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PURPOSE: We describe a method of primary closure of a large skin defect. MATERIALS AND METHODS: A 44-year-old man was treated for penile cancer. After left inguinal lymphadenectomy a large skin defect in the groin remained that could not be closed primarily. Allowing skin to stretch beyond its inherent extensibility with a skin stretching system (Sure-Closure) the wound edges were closed without tension. RESULTS: Primary closure of a large skin defect was possible after cyclic stretching and relaxation of the skin with a skin stretching device. CONCLUSIONS: Large skin defects can be closed primarily using a skin stretching device. The primary advantage of the procedure are its simplicity and avoidance of the need for more complicated reconstructive surgery.
Substance P is located in cutaneous nerve fibres and induces wheal and flare responses, accompanied by granulocyte infiltration, upon intradermal injection. Studies with animal skin and rat peritoneal mast cells have suggested that substance P induces the release of histamine and leukotriene B4 (LTB4), a potent chemoattractant for granulocytes, from skin mast cells. However, the release of LTB4 has not been detected from mast cells enzymatically isolated from human skin. In order to investigate the mechanism of granulocyte infiltration induced by substance P in human skin, we studied the release of LTB4 and histamine in response to substance P, and the effect of dexamethasone using human skin obtained from 22 nonallergic individuals. Histamine was released from all skin tissue samples in a dose-dependent manner. However, the amount of LTB4 release, both constitutive and inducible, was variable among skin preparations. Substance P induced a large release of LTB4 from the skin of eight donors (twice to six times that of the spontaneous release), but no or only negligible release from the skin of 14 donors. The amount of constitutive release of LTB4 correlated with the amount of tissue histamine. Dexamethasone selectively abolished the inducible release of LTB4, without an effect on histamine release and the constitutive release of LTB4. These results suggest that substance P induces the release of LTB4 in a certain population of human individuals by a glucocorticosteroid-dependent mechanism, and plays an important role in neurogenic inflammation with granulocyte infiltration.
Skin traction based on an Ilizarov frame has been used to achieve skin closure in five cases of infected non-union of the tibia including one case of infected knee arthrodesis. Five patients presented with infected non-union of the tibia (all Staph. aureus, two of them MRSA) with overlying sinuses discharging pus at an average 16 months from injury (range 3-36 months). The infections were treated by excision of the sinus and infected skin, excision of the infected non-union, stabilisation of bone with an Ilizarov circular frame and either acute shortening with compression followed by distraction (3 patients), or bone transport (2 patients). After excision of the sinus, the skin defect was gradually closed using a skin traction device placed on an Ilizarov circular frame. The size of the wounds ranged from 5 x 14 cm to 3 x 5 cm and skin traction was completed at 4 weeks (range 2-8 weeks). When the wound edges were approximated, the wires were left in place until healthy granulation tissue built up to seal the remaining gap (sutures were used in two patients). At follow-up assessment at 18 months (range 7-24 months), all non-union were solidly united with no signs of infection of either the bone or underlying skin. The quality of skin at the stretching site was found to be of normal sensation, colour, mobility but thinner than normal. The quality of the skin at the docking site (left to granulate) was found to be adherent to the underlying bone, red or pink in colour, hypersensitive in 2 patients and numb in 3 patients.
BACKGROUND: In spite of leprosy being a disease of nerves, ROM therapy for single skin lesion leprosy was based on clinical trials without much evidence-based studies of nerve pathology. The present study was undertaken to compare the histology of skin and nerve in single skin lesion leprosy, and to assess the scientific rationale and justification of single dose ROM therapy. METHODS: Twenty-seven untreated patients with single skin lesion without significantly thickened peripheral nerves were selected. Skin and nearby pure cutaneous nerve biopsies were studied under both H&E and Fite's stain. RESULTS: All the skin biopsies were negative for AFB and clinico-pathological correlation was positive in 51.85% of skin biopsy specimens. Histopathological diagnosis of leprosy was evident in 55.5% of clinically normal looking nerves, with AFB positivity in 29.6% of nerve biopsy specimens. Correlation between clinical diagnosis and nerve histopathology was poor (26%). CONCLUSIONS: Single skin lesion without thickened peripheral nerves as criteria for single dose ROM therapy is not logical, since the histological diagnosis of leprosy in normal looking nerves with presence of AFB is revealed in this study. Pure cutaneous nerve biopsy is a simple outpatient procedure, without complications. This study emphasizes the need to consider nerve pathology as an important tool for further therapeutic recommendations, than just clinical trials and skin pathology alone. Though single dose ROM therapy has been withdrawn recently, the principle holds good for any future therapeutic recommendations.
During the years 1949 to 1975, 14,237 patients received therapeutic doses of grenz rays for the treatment of benign skin disorders such as chronic eczema, psoriasis, and warts. The records of 14,140 of these patients (99.3%) formed the basis for an epidemiologic study of the incidence of skin malignancies in this population. Information about the patients, diagnoses, doses, and sites of treatment was obtained from separate records. The follow-up time was 15 years on the average. We searched the Swedish Cancer Registry, Stockholm, for records reporting the incidence of malignant skin tumors in the study population (incidences of basal cell carcinoma are not registered). The expected number of malignancies was calculated on the basis of age- and sex-standardized incidence data from the Swedish Cancer Registry. In 58 patients, a malignant skin tumor was diagnosed more than five years after grenz-ray therapy had first been administered. Nineteen patients had malignant melanomas, and 39 patients had other malignant skin tumors. The expected number of melanomas was 17.8, and that of other malignant skin tumors was 26.9. None of the patients with melanomas, and only eight of the patients with other malignant skin tumors, had received grenz-ray therapy at the site of the tumor. Six of these eight patients had also been exposed to other known carcinogens. Four hundred eighty-one patients had received an accumulated high dose of grenz rays (greater than or equal to 10 000 rad [greater than or equal to 100 Gy]) on one and the same area. No malignancies were found on those areas. Although we cannot exclude grenz-ray therapy as a risk factor in the development of nonmelanoma skin malignancies, this risk, if any, is small, if recommendations for therapy are followed.
The in vitro permeabilities of alkyl p-aminobenzoates through living skin equivalent (LSE) and cadaver skin were compared. Methyl, ethyl, and butyl p-aminobenzoates were used as model compounds. The permeabilities of these compounds through LSE and cadaver skin from an aqueous drug suspension were determined with a flow-through diffusion cell. The permeability coefficients of these esters in LSE were an order of magnitude higher than in cadaver skin. This was primarily because of low resistances offered by the outermost layer (i.e., stratum corneum) of LSE. In the case of cadaver skin, the permeability coefficient increased as the carbon chain length increased, whereas no appreciable change in the permeability coefficients of these esters in LSE was observed. These results clearly suggest that the LSE membrane offered very little resistance as opposed to cadaver skin. Therefore, the LSE membrane may not quantitatively represent a good human skin model for evaluating skin permeation of a drug from topical or transdermal formulations.
BACKGROUND: The skin flap technique is widely used in reconstructive surgery for the coverage of deep burns of the face, neck, and joints. Facial deformities and joint contractures are avoided by transplanting vascularized full-thickness skin on wounds. The major drawback of this technique is the injury inflicted upon the donor site, which corresponds to a third degree burn. The usual technique to cover the flap donor site is the transplantation of split-thickness autografts. In the case of patients with deep and extensive burns, the harvesting of good quality autografts is often difficult because of multiple scars. In order to avoid additional trauma to the patient by split-thickness skin harvesting, we have experimented the use of a new model of in vitro reconstructed skin graft for flap donor site coverage in a mouse model. MATERIALS AND METHODS: The reconstructed skin was grafted on the back of nude mice at the skin flap donor site, while flap was used to cover a wound generated on joint of the posterior leg. RESULTS: A 100% graft take was achieved (16 mice were used) and a limited contraction of the reconstructed skin was observed 30 days posttransplantation (78% of the initial surface area of the graft remained). Histological analysis of the graft demonstrated healing of a well differentiated epidermis laying on a dense dermis. CONCLUSIONS: Since this technique would prevent additional trauma to the patient while achieving a good healing of the wound, it may be a useful approach in the coverage of skin flap donor site in humans.
Human autopsy skin was sliced into three sections; an outer epidermis-rich layer, a middle dermis layer, and an inner dermis and subcutaneous fat layer. Each slice was bathed in lindane solutions over a 50-fold concentration range for 48 h at 37 degrees C. Lindane uptake by the skin was extensive (less than 90%) for all concentrations and all skin slices. Equilibrium dialysis with lindane at 37 degrees C for 24 h showed binding affinities by the skin sections to exceed 98%. The binding constants of the outer skin section (epidermis-rich) were higher than those of the middle and inner sections. The binding attraction for lindane by United States Pharmacopeia (USP) human plasma protein fraction (mean 90.5% bound) resulted in its competitive extraction from the skin slices in a three-compartment dialytic procedure. Since the least binding constants were in the middle and inner layers, and since lindane has a preference for plasma over skin, the two (inner skin and plasma) may combine to create the sink conditions necessary for lindane percutaneous absorption into the body. This plus the high epidermis capacity for lindane explains why in some instances (such as occlusion) high levels of lindane can be percutaneously absorbed.
Human autopsy skin was sliced into three sections: an outer epidermis-rich layer, a middle dermis layer, and an inner dermis and subcutaneous fat layer. Each skin slice was bathed in malathion solutions over a 100-fold concentration range of 0.02-3.0 microM/g skin for 48 h at 37 degrees C. Malathion uptake approximated 50% for each skin layer over the total concentration range. Skin capacity for malathion is thus large. Single and double compartment dialysis was used to determine free and bound malathion. Isotherm calculations gave a partition coefficient intercept for epidermis-rich and dermis tissues with aqueous buffer of 2.72 and 2.74, respectively. That of the inner layer of skin was less at 1.70. When malathion was dialyzed against simulated plasma, the binding decreased 2-fold. Since the least partition coefficient (less bound malathion) was in the inner layer of skin, and since malathion has a preference for plasma over water, the two (inner skin and plasma) may combine to create the sink conditions necessary for malathion percutaneous absorption into the body.
Porokeratosis (PK), an autosomal dominant inherited skin disorder, is known to develop malignant skin tumors on its skin lesions. Our recent literature survey has revealed that large PK skin lesions are frequently a precursor of malignant changes. In the study, large and small PK skin lesions were investigated in terms of histological features of the epidermis and of the cellular DNA content of epidermal cells. Large PK lesions frequently showed hypertrophic epidermis with many mitotic cells, while small lesions usually presented atrophic epidermis without such mitotic cells. Abnormal cells, like those containing hyperchromatic, large, and/or irregularly shaped nuclei, were present in the epidermis of both large and small lesions with a preponderance in the former over the latter. DNA polyploidy was seen more frequently in large PK lesions than in small ones. DNA index values were significantly higher in large lesions than in small ones. The histological features and DNA ploidy abnormalities probably reflect the higher proliferation and the greater potential for malignant changes of large PK skin lesions. Our study helps to explain the clinical evidence that large PK skin lesions are frequently a precursor of malignant skin tumors.
The feasibility of skin penetration was studied for aspalatone (AM, acetylsalicylic acid maltol ester), a novel antithrombotic agent. In this study, hairless mouse dorsal skins were used as a model to select composition of vehicle and AM. Based on measurements of solubility and partition coefficient, the concentration of PG that showed the highest flux for AM across the hairless mouse skin was found to be 40%. The cumulative amount permeated at 48 h, however, appear inadequate, even when the PG concentration was employed. To identify a suitable absorption enhancer and its optimal concentration for AM, a number of absorption enhancers and a variety of concentration were screened for the increase in transdermal flux of AM. Amongst these, linoleic acid (LOA) at the concentration of 5% was found to have the largest enhancement factor (i.e., 132). However, a further increase in AM flux was not found in the fatty acid concentration greater than 5%, indicating the enhancement effect is in a bell-shaped curve. In a study of the effect of AM concentration on the permeation, there was no difference in the permeation rate between 0.5 and 1% for AM, below its saturated concentration. At the donor concentration of 2%, over the saturated condition, the flux of AM was markedly increased. A considerable degradation of AM was found during permeation studies, and the extent was correlated with protein concentrations in the epidermal and serosal extracts, and skin homogenates. In rat dorsal skins, the protein concentration decreased in the rank order of skin homogenate > serosal extract > epidermal extract. Estimated first order degradation rate constants were 6.1 5 +/- 0.14, 0.57 +/- 0.02 and 0.011 +/- 0.004 h(-1) for skin homogenate, serosal extract and epidermal extract, respectively. Therefore, it appeared that AM was hydrolyzed to some extent into salicylmaltol by esterases in the dermal and subcutaneous tissues of skin. Taken together, our data indicated that transdermal delivery of AM is feasible when the combination of PG and LOA is used as a vehicle. However, since AM is not metabolically stable, acceptable degradation inhibitors may be necessary to fully realize the transdermal delivery of the drug.
Twenty-one healthy volunteers took part in the study, the aim of which was to determine the influence of acute pain on skin impedance, skin temperature and heart rate. Acute pain was induced by cold exposure. Skin impedance, heart rate and facial skin temperature were recorded before, during and after the painful stimulation. The skin impedance increased during the stimulation by 24%, heart rate by 6% and skin temperature by 6%. The results show that changes in skin impedance as a result of acute pain can easily be recorded and could be a useful tool in monitoring acute pain. The technique is better than monitoring heart rate or skin temperature.
Skin blister fluid (SBF) samples obtained after allergen skin testing in a total of 26 patients with late cutaneous reactions (LCRs) were examined for the presence of various vasoactive mediators. Histamine was predominant during the early phase of the wheal and flare reaction(206 +/- 40 ng/ml) and decreased with the development of the LCR toward normal SBF levels (around 20 ng/ml). Kallikrein activity was measurable in low amounts (around 5 ng/ml) in three out of 13 SBF samples taken 30 min after skin testing and in five of 13 SBF samples taken 6 hr after allergen testing. The thromboxane B2 content of SBF showed an increase with the development of LCR (control skin 976 +/- 483 ng/ml; allergen-tested skin 30 min after allergen injection, 1465 +/- 1566 ng/ml; allergen-tested skin 6 hr after antigen injection, 1775 +/- 731 ng/ml). SBF obtained from normal skin as well as from allergen-tested skin showed significant platelet-activating property as measured in an in vitro serotonin-release assay from washed human platelets. It is concluded that during the development of late-phase reactions a complex interaction of various mediator systems takes place.