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1.
Clin Plast Surg ; 46(1): 91-103, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30447834

RESUMO

Excess thigh laxity is a problem for many patients following significant weight loss. Thigh laxity has both vertical and horizontal components that require correction to optimize the aesthetic appearance of the thigh. The vertical vector is best corrected first with a lower body lift or extended abdominoplasty. The remaining loose skin in the medial thigh can then be removed using a horizontal vector resulting in a vertical incision. Residual vertical skin excess is also removed parallel to the groin crease. This article describes the author's surgical approach and management of medial thigh deformity in the significant weight loss patient.


Assuntos
Contorno Corporal/métodos , Procedimentos de Cirurgia Plástica/métodos , Coxa da Perna/cirurgia , Redução de Peso , Feminino , Humanos
2.
Aesthetic Plast Surg ; 42(2): 369-375, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29270696

RESUMO

The obesity pandemic continues to produce an inexorable increase in the number of patients requiring surgical treatment of obesity and obesity-related complications. Along with this growing number of patients, there is a concomitant increase in the complexity of management. One particular example is the treatment of patients with an exceptionally large and morbid pannus. In this report, we detail the management of seven patients suffering from a giant pannus. Medical and surgical variables were assessed. A quality of life questionnaire was administered pre- and postoperatively. All seven patients suffered some obesity-related medical morbidity and six of seven (86%) had local complications of the giant pannus. Each patient underwent giant panniculectomy [resection weight > 13. 6 kg (30 lb)]. The mean resection weight was 20.0 kg. Four of seven (57%) patients experienced postoperative complications, with two (29%) requiring re-operation and blood transfusion. Six patients were available for long-term follow-up; 100% of participants indicated an increased quality of life while five (83%) reported additional postoperative weight loss, increase in exercise frequency and walking ability, and improved ability to work. Our results indicate that giant panniculectomy is a challenging and risky procedure, but careful patient selection and intraoperative scrutiny can ameliorate these risks and afford patients a dramatically improved quality of life. Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Assuntos
Gordura Abdominal/cirurgia , Abdominoplastia/métodos , Índice de Massa Corporal , Obesidade Mórbida/cirurgia , Redução de Peso , Abdominoplastia/efeitos adversos , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/fisiopatologia , Qualidade de Vida , Estudos Retrospectivos , Medição de Risco , Estudos de Amostragem , Resultado do Tratamento
3.
Aesthetic Plast Surg ; 39(4): 616-24, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26044391

RESUMO

OBJECTIVE: To evaluate the safety and effectiveness of a lysine-derived urethane adhesive as a noninvasive alternative to closed suction drains in a commonly performed large flap surgical procedure. METHODS: One hundred thirty subjects undergoing abdominoplasty at five centers were prospectively randomized to standard flap closure with surgical drains (Control group) or a lysine-derived urethane adhesive (Treatment group) without drains. The primary outcome measured was the number of post-operative procedures, including drain removals (as the event marking the use of a surgical drain) and needle aspirations. Secondary endpoints included total wound drainage, cumulative days of treatment, and days to drain removal. A patient questionnaire evaluating quality of life measures was also administered. RESULTS: Subjects in the Treatment group required significantly fewer post-operative procedures compared to the Control group (1.8 ± 3.8 vs. 2.4 ± 1.2 procedures; p < 0.0001) and fewer cumulative days of treatment (1.6 ± 0.4 vs. 7.3 ± 3.3; p < 0.0001). A procedure to address fluid accumulation was required for only 27.3 % of the subjects in the Treatment group versus 100 % of Control group, which by study design required the use of drains. The mean duration of use of indwelling surgical drains for the Control group was 6.9 ± 3.3 days. All fluid collections treated with percutaneous aspiration were resolved and there were no unanticipated adverse events. CONCLUSION: The results of the study support that the use of a lysine-derived urethane adhesive is a safe and effective alternative to drains in patients undergoing a common large flap surgical procedure.


Assuntos
Lisina , Procedimentos de Cirurgia Plástica , Retalhos Cirúrgicos , Adesivos Teciduais , Uretana , Adulto , Drenagem , Feminino , Humanos , Masculino , Estudos Prospectivos
4.
Plast Reconstr Surg ; 135(4): 1027-1032, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25811569

RESUMO

BACKGROUND: Studies describing recent abdominoplasty modifications have reported a decreased incidence of seroma, attributed to preservation of abdominal lymphatics. However, there are limited anatomical data to support this hypothesis. The authors sought to characterize the lymphatic architecture of the abdominal wall and provide a conceptual basis for further refinement of abdominoplasty techniques. METHODS: Fifteen tissue samples from five patients undergoing abdominoplasty were sectioned and analyzed. Slides were stained with hematoxylin and eosin, CD31, and D2-40 and assessed by a pathologist and a plastic surgeon for the presence and number of lymphatics. Results were reported as mean percentage of lymphatic-specific antibody per analyzed area. RESULTS: Lymphatic vessels were observed in the dermis, superficial fascia, and loose areolar tissue but not in deep or superficial fat. The highest concentration was in the dermis (mean, 82.6 percent; range, 69 to 89.2 percent). The Scarpa fascia contained 9.4 percent of lymphatics (range, 7.0 to 11.4 percent), whereas the loose areolar tissue at the specimen base contained an average of 7.9 percent (range, 2.6 to 19.5 percent). These lymphatics were consistently located in the deepest third, with the Scarpa fascia lying an average of 34 percent of the total tissue thickness above muscle fascia. Lymphatic prevalence did not increase in specimens near the superficial epigastric vessels. CONCLUSIONS: Abdominoplasty flap lymphatics are most common in the dermis, with a significant proportion (approximately 17 percent) also appearing near fascial layers. This confirms the presence of deep lymphatic channels that could potentially be preserved during abdominoplasty or lipoabdominoplasty.


Assuntos
Parede Abdominal/anatomia & histologia , Sistema Linfático , Abdominoplastia , Humanos , Vasos Linfáticos
5.
Ann Plast Surg ; 74(6): 699-702, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24727447

RESUMO

BACKGROUND: Measures that can reduce the incidence of venous thromboembolism (VTE) are of great clinical importance. In addition to the use of sequential compression devices (SCDs), chemoprophylaxis with low-molecular-weight heparin (LMWH) has been recommended by the American College of Chest Physicians for major general surgery procedures. There remains inconclusive evidence to support guidelines for the plastic surgery population, and some surgeons hesitate to use anticoagulation due to concerns about bleeding in broad planes of dissection. The purpose of this study was to evaluate the risk of postoperative complications secondary to chemical thromboprophylaxis in massive weight loss patients. METHODS: Five hundred forty-six surgical cases were enrolled in an institutional review board-approved prospective clinical database in the 2 years before and after routine LMWH use was initiated. Inclusion required weight loss of greater than 50 lb. Group 1 had SCDs only (n = 334), whereas group 2 had SCDs and LMWH 6 hours postoperatively (n = 212). Risk of VTE was calculated and complications of LMWH administration were analyzed. RESULTS: The overall risk of deep venous thrombosis and pulmonary embolism was 0.18%. There was no statistical difference between the groups (P > 0.05). Overall risk of hematoma was 5.4%, in concordance with the literature. There was no difference in hematoma risk between the groups (4.6% before and 6.6% after LMWH; P = 0.3). The transfusion rate was 8.5% before use of LMWH (group 1) and 7.6% after (group 2; P = 0.7). CONCLUSIONS: Strategies to reduce VTE rates remain important in all areas of plastic surgery. We have demonstrated no increased risk of transfusion or hematoma and a low overall incidence of VTE after implementing a chemoprophylaxis regimen. Postoperative LMWH can provide an excellent balance between VTE prophylaxis and the risk of bleeding complications.


Assuntos
Anticoagulantes/efeitos adversos , Heparina de Baixo Peso Molecular/efeitos adversos , Procedimentos de Cirurgia Plástica , Complicações Pós-Operatórias/prevenção & controle , Hemorragia Pós-Operatória/induzido quimicamente , Tromboembolia Venosa/prevenção & controle , Redução de Peso , Adulto , Idoso , Anticoagulantes/uso terapêutico , Terapia Combinada , Bandagens Compressivas , Feminino , Hematoma/induzido quimicamente , Hematoma/epidemiologia , Hematoma/prevenção & controle , Hematoma/terapia , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios/métodos , Complicações Pós-Operatórias/induzido quimicamente , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/terapia , Hemorragia Pós-Operatória/epidemiologia , Hemorragia Pós-Operatória/prevenção & controle , Hemorragia Pós-Operatória/terapia , Estudos Prospectivos , Resultado do Tratamento , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia
6.
Neuroimage ; 69: 120-5, 2013 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-23261640

RESUMO

Cognition that is not based on perception can lead to at least two different outcomes. In some situations, cognition that is independent of perception can allow actions to be selected other than those prescribed by immediate perceptual input. In others, cognition can be independent of perception and unrelated to the current behavioral goal allowing thoughts to develop that are largely independent of the actions involved in an external task. The default mode network (DMN) has been implicated in both of these kinds of perceptually decoupled thought. The current experiment used functional magnetic resonance imaging to explore whether a common region of this network was co-activated by both of these states. Both the medial pre-frontal cortex and the posterior cingulate - two major hubs of the DMN - showed greater activity when (i) actions that did not depend upon immediate perceptual input were faster and (ii) when actions based on perceptual input were slower. Together these data suggest that the DMN is important in cognition that is independent from perceptual input regardless of whether such thoughts result in action, or, instead compete with the behavioral goals of the moment.


Assuntos
Mapeamento Encefálico , Encéfalo/fisiologia , Cognição/fisiologia , Percepção/fisiologia , Adolescente , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Adulto Jovem
7.
Plast Reconstr Surg ; 130(2): 443-448, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22842417

RESUMO

BACKGROUND: Postbariatric body contouring represents a rapidly growing field. With long operative times and high rates of minor complications, evidence-based guidelines for operative management are needed. Data analyzing the impact of perioperative factors on patient outcomes are currently limited. METHODS: Patients who lost 50 pounds or more and underwent body contouring were enrolled in an institutional review board-approved prospective registry over 4 years. All cases were performed by the senior author at two community hospitals and two academic hospitals. Hypothermia was defined as a minimum temperature of 35°C or lower. RESULTS: Three hundred eight patients (272 women and 36 men) were analyzed. The average operative time was 4.7 hours, and 71.4 percent of cases were performed in an academic hospital. The average minimum operative temperature was 35.6±0.63°C (range, 34.0 to 38.0°C), and the average maximum operative temperature was 36.5±0.75°C (range, 34.8 to 39.0°C). On multivariate analysis, a lower minimum temperature was associated with both seroma (p=0.003; odds ratio, 3.1 per 1°C decrease) and transfusion (p=0.005; odds ratio, 2.4 per 1°C decrease). CONCLUSIONS: Operative hypothermia was present in one-fifth of cases. Lower intraoperative temperature was associated with an increased risk of seroma formation, blood loss, and the need for transfusion. Despite this, there were few major complications in lengthy cases involving substantial blood loss. Maintaining normothermia is a critical component of perioperative management. The authors have adopted a protocol involving patient prewarming, a higher operating room temperature, and the routine use of warmed fluids. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.


Assuntos
Cirurgia Bariátrica , Técnicas Cosméticas , Hipotermia/etiologia , Complicações Intraoperatórias , Obesidade Mórbida/cirurgia , Complicações Pós-Operatórias/etiologia , Adolescente , Adulto , Idoso , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Transfusão de Sangue/estatística & dados numéricos , Feminino , Humanos , Hipotermia/epidemiologia , Hipotermia/prevenção & controle , Complicações Intraoperatórias/epidemiologia , Complicações Intraoperatórias/prevenção & controle , Modelos Lineares , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Assistência Perioperatória , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Sistema de Registros , Seroma/epidemiologia , Seroma/etiologia , Resultado do Tratamento , Redução de Peso , Adulto Jovem
8.
Plast Reconstr Surg ; 130(2): 325e-330e, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22495205

RESUMO

BACKGROUND: Growing numbers of men are presenting for consultation and potential postbariatric body contouring surgery. Due to concerns about whether men might have increased rates of complications or dissatisfaction with aesthetic surgery, the authors assessed their clinical experience with male patients. METHODS: The authors examined male patients in their prospective database who had undergone body-contouring surgery. Chi-square analysis, regression analysis, and a binary logistic regression model were used to study categorical variables, surgical outcomes, continuous variables, and significant factors. Odds ratios were calculated. RESULTS: Of 481 patients, 48 (10 percent) were male. There were no significant differences in baseline comorbidities between the genders, except that women had a higher incidence of anxiety/depression. Men had a greater weight loss before body-contouring surgery, but this did not correlate with greater operative time or estimated blood loss. Male gender, however, was associated with a 14.6 percent incidence of postoperative hematoma and a 25 percent incidence of seroma, in contrast to female gender, with 3.5 and 13 percent, respectively. Logistic regression showed that male gender was associated with an increased incidence of hematoma, seroma, and postoperative complications. It was an independent risk factor for hematoma and seroma formation, with odds ratios of 3.76 and 2.65, respectively. Gender was not an independent predictor of wound dehiscence, flap loss, transfusion, or surgical-site infection. CONCLUSIONS: Men who are considering body-contouring surgery should be advised that they are at an increased risk of postoperative hematoma and seroma formation. The causal relationship between gender and postoperative complications is an area for further study. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.


Assuntos
Procedimentos Cirúrgicos Dermatológicos , Obesidade Mórbida , Procedimentos de Cirurgia Plástica , Redução de Peso , Adulto , Distribuição de Qui-Quadrado , Feminino , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Fatores Sexuais , Resultado do Tratamento
9.
Plast Reconstr Surg ; 127(4): 1693-1700, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21460677

RESUMO

Proper postoperative management of body contouring patients is essential to satisfactory long-term outcomes. Standard issues such as drain management, nutrition, and activity limitations will be relevant to all patients. Although major complications are infrequent, effective strategies for management of common minor wound complications are invaluable.


Assuntos
Cirurgia Bariátrica/efeitos adversos , Cuidados Pós-Operatórios , Cicatriz/etiologia , Cicatriz/prevenção & controle , Necrose Gordurosa/etiologia , Necrose Gordurosa/terapia , Hematoma/etiologia , Hematoma/terapia , Humanos , Linfedema/etiologia , Linfedema/prevenção & controle , Necrose , Nervos Periféricos , Seroma/etiologia , Seroma/prevenção & controle , Seroma/terapia , Pele/inervação , Pele/patologia , Deiscência da Ferida Operatória/terapia , Infecção da Ferida Cirúrgica/terapia , Suturas/efeitos adversos , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle
11.
Plast Reconstr Surg ; 127(3): 1352-1357, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21364438

RESUMO

Massive weight loss patients present specific challenges to the plastic surgeon. Review of these issues may be valuable for the surgeon who does not specialize in this area. Obtaining excellent results involves a comprehensive perioperative approach, beginning with proper patient selection and appropriate expectations. Operative considerations such as hypothermia prevention and thromboembolic prophylaxis can play a role in improving outcomes and reducing morbidity. Appropriately focused postoperative care completes the surgical plan, leading to satisfying results for both patient and surgeon.


Assuntos
Cirurgia Bariátrica , Obesidade Mórbida/cirurgia , Avaliação de Resultados em Cuidados de Saúde , Procedimentos de Cirurgia Plástica/métodos , Complicações Pós-Operatórias/prevenção & controle , Guias de Prática Clínica como Assunto , Humanos
14.
Plast Reconstr Surg ; 125(2): 691-698, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20124854

RESUMO

BACKGROUND: Unlike traditional plastic surgery patients who present with a specific anatomical complaint, massive weight loss patients often have multiple regions of concern. No single procedure can address the whole-body deformities associated with massive weight loss. The authors sought to quantify their clinical experience to provide evidence-based analysis of procedural combination in body contouring. METHODS: Patients were enrolled in an institutional review board-approved prospective clinical database over a 5-year period. Procedure categories included breast, medial thigh lift, buttock and lateral thigh lift, upper back lift, brachioplasty, and abdomen. Analysis of variance was used to analyze differences between procedure combinations. RESULTS: Six hundred nine massive weight loss patients underwent 661 cases involving 1070 procedures. Length of hospital stay increased with the number of procedures performed (p < 0.001). Second-stage cases (n = 60) had similar complication rates and length of hospital stay. Seroma and dehiscence were strongly correlated with the number of procedures (p < 0.001), as were tissue necrosis and infection (p = 0.02), whereas hematoma was unrelated (p = 0.25). Major complications did not increase in multiple-procedure cases. CONCLUSIONS: In a large experience at a high-volume center, concomitant procedures were performed safely in carefully selected patients with low major complication rates. Although aggregate minor complication rates were predictably higher than in single-procedure cases, there was no significant increase on a per-procedure basis. Multiple procedures can be combined safely in the body contouring patient, with surgical staging offering a viable alternative for patients who are unable to undergo combined procedures.


Assuntos
Obesidade Mórbida/cirurgia , Complicações Pós-Operatórias/cirurgia , Cirurgia Plástica/métodos , Redução de Peso , Abdome/cirurgia , Adulto , Dorso/cirurgia , Mama/cirurgia , Nádegas/cirurgia , Bases de Dados Factuais , Feminino , Hematoma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Reoperação , Seroma/cirurgia , Deiscência da Ferida Operatória/cirurgia , Infecção da Ferida Cirúrgica/cirurgia , Coxa da Perna/cirurgia
16.
FASEB J ; 23(3): 906-15, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19001054

RESUMO

Classic tissue engineering paradigms are limited by the incorporation of a functional vasculature and a reliable means for reimplantation into the host circulation. We have developed a novel approach to overcome these obstacles using autologous explanted microcirculatory beds (EMBs) as bioscaffolds for engineering complex three-dimensional constructs. In this study, EMBs consisting of an afferent artery, capillary beds, efferent vein, and surrounding parenchymal tissue are explanted and maintained for 24 h ex vivo in a bioreactor that preserves EMB viability and function. Given the rapidly advancing field of stem cell biology, EMBs were subsequently seeded with three distinct stem cell populations, multipotent adult progenitor cells (MAPCs), and bone marrow and adipose tissue-derived mesenchymal stem cells (MSCs). We demonstrate MAPCs, as well as MSCs, are able to egress from the microcirculation into the parenchymal space, forming proliferative clusters. Likewise, human adipose tissue-derived MSCs were also found to egress from the vasculature and seed into the EMBs, suggesting feasibility of this technology for clinical applications. We further demonstrate that MSCs can be transfected to express a luciferase protein and continue to remain viable and maintain luciferase expression in vivo. By using the vascular network of EMBs, EMBs can be perfused ex vivo and seeded with stem cells, which can potentially be directed to differentiate into neo-organs or transfected to replace failing organs and deficient proteins.


Assuntos
Microcirculação/fisiologia , Técnicas de Cultura de Tecidos/métodos , Engenharia Tecidual/métodos , Animais , Reatores Biológicos , Feminino , Regulação Enzimológica da Expressão Gênica , Humanos , Luciferases/genética , Luciferases/metabolismo , Masculino , Células-Tronco Mesenquimais/fisiologia , Ratos , Ratos Nus , Pele/irrigação sanguínea , Transfecção
17.
Wound Repair Regen ; 15(5): 665-70, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17971012

RESUMO

The pathophysiology of diabetic wound healing and the identification of new agents to improve clinical outcomes continue to be areas of intense research. There currently exist more than 10 different murine models of diabetes. The degree to which wound healing is impaired in these different mouse models has never been directly compared. We determined whether differences in wound impairment exist between diabetic models in order to elucidate which model would be the best to evaluate new treatment strategies. Three well-accepted mouse models of diabetes were used in this study: db/db, Akita, and streptozocin (STZ)-induced C57BL/6J. Using an excisional model of wound healing, we demonstrated that db/db mice exhibit severe impairments in wound healing compared with STZ and Akita mice. Excisional wounds in db/db mice show a statistically significant delay in wound closure, decreased granulation tissue formation, decreased wound bed vascularity, and markedly diminished proliferation compared with STZ, Akita, and control mice. There was no difference in the rate of epithelialization of the full-thickness wounds between the diabetic or control mice. Our results suggest that splinted db/db mice may be the most appropriate model for studying diabetic wound-healing interventions as they demonstrate the most significant impairment in wound healing. This study utilized a novel model of wound healing developed in our laboratory that stents wounds open using silicone splints to minimize the effects of wound contraction. As such, it was not possible to directly compare the results of this study with other studies that did not use this wound model.


Assuntos
Cicatrização/fisiologia , Animais , Diabetes Mellitus Experimental , Modelos Animais de Doenças , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Silicones , Contenções
18.
J Investig Dermatol Symp Proc ; 11(1): 57-65, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17069011

RESUMO

Calreticulin (CRT), an intracellular chaperone protein crucial for the proper folding and transport of proteins through the endoplasmic reticulum, has more recent acclaim as a critical regulator of extracellular functions, particularly in mediating cellular migration and as a requirement for phagocytosis of apoptotic cells. Consistent with these functions, we show that the topical application of CRT has profound effects on the process of wound healing by causing a dose-dependent increase in epithelial migration and granulation tissue formation in both murine and porcine normal and impaired animal models of skin injury. These effects of CRTare substantiated, in vitro, as we show that CRT strongly induces cell migration/wound closure of human keratinocytes and fibroblasts, using a wound/scratch plate assay, and stimulates cellular proliferation of human keratinocytes, fibroblasts, and vascular endothelial cells, providing mechanistic insight into how CRT functions in repair. Similarly, in both animal models, the histology of the wounds show marked proliferation of basal keratinocytes and dermal fibroblasts, dense cellularity of the dermis with notably increased numbers of macrophages and well-organized collagen fibril deposition. Thus, CRT profoundly affects the wound healing process by recruiting cells essential for repair into the wound, stimulating cell growth, and increasing extracellular matrix production.


Assuntos
Calreticulina/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Calreticulina/fisiologia , Calreticulina/uso terapêutico , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Tecido de Granulação/fisiologia , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/fisiologia , Macrófagos/efeitos dos fármacos , Macrófagos/fisiologia , Fator A de Crescimento do Endotélio Vascular/farmacologia , Cicatrização/fisiologia
19.
Plast Reconstr Surg ; 118(1): 54-65; discussion 66-8, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16816674

RESUMO

BACKGROUND: Gene therapy for cancer holds enormous therapeutic promise, but its clinical application has been limited by the inability to achieve targeted, high-level transgene expression with limited systemic toxicity. The authors have developed a novel method for delivering genes to microvascular free flaps (commonly used during reconstructive surgery) to avoid these problems. METHODS: During the finite period in which a free flap is separated from the host (ex vivo), it can be perfused with extremely high titers of genetic material through the afferent artery, resulting in efficient transduction of the tissue. Before reanastomosis, unincorporated genetic material is flushed from the flap, minimizing systemic toxicity. RESULTS: In a rodent model using an adenoviral vector containing the lacZ reporter gene, high regional expression of beta-galactosidase was achieved in all the different cells in a microvascular free flap. Moreover, no beta-galactosidase staining was observed outside of the transduced flap, and viral sequence was undetectable by polymerase chain reaction analysis in other tissues. Further analysis confirmed that high-level transgene expression was precisely localized to the explanted tissue, with no collateral transduction. CONCLUSIONS: Targeting gene delivery with minimal systemic toxicity is essential for successful gene therapy. This form of "biological brachytherapy" provides a new opportunity to deliver targeted therapeutic transgenes to patients undergoing reconstructive surgery and allows microvascular free flaps to perform therapeutic and reconstructive functions.


Assuntos
Braquiterapia , Terapia Genética/métodos , Retalhos Cirúrgicos , Adenoviridae/genética , Animais , Ensaio de Imunoadsorção Enzimática , Óperon Lac , Masculino , Modelos Animais , Ratos , Ratos Sprague-Dawley , Retalhos Cirúrgicos/irrigação sanguínea , beta-Galactosidase/metabolismo
20.
Wound Repair Regen ; 13(5): 506-12, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16176459

RESUMO

The prevention of new blood vessel growth is an increasingly attractive strategy to limit tumor growth. However, it remains unclear whether anti-angiogenesis approaches will impair wound healing, a process thought to be angiogenesis dependent. Results of previous studies differ as to whether angiogenesis inhibitors delay wound healing. We evaluated whether endostatin at tumor-inhibiting doses delayed excisional wound closure. C57/BL6J mice were treated with endostatin or phosphate-buffered solution 3 days prior to the creation of two full-thickness wounds on the dorsum. Endostatin was administered daily until wound closure was complete. A third group received endostatin, but also had daily topical vascular endothelial growth factor applied locally to the wound. Wound area was measured daily and the wounds were analyzed for granulation tissue formation, epithelial gap, and wound vascularity. Endostatin-treated mice showed a significant delay in wound healing. Granulation tissue formation and wound vascularity were significantly decreased, but reepithelialization was not effected. Topical vascular endothelial growth factor application to wounds in endostatin-treated mice resulted in increased granulation tissue formation, increased wound vascularity, and wound closure approaching that of control mice. This study shows that the angiogenesis inhibitor endostatin delays wound healing and that topical vascular endothelial growth factor is effective in counteracting this effect.


Assuntos
Substâncias de Crescimento/administração & dosagem , Pele/irrigação sanguínea , Pele/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/administração & dosagem , Cicatrização/efeitos dos fármacos , Administração Tópica , Inibidores da Angiogênese/farmacologia , Animais , Endostatinas/farmacologia , Tecido de Granulação/irrigação sanguínea , Tecido de Granulação/efeitos dos fármacos , Camundongos , Pele/fisiopatologia , Cicatrização/fisiologia
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