Dichloro-tetrafluoro-ethane as a Freezing Agent

Surgical skin planing is, in the hands of an experienced operator, a safe and highly effective procedure for treating a number of cutaneous defects, most notably pitted acne scars.The operation is facilitated by the use of a new instrument (jet-spray handpiece) which allows the operator to freeze the skin and plane it almost simultaneously, and by a new freezing agent, dichlorotetrafluoro-ethane, which adds to the safety by eliminating the old hazards of inflammability, explosion, and the toxic inhalation of ethyl chloride.The ability to sharply differentiate between keloid and hypertrophic scar is fundamental to surgical skin planing. A hypertrophic scar results from the removal or destruction of the cutaneous appendages (hair follicles, oil and sweat glands and ducts); whereas a keloid is an idiosyncratic response without regard to damage of the appendages.Properly performed surgical planing does not entirely remove these appendages and therefore healing occurs without scarring.     

Matrix metalloproteinase‐2 and ‐9 activities in human keloids,hypertrophic and atrophic scars: a pilot study

Proteolytic degradation of extracellular matrix is one of the principal features of cutaneous wound healing but little is known about the activities of gelatinases; matrix metalloproteinase‐2 (MMP‐2) and matrix metalloproteinase‐9 (MMP‐9) on abnormal scar formation. The aim of this study is to determine collagen levels and the gelatinase activities in tissue from hypertrophic scars, atrophic scars, keloids and donor skin in 36 patients and 14 donors. Gelatinase levels (proenzyme + active enzyme) were determined by ELISA and their activities by gelatin zymography. MMP‐9 activity was undetectable in gelatin zymography analysis. Pro‐MMP‐2 levels (median) were highest in normal skin group 53.58 (36.40–75.11) OD µg^?1 protein, while active MMP‐2 levels were highest in keloid group 52.53 (42.47–61.51) OD µg^?1 protein. The active/pro ratio was the highest in keloid group 0.97 followed by hypertrophic scar, normal skin and atrophic scar groups 0.69 > 0.54 > 0.48, respectively. According to results of our study, the two‐phase theory of the duration of hypertrophic scar and keloid formation can be supported by the data of tissue collagen and gelatinase analysis. This study is the first to relate scar formation relationship in regard to gelatinase activation ratio in a keloid, hypertrophic and atrophic scar patient group which is chosen appropriate in age and sex. Copyright © 2009 John Wiley & Sons, Ltd.     

瘢痕疙瘩及增生性瘢痕中MMP-2、MMP-9的表达

目的探讨基质金属蛋白酶-2、基质金属蛋白酶-9(MMP-2、MMP-9)在瘢痕疙瘩(keloid,Ke)及增生性瘢痕中(hypertrophic scar,HS)的表达。方法免疫组织化学SP法检测MMP-2、MMP-9在20例瘢痕疙瘩、15例增生性瘢痕及10例正常皮肤中的表达,采用图像分析技术对免疫组化结果进行定量分析。结果Ke中MMP-2表达高于正常皮肤(t=2.366,P<0.05),高于HS(t=2.223,P<0.05);MMP-9表达高于正常皮肤(t=3.198,P<0.01),高于HS(t=2.110,P<0.05)。HS中MMP-2表达与正常皮肤无差异(t=0.218,P>0.05),MMP-9表达与正常皮肤无差异(t=1.873,P>0.05)。正常人皮肤仅见MMP-2、MMP-9蛋白的弱阳性或阴性表达。结论MMP-2、MMP-9蛋白的表达与皮肤损伤后的过度增殖及肿瘤化倾向有关。     

Congenital dislocation of the hip

In surgical skin planing steel wire brushes have been largely replaced by the less hazardous diamond chip burs or "fraises" and serrated steel wheels. In addition to acne pits and wrinkling, multiple actinic (senile) keratoses are an important indication for planing. Planing provides a nonscarring method for the treatment of existing keratoses, as well as a prophylaxis against skin cancer by replacing the sun-damaged, precancerous epidermis with new epidermal cells derived from the cutaneous adnexa (pilosebaceous and sweat gland units). There are clinical landmarks indicating the depth of planing which can serve as a guide to the operator and can be correlated with microscopic findings. The results of experiments on the comparative effects of refrigerants on animal and human skin indicate that human facial skin can tolerate considerable freezing with ethyl chloride or dichlorotetrafluoroethane (Freon 114) but that mixtures containing large proportions of the much colder dichlorodifluoromethane (Freon 12) may be undesirable. Refreezing an area of the skin in order to perform a more adequate planing is not considered hazardous.THE REGENERATION OF THE SKIN FOLLOWING PLANING HAS THREE COMPONENTS: Epidermal, adnexal and dermal. The cells of the epidermis and the adnexa are equipotential. A knowledge of the anatomy of the acne pit enables the operator to decide which pits can be benefited by planing and which should be excised before planing. The successful treatment of acne pits of the face by planing in patients having keloids elsewhere on the body is reported.     

Effects of platelet derived growth factor (PDGF) on fibronectin (FN) production by human skin and scar fibroblasts

The fibroblast-type cell found in hypertrophic scars and keloids demonstrates an elevated fibronectin (FN) production, compared to the same type of cell in normal dermis. We wished to determine if the effects of platelet derived growth factor (PDGF) on FN production in these cell types would be equivalent or different. Cell lines were established from the dermis (reticularis) of hypertrophic scars, keloids, uninvolved normal skin adjacent to the lesions, including an assumed normal skin adjacent to a keloid (AS), and normal skin from a different uninjured patient (DS). Each parent tissue from which the cell lines originated was diagnosed histologically. Each hypertrophic scar, keloid and normal adjacent skin, with one exception, showed typical histologic findings confirming the clinical diagnosis. DS was also normal. AS, although assumed to be normal, in fact, demonstrated portions of nodules from the adjacent keloid. All cell lines were grown under standard conditions with subconfluent cells metabolically labeled for radioimmunoassays measuring FN at passage 3 (8 to 9 weeks in culture) in the absence and presence of PDGF. Significant differences in production of FN/cell and FN/PR/cell between two hypertrophic scars and their matched normal skins and for one keloid and its matched normal skin were observed. However, no significant difference was observed between the other keloid and AS, nor between the other hypertrophic scar and DS. PDGF significantly stimulated FN production in 2 of 4 NS cell lines, and in the AS cell line. By FN/cell values, 2 of 5 cell lines from the lesions were inhibited and one was increased. In terms of FN/PR/cell, 1 of 5 cell lines from the lesions was stimulated and the others showed no differences. The mixed results may be attributable to the likelihood that the cell lines represent mixed populations. This study demonstrates the importance of: 1) histological characterization of all parent tissues from which cell lines are derived, and 2) matching cell lines from lesions with cell lines from uninvolved normal dermis, in the same individual.     

Genetic susceptibility to keloid disease and hypertrophic scarring: transforming growth factor beta1 common polymorphisms and plasma levels

Keloid disease and hypertrophic scars are dermal tumors that are often familial and typically occur in certain races. Their exact etiology is still unknown. Transforming growth factor beta1 (TGF-beta1) plays a central role in wound healing and fibrosis and has been implicated in the pathogenesis of keloid disease and hypertrophic scar. The aims of this study were to measure the plasma level of TGF-beta1 in patients compared with controls, and to investigate the association of five common single nucleotide polymorphisms in TGF-beta1 with the risk of keloid disease and hypertrophic scar formation. Platelet-poor plasma levels of TGF-beta1 in 60 patients (15 with hypertrophic scar and 45 with keloid disease) and 18 controls were measured using an enzyme-linked immunoabsorbent assay technique. A polymerase chain reaction-restriction fragment length polymorphism method was used for genotyping TGF-beta1 polymorphisms. DNA samples from 133 patients (101 with keloid disease and 32 with hypertrophic scar) and 200 controls were examined. All patients and controls were Caucasians of Northern European extraction. There was no statistically significant difference in TGF-beta1 plasma levels between patients with keloid disease and hypertrophic scar and controls. There was also no statistically significant difference in genotype or allele frequency distributions between patients and controls for codons 10, 25, and 263 and for -509 and -800 single nucleotide polymorphisms of the TGF-beta1 gene. These results suggest that TGF-beta1 plasma levels and common polymorphisms are not associated with a risk of keloid disease and hypertrophic scar formation. This lack of association may be significant in view of the importance attached to the role of TGF-beta1 in dermal scarring. To the authors' knowledge, this is the first report of a case-control association study in keloid disease and hypertrophic scars using any single nucleotide polymorphisms.     

Periareolar approach for the correction of congenital symmastia

This report elucidates the continued and relatively rare problem of congenital symmastia and its surgical repair without concomitant bilateral breast reduction. This case highlights the use of suction-assisted lipectomy techniques to address the excess fat in the presternal web and a periareolar approach for access to the intermammary space. The periareolar incision allows for the use of a concealed approach and the avoidance of a central scar that could result in hypertrophy or keloid formation, especially in this patient who is more prone to hypertrophic scarring. Furthermore, plication of the central web dermis to the sternal periosteum in a more superior position serves to not only correct the symmastia but also redrape the excess skin and restore the blunted inframammary folds.     

Epithelial–mesenchymal transition in the formation of hypertrophic scars and keloids

Abnormal wound healing is likely to induce the formation of hypertrophic scars and keloids, which leads to dysfunction, deformity, and mental problem in the patients. Despite the advances in prevention and management of hypertrophic scar and keloids, the mechanism underlying scar and keloid formation has not been fully elucidated. Recent insights into the role of the epithelial–mesenchymal transition (EMT) in development, wound healing, stem cell regulation, fibrosis, and tumorigenesis have increased our understanding of the pathophysiology of hypertrophic scarring and keloids and suggested new therapeutic targets. This review summarizes recent progress in the elucidation of the role of EMT in physiologic wound healing and pathologic scar formation. This knowledge will facilitate an understanding of EMT roles in scar formation and shed new light on the modulation and potential treatment of hypertrophic scars and keloids.     

Mathematical modelling of nitric oxide activity in wound healing can explain keloid and hypertrophic scarring

Keloid and hypertrophic lesions are both types of scarring pathologies which arise as a consequence of excess collagen deposition during the wound healing process. The exact mechanism by which this occurs is not understood and currently no effective treatment exists. In this paper, we study the possible role of nitric oxide in excess scar formation. In recent years, the physiological role of this free radical in mammalian tissue has been extensively studied; in particular numerous groups have studied its role in wound healing. We describe a mathematical model which offers a possible explanation for keloid scarring in terms of the presence of higher than normal nitric oxide concentrations related to the fact that nitric oxide stimulates synthesis of collagen by fibroblasts. As a consequence of this, we put forward a suggestion for a treatment strategy involving the surgical excision of the keloid lesion combined with the application of a low-dose nitric oxide inhibitor. In addition, we show that a quasi-steady-state analysis of our model reveals a possible approach to distinguishing between hypertrophic and keloid lesions, a task which has to date proven to be clinically difficult. We also present an extended model which confirms these results in the context of a more complicated and biologically more realistic system. The fuller model demonstrates additional features of keloid and hypertrophic scarring which we were not able to consider in the basic model, and as a consequence further supports our hypothesis that nitric oxide activity could play a key role in keloid scarring.     

Treatment of extensive sternum keloid scar with surgical removal and immediate reconstruction with skin flaps from a combined mammaplasty

We report the case of a 47-year-old woman with a large keloid scar on the sternum who was submitted to a simultaneous scar removal with bilateral breast-reduction mammaplasty. Breast reduction was performed to reduce local skin tension and to provide a skin flap for the full reconstruction of the scar-removal site. The association of these surgical procedures stands as a viable alternative for the reconstruction of the sternum region, producing less keloid scarring.     

Fibronectin (FN) in hypertrophic scars and keloids

Summary Fibronectin (FN) distribution was compared among samples of normal human dermis, hypertrophic scar, keloid, and granulation tissues from deep injuries. Localization was established by use of fibronectin antibodies and the indirect immunofluorescence method. Fresh-frozen tissue was sectioned on a cryostat and examined by epifluorescence. Hypertrophic scar and keloid demonstrated heavy deposition of FN, which conformed to the nodular characteristics of the lesions. Intense localization occurred in granulation tissue over fibroblasts which were stellate and vesiculated, and over small blood vessels. FN-staining was weak in areas over fibroblasts which were more rounded and nonvesiculated. Staining for FN was also minimal over the collagen in normal dermis and the deeper, larger collagen fascicles in the lesions. Fibroblasts cultured from normal dermis, hypertrophic scar, and keloid for 5–6 weeks were intensely stained for FN. Extracellular matrix was heavily positive in cultures from the lesions compared with those from normal dermis.Supported in part by NIH Research Grant 1 R01GM 25159     

Mechanical characterisation of human postburn hypertrophic skin during pressure therapy

Postburn hypertrophic scar commonly occurs among the Chinese resulting from serious burn injuries. A non-invasive method of preventing and controlling such scars is using pressure therapy. Its mechanical properties are used as a quantitative indicator for scar assessment and maturation. The non-linear properties of the skin tissue are characterised in this study by a modulus of elasticity and a percentage extension (strain) at load intensities of 20, 40 and 100 g. The latter is a measure of the scar extensibility while the former the scar stiffness. A correlation is obtained between the clinical scar grading and these mechanical properties. Altogether 300 individual measurements were made on fifteen Chinese patients of ages ranging from 18 to 44 with burn injuries of superficial to whole skin thickness burns which necessitated surgical graft procedures. This in vivo study of the mechanical properties of hypertrophic scar tissue lasted 2 yr.     

超脉冲CO2激光联用康瑞保治疗陈旧性瘢痕临床疗效

目的：观察超脉冲CO2激光术后外用康瑞保凝胶对小面积增生性瘢痕及瘢痕疙瘩的临床疗效。方法：随机将患者分为单一激光治疗组（激光组）、激光加康瑞保治疗组（治疗组）及单一康瑞保治疗组（药物组）,激光组及治疗组每2个月激光治疗一次,6个月后观察瘢痕的面积、硬度及患者瘙痒,紫绷感等自觉症状改善情况进行记分。结果：治疗组总有效率为77．42％,而激光组及药物组总有效率分别为45．45％,44．44％。单纯激光治疗也可明显改善瘢痕的硬度及紧绷感,单纯药物可明显减轻瘙痒感。结论：对陈旧性小面积瘢痕,超CO2激光配合康瑞保疗效明显优于单一用药物或激光治疗。为临床上治疗陈旧性增生性瘢痕及瘢痕疙瘩提供了有效的可供选择的方法。     

Hypertrophic scarring and keloids: pathomechanisms and current and emerging treatment strategies

Excessive scars form as a result of aberrations of physiologic wound healing and may arise following any insult to the deep dermis. By causing pain, pruritus and contractures, excessive scarring significantly affects the patient's quality of life, both physically and psychologically. Multiple studies on hypertrophic scar and keloid formation have been conducted for decades and have led to a plethora of therapeutic strategies to prevent or attenuate excessive scar formation. However, most therapeutic approaches remain clinically unsatisfactory, most likely owing to poor understanding of the complex mechanisms underlying the processes of scarring and wound contraction. In this review we summarize the current understanding of the pathophysiology underlying keloid and hypertrophic scar formation and discuss established treatments and novel therapeutic strategies.     

微小RNA miR-21在皮肤创伤愈合中的研究进展

微小RNA是一类真核细胞中广泛存在的内源性转录后调控分子,其在细胞的增殖、分化、凋亡、迁移等过程中发挥了重要的调控作用。皮肤创伤修复涉及复杂的细胞与分子的相互作用网络。近年来研究表明micro RNAs在皮肤创伤修复中发挥调控作用,引人关注。miR-21作为重要的癌基因是目前研究的最多的miRNAs分子之一,其在皮肤创伤修复中的作用研究也越来越受到重视。研究表明miR-21参与了细胞增殖与迁移、炎症反应、血管生成和细胞外基质合成等重要修复相关事件的调控。因此,阐明miR-21分子在正常皮肤创伤愈合中的作用,厘清miR-21表达失调在修复不足和修复过度中的功能,将深化我们对于皮肤创伤愈合基本理论的认识,并为促进创面愈合与防治修复不足和过度提供潜在的治疗靶点。本文就miR-21分子在正常皮肤创伤修复、慢性难愈性创面和增生性瘢痕中作用的研究进展进行综述展望。     

Low-dose enalapril in the treatment of surgical cutaneous hypertrophic scar and keloid--two case reports and literature review

Hypertrophic scars and keloids are 2 forms of excessive cutaneous scarring that occur in predisposed individuals. The healing process varies greatly among patients, and the risk of a bad scar evolution is unpredictable. Keloids create disfiguring scars with associated erythema and pain or pruritus or restricted range of motion, and are a major cause of morbidity. A fortuitous observation was made by the first author of this study who, at age 54, developed an erythematous and painful postsurgical abdominal keloid scar after undergoing left colectomy for colon adenocarcinoma. Four months later, after treatment with low-dose enalapril (10 mg, once a day) for mild arterial hypertension, her keloid scar rapidly improved and she eventually made a complete recovery. second case involved a 70-year-old female with diabetes who was affected by a long-standing postsurgical abdominal keloid scar of 2 years' duration. She was intentionally treated with the same low dose of enalapril, and, after 6 months of therapy, the bad scar showed marked improvement. We conducted an exhaustive search of the literature pertaining to the wound healing process, specifically to determine whether angiotensin-converting enzyme (ACE) inhibitors have a healing effect on wounds. ACE inhibitors are known to induce reduction of left ventricular collagen content and to attenuate remodeling during the postinfarctual period (thus improving ventricular function), and they have been shown to exert a pulmonary antifibrotic effect. After conducting this literature search, it became apparent that no data on cutaneous scars and ACE inhibitors are available. During the posttraumatic or postoperative stage, it is useful to achieve the best possible aesthetic results and to decrease the risk of a disfiguring keloid scar, thereby avoiding revision surgery; to this purpose, an early treatment with a low dose of enalapril is a possible solution, even if further confirmatory observations are needed.     

Hypertrophic scar: an interruption in the remodeling of repair--a laser Doppler blood flow study.

Soft-tissue dermal loss does not regenerate; instead, it is replaced with scar. The extent of scarring is directly related to the severity of tissue loss (in terms of volume and depth). Commonly, an acute dermal loss will heal with excessive scar, hypertrophic scar. A hypertrophic scar is elevated but is contained within the boundaries of the initial injury. Hypertrophic scars have a reddish appearance, indicating an elevated local circulation. A laser Doppler blood flow monitor was employed to measure blood flow changes in healed wounds. It was speculated that local circulation in a developing hypertrophic scar would be elevated. Patients with recently healed wound sites were monitored and exhibited an average blood flow reading of 365 +/- 325 mV (n = 131). This average value, ranging from 98 to 1450 mV, was 18 times greater than the average reading from normal skin, which was 43 +/- 13 mV (n = 212). Blood flow declined to 32 +/- 21 mV (n = 7) at 16 to 18 weeks (74 percent of normal skin values) in healed wounds that developed normal scar. However, a closed wound that developed into a hypertrophic scar had a blood flow reading of 148 +/- 78 mV (n = 59) at 16 to 18 weeks. This value was three times greater than in normal skin and four times greater than in normal scar. At 38 to 50 weeks postinjury, hypertrophic scar remained elevated (102 +/- 34 mV; n = 10). Hypertrophic scars sustain an elevated blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nitric oxide produced by iNOS is associated with collagen synthesis in keloid scar formation

Nitric oxide (NO) has emerged as an important mediator of many physiological functions. Recent reports have shown that NO participates in the wound healing process, however, its role in keloid formation remains unclear. This study aimed to investigate the effect of NO on keloid fibroblasts (KF) and to determine the levels of inducible nitric oxide synthase (iNOS) expression in clinical specimens of keloid. Scar tissue from seven keloid patients with matched perilesion skin tissue controls was studied for inducible nitric oxide synthase expression and location. In addition, primary keloid and normal scar skin fibroblast cultures were set up to investigate the effects of NO in inducing collagen type I expression. Inducible nitric oxide synthase expression, and NO production were elevated in keloid scar tissues but not in matched perilesion skin tissues. Furthermore, exposure of KF to exogenous NO resulted in increased expression of collagen type I in a dose-dependent manner. NO exposure also induced time-course dependent collagen I expression that peaked at 24h in KF. Taken together, these results indicate that excess collagen formations in keloid lesion may be attributed to iNOS overexpression.     

Spatiotemporal expression of periostin during skin development and incisional wound healing: lessons for human fibrotic scar formation

Differentiation of fibroblasts to myofibroblasts and collagen fibrillogenesis are two processes essential for normal cutaneous development and repair, but their misregulation also underlies skin-associated fibrosis. Periostin is a matricellular protein normally expressed in adult skin, but its role in skin organogenesis, incisional wound healing and skin pathology has yet to be investigated in any depth. Using C57/BL6 mouse skin as model, we first investigated periostin protein and mRNA spatiotemporal expression and distribution during development and after incisional wounding. Secondarily we assessed whether periostin is expressed in human skin pathologies, including keloid and hypertrophic scars, psoriasis and atopic dermatitis. During development, periostin is expressed in the dermis, basement membrane and hair follicles from embryonic through neonatal stages and in the dermis and hair follicle only in adult. In situ hybridization demonstrated that dermal fibroblasts and basal keratinocytes express periostin mRNA. After incisional wounding, periostin becomes re-expressed in the basement membrane within the dermal-epidermal junction at the wound edge re-establishing the embryonic deposition pattern present in the adult. Analysis of periostin expression in human pathologies demonstrated that it is over-expressed in keloid and hypertrophic scars, atopic dermatitis, but is largely absent from sites of inflammation and inflammatory conditions such as psoriasis. Furthermore, in vitro we demonstrated that periostin is a transforming growth factor beta 1 inducible gene in human dermal fibroblasts. We conclude that periostin is an important ECM component during development, in wound healing and is strongly associated with pathological skin remodeling.     

Keloids in rural black South Africans. Part 1: general overview and essential fatty acid hypotheses for keloid formation and prevention

In the first part of this study a general overview on the hypertrophic scar and keloid phenomena regarding history, epidemiology, histopathology and aetiology, in general, together with an essential fatty acid approach as basis for hypotheses of keloid formation and prevention are given. Upon reviewing the literature in planning a strategy for prevention and treatment of keloids, one encounters an overwhelming amount of hypotheses on this topic. Based on a preliminary study on total fatty acid compositions in keloids, compared with normal skin of keloid prone and non-keloid prone patients, there can be argued as follows: an essential fatty acid deficiency of precursors and inflammatory competitors for arachidonic acid may be a factor in the multifactorial aetiology of keloid formations, and apart from a local essential fatty acid deficiency in the wound area, nutrition may also be a contributing factor in rural black South Africans. To confirm or refute the stated hypotheses of the role of essential fatty acids in keloid formation and prevention (outlined in this part of the study), dietary questionnaires and blood (plasma and red blood cell) phospholipid analyses for general information and true fatty acid intake and metabolism, respectively, in the diets of these patients (outlined in part II of this study), as well as a lipid model for keloid formations regarding phospholipids, triglycerides, cholesterol esters and free fatty acids (outlined in part III of this study), are given. The purpose of this comprehensive fatty acid study was an attempt to assess the enigma surrounding keloids and to end the nightmare of the plastic and reconstructive surgeon, since these dermal tumours are notoriously recurrent.