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[Gene therapy of vascular diseases].

Gene therapy of vascular diseases represents a new perspective field in the modern biomedical science. It is based on the employment of genetic constructions for medical treatment. The paper reviews major directions in gene therapy of vascular diseases: inhibition of proliferative processes in the vascular wall; administration into the elements of vascular wall of genes responsible for nitric oxide synthesis; normalisation of blood pressure regulatory system; synthesis of thromboembolic factors and anticoagulants; gene therapy of atherosclerosis; revascularisation of ischaemic myocardium and inhibition of tumor vascularisation.

Animals↗

Diagnosis and management of vascular disease in systemic sclerosis.

Vascular disease is seen in virtually all patients with systemic sclerosis and presents several challenges to physicians caring for them. Early recognition of isolated pulmonary hypertension and scleroderma renal crisis may be keys to successful outcomes. Although complete reversal of vascular disease is usually not possible, the availability of calcium channel blocking agents for RP and isolated pulmonary hypertension and ACE inhibitors for hypertensive renal disease has improved the morbidity and mortality of these patients. Optimal management of the vascular events in systemic sclerosis will ultimately depend on a clearer understanding of their pathogenesis. Treatment may ultimately be directed at preventing the development of these vascular syndromes. This may occur through combined therapy directed at both the abnormal immune response and disregulated fibroblast function seen in the disease, as well at the abnormal vascular responses. Such therapies have yet to be identified.

Humans↗

[Prevalence of vascular disease in candidates for myocardial revascularization with aortocoronary bypass: review of the literature and practical implications].

BACKGROUND: Cardiovascular disease remains the main cause of death and morbidity in the industrialized world. Atherosclerosis is a slowly progressive disease; coronary artery disease may be the first presentation of a systemic pathology. The association between coronary artery disease and peripheral vascular disease has often been confirmed by multicenter trials; nevertheless it still remains a subject of debate. METHODS: In order to assess the incidence of coronary artery disease and the degree of associated vascular lesions, between January 1997 and September 1999, in the Department of Cardiothoracic Surgery of the Second University of Naples (Italy), all candidates to coronary artery bypass grafting (CABG) were submitted to routine preoperative echo color Doppler study of the carotid vessels, abdominal aorta and iliac-femoral arteries. The correlation between the echo color Doppler findings, the angiographic patterns of coronary lesions and atherosclerotic risk factors was analyzed in all cases. RESULTS: Among 540 patients undergoing CABG, 418 (77.4%) had carotid disease, with a stenosis > 70% in 62 (11.3%). Forty-nine (79%) patients had asymptomatic severe carotid disease. A significant correlation between the severity of coronary disease and the incidence of severe carotid disease was found (p = 0.02). An abdominal aortic dilation was found in 37 cases (6.7%). Its diameter exceeded 35 mm in 14 patients (2.5%) and in 8 it was associated with triple vessel coronary disease. Atherosclerotic lesions of the iliac-femoro-popliteal axis were found in 394 (72.9%) patients and strongly correlated with the severity of coronary artery disease (p = 0.02); lesions were hemodynamically significant in 91 (16.8%) cases. CONCLUSIONS: Our study emphasizes the association between coronary artery disease and vascular disease. Non-invasive complete arterial investigation should be routinely performed in patients undergoing CABG.

Adult↗

High-resolution CT of lung disease related to collagen vascular disease.

Although connective tissue diseases may have similar radiographic appearances, a variety of pathologic processes can be seen in the lung of these patients. In such circumstances, early recognition of lung involvement is now easily demonstrated by imaging methods. The development of thin-section and dynamic CT techniques has significantly improved diagnostic accuracy. Moreover, expiratory HRCT is a helpful technique in demonstrating air trapping in these patients. The radiologist plays a significant role in the evaluation of pulmonary manifestations of connective tissue diseases.

Connective Tissue Diseases↗

Effects of nutrition of disease and life span. II. Vascular disease, serum cholesterol, serum thromboxane, and heart-produced prostacyclin in MRL mice.

Mice of the autoimmune strain MRL/1, the congenic strain MRL/n, and two control strains, Balb/c and C57BL/6 mice, were fed diets which varied in the content of lipid and cholesterol. Serum cholesterol levels were highest in mice fed diets containing cholesterol and lowest in mice fed laboratory "chow." Animals fed diets that increased serum cholesterol had decreased production of prostacyclin by vascular tissue and increased production of thromboxane A2 by platelets. Prostacyclin production by heart tissue in response to arachidonic acid showed a negative correlation (r = -0.86) with serum cholesterol. In contrast, serum thromboxane demonstrated a positive correlation (r = 0.70) with serum cholesterol. The prevalence of autoimmune vasculitis seen in MRL/lpr mice was not affected by diet. However, MRL/lpr mice fed a high-fat, cholesterol-containing diet had intimal vascular lesions containing foam cells typical of arteriosclerosis. It is suggested that diets that raise serum cholesterol may influence the nature of autoimmune-mediated vascular disease by altering the balance between thromboxane and prostacyclin.

Animal Nutritional Physiological Phenomena↗

Pathophysiology of vascular disease in diabetes: effects of gliclazide.

Diabetes mellitus is a major risk factor for coronary heart disease, peripheral vascular disease, and cardiovascular disease. The prevalence of these complications is increased about two- to four-fold in people with diabetes in the United States, and they contribute substantially to morbidity, mortality, and healthcare costs. The pathogenesis of macrovascular disease in diabetes is multifactorial. Endothelial injury is an early event, followed by macrophage adherence and uptake of lipids to produce a fatty streak. Platelet adherence, aggregation, and release of thromboxane and platelet-derived growth factors may then occur. Quantitative and qualitative alterations of lipoproteins are seen, particularly in uncontrolled insulin-dependent and non-insulin-dependent diabetes. Hyperinsulinemia may be contributory, as may elevated plasma proinsulin levels. Glycation of plasma proteins and of components of the vascular wall occurs, and altered coagulation and/or fibrinolysis may lead to thrombosis. The process is accelerated by hypertension, smoking, and hypercholesterolemia. Gliclazide is an oral sulfonylurea agent that has been reported to have actions on platelet function and fibrinolysis in addition to its effects on glycemia. The evidence for this is reviewed, and recommendations for future studies are made.

Arteriosclerosis↗

Drug-induced pulmonary vascular disease--mechanisms and clinical patterns.

An extensive vascular surface area places the lungs at risk for damage by blood-borne drugs. Drug-induced pulmonary vascular disease may present clinically as acute pulmonary edema, pulmonary edema followed by diffuse interstitial lung disease, pulmonary vascular occlusion, pulmonary hypertension or hemorrhage. It is important to recognize these reactions as drug-related because many are reversible with discontinuation of the drug and supportive therapy. Failure to recognize drug-induced pulmonary vascular disease can lead to significant morbidity and, in some cases, death.

Adult↗

RHO SIGNALING in vascular diseases.

Rho signaling pathways in vascular smooth muscle cells are highly activated in hypertension, a condition associated with a variety of vascular diseases, including restenosis injury and atherosclerosis. In this review we suggest that inflammatory cytokines and agonists of G protein-coupled receptors that activate Rho are effective triggers of vascular disease. Accordingly, Rho kinase inhibitors and statins may have therapeutic potential for preventing vascular disease characterized by Rho-mediated cell proliferation and gene expression.

Cell Proliferation↗

Intraaortic balloon pump insertion after percutaneous revascularization in patients with severe peripheral vascular disease.

Severe aortoiliac peripheral vascular disease (PVD) is considered a contraindication for the placement of an intraaortic balloon pump (IABP) because of a high risk of limb ischemia. Recent advances in percutaneous transluminal angioplasty (PTA) and stenting have altered the treatment of iliac stenoses such that the results of PTA with stenting compare favorably with surgery. We reviewed our experience with placement of IABP between July 1994 and February 1996. Of 64 patients receiving IABP, 17 had known or suspected peripheral vascular disease. Severe iliac or distal aortic stenoses were present in 9. These 9 patients underwent PTA with or without stenting prior to 10 IABP insertions. Limb ischemia occurred in 10% of PVD patients treated with percutaneous revascularization, compared to 11% in patients without PVD. No patient had a serious vascular complication or required vascular surgery. We conclude that percutaneous revascularization in patients with severe aortoiliac PVD, for whom this IABP insertion had previously been considered contraindicated, results in a low rate of limb ischemia.

Aged↗

Mitochondrial dysfunction in chronic ischemia and peripheral vascular disease.

In peripheral vascular disease, impaired muscle energy metabolism is assumed to be due mainly to defective vascular O2 supply, the resulting cellular hypoxia inhibiting oxidative ATP synthesis. Older work suggested a compensatory increase in muscle aerobic enzymes, but more recent studies suggest a relative decrease in some mitochondrial components and an accumulation of damage in mitochondrial DNA, perhaps due to reactive oxygen species. However, to establish whether in vivo muscle mitochondria suffer from anything other than a low concentration of O2 will require more knowledge of the mitochondrial behaviour at low PO2, and the actual cell PO2 during exercise.

Journal Article↗

Aortoiliac occlusive disease in patients with known or suspected peripheral vascular disease: safety and efficacy of gadofosveset-enhanced MR angiography--multicenter comparative phase III study.

PURPOSE: To prospectively determine the safety and efficacy of the gadolinium-based blood pool magnetic resonance (MR) imaging contrast agent gadofosveset in patients known to have or suspected of having peripheral vascular disease. MATERIALS AND METHODS: Ethical committee approval and patient written informed consent were obtained. This study was compliant with the Health Insurance Portability and Accountability Act. Adults known or suspected to have peripheral vascular disease received gadofosveset (0.03 mmol per kilogram of body weight) for MR angiography of the aortoiliac region. Gadofosveset-enhanced MR angiography and unenhanced two-dimensional time-of-flight MR angiography were compared with the reference standard, conventional angiography, for the presence of vascular stenosis. All patients were monitored for adverse events with hematologic analysis, analysis of blood chemistry, urinalysis, and electrocardiographic parameters; these methods were analyzed to determine safety. RESULTS: A total of 274 patients were enrolled at 37 centers. Gadofosveset-enhanced MR angiography showed significant improvement (P < .001) compared with unenhanced MR angiography for each of the readers for diagnosis of clinically significant (> or = 50%) stenosis. Specificity and accuracy were significantly greater for three readers, and sensitivity increased significantly for two readers. For all readers, the area under the receiver operator characteristic curve for both quantitative and qualitative measures of significant disease increased (P < .001) for gadofosveset-enhanced MR angiography versus two-dimensional time-of-flight MR angiography. All readers also expressed more confidence in diagnosis (P < .001) and found fewer images to be uninterpretable (0.5% vs 11.0%). The most common adverse events were as follows: feeling hot, 12 (4.4%) patients; nausea, 10 (3.6%) patients; headache, nine (3.3%) patients; and burning sensation, eight (2.9%) patients. Only four serious adverse events were reported, in three patients, and all events were rated as unlikely related to the drug. No patients were excluded because of adverse events or laboratory abnormalities. There were no clinically important trends in the findings of hematologic analysis, blood chemistry, urinalysis, electrocardiography, or physical examination. CONCLUSION: On the basis of substantial improvements over non-contrast MR angiography in efficacy and a minimal and transient side-effect profile, gadofosveset was found to be safe and effective for MR angiography in patients known or suspected to have peripheral vascular disease.

Aged↗

Electrostimulation of the nervous system for patients with demyelinating and degenerative diseases of the nervous system and vascular diseases of the extremities.

The results of electrostimulation of the spinal cord for symptoms other than that of pain are recorded in this publication. 50% of patients with multiple sclerosis, primary lateral sclerosis and hereditary spino-cerebellar disorders were observed to have enduring favourable changes in neurological function during the 15 to 27 months they have been followed. The patients who were the least severely disabled had the greatest amount of increased function and were benefitted the most by the stimulation. Those who had the fewest neurological pathways affected make the most rapid progress. For example, the patient with only an ataxic or spastic gait was observed to improve faster than the patient with an ataxic and a spastic gait. The long-term effect of electrostimulation of the spinal cord on patients with these diseases is unknown at the present time. The purpose of the stimulation is to increase neurological function so that the patient can live a better life style. It is not thought that the electrical current is responsible for a 'cure' of the basic disease process. Electrostimulation of the posterior spinal roots and spinal cord, while not new, has not been used extensively for the treatment of patients with arterial disease. The patients who have responded the most dramatically to electrostimulation are those with vasospastic disorders. A larger percentage of patients showed a greater response to implanted stimulation than to transcutaneous stimulation. Electrostimulation of the nervous system is not designed to replace standard therapeutic measures of treatment of patients with vascular disease but to supplement them.

Ataxia↗

Peripheral neurological complications of aortoiliac vascular disease.

Six patients with an aortoiliac vascular disease and a peripheral neurological deficit are presented. Clinical and electromyographic findings revealed lumbosacral plexus, sciatic and femoral nerve lesions. A correlation is made between the level of the vascular lesion (aortic, aortoiliac or distally) and the type of peripheral nerve deficit observed. In a patient complaining of pain, weakness, or numbness in a leg, the differential diagnosis should include aortoiliac vascular disease. The peripheral neurological symptoms may be the initial manifestation of the vascular disease or may appear in the early post-operative period.

Aged↗