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[Pulse wave velocity, thermography in the diagnosis of arteriosclerosis].

1. Pulse wave velocity (PWV) increased with increasing organic stiffness of the arterial wall mainly caused by arterio-sclerosis and also increasing functional stiffness of the arterial wall mainly caused by elevation of blood pressure. Age related changes in PWV have been recognized in variable countries. The PWV in the ascending aorta calculated by the characteristic impedance (378 +/- 141 cm/sec) was lower than that of conventional measurement in the descending aorta (697 +/- 144 cm/sec). 2. Thermography provide us indirect information of arteriosclerosis through reduction of skin temperature caused by disturbance of blood flow.

Aged↗

[Arteriosclerosis obliterans].

Arteriosclerosis obliterans (ASO) has become one of major health problems in the elderly people in Japan. This paper reviews the recent progress in the diagnosis and treatment of ASO. Both medical and surgical treatments, such as atherectomy catheters, endovascular metallic stenting, laser angioplasty and LDL-apheresis have recently been greatly developed. As atherosclerosis is a generalised disease, patients with ASO tend to have other atherosclerotic diseases, i.e., cerebrovascular disease, coronary heart disease and renal vascular disease. For the selection of treatments, we have to consider the whole background of the patients, including a quality of life.

Angioplasty, Laser↗

Chronic rejection in rat aortic allografts. IV. Effect of hypercholesterolemia in allograft arteriosclerosis.

Rat aortic allografts transplanted across histoincompatible strains develop arteriosclerotic alterations in the vascular wall that are virtually indistinguishable from those observed in human heart allografts during chronic rejection. In this study we have investigated whether hypercholesterolemia in the recipient rat accelerates allograft arteriosclerosis. Hypercholesterolemia was induced by a 4% cholesterol and 0.5% cholic acid diet, added to the normal rat diet. The cholesterol and cholic acid diet increased the level of serum total cholesterol from 1.3 +/- 0.0 to 4.8 +/- 0.9 (+/- SD) mmol/L and the level of low-density lipoprotein cholesterol from 0.3 +/- 0.0 to 2.6 +/- 1.0 mmol/L (p < 0.05) but caused no change in the level of high-density lipoprotein cholesterol, 1.0 +/- 0.1 versus 0.7 +/- 0.3 mmol/L. The level of plasma triglycerides remained also unchanged. Quantitation of two major chronic rejection-associated eicosanoids from the allograft vascular wall showed a significant increase in the synthesis of thromboxane B2 in the hyperlipidemic animals from 6.0 +/- 5.0 to 8.0 +/- 5.0 ng/mg dry weight and a slight reduction in the synthesis of 6-keto-prostaglandins F1 alpha. In vivo labeling of the recipient rat with tritiated thymidine and autoradiography showed that hypercholesterolemia did not affect the proliferation of inflammatory cells in the allograft adventitia, slightly increased the proliferation of smooth muscle cells in the media from 23 +/- 14 cells to 34 +/- 13 cells (+/- SEM) per cross section (p = ns), but slightly reduced the proliferation of smooth muscle cells in the intima from 13 +/- 6 to 6.2 +/- 1.5 (p = ns). Hypercholesterolemic recipients did not show any significant enhancement but, in fact, showed a delay in the generation of arteriosclerotic changes in the allograft intima. We conclude that although hypercholesterolemia, in the absence of hypertriglyceridemia, induces significant alterations in the eicosanoid metabolism and minor alterations in smooth muscle cell proliferation in the transplant vascular wall, it does not enhance arteriosclerotic alterations in chronically rejecting rat aortic allografts.

6-Ketoprostaglandin F1 alpha↗

[Arteriosclerosis obliterans that was improved by LDL apheresis].

We reported here a case of arteriosclerosis obliterans (ASO) in which clinical symptoms and signs were improved after repeated LDL apheresis. The patient was a 70-year-old man who was diagnosed as having ASO in 1989. Although drug treatment started for the arterial disease, such clinical manifestations as rubor and intermittent claudication were gradually worsening. In 1991, the patient was also found to have diabetes mellitus (DM), leading to admission for its treatment. Insulin therapy was initially required, but it finally became possible to maintain a good control of DM with diet therapy alone. Since hypercholesterolemia (402 mg/dl) was noted on admission, we began to give the patient pravastatin. In response to the medication, serum total cholesterol (TC) levels declined to 270 mg/dl, but no further improvement was obtained. We therefore decided to perform LDL apheresis on the patient, hoping the improvement of both ASO and hypercholesterolemia. After six series of LDL apheresis were performed during 4 weeks, ASO-related signs and symptoms (i. e., intermittent claudication) were remarkably improved, and serum TC levels were decreased below 200 mg/dl. Our experience in the present case suggested that this procedure would be useful as an effective choice of treatment for ASO, but further studies as to the indication and protocol of this therapeutic maneuver will be clearly needed.

Aged↗

Evaluation of arteriosclerosis progression with ultrasonic biopsy and intima-media thickness measurements.

Noninvasive ultrasonic biopsy (UB) can be used to classify arteriosclerotic lesions and their progression in the carotid and femoral bifurcation. Six UB classes have been defined. The rate of progression (ROP) to the next UB class in four years has been defined in 1270 normal subjects: it was 1.4% from class I to class II, 3.1% from II to III, 10.7% from III to IV, 17.9% from IV to V and 79.2% from class V to VI. In high risk subjects (HRS)--305 hyperlipidemics, 269 diabetics and 381 hypertensives--the ROP in 4 years was significantly higher considering all classes. This finding was matched by a more significant increase in intima-media thickness (IMT) increase in HRS in comparison with normal subjects. In conclusion UB and IMT measurements can be used to monitor arteriosclerosis progression. HRS have a comparable increase in ROP and IMT in four years indicating rapid progression in comparison with normals. UB appear to be more effective in evaluating progression when plaques and wall irregularities make IMT measurements difficult.

Adult↗

Beneficial effect of proteases on allograft arteriosclerosis in a rat aortic model.

Recently it has been shown that protease therapy ameliorates certain immune-mediated diseases. Thus we studied the effect of administration of a protease mixture on aortic transplant arteriosclerosis in rats. Segments of abdominal aorta from SHR strain were transplanted orthotopically into WKY recipients. Two groups of allografted rats were used. One group (n = 8) was treated with daily intraperitoneal injections of 12 mg of a protease formulation containing trypsin, bromelain and rutosid, and another group (n = 8) with placebo. Eight WKY rats were transplanted with syngenic aortas and treated with placebo. After 8 weeks, structural changes of the grafted segment were evaluated by morphometric analysis of formalin-fixed sections with specific stains. In untreated allografts there was a marked intimal thickening, medial necrosis with disruption of elastic fibres, and inflammatory infiltrates in the adventitia. Administration of proteases inhibited formation of neointima by 59.0% when cross-sectional areas were compared (80+/-11 versus 195+/-11 microm2, P<0.01; protease-versus placebo-treated allograft recipients respectively) and decreased medial injury as estimated by the integrity of elastic fibres and smooth-muscle cell density. Thus, in an experimental model of rat aortic allograft, protease administration ameliorates rejection-induced arterial wall remodelling.

Animals↗

Economic costs of neoplasms, arteriosclerosis, and diabetes in the United States.

Substantial economic resources are used for treatment of neoplasms, arteriosclerotic diseases, and diabetes (direct costs), and substantial productivity is lost due to morbidity and mortality (indirect costs). Costs of these disease groups in the U.S. in 1993 are estimated from national health expenditures from the Health Care Financing Administration and survey data from the National Center for Health Statistics. Based on primary diagnosis, direct costs are $37 billion for neoplasms, $126 billion for arteriosclerosis, and $15 billion for diabetes, and indirect costs are $70, $83, and $5 billion respectively. Costs would be higher, particularly for diabetes ($92-138 billion), if based on primary and secondary diagnosis.

Arteriosclerosis↗

[The current status of arteriosclerosis obliterans in Japan].

In Japan, the number of patients suffering from arteriosclerosis obliterans has increased remarkably in recent years, especially among the aged population. This paper presents an overivew of the current status of vascular surgery for atherosclerotic occlusive disease and the outlook for the future. It is important that endovascular surgery be further evaluated as an alternative to conventional arterial reconstruction, however, its precise indications and limitations can only be discussed with the accumulation of experience. The history of vascular surgery is extensive and not limited to the development of new techniques and methods of surgery alone. Further development in many fields will surely lead to great possibility in the future.

Angioplasty, Balloon, Coronary↗

[Risk factor, natural history and prognosis of the patients with arteriosclerosis obliterans].

A sufficient understanding of the risk factor and the natural history of arteriosclerosis obliterans, ASO, is essential for selecting the optimal treatment for this condition. Hypercholesterolemia, hypertension and cigarette smoking have been identified as independent major risk factors of ASO, and diabetics, obesity, hypertrigriceridemia, low HDL-cholesterol level, aging, gender, etc, as minor factors. The patients with ASO often have multiple risk factors, synergistically accelerating the disease progression. Recent objective studies on natural history of claudicants have demonstrated a more morbid prognosis, especially in the patients with disabling claudication, than that outlined by previous historical studies. Mortality rates for ASO patients in long-term follow-up have revealed to be significantly higher than those observed in control groups. The causes of death are mostly arteriosclerotic vascular disease, particularly coronary artery and cerebrovascular diseases, which indicate the significance of the systemic evaluation in treating patients with ASO.

Arteriosclerosis Obliterans↗

[Blood coagulation disorders observed in arteriosclerosis obliterans].

Activated platelet function indicated by beta-TG and PF4 is observed in the patients from arteriosclerosis obliterans (ASO) with severe disturbance of peripheral circulation. Increase in FpA, TAT, FDP and PIC suggest that blood coagulation and fibrinolysis are accelerated. Fibrinolysis might be activated in response to thrombus formation in screlotic peripheral artery. It is suggested that antiplatelet and/or anticoagulation therapy is acceptable for ASO with disorders of blood coagulation and fibrinolysis. Adequate antithrombotic therapy is necessary not only to treat ASO but also to prevent progression of arterioscrelosis. It is important to recognize harmful influence of antithrombotic therapy (antiplatelet, anticoagulation or thrombolysis) on blood coagulation and fibrinolysis, on the patient being canditate for vascular surgery.

Arteriosclerosis Obliterans↗

[The clinico-pathological aspects of acute exacerbation of arteriosclerosis obliterance].

Arteriosclerosis obliterance (ASO) is defined as the ischemic status of lower extremity produced by a stenotic and/or occlusive lesion of lumens of major arterial stress based on the pathology of atherosclerotic change. The sign and symptom of ASO are usually thought to be progressed slowly by natural progression process of atherosclerosis, however, in certain occasion, the progression of clinicopathological status of leg ischemia is acute as well as grave, so as to manifest rest pain or necrosis of the lower extremity. The basic mechanism of acute exacerbation of lower leg ischemia is attributed to the acute extended thrombus formation in arterial lumen. The factors influencing to the thrombus formation are represented as Virchow's Trias such as the changes in arterial wall, the stasis of blood flow and the coagulability of blood. One of the characteristic feature associated with massive and extended ischemia of lower leg is myonephropathic metabolic syndrome proposed by Haimovich in 1960. This syndrome is particularly seen immediately following the restoration of blood flow to the severely damaged leg and characterized by renal as well as systemic organs disorder. The relationship between the extent of muscle damage and the duration of ischemia is analysed through our data.

Acute Kidney Injury↗

[Clinical diagnosis of arteriosclerosis obliterans].

The diagnosis of arteriosclerosis obliterans of the lower extremities can be made by the history alone or by the physical examination alone in the most patients. It is very important to evaluate the hemodynamic study in determination of indication for operation and operative procedures. The two major symptoms, each of which diagnostic, are intermittent claudication and ischemic rest pain. Intermittent claudication is pain or fatigue that occurs in a muscle or muscle group on repititive use. The anatomical level of claudication is significant. When aorto-iliac artery is obstructed, pain may occur first in the hip or thighs. Pain occurs in the calf in the occlusion of the femoral artery and foot pain indicates the occlusion of distal popliteal artery. Ischemic rest pain indicates an advanced stage of the disease. Fontaine classification is usually used as the stage of ischemia on the extremity. There are many laboratory evaluations of circulatory insufficiency in the diagnosis of arteriosclerotic obliterans. Measurement of segmental blood pressure is most valuable and useful among various measurements. We can get critical informations of circulatory insufficiency in the leg using segmental blood pressure. In order to differentiate from arteriosclerotic obliterans there are thromboanyitis obliterans aortitis syndrome, popliteal arterial entrapment syndrome, spinal canal stenosis, and diabetic arterial occlusive disease.

Arteriosclerosis Obliterans↗

[Atherectomy in patients with arteriosclerosis obliterans: angiographic follow-up study of 186 lesions in 146 patients].

Atherectomy (ATE) is a new catheter-mediated technique for the removal of atheroma in patients with arteriosclerosis obliterans (ASO). ATE was performed using 7-10 Fr. Simpson Peripheral Athero Track catheters at 186 sites in 146 patients, whose lesions involved 49 common iliac arteries, 66 external iliac arteries, 68 femoral arteries and three other arteries. The initial success rate was 94.1%. The mean percent of the diameter stenosis was reduced from 79.0 +/- 1.2% (mean +/- SD) to 22.7 +/- 1.0%. There were two cases of perforation that required surgical treatment (1.1%). The complication rate was 4.4%. The 0.5-, 1-, 2- and 3-year patency rates were 87.6%, 79.6%, 62.5% and 62.5%, respectively. The rate of long-term patency in each segment of arterial lesions revealed that the patency rate in the common iliac artery was significantly higher than the rates in the external iliac artery (p < 0.05) and femoral artery (p < 0.01). The patency rates for long lesions (> or = 2.0 cm) and occluded lesions were significantly (p < 0.01) lower than those for short lesions (< 2.0 cm). Diabetic patients had a higher re-stenosis rate than nondiabetic patients (p < 0.05). In conclusion, ATE is an effective new method for the treatment of patients with ASO.

Aged↗

[Do increased lipoprotein(a) levels in euthyroid autoimmune thyroid diseases predict an increased risk of arteriosclerosis?].

Elevated serum levels of lipoprotein(a) [Lp(a)] represent an independent risk factor in the development of arteriosclerosis and coronary heart disease. In overt but also in subclinical hypothyroidism a reversible increase of Lp(a) occurs. We compared Lp(a) serum levels, cholesterol, triglyceride, HDL- and LDL-cholesterol in 19 hypothyroid patients prior to and following the state of euthyroidism (group 1). On the other hand in group 2 we investigated 20 euthyroid patients having elevated thyroid antibodies as against 50 euthyroid normolipemic control subjects without detectable thyroid antibodies. Group 1: The elevated Lp(a) serum levels of the hypothyroid patients decreased significantly in the euthyroid state (37.9 +/- 8.24 vs. 28.1 +/- 6.13 mg/dl, mean +/- SEM). Group 2: The mean Lp(a) serum levels of the patients with increased thyroid antibodies were significantly higher than those of the control group (24.8 +- 5.78 vs. 9.6 +/- 1.56 mg/dl, mean +/- SEM). In other parameters of lipid metabolism and thyroidal function no significant differences between both groups could be seen. The question arises whether such isolated Lp(a) elevation will lead to an increased arteriosclerotic risk. To minimize this possible risk regular controls of thyroid function should be carried out in euthyroid patients with elevated thyroid antibodies. In this way hypothyroidism may be detected and treated at an early stage.

Adult↗

Inducible and endothelial nitric oxide synthase expression during development of transplant arteriosclerosis in rat aortic grafts.

In the vascular system, distinct isoforms of nitric oxide synthase (NOS) generate nitric oxide (NO), which acts as a biological messenger. Its role in the development of transplant arteriosclerosis (TA) is still unclear. To investigate whether NO is involved in TA, we studied the expression of NOS isoforms, inducible NOS (iNOS) and endothelial NOS (eNOS), by immunohistochemistry and in situ hybridization during the first two post-transplantation months and their relation with cold ischemia (1 to 24 hours) and reperfusion injury using an aortic transplantation model in the rat. We found an increased iNOS expression in the intima and adventitia and a decreased expression in the media, whereas eNOS expression was not significantly altered during the development of TA. Co-localization studies suggested that iNOS-positive cells were vascular smooth muscle cells, monocyte-derived macrophages, and endothelial cells. Prolonged ischemic storage time resulted in an increase in eNOS expression in the neointima. In situ hybridization showed iNOS mRNA expression by vascular cells in the neointima and media. NO produced by iNOS and eNOS may be involved, at least in part, in the pathogenesis of TA in aortic grafts. Additional studies are needed to confirm the modulatory mechanism of NO during the development of TA.

Amino Acid Sequence↗

Arteriosclerosis in dialysis patients.

Arteriosclerosis is a constant problem in long-term hemodialysis patients. Computer tomography of the abdominal aorta allows a well-defined and reproducible evaluation of aortosclerosis. In the cross-sectional study, aortosclerosis was significantly accelerated in 84 chronic hemodialysis patients and was comparable to the results found in 20-year older control patients without renal disease. The increase of aortosclerosis correlated significantly with age of the patient, smoking, and duration of dialysis therapy. Furthermore, increased VLDL cholesterol and decreased HDL cholesterol seem to enhance aortosclerosis in our dialysis patients. In the longitudinal study (two CT scans with a time interval of 87 +/- 62.7 months) in 36 dialysis patients, progressed aortosclerosis correlated significantly with the long duration of hypertriglyceridemia, VLDL cholesterol, uric acid, and calcium phosphate products. Progression of aortosclerosis was reduced in parathyroidectomized patients. The study suggests that premature aortosclerosis is found in dialysis patients. In addition to the common risk factor of aortosclerosis disturbed calcium phosphate and parathyroid hormone metabolism seem to enhance aortosclerosis in patients under maintenance hemodialysis.

Adult↗

Femoro-femoral cross-over grafting. A limb-saving operation in poor-risk patients with obliterative arteriosclerosis.

A series of 12 femoro-femoral cross-over grafting procedures is reported. Eleven patients were operated on for severe ischaemia and one for disabling claudication. Nine of the reconstructions were profunda revascularizations. Concomitant femorotibial reconstruction was carried out in one case. There were no operative deaths or postoperative complications. Peroperative blood flow measurements and clinical symptoms gave no evidence of any "steal" phenomenon. One graft became occluded primarily, but the others remained patent during an observation period ranging from two months to four years and ten months. Despite a functioning graft, one major amputation was necessary due to severe distal arteriosclerotic lesions. In all other patients, either the limb was saved or claudication was relieved. This operation seems to be suitable for poor-risk patients with predominantly unilateral iliac arteriosclerosis together with impending gangrene or disabling claudication.

Aged↗

Elastin receptor and cell-matrix interactions in heart transplant-associated arteriosclerosis.

Vascular cells, as well as monocytes, neutrophils, and lymphocytes which may infiltrate vascular walls and tissues express a multifunctional 67 kD protein which also serves as a subunit of the cell surface "elastin receptor". This protein differs structurally and functionally from other matrix adhesion molecules. Unlike the integrins or cadherins, it is not a transmembrane molecule, but can be immobilized on the cell surface by association with two other membrane-anchored proteins. Once expressed on the cell surface, it may mediate cell-matrix interaction in a calcium-independent manner. Unlike most integrins, which recognize the linear sequence on the matrix ligands (RGD), it recognizes the secondary structure of the matrix macromolecules and binds to several non identical domains on different matrix components, as long as they form the appropriate hydrophobic conformation. Similarly to the transmembrane selectins, the 67 kD protein has lectin-like properties with the galactosugars' binding specificity. However, binding of galactosugar-bearing ligands interrupts its contacts with matrix proteins and displaces the 67 kD protein from the cell surface. Moreover, the 67 kD protein also serves as an intracellular chaperone which facilitates secretion of tropoelastin and assembly of elastic fibers. In this review I will address the role of this 67 kD protein in mechanisms of mutual interaction between vascular smooth muscle cells, infiltrating leukocytes, and several components of extracellular matrix during the development of heart-transplant associated arteriosclerosis.

Animals↗