RESUMO
We here report the results of a Phase I/IIa open-label four dose-escalation clinical study assessing the safety, tolerability, and possible therapeutic efficacy of a single intramuscular administration of DVC1-0101, a new gene transfer vector based on a nontransmissible recombinant Sendai virus (rSeV) expressing the human fibroblast growth factor-2 (FGF-2) gene (rSeV/dF-hFGF2), in patients with peripheral arterial disease (PAD). Gene transfer was done in 12 limbs of 12 patients with rest pain, and three of them had ischemic ulcer(s). No cardiovascular or other serious adverse events (SAEs) caused by gene transfer were detected in the patients over a 6-month follow-up. No infectious viral particles, as assessed by hemagglutination activity, were detected in any patient during the study. No representative elevation of proinflammatory cytokines or plasma FGF-2 was seen. Significant and continuous improvements in Rutherford category, absolute claudication distance (ACD), and rest pain were observed (P < 0.05 to 0.01). To the best of our knowledge, this is the first clinical trial of the use of a gene transfer vector based on rSeV. The single intramuscular administration of DVC1-0101 to PAD patients was safe and well tolerated, and resulted in significant improvements of limb function. Larger pivotal studies are warranted as a next step.
Assuntos
Fator 2 de Crescimento de Fibroblastos/genética , Terapia Genética/métodos , Doença Arterial Periférica/terapia , Idoso , Idoso de 80 Anos ou mais , Citocinas/metabolismo , Feminino , Técnicas de Transferência de Genes , Vetores Genéticos , Humanos , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/genética , Vírus Sendai/genética , Resultado do TratamentoRESUMO
PURPOSE: The clinical characteristics and long-term results of patients with solitary iliac aneurysms (SIAs) were investigated. METHODS: 28 consecutive patients who underwent repair of SIAs between 1985 and 2004 were reviewed retrospectively, and compared with those of 536 patients who underwent elective repair of an abdominal aortic aneurysm (AAA) during the same period. RESULTS: The incidence of SIAs among all aorto-iliac aneurysms was 5.0%. The 28 patients with SIAs were men with a mean age of 69.1 years. There were a collective total of 42 iliac aneurysms in the 28 patients, with 12 patients having multiple aneurysms. Thirty aneurysms involved the common iliac artery, and 12 involved the internal iliac artery. Twenty-two patients had symptoms, although none of the SIAs ruptured. Four patients had coexistent iliac occlusive disease and two patients had femoral occlusive disease. The 5-and 10-year survival rates of the patients with SIAs were 90.5% and 75.4%, whereas those of the patients with AAAs were 76.3% and 54%, respectively (P = 0.089). CONCLUSION: Routine imaging is necessary not only to evaluate the SIAs, but also to detect multiple aneurysms or arterial occlusive disease. Close and long-term followup is mandatory for the early detection of the formation of new aneurysms.
Assuntos
Aneurisma Ilíaco/cirurgia , Idoso , Aneurisma da Aorta Abdominal/epidemiologia , Aneurisma da Aorta Abdominal/cirurgia , Arteriopatias Oclusivas/epidemiologia , Feminino , Humanos , Aneurisma Ilíaco/epidemiologia , Aneurisma Ilíaco/mortalidade , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do TratamentoRESUMO
An abdominal aortic aneurysm associated with polycystic kidney disease is a comparatively rare but quite important condition because treating this disease is difficult, especially regarding the aortic approach. We herein present two such patients who underwent a left nephrectomy followed by an aneurysmectomy which was reconstructed with a bifurcated prosthetic graft. In both cases, the left nephrectomy enabled us to obtain an adequate operative field to expose the abdominal aorta and the surgical procedures could thus all be safely completed. The left nephrectomy is therefore considered to be a preferable surgical method for treating those patients with both conditions described here.
Assuntos
Aneurisma da Aorta Abdominal/epidemiologia , Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular , Nefrectomia , Doenças Renais Policísticas/epidemiologia , Doenças Renais Policísticas/cirurgia , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Renais Policísticas/diagnóstico por imagem , RadiografiaRESUMO
The premature endothelialization of tissue-engineered grafts had often induced cellular detachment at an early period of implantation in arterial circulation, resulting in occlusion at an early period of implantation. This study was aimed to determine whether gradually increased shear stress applied ex vivo improves cell retention and tissue morphological integrity including cell shape and alignment, actin fiber alignment and expression of vascular endothelial (VE) cadherin. Tissue-engineered grafts used for this study were human umbilical vein endothelial cell (HUVEC)-seeded compliant small-diameter grafts made of poly(L-lactide-co-epsilon-caprolactone) fiber meshes fabricated by electrospinning. The shear stresses applied to grafts, generated using a custom-designed mock circulatory apparatus, were 3.2, 8.7 and 19.6 dyn/cm(2). The grafts completely monolayered prior to shear stress exposure exhibited a polygonal cobblestone morphology with randomly distributed actin fibers and VE cadherin at the continuous peripheral region of adjacent cells. The 24-h-loading of high shear stresses (8.7 and 19.6 dyn/cm(2)) equivalent to those of the arterial circulatory system resulted in severe cellular damage resulting in the complete loss of cells. However, a gradually increased graded exposure from a low (3.2 dyn/cm(2)) to a high shear stress (19.6 dyn/cm(2)) resulted in a markedly reduced cell detachment, a highly elongated cell shape, and orientation or alignment of both cells and actin fibers, which were parallel to the direction of flow. Although VE-cadherin expression was not detected yet, a higher degree of tissue integrity was achieved, which may greatly improve the performance particularly at an early period of implantation.
Assuntos
Prótese Vascular , Endotélio Vascular/citologia , Engenharia Tecidual/métodos , Veias Umbilicais/citologia , Artérias/patologia , Células Cultivadas , Colágeno/química , Citoesqueleto/metabolismo , Endotélio Vascular/patologia , Humanos , Teste de Materiais , Microscopia Eletrônica de Varredura , Poliésteres/química , Estresse Mecânico , Fatores de TempoRESUMO
To design a "mechano-active" small-diameter artificial vascular graft, a tubular scaffold made of elastomeric poly(L-lactide-co-epsilon-caprolactone) fabrics at different wall thicknesses was fabricated using an electrospinning (ELSP) technique. The wall thickness of the fabricated tube (inner diameter; approximately 2.3-2.5 mm and wall thickness; 50-340 microm) increased proportionally with ELSP time. The wall thickness dependence of mechanical responses including intraluminal pressure-induced inflation was determined under static and dynamic flow conditions. From the compliance-related parameters (stiffness parameter and diameter compliance) measured under static condition, the smaller the wall thickness, the more compliant the tube. Under dynamic flow condition (1 Hz, maximal/minimal pressure of 90 mmHg/45 mmHg) produced by a custom-designed arterial circulatory system, strain, defined as the relative increase in diameter per pulse, increased with the decrease in wall thickness, which approached that of a native artery. Thus, a mechano-active scaffold that pulsates synchronously by responding to pulsatile flow was prepared using elastomeric PLCL as a base material and an ELSP technique.
Assuntos
Materiais Biocompatíveis , Implante de Prótese Vascular , Teste de Materiais , Poliésteres , Animais , Aorta Abdominal/fisiologia , Aorta Abdominal/transplante , Aorta Abdominal/ultraestrutura , Aorta Torácica/fisiologia , Aorta Torácica/transplante , Aorta Torácica/ultraestrutura , Velocidade do Fluxo Sanguíneo/fisiologia , Implante de Prótese Vascular/instrumentação , Complacência (Medida de Distensibilidade) , Teste de Materiais/instrumentação , CoelhosRESUMO
To fabricate a "mechano-active" tubular scaffold of nonwoven mesh-type small-diameter artificial graft made of the synthetic durable elastomer, segmented polyurethane, the fabrication technique of electrospinning on a mandrel under a high rotation speed and transverse movement was used. Emphasis was placed on how the rotation speed of the mandrel and the fusion or welding states of fibers at contact points affect the compliance (ease of intraluminal pressure-dependent circumferential inflation) and Young's modulus determined by uniaxial stretching in the longitudinal and circumferential directions. The results showed that a high rotation speed is attributed to exhibit isotropic mechanical properties in the entire range of applied strain but reduces the compliance, and a high fusion state, which is produced using a mixed solvent with a high content of high-boiling-point solvent, reduces the compliance but is expected to exhibit high durability in a continuously loaded pulsatile stress field in an arterial circulatory system.
Assuntos
Órgãos Artificiais , Elétrons , Poliuretanos/química , Dimetilformamida/química , Mecânica , Microscopia Eletrônica de Varredura , Rotação , Telas CirúrgicasRESUMO
We herein present the case of a 53-year-old man who suffered from portal vein thrombosis complicated with disseminated intravascular coagulation due to acute cholecystitis. Although gabexate mesilate and antibiotics were administered and endoscopic nasobiliary drainage was performed, only percutaneous transhepatic gallbladder drainage performed on the sixth hospital day improved his systemic condition and a recanalization of the portal vein was achieved. Regarding the strategy for the treatment of patients with disseminated intravascular coagulation, both an early diagnosis and prompt treatment for the underlying diseases are considered to be extremely important. Since both a hypercoagulate state and cholecystitis are considered to be etiological causes of portal vein thrombosis, clinicians should be aware that thrombosis may present as a complication in such patients.
Assuntos
Colecistite/complicações , Coagulação Intravascular Disseminada/complicações , Veia Porta , Trombose/complicações , Doença Aguda , Coagulação Intravascular Disseminada/etiologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
We herein report a case of aortocaval fistula complicated with bacteremia due to Escherichia coli in a 78-year-old man who underwent an emergency operation. A surgical resection of the abdominal aortic aneurysm with a closure of the fistula, and reconstruction with an expanded polytetrafluoroethylene bifurcated graft and wrapping with an omental flap, were performed followed by a 9-week continuous administration of antibiotics. Thereafter, antifungal agents were administered and the results were good. Both an early diagnosis and prompt surgery are important for such patients, and long-term administration of antibacterial agents is also necessary.
Assuntos
Fístula Arteriovenosa/complicações , Bacteriemia/complicações , Infecções por Escherichia coli/complicações , Veia Cava Inferior , Idoso , Aneurisma da Aorta Abdominal/complicações , Aneurisma da Aorta Abdominal/cirurgia , Ruptura Aórtica/complicações , Ruptura Aórtica/cirurgia , Fístula Arteriovenosa/cirurgia , Humanos , Masculino , Veia Cava Inferior/cirurgiaRESUMO
BACKGROUND: Late graft failure is still a problem for vascular surgeons. A previous study showed superior patency of arterial grafts compared with venous grafts. In this review we discuss the differences in functional and morphologic modulation of experimental autogenous venous and arterial grafts. RESULTS: In canine venous grafts, the endothelium of the graft was denuded and recovered within 3 or 4 weeks. In contrast, in arterial grafts, denudation of the endothelium was minimal, and no platelet adherence was observed. Instead, nearly normal intact endothelial cell surface had covered the intima within 3 days after grafting. The histologic findings for arterial grafts thus were quite different from those for venous grafts. Different responses to flow changes between venous and arterial grafts were observed. In the venous grafts, pronounced intimal thickening was associated with impairment of endothelial responses, whereas in the arterial grafts, intact endothelial function and no intimal thickening were observed. CONCLUSIONS: The intact endothelial function and absence of intimal thickening under the arterial grafts may explain the superior patency of autogenous arterial grafts in comparison with venous grafts.
Assuntos
Artérias/transplante , Endotélio Vascular/patologia , Veias/transplante , Animais , Artérias/patologia , Cães , Sobrevivência de Enxerto , Transplante Autólogo , Túnica Íntima/patologia , Veias/patologiaRESUMO
BACKGROUND: The optional therapeutic strategy for patients with intermittent claudication remains controversial. In this study, we investigated the influence of surgical and conservative therapies on improving the quality of life in patients with intermittent claudication. METHODS: We analyzed 427 patients who were admitted to our hospital with intermittent claudication in their legs during a 15-year period from January 1984 to December 1999. We separated them into 2 groups; 259 patients (362 legs) were treated surgically and 168 patients were treated conservatively. RESULTS: At the suprainguinal and infrainguinal (above knee) region, the surgery group showed significantly better rate of improvement than did the conservative group, but in the infrainguinal (below knee) region, there was no significant difference between the 2 groups. The 3-year and 5-year patency rates for the arterial reconstruction of the suprainguinal and infrainguinal region was satisfactory, but that of the infrainguinal region was not very good even if an auto vein graft was used. CONCLUSIONS: Aggressive surgical treatment is therefore recommended in patients whose distal anastomotic region is above the knee, because there are great benefits from surgical reconstruction. However, in patients whose distal anastomotic region is below the knee, conservative treatment might be just as effective as surgery.
Assuntos
Claudicação Intermitente/cirurgia , Claudicação Intermitente/terapia , Idoso , Feminino , Seguimentos , Oclusão de Enxerto Vascular/epidemiologia , Humanos , Claudicação Intermitente/epidemiologia , Joelho , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: The activation of platelets or leukocytes plays an important role in development of intimal hyperplasia. We investigated whether the local blood serotonin and soluble P-selectin levels changed during endovascular therapy of the iliac artery. METHODS: Blood samples were obtained from the iliac artery of 18 lower limbs undergoing percutaneous balloon angioplasty alone (8 limbs, group I) or percutaneous balloon angioplasty and primary stenting (10 limbs, group II). The serotonin levels in platelet-poor plasma were measured in all limbs. In group I the urinary level of the serotonin metabolite 5-hydroxyindoleacetic acid was also measured 24 hours before and 24 hours after the procedures. The soluble P-selectin levels were measured in the 6 patients in group II. RESULTS: Before angioplasty the mean (+/- SEM) serotonin concentrations were 1.2 +/- 0.2, 1.2 +/- 0.4, and 1.2 +/- 0.3 ng/mL in all cases, group I, and group II, respectively. After angioplasty these values changed to 1.7 +/- 0.4 (P =.0750), 1.2 +/- 0.4 (P =.8001), and 2.1 +/- 0.6 ng/mL (P =.0529), respectively. In group I urinary 5-hydroxyindoleacetic acid concentrations 24 hours before and 24 hours after the procedures were 0.0026 +/- 0.0004 and 0.0031 +/- 0.0006 mg/mg creatinine, respectively (P =.2566). In group II the soluble P-selectin levels significantly increased after intervention, from 26.0 +/- 5.7 to 33.9 +/- 5.3 ng/mL (P =.0296). CONCLUSIONS: Although the serotonin levels did not change significantly, the soluble P-selectin levels increased significantly after intervention. Leukocyte activation may therefore contribute to the progression of restenosis after peripheral endovascular therapy.
Assuntos
Angioplastia Coronária com Balão , Arteriopatias Oclusivas/terapia , Artéria Ilíaca/metabolismo , Selectina-P/sangue , Serotonina/sangue , Idoso , Idoso de 80 Anos ou mais , Plaquetas , Feminino , Humanos , Ácido Hidroxi-Indolacético/urina , Artéria Ilíaca/imunologia , Leucócitos/imunologia , Masculino , Pessoa de Meia-Idade , Solubilidade , StentsRESUMO
Solitary fibrous tumors (SFTs) are spindle-cell neoplasms originally described in the pleura. It is now known that these tumors can develop in many sites. This report describes the case of a well-circumscribed tumor located around the superior mesenteric artery (SMA), which was initially thought to be either a superior SMA aneurysm, a lymphoma, or a neurogenic tumor. Histological examination demonstrated the tumor to be composed of a cellular proliferation of ovoid to spindle cells with a fine collagenous matrix in the short fascicles. Immunohistochemical staining was strongly positive for CD34 and negative for factor VIII, cytokeratin, desmin, and muscle-specific actin (HHF-35). These findings suggested a diagnosis of SFT in the retroperitoneal space. To our knowledge, this is the first report of an SFT located around the SMA. Based on the above findings, it is important to include SFT in the differential diagnosis of retroperitoneal tumors located around the SMA.