[Morphological, immunohistochemical and radiological manifestation of lung tissue remodeling at lung sarcoidosis].

Sarcoidosis is a group of diseases with chronic immune inflammation and granulomas formation in the lung, lymph nodes, and others organs. Under progress of disease remodeling of the lung tissue occurs and at 20-25% of patient with sarcoidosis lung fibrosis is developed. We studied biopsies from 50 patients with sarcoidosis and 10 biopsies of pathological intact lung tissue as a control group. Roentgenologic, morphologic and immunohistochemical methods with using of mono- and polyclonal antibody to MMP 1, 2, 9 and TIMP-1, PCNA, aSMA, apo-CAS were realized. The expression levels of growth factors, apoptosis, MMPs, TIMPs were different in various clinic-morphological courses of sarcoidosis. As a rule under sarcoidosis deep remodeling of lung tissue didn't occur in spite of granulomatous inflammation. Granulomatous process, alveolitis (bronchiolitis) and sclerotic changes resulted in alteration of the lung. Cells of sarcoidosis granulomas, produced low level of MMPs and TIMP can't induce evident fibrosis and so hypertension is absent or becomes apparent in the slight form. It apparently can be link with localization of pathologic process in lung tissue without any alterations in the bronchoalveolar zone. Alveolitis under sarcoidosis conditions is notable for low activity of inflammation and doesn't result in interstitial fibrosis developing.

[Pulmonary lesions in Wegener's granulomatosis].

Pulmonary lesions are the commonest and prognostically unfavourable visceral pathology in Wegener's granulomatosis. The author discusses clinically and reongenologically detectable lesions associated with this systemic vasculitis with special reference to its most severe forms (alveolar bleeding and infectious complications frequently caused by active immunosuppressive therapy). Diagnostic (including early) and modem therapeutic modalities of Wegener's granulomatosis are considered.

[Severe Wegener's granulomatosis successfully treated with rituximab].

The paper discusses the problems of the diagnosis and treatment of Wegener's granulomatosis, the most common anti-neutrophil cytoplasmic antibody-associated systemic vasculitis. It describes a clinical case in which the administration of rituximab could achieve remission of severe Wegener's granulomatosis in a young man having numerous adverse reactions associated with the long-term use of high- and average-dose glucocorticoids and nonselective immunosuppressive agents. A place of rituximab in current drug therapy for Wegener's granulomatosis is shown.

[Cerebral sodium-uretic peptide: pathogenetic and clinical significance in pulmonary arterial hypertension associated with interstitial diseases of the lungs].

Sodium-uretic peptides (SUP) are the main humoral system opposing pathological remodeling of vascular bed in diseases of cardiovascular system and kidneys. In the paper, pathogenetic and clinical significance of the cerebral SUP in pulmonary arterial hypertension, including the one associated with interstitial diseases of the lungs.

[Clinical significance of markers of endothelial dysfunction and angiogenesis in progressing of the lung interstitial diseases].

The data obtained suggest an important role of the FRES and ET-1 in progressing of the lung interstitial diseases; they can be used as diagnostic criteria of the disease activity, risk of pulmonary hypertension, and extra-pulmonary manifestations.

[Estimation of plasmic concentration of the brain natriuretic peptide in interstitial pulmonary diseases with pulmonary hypertension: clinical role].

AIM: To study a plasmic concentration of the brain natriuretic peptide (BNUP) in patients with interstitial pulmonary disease (IPD) as a possible diagnostic parameter in pulmonary hypertension (PH). MATERIAL AND METHODS: Plasmic BNUP concentration, external respiration function were studied in 24 patients with IPD. The following tests were also made: 6-min walk, echocardiography (echo-CG) with estimation of systolic pressure in the pulmonary artery, multislice computed tomography of the chest with measurement of the mean diameter of the pulmonary artery trunk. RESULTS: As shown by echo-CG and chest MSCT half of the IPD patients had PH. IPD patients with PH had a significant elevation of plasmic BNUP concentration which, in intact left ventricular contractile function indicates development of secondary PH characterized by reduction of volume parameters of the respiratory pulmonary function. The rise of BNUP concentration correlated with reduction of 6-min walk distance and functional lung capacity. CONCLUSION: Plasmic BNUP can be used for diagnosis of PH in IPD patients.

[Endothelin-1 and brain natriuretic peptide in the development of pulmonary hypertension in interstitial lung diseases].

AIM: To study the plasma concentration of brain natriuretic peptide (BNP) and endothelin-1 (ET-1) as markers of pulmonary hypertension (PH) developed in interstitial lung diseases (ILD). SUBJECTS AND METHODS: Along with physical examination, 97 patients with ILD underwent measurements of the plasma concentrations of BNP and ET-1, 6-minute walk test, external respiration function test, echocardiography, by measuring pulmonary artery systolic pressure (P(syst)), and chest multispiral computed tomography, by estimating the mean diameter of the pulmonary artery trunk. RESULTS: The plasma concentration of ET-1 proved to be significantly higher in the presence of active lung lesion (5.2 +/- 3.9 and 2.8 +/- 1.8 pg/ml; p = 0.0001). In patients with ILD, persistent PH was associated with the significantly elevated plasma concentrations of BNP (69.3 +/- 341.35 and 23.7 +/- 26.69 pg/ml; p = 0.018). The increase of plasma BNP concentrations correlated with the shorter distance covered during a 6-minute walk test and diminished functional vital capacity. CONCLUSION: The increased plasma levels of ET-1 in ILD reflects the transient pulmonary artery pressure elevation associated with the activity of the pulmonary process while those of BNP are indicative of developed persistent PH.

[Vasaprostan treatment of fibrosing alveolitis in patients with pulmonary hypertension]. / Primenenie vazoprostana u bol'nykh legochnoi gipertoniei pri fibroziruiushchem al'veolite.

AIM: To study clinical efficacy of vasaprostan in patients with fibrosing alveolitis (FA) complicated by pulmonary hypertension (PH), its effect on functional activity of platelets and endothelium, intensity of free radical processes. MATERIAL AND METHODS: Seven FA patients were examined. They had either idiopathic FA or FA with diffuse diseases of the connective tissues. The following methods were used to assess the effect: standard clinical tests, high resolution computer tomography, Doppler echocardiography, definition of the complex thrombin-antithrombin (TAT) and thrombocytic factor 4 (TF-4). Generation of oxygen active forms by leukocytes was measured by luminol-dependent chemiluminescence. Morphological verification of the diagnosis was made by the results of open pulmonary biopsies. RESULTS: Vasaprostan reduced pressure in the pulmonary artery from 31.6 +/- 2.31 to 19.58 +/- 3.90 mm Hg (p < 0.05) and coagulation parameters. TAT decreased after 2 and 8 weeks of treatment from 15.25 +/- 4.5 to 5.1 +/- 0.33 and 2.4 +/- 0.31 pg/ml (p < 0.05). Initially low TF-4 (2.11 +/- 0.39 pg/ml) elevated to the end of the treatment and reached values close to control (4.37 +/- 0.25 pg/ml, p < 0.05). Moreover, vasaprostan enhanced the ability of platelets to inhibit generation of active oxygen forms (from 0.9 +/- 0.18 to 1.23 +/- 0.16 r. u., p < 0.05) and thus depressed activity of lipid peroxidation. CONCLUSION: Good effect of vasaprostan on platelet activity, free radical processes validates its use in combined treatment of various FA forms for correction of PH, its complications and as an antifibrogenic agent.

[Markers of thrombophilia in pulmonary fibrosis complicated by pulmonary hypertension]. / Markery trombofilii pri legochnom fibroze, oslozhnennom legochnoi gipertoniei.

AIM: To determine the role of enhanced blood coagulation in pathogenesis of pulmonary hypertension (PH) at an early stage of fibrosing alveolitis (FA). MATERIAL AND METHODS: Clinical, functional, roentgenological, coagulation and immunological examinations were performed in 17 patients with idiopathic FA (IFA), in 6 patients with exogenic allergic alveolitis (EAA), in 15 FA patients with diffuse diseases of the connective tissue (FA-DDCT). The diagnosis was verified with high resolution computed tomography (HRCT). Lesser circulation was assessed by Doppler echocardiography. Morphological impairment of the lungs was specified in all the patients using analysis of the bronchoalveolar lavage. In 9 FA patients the diagnosis was verified at thoracoscopic biopsy of the lung. The control group consisted of 16 healthy volunteers. Thrombin-antithrombin complex (TAT) and thrombocytic factor 4 (TF-4) were estimated with ELISA as stable, highly sensitive markers of thrombophilia. RESULTS: The TF-4 level was elevated in all IPD patients (p < 0.05), the elevation being highest in FA-DDCT (p < 0.007). With FA progression, TF-4 concentration went down. A weak negative correlation (p < 0.047, r = -0.38) was found with average pressure in the pulmonary artery (PAAP). TAT was higher than control in all the groups (p < 0.05). Maximal TAT values were registered in EAA. If HRCT detected active inflammation and in development of irreversible fibrous changes TAT was higher vs control. A direct correlation between TAT level and PAAP was not found. CONCLUSION: Disorders in thrombocytic and plasmic links of hemostasis are detectable early in IPD. Stable markers of thrombophilia (TAT and TF-4) reflect activity of inflammation in FA. They can be also used as sensitive diagnostic tests for diagnosis of PH and diagnosis of patients with activated coagulation system in IPD.

[Role of certain neurohumoral factors in development of pulmonary hypertonia in patients with interstitial lung diseases]. / Rol' nekotorykh neirogumoral'nykh faktorov v razvitii legochnoi gipertonii u bol'nykh interstitsial'nymi bolezniami legkikh.

AIM: To ascertain the role of some neurohumoral factors--nitric oxide (NO), ACE, histamine--in development of pulmonary hypertension (PH) in patients with interstitial lung diseases (ILD). MATERIAL AND METHODS: A total of 32 ILD patients were examined. Of them 14 had idiopathic fibrosing alveolitis (IFA), 6 had exogenous allergic alveolitis (EAA) and 12 patients had ILD in diffuse disease of the connective tissue (ILD-DDCT). In addition to routine tests, those for NO, ACE, histamine, serotonin in plasma were performed; Doppler echocardiography and high-resolution computed tomography were conducted. In 9 patients the diagnosis was verified at thoracoscopic biopsy of the lung. The control group consisted of 16 healthy subjects. RESULTS: The highest mean pressure in the pulmonary artery (PmPA) was registered in IFA vs EAA and ILD-DDCT patients (p < 0.001). NO concentration in plasma was higher in ILD-DDCT than in control patients. In IFA and EAA the level of NO was like in controls. Concentration of NO in plasma of IDL patients correlated with high activity of the process. No correlation was found between ACE in plasma and PmPA, ACE levels were much higher in controls than in the ILD patients (p < 0.05). Histamine levels were higher in ILD patients than in controls being the highest in ILD-DDCT. Serotonin was insignificantly higher in ILD patients than in controls. CONCLUSION: Damage to the endothelium of the pulmonary arteries and imbalance of neurohumoral factors may be considered as a mechanism of development and stabilization of PH in ILD patients.

[Pulmonary hypertension in interstitial diseases of the lungs]. / Legochnaia gipertenziia pri interstitsial'nykh bolezniakh legkikh.

Clinical, functional, immunological and x-ray examinations were performed in 32 patients with interstitial pulmonary diseases (14 with idiopathic fibrosing alveolitis, 6 with exogenic allergic alveolitis and 12 with diffuse affection of the connective tissue). The diagnosis was verified using high resolution computed tomography. Lesser circulation was studied with doppler-echocardiography. In 9 patients the diagnosis was verified by thoracoscopic biopsy of the lung. Control group consisted of 16 healthy subjects. The highest pressure in the trunk of the pulmonary artery (31 +/- 4.3 mmHg) was registered in patients with idiopathic fibrosing alveolitis. The severity of pulmonary arterial hypertension correlated with that of respiratory disorders, clinical symptoms and changes in the lungs. Blood pressure in the pulmonary artery trunk tended to elevation with progression of alterations in the lungs registered by computed tomography.

[Systemic AL-amyloidosis with extensive pulmonary and vascular lesions]. / Sistemnyi AL-amiloidoz s preimushchestvennym porazheniem legkikh i sosudov.

Here is an observation data on systemic AL-amiloidosis with primary lesion of lungs and vessels (a false hemorrhagic syndrome, ischemic insult in the region of middle cerebral artery). At the same time lesions of kidneys and heart became of minor significance. Amiloid lesion of lungs was characterized by unusual combination of symptoms: a galloping hydrothorax, a vast focus in the consolidation of pulmonary tissue with focuses of calcification, relapsing pneumothorax.

[Combination of pulmonary lymphangioleiomyomatosis with skin leiomyomatosis and uterine leiomyoma]. / Sochetanie limfangioleiomiomatoza legkikh, leiomiomatoza kozhi i leiomiomy matki.

Clinical observation with morphological verification of the above combination in a 48-year-old patient is presented. Large cysts, dystelectasia, fibrosis and smooth muscle proliferation were found in the lungs. The characteristic feature of smooth muscle cells was their differentiation in the direction of myofibroblasts and expression of antigen interacting with HMB-45 antibodies as well as protein products involved in catecholamine metabolism and estrogen receptors.