The "drumhead" graft repair of deep nasal alar defects.

BACKGROUND: Extirpation of tumors on the perialar region often results in deep surgical defects. The nares and internal nasal valves are supported not just by alar cartilage, but also by the suspension effect of the overlying skin and subcutaneous tissue. Surgical loss of tissue may result in inward collapse of the nasal vestibule with resultant difficulty in breathing. The use of full-thickness skin grafts (FTSGs) on deep alar defects commonly results in a sunken or depressed graft that is functionally and cosmetically unacceptable. OBJECTIVE: We describe a novel technique that enables the use of FTSGs in the repair of deep nasal alar defects through the application of an overlying, rigid plastic suspension strut coupled with an undersized graft. RESULTS: The drumhead FTSG is effective in preventing collapse of the nasal vestibule as well as undesirable contour irregularities due to a depressed or sunken graft. Patients were seen at 1 week, 4 weeks, and 3 months postoperatively. At each time point, there was no nasal vestibular collapse and only very slight graft depression, which replicated the normal mild concavity of the alar crease region. All patients had excellent functional and cosmetic outcomes. No adverse effects were noted. CONCLUSION: The "drumhead" graft is a novel technique, which enables the use of FTSGs for deep alar defects by inhibiting undesirable depression of the graft and preventing collapse of the nasal vestibule.

Diffuse dermal angiomatosis.

Diffuse dermal angiomatosis (DDA) is an acquired, benign vascular proliferation characterized clinically by poorly circumscribed, violaceous, livedoid plaques with frequent ulceration. Histologically, a diffuse interstitial proliferation of CD31-positive endothelial cells is present within the papillary and reticular dermis. Endothelial atypia, atypical mitoses, and vasculitis are lacking. We describe a case of DDA in a 53-year-old man with peripheral vascular atherosclerosis that resolved following revascularization. Early correction of the associated ischemic peripheral vascular disease promotes resolution of this unusual clinicopathologic entity.

Bullous Sweet's syndrome in congenital neutropenia: association with pegfilgrastim.

Sweet's syndrome is an acute febrile neutrophilic dermatosis marked by attacks of painful, plaque-forming inflammatory papules accompanied by fever, arthralgias, peripheral leukocytosis, a diffuse dermal neutrophilic infiltrate, and prompt resolution of symptoms and lesions with glucocorticoid therapy. There are many reports of drug-induced Sweet's syndrome to various medications including all- trans -retinoic acid, carbamazepine, hydralazine, levonorgestrel/ethinyl estradiol, minocycline, trimethoprim/sulfamethoxazole, and granulocyte colony-stimulating factor. We describe the first known case of Sweet's syndrome induced by pegfilgrastim, a pegylated form of granulocyte colony-stimulating factor with unique pharmacologic properties that may induce Sweet's syndrome in patients with no history of neutrophilic dermatoses associated with granulocyte colony-stimulating factor therapy.

Epiregulin is more potent than EGF or TGFalpha in promoting in vitro wound closure due to enhanced ERK/MAPK activation.

Epiregulin (EPR) is a broad specificity EGF family member that activates ErbB1 and ErbB4 homodimers and all possible heterodimeric ErbB complexes. We have previously shown that topical EPR enhances the repair of murine excisional wounds. The purpose of this study was to determine whether EPR was more effective than EGF or TGFalpha in promoting in vitro wound closure and to compare the EPR induced signal transduction pathways with those activated by EGF and TGFalpha. Normal human epidermal keratinocytes or A431 cells were scratch wounded and treated for 24 h with varying doses of EPR, EGF or TGFalpha. Five-fold lower doses of EPR were significantly better than EGF or TGFalpha in stimulating in vitro wound closure. Mitomycin-c reduced EPR induced wound closure by 59%, versus a 9% and 25% decrease in EGF and TGFalpha induced closure. The ERK/MAPK inhibitor PD-98059 decreased EPR induced wound closure by 88%. By contrast, the PLC inhibitor U-73122, only reduced the EPR induced response by 21%. Immunoblot analysis revealed that 2 nM EPR stimulated a six-fold increase in p-ERK1/2, whereas 10 nM EGF or TGFalpha stimulated only a 3- and 2.5-fold increase in p-ERK1/2. When compared with EGF or TGFalpha, EPR is a more potent and more effective inducer of in vitro wound closure due to its ability to promote significantly greater ERK/MAPK activation.

Topical epiregulin enhances repair of murine excisional wounds.

Epiregulin is a broad specificity epidermal growth factor family member that activates ErbB1 and ErbB4 homodimers and all possible heterodimeric ErbB complexes. Our objective was to determine whether topical epiregulin enhanced repair of murine excisional wounds. Wounds were treated on days 0-4 with either topical epiregulin (1 micro g/ml), epidermal growth factor (10 micro g/ml), or vehicle. At day 5 postinjury, wounds receiving epiregulin were significantly smaller than those treated with epidermal growth factor or vehicle. Treatment with epiregulin promoted greater epidermal proliferation and thickening than epidermal growth factor or vehicle due to an expansion of the proliferative compartment of keratinocytes. Dermal thickness was also increased in epiregulin-treated wounds as compared to those treated with epidermal growth factor or vehicle. In day 5 wounds, matrix metalloproteinase-3 (stromelysin-1) mRNA levels were significantly lower in epiregulin- or epidermal growth factor-treated wounds than in vehicle-treated controls, suggesting that growth factor-treated wounds were more mature and required less ongoing proteolytic activity than their same-day vehicle-treated counterparts. This is the first report that topical epiregulin accelerates repair of full-thickness murine excisional wounds as compared to vehicle or epidermal growth factor. Furthermore, epiregulin is more potent and more effective than epidermal growth factor in promoting proliferation and maturation of the epidermis as well as enhancement of the neodermis.

MMPs and TIMP-1 are differentially expressed between acute murine excisional and laser wounds.

BACKGROUND AND OBJECTIVES: Matrix metalloproteinases (MMPs) and their physiological inhibitors, the tissue inhibitors of metalloproteinases (TIMPs) play significant roles in wound repair. The aim of this study was to determine whether MMP and TIMP-1 mRNA is differentially expressed between laser-created and excisional skin wounds. STUDY DESIGN/MATERIALS AND METHODS: Full-thickness wounds were created on the dorsal surface of Balb/c mice by either excision of the skin or with a CO2 laser. Animals were sacrificed at days 1, 3, 5, 7, 10, and 13, and their wounds processed for RNA isolation or histology and immunohistochemistry. RESULTS: Northern hybridization for MMP-3, -10, -13, and TIMP-1 mRNA demonstrated higher expression on days 1, 3, and 5 in the laser wounds as compared to the excisional wounds. Histological evaluation revealed a two day delay in the resurfacing of laser wounds as compared to excisional wounds. Immunohistochemistry of Day 5 and 7 excisional and laser wounds showed MMP-3 within the epidermal compartment and the neo-dermis. No remarkable differences were noted in the spatial distribution patterns of MMP-3 between wound types. CONCLUSIONS: Our findings demonstrate that MMPs and TIMP-1 mRNA expression is higher on days 1-5 post injury in full thickness laser-created wounds than in comparable same day excisional wounds.