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Novel method for training skin flap surgery: polyurethane foam dressing used as a skin equivalent.

BACKGROUND: With a substantial rise in the incidence of skin cancer, skin surgery has become an increasingly large part of dermatology. Skin surgery is best performed by dermatologists. This demands effective training in dermatologic surgery, including flap surgery. OBJECTIVE: To find a modern alternative to traditional training on pig's feet skin in teaching flap surgery to residents in dermatology. MATERIALS AND METHODS: A face with expression lines printed on a nonadhesive hydrocellular polyurethane dressing (Allevyn, #66007638, 20 x 20 cm, Smith & Nephew Medical Limited, Hull, England). Tumors were marked in suitable locations, necessitating the use of transposition, advancement, and rotation flaps. Twenty-two residents were trained in flap construction, excision, and closure. RESULTS: Training on Allevyn was rated high by participants. CONCLUSION: Allevyn has unlimited storing qualities and skinlike qualities when incised, extended, and sutured. Sutures stay tight without the help of an assistant. Training on Allevyn gives students a good understanding of the mechanics of skin flaps, including transposition, advancement, and rotational flaps. The Allevyn is kept by the student after the course and can be studied afterward. Skin surgery training on Allevyn is superior to traditional training in pig's feet skin.

Audiovisual Aids↗

Full-thickness skin grafts from flaky skin mice to nude mice: maintenance of the psoriasiform phenotype.

Flaky skin (fsn) is an autosomal recessive mouse mutation with papulosquamous disease features similar to human psoriasis. In fsn/fsn skin, one sees marked acanthosis and hyperkeratosis with focal parakeratosis, subcorneal pustules, dermal capillary dilation, and a marked diffuse dermal infiltration of mixed inflammatory cells, predominantly lymphocytes. To determine if these pathologic features are a characteristic of the skin or a chronic autoimmune attack, we placed full-thickness skin grafts from affected homozygous (fsn/fsn) and normal littermate control (+/?) mice on the dorsal skin of genetically athymic nude (nu/nu) mice. After 10 weeks of observation, the grafts maintained the histologic phenotype of the donor animal. In the fsn/fsn grafts, there was persistence of both epidermal proliferation and dermal inflammation, characteristics of the mutation. The fsn/fsn phenotype was also confirmed by immunohistochemical evaluation for specific mouse keratinocyte marker expression. Based on tritiated thymidine uptake, we found DNA synthesis rates elevated threefold or more in fsn/fsn epidermis compared to littermate control mouse skin. Elevated rates of DNA synthesis remained a feature of the fsn/fsn grafts but not that of littermate control skin grafts. This study demonstrates that the psoriasiform phenotype of this mouse mutation can persist independent of the host thymic-derived immune system.

Animals↗

Cyclic AMP-dependent protein kinase isozymes of pig skin and human skin from normal and psoriatic subjects.

Cyclic AMP-dependent protein kinase isozymes of pig and human skin (epidermis) were separated by DEAE-cellulose column chromatography after micromodification for small biopsy samples. Clear-cut separations of type I and type II isozymes, which were of about equal amounts, could be obtained only when the ischemia effect was avoided by in vivo freezing of skin and homogenization for less than 10 s. Intradermal injections of epinephrine caused dose-dependent activation of type I isozyme, but not of type II. Injections of other skin adenylate cyclase stimulators such as histamine, adenosine, and prostaglandin E2 elevated the local cyclic AMP levels to not more than 5 pmol/mg protein and also stimulated only the type I isozyme. Incubation of keratome-sliced pig skin under various conditions caused both activation by dissociation and inactivation by reassociation of the subunits, which appeared to be dependent on the cyclic AMP content. Epinephrine added to the incubation medium led to complete activation of both type I and type II isozymes (the intraepidermal cyclic AMP contents ranged from 20-50 pmol/mg protein). The isozymes of normal skin and involved skin of psoriatics showed identical peaks of type I and type II isozymes of equal amounts. The data indicate that protein kinase in the involved skin is not in an activated (by cyclic AMP) state.

Animals↗

The origin of plant sterols in the skin surface lipids in humans: from diet to plasma to skin.

To test the hypothesis that plant sterols found in the skin surface lipids of humans originated from diet after their absorption from intestine into plasma and then transferred to skin, we studied the 24-h excretion of plant sterols and cholesterol from skin and in feces in a hyperlipoproteinemic (type IIa) patient fed formula diets providing varying quantities of plant sterols (0-30 g/day) and cholesterol (0-1000 g/day). Upon feeding a sterol-free diet, the beta-sitosterol excretion from the skin decreased progressively, from about 6 mg/day to 0.08 mg/day by 83 days and then completely disappeared. With addition of plant sterols (about 30 g/day) to the diet, beta-sitosterol reappeared in the skin surface lipids and rose to nearly 5 mg/day by 6 weeks. With feeding of the sterol-free diet, the fecal excretion of beta-sitosterol and the 2 other plant sterols decreased gradually and by week 4 disappeared completely from the feces and continued to be absent from the feces as long as the diet was free of plant sterols. The results demonstrated clearly that plant sterols which were absorbed into the plasma from the diet were excreted into the skin surface lipids after being transferred from the plasma to the skin.

Cholesterol↗

Acitretin and skin cancer in kidney transplanted patients. Clinical and histological evaluation and immunohistochemical analysis of lymphocytes, natural killer cells and Langerhans' cells in sun exposed and sun protected skin.

BACKGROUND: Renal transplanted recipients have an increased incidence of actinic keratosis and skin cancer. METHODS: In order to examine the chemoprophylatic effects of low-dose acitretin on keratosis and skin cancer development we submitted 13 renal transplanted patients who presented actinic keratosis to acitretin therapy (20 mg/d) for 12 months. The patients were assessed at monthly intervals during the first 6 months and every 2 months until the 12th month for new skin lesions and for acitretin toxicity. Normal skin biopsies of sun exposed and sun protected areas were taken for histopathological examination and submitted to immunohistochemistry technique to demonstrate CD4+ and CD8+ T lymphocytes, natural killer (NK) cells and Langerhans' cells which were counted and compared before, after 6 and 12 months of the treatment. RESULTS: There was an improvement of actinic keratosis in all patients. Only one patient developed new skin cancer. Side-effects were well tolerated and no significant biochemical effects were observed. There were no differences in the microscopic aspects of the skin and in the number of CD4+ and CD8+ T lymphocytes and NK cells. There was a significant increase in the number of epidermal Langerhans' cells after 12 months of acitretin therapy. CONCLUSIONS: The data obtained permit us to conclude that low dose acitretin therapy is safe, well tolerated and partially effective in chemoprophylaxis of skin cancer in renal transplant recipients. The increase in epidermal Langerhans' cells observed may be an expression of the immunomodulatory effect of acitretin.

Acitretin↗

Skin permeability barrier and occlusion: no delay of repair in irritated human skin.

It has been reported that occlusive treatment of irritated skin results in a reduction of barrier repair activities in hairless mice. In contrast, the clinically observed benefit of occlusion in the treatment of hand eczema and other chronic skin diseases with a perturbed barrier function is well-known. While the beneficial effect of occlusion has been proven for the treatment of psoriasis there are no controlled clinical studies of the effect of occlusion on irritated human skin. We have therefore evaluated the effect of various occlusive treatments on repair of the human skin permeability barrier under controlled experimental conditions. Barrier perturbation was induced either by application of sodium lauryl sulfate (SLS) or by repeated tape stripping. This was followed by treatment with different occlusive and semipermeable dressings, partly after pre-treatment with petrolatum. Repair of water barrier function was evaluated by daily measurements of transepidermal water loss (TEWL) for 1 week. SLS irritation and tape stripping led to a 6-fold increase in TEWL as a sign of severe water barrier perturbation, followed by a stepwise decrease over the following days. Occlusion did not significantly delay barrier repair as measured by TEWL. Only in tape-stripped skin did TEWL stay at high levels during treatment with self-adhesive dressings. This may be explained by damage of newly formed stratum corneum caused by changing of these membranes. Our results indicate that, in contrast to earlier observations in hairless mouse skin, permeability barrier repair activities are not significantly delayed by occlusive treatment in human skin.

Adult↗

An evaluation of the relationship between 'atopic skin' and skin irritability in metalworker trainees.

Skin hyperirritability to irritants as well as atopy are considered to be predisposing factors for contact dermatitis. The aim of the study was to evaluate whether these predictive factors are independent or whether they are so closely related that one could possibly replace the other 205 metalworker trainees underwent skin examination for skin atopy, including standardized questionnaire, clinical examination of the skin and a series of skin irritability tests. These tests included measurements of transepidermal water loss (TEWL) before and after irritation with 3 different irritants: sodium lauryl sulfate (SLS), dimethylsulfoxide (DMSO) and sodium hydroxide (NaOH). The results of the linear regression analysis demonstrate that skin atopy is not associated with increased skin irritability, as assessed by the irritability testing methods presented.

Adolescent↗

Oxidative defense in cultured human skin fibroblasts and keratinocytes from sun-exposed and non-exposed skin.

Skin fibroblasts and keratinocytes cultivated from chronically light-exposed skin sites have higher levels of the protective protein ferritin than cells derived from unexposed areas of the body, suggesting an adaptive response of cells exposed to chronic external insults. In the same line, ferritin levels were always found to be 2- to 7-fold higher in epidermal keratinocytes than in the underlying dermal fibroblasts of the same person thus providing the keratinocyte with continuous protection by the higher cellular ferritin content. The activation of ferritin by oxidative stress including UVA radiation could represent an important cellular defense mechanism that operates in human skin. Following low fluences of UVA radiation (2-4 x 10(5) J/m2), ferritin levels increased by 20-30% in normal adult skin fibroblasts and showed a subsequent decrease at higher UVA fluences. In contrast, skin keratinocytes were not perturbed by UVA radiation exposure except for very high fluences (1.25 x 10(6) J/m2) where slight decreases in cellular ferritin were noted in 7 of the 12 cell lines. Fibroblasts derived from light-exposed skin sites that possessed higher levels of cellular ferritin were highly protected against UVA-induced membrane damage as measured by lactate dehydrogenase release compared with fibroblasts from nonexposed body sites with lower levels of ferritin. It is clear from our results that ferritin plays an important role in protection at the cellular level in human skin cells, but the role of this putative protective protein in vivo remains to be defined.

Adaptation, Physiological↗

The determination of ofloxacin in human skin tissue by high-performance liquid chromatography and correlation between skin tissue concentration and serum level of ofloxacin.

A simple high-performance liquid chromatographic (HPLC) assay was developed for the measurement of ofloxacin in skin tissue, and the correlation between serum levels and skin tissue levels of ofloxacin was determined. The homogenized skin samples were directly introduced into an HPLC system after filtering through a Molcut II membrane filter to remove proteins. The filtrate was concentration on a pre-column using a phenyl-stationary phase and was then introduced to an analytical column using an ODS-stationary phase by column-switching techniques. Ofloxacin and lomefloxacin as an internal standard were detected by UV absorbance at 300 nm. Determination was possible for ofloxacin over the concentrated range 250-3000 ng (g skin tissue)-1; the limit of detection was 100 ng g-1. The absolute recovery of ofloxacin added to skin tissue homogenate was over 72% with a coefficient of variation of less than 4.1%. This method is applied to determination of skin tissue level of ofloxacin in patients after treatment with ofloxacin. The correlation between serum levels and skin tissue levels of ofloxacin was determined for 30 patients after oral administration of ofloxacin. Good correlation was obtained and the coefficient of correlation was 0.84.

Administration, Oral↗

Risk group, skin lesion history, and sun sensitivity reliability in squamous cell skin cancer progression.

In studies of skin cancer, participants are often classified into risk groups based on self-reported history of sun exposure or skin characteristics. We sought to determine the reliability of self-reported skin characteristics among participants of a study to evaluate markers for nonmelanoma skin cancer (NMSC). Multiple questionnaires and screening protocols were administered over a 3-month period to individuals from three risk groups: existing sun damage on forearms but no visible actinic keratoses (n = 91), visible actinic keratoses (n = 38), and history of resected squamous cell skin cancer in the last 12 months (n = 35). We assessed consistency of risk group assignment between telephone screen and study dermatologist assignment, self-reported sun sensitivity (telephone recruitment form versus participant completed profile), and self-reported history of NMSC skin lesions (telephone recruitment form versus health history). There was substantial agreement between probable risk group and final assignment (kappa = 0.76; 95% confidence interval, 0.65-0.85) and agreement did not differ by gender. Agreement for self-reported sun sensitivity was moderate (kappa weighted = 0.46; 95% confidence interval, 0.36-0.56) with higher agreement for women. For self-reported NMSC lesion history between two interviews, 24 days apart, kappa estimates ranged from 0.66 to 0.78 and were higher for women than men. Overall, there was evidence for substantial reproducibility related to risk group assignment and self-reported history of NMSC, with self-reported sun sensitivity being less reliable. In all comparisons, women had higher kappa values than men. These results suggest that self-reported measures of skin cancer risk are reasonably reliable for use in screening subjects into studies.

Adult↗

Biophysical characteristics of healthy skin and nonlesional skin in atopic dermatitis: short-term effects of ultraviolet A and B irradiation.

The present study was designed to evaluate basic differences in surface structure and viscoelastic properties of nonatopic versus atopic skin and facultative acute changes following ultraviolet irradiation. Therefore, biophysical measurements by means of profilometry and cutometry were carried out on sun-protected unaffected gluteal skin areas in both groups before and 24 h after single UVA and UVB irradiations. The results indicate that the clinically unaffected skin of patients with atopic eczema differs from normal skin in terms of increased roughness parameters, but not concerning depth of furrows or viscoelastic properties (viscosity and biological elasticity, cutometrically calculated). Single UVA irradiation with 50 J/cm(2) induced neither measurable changes in the skin's surface structure nor in its viscoelastic properties in both groups after 24 h. However, irradiation with a single erythemogenic dose of 1 MED UVB was followed by a short-term significant increase in the depths of furrows and decrease in biological elasticity in normal and atopic skin, accompanied by an increase in viscosity in normal skin.

Adult↗

Comparison of the effects of calcipotriol, prednicarbate and clobetasol 17-propionate on normal skin assessed by ultrasound measurement of skin thickness.

In this study, we investigated the effect of calcipotriol, prednicarbate and clobetasol 17-propionate on skin thickness over a treatment period of 6 weeks. The study was conducted as a controlled, randomized, double-blind comparison. The influence of these drugs on normal skin under occlusive conditions was assessed visually and by measuring skin thickness using 20 MHz B mode ultrasound. Both topically applied glucocorticosteroids lead to a significant decrease in skin thickness. In contrast to the glucocorticosteroid-induced atrophy, calcipotriol application on normal skin leads to an increase in skin thickness in all volunteers. The effect remains constant for the duration of treatment. The cause of this increase seems to be an irritative reaction of the skin which was histologically investigated in one volunteer. The histological features of this reaction are characteristic for a subacute dermatitis. The implications of these findings for the therapeutic mechanism of calcipotriol are discussed.

Administration, Topical↗

Investigation of skin-derived lymph: an approach to get insight into the skin immune system.

The skin acts as a mechanical, physicochemical and immunological control and defense system, and its lymphatic vessels play a role in the regulation of cell hydration and osmosis, as well as in immunological responses. Skin-derived signals, produced in response to various agents acting on the skin, arrive with the afferent lymph at the regional lymph nodes. These signals reflect the immunological processes in the skin and may also determine the reactions in the lymph node. By analyzing afferent lymph derived from specific skin lesions it should therefore be possible to get insight into local pathomechanisms as well as the signal transmission in skin disorders. In this report, we present methodological aspects of such skin-derived lymph studies and review the results obtained from studies of sodium-lauryl-sulfate-induced irritative contact dermatitis in humans.

Cytokines↗

Demonstration and localization of growth hormone receptor in human skin and skin fibroblasts.

Clinical evidence suggests that skin is responsive to GH status in vivo. We sought to demonstrate the presence of GH receptors in human skin and in cultured skin fibroblasts using the techniques of immunohistochemistry and northern blotting. Human foreskin was obtained at surgery for preparation of sections and primary fibroblast cultures. Skin sections and fibroblast monolayers were immunostained using a monoclonal antibody which recognizes the hGH receptor (MAb 263). Positive immunoperoxidase staining was seen in all epidermal layers except the stratum corneum, in dermal sweat and sebaceous glands, and in dermal fibroblasts. In cultured fibroblasts capping of surface GH receptor was observed after aqueous formaldehyde fixation, whereas fixation in Carnoy's solution resulted in granular cytoplasmic staining. Fibroblast poly A+ RNA was prepared from cultured skin fibroblasts, separated by denaturing agarose gel electrophoresis, blotted onto nitrocellulose, and hybridized to a 32P-labeled, 847 base pair (bp) hGH receptor complementary DNA (cDNA) clone. Human liver and non-pregnant rabbit liver total RNA were used as controls. Fibroblast poly A+ RNA contained a single hybridizing species of approximately 5.2 kilobase. Human liver total RNA also contained a single hybridizing species of 4.9 kilobase. We have demonstrated the presence of GH receptor protein in human skin and growth hormone receptor mRNA and protein in cultured human skin fibroblasts. These observations suggest that GH may indeed have a direct role in modulating keratinocyte and fibroblast function.

Adolescent↗

Modulation of eicosanoid formation by lesional skin of psoriasis: an ex vivo skin model.

The purpose of the present study was to develop an ex vivo skin model to determine the capacity of lesional skin of psoriasis to form leukotriene B4 and other eicosanoids. Keratomed skin samples were incubated in the presence of the calcium ionophore A23187 and arachidonic acid for 45 min at 37 degrees C. After extraction of lipids, eicosanoids were determined by quantitative reversed-phase high-performance liquid chromatography in combination with specific radioimmunoassays. We found that stimulation of skin samples with A23187 and arachidonic acid increased the amount of leukotriene B4 4.0-fold. The 12-lipoxygenase product, 12-hydroxy-eicosatetraenoic acid, and the 15-lipoxygenase product, 15-hydroxy-eicosatetraenoic acid, were both increased 2.7-fold. The cyclooxygenase product, prostaglandin E2, was increased 8.0-fold. Similar incubations using psoriatic scales did not result in formation of eicosanoids. Incubations with the 5-lipoxygenase inhibitor RS43179 inhibited the formation of leukotriene B4 and prostaglandin E2 without significantly affecting the formation of 12-hydroxy-eicosatetraenoic acid and 15-hydroxy-eicosatetraenoic acid. These results reveal that lesional psoriatic skin ex vivo has the enzymatic capacity to increase the levels of eicosanoids. This provides an ex vivo skin model to determine whether putative lipoxygenase inhibitors are able to modulate the formation of eicosanoids in psoriatic skin.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Low frequency changes in skin surface potentials by skin compression: experimental results and theories.

Human living skin generates an increase in the skin potential when compressed. This was measured on eight subjects with a matrix of nine Ag/AgCl electrodes. The potential increased with the pressure until it reached a maximum. When the pressure was increased stepwise, the response showed an overshoot at each step. Human cadaver skin did not show these potential increments. Neither did pads of collagen, paper tissue soaked in a KCl solution, nor layers of cultured keratinocytes. Three theories are described that may explain the origin of the measured skin potentials. The first is based on the piezoelectric characteristics of proteins in the skin. The second theory assumes that the skin is a charged membrane which generates a streaming potential when deformed. A third theory is proposed in which deformation of absorbed charged protein layers on structures in the skin change the alignment of Donnan potentials in the surrounding tissue.

Collagen↗

Single-pass CO2 laser skin resurfacing of light and dark skin: extended experience with 52 patients.

BACKGROUND: Multiple-pass carbon dioxide (CO2) laser skin resurfacing has been a favored treatment modality for photodamaged and acne-scarred skin over the past several years. Its association with numerous side effects and complications, particularly prolonged erythema and dyspigmentation, however, has dampened the initial enthusiasm reserved for its use. By reducing the laser-associated tissue ablation depth and degree of thermal necrosis, it is possible that the incidence of these side effects can also be reduced. PURPOSE: To evaluate the clinical efficacy and side effect profile of single-pass CO2 laser skin resurfacing in a large series of patients. MATERIALS AND METHODS: A total of 52 consecutive patients (skin photo-types I-VI) with mild facial rhytides,atrophic scars, or infraorbital hyper-pigmentation underwent single-pass treatment with a high-energy, pulsed CO2 laser. Side effects to treatment were closely monitored and tabulated. Clinical improvement using a quartile grading scale was assessed independently by two masked medical evaluators at 1, 3, 6, and 12 months postoperatively. RESULTS: Significant clinical improvement was seen in all patients, with peak improvement scores noted 12 months. Greater clinical improvement was seen in patients with darker skin tones despite the near universal incidence of transient postoperative hyperpigmentation in these patients. CONCLUSIONS: Single-pass CO2 laser skin resurfacing can improve the appearance of fine rhytides, mild atrophic scars, and infraorbital hyperpigmentation in all skin types. The severity and duration of side effects and complications are reduced with this technique (compared with multiple-pass procedures)and may offer a possible solution to the problem of treating patients with darker complexions.

Adolescent↗

The effect of a daily facial cleanser for normal to oily skin on the skin barrier of subjects with acne.

Acne vulgaris is a common skin disorder that affects many people every year, especially the teenaged population. People with acne find the condition especially difficult to manage because of the disease's chronicity and variability in response to treatment. Acne is the result of pores clogged with shed skin cells combined with sebum in the hair follicle. Successful treatment of acne is important because acne has the potential to result in lasting physical and emotional scarring. For many years, physicians have agreed that although cleansing is not effective on its own, effective cleansing is an important part of any acne treatment regimen. However, patients have not been satisfied with the types of cleansers available. In addition to containing dyes and perfumes that can irritate and exacerbate acne, these cleansers often are too harsh and can result in excessive drying of the skin, which leads to overcompensation by the oil glands and ultimately to more oil on the surface of the skin. This study examined the use of a daily facial cleanser formulated for normal to oily skin in subjects with mild facial acne. The cleanser was studied for 2 weeks in the absence of additional treatments to eliminate the confounding effects of various treatments. Subjects were monitored for skin barrier function through transepidermal water loss (TEWL) and corneometry, sebum level, and lesion counts. The results of the study indicate that the facial cleanser is gentle and does not damage the skin barrier or result in sebum overcompensation; additionally, the cleanser is effective at deep-pore cleansing, which may help to manage some acne-associated symptoms.

Acne Vulgaris↗