Medial lower leg perforators: An anatomical study of their distribution and characteristics.

PURPOSE: The integument of the medial lower leg is underestimated as a donor site for local and distant reconstructions. Comprehensive knowledge of its perforator anatomy is lacking. This study aims to determine perforator location and characteristics and to compare these regarding the proximal, middle and distal third of the medial lower leg. MATERIALS AND METHODS: The medial lower leg region (MLLR) of 16 cadavers was delineated and investigated after injecting the popliteal artery with acrylic paint. Following dissection, all perforators larger than 0.3 mm were localized and mapped. Their course, source vessel, length and diameter were subsequently documented. RESULTS: Overall, 122 perforators were found, 102 (83.6%) originating from the posterior tibial artery, 16 (13.1%) from the medial sural artery and 4 (3.3%) from the anterior tibial artery. A mean of 7.6 ± 2.4 perforators (range 4-13) per MLLR was found. Most perforators (42.6%) were localized in the distal third of the MLLR, followed by the middle (36.9%) and proximal third (20.5%). The largest and longest perforators were found in the proximal third of the MLLR (diameter 1.4 mm, length 9.1 cm), followed by the middle and distal third respectively. Of all musculocutaneous perforators, the majority (78.6%) was located in the middle third of the MLLR. Of all septocutaneous perforators, most (55.3%) were found in the distal third of the MLLR. A small number of unexpected anatomical variants were found. CONCLUSION: In each third of the MLLR different perforator characteristics were found. Knowledge of these characteristics can be used to direct the reconstructive plan. © 2016 Wiley Periodicals, Inc. Microsurgery 37:319-326, 2017.

Comparison of three different incision techniques in A1 pulley release on scar tissue formation and postoperative rehabilitation.

INTRODUCTION: The optimal surgical approach for trigger finger release remains controversial in hindsight of postoperative rehabilitation as well as scar tissue formation. In this study, we comparatively evaluated the outcome of three different types of skin incision by employing the "Disability of the Arm Shoulder and Hand Score" (DASH) and by quantitative ultrasound measurements of scar tissue volume. MATERIALS AND METHODS: Thirty patients (32 triggerfingers) were enrolled in this study and randomly assigned to one of three groups: incision placed (1) transversal in distal palmar crease, (2) transversal and 2 mm distal from distal palmar crease, (3) longitudinally over MCP joint without crossing the distal palmar crease. Patients characteristics were noted and DASH scores were retrieved at four time points, (1) preoperatively (baseline), (2) 1 month, (3) 3 months, (4) 12 months postoperatively. Scar volume formation was assessed by ultrasound at 3 months postoperatively in 28 patients. RESULTS: All groups showed a significant reduction in DASH values at 3 and 12 months postoperatively when compared to their own baseline levels. Group 3 showed the fastest and most pronounced reduction in DASH values at 1 month. Scar tissue formation was almost 57 % increased in group 1 vs group 2 and 3, however, not significant. CONCLUSION: There is no clear benefit of one incision technique over another. However, based on scar volume parameters, the significant faster recovery in the first month and the surgical ease of exposure and wound closure inclines us to favor the longitudinal incision (group 3) in future patients.

Prospective and randomised evaluation of the protease-modulating effect of oxidised regenerated cellulose/collagen matrix treatment in pressure sore ulcers.

In chronic wounds, excess levels and activity of proteases such as elastase and plasmin have been detected. Oxidised regenerated cellulose/collagen matrix (ORC/collagen matrix) has been reported to ameliorate the wound microenvironment by binding and inactivating excess proteases in wound exudates. In this study, the levels and activity of elastase and plasmin in wound exudates of pressure sore ulcers were measured to determine the beneficial effect of ORC/collagen matrix treatment compared with control treatment with a foam dressing. A total of 33 patients with pressure sores were enrolled in the study and were followed up for 12 weeks after treatment. Ten control patients were treated with a foam hydropolymer dressing (TIELLE® , Systagenix), and the remaining 23 patients were treated with ORC/collagen matrix plus the foam dressing (TIELLE® , Systagenix) on top. Wound assessments were carried out over 12 weeks on a weekly basis, with dressing changes twice a week. Ulcers were photographed and wound exudates were collected on admission and at days 5, 14 and then every 14 days to provide a visual record of any changes in appearance of the ulcer and healing rate and for biochemical analysis of the wound. The levels and activity of elastase and plasmin were measured in wound exudates. Statistical analysis was performed using ANOVA and Bonferroni's post hoc test with P-values <0·05 considered to be significant. Compared with controls, ORC/collagen matrix-treated pressure sore wounds showed a significant faster healing rate, which positively correlated with a decreased activity of elastase and plasmin in wound exudates. No signs of infection or intolerance to the ORC/collagen matrix were observed.

Expression of leptin, leptin receptor, and connective tissue growth factor in degenerative disk lesions in the wrist.

PURPOSE: The purpose of this study was to identify whether leptin and connective tissue growth factor (CTGF) occur in the degenerative fibrocartilage disk and whether cartilage cells express leptin receptors. METHODS: The study included 23 patients diagnosed with degenerative articular disk tears of the triangular fibrocartilage (TFC) (Palmer type 2C). Patients were divided into 2 groups based on ulna length: 1 group consisted of patients with an ulna-positive variance (group A), and the other group included patients with ulna-negative or -neutral variance (group B). After arthroscopic debridement of the TFC, histologic sections of biopsy specimens were prepared. The biopsy specimens were immunohistochemically analyzed, and the quantity of leptin-, CTGF-, and leptin receptor-positive cells was assessed. RESULTS: Cells positive for leptin, leptin receptor, and CTGF were found. The number of cells positive for leptin was significantly increased in specimens of patients with an ulna-negative variance (group B). In contrast, no significant difference was found for leptin receptor and CTGF in biopsy specimens of patients with ulna-positive or ulna-negative/neutral variance. The inner, middle, and outer zones of the disk do not express significantly different quantities of marker-positive cells. CONCLUSIONS: Degenerative fibrocartilage disk tissue cells exhibit leptin receptors and are exposed to the markers leptin and CTGF, providing evidence of a local paracrine system and regenerative processes. Cells of disks from patients with an ulna-neutral/negative length express significantly higher numbers of leptin-positive cells. LEVEL OF EVIDENCE: Level II, diagnostic study.

Severe frostbite injury in a 19-year-old patient requiring amputation of both distal forearms and lower legs due to delayed rescue: a need for advanced accident collision notification systems?

Frostbite injury is a rare but severe injury especially when rescue triage is prolonged. We here report the case of a 19-year-old male patient with severe frostbite injuries requiring amputation of both distal forearms and both lower legs due to delayed admission to medical care. This case demonstrates that even mild ambient temperatures can cause deleterious injuries if the exposure time is long enough paralleling our knowledge of burn trauma. Immediate admission to medical care is, therefore, paramount and GPS-based automated accident collision notification systems would therefore be of great benefit especially in rural areas.

Revitalization of cortical bone allograft by application of vascularized scaffolds seeded with osteogenic induced adipose tissue derived stem cells in a rabbit model.

BACKGROUND: Adipogenous tissue derived stem cells (ASC) are available in abundance in the human body and can differentiate in the presence of lineage-specific induction factors, for example, in myogenic, adipogenic, chondrogenic and osteogenic cells. The aim of this study was to evaluate the impact of osteogenic induced ASC's (O-ASC) on revascularization and cellular repopulation of avital cortical bone employing a vascularized bovine scaffold. METHODS: An inguinal arterio-venous bundle was dissected in the groin of female white New Zealand rabbits (n = 6) and placed centrally inside an O-ASC seeded scaffold via a central drill hole. In the same surgical session this construct was placed into a segment of avital cortical bone allograft from a donor rabbit. Unseeded scaffolds that were implanted and treated in the same fashion served as controls (n = 6). In order to prevent external revascularization, all constructs were wrapped in silicon foil and finally implanted in the rabbits' groin. Three months later, the constructs were explanted and investigated for vascularization of (a) the scaffold (b) the surrounding bone allograft. Histological stainings to determine cell growth, cellular repopulation of the scaffold and the cortical bone matrix, as well as inflammatory parameters were carried out. RESULTS: O-ASC seeded scaffolds showed a significant increase in new vessel formation in the scaffold as well as in the bone allograft compared to unseeded scaffolds. Furthermore, new vital osteocytes as a sign of cellular repopulation inside the bone allograft were found only in the treatment group. Vital chondrocytes were only found in the O-ASC seeded scaffolds as well. CONCLUSION: The presence of O-ASC significantly induce neo-vascularization and osteocytic repopulation of previously avital bone allograft as opposed to unseeded scaffolds in a rabbit model. Hence, this model might be of relevant value for future bone tissue engineering research and for re-vitalizing marginally nourished bone such as in avascular bone necrosis.

Suprathel-antiseptic matrix: in vitro model for local antiseptic treatment?

Acetic acid is a traditional antiseptic agent that has been used for more than 6000 years. The main goal of this study was to demonstrate the suitability of Suprathel (PolyMedics Innovations GmbH, Denkendorf, Germany) in combination with various antiseptic agents to create an "antiseptic-matrix" especially designed for problematic microorganisms such as Proteus vulgaris, Acinetobacter baumannii, or Pseudomonas aeruginosa, which are frequently associated with burns. The study was designed to test the in vitro antimicrobial effect of a "Suprathel-antiseptic matrix" (Suprathel combined with acetic acid 3%, povidone-iodine 11% [Betaisodona], polyhexanide 0.04% [Lavasept], phenoxyethanol 2%/octenidine dihydrochloride 0.1% [Octenisept], mafenide acetate 5%, and chlorhexidine gluconate 1.5%/cetrimid 15% [Hibicet]). As a means to assess the typical bacterial spectrum of a burn unit, the following Gram-negative and Gram-positive bacteria strains were tested: Escherichia coli, P vulgaris, P aeruginosa, A baumannii, Enterococcus faecalis, Staphylococcus epidermidis, Staphylococcus aureus, methicillin-resistant S aureus, and ß-hemolytic streptococcus groups A and B. The tests showed a positive bactericidal effect of the Suprathel-antiseptic matrix, particularly with problematic Gram-negative bacteria such as P vulgaris, P aeruginosa, and A baumannii, except for the combination of Suprathel and mafenide acetate. It can be concluded that Suprathel-antiseptic matrix appears to be suitable as a local antiseptic agent, but clinical studies need to be performed to confirm these in vitro observations. The authors' previous studies have shown that acetic acid demonstrates a wide antiseptic spectrum for microorganisms typically found in burn patients. The combination of Suprathel and acetic acid worked well in this study and appears to be promising for future clinical application.

Suprathel-acetic acid matrix versus acticoat and aquacel as an antiseptic dressing: an in vitro study.

BACKGROUND: The treatment of burn wounds is still a challenge regarding the management of antiseptic wound conditioning. Especially, in the United States, silver-containing dressings, such as Acticoat and Aquacel are frequently used. Because silver-containing dressings have well-known drawbacks such as an antimicrobial lack against Pseudomonas aeruginosa, we sought to develop an alternative dressing method. In previous studies, we could demonstrate the excellent antiseptic properties of acetic acid against common burn unit germs, and in another study, the feasibility and suitability of a Suprathel-acetic acid matrix as an antiseptic dressing. MATERIALS AND METHODS: This study was designed to test the in vitro antimicrobial effect of a Suprathel-acetic acid matrix versus Acticoat and Aquacel. To cover the typical bacterial spectrum of a burn unit, the following Gram-negative and Gram-positive bacteria strains were tested: Escherichia coli, extended-spectrum beta-lactamase-positive Klebsiella pneumoniae, P. aeruginosa, Acinetobacter baumannii, Enterococcus faecalis, and methicillin-resistant Staphylococcus aureus. RESULTS: The tests showed an excellent bactericidal effect of the Suprathel-acetic acid matrix particularly with problematic Gram-negative bacteria such as Proteus vulgaris, P. aeruginosa, and Acinetobacter baumannii. The efficiency was superior to that of Acicoat and Aquacel. CONCLUSIONS: Our results support the notion, that the Suprathel-acetic acid matrix has an excellent bactericidal effect and therefore seems to be suitable as a local antiseptic agent in the treatment of burn wounds.

Reverse homodigital dorsoradial flap for thumb soft tissue reconstruction: surgical technique.

A variety of local flaps are described for reconstruction of soft tissue defects of the thumb. Restored sensibility, low donor-site morbidity, full restoration of function and range of motion, and an acceptable aesthetic outcome are requirements in thumb reconstruction. Reverse homodigital dorsal radial flap of the thumb provides most of these requirements and allows for dependable coverage of radiopalmar or dorsal thumb defects without affecting other digits.

Necrotizing fasciitis of the extremities: 34 cases at a single centre over the past 5 years.

BACKGROUND: Worldwide the incidence of necrotizing fasciitis (NF) is on the rise. This rapidly progressive infection is a true infectious disease emergency due to its high morbidity and mortality. The mainstay of therapy is prompt surgical debridement, intravenous antibiotics, and supportive care with fluid and electrolyte management. Because of its high mortality rate, patients are increasingly referred to burn centres for specialized wound and critical care issues. METHODS: A retrospective chart review was performed of 34 consecutive patients over a 5-year period with NF of the upper and/or lower extremities that required surgical debridement and reconstruction. RESULTS: The overall survival rate was 96%, with an average length of hospital stay of 64.0 ± 5.5 days. The time until the first operation was 1.3 days. The average age of the patients was 56.7 ± 10.6 years. The patients averaged 1.6 relevant comorbidities. One patient who had five comorbidities died. The affected total body surface (TBS) averaged 8.2 ± 2.1%. CONCLUSION: Early recognition and treatment remain the most important factors influencing survival in NF. Yet, early diagnosis of the condition is difficult due to its similarities with other soft-tissue disorders. Repeated surgical debridement and incisional drainage continues to be essential for the survival. However, these infections continue to be a source of high morbidity, mortality and significant healthcare resource consumption. These challenging patients are best served with prompt diagnosis, immediate radical surgical debridement and aggressive critical care management. Referral to a major burn centre may help to provide optimal surgical intervention, wound care and critical care management.

Risk factors for compartment syndrome in traumatic brachial artery injuries: an institutional experience in 139 patients.

BACKGROUND: The brachial artery is the most common vascular injury encountered in upper extremity trauma. If not treated promptly, it can result in compartment syndrome (CS) and long-term disability. Here, we report an institutional experience of traumatic brachial artery injuries and establish risk factors for the development of upper extremity CS in this setting. METHODS: A retrospective review of 139 patients with traumatic brachial artery injury from 1985 to 2001 at a single institution. Patients were divided into two cohorts, those with evidence of CS and those without CS (NCS), for comparison. RESULTS: One hundred thirty-nine patients presented with traumatic brachial artery injuries (mean age, 28.4 years). Twenty-nine patients (20.9%) were diagnosed with upper extremity CS, and 28 of these patients underwent fasciotomy on recognition of their CS. Seven patients (6.4%) in the NCS cohort underwent fasciotomy as a result of absent distal pulses on initial examination. Mean follow-up was 51.6 days. Two patients required revision of their arterial repair, and one patient underwent amputation. The risk of CS was increased in the presence of combined arterial injuries (p = 0.03), combined nerve injuries (p = 0.04), motor deficits (p < 0.0001), fractures, and increased intraoperative blood loss (p = 0.001). Multivariate logistic regression performed on these variables revealed that elevated intraoperative blood loss, combined arterial injury, and open fracture were independent risk factors for the development of CS (OR 1.12, 5.79, and 2.68, respectively). CONCLUSION: Prompt evaluation and management of traumatic brachial artery injuries is important to prevent CS, which can lead to functional deficits. In the setting of combined arterial injury, open fracture, and significant intraoperative blood loss, prophylactic fasciotomy should be considered.

A prognostic model for the risk of development of upper extremity compartment syndrome in the setting of brachial artery injury.

A potentially devastating sequela of brachial artery injury in the setting of upper extremity trauma is the development of compartment syndrome (CS). We performed a retrospective review of 139 trauma patients with brachial artery injury from 1985-2001. Objective characteristics of each case were extracted and analyzed using multivariate logistic regression. Three variables were found to be significant in the final model: estimated intraoperative blood loss as a continuous variable, and presence of a multiple arterial injury and presence of an open fracture as categorical variables. Odds ratio were 1.12, 5.79, and 2.68, respectively. We used these variables to create a summative score for the development of CS with weights assigned proportional to the adjusted odds ratio. Odds of having CS for subjects in group 2 and group 3 are 5.3 and 15.1 times the odds for subjects in group 1, respectively. Applying multivariate regression analysis to the largest series of brachial artery injuries to date, we have developed a predictive scoring model of CS.

The use of a semiocclusive dressing reduces epidermal inflammatory cytokine expression and mitigates dermal proliferation and inflammation in a rat incisional model.

Occlusive wound dressings are utilized clinically to accelerate wound healing and improve the final appearance of scars. In vivo and in vitro evidence suggests that one mechanism for this effect is maintenance of normal hydration in the epidermis, although the molecular signals remain uncharacterized. We sought to elucidate histological changes and some of the molecular signals involved in this effect in a rat model of wound semiocclusion. We utilized a rat linear incision model with surgical tape occlusion. Histological stains and quantitative real-time PCR analysis were used to characterize the cellular and molecular effects of semiocclusion on the wound healing response. Semioccluded wounds demonstrated decreased epidermal thickness and cellularity and less mitotic epidermal activity when compared with nonoccluded control wounds. Associated dermal cellularity was similarly attenuated by semiocclusion. Finally, levels of proinflammatory cytokines interleukin-1-alpha and tumor necrosis factor-alpha were significantly decreased on postoperative day 3 at the transcriptional level when compared with nonoccluded wounds. Semiocclusive wound treatments significantly decrease epidermal thickness, cellularity, mitotic activity, and dermal cellularity as well as transcriptional levels of important epidermal mediators of inflammation in a rat incisional wound model.

Uroguanylin inhibits proliferation of pancreatic cancer cells.

OBJECTIVE: The peptide hormones guanylin and uroguanylin and their receptor, guanylate cyclase C (GC-C), are expressed in pancreatic duct cells. In colon cancer, guanylin peptides are shown to exert strong anti-tumor activity through the GC-C pathway. The objective of this study was to analyze the role of guanylin and uroguanylin in human pancreatic cancer. MATERIAL AND METHODS: Quantitative real-time polymerase chain reaction (QRT-PCR) was used to show the expression of guanylin, uroguanylin and GC-C in specimens of human pancreatic cancer, chronic pancreatitis donor and in pancreatic tumor cell lines. The presence of guanylins and GC-C in tumor cell lines and in pancreatic cancer tissues was shown by immunofluorescence and immunohistochemistry. The effect of guanylin and uroguanylin on cell cycle and cell death of pancreatic cancer cells was investigated by fluorescence activated cell sorter (FACS) analysis using annexin and propidium iodide. In addition, the growth inhibitory effect of guanylins on pancreatic cancer cells was assessed using the MTT assay. RESULTS: Guanylin, uroguanylin and GC-C were expressed at mRNA and protein levels in pancreatic cancer and cancer cell lines. As shown by QRT-PCR, GC-C expression was significantly up-regulated in pancreatic cancer compared with that in healthy pancreatic tissues (p<0.00001) and chronic pancreatitis (p<0.05). Guanylin and uroguanylin were not up-regulated in pancreatic cancer. The MTT assay revealed significant inhibition of pancreatic cancer cell proliferation by uroguanylin in a dose-dependent fashion, whereas Panc1 and Capan1 cell lines were significantly inhibited already at the lowest uroguanylin concentration (2 nM, p<0.05). CONCLUSIONS: Our data suggest therapeutic properties of uroguanylin in pancreatic cancer via GC-C-dependent mechanisms. In addition, determination of GC-C expression might be a useful marker for differentiation between pancreatic cancer and chronic pancreatitis.

The double-pedicled dorsal-metacarpal-artery (dpDMCA) flap of the hand: a novel DMCA-derived flap.

The dorsal-metacarpal-artery (DMCA) flap in its standard or extended version is considered as the working horse to cover dorsal soft tissue finger defects with exposed extensor tendon or bone. We hereby present a clinical case of an 80-year-old male patient who is right-handed and sustained a soft tissue defect of the proximal dorsal aspect of his left 5th finger and the postoperative outcome employing a modified transposition flap. The double-pedicled DMCA flap (dpDMCA flap) of the hand poses in adequate clinical scenarios a comparably fast and safe solution to cover dorsal finger defects extending just distal to the PIP joint. To the best of our knowledge, this is the first report of a DMCA-based flap with a double pedicle to cover soft tissue defects at the dorsum of the hand. LEVEL OF EVIDENCE: Level V, therapeutic study.

Markers of blood coagulation and fibrinolysis in patients with early and delayed microsurgical reconstructions in the lower extremities.

BACKGROUND: In this study, markers of coagulation and fibrinolysis were assessed during early and delayed microsurgical reconstruction in patients with traumatic defects of their lower legs to analyse whether an imbalance of the hemostasis after trauma might predispose the development of vascular complications. METHODS: The prospective study included 70 patients. In 35 patients, surgery was performed within 72 hours after injury. In 35 other patients, delayed free flap transfer was performed between 14-21 days after trauma. In each group, reconstruction was performed with a fasciocutaneous anterior-lateral thigh flap (ALT, n = 18) or a myocutaneous flap (latissimus dorsi flap; n = 17). Blood samples were collected preoperatively, intraoperatively, and 3, 6, 12, 24, 36, 48, 72, 96 and 120 hours after the operation. Analysed parameters included markers of coagulation such as prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin III-complex (TAT), and antithrombin, as well as fibrinolysis markers such as plasminogenactivator inhibitor-I (PAI-1), tissue-plasminogenactivator (t-PA), and plasminogen. RESULTS: Preoperatively, levels of F1 + 2, TAT, and PAI-1 were significantly higher in patients with delayed reconstruction (p < .05). Patients with later vascular complications in this group (n = 5) presented a significant higher concentration of TAT, F1 + 2, and PAI-1 (p < .05). Twelve and 24 hours after free flap surgery, patients with vascular complications presented significant elevated levels of these markers (p < .05). CONCLUSIONS: Patients with delayed free flap surgery after lower leg trauma present a hypercoagulable state in their blood due to activation of the coagulation system and hypofibrinolysis. Early reconstruction might minimise the risk of flap failure caused by hypercoagulability.

Hypertrophic scar model in the rabbit ear: a reproducible model for studying scar tissue behavior with new observations on silicone gel sheeting for scar reduction.

Hypertrophic scarring poses a clinically relevant problem as it can be cosmetically disfiguring and functionally debilitating. A lack of animal models has hindered an understanding of the pathogenesis and development of new treatment strategies therefore has largely been empiric. Our group has developed a unique hypertrophic scar (HS) model in the rabbit ear. The model has been reproducible, quantifiable, and measurable over a time period of 1 month. We describe the development as well as the reliability and responsiveness of this model to different therapeutic agents, such as TGF-beta blockade, silicone occlusion, and application of collagen-synthesis inhibitors. Moreover, it has given insights into the mechanism of action of silicone sheeting occlusive treatment and ultimately suggests that the epidermis plays a critical role in the development of HS. Additionally, we will present new data supporting the importance of the epidermis and further clarify the mechanism of action of silicone sheeting. When a semi-occlusive polyurethane film was left in place for an additional time period, scar formation was reduced. HSs of this model covered with silicone sheets and five layers of Tegaderm showed a significant scar reduction by 80% compared with wounds with only one layer of Tegaderm. The HS model in the rabbit ear is a highly reliable, responsive, and practical model for studying scar tissue behavior. Furthermore, our data suggest that the degree and the duration of occlusion are most important for reducing scar tissue formation.

Alteration of Smad3 signaling in ischemic rabbit dermal ulcer wounds.

Impaired reepithelialization is a hallmark of chronic, ischemic wounds; however, the pathogenesis of the delayed reepithelialization in these wounds remains poorly understood. Transforming growth factor beta is involved in both the normal and hypoxic wound-healing response and exogenous overexpression of Smad3, which has been known to accelerate reepithelialization. Recently, it was shown in the rabbit ear dermal ulcer model that Ad-Smad3 injection enhanced reepithelialization and granulation tissue formation suggesting a positive effect of Smad3 on wound healing. However, little is known about the role of Smad3 in the ischemic wound healing process. In this study, we examined the effect of Smad3 in an ischemic wound model. Ad-Smad3 or Ad-LacZ (10(8) pfu/wound) was injected into either ear of white New Zealand rabbits. Twenty-four hours later, these ears were rendered ischemic using an established model, and four 7 mm full-thickness punch wounds were made on each ear. Histological evaluation showed a significant increase in reepithelialization parameters in Ad-Smad3-transfected wounds (p<0.01). In contrast, granulation tissue parameters were not affected by Smad3 in ischemia. Smad4 and Smad7 mRNA-expression was not affected by Smad3 overexpression. Connective tissue growth factor protein was up-regulated under ischemic conditions but was unaffected by Smad3 transfection in both ischemic and nonischemic wounds. Our results suggest an enhancing effect of Smad3 on reepithelialization in an ischemic wound model that, in turn, might provide novel therapeutic options. Furthermore, the lack of alteration of Smad-dependent intermediates by Smad3 overexpression suggests the activation of Smad-independent pathways in ischemia.

Reconstruction of a recurrent first dorsal web space defect using acellular dermis.

Oncologic defects of the hand can be problematic for the reconstructive surgeon. These defects may require a delay in definitive coverage until clear margins of resection can be obtained, which can result in a prolonged period of painful dressing changes and increased risk of soft-tissue infection. In addition, reconstructive options for oncologic defects are often limited to skin grafting, which can yield functional deficits secondary to contracted healing. Currently, there is no definitive method for preventing skin graft contracture; however, acellular dermis has been proposed as a biomechanical scaffold to enhance subsequent skin graft healing and slow this functionally debilitating process. Here, we present a patient with recurrent melanoma of the first dorsal web space. After re-resection of the melanoma, the 11 cm x 5 cm defect was reconstructed using acellular dermis as temporary coverage to allow ample time for permanent section results. Ten days later, after confirming negative margins of resection, a split-thickness skin graft (STSG) was applied over the vascularized neo-dermis. Follow-up clinical examination and the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaires were used to assess outcome. At 7 months, the patient had no recurrence of melanoma and a DASH functional reduction of only 6.9%. After approximately 18 months, the patient's wounds had healed with excellent cosmetic and functional results, without any evidence of a web space contracture. These observations suggest that acellular dermis is a useful adjunct for wound coverage of the hand, particularly in areas of functional importance, such as the first dorsal web space.

Hydrated keratinocytes reduce collagen synthesis by fibroblasts via paracrine mechanisms.

Regulating collagen metabolism can control hypertrophic scars in cutaneous wounds. Hypertrophic scars can be reduced by occlusive dressings such as silicone sheeting; however, their mechanism is still unknown. We hypothesized that hydration of keratinocytes reduces the collagen secretion of fibroblasts by modifying the cytokine levels. Stratified human epidermal keratinocytes and confluent human dermal fibroblasts were co-cultured serum free for 72 hours. Keratinocytes were either kept at the air interface or hydrated. Messenger RNA (mRNA) levels of interleukin-1 (IL-1)alpha, IL-1beta, tumor necrosis factor alpha (TNF-alpha), keratinocyte growth factor (KGF), and procollagen-1 were analyzed by real-time reverse transcription-polymerase chain reaction. Secretion of cytokines into conditioned media was quantified by enzyme-linked immunosorbent assay and collagen content by Western blot. The content of collagen-I decreased by 44% in the presence of hydrated keratinocytes. Co-culture with air-treated keratinocytes decreased collagen-I only by 23%. Co-cultured hydrated keratinocytes had significantly higher TNF-alpha mRNA (172%) than hydrated keratinocytes. At the protein level, there was an overall trend toward increased TNF-alpha levels in hydrated cultures. IL-1beta secretion decreased significantly under hydration (42% monoculture, 58% co-culture). Co-culture stimulated a 240% increase of KGF mRNA in fibroblasts compared with monocultured fibroblasts. Fibroblasts secreted 4.5-fold more KGF in hydrated co-cultures and sixfold more KGF in air-treated co-cultures. Hydration of keratinocytes modifies important paracrine interactions between keratinocytes and fibroblasts and reduces collagen-1, which supports the hypothesis that hydration of the epidermis and restoration of water barrier function play an important role in scar formation.