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Biomedical subjects

M Sesto

Publications and source records attributed to M Sesto.

At least 19 recordsLinked to original sources

Products of advanced glycation in patients with type 2 diabetes and vascular disease.

BACKGROUND: Non-enzymatic glycation leading to advanced glycation endproduct (AGE) formation is thought to contribute to vascular pathology. In the present study, AGEs and anti-AGE antibodies in free and immune complex-bound form were assayed in the serum of diabetic (DMCAD) (n = 69) and nondiabetic (n = 78) patients with coronary artery disease (CAD) and in control subjects (n = 47) free from vascular disease. METHODS: A blocking enzyme-linked immunosorbent assay (ELISA) was used to test immunoreactivity against AGE epitope(s) and a competitive ELISA was used to measure total AGE content. RESULTS: Anti-AGE immunoreactivity was significantly higher in diabetic than in control subjects (P = 0.045). Although a wide range of anti-AGE antibody titres were observed in nondiabetic CAD patients, there was no significant difference from those of control subjects. Both diabetic and nondiabetic CAD patients had a higher concentration of circulating immune complexes containing the AGE moiety as antigen than did control subjects (DMCAD versus control, P = 0.041; CAD versus control, P = 0.047). Study patients showed a positive correlation between serum AGE and AGE-immune complexes (DM, r = 0.29, P = 0.014; CAD, r = 0.26, P = 0.019), whereas no such correlation was recorded in controls (r = 0.08, P = 0.89). CONCLUSION: To our knowledge, this is the first study demonstrating increased AGE-immune complexes in patients with CAD, either with or without diabetes, suggesting that AGE-immune complexes might be involved in the atherosclerotic process, either as the result of it or as part of the pathophysiologic process.

Adult↗

Soluble LDL-immune complexes in type 2 diabetes and vascular disease.

BACKGROUND AND AIMS: The oxidative modification of LDL has been shown to affect its clearance and to exert cytotoxic and immunogenic effects. The objective of our study was to analyse markers of LDL oxidation-soluble LDL containing immune complexes (LDL-ICs) in type 2 diabetes with micro- and macrovascular disease. PATIENTS AND METHODS: The study included 69 diabetic patients with coronary artery disease (DM + CAD), 78 non-diabetics with CAD, 47 controls, and 27 diabetics with nephropathy and 36 free from complications. OxLDL antibodies and advanced glycated end-products were measured by ELISA, and LDL-IC apo B content after PEG precipitation. RESULTS: Determination of a broad range of oxLDL antibody activity in all study groups showed no significant differences. In contrast, the content of apo B, a component of the antigen moiety of oxLDL-ICs, was higher in CAD and diabetes (+ CAD) than in LDL-ICs isolated from controls (p < 0.001). LDL-ICs did not differ between patients with CAD + DM and CAD patients free from diabetes. LDL-IC levels in diabetic patients with or without microangiopathy were significantly higher than in healthy volunteers (PEG-apo B 0.278 +/- 0.107 vs. 0.165 +/- 105 g/l, p < 0.002; PEG-IgG 151.7 +/- 76 vs. 115.4 +/- 62 g/l, p < 0.05). However, there was no significant difference in the level of circulating LDL-ICs between the subgroup of diabetic patients with nephropathy/retinopathy and patients free of microvascular disease (Ab-oxLDL 27.7 +/- 10.4 vs. 27.1 +/- 9.3 AU, NS; PEG-apo B 0.324 +/- 0.111 vs. 0.287 +/- 0.124 g/l, NS; PEG-IgG 1.68 +/- 0.68 vs. 1.42 +/- 0.80 g/l, NS). There was a statistically significant positive correlation between AGE content and LDL-ICs (r = 0.35, p < 0.009). A significant but inverse correlation was recorded between triglyceride concentration and level of LDL-ICs in DM + CAD (r = - 0.32, p < 0.016) and CAD patients (r = - 0.35, p < 0.002). A highly significant negative correlation between triglycerides and circulating LDL-ICs (r = - 0.54, p < 0.039) was observed in patients with early nephropathy, but not in those with physiological proteinuria. It is known that at a high triglyceride level in type 2 diabetes, the majority of LDL are small and dense, thus being more susceptible to oxidative modification. This could be a possible mechanism explaining why more LDL-ICs, with a level inversely correlating with triglyceride concentration, are generated in diabetes. CONCLUSION: The increased level of circulating LDL-ICs is a risk factor for the general population, including those with diabetes. Our results suggested the contribution of LDL-ICs to the development of atherosclerosis to probably be more significant than the direct contribution of oxLDLAb itself.

Antigen-Antibody Complex↗

Lecithin-cholesterol acryltransferase activity in patients with coronary artery disease examined by coronary angiography.

This study grew out of observations of certain lecithin:cholesterol acyltransferase (LCAT) abnormalities in patients with atherosclerosis. We studied the interrelationships among LCAT, and total cholesterol, free and esterified cholesterol, cholesterol in individual lipoprotein fractions, triglycerides, phospholipids, free fatty acids, L-lactates in 90 angiographically examined patients with coronary artery disease and 30 control subjects without clinical manifestations of coronary artery disease. Results of the study showed LCAT activity to be significantly decreased (P < 0.05) in patients with single-, double-, or triple-vessel disease than in disease-free subjects. LCAT was also found to follow the stage of coronary artery disease in angiographically examined patients. Decreased LCAT activity was accompanied by lower high-density lipoprotein cholesterol, elevated ratio of unesterified to esterified cholesterol, and increased levels of L-lactates, free fatty acids, and low-density lipoprotein cholesterol. Total cholesterol and triglycerides were within or slightly above the normal limits. The results show LCAT to be a significantly better indicator of the risk of coronary artery disease than either total cholesterol or triglycerides.

Adult↗

The patent ductus arteriosus as a source of recurrent peripheral embolisations.

A patient with a multiple peripheral embolisation of unknown origin is presented. Because of her extreme obesity, some diagnostic procedures could not be performed (CAT), and some were performed with great difficulty (conventional ECHO, DSA of the aorta). Transesophageal echocardiography was the key procedure in the diagnosis of the floating thrombotic mass in the descending aorta. A surgical operation was performed, and a thrombus was found in the aortic orifice of the hemodynamically insignificant patent ductus arteriosus. The patient has now been 18 months in good condition and free of thromboembolic events.

Adult↗

Lecithin:cholesterol acyltransferase activity in patients with acute myocardial infarction and coronary heart disease.

Literature data suggest that identification of the conditions preventing lecithin:cholesterol acyltransferase (LCAT) to produce normal cholesterol esterification might be of utmost importance in the follow-up of atherosclerosis. Interrelationship between LCAT activity, and total cholesterol (TC), unesterified cholesterol (UC), esterified cholesterol (EC), low and high density lipoprotein cholesterol (LDL-C, HDL-C), triglycerides (TG), phospholipids (PL), free fatty acids (FFA), l-lactate (LAC), and electrolytes, i.e. zinc (Zn), calcium (Ca) and magnesium (Mg), was investigated in 60 patients with acute myocardial infarction (AMI), 30 patients with coronary heart disease (CHD) and 30 healthy control subjects. Results of the study revealed LCAT activity to be significantly decreased in atherosclerotic patients, with a significantly increased ratio of unesterified-esterified cholesterol (UC/EC), as compared to the control group of normal subjects. A decreased LCAT activity was accompanied by elevated values of phospholipids and LDL-C, a moderate increase in triglycerides, and a decreased quotient of HDL3/HDL2 cholesterol. Accordingly, a decreased activity of LCAT could with great certainty be considered a high-risk biochemical factor for atherosclerosis.

Adult↗

The incidence of myocarditis in endomyocardial biopsy samples from patients with congestive heart failure.

We present the combined experience of three Yugoslavian cardiovascular centers in the application of endomyocardial biopsy for the diagnosis of myocarditis in patients who present clinically with congestive heart failure. The study group comprised 107 patients (mean age, 40.8 years; range, 19 to 61 years). On the basis of patient history and diagnostic tests, the following clinical diagnoses were established: dilated cardiomyopathy (85), myocarditis (16), and alcohol-induced heart disease (6). EMB samples were taken from the left ventricle (95) or both ventricles (12) by use of a King's College bioptome, with a mean of 3.2 samples per patient. Histologic evidence of myocarditis was noted in 10 of 85 patients (12%) with a clinical diagnosis of dilated cardiomyopathy, in 2 of 6 patients (33%) with alcohol-induced heart disease, and in 12 of 16 patients (75%) with a clinical diagnosis of myocarditis. There was confirmation of the clinically suspected diagnosis in 63% of cases, a change of diagnosis based on histology in 15% of cases, and nonspecific findings in 22%. However, useful information was obtained in 78% of the cases, and there was a 22% incidence of histologically proven myocarditis for the entire group. Our results indicate that endomyocardial biopsy is beneficial in determining the true incidence of myocarditis in patients with a clinical presentation of dilated cardiomyopathy.

Adult↗

Native collaterals in the development of collateral circulation after chronic coronary stenosis in mongrel dogs.

The response of native collateral circulation to chronic stenosis of the left circumflex coronary artery (LCx) was studied in 17 mongrel dogs. Stenosis restricted reactive hyperemia of the LCx without affecting resting flow. Regional myocardial blood flow was measured by the tracer microsphere technique. Coronary collateral blood flow to the LCx was determined during maximal reactive hyperemia of the left anterior descending branch before and 5 weeks after implantation of a fixed LCx stenosis in the open-chest preparation. The protective effect of collaterals was tested by LCx ligation 5 weeks after implantation of stenosis. Presence of acute myocardial infarction was determined by nitroblue tetrazolium staining. Eleven dogs had a myocardial infarction (group A), but six dogs showed no evidence of infarction at autopsy (group B). In group A, collateral flow and minimal coronary resistance of the LCx bed changed little after LCx stenosis, from 12 to 15 ml/min/100 g and from 10.5 to 10.0 mm Hg/ml/min/100 g, respectively (both p less than 0.05). In contrast, collateral flow in group B increased from 22 to 102 ml/min/100 g (p less than 0.05), and minimal coronary resistance of the LCx bed decreased from 4.8 to 1.4 mm Hg/ml/min/100 g (p less than 0.01). Group A had lower native collateral flow (p less than 0.05) and higher native minimal coronary resistance of the LCx bed than group B (p less than 0.05). Postobstructive LCx pressure correlated well with blood flow data. The LCx risk region was of comparable size in groups A and B, 36.4% vs 39.0% of total left ventricle (p greater than 0.05). Two responses of collateral circulation to chronic stenosis were documented: lack of collateral growth in group A, but significant collateral growth in group B. The natural variation of collateral circulation was the major determinant of the different responses that were important with stenosis of a major coronary artery.

Animals↗

Failure of aneurysmectomy to improve left ventricular function.

Biplane left ventricular angiography was performed in 22 patients with isolated obstructive disease of the anterior descending branch of the left coronary artery and with an anterior aneurysm following transmural myocardial infarction. Six patients were restudied between 6 and 10 months after aneurysmectomy. Left ventricular reserve was estimated by analysis of a spontaneous postextrasystolic beat. Using angiographic techniques a contractile section, a transitional section, and a noncontractile section were identified. From the surgical patients the excised aneurysm and a transmural needle biopsy of the transitional section were investigated by light microscopy. With increasing volumes of noncontractile and transitional sections, total end-diastolic volume (r = 0.81, P less than 0.001) and end-systolic volume (r = 0.94, P less than 0.001) increased linearly, while the ejection fraction decreased (r = 0.70, P less than 0.001). No relation was found between the combined volumes of the noncontractile and transitional sections on the one hand, and the end-diastolic volume, the end-systolic volume, or the ejection fraction of the contractile section on the other hand. After aneurysmectomy a significant decrease was found in end-diastolic volume (194 to 133 ml/m2, P less than 0.001) and end-systolic volume (124 to 83 ml/m2, P less than 0.001) but no change occurred in ejection fraction (35 to 37%) and left ventricular end-diastolic pressure (23 to 25 mmHg). Surgical resection included part of the transitional section, which before surgery had an average ejection fraction of 27 per cent during a normal beat, rising to 41 per cent in a postextrasystolic beat. The transitional section after surgery now formed a large akinetic area of the anterior wall. We conclude that aneurysmectomy in isolated left anterior descending artery disease with anterior aneurysm fails to improve left ventricular function because the effect of reduction of left ventricular volumes is offset by the destruction of contractile behaviour in the transitional section.

Adult↗

Impaired left ventricular function in chronic aortic valve disease: survival and function after replacement by Björk-Shiley prosthesis.

Postoperative survival and left ventricular function were studied in 128 patients who underwent isolated aortic valve replacement by the Björk-Shiley valve between 1973 and 1977. The average follow-up was 2.1 years. Patients with associated coronary artery disease or mitral valve disease were excluded. Preoperative ejection fraction ranged from 15-84%. Forty-two patients were restudied by cardiac catheterization 9.1 +/- 1.1 months (mean +/- SEM) after valve replacement. The hospital mortality was 11%. Preoperative type of valve lesion, functional class, cardiothoracic ratio, and ejection fraction (EF) had no significant effect on postoperative survival up to 4 years. After operation, left ventricular mass (LVMI) and peak systolic wall stress (PSWS) fell significantly, while EF and mean normalized systolic ejection rate (MNSER) increased in aortic stenosis and in aortic insufficiency. Neither in aortic stenosis nor in aortic insufficiency was there a significant relation between preoperative ejection fraction and postoperative LVMI, EF, MNSER and PSWS. We attributed this to a marked improvement of left ventricular function in patients with preoperative impaired ventricular function. Six patients with paravalvular leak to restudy has a significantly lower EF and MNSER, and a higher PSWS than patients without leak. Patients without leak had normal EF, MNSER and PSWS when compared with 10 normal persons, but LVMI remained moderately elevated. Postoperative transprosthetic gradient was 11.9 mm Hg (range 0-64 mm Hg). We conclude that impaired cardiac function is completely restored after aortic valve replacement by Björk-Shiley valve, if valve function is good. Patients with impaired cardiac function preoperatively did not have a poorer prognosis after operation than patients with normal function.

Adolescent↗