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Biomedical subjects

B Kozlovszky

Publications and source records attributed to B Kozlovszky.

11 recordsLinked to original sources

[In vitro study of endothelium-dependent relaxation and contraction of human atherosclerotic femoral artery].

According to present knowledge, altered arterial reactivity associated with hypertension, atherosclerosis and hypercholesterolemia is related to impaired release of endothelial derived relaxing factor (EDRF). Impaired relaxation followed by enhanced vasoconstriction leads to a well known clinical entities such as unstable angina, acut myocardial infarction. Impairment of EDRF may also account for smooth muscle cell proliferation and migration. Aim of present study was to examine the endothelial dependent response during in vitro conditions in human femoral arteries taken from bypass operation and leg amputation. Examining the contractility, the effect was modulated with nifedipin, EDTA and pertussis toxin, respectively. Endothelium dependent relaxation to acethylcholin and histamine were markedly diminished, while those to calcium ionophore were maintained throughout the study. These results suggest that at least two or more receptor-coupled system may be involved in generation of EDRF. However, direct relaxation of femoral artery to nitrovasodilatators (nitroglycerine) were comparable between control and atherosclerotic artery. Another striking change in atherosclerotic artery was the increased sensitivity to the vasoconstrictions. To eluciadate to exact biochemical mechanism underlying the endothelial dysfunction may help to develop a new vasodilatator drug.

Arteriosclerosis↗

Neutrophils obtained from obliterative atherosclerotic patients exhibit enhanced resting respiratory burst and increased degranulation in response to various stimuli.

Tissue destruction in atherosclerosis is partly due to uncontrolled protease and oxygen radical release. In this study we investigated the release of elastase and myeloperoxidase, as well as the production of reactive oxygen species by polymorphonuclear leukocytes (PMNLs) obtained from patients with obliterative atherosclerotic of the lower legs. In addition we measured the plasma concentration of xanthine oxidase. PMNLs of atherosclerotic patients have a greater ability to increase elastase and myeloperoxidase release after their stimulation with formyl-methionin-leucyl-phenylalanin (fMLP) and calcium ionophore, A23187, independently of their age, than PMNLs of healthy middle-aged subjects. Similarly to healthy elderly subjects there was an increased superoxide anion (O2-) production under basal condition in both atherosclerotic patient age-groups. The activation of PMNLs with fMLP and A23187 enhanced O2- formation both in healthy subjects and in patients with atherosclerotic disease of the lower legs, however the increase was significantly less in the latter group. No biochemical parameters showed significant correlation with patient's risk factors, however myeloperoxidase production was significantly higher in less severe stage of the disease (P < 0.05). We found that patients with atherosclerotic disease of the lower legs have higher plasma xanthine oxidase level than control subjects. This study indicates an other piece of evidence suggesting the activation and involvement of neutrophils in the pathogenesis of atherosclerosis of the lower legs. The similar tendencies in the reactivity of neutrophils during aging and in atherosclerosis suggest that atherosclerosis may be an early aging process.

Adult↗

[Serum elastin peptide concentration and human leukocyte elastase/antiproteinase balance in peripheral obstructive atherosclerosis].

In some pathological states such as therosclerosis tissue destruction may be accelerated due to uncontrolled protease release of polymorphonuclear leukocytes and other events such as decreased concentration and/or the inactivation of main protease inhibitor molecules in the serum. In this study, the authors measured the elastase release of polymorphonuclear leukocytes which increased in atherosclerosis independently of the patients aged compared to healthy young subjects. These findings were similar to the response of polymorphonuclear leukocytes separated from healthy elderly subjects. Simultaneously, the main plasma proteinase inhibitors such as alpha-1-antitrypsin and alpha-2-macroglobulin in healthy and atherosclerotic subjects were determined. alpha-1-antitrypsin did not decrease significantly, whereas alpha-2-macroglobulin did in sera of atherosclerotic patients compared to age matched subjects (p < 0.05). In contrast, the activity of porcine pancreatic elastase was more effectively neutralized by the plasma obtained from healthy subjects suggesting diminished antiprotease activity of sera obtained from patients. The authors concluded that increased elastase release and decreased antiproteinase activity should be considered in atherosclerotic arterial wall damage. The similarity of the results in aged and therosclerotic subjects suggests that arteriosclerosis is an earlier aging process.

Arteriosclerosis↗

[Clinical and biochemical parameters of patients with vascular stenosis in the lower extremities in the stage of intermittent claudication].

Clinical and biochemical parameters obtained by complex investigation of 100 patients suffering from intermittent claudication are presented by the authors. After taking the family and case history, we examined the patients and took laboratory tests including several lipid components, blood clotting factors and parameters influencing blood viscosity. The severity of peripheral vascular disease was defined by ankle/arm ratio, carotid arteries were studied by duplex sonography, coronary circulation was examined by ECG, exercise ECG and Thallium-201 isotopic myocardium scintigraphy. In conjunction with lower extremity vascular disease internal carotid stenosis was diagnosed in 62% and coronary stenosis in 52% of cases examined. In 35% all three regions were affected. The degree of carotid stenosis showed a strong correlation to the severity of the claudication, while in case of the coronary disease there was no connection proved, in spite of its high prevalence. Among the risk factors smoking was present in 89%, hypercholesterolaemia in 84%, hypertension in 54%, diabetes mellitus in 13%, impaired glucose tolerance in 42% and positive family history in 39% of cases. Smoking and accumulation of the risk factors showed correlation to the severity of the lower extremity vessel stenosis, while hypertension and carbohydrate metabolism disturbances showed significant correlations to the degree of carotid stenosis. From different lipid parameters only the cholesterol/HDL-cholesterol ratio showed significant correlation to the severity of the arteriosclerosis. The authors refer to intermittent claudication as the risk factor for carotid and coronary disease. They suggest the assessment of the cerebrovascular and cardiac risk in the patients. This way the optimal order of operative and/or non-operative therapy can be realized.

Adult↗

[Estimation of perioperative cardiac risk by means of dipyridamole myocardial scintigraphy in patients undergoing vascular surgery on the lower limbs].

UNLABELLED: The vascular surgery of lower limbs has an increased cardiac risk that is related to the special surgical procedure and the high risk patient population. The myocardium scintigraphy after the administration of dipyridamole is a reliable stress testing, even despite claudication complaints. The authors performed dipyridamole stressed quantitative MIBI scintigraphy in 35 patients with peripheral arterial disease for the assessment of prognostic importance of the test. Twenty seven of the 29 patients (92%) referred for vascular surgery had a positive scintigram. In the two thirds of abnormal investigations (18 patients) there had been rest perfusion defects too, despite the fact that only one patient had a positive history regarding myocardial infarct (MI). Six cardiac complications occurred; all in the aorta crossclamping group (6/21, 29%): 5 nonfatal postoperative MI (4 of them were silent) and 1 patient died. All of the complicated cases showed positive preoperative scintigraphy but only 2 of them had stress induced perfusion defect; 4 patients presented fixed defects. CONCLUSIONS: 1. Especially the operations necessitating the cross-clamping of aorta are harmful. 2. Cardiac complications are frequently atypical in their clinical appearance. Thus, 24 and 48 hour after the vascular surgery ECG an enzyme investigations are indicated. 3. The fixed MIBI defects that can also be found at rest, have significant implications. 4. The most effective cardiac risk stratification before vascular surgery is a complex approach in which the clinical, ECG and imaging data are incorporated.

Adult↗

Technetium-99m sestamibi scintigraphy for the assessment of lower extremity ischaemia in peripheral arterial disease.

Technetium-99m sestamibi was used for functional investigation of the muscle perfusion of lower extremities in 35 patients with peripheral vascular disease. The aim was to test what useful information could be obtained by additional imaging of the legs in patients referred for risk stratification with dipyridamole myocardial scanning. Posterior images were acquired over the thighs and calves after postocclusive reactive hyperaemia and at rest. Inter- and intraextremity ratios and differences between the stress and rest data were used for the assessment of abnormal circulation. Arteriography was performed in every case, and surgical procedures or transluminal angioplasty in 31 patients. To estimate diagnostic accuracy, the results of 99mTc-sestamibi scintigraphy were compared with those of angiography and the functional consequences of revascularization procedures. The sensitivity and specificity of 99mTc-sestamibi scintigraphy were 55% and 25%, respectively, with an overall accuracy of 50%. Apparently methodological error was not responsible for these poor results. Instead, a paradoxically high uptake of the radiopharmaceutical in muscles supplied by significantly stenosed vessels was identified as the main source of both false-negative and false-positive results. The phenomenon resembles the findings of a previous study involving delayed administration of thallium-201 after exercise. In conclusion, 99mTc-sestamibi scintigraphy has not proved sufficiently reliable to help in the management strategy for patients with peripheral vascular disease.

Dipyridamole↗

Superoxide anion production and intracellular free calcium levels in resting and stimulated polymorphonuclear leukocytes obtained from healthy and arteriosclerotic subjects of various ages.

It has been established that phagocytic cells are integral components of advanced arteriosclerotic plaques but their role in plaque formation remains unclear. Therefore, toxic agents, such as superoxide anion produced by polymorphonuclear leukocytes (PMNLs) were studied in a clinically defined group of arteriosclerotic patients suffering from obliterative arteriosclerosis of the lower legs. Owing to a close correlation between O2- generation and calcium, the intracellular free calcium concentrations of PMNLs were measured in a resting state and after stimulation with various agents, for example, opsonized zymosan (OZ), the chemotactic peptide f-met-leu-phe (FMLP), and the calcium ionophore A23187. Healthy aged-matched controls were employed. The patients were divided into two age groups: 30-59 years and 60-80 years. We found that in the younger group of arteriosclerotic patients, superoxide anion production and intracellular free calcium concentrations were increased even in the resting state, and only a slight increase was observed after stimulation compared with healthy controls. Granulocyte responses seemed to be similar, independent of the patient's age, to those found in healthy elderly subjects. Arteriosclerosis appears to be associated with an early aging process expressing marked alterations that are greater than those associated with normal aging.

Adult↗

Sera and leukocyte elastase-type protease and antiprotease activity in healthy and atherosclerotic subjects of various ages.

Serum and granulocyte elastase-type protease activities were determined simultaneously with their main plasma proteinase inhibitors such as alpha-1-antitrypsin and alpha-2-macroglobulin in healthy control and atherosclerotic (ATS) subjects. The age-related associations of these parameters were also investigated. Serum elastase-type protease activity increased, but not statistically significantly, with aging in both control and ATS subjects. The enhancement of elastase-type protease activity in sera of ATS patients was significantly (p less than .02) greater than control subjects only in the case of the elderly. The granulocytes' elastase activity was significantly greater in granulocytes derived from both middle-aged and elderly ATS patients (p less than .03 and p less than .06) compared to age-matched control subjects. Alpha-1-antitrypsin was not significantly lower, whereas alpha-2-macroglobulin was significantly lower in sera of ATS subjects compared to age-matched control subjects (p less than .01). The conclusion is that increased elastase-type activity and decreased antiproteinase activity should be considered as potential factors in atherosclerotic arterial wall damage. The similarity of the results in the elderly and the ATS subjects suggest that atherosclerosis is an early aging process.

Adult↗

Dipyridamole thallium-201 scintigraphy in patients with arteriosclerosis obliterans. Increased accuracy in identifying cardiac risk.

Forty-eight preselected patients (pts) with arteriosclerosis obliterans were investigated by dipyridamole thallium scintigraphy (DTS). No correlation was found between the distribution of positive or negative exercise ECG testing (ExECG) and isotopic risk-scores (P > 0.1 in the chi-square test). We assessed cardiac ischaemia in 12 pts with insufficient ExECG. Although only 2 pts had documented previous myocardial infarction, 20 pts exhibited irreversible perfusion defect. Silent reversible or irreversible ischaemia was identified in 12 pts (25%). Seven pts would not have been diagnosed to have coronary artery disease (CAD) even by ExECG. In conclusion, DTS was found very useful in these cases. We support a stepwise cardiac risk stratification before major vascular surgery.

Adult↗