus counts than individuals without these characteristics. Subjects who acquired deeper tans tended to have fewer nevi than those who did not tan. Finally, children who freckled had higher nevus counts than those who did not freckle. These findings in children are similar to those seen in studies of malignant melanoma among adults and suggest that strategies to reduce melanoma incidence should begin with young children.

Spectroscopic and microscopic characteristics of human skin autofluorescence emission.

To improve the understanding of human skin autofluorescence emission, the spectroscopic and microscopic characteristics of skin autofluorescence were studied using a combined fluorescence and reflectance spectroanalyzer and a fiber optic microspectrophotometer. The autofluorescence spectra of in vivo human skin were measured over a wide excitation wavelength range (350-470 nm). The excitation-emission matrices of in vivo skin were obtained. An excitation-emission maximum pair (380 nm, 470 nm) was identified. It was revealed that the most probable energy of skin autofluorescence emission photons increases monotonically and near linearly with increasing excitation photon energy. It was demonstrated that the diffuse reflectance, R, can be used as a first order approximation of the fluorescence distortion factor f to correct the measured in vivo autofluorescence spectra for the effect of tissue reabsorption and scattering. The microscopic in vitro autofluorescence properties of excised skin tissue sections were examined using 442 nm He-Cd laser light excitation as an example. It was demonstrated that the fluorophore distribution inside the skin tissue is not uniform and the shapes of the autofluorescence spectra of different anatomical skin layers vary. The result of this study confirms that the major skin fluorophores are located in the dermis and provides an excellent foundation for Monte Carlo modeling of in vivo autofluorescence measurements.

Oral aminolevulinic acid induces protoporphyrin IX fluorescence in psoriatic plaques and peripheral blood cells.

Photodynamic therapy (PDT) with topical aminolevulinic acid (ALA) has been shown in previous studies to improve psoriasis. However, topical ALA-PDT may not be practical for the treatment of extensive disease. In order to overcome this limitation we have explored the potential use of oral ALA administration in psoriatic patients. Twelve patients with plaque psoriasis received a single oral ALA dose of 10, 20 or 30 mg/kg followed by measurement of protoporphyrin IX (PpIX) fluorescence in the skin and circulating blood cells. Skin PpIX levels were determined over time after ALA administration by the quantification of the 635 nm PpIX emission peak with in vivo fluorescence spectroscopy under 442 nm laser excitation. Administration of ALA at 20 and 30 mg/kg induced preferential accumulation of PpIX in psoriatic as opposed to adjacent normal skin. Peak fluorescence intensity in psoriatic and normal skin occurred between 3 and 5 h after the administration of 20 and 30 mg/kg, respectively. Ratios of up to 10 for PpIX fluorescence between psoriatic versus normal skin were obtained at the 30 mg/kg dose of ALA. Visible PpIX fluorescence was also observed on normal facial skin, and nonspecific skin photosensitivity occurred only in patients who received the 20 or 30 mg/kg doses. PpIX fluorescence intensity was measured in circulating blood cells by flow cytometry. PpIX fluorescence was higher in monocytes and neutrophils as compared to CD4+ and CD8+ T lymphocytes. PpIX levels in these cells were higher in patients who received higher ALA doses and peaked between 4 and 8 h after administration of ALA. There was only a modest increase in PpIX levels in circulating CD4+ and CD8+ T lymphocytes. In conclusion oral administration of ALA induced preferential accumulation of PpIX in psoriatic plaques as compared to adjacent normal skin suggesting that PDT with oral ALA should be further explored for the treatment of psoriasis.

The dynamics of laser-induced changes in human skin autofluorescence--experimental measurements and theoretical modeling.

To study the temporal dynamics of human skin autofluorescence photobleaching, we measured the autofluorescence spectral changes of skin in vivo during continuous exposure to 442 nm (He-Cd) laser light. Integral intensities were calculated for various spectral wavelength bands and plotted as a function of time. Mathematical analysis of the time function revealed a double-exponential photobleaching process: I(t) = a exp (-t/tau 1) + b exp(-t/tau 2) + c, in which tau 1 and tau 2 differed by an order of magnitude. A hypothesis for the mechanism of the double-exponential photobleaching dynamics was proposed and evaluated using Monte Carlo modeling of light propagation in the skin and autofluorescence escape from skin. By combining the fluorophore microdistributions, Monte Carlo simulation results and the variation in fluorescence decrease parameters (a, b, c, tau 1, tau 2) with increasing exposure intensities a biophysical explanation for the double-exponential photobleaching function was elucidated. The fast decrease term corresponds to laser-induced photobleaching in the stratum corneum, while the slow decrease term represents fluorophore changes in the dermis. The measured autofluorescence photobleaching dynamics can be used to determine the fractional contributions of different skin layers to the total autofluorescence signal measured in vivo.

A computerized autofluorescence and diffuse reflectance spectroanalyser system for in vivo skin studies.

A microcomputer-controlled spectroanalyser system has been set up to study optical properties of normal and abnormal human skin in vivo. The system can measure both tissue autofluorescence and diffuse reflectance at selected skin locations. The sample holder allows adjustment of the incident angle of the illumination light and the pick-up angle of the collected light providing the means to examine different depths of skin tissue. Using this system, we detected measurable skin autofluorescence with a maximum at about 470 nm when excited with 380 nm UV radiation. In this work, we also show that the absorption and scattering properties of the skin tissue (which can be determined from the measured diffuse reflectance spectrum) affect the shape of the autofluorescence spectrum. We believe that the combination of autofluorescence and diffuse reflectance measurements will lead to better understanding of the optical properties of normal and abnormal skin tissue.

The epidemiology of acquired melanocytic nevi. A brief review.

Presence of large numbers of acquired melanocytic nevi is a strong risk factor for malignant melanoma in adults. A series of studies conducted over the past 10 to 15 years have shown that the lighter skin color, propensity to burn rather than to tan in the sun, and frequent episodes of childhood sunburn increase nevus prevalence in childhood and adolescence. Solar ultraviolet radiation exposure itself has been implicated in both the genesis of new nevi in children and the disappearance of nevi in older adult life.

Sunscreens. Use and misuse.

Although sunscreens are widely available and in common use, surveys show that an average of only half of the people on a beach on a given day wear sunscreens. Many people go to the beach to get or maintain a suntan, but many people also leave their skin unprotected. This article discusses the proper use of sunscreens, common misunderstandings, and how unprotected long-term exposure to the sun can effect your skin.

Reconstruction of in vivo skin autofluorescence spectrum from microscopic properties by Monte Carlo simulation.

The in vivo skin autofluorescence spectrum was reconstructed by Monte Carlo simulation using microscopic fluorophore distributions and intrinsic fluorescence spectra measured from excised skin tissue sections as well as employing published skin tissue optical parameters. The theoretical modeling took into account the light-tissue interactions of scattering, absorption, and regeneration of fluorescence photons. The modification of the intrinsic spectra by tissue optical properties to generate the in vivo spectrum observed at the tissue surface can be represented by a fluorescence detection efficiency function (eta) which equals the integral of the product of the excitation light distribution inside the tissue and the fluorescence escape efficiency. Comparison of the reconstructed in vivo spectrum with the measured spectra showed good agreement, outside of the blood absorption bands, suggesting that (i) the theoretical modeling, (ii) the skin optical parameters used, and (iii) the measured microscopic morphology and spectral data are consistent. The divergence which exists over the strong blood absorption wavelength band (530-600 nm) suggests that the effect of blood contents on in vivo tissue optical properties deserves further investigations.

Management of recurrent aphthous stomatitis. A review.

The management of recurrent aphthous ulceration is discussed. It appears that the treatment of choice in mild to moderately severe aphthous stomatitis is repeated application of topical tetracycline hydrochloride. Viscous lidocaine (2 percent) provides symptomatic relief and is therefore a useful adjunct to therapy. Cyclical estrogens appear to be helpful in recurrent premenstrual aphthosis. Immune-regulating agents such as levamisole hold promise for the future.