[The study of activity of matrix metalloproteinases abd reactants of inflammation in patients with endocarditis.]

The purpose of study is to establish and compare concentration of acute-phase indices, total activity of matrix metalloproteinases-2, -7 (MMP-2, MMP-7) of blood serum in patients with vegetations on heart valvular apparatus of infectious and noninfectious nature; to apply a correlation analysis between these indices; to evaluate advantages of technique of detection of total activity of MMP-2 and MMP-7 in patients with endocarditis of various etiology. The sampling consisted of 175 examined patients separated on two groups. The first group included 81 patients with noninfectious endocarditis; the second group included 94 patients with infectious endocarditis. The activity of MMP-2 and MMP-7 was detected using fluorescent substrate, specific to MMP-2 and MMP-7. The significant increasing of activity of MMP-2 and MMP-7 in blood serum of patients with vegetation syndrome as compared with activity of enzymes in blood of healthy individuals (control group). In the group with noninfectious endocarditis activity of MMP-2 and MMP-7 made up to 84,10 ± 12,37; in the group with infectious endocarditis - 227,30 ± 44,70; in the control group - 4,16 ± 2,28 mkmol/MCA/l per hour (р < 0,05). No reliable difference between endocarditis of various nature was established. The correlation was observed between activity of matrix metalloproteinases and reactants of acute phase of inflammation.

[The hemostatic system in patients with antiphospholipid syndrome].

The objective of the investigation was to study the hemostatic system in patients with antiphospholipid syndrome (APS). The study enrolled 72 subjects (26 patients with APS (mean age 45.5 +/- 10.2 years) and their 46 relatives, including 37 and 9 first- and- second-degree relatives, respectively; mean age 29.5 +/- 16.4 years) from 26 families. A battery of standardized tests was used to evaluate the hemostatic system. At the examination, most relatives were found to have signs of thrombophilia: activated intravascular coagulation and suppressed fibrinolysis. The high detection rate for lupus anticoagulant (LA) amongst the relatives of patients with APS (39.1%) is likely to suggest its heritability. Logistic regression analysis showed the prognostic value of thrombocytic aggregatory disorders in the development of hemorrhagic manifestations, as well as an association of LA and thrombocytopenia.

[Affection of cardiovascular system in antiphospholipid syndrome with non-bacterial thrombotic endocarditis].

AIM: To study characteristics of cardiovascular affection in antiphospholipid syndrome (APS) with nonbacterial thrombotic endocarditis (NBTE). MATERIAL AND METHODS: The trial included 28 patients with APS and NBTE (26 females, mean age 44 <+/- 13 years). Primary APS was diagnosed in 21 patients, secondary APS associated with systemic lupus erythematosus--in 7 patients. Transthoracic echocardiography was performed in all the patients, transesophageal echocardiography--in 86% of them. Statistic processing was made with logistic regression analysis. RESULTS: All the patients had structural valvular changes: leaflet thickening, sclerosis, vegetations, focuses of calcinosis and valvular dysfunction. Vegetations located on mitral and aortic valves in 64% and occurred on damaged heart valves in 36% patients. An important problem in APS with NBTE was systemic embolism (54%), especially with involvement of central nervous system. Logistic regression revealed association of NBTE with structural changes of aortic and mitral valves, myocardial focal fibrosis and valvular insufficiency. CONCLUSION: APS with NBTE is characterized by absolute predominance of valvular heart lesion with vegetations location on the left heart valves and high risk of embolic complications.

[Pseudoinfectious endocarditis in antiphospholipid syndrome].

The antiphospholipid syndrome (APhS) is autoimmune non-inflammatory trombotic vasculopathy, associated with damage of vessels of any caliber and localization that determines the diversity of clinical manifestations of this syndrome. One of possible localizations of thrombosis in AphS is pseudoinfective endocarditis (PsIE). We have performed analysis of clinical and laboratory features of APhS, associated with PsIE. 28 APhS patients with PsIE, average age--44+/-13 years, were included in the study. Among them 21 patients had primary form of APhS, 7 cases had secondary form of APhS. For statistical treatment of the results the logistic regression (SPSS for Windows. Release 11.5.0.) was used, the confidence level of differences between groups was determined with the use of Student's test. Heart valve abnormalities occurred in 100% of patients and included valvular thickening, induration and sclerosis, the presence of valve vegetations, focip of calcinosis and different grade of valve dysfunction. Mitral and aortal valve vegetations occurred with the same incidence (64%), both valves were been involved in 29% of cases. Positive associations with presence/development of PsIE in APhS from multivariant model data included mitral valve lesion (OR: 0.029), focal cardiofibrosis (OR: 0.084), prior valve lesion (OR: 0.087), negative associations--hemicrania (OR: 8.627) and secondary form of APhS (OR: 6.425). Moderately high titer of lupous anticoagulant (multivariant model) (OR: 3.753) seemed to be prognostic marker of PsIE. In half of patients with APhS and PsIE systemic embolisms appeared, embolic cerebrovascular complications were the most frequent (32%). The possibility of development of hemodynamically significant valve dysfunction that needs valve replacement and nececcity of making of differential diagnosis with infective endocarditis are related to other aspects, important for clinical practice.

[Pseudoinfectious endocarditis].

Nonbacterial thrombotic (noninfectious, pseudoinfectious--PIE) endocarditis is characterized by precipitation of thrombus, not containing bacteria, on the valve cusps. Mitral and aortal valves are affected most frequently. Vegetations, as a rule, do not exceed 6-7 mm and have a high inclination to embolism. Hypercoagulation plays a leading role in PIE pathogenesis. The most frequent acquired causes of sterile vegetation forming are malignant tumors and rheumatic diseases (especially systemic lupus erythematosus--SLE and antiphospholipid syndrome--APS). Valve pathology is most frequent lesion of heart in APS patients. It is supposed, that antibodies to phospholipids (aPL) have a special importance in valve lesion pathogenesis at APS, besides, changes in valve apparatus at SLE are associated exactly with aPL. Main problems of PIE patients are recurrent thromboembolism, development of valve dysfunction with clinical signs of heart failure (4-6% cases), difficulties in differential diagnostics: PIE is hard to diagnose if basic disease is accompanied by fever (diffuse diseases of connective tissue etc.). Transesophageal echocardiography is a leading method in PIE diagnostics. The main therapeutic option in PIE treatment is anticoagulant therapy: nonfractional or subcutaneous heparin in presence of systemic or pulmonary embolism, in patients with disseminated malignant tumors--complete doses of nonfractional heparin.

[Clinical and immunological characteristics of primary and secondary antiphospholipid syndrome]. / Kliniko-immunologicheskaia kharakteristika pervichnogo i vtorichnovo antifosfolipidnogo sindroma.

A prospective study was made of 93 patients with antiphospholipid syndrome (APS), including 34 patients with primary APS (PAPS) and 59 with secondary APS (SAPS) associated with exanthematous lupus erythematosus (ELE). According to the clinical outcomes, PAPS is heterogeneous since the clinical and laboratory signs of ELE or lupus-like syndrome occurred in two thirds of the patients with PAPS. The clinical manifestations of PAPS and ELE-associated SAPS differed at the height of disease: the signs of vascular diseases were prevalent in patients with PAPS and ELE-associated systemic manifestations were predominant in those with SAPS. In the patients with APS who further developed ELE, unlike those with PAPS showed a high incidence of transient erythema and arthralgias. The levels of serological markers in patients with APS at its height did not differ. As compared with healthy individuals, patients with APS were found to have the similar changes in the nonspecific immunological parameters manifested by absolute lymphopenia, by the diminished Fc-phagocytosis of monocytes and neutrophils, by the elevated levels of circulating immune complexes, and by the high biocidal activity of neutrophils. There were no significant differences in the immunity of patients with PAPS and in those with SAPS.

Ultrastructural and biosynthetic characteristics of glomerular endotheliocytes and periglomerular arterioles during systemic lupus erythematosus.

We studied ultrastructural characteristics of renal cortical cells in patients with systemic lupus erythematosus. Endotheliocytes in periglomerular arterioles underwent primary and most pronounced changes. Examination of glomerulocytes revealed early alterations in endotheliocytes, compensatory proliferation of mesangial cells, overproduction of the mesangial matrix, and metaplasia of podocytes. Biosynthetic reactions reflected the structural and functional heterogeneity of endotheliocytes associated with their damages and regeneration.

Antiphospholipid syndrome: ultrastructure of microvascular endotheliocytes in musculocutaneous bioptates during systemic lupus erythematosus.

Degeneration and atrophy of the epidermis, disorganization of the connective tissue, focal atrophy of skeletal myocytes, and diffuse vasculopathy are the main pathomorphological signs found in musculocutaneous bioptates during the antiphospholipid syndrome associated with systemic lupus erythematosus. The major morphogenetic disorder is alteration of microvascular endotheliocytes accompanied by the formation of concentric perivascular mononuclear infiltrates.