ABSTRACT
BACKGROUND: Although surgical excision and intralesional collagenase injection are mainstays in Dupuytren disease treatment, no effective medical therapy exists for recurrent disease. Compound 21, a selective agonist of the angiotensin II type 2 receptor, has been shown to protect against fibrosis in models of myocardial infarction and stroke. The authors investigated the potential use of compound 21 in the treatment of Dupuytren disease. METHODS: Human dermal fibroblasts were treated in vitro with compound 21 and assessed for viability using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, migration by means of scratch assay, and profibrotic gene transcription by means of quantitative reverse transcription polymerase chain reaction. Compound 21 effects in vivo were assessed using a xenograft model. Dupuytren disease cord specimens from patients undergoing open partial fasciectomy were divided into two segments. Segments were implanted under the dorsal skin of nude mouse pairs. Beginning on day 5, one mouse from each pair received daily intraperitoneal injections of compound 21 (10 µg/kg/day), and the other received vehicle. On day 10, segments were explanted and submitted for immunohistochemistry. RESULTS: Human dermal fibroblasts treated with compound 21 displayed decreased migration and decreased gene expression of connective tissue growth factor, fibroblast specific protein-1, transforming growth factor-ß1, Smad3, and Smad4. Dupuytren disease segments from compound 21-treated mice demonstrated significantly reduced alpha-smooth muscle actin and Ki67 staining, with increased density of CD31 staining vessels. CONCLUSIONS: Compound 21 significantly decreases expression of profibrotic genes and decreases myofibroblast proliferation as indicated by reduced Ki67 and alpha-smooth muscle actin expression. These findings support compound 21 as a potential novel treatment modality for Dupuytren disease.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Dupuytren Contracture/drug therapy , Receptor, Angiotensin, Type 2/agonists , Sulfonamides/therapeutic use , Thiophenes/therapeutic use , Animals , Anti-Inflammatory Agents/pharmacology , Biomarkers/metabolism , Cell Movement/drug effects , Cell Survival/drug effects , Cells, Cultured , Drug Administration Schedule , Dupuytren Contracture/metabolism , Female , Fibroblasts/drug effects , Fibroblasts/metabolism , Humans , Injections, Intraperitoneal , Mice , Mice, Inbred BALB C , Mice, Nude , Random Allocation , Sulfonamides/pharmacology , Thiophenes/pharmacologyABSTRACT
Nerve injuries of the foot and ankle can result in pain, numbness, or loss of motor function. A thorough history and physical examination are required to diagnose the injury correctly and guide treatment. Treatment may involve conservative measures, primary nerve repair or nerve grafting, or resection and relocation of painful neuroma. Potential complications include the development of chronic pain syndromes.
Subject(s)
Ankle Injuries/surgery , Ankle/innervation , Foot Injuries/surgery , Foot/innervation , Peripheral Nerve Injuries , Humans , Lacerations/surgery , Plastic Surgery ProceduresABSTRACT
BACKGROUND: The purpose of this study was to prospectively assess changes in overall health-related quality of life and breast-related symptoms in women undergoing reduction mammaplasty, and to compare preoperative and postoperative health-related quality of life with that of the normal population. METHODS: Fifty-six patients were evaluated preoperatively and 6 months postoperatively with three questionnaires: the Short Form-36 Health Survey, the Symptom Inventory Questionnaire, and the Rosenberg Self-Esteem Scale. Surgeons completed preoperative patient assessment forms, operative note forms, and postoperative patient assessment forms. RESULTS: Comparison of preoperative and postoperative health-related quality of life showed significant improvements in Short Form-36 Health Survey scores (p < 0.005), the Rosenberg Self-Esteem Scale (p < 0.001), and all symptoms on the Symptom Inventory Questionnaire (p < 0.003). Preoperative mean Short Form-36 Health Survey scores were lower than in the normal population in several areas (p < 0.005). Postoperatively, none of the mean Short Form-36 Health Survey scores were significantly lower than population norms. CONCLUSIONS: This study determined that there is a significant improvement of physical symptoms and health-related quality of life in women undergoing reduction mammaplasty at 6 months after surgery. Before surgery, these patients have a significantly worse health-related quality of life than the normal population, but they normalize postoperatively.
