Effective treatment of chronic lower limb ischemia is one of the most challenging issues confronting vascular surgeons. There are a number of choices available to the vascular surgeon. Open or endovascular revascularization is the treatment of choice when applicable. Current pharmacological therapies play an auxiliary role and cannot prevent disease progression. Therefore, new methods of treatment are needed. We conducted a phase 2b/3 multicenter randomized controlled clinical trial of the intramuscular transfer of a plasmid DNA encoding vascular endothelial growth factor (VEGF) 165 with cytomegalovirus promotor (CMV) in patients with atherosclerotic lower limb ischemia. A total of 100 patients were enrolled in the study, that is, 75 patients were randomized into the test group and received 2 intramuscular injections of 1.2 mg of pCMV-vegf165, 14 days apart together with standard pharmacological treatment. In all, 25 patients were randomized into the control group and received standard treatment only. The following end points were evaluated within the first 6 months of the study and during a 1.5-year additional follow-up period: pain-free walking distance (PWD), ankle-brachial index (ABI), and blood flow velocity (BFV). The pCMV-vegf165 therapy appeared to be significantly more effective than standard treatment. The PWD increased in the test group by 110.4%, 167.2%, and 190.8% at 6 months, 1 year, and 2 years after treatment, respectively. The pCMV-vegf165 intramuscular transfer caused a statistically significant increase in ABI and BFV. There were no positive results in the control group. Thus, pCMV-vegf165 intramuscular gene transfer is an effective method of treatment of moderate to severe claudication due to chronic lower limb ischemia.
The therapeutic effect of angiogenesis induction by gene therapy persists for 5 years.
Objective: To determine the capabilities of a sonographic examination to evaluate local and systemic hemodynamic disorders in patients with varicose disease. Materials and Methods: This study included 583 patients with varicose veins, among whom 348 had trophic disorders. All subjects underwent lower limb duplex sonography and superficial, perforator, and deep venous diameter measurements, as well as had a calculated velocity for antegrade and reflux flow. Peripheral resistive index (RI) in the arteries, accompanying perforator veins (PVs), was analyzed. In addition, echocardiography was performed on 46 of the participants. Results: A statistically significant difference in the diameter of the great saphenous vein was obtained between class C2 and C4 varicose veins ( P < .05). Similar findings were obtained for the diameter of the PVs and the velocity reflux flow through PVs. Arteries in the perforator bundles demonstrated low RI, which may be attributed to the presence of arteriovenous shunts. Varicose veins were associated with an increased incidence of nonrestrictive type of blood flow through the tricuspid valve. Conclusions: Sonography demonstrated that additional factors rather than hemodynamics may be attributable to the development of venous ulcers. The most informative parameters of cardiac function, in a patient with varicose veins, are the indicators of diastolic function in both ventricles.
Purpose We aimed to evaluate the impact of intrinsic coagulation factors and hemostatic markers of endothelial dysfunction on complications in patients with atherosclerotic peripheral arterial disease (PAD). Methods Materials and This prospective study enrolled 120 PAD patients at Fontaine stages 2b to 3 who underwent open surgical, endovascular, or conservative treatment. Coagulation factors (FVIII, FIX, and FXI) and endothelial hemostatic markers, including von Willebrand factor (vWF) activity and level, soluble endothelial protein C receptor, and plasminogen activator inhibitor-1 (PAI-1) levels, were assessed. Results At 3 months after open bypass grafting, activity of FVIII significantly increased from a median of 175% to 233% (P<0.001). At 3 months after endovascular treatment, the activities of FVIII, FIX, and FXI significantly increased from medians of 157%, 180%, and 156% to 184%, 218%, and 181%, respectively (P<0.05). Six patients with increased FVIII activity developed bypass graft thrombosis. Four patients in the endovascular group and three patients in the conservative treatment group with increased activity of vWF developed myocardial infarction (P=0.049). The subjects who developed restenosis had increased vWF activity (P=0.023) and decreased nitric oxide metabolite levels (P=0.003). Three subjects who received conservative treatment and developed PAD progression at 12 months had increased PAI-1 activity (P=0.028). Conclusion Patients with advanced PAD had a hypercoagulable status, and performance of open or endovascular revascularization was associated with further hypercoagulability. Increased activity of coagulation factors and altered levels of hemostatic markers of endothelial dysfunction were associated with PAD complications such as graft thrombosis, myocardial infarction, disease progression, and restenosis.
Рязанский государственный медицинский университет имени академика И.П. Павлова, ул. Высоковольтная, 9, 390026, г. Рязань, Российская Федерация (1) ГБУ РО ОККД, ул. Стройкова, 96, 390026, г. Рязань, Российская Федерация (2) Подход к лечению больных с полными блокадами сердца (атрио-вентрикулярными блокадами III степени) врожденного характера не является одно-значным. Особенные трудности ведения данной категории пациентов представляют бе-ременные женщины, нарушение ритма сердца у которых впервые выявляется при по-становке на учет по поводу беременности. Тактика лечения определяется особенностя-ми нарушения ритма, расстройствами гемодинамики, наличием синкопальных состоя-ний, анатомическими особенностей строения камер и клапанов сердца, сроками и осо-бенностями течения беременности. Данная статья представляет детальную информа-цию относительно этиологии, патогенеза, диагностики и возможных вариантов лечения полной врожденной блокады сердца у беременных женщин. Treatment options in patients with complete congenital heart block (atrioventricular block of III degree) may be controversial. Major obstacles are faced in pregnant women with newly detected heart block. Type of arrhythmia, presence of hemodynamic instability or syncope, anatomy of heart chambers and vessels, gestational age significantly influence the treatment. This article presents substantial information on etiology, pathogenesis, diagnostics, and possible treatment options in pregnant women with complete congenital heart block.Keywords: pregnancy, complete heart block, congenital heart block in pregnant, atrioventricular block in pregnant. _____________________________________________________________________________
We present a case of a 64-year-old woman with signs of debilitating condition including anginal chest pain, exertional dyspnea, and depression. The patient had previously suffered from a myocardial infarction after a loss of a close family member. Workup showed a posterobasal left ventricular aneurysm and moderate to severe mitral regurgitation in the absence of coronary atherosclerosis. Routine ultrasonography revealed abdominal aortic aneurysm and intraabdominal aortic deviation. The patient was immediately started on optimal medical treatment. On repeat assessment general condition was satisfactory, vital signs were normal, and investigations showed no signs of progressive heart failure or other significant clinical changes. Although prognosis in patients with myocardial infarction with normal coronary arteries is generally considered favorable, mechanical complications such as posterobasal left ventricular aneurysm with moderate to severe mitral regurgitation are possible.
Рязанский государственный медицинский университет имени академика И.П. Павлова, Рязань, Российская Федерация _____________________________________________________________________________ Эндотелиальные клетки являются функционально-ведущим типом клеток внутренней оболочки сосудов и выполняют множество важных функций, включая поддержание гемостаза, регуляцию сосудистого тонуса, роста сосудов и процессов воспаления. Дисфункция эндотелия ассоциирована с широким спектром заболеваний, включая атеросклероз, артериальную гипертензию, сахарный диабет, аутоиммунные, инфекционные, онкологические заболевания и другие. В обзоре рассмотрены основные аспекты эмбрионального развития и морфологические особенности эндотелиальных клеток, описаны процессы васкуло-, ангио-и артериогенеза, представлены ключевые биологически активные вещества эндотелиального происхождения, а также иммуноцитохимические маркеры, позволяющие идентифицировать принадлежность к эндотелиоцитам. Информация, изложенная в статье, поможет читателю получить знания об эндотелиоцитах, что в эру активного развития клеточной биологии и молекулярной медицины важно для понимания патофизиологии и современных методов лечения пациентов с заболеваниями, ассоциированными с дисфункцией эндотелия. Ключевые слова: эндотелий; ангиогенез; васкулогенез; эндотелиальные маркеры; эндотелиальная дисфункция.
Aim. To study and compare cytotoxicity of the main types of synthetic prostheses used in arterial reconstructive surgery, including polytetrafluoroethylene (PTFE) and polyethylene-terephthalate (Dacron). Materials and Methods. On the culture of human umbilical vein endothelial cells (HUVEC) of the 3rd passage, MTS test was conducted that is used in laboratory examinations with attraction of cellular technologies to study cytotoxicity of medical drugs and medical products. The test implies use of MTS reagent that is 3-(4,5-dimethylthiazol-2-il)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium; additionally phenazine methosulfate (PMS) was used that plays the role of electron-binding reagent. In the experiment, cells were incubated with PTFE and Dacron within 24 hours at 37ᵒC with 5% CO2. For control, HUVEC cultured in the standard growth medium, were used. In the presence of PMS, MTS was reduced by mitochondrial dehydrogenases of endothelial cells to formazan staining blue. Supernatant of cell cultures was evaluated by photocolorimetric method on Stat Fax 3200 analyzer (microplate reader) of Awareness technology Inc. Palm City Fl. (USA). Results. The lowest mean values were noted in Dacron group 0.21 (0.20-0.22) optical density units, the highest values were noted in the control group 0.36 (0.35-0.38); parameters in PTFE group were 0.35 (0.33-0.36). In comparison of the groups statistically significant differences were found between the control group and Dacron group (р0.001), control and PTFE group (р=0.037), Dacron and PTFE (р0.001). Incubation with Dacron led to suppression of metabolic activity of cells by 41.7% as compared to the control group (р0.001). Metabolic activity of cells exposed to PTFE, approached that of the control group, that is, it corresponded to the optimal conditions of culturing of endothelial cells in vitro. Conclusion. In comparison with polyethylene-terephthalate (Dacron), polytetrafluoro-ethylene (PTFE) showed the least suppression of metabolic activity of endothelial cells in vitro.
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