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Vertical (two-layer) skin grafting: new reserves for autologic skin.

The main, permanent source of burn coverage continues to be autologic skin. In patients with major burns, the amount of available autologic skin may be insufficient. Consequently, severe wounds are covered after debridement with other biological or synthetic skin substitutes. Another source of skin reserves for wound coverage is the use of cultured keratinocyte sheet graft alone or with any dermal substitute. Some of these materials provide only temporal coverage and are often costly and time-consuming in preparation. These factors can be critical in burned patients. To expand the effective means of wound coverage, the authors sought a new source of autologic skin. The dermal grafts that were the marginal product of skin harvesting were meshed and grafted on the debrided third-degree burn, granulated wound, or muscle. The authors observed good dermal grafts "take" with rapid or slow epithelialization. They saw no the delay in donor site healing where the skin grafts overlapped. The histological difference in usual skin grafts and dermal grafts was studied after their harvesting and "taking."

Burns↗

Studies in porphyria. VI. Biosynthesis of porphyrins in mammalian skin and in the skin of porphyric patients.

Porphyrin biosynthesis in mammalian skin and in skin obtained from patients with selected types of porphyria has been studied. Cutaneous porphyrinogenesis required the precursor delta-aminolevulinic acid (ALA) which, when added to murine, rat, and human skin in vitro, was rapidly converted to porphyrins. Total porphyrin content was quantitated by fluorescence assay, and spectral studies indicated that more than 80% of the porphyrin produced was protoporphyrin. The majority of skin porphyrinogenesis occurrred in epidermis or in epidermal derivatives such as hair roots. Known inducers of hepatic delta-aminolevulinic acid synthetase (ALAS), the rate-limiting enzyme for heme biosynthesis, were not inducers when added to skin in vitro. Skin from patients with acute intermittent porphyria demonstrated a 43% decrease in cutaneous porphyrin production as compared to unaffected normals. This is consistent with the known deficiency of uroporphyrinogen synthetase that has been previously demonstrated in the liver and red blood cells of these patients. Porphyrinogenesis in skin of patients with porphyria cutanea tarda was not different from controls. These studies demonstrate that skin has the enzymatic capacity to synthesize porphyrins from added ALA and that cutaneous porphyrinogenesis from ALA is deficient in patients with acute intermittent porphyria.

Allylisopropylacetamide↗

Drug permeation through human skin: I. Effect of storage conditions of skin.

The purpose of this study was to establish conditions for the preparation and storage of excised human skin such that it most closely retained the permeation characteristics seen with skin samples studied immediately after having been removed from cadavers. Using skin taken from the inner thighs of cadavers within 48 hr post mortem, we have compared drug permeation through samples that were used immediately following removal with samples that had been stored in either the frozen or dried state. With the chromone acid under investigation, it was found that samples of stratum corneum attached to the underlying epidermis used without prior storage consistently showed less permeation than samples taken from the same individual that had been frozen at -17 degrees C upon removal and then thawed before permeation studies were started. However, drug permeation through samples of stratum corneum plus epidermis that had been allowed to dry under controlled humidity conditions at room temperature were found to be similar to those obtained with fresh skin. These results indicate that dried skin, when appropriately rehydrated before use, exhibits rates of drug permeation similar to those found with fresh skin. With the chromone acids under investigation, the use of frozen samples of excised skin should be avoided since the extent of permeation exceeds that obtained with fresh skin samples.

Adult↗

Skin-infiltrating lymphocytes in normal and disordered skin: activation signals and functional roles in psoriasis and mycosis fungoides-type cutaneous T cell lymphoma.

T lymphocytes recruited into the skin can experience several different outcomes. On the one hand, they may be recruited by adhesion molecules and chemoattractants to enter the perivascular space, but never undergo activation. Other T cells undergo activation and further differentiation under the influence of the cutaneous milieu. These activated lymphocytes then coordinate specific and non-specific immune responses characteristic of inflamed tissue. We have explored two models for studying the activation and function of skin infiltrating T lymphocytes (SIL's). In the first model, we have identified a family of Langerhans cell-related professional dendritic antigen presenting cells that exist in the epidermis and dermis of normal skin, atopic skin, and mycosis fungoides skin. These have APC abilities to activate freshly recruited resting blood T cells that are distinct from another family of macrophage-related cells abnormally present in sunburned or psoriatic skin. In the second model, we examined the function of cells that have already been recruited into the skin of patients with psoriasis and mycosis fungoides. Lesional psoriasis and mycosis fungoides T cells exhibited a variety of T cell receptor gene rearrangements, conclusively demonstrating that heterogeneous populations of T lymphocytes exist in inflamed human skin. From psoriasis, clones were identified that were particularly effective at inducing normal keratinocytes to assume "psoriatic" phenotypic features and functions. Thus, lesional psoriatic SIL's could induce HLA-DR, ICAM, and CDw60 on normal keratinocytes. In addition, psoriatic SIL's induced increased keratinocyte proliferation and cytokine profile changes characteristic of psoriatic epidermis.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigen-Presenting Cells↗

Activator protein 1 DNA binding activity is decreased in lesional psoriatic skin compared with nonlesional psoriatic skin.

BACKGROUND: Psoriasis is a common benign skin disease characterized by hyperproliferation and abnormal differentiation of keratinocytes. The transcription factor activator protein 1 (AP-1) is known to play an important role in cell proliferation and differentiation. OBJECTIVES: To investigate AP-1 DNA binding activity in psoriatic skin. METHODS: Keratome biopsies were taken from patients with plaque-type psoriasis. Electrophoretic mobility shift assays were used to determine the AP-1 DNA binding activity, whereas Western and Northern blotting was used to determine Jun and Fos protein and mRNA expression. RESULTS: We found that AP-1 DNA binding activity was almost completely abolished in lesional psoriatic skin compared with nonlesional psoriatic skin. Furthermore, experiments revealed that the protein and mRNA expression of the AP-1 subunits c-Fos, Fra-1 and c-Jun was reduced in lesional psoriatic skin compared with nonlesional psoriatic skin, whereas the protein and mRNA expression of the subunit JunB was increased. Topical application of the vitamin D analogue calcipotriol under occlusion to involved psoriatic skin for 4 days resulted in an increase in AP-1 DNA binding activity, and an increase in the protein and mRNA expression of c-Fos, Fra-1 and c-Jun, together with a decrease in JunB protein and mRNA expression. CONCLUSIONS: Together, these results suggest that the activity of the transcription factor AP-1 is impaired in lesional psoriatic skin and that this impairment may be important for the disturbed epidermal growth observed in psoriasis.

Adult↗

Wound related complications following full thickness skin graft versus split thickness skin graft on patients with bone anchored hearing aids.

OBJECTIVES: The aim of this study was to review complications occurring in bone anchored hearing aid (BAHA) patients in relation to wound healing following full thickness skin graft versus split thickness skin graft. DESIGN: Retrospective study. The medical notes of 22 patients who underwent insertion of BAHA over 24 months were reviewed. SETTING: ENT Department at a District General Hospital in the UK. PARTICIPANTS: All patients were adults and underwent one stage procedure following the standard Branemark technique. In 11 cases the skin abutment interface was established by use of full thickness skin graft inset around the implant, and in the other 11 by use of split thickness skin graft. MAIN OUTCOMES MEASURES: The incidence of delayed wound healing resulting in an increase of number of visits for change of wound dressings. In addition the degree of soft tissue reactions around the interface was examined. RESULTS: There was a clear difference between the split and full thickness skin graft groups in relation to the severity of adverse skin reactions and number of visits required for change of dressings. The split thickness group required from three minimum to 13 maximum (median 4) visits in outpatients during the initial observation period until healing was complete. The full thickness group demonstrated one minimum and three maximum (median 2) visits. CONCLUSIONS: In our hands the full thickness skin graft is superior to a split thickness graft.

Adolescent↗

Skin cancers at Tertiary Referral Skin Hospital in Singapore.

BACKGROUND: Skin cancer is the seventh most common cancer in Singapore. This study was performed to determine the pattern of skin cancers seen in a tertiary referral skin hospital. METHODS: Histologically confirmed skin cancers, seen between 1980 and 1991, were analyzed according to age, sex, race, site, and presence/absence of preexisting skin conditions. RESULTS: Of a total of 520 patients, the commonest skin cancer was basal cell carcinoma (BCC) (36.5%), followed by squamous cell carcinoma (SCC) (24.4%), Bowen's disease (16.7%), and mycosis fungoides (9.0%). Malignant melanomas (2.7%) were rare. The sharp increase (26.2%) in BCC in the recent 3 years was largely contributed by a fivefold increase of non-resident Caucasian patients with BCC. All types of skin cancers were more common in Chinese (78.1%) and less frequent in the more pigmented races (9.4%). The men to women ratio was 1.72:1. The peak age distribution was in the 51-70-year group, with the exception of mycosis fungoides (31-50 years). The commonest site involved in BCC was the head and neck (67.0%) and in Bowen's disease the trunk (33.3%). Squamous cell carcinoma was found on the head and neck and the lower extremities with equal frequency (29.3%) and 46.2% of all SCC on the lower extremities occurred in leprosy patients with chronic trophic ulcers. Of patients with Bowen's disease involving the nonsunexposed parts (trunk and upper extremities), 42.6% had probable arsenic exposure evident either from the history or clinical examination. Malignant melanomas were commonly located on the foot (71.4%). CONCLUSIONS: The commonest skin cancers seen were BCC, SCC, Bowen's disease, and mycosis fungoides. There were differences in the site distribution of SCC, Bowen's disease, and malignant melanomas in our study when compared to studies in Caucasians.

Adult↗

Skin temperature and skin symptoms among workers in the fish processing industry.

196 workers employed in the fish processing industry participated in a survey of skin disorders. 156 (80%) had experienced skin problems during their work with fish on some occasions. The symptoms were itching, redness and stinging. Although the fingers are in direct contact with fish meat and juice, skin symptoms only seldom occur here, but instead almost exclusively on the forearms (70%) and the backs of the hands (26%). The skin temperature of the fingers and palms of the hands ranged from 17 degrees C to 20 degrees C, while the temperature on the backs of the hands and forearms ranged from 25 degrees C to 30 degrees C. Skin temperatures less than 20 degrees C abolish itch and reduce vasodilation by half. We suggest that the low temperature on the fingers affords protection against the development of some irritant skin reactions and that differences in skin temperature may be an important reason for the location of skin symptoms.

Adolescent↗

Susceptibility to skin stinging, non-immunologic contact urticaria and acute skin irritation; is there a relationship?

Adverse skin reactions cover many types of response: toxic, irritant, allergic, urticarial, sensory, etc. The relationships between an individual's tendency to develop different types of skin response are not well-described. We examined whether those who perceive stinging might be more likely to experience urticarial, sensory and irritation reactions in skin. A panel of 86 volunteers was tested with 10% lactic acid in the nasolabial fold to assess their ability to perceive stinging. At the same time, their capacity to develop non-immunologic contact urticaria was evaluated using chemicals of different structural type and urticant ability: methyl nicotinate, benzoic acid, cinnamic acid, cinnamaldehyde and dimethyl sulfoxide (DMSO). DMSO was also used to assess sensory effects and skin irritation. 44 were classes as "stingers" and 42 as "non-stingers". The pattern of urticant reactivity in the stingers and non-stingers was essentially the same, with neat DMSO generating the strongest reactions in both groups. Sensory reactions to DMSO (stinging, itching, tingling or burning) were similar in stingers and non-stingers; although the former may have reacted more quickly, a smaller proportion reacted (64% versus 76%). The skin irritation response to DMSO was also identical in stingers and non-stingers and the intensity of the urticant response in an individual did not correlate with the intensity of their subsequent irritant reaction. In conclusion, this study demonstrated that an individual's ability to perceive skin stinging does not give a general indication of their susceptibility to other types of non-immunologic skin response. Indeed, there appeared to be little evidence of correlations between any of the skin effects studied.

Acrolein↗

The effects of cyclophosphamide and azathioprine on collagen in skin and granulation tissue in rats, and the effects of cyclophosphamide on collagen in human skin.

Granulation tissue was produced in rats by subcutaneous implantation of cellulose sponges. The effect of daily intraperitoneal injections of cyclophosphamide or azathioprine on rat skin and granulation tissue was examined after 14 and 42 days. Skin biopsies from patients with glomerulonephritis were analyzed before and after 42 days of treatment with cyclophosphamide or placebo. In the rats, cytostatic treatment caused an increase in the dry weight of the skin, and azathioprine increased the dry weight and the protein content of the granulomas. The increase in the dry weight was accompanied by a decrease in water percentage. The alpha-amino nitrogen/OH-proline ratio in purified acid soluble collagen from skin and granulation tissue increased with the dose and duration of cytostatic treatment. No effect on the aldehyde content was observed. Cyclophosphamide caused a decrease in the alpha/beta ratio in acid soluble collagen from granulation tissue, but not in the collagen from the skin. Salt soluble collagen was increased in the skin after 14 days of cytostatic treatment, but remained unchanged in the granulation tissue. In human skin cyclophosphamide caused no statistically significant changes in the amount of salt soluble or total collagen. It is concluded, that daily treatment of rats with cyclophosphamide or azathioprine from 14 to 42 days seems to inhibit the catabolic processes in the skin and granulation tissue, to decrease the hydroxylation of proline in collagen, and to inhibit the intermolecular cross-linking in collagen.?222

Animals↗

Vitamin E delivery to human skin by a rinse-off product: penetration of alpha-tocopherol versus wash-out effects of skin surface lipids.

alpha-Tocopherol, the major biologically active form of vitamin E, represents a frequently added lipophilic compound of skin care products. Despite its emerging use in rinse-off formulations, little is known on its efficacy with respect to its deposition or its antioxidant potential in human skin. The objective of this study was to investigate whether the single use of an alpha-tocopherol-enriched rinse-off product provides effective deposition of alpha-tocopherol on human stratum corneum. To test this, forearm skin of 13 volunteers was washed either with an alpha-tocopherol-enriched rinse-off product (test product, TP) or with an alpha-tocopherol-free vehicle control (control product, CP) (contralateral arm) using a standardized wash protocol. Thereafter, skin surface lipids were extracted with pure ethanol after the wash procedure as well as after 24 h. Additionally, one group of volunteers was subjected to irradiation of their forearms with low-dose UVA (8 J/cm(2)) prior to lipid extraction. Skin lipid extracts were analyzed by high performance liquid chromatography using electrochemical detection for vitamin E and UV detection for squalene (SQ) and squalene monohydroperoxide. The results of this in vivo study demonstrated that (1) while CP treatment lowers, TP treatment strongly increases alpha-tocopherol levels of skin barrier lipids; (2) increased vitamin E deposition levels were maintained for a period of at least 24 h, and (3) TP treatment significantly inhibited photooxidation of SQ. In conclusion, the use of alpha-tocopherol-enriched rinse-off products may help to maintain the integrity of the skin barrier by providing protection against photooxidative stress at the level of skin surface lipids.

Administration, Cutaneous↗

Influence of ketamine and pentobarbital on microvascular perfusion in normal skin and skin flaps.

The influence of two anesthetics, ketamine and sodium pentobarbital, on the microvascular perfusion of normal skin and skin flaps was evaluated by the use of a laser Doppler perfusion imager which allows the rapid scanning of tissue perfusion. Arterial skin flaps with a distal random random portion were created on the ears of hairless mice (n = 20), and perfusion was measured in the proximal, central, and distal parts of the flap. No differences in microvascular perfusion throughout the whole experiment were found between the ketamine and the pentobarbital group. In normal skin microvascular perfusion decreased to 83-73% of baseline values after induction of anesthesia. After flap creation, the perfusion was further reduced in the distal and central parts of the flap to 48-43% of baseline values, whereas no significant change was found in the proximal part. Six hours after flap creation, with the animal awake, perfusion had increased again in all parts of the flap, remaining at a constant level during the rest of the experiment. Anesthesia had less effects on microvascular perfusion in skin flaps as observed 1 day after flap creation. Perfusion of the central and distal parts of the flap decreased by 10-16%, whereas, in contrast to normal skin, the proximal part remained unaffected. Our study shows that baseline measurements are required in skin flap models when the microvascular perfusion in skin flaps is analyzed under general anesthesia.

Animals↗

The development of non-melanocytic skin cancers in people with a history of skin cancer.

OBJECTIVE: To determine the incidence of new skin cancer formation in people who have had skin cancer removed. STUDY DESIGN: A prospective study of Melbourne out-patients with histologically confirmed non-melanoma skin cancer (NMSC). All patients with NMSC seen by one author (D.C.) between November 1988 and November 1989 were entered into the study and reviewed regularly. New skin cancers were removed and recorded. RESULTS: Four hundred and eighty-one patients were entered and 420 followed for at least 3 years. New NMSC developed in 60% (adjusted for losses) by the end of 3 years. A multivariate analysis determined that the main risk factor for new NMSC formation was the number of previous skin cancers that a patient had. Those who had had multiple skin cancers (3 or more) were at significantly greater risk than those with less than 3. Age, sex and type of NMSC were not risk factors for new skin cancer formation. CONCLUSION: Patients with NMSC require long-term follow-up because of the risk of new skin cancer formation. Those with multiple NMSC need more careful follow-up, and possibly more frequent examinations, because they are at greater risk.

Adult↗

All-trans retinoic acid (RA) stimulates events in organ-cultured human skin that underlie repair. Adult skin from sun-protected and sun-exposed sites responds in an identical manner to RA while neonatal foreskin responds differently.

Adult human skin from a sun-protected site (hip) and from a sun-exposed site (forearm) was maintained in organ culture for 12 d in the presence of a serum-free, growth factor-free basal medium. Cultures were incubated under conditions optimized for keratinocyte growth (i.e., in 0.15 mM extracellular Ca2+) or for fibroblast growth (i.e., in 1.4 mM extracellular Ca2+). Treatment with all-trans retinoic acid (RA) induced histological changes in the organ-cultured skin under both conditions which were similar to the changes seen in intact skin after topical application. These included expansion of the viable portion of the epidermis and activation of cells in the dermis. In sun-damaged skin samples, which were characterized by destruction of normal connective tissue elements and presence of thick, dark-staining elastotic fibers, a zone of healthy connective tissue could be seen immediately below the dermo-epidermal junction. This zone was more prominent in RA-treated organ cultures than in matched controls. Associated with these histological changes was an increase in overall protein and extracellular matrix synthesis. In concomitant studies, it was found that RA treatment enhanced survival and proliferation of adult keratinocytes and adult dermal fibroblasts under both low- and high-Ca2+ conditions. In all of these assays, responses of sun-protected and sun-exposed skin were identical. In contrast, responses of neonatal foreskin to RA were similar to those of adult skin in the presence of low-Ca2+ culture medium, but under conditions of high extracellular Ca2+ RA provided little or no additional stimulus. Together these studies suggest that the ability of RA to enhance repair of sun-damaged skin (documented in previous studies) may reflect its ability to influence the behavior of skin in a manner that is age dependent but independent of sun-exposure status.

Adult↗

Parents' skin to skin holding of small premature infants: differences between fathers and mothers.

AIM: Both mothers and fathers should achieve early skin to skin holding of their small premature infants, despite the infants' need for breathing equipment, including respirator. If the mother needs to wait to hold her newborn due to her medical condition, this is not reason enough for the father also to wait. PURPOSE/QUESTION: Do fathers wait significantly longer post delivery to hold their small premature infants skin to skin (kangaroo) than mothers do? METHODS: Registration-schedule, existing sources of data, and interviews were used. FINDING/CONCLUSION: The time from birth (hours) until fathers held their small premature infants skin to skin was significantly different (p = 0.0004) compared to mothers. Fathers held their infants later than did mothers, despite the fact that fathers saw their infants before the mothers did. Compared to the mothers the average waiting time before fathers first held their infants skin to skin showed a difference of 120.9% (difference of the median).

Adolescent↗

Follow-up to the ECVAM prevalidation study on in vitro tests for acute skin irritation. The European Centre for the Validation of Alternative Methods Skin Irritation Task Force report 2.

The European Centre for the Validation of Alternative Methods (ECVAM) Skin Irritation Task Force was established in 1996, to review the status of the development and validation of alternative tests for skin irritation and corrosion, and to identify appropriate non-animal tests for predicting human skin irritation that were sufficiently well-developed to be prevalidated and validated by ECVAM. The EpiDerm method, based on a reconstituted human skin model, was proposed as being sufficiently well advanced to enter a prevalidation (PV) study. Based on a review of test protocols, prediction models (PMs), and data submitted by test developers on ten specified chemicals, with 20% sodium lauryl sulphate as a reference standard, the task force recommended the inclusion of four other tests: EPISKIN and PREDISKIN, based on reconstituted human epidermis or on human skin; the non-perfused pig-ear test, based on pig skin; and the skin integrity function test (SIFT), with ex vivo mouse skin. The prevalidation study on these methods was funded by ECVAM, and took place during 1999-2000. The outcome of the PV study was that none of the methods was ready to enter a formal validation study, and that the protocols and PMs of the methods had to be improved in order to increase their predictive abilities. Improved protocols and PMs for the EpiDerm and EPISKIN methods, the pig ear test, and the SIFT were presented at an extended Task Force meeting held in May 2001. It was agreed that, in the short term, the performance of the revised and harmonised EpiDerm and EPISKIN methods, as well as the modified SIFT, should be evaluated in a further study with a new set of 20 test chemicals. In addition, it was decided that the SIFT and the pig ear test would be compared to see if common endpoints (transepidermal water loss, methyl green-pyronine stain) could be identified.

Animal Testing Alternatives↗

Effects of skin blood flow and temperature on skin--electrode impedance and offset potential: measurements at low alternating current density.

Skin--electrode impedance was determined at 100 Hz and 1 kHz between two disposable electrodes, 5 cm apart, at current densities < 65 microA.cm-2. Measurements were made on the volar skin of the forearm during cooling on cardiopulmonary bypass, and on the dorsum of the foot in the absence of skin blood flow during aortic aneurysm repair. Both the resistive and reactive components of the skin-electrode impedence showed an inverse linear relationship to temperature between 26 and 36 degrees C. The magnitude of the impedance change was different for each patient studied; resistance changes ranged from 0.03 to 23.2 k omega. Degrees C-1 at 100 Hz and from 0.03 to 2.7 k omega. Degrees C-1 at 1 kHz, while reactance changes ranged from 0.4 to 2.1 k omega. Degrees C-1 at 100 Hz and from 0.04 to 0.18 k omega. Degrees C-1 at 1 kHz. Changes in skin-electrode impedance were not due to changes in skin blood flow. There was no consistent change in offset potential with temperature. Although the skin-electrode impedance increases as temperature falls, it is concluded that temperature effects at the skin-electrode interface are not responsible for the observed failure of evoked electromyography during clinical monitoring of neuromuscular function.

Adult↗

Epidermal hydration and skin mechanics. The relationship between electrical capacitance and the mechanical properties of human skin in vivo.

The possible relationship between skin capacitance and the mechanical properties of the skin was studied using non-invasive techniques. Skin hydration was changed by soaking skin with tap water. Hydration of the skin increased the capacitance significantly (p less than 0.01) and hysteresis (creeping phenomenon) (p less than 0.01). The elasticity of the skin was reduced by hydration (p less than 0.01). Capacitance was found to be a poor predictor of the mechanical properties of untreated skin; while increases in hysteresis (creeping phenomenon) and decreases in elasticity were significantly (p less than 0.0001) related to changes in the capacitance of hydrated skin.

Adult↗