RESUMO
A multi-disciplinary work group involving stakeholders from various backgrounds and societies was convened to develop guidelines for the management of reconstruction after skin cancer resection. The goal was to identify areas of common ground and provide evidence-based recommendations to improve patient care. Given the heterogeneity of reconstructive techniques and clinical scenarios, investigation centered around common elements in the process. In some cases, a distinction was made between treatment options in the office-based setting as opposed to those in the facility setting. A systematic literature review was performed, and an established appraisal process was used to rate the quality of relevant scientific research (Grading of Recommendations Assessment, Development, and Evaluation methodology). Final recommendations are related to concepts concerning the timing of reconstruction, management of anticoagulation, use of antibiotics, methods of pain control, and follow-up assessment. At times, there was insufficient evidence to make high-level recommendations. The literature analysis highlights the need for additional methodologically robust studies in this area, to help guide clinical practice.
Assuntos
Procedimentos Cirúrgicos Dermatológicos/normas , Neoplasias Cutâneas/cirurgia , Medicina Baseada em Evidências , Humanos , Guias de Prática Clínica como AssuntoRESUMO
SUMMARY: A multi-disciplinary work group involving stakeholders from various backgrounds and societies was convened to develop guidelines for the management of reconstruction after skin cancer resection. The goal was to identify areas of common ground and provide evidence-based recommendations to improve patient care. Given the heterogeneity of reconstructive techniques and clinical scenarios, investigation centered around common elements in the process. In some cases, a distinction was made between treatment options in the office-based setting as opposed to those in the facility setting. A systematic literature review was performed, and an established appraisal process was used to rate the quality of relevant scientific research (Grading of Recommendations Assessment, Development, and Evaluation methodology). Final recommendations are related to concepts concerning the timing of reconstruction, management of anticoagulation, use of antibiotics, methods of pain control, and follow-up assessment. At times, there was insufficient evidence to make high-level recommendations. The literature analysis highlights the need for additional methodologically robust studies in this area, to help guide clinical practice.
Assuntos
Procedimentos Cirúrgicos Dermatológicos/normas , Medicina Baseada em Evidências , Neoplasias Cutâneas/cirurgia , Humanos , Guias de Prática Clínica como AssuntoRESUMO
SUMMARY: A multi-disciplinary work group involving stakeholders from various backgrounds and societies was convened to develop guidelines for the management of reconstruction after skin cancer resection. The goal was to identify areas of common ground and provide evidence-based recommendations to improve patient care. Given the heterogeneity of reconstructive techniques and clinical scenarios, investigation centered around common elements in the process. In some cases, a distinction was made between treatment options in the office-based setting as opposed to those in the facility setting. A systematic literature review was performed, and an established appraisal process was used to rate the quality of relevant scientific research (Grading of Recommendations Assessment, Development, and Evaluation methodology). Final recommendations are related to concepts concerning the timing of reconstruction, management of anticoagulation, use of antibiotics, methods of pain control, and follow-up assessment. At times, there was insufficient evidence to make high-level recommendations. The literature analysis highlights the need for additional methodologically robust studies in this area, to help guide clinical practice.
Assuntos
Procedimentos Cirúrgicos Dermatológicos , Medicina Baseada em Evidências , Neoplasias Cutâneas/cirurgia , Humanos , Guias de Prática Clínica como AssuntoRESUMO
BACKGROUND: Plasminogen activators are used routinely for thrombolysis. They lead to the generation of the protease, plasmin, which can induce smooth muscle cell proliferation and may thus promote further intimal hyperplasia in the thrombolysed vessel. We have shown recently that plasmin induces extracellular signal-regulated kinase 1/2 (ERK1/2)-mediated cell proliferation. Plasmin can also activate metalloproteinases on the cell surface, which can release the tethered ligand heparin-binding epidermal growth factor (HB-EGF), which can in turn activate the epidermal growth factor receptor (EGFR). METHODS: Murine aortic smooth muscle cells were cultured in vitro. Assays of DNA synthesis and cell proliferation, EGFR phosphorylation, and ERK1/2 activation were examined in response to plasmin in the presence and absence of the plasmin inhibitors (epsilon-aminocaproic acid and aprotinin), matrix metalloproteinase (MMP) inhibitor GM6001, HB-EGF inhibitor CRM197, HB-EGF inhibitory antibodies, EGF inhibitory antibodies, and the EGFR inhibitor AG1478. RESULTS: Plasmin-induced smooth muscle cell DNA synthesis, which was blocked by EGFR and HB-EGF inhibition. Plasmin-induced time-dependent EGFR phosphorylation and ERK1/2 activation, which were inhibited by AG1478. This response was dependent on the proteolytic activity of plasmin since both plasmin inhibitors blocked the response. EGFR phosphorylation by plasmin was blocked by inhibition of MMP activity and the ligand HB-EGF. EGFR phosphorylation by EGF was not interrupted by inhibition of plasmin, MMPs, or HB-EGF. Direct blockade of the EGFR prevented activation by both plasmin and EGF. CONCLUSIONS: Plasmin can induce smooth muscle cell proliferation through activation of EGFR by an extracellular MMP-mediated, HB-EGF-dependent process.
Assuntos
Fator de Crescimento Epidérmico/metabolismo , Fibrinolisina/farmacologia , Fibrinolíticos/farmacologia , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacos , Animais , Aorta/citologia , Divisão Celular/efeitos dos fármacos , Receptores ErbB/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Muridae , Músculo Liso Vascular/metabolismo , FosforilaçãoRESUMO
OBJECTIVE: CCL11 (Eotaxin) is a potent eosinophil chemoattractant that is abundant in atheromatous plaques. The major receptor for CCL11 is CCR3, which is found on leukocytes and on some nonleukocytic cells. We sought to determine whether vascular smooth muscle cells (SMCs) possessed functional CCR3. METHODS AND RESULTS: CCR3 mRNA (by RT-PCR) and protein (by Western blot analysis and flow cytometry) were present in mouse aortic SMCs. CCL11 induced concentration-dependent SMC chemotaxis in a modified Boyden chamber, with maximum effect seen at 100 ng/mL. SMC migration was markedly inhibited by antibody to CCR3, but not to CCR2. CCL11 also induced CCR3-dependent SMC migration in a scrape-wound assay. CCL11 had no effect on SMC proliferation. CCR3 and CCL11 staining were minimal in the normal arterial wall, but were abundant in medial SMC and intimal SMC 5 days and 28 days after mouse femoral arterial injury, respectively, times at which SMCs possess a more migratory phenotype. CONCLUSIONS: These data demonstrate that SMCs possess CCR3 under conditions associated with migration and that CCL11 is a potent chemotactic factor for SMCs. Because CCL11 is expressed abundantly in SMC-rich areas of the atherosclerotic plaque and in injured arteries, it may play an important role in regulating SMC migration.
Assuntos
Quimiocinas CC/farmacologia , Fatores Quimiotáticos/farmacologia , Quimiotaxia/efeitos dos fármacos , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , Receptores de Quimiocinas/efeitos dos fármacos , Animais , Aorta/citologia , Becaplermina , Movimento Celular/efeitos dos fármacos , Células Cultivadas/efeitos dos fármacos , Células Cultivadas/fisiologia , Quimiocina CCL11 , Quimiocinas CC/fisiologia , Eosinófilos/química , Artéria Femoral/lesões , Artéria Femoral/patologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Miócitos de Músculo Liso/fisiologia , Fator de Crescimento Derivado de Plaquetas/farmacologia , Proteínas Proto-Oncogênicas c-sis , RNA Mensageiro/biossíntese , Receptores CCR3 , Receptores de Quimiocinas/biossíntese , Receptores de Quimiocinas/genética , Receptores de Quimiocinas/fisiologia , Proteínas Recombinantes/farmacologia , Túnica Íntima/patologia , Túnica Média/patologiaRESUMO
Modern therapy, including endoluminal procedures and improved medical management, still yield less than desired results for tibial vessel occlusive disease. Despite the recent focus on these newer interventions, few modern series have evaluated the efficacy of popliteal-to-distal bypass procedures. The authors aimed to determine the efficacy of popliteal-distal bypass and to identify adverse prognostic factors for ultimate limb salvage. Eighty-seven patients (54 men; average age: 63 years) underwent 92 popliteal-distal bypasses. Duplex ultrasound was utilized to assess patency of all grafts. Data were analyzed by life-table analysis to determine patency rates at postoperative intervals. Median patient follow-up was 2.4 years. Major indications for bypass included chronic limb ischemia (86%) and disabling claudication (8%); 62% of the limbs were considered threatened, and 74% of the proximal anastomoses were above-knee. All procedures were technically successful. There were no perioperative (< 30 days) deaths, and 86% of patients were alive at 5 years. Cumulative patency rates were 74% at 6 months, 70% at 2 years, and 63% at 5 years. Limb salvage rates closely paralleled patency rates. At 5 years, 62% of the affected limbs were intact; 72% of the limbs lost were associated with early (< 180 days) bypass failures. Predictors of limb loss included early graft failure (84 days vs 1,288 days, p < 0.0001), younger age (57 years vs 64 years, p = 0.039), history of previous ipsilateral vascular procedures (50% vs 21%, p = 0.03), heavy (> 1 ppd) tobacco use (p = 0.001), and a thrombosed femoral-popliteal bypass at presentation (p = 0.002). When successful, popliteal-distal bypass is associated with excellent long-term patency and limb salvage rates. Early failures are often associated with limb loss. Heavy tobacco use, younger age, early graft failures, repeat revascularization, and presentation with a thrombosed femoral-popliteal graft are associated with limb loss.
Assuntos
Implante de Prótese Vascular , Extremidade Inferior/irrigação sanguínea , Artéria Poplítea/cirurgia , Artérias da Tíbia/cirurgia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Arteriopatias Oclusivas/diagnóstico por imagem , Arteriopatias Oclusivas/mortalidade , Arteriopatias Oclusivas/cirurgia , Feminino , Artéria Femoral/cirurgia , Seguimentos , Oclusão de Enxerto Vascular/diagnóstico por imagem , Humanos , Claudicação Intermitente/diagnóstico por imagem , Claudicação Intermitente/mortalidade , Claudicação Intermitente/cirurgia , Isquemia/diagnóstico por imagem , Isquemia/mortalidade , Isquemia/cirurgia , Tábuas de Vida , Extremidade Inferior/diagnóstico por imagem , Extremidade Inferior/fisiopatologia , Masculino , Pessoa de Meia-Idade , Artéria Poplítea/diagnóstico por imagem , Artéria Poplítea/fisiopatologia , Falha de Prótese , Estudos Retrospectivos , Fatores de Risco , Terapia de Salvação , Análise de Sobrevida , Artérias da Tíbia/diagnóstico por imagem , Artérias da Tíbia/fisiopatologia , Ultrassonografia Doppler Dupla , Grau de Desobstrução VascularRESUMO
The role of endovascular therapy for thrombosed dialysis access has grown despite the paucity of data on its viability. The purpose of this study was to characterize the outcomes of a universal endovascular dialysis declot policy at a tertiary medical center. A database of patients undergoing endovascular treatment of thrombosed dialysis access between 1997 and 2003 was maintained. A two-puncture, combined percutaneous mechanical and pharmacologic thrombectomy technique was used. Data were collected on the success rate, complication rate, long-term patency, and presence and location of stenosis. Fistulograms were reviewed in all cases to assess lesion characteristics and pre- and postprocedure results. Results were standardized to current Society of International Radiology and Society for Vascular Surgery criteria. Failure was considered as either an anatomic defect requiring therapy or loss of functionality of the fistula. Life-table analyses were performed to assess time-dependent outcomes. Cox's proportional hazard analyses were performed to identify factors associated with outcomes. Values are the mean +/- standard error of the mean. There were 114 patients (50% male; average age 58 years, range 21-78) who presented with 174 thrombosed grafts. Therapy was performed for 237 thrombotic events (median 2, range 1-5 thrombotic events per hemodialysis access). After successful declot, anastomotic venous stenoses were encountered in 72% and central venous stenoses in 18% of cases; no cause was found in 10%. All stenoses were treated with balloon angioplasty. The technical failure rate was 4.6%. The 30-day all-cause mortality rate was 1.7%, and major morbidity rate was 2.4%. There were 413 interventions (236 percutaneous transluminal angioplasty and/or 183 declot) performed to maintain patency, which amounted to 2.3 interventions per patient. Average primary functional dialysis life span was 6.7 months up to the primary thrombotic event. Aggressive endoluminal therapy added a further average of 12 months of functionality (defined as continued dialysis access). A universal policy of endovascular therapy for occluded dialysis access results in reestablishment of function in the majority of patients and will triple functional longevity. Furthermore, while this approach remains procedure-intensive, it carries low morbidity and mortality and preserves future sites of access.
Assuntos
Angioplastia com Balão , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Oclusão de Enxerto Vascular/terapia , Trombectomia/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Nefropatias Diabéticas/epidemiologia , Feminino , Insuficiência Cardíaca/epidemiologia , Humanos , Hipotireoidismo/epidemiologia , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Tábuas de Vida , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Trombofilia/epidemiologia , Resultado do Tratamento , Grau de Desobstrução VascularRESUMO
Severe pulmonary arterial hypertension (PAH) occurs in idiopathic form and in association with diverse diseases. The pathological hallmarks are distal smooth muscle hypertrophy, obliteration of small pulmonary arteriole lumens, and disorganized cellular proliferation in plexiform lesions. In situ thrombosis is also observed. A detailed understanding of the disease progression has been hampered by the absence of an animal model bearing all the pathological features of human disease. To create a model with these characteristics, we gave young (200-g) rats monocrotaline 1 wk following left pneumonectomy; controls with vehicle treatment or sham operation were also studied. In experimental rats, pulmonary arteries had distal smooth muscle hypertrophy and proliferative perivascular lesions. The lesions had a plexiform appearance, occurred early in disease development, and were composed of cells expressing endothelial antigens. Three-dimensional microangiography revealed severe vascular pruning and disorganized vascular networks. We found that expression of tissue factor (TF), the membrane glycoprotein that initiates coagulation, facilitates angiogenesis, and mediates arterial injury in the systemic circulation, was increased in the pulmonary arterioles and plexiform-like lesions of the rats. TF was also heavily expressed in the vessels and plexiform lesions of humans with pulmonary arterial hypertension. We conclude that plexiform-like lesions can be reproduced in rats, and this model will facilitate experiments to address controversies about the role of these lesions in PAH. Increased TF expression may contribute to the prothrombotic diathesis and vascular cell proliferation typical of human disease.
Assuntos
Modelos Animais de Doenças , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/patologia , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Tromboplastina/metabolismo , Angiografia , Animais , Proliferação de Células/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Humanos , Hipertensão Pulmonar/induzido quimicamente , Hipertrofia Ventricular Direita/induzido quimicamente , Hipertrofia Ventricular Direita/patologia , Masculino , Monocrotalina/administração & dosagem , Monocrotalina/farmacologia , Pneumonectomia , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Fator de von Willebrand/metabolismoRESUMO
Percutaneous transluminal intervention for atherosclerotic iliac occlusive disease is now commonplace. We examine the long-term outcomes of TransAtlantic Inter-Society Consensus (TASC) A and B lesions. We performed a retrospective anonymous analysis of records from patients who underwent iliac artery angioplasty with or without stenting between January 1990 and June 1999. Indications for intervention were symptomatic claudication (77%) or critical ischemia (23%). Altogether, 276 patients (all men; average age 64 +/- 11 years range 32-87 years) underwent 394 interventions. Co-morbidities included hypertension (61%), hypercholesterolemia (45%), diabetes (28%), and chronic renal insufficiency (26%). A total of the 62% of the lesions were TASC category A, and the remainder were category B. Of the 394 primary interventions, 51% included placement of stents. Technical success (defined by < 30% residual stenosis) was achieved in 98% of treated vessels. The procedure-related mortality rate was 1.8% at 30 days and 4.7% at 90 days; the procedure-related complication rate was 7%. Hemodynamic success (defined as a rise in the ankle/branchial index > 0.15) was achieved in 82%. The average Society for Vascular Surgery symptom score was 3.4 +/- 0.9 before intervention, which improved to 1.9 +/- 0.8 following intervention. Within 3 months, 84% of patients demonstrated clinical improvement. Patient survival by life-table analysis was 38% at 10 years. The cumulative assisted patency rate was 71 +/- 7% at 10 years. The presence of two-vessel femoral runoff, two or more patent tibial vessels, or both was associated with improved patency. Limb salvage was 95 +/- 2% and 87 +/- 9% at 5 and 10 years, respectively. Using Cox proportional hazards analysis, the presence of hypertension, hypercholesterolemia, or chronic renal insufficiency was associated with the occurrence of primary failure, whereas increased patency intervals were associated with the presence of immediate hemodynamic improvement. Use of a stent did not influence outcome. Endoluminal iliac intervention for TASC A and B lesions is a safe, durable intervention in patients with good femoral and tibial runoff. The presence of hypertension, hypercholesterolemia, or poor tibial runoff is associated with failure.
Assuntos
Angioplastia com Balão , Arteriopatias Oclusivas/terapia , Artéria Ilíaca , Idoso , Idoso de 80 Anos ou mais , Arteriopatias Oclusivas/epidemiologia , Comorbidade , Humanos , Tábuas de Vida , Salvamento de Membro , Estudos Retrospectivos , Fatores de Risco , Grau de Desobstrução VascularRESUMO
OBJECTIVE: To examine the role of the phospho-inositol-3'-kinase (PI3-K)-akt signaling axis during smooth muscle cell (SMC) migration in response to the aminoterminal fragment of urokinase (ATF). BACKGROUND: Urokinase (uPA) is involved in vessel remodeling and mediates smooth muscle cell migration. Migration in response to urokinase is dependent on ATF. The role of PI3-K/akt signaling during migration in response to the uPA fragments is not understood. METHODS: Murine arterial SMCs were cultured in vitro. Linear wound and Boyden microchemotaxis assays of migration were performed in the presence of ATF with and without the PI3-K inhibitors (Wortmannin, Wn [10 nm] and LY294002, LY [10 microm]) and an akt inhibitor (aktI, [10 microm]). Western blotting was performed for akt, ERK1/2, and GSK3beta phosphorylation after cells were stimulated with ATF in the presence and absence of the inhibitors. Statistics were analyzed by one-way ANOVA. RESULTS: Both PI3-K and akt inhibitors blocked the migratory response to ATF in both assays. ATF induced time-dependent increases in akt phosphorylation at both S472 and T308 sites and ERK1/2 phosphorylation. Activation of akt and ERK1/2 was inhibited by Wn and LY. Manumycin A, a ras inhibitor, did not inhibit activation of akt but did inhibit ERK1/2 activation. Activation of akt and the dephosphorylation of its downstream kinase GSK3beta were inhibited by the akt inhibitor. Direct inhibition of akt did not influence ERK1/2 activation and inhibition of ERK1/2 did not influence akt activation. CONCLUSION: ATF mediated migration is PI3-K dependent and activates two separate pathways: ERK1/2 and akt. ATF induces akt phosphorylation through a PI3K-mediated but ras-independent mechanism while both ras and PI3K are required for ERK1/2 activation. Defining key signaling pathways is vital to regulate vessel remodeling.
Assuntos
Movimento Celular/fisiologia , Músculo Liso Vascular/fisiologia , Fragmentos de Peptídeos/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Androstadienos/farmacologia , Animais , Aorta , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Quimiotaxia/efeitos dos fármacos , Quimiotaxia/fisiologia , Cromonas/farmacologia , Ativação Enzimática , Inibidores Enzimáticos/farmacologia , Camundongos , Morfolinas/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Inibidores de Fosfoinositídeo-3 Quinase , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , WortmaninaRESUMO
BACKGROUND: Plasminogen activators are routinely used for thrombolysis. They lead to the generation of the protease, plasmin, which can induce smooth muscle cell proliferation and may thus promote further intimal hyperplasia in the thrombolysed vessel. The signaling pathways used by plasmin are not understood. METHODS: Murine aortic smooth muscle cells were cultured in vitro. Assays of DNA synthesis, cell proliferation, MAPKK and MAPK activation were examined in response to plasmin alone and in the presence of plasmin inhibitors (epsilon-aminocaproic acid and aprotinin), pertussis toxin (Galphai inhibitor, PTx), GP-2A (Galphaq inhibitor), wortmannin (PI3-K inhibitor, Wn), LY294002, (PI3-K inhibitor, LY), PD98059 (MEK inhibitor, PD), and SB203580 (p38MAPK inhibitor, SB). RESULTS: Plasmin produced concentration dependent smooth muscle cells DNA synthesis and proliferation and induced ERK1/2 and p38MAPK phosphorylation. Inhibition of the proteolytic activity of plasmin prevented these responses. The ERK1/2 inhibitor, PD, but not the p38MAPK inhibitors, SB, blocked cell proliferation. The activation of the MEK1/2 and ERK1/2 pathway was both Galphai dependent (PTx-sensitive) and Galphaq dependent (GP-2A-sensitive). It was blocked by the PI3-K inhibitors, Wn and LY. PI3-K activation as measured by akt phosphorylation was dependent on Galphai, but was independent of Galphaq. CONCLUSION: Plasmin induces smooth muscle cell proliferation. Plasmin induced ERK1/2 phosphorylation occurs through two pathways: one which is Galphai mediated/PI3-K dependent and a second which is Galphaq mediated/PI3K independent. p38MAPK appears not to be involved in plasmin-mediated cell proliferation. This pattern of activation is distinct from that seen with urokinase plasminogen activator.
Assuntos
Divisão Celular/efeitos dos fármacos , Fibrinolisina/farmacologia , Músculo Liso/citologia , Animais , Aprotinina/farmacologia , Células Cultivadas , Replicação do DNA/efeitos dos fármacos , Ativação Enzimática , Cinética , Camundongos , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Músculo Liso/efeitos dos fármacos , Fosforilação , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-aktRESUMO
Although the long-term (>30 days) effects of endoluminal treatment of superficial femoral artery (SFA) disease have been well studied, the implications of early (< or =30 days) failure are still unclear. We examined the consequences of early failure after endovascular treatment of the SFA. We anticipate that early failure will not be associated with significant morbidity and mortality and will not interfere with surgical bypass options. A prospective database of patients undergoing endovascular treatment of the SFA between 1986 and 2004 was maintained. Intention-to-treat analysis was performed. Angiograms were reviewed in all cases to assess lesion characteristics and pre- and post procedure runoff. Results were standardized to current Transatlantic Intersociety Consensus (TASC) and Society for Vascular Surgery (SVS) criteria. There were 441 limbs in 360 patients (70% male, average age 65 years) that underwent endovascular treatment. There was early failure in 39 procedures (8%). Twenty-nine cases (74%) failed immediately (<24 hr), and 10 cases (26%) failed within the first 30 days following intervention. Factors that predicted failure were TASC category D and preprocedural SVS symptom grade > or =5. The 90-day mortality in the group was 0%, and major morbidity was 4%. No emergent endovascular intervention, bypass, or unplanned amputation occurred within 30 days of these failures. There was no change in the level of amputation or the level of distal anastomosis of a bypass graft as a result of an early failure. Early failure of endoluminal therapy for SFA disease is not associated with significant morbidity and mortality. Options for surgical bypass are not compromised, and the amputation level is not altered. Aggressive endoluminal approaches to SFA disease should be considered as a first-line therapy in all patients.
Assuntos
Arteriopatias Oclusivas/cirurgia , Implante de Prótese Vascular , Artéria Femoral/cirurgia , Idoso , Feminino , Oclusão de Enxerto Vascular , Humanos , Salvamento de Membro , Masculino , Estudos Retrospectivos , Falha de TratamentoRESUMO
Atherosclerotic renal artery stenosis is a significant cause of poorly controlled hypertension and progressive renal dysfunction leading to ischemic nephropathy and other end-organ damage. The optimal treatment of renovascular disease contributing to hypertension and renal dysfunction is not known. This study compares the anatomic and functional outcomes of both open and endovascular therapy for chronic, symptomatic atherosclerotic renal artery disease. We performed a retrospective analysis of records from patients who underwent renal arterial interventions, endovascular or open bypass, between January 1984 and January 2004. Principal indications for intervention were hypertension (51%), chronic renal insufficiency (13%), and hypertension and elevated creatinine (36%). A total of 247 patients (109 males; mean age 69 +/- 10, range 44-89 years) underwent 314 interventions (109 open procedures; 205 angioplasties, 71% with stent placement). There was a significant difference in 30-day mortality (4% vs. <1%; p < 0.005) between the open and endoluminal groups, but not at 1, 3, or 5 years. Patients in the open group had a higher primary patency rate at 5 years (83 +/- 5% vs. 76 +/- 6%; p = 0.03), but patients in the endoluminal group had a higher assisted primary patency rate at 5 years (92 +/- 5% vs. 84 +/- 5; p = 0.03). There was no significant difference between both treatment groups in cumulative freedom from presenting symptom or in freedom from dialysis and renal-related death. Patients who presented with hypertension were more likely to have shown improvement in their blood pressure with endoluminal intervention at 1, 3, and 5 (59 +/- 6% endoluminal vs. 83 +/- 5% open; p = 0.01) years. From these results we conclude that open repair and endoluminal repair of atherosclerotic renal artery stenosis have similar immediate and long-term functional and anatomic outcomes. Patients who present with hypertension may have greater benefit with an endoluminal repair.
Assuntos
Arteriosclerose/cirurgia , Obstrução da Artéria Renal/cirurgia , Idoso , Angioplastia , Arteriosclerose/mortalidade , Feminino , Humanos , Hipertensão Renovascular/mortalidade , Hipertensão Renovascular/cirurgia , Tábuas de Vida , Masculino , Complicações Pós-Operatórias/epidemiologia , Artéria Renal/cirurgia , Obstrução da Artéria Renal/mortalidade , Estudos Retrospectivos , Stents , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução VascularRESUMO
OBJECTIVE: To determine the role of rhosignaling in sphingosine-1-phosphate (S-1-P)-induced smooth muscle cell migration. BACKGROUND: S-1-P is a bioactive sphingolipid released from activated platelets stimulating migration of smooth muscle cells (SMC) in vitro through Galphai G-proteins and MAPK activation. Rho is one of the key small GTPases required for cytoskeletal reorganization and MAPK activation during migration. We hypothesized that S-1-P-stimulated migration is regulated by the rho-signaling pathway. METHODS: Rat arterial SMCs were cultured in vitro. Linear wound assays of migration were performed in the presence of S-1-P with and without C3 (a rho antagonist) and Y (Y27632, a Rho kinase inhibitor). Western blotting was performed for MEK1-ERK1/2 and MMK3/MKK6-p38(MAPK) phosphorylation after stimulation with S-1-P with and without pre-incubation with the inhibitors. Statistics were analyzed by one-way ANOVA. RESULTS: S-1-P stimulated migration of SMCs in a wound assay (2-fold over control; P < 0.01), which was blocked by Rho inhibition (P < 0.05). S-1-P activated rho and induced a time-dependent increase in ERK1/2 and p38(MAPK) activation. In the presence of C3, MEK1 and ERK1/2 phosphorylation were significantly decreased, while MKK3/6 and p38(MAPK) phosphorylation were unchanged. In contrast, when rho kinase was inhibited, there was an increase in ERK1/2 and a decrease in p38(MAPK) phosphorylation. Rho kinase inhibition resulted in a decrease in MEK1/2 and MKK3/6 phosphorylation. CONCLUSIONS: S-1-P differentially regulates the MAPK pathway through components of the rho pathway. Rho regulates ERK1/2 activation through MEK1/2, while Rho kinase negatively modulates ERK1/2 in a MEK1/2-independent manner and regulates p38(MAPK) through MKK3/6. This is the first description of differential MAPK regulation by a G-protein-coupled receptor through the rho pathway. Understanding signal transduction in SMCs will contribute to the development of molecular therapeutics for intimal hyperplasia.