The use of silicone occlusive sheeting (Sil-K) and silicone occlusive gel (Epiderm) in the prevention of hypertrophic scar formation

The development of hypertrophic scars and keloids is an unsolved problem in the process of wound healing. For this reason, a successful treatment to prevent excessive scar formation still has not been found. Over the last decade, however, a promising new treatment has been introduced. Silicone materials have proved to reduce the amount of scar tissue and are believed even to prevent hypertrophic scar and keloid formation. In this study, the prophylactic effect of a silicone occlusive sheeting (Sil-K, Degania, Israel) and a silicone occlusive gel (Epiderm, Inamed B.V., The Netherlands) was investigated in a bilateral breast-reduction scar model in which the nontreated scars were supported by nonocclusive Micropore (3M, The Netherlands). The inframammary scars of 129 female patients with a mean age of 31 years ( 14 to 69 years) were studied up to 1 year after the operation. The width and height were measured, and B-scan ultrasound, laser-Doppler flowmetry, and color measurements were used as objective indicators to distinguish between normal and exuberant scars. Three months following the operation, 64.3 percent of the patients developed a hypertrophic scar, which was reduced to 56.6 percent after 6 months and down to 35.3 percent after 1 year. No keloids were seen. Patients with an easily tanning skin, nonsmokers, and patients with an allergy showed more hypertrophic scar formation. Neither Sil-K, used in 68 patients, nor Epiderm, used in 61 patients, could prevent the formation of hypertrophic scars. If both groups were taken together, the scars treated with silicone materials even developed significantly more hypertrophy compared with the Micropore-applicated scars.     

Identification of childhood vaccine providers in Maryland

Chronic inflammation seems to play a major role in skin and muscle cell damage in dermatomyositis. Adhesion molecules and their ligands are fundamental in regulating inflammation. We have carried out an immunohistochemical analysis of different activation-inducible adhesion markers in 15 biopsy specimens from dermatomyositis skin lesions. Consistent findings were the increased expression of intercellular adhesion molecule-1 (ICAM-1) on endothelial cells, inflammatory cells and focally grouped keratinocytes in contact with subepidermal inflammatory infiltrates. Immunoreactivity for vascular cell adhesion molecule-1 (VCAM-1) was predominant on endothelial cells of the upper reticular dermis and dermal stellate-shaped cells. E-selectin (endothelial leukocyte adhesion molecule-1) immunoreactivity was less extensive, detected mostly on segments of vessels of the papillary dermis and upper reticular dermis, and sometimes independent of inflammation. This pattern of adhesion molecule expression is similar to that described in other immunemediated dermatoses. The up-regulation of the adhesion molecules appears to play a role in the development and perpetuation of dermatomyositis skin lesions.     

Laser treatment of hypertrophic scars, keloids, and striae

Lasers are now being used successfully to improve various types of scars and striae. It is not only imperative to properly categorize the type of scars and striae present, but to determine which laser or lasers can best treat them. A 585-nm flashlamp pumped pulsed dye laser is preferred for the treatment of hypertrophic scars, keloids, and striae distensae. CO2 laser vaporization of scars that are proliferative, such as hypertrophic scars and keloids, is not advised due to the high rate of recurrence or worsening. When properly used, lasers can effect the best clinical responses in hypertrophic scars and keloids ever observed. Future laser technologic advances as well as the addition of concomitant lasers or other treatments may enhance clinical results. It appears evident that by promoting the remodeling phase of wound healing, abnormal scarring may be prevented or improved. Laser surgery may best be able to accomplish this by triggering regression of blood vessels and, therefore, fibroblasts within the scar. By so doing, further deposition of connective tissue may be halted.     

Acute and chronic animal models for excessive dermal scarring: quantitative studies

Excessive scarring in the form of keloids and hypertrophic scars continues to be a clinical problem for some patients. The lack of an animal model for such scarring has been an obstacle to studying the cellular and molecular biology of these entities. Previous observations made by the authors that some surgical scars in the rabbit ear remain raised for months after wounding prompted us to investigate whether the rabbit ear might provide a model by which to study excessive dermal scarring. After establishing the model in preliminary study, 40 excisional wounds, 6 mm in diameter, were created over the ventral surface of rabbit ears. Elevated scars were treated with either intralesional triamcinolone acetonide or saline at day 16 postwounding. On day 22, 25 scar wounds were used for thorough histomorphometric analysis, 15 wounds were eliminated prior to analysis because of invagination of epithelial tissue, which made analysis difficult. Total area of scar and Hypertrophic Index, a ratio comparing scar prominence with the thickness of adjacent unwounded tissue, were measured for 25 (62 percent) of the resulting scars. Both total area of scar and Hypertrophic Index were found to be significantly decreased in the steroid-treated group (p < 0.02 and < 0.03, respectively). In a chronic form of this model, in which larger excisions were taken, an excessive accumulation of both new collagen and cartilage over 9 months was observed. An animal model for excessive dermal scarring that allows quantitation of scar formation and, at an early stage, can be modulated in a predictable way with intralesional corticosteroid treatment is presented. This model may parallel hypertrophic scarring in humans and thus might provide a tool by which to study its pathophysiology and objectively evaluate therapeutic modalities.     

Cytokine expression is downregulated by collagen-polyvinylpyrrolidone in hypertrophic scars

We evaluated the in situ expression of adhesion molecules (E-selectin and vascular cell-adhesion molecule) and proinflammatory/fibrogenic cytokines (IL-1beta, TNF-alpha, TGF-beta1, and PDGF) in sections of normal skin, hypertrophic scar, and hypertrophic scar previously treated with an irradiated mixture of collagen-polyvinylpyrrolidone and completely resolved. Expression of these proteins was detected by indirect immunoperoxidase staining. The hypertrophic scar group displayed an increased amount of IL-1beta, TNF-alpha, TGF-beta1, and PDGF compared with the normal skin and treated scar groups. Values were statistically significant when cytokines in hypertrophic scar and hypertrophic treated sections were compared. Surprisingly, no differences were detected between normal skin and treated scars. On the other hand, differences in levels of E-selectin and vascular cell-adhesion molecule were not statistically significant between the groups, except for vascular cell-adhesion molecule, which decreased in treated scars. Also, supernatants from fibroblast cultures derived from treated hypertrophic scar, showed a reduction in TGF-beta1 and PDGF expression, although apparently collagen synthesis was not affected. Based on previous data from clinical studies in human dermal fibrosis remodeling, and the results presented here, we suggest that collagen-polyvinylpyrrolidone modulates extracellular matrix turnover, mainly of collagen, because expression levels of IL-1beta, TNF-alpha, TGF-beta1, and PDGF were diminished. We infer that collagen-polyvinylpyrrolidone participation could also modify the inflammatory process observed in hypertrophic scarring, by diminishing the expression of adhesion molecules, as a consequence of lower levels of proinflammatory cytokines, mainly IL-1beta and TNF-alpha.     

IgA class serum antibodies against three different Klebsiella serotypes in ankylosing spondylitis

BACKGROUND: Over the past decade, the 585-nm pulsed dye laser (PDL) has been used successfully to treat a variety of cutaneous vascular lesions as well as hypertrophic scars. Laser scar revision has been revolutionized by the recent development of high-energy, pulsed carbon dioxide (CO2) laser systems. These new CO2 lasers allow controlled vaporization of thin layers of skin while minimizing damage to surrounding dermal structures. OBJECTIVE: To determine the effect of a high-energy, pulsed CO2 laser alone and in combination with a 585-nm PDL on nonerythematous hypertrophic scars. METHODS: Twenty patients with nonerythematous hypertrophic scars were treated with a high-energy, pulsed CO2 laser. One-half of each scar was additionally treated with the 585-nm PDL laser. Sequential clinical and photographic analyses were performed independently by two blinded assessors. In addition, erythema reflectance spectrometry measurements were obtained from the scars before and at regular postoperative intervals. RESULTS: Global assessment scores and erythema spectrometry measurements were significantly improved after laser treatment. Combination CO2 and PDL laser treatment resulted in more significant improvement than CO2 laser irradiation alone. CONCLUSION: Concomitant use of the high-energy, pulsed CO2 and PDL laser systems was superior to CO2 laser vaporization alone for revision of nonerythematous hypertrophic scars. Once again, the vascular specificity of the 585-nm PDL has been linked to improvement in hypertrophic scar tissue.     

Characterization of T-cell subsets infiltrating post-burn hypertrophic scar tissues

In this study, skin-infiltrating cells were characterized in both the active and remission phases of post-burn hypertrophic scar biopsies. Immunohistochemistry examination of active phase samples showed an abundant presence of Langerhans cells, T cells, macrophages, a low presence of natural killer cells and the lack of B lymphocytes. In active hypertrophic scars T lymphocytes infiltrate deep into the superficial dermis and are also observed in the epidermis: CD3+ cells were present at about 222 +/- 107 per 0.25 mm2. In particular the analysis of lymphocyte subpopulations showed that CD4+ T cells predominate in the dermis as well as in the epidermis of active hypertrophic scars whereas CD8+ cells were less well represented (CD4/CD8 ratio is 2.06). This distribution was also shown in remission phase samples and in normotrophic scar specimens, although the lymphocyte number was significantly lower. Approximately 70 per cent of T lymphocytes present in the tissue involved in active phase hypertrophic scar samples were activated (positive with anti-HLA-DR and IL-2 receptor antibodies) which is significantly higher than remission phase hypertrophic and normotrophic scars, in which positivity was 40 and 38 per cent, respectively. Upon activation, the lesional lymphocytes release several cytokines, locally and transiently, that interact with specific receptors in response to different stimulation. Central to the immune hypothesis of hypertrophic scars is that some of the T-cell lymphokines act on keratinocytes, fibroblasts and other cell types to induce changes characteristic of these scars. The presence and close proximity of activated T lymphocytes and antigen-presenting cells of various phenotypes in both the epidermis and dermis of hypertrophic tissues provides strong circumstantial evidence of a local immune response. However, the manner in which T cells achieve and maintain their activated state in hypertrophic tissues is not yet known, and both antigen-dependent and independent mechanisms may contribute.     

Apoptosis, necrosis, and proliferation: possible implications in the etiology of keloids

Keloids are collagenous lesions acquired as a result of abnormal wound heating. In this study we have assessed the potential role of proliferation, apoptosis, and necrosis in keloids. Samples were immunolabeled for proliferating cell nuclear antigen or DNA strand breaks or stained with acridine orange. Proliferating cells were observed in the basal layer of the epidermis and fibroblasts in the dermis, the numbers of the latter being increased in comparison with normal skin. No proliferating cells were observed in the central region of the keloid. In normal skin, apoptotic cells were restricted to the basal layer of the epidermis. In keloid samples, numerous apoptotic cells were observed in the epidermis and dermis; the number and distribution of positive cells decreased more distal to the keloid lesion. Apoptotic endothelial cells of a small proportion of blood vessels in the dermis were also observed. Evidence of necrosis was also seen in the dermis. These results suggest that, with maturity, progressive cell degeneration primarily by apoptosis results in clearance of certain cellular populations resulting in the typical keloid lesion. However, the persistence of fibroblast proliferation at the dermal/keloid interface propagates the fibrosis.     

Pulsed dye laser treatment of hypertrophic burn scars

Hypertrophic burn scars are notoriously difficult to treat because of their extensive tissue involvement and tendency to worsen with hypertrophy and contracture formation. Various therapies have been advocated in the past, including surgical excision and grafting, dermabrasion, and corticosteroids, with distinct cosmetic limitations. The 585-nm pulsed dye laser has been shown previously to be effective in the treatment of a variety of traumatic and surgical scars with improvement in scar texture, color, and pliability with minimal side effects. Sixteen patients with 40 hypertrophic burn scars resulting from chemical peels, carbon dioxide laser procedures, and accidental thermal injury were treated with a 585-nm pulsed dye laser. Sequential photographic and clinical assessments were recorded in all patients. Histologic evaluations of skin punch biopsies before and after laser irradiation were performed when possible. Symptomatic improvement of scars was reported after one treatment. Decreased scar erythema with improved texture and pliability was observed after an average of 2.5 treatments. No correlation was found between scar duration, location, or etiology and response to treatment. Normal number of dermal fibroblasts with decreased sclerosis was observed on histologic examination of laser-irradiated scars. The 585-nm pulsed dye laser irradiation of hypertrophic burn scars can effectively improve scar pliability and texture and decrease erythema and associated symptoms yielding cosmetically and functionally acceptable clinical results.     

Distinct patterns of collagen gene expression are seen in normal and keloid fibroblasts grown in three-dimensional culture

The purpose of this study was to examine collagen gene expression in various types of scar fibroblasts as well as normal fibroblasts in a novel three-dimensional culture system and to compare them with those in a monolayer culture system. Cells in three-dimensional culture formed multiple layers within the self-produced dense extracellular matrix and formed a dermis-like structure. In monolayer culture, both normal and scar fibroblasts continued to express high levels of mRNA for pro alpha 1(I) and pro alpha 1(III) collagens. However, in three-dimensional culture, the mRNA levels gradually declined in normal fibroblasts. In contrast, mRNA levels remained high in keloid and hypertrophic scar fibroblasts. Atrophic scar fibroblasts demonstrated similar changes to normal fibroblasts in three-dimensional culture. When we compared mRNA expression in fibroblasts from the centre and the edge of hypertrophic scar, cells from the centre showed a persistently decreased level of collagenase mRNA expression. These results suggest that the mRNA expression pattern of pro alpha 1(I) and pro alpha 1(III) collagens varies depending on the culture system. Fibroblasts from keloids and hypertrophic scar may have a defective system of down-regulation in extracellular matrix metabolism.     

Cryosurgery in dermatology

The aim of this article is to provide current information on the clinical development of cutaneous cryoreaction and the indications, complications and contraindications of cutaneous cryosurgery. Successful cutaneous cryosurgery requires rapid freezing and slow thawing, minimum tissue temperatures of -25 degrees C to -60 degrees C and, in malignant lesions, repeated freeze-thaw cycles. Frozen tissue reacts with peripheral erythema immediately following thawing, and consequently with oedema, bulla formation, exudation, mummification, and usually heals with a fine atrophic scar within a 4-week period. Cryosurgery is now considered the treatment of choice in hypertrophic scars and keloids, granuloma annulare and capillary haemangioma of the newborn. It also represents a valuable alternative therapy for various skin diseases, including common warts, solar lentigo, actinic keratoses, superficial basal cell carcinoma and Kaposi's sarcoma. Cryosurgery is a safe regimen with only a few adverse effects and contraindications. Pain during and/or shortly after treatment, bulla formation and local oedema are the major, temporary adverse effects; lesional hypopigmentation and/or peripheral hyperpigmentation is the most common by occurring long-term complication.     

One-stage open cancellous bone grafting of infected fracture and nonunion

BACKGROUND: A quantitative study of dermal and arterial elastic fibers as a function of age was carried out by computerized image analysis. OBJECTIVE: We investigated whether any parallelism can be established between the morphometric parameters of elastic fibers from the skin and the temporal artery in elderly subjects. METHODS: we quantitated the skin elastic fibers of the reticular dermis and the elastic fibers of the temporal artery using a specific staining procedure followed by automated image analysis in 16 subjects of age range 63-87 years. RESULTS: There was a good correlation between the area fraction occupied by the elastic fibers in the unexposed skin (inner part of the upper arm) and aging (r = 0.669, p < 0.01). The area fraction occupied by elastic fibers in unexposed skin was correlated with the area fraction occupied by elastic fibers in the deep part of the temporal artery (r = 0.498, p < 0.05). Actinic elastosis affected both tissues, but there was no correlation between the amount of elastotic material in the exposed skin and the area fraction of elastic fibers in the superficial part of the temporal artery. CONCLUSION: We provided evidence that in sun-protected tissues the area fraction occupied by elastic fibers in dermis and deep part of the temporal artery showed a significant correlation. We proposed that skin biopsies were a valuable diagnostic tool for predicting arterial wall abnormalities of elastic fibers.     

In vitro reconstruction of a human capillary-like network in a tissue-engineered skin equivalent

For patients with extensive burns, wound coverage with an autologous in vitro reconstructed skin made of both dermis and epidermis should be the best alternative to split-thickness graft. Unfortunately, various obstacles have delayed the widespread use of composite skin substitutes. Insufficient vascularization has been proposed as the most likely reason for their unreliable survival. Our purpose was to develop a vascular-like network inside tissue-engineered skin in order to improve graft vascularization. To reach this aim, we fabricated a collagen biopolymer in which three human cell types keratinocytes, dermal fibroblasts, and umbilical vein endothelial cells were cocultured. We demonstrated that the endothelialized skin equivalent (ESE) promoted spontaneous formation of capillary-like structures in a highly differentiated extracellular matrix. Immunohistochemical analysis and transmission electron microscopy of the ESE showed characteristics associated with the microvasculature in vivo (von Willebrand factor, Weibel-Palade bodies, basement membrane material, and intercellular junctions). We have developed the first endothelialized human tissue-engineered skin in which a network of capillary-like tubes is formed. The transplantation of this ESE on human should accelerate graft revascularization by inosculation of its preexisting capillary-like network with the patient's own blood vessels, as it is observed with autografts. In addition, the ESE turns out to be a promising in vitro angiogenesis model.     

Fetal tissue repair and wound healing

The fibrosis and scar formation that characterize adult wound healing are also the cause of clinical problems; scar contracture, hypertrophic scar, and pulmonary and hepatic fibrosis are only a few examples. Studies of fetal wound healing can provide an insight into the initiation and regulation of a scarless repair process akin to regeneration. Studies of fetal repair have already suggested mechanisms that might favorably alter adult healing. Topical application of hyaluronic acid to wounds in adult diabetic rats leads to enhanced epithelial migration. It has been recognized that the addition of TGF-beta to fetal wounds causes an adultlike healing response with fibrosis and inflammation. A subsequent study using neutralizing antibody to TGF-beta in adult wounds showed enhanced healing with a more normal dermal architecture with fewer macrophages, fewer blood vessels, and less collagen. As our understanding of regenerative tissue repair increases, the opportunities to modulate adult fibrotic conditions should expand.     

Anti-B4-blocked ricin: a phase II trial of 7 day continuous infusion in patients with multiple myeloma

Skin ultrastructure was examined in patients undergoing CO2 laser resurfacing for facial rejuvenation. The lasers used in this study were the Coherent Ultrapulse CO2 laser with computerized pattern generator, the Sharplan Feathertouch laser, and the Laserscope Paragon-70 pulsed CO2 laser with computerized pattern generator. Results showed that the epidermis was totally removed with one pass of the CO2 laser. After one laser pass, there was little compaction of collagen in the dermis, but after two and three passes, there were sequential graded increases in collagen compaction with loss of the intervening extracellular gel matrix. There was no "collagen shrinkage," and the collagen itself was marginally affected, except for occasional losses in striations at the surface of the specimens. Elastin was very much affected by the laser such that with only one pass, the elastin was abnormal, presenting with a mottled heterogeneous structure. This elastin aberrancy was present in both the papillary and reticular dermis. After one laser pass, fibroblast necrosis was present in the papillary dermis and the reticular dermis (depending on which laser was used), and the extent and depth of necrosis increased with multiple laser passes.     

Hypertrophic scars and keloids: a recurrent problem revisited

Excess scarring caused by pathologically overabundant collagen deposition is a problem known by all surgeons. Such complications to wound healing known as hypertrophic scars and keloids might turn out aesthetically unacceptable to the patient and some scars might even cause anatomic dysfunction. Reviewing the literature in planning a strategy of treatment the surgeon encounters an overwhelming amount of hypotheses on the topic. There seems to be no absolutely effective treatment for hypertrophic scars and keloids and the number of treatment modalities illustrate the lack of understanding concerning this kind of pathologic scarhealing. Most studies have not been well controlled and have produced conflicting results. This review outlines the nature of hypertrophic scars and keloid. Based on a critical assessment of current treatment modalities some guidelines for the choice of treatment is proposed.     

Measurement using a non-contact 3-D measurement system and histopathologic study of surface of skin scar formation after cheiloplasty

As to postoperative scar formation of maxillofacial lesions, a number of authors have reported on the clinical classification and light or electron microscopic observations of hypertrophic scars. However, there has been no quantitative study to evaluate the surface of the postoperative scar and its relevance to changes in histopathology. The purpose of this study was to assess postoperative scar formation on patients with cleft lip quantitatively by using a non-contact 3-D measurement system and to compare the findings with the histopathologic changes. Thirty-six specimens were obtained from patients when they underwent corrective surgery of the lip. The depth of the scar was measured by using a non-contact 3-D measurement system. The results were compared with morphological findings of fibroblasts and collagen fibers of the scar tissues under a light microscope. The results were following as follows: 1. The depth of the CLP group was 181.4 +/- 78.4 microns, significantly higher than 55.7 +/- 24.8 microns of the non-cleft group (p < 0.05). 2. Histologically, the scar, which formed a diffuse mass of irregularly arranged thick collagen fibers, showed a higher value in the depth of the scar than the one which formed a regular pattern. 3. The scar with mature spindle fibroblasts showed a higher value in the depth of the scar than the one with immature round fibroblasts. In conclusion, it was suggested that a non-contact 3-D measurement system is useful for measuring the depth of the scar surface, and the histologic changes of the scar influence the depth.     

Reduction of pain on injection of propofol: a comparison of fentanyl with lidocaine

BACKGROUND: Keloids are the result of a dysregulated wound healing process. They are characterized by the formation of excess scar tissue that proliferates beyond the boundaries of the original wound. Somatic mutations of p53 have been implicated as causal events in up to 50% of all human malignancies. In addition, p53 has been shown to play an important role in controlling cell proliferation and apoptosis. We hypothesize that mutations in p53 can lead to a hyperproliferative state that can result in keloid formation. OBJECTIVE: To detect p53 DNA mutations in tissues and cultured fibroblasts from skin lesions of 7 patients with keloids. DESIGN: The polymerase chain reaction followed by single-strand conformational polymorphism analysis and direct DNA sequencing were used to detect p53 gene mutations. SETTING: The Department of Dermatology, Henry Ford Hospital, Detroit, Mich. PATIENTS: Seven patients with keloids seen for routine surgical excision of their lesions. Normal DNA specimens were obtained from buccal smears and healthy skin samples from these patients. RESULTS: Mutations in the p53 were identified in all patients by polymerase chain reaction followed by single-strand conformational polymorphism analysis and subsequently confirmed by DNA sequencing. A mutation in exon 5 resulting in amino acid substitution was found in 1 of the patients in keloid tissue and cultured keloid fibroblasts (codon 156, CGC-->CCC, arginine-->proline). Frameshift mutations in exons 5 and 6 caused by the insertion or deletion of a nucleotide at different positions were found in 6 patients with keloids in both keloid tissues and cultured fibroblasts. Mutations in exon 4 resulting in amino acid substitution were found in all patients in both keloid tissues and cultured fibroblasts (all in codon 72, CGC-->CCC, arginine-->proline). No p53 mutations were detected in buccal smears or cultured fibroblasts from healthy skin samples of any of the patients. CONCLUSIONS: Focal mutations in p53 may increase cell proliferation and decrease cell death in the dysregulated growth patterns that have been clinically documented. An understanding of the pattern of all growth dysregulation related to keloids may lead to new therapeutic strategies.     

Topical silicone gel sheeting in the treatment of hypertrophic scars and keloids. A dermatologic experience

BACKGROUND: Topical silicone gel sheeting has been used successfully in the management of hypertrophic and keloid scars resulting from thermal burn wounds. METHODS: An open-labelled approach using the silicone gel sheets was performed using hypertrophic and keloid scars secondary to surgical procedures or traumatic insults. RESULTS: The silicone gel sheets resulted in moderate improvement in scar thickness, scar color and was noted to be effective to some degree in all tested. The material was easy to use and painless. CONCLUSION: Topical silicone gel sheeting is an effective method for the treatment of hypertrophic and keloid scars and may be considered useful in the treatment of these difficult cutaneous lesions.