[Molecular genetic analysis of the isoniazid-resistant strains of M. tuberculosis circulating over the Saratov region].

257 patients with active lung tuberculosis in the Saratov region were tested for distribution and mutation spectrum of the genes katG, inhA, ahpC encoding Isoniazid-resistance. The tests were implemented using the biological microchips with pharmacological kits TV-Biochip MDR (Russia). The rate of the Isoniazid-resistant M. tuberculosis strains incidence was found to be 55.7%. The Isoniazid-resistant strains demonstrated high rate (26.9%) of combined mutations in 2 and 3 genes simultaneously, domination in the katG ser315 -> Thrl (91.1%), thereby inducing high resistance to Isoniazid. The sensitivity of the TV-Biochip MDR test-system was 88.2%; the specificity, 91.3%. The results ofthis work show that the incidence of the Isoniazid-resistant strains should be limited using additional measures.

[The characteristics of production of cytokines in patients with tuberculosis of lungs].

The sample of 36 patients with primarily diagnosed mostly infiltrative tuberculosis of lungs was used to investigate the characteristics of spontaneous and stimulated by specific antigens production of cytokines FNO-alpha, IFN-beta, IL-8 playing the most significant role in pathogenesis of tuberculosis. The production of FNO-alpha and IFN-gamma was analyzed in the culture of peripheral mononuclear cells using antigen M. bovis (BCG). The cytokines IFN-gamma and IL-8 were analyzed in the cultures of whole heparinized blood using antigens H37Rv and ESAT-6. The significant inhibition of stimulated by antigens production of FNO-alpha and IFN-gamma in patients with severe, destructive and complicated forms of tuberculosis as compared with to patients with limited and favorably developing tuberculosis. The differences in production of lL-8 in patients with different degree of severity of tuberculosis process are not revealed.

[Tuberculosis in children and adolescents in the Saratov Region in 2001-2007].

Tuberculosis in children and adolescents is closely associated with the tuberculous infection reservoir existing in the Saratov Region. In this region, the tuberculosis epidemiological situation has improved and stabilized in the past 7 follow-up years, which is undoubtedly associated with the better organization of performed tuberculosis-controlling measures.

[Real-time polymerase chain reaction in the diagnosis of pulmonary tuberculosis].

To enhance the efficiency of diagnosis of oligo- and abacillar pulmonary tuberculosis and its differential diagnosis with other lung diseases, the authors studied the informative value of real-time polymerase chain reaction (PCR) used in 62 patients with different clinical forms of tuberculosis and 108 differentially diagnostic patients. Real-time PCR has been ascertained to be a significantly more sensitive and highly specific tool in tuberculosis diagnosis, which considerably improves the specific recognition of the etiology of a pathogenetic process in oligo- and abacillar patients. Particularly encouraging results have been obtained when examining differentially diagnostic patients with the rounded shadows being formed in the lung.

[Up-to-date technologies of laboratory diagnosis of tuberculosis (efficiency of their use in clinical practice)].

To explore the diagnostic informative value of using new diagnostic methods for tuberculosis, the authors made a comparative study of the use of real-time polymerase chain reaction (PCR) and enzyme immunoassay (EIA) to determine Mycobacterium tuberculosis antibodies in 96 patients diagnosed at the Saratov regional tuberculosis dispensary. Real-time PCR was found to be highly effective in improving the quality of diagnosis of tuberculosis and its differential diagnosis from another lung abnormality, by increasing the prognostic value of a positive result in PCR up to 95.2% versus 85.3% in EIA (p=0.0220) and that of a negative result to 77.7% versus 62.9%, respectively (p=0.0238).

[Interpretation of complex cohort assessment of the results of tuberculin diagnosis].

Tuberculin tests were assessed from the results of a planned Mantoux test with 2 TE, which were presented in the annual reports over the past years (2000-2006 and 2001-2006). Cohorts of children born in 1999 and 2000 who were in 2006, 7 and 6 years, respectively, were formed. This made it possible to monitor the time course of changes in tuberculin tests, postvaccinal allergy (PVA), primary Mycobacterium tuberculosis infection (PMBTI) and MBT infection. A cohort study of the results of tuberculin diagnosis has indicated that annual underestimation of children with PVA results in an increase in the rates of PMBTI. The authors prove that the rates of PMBTI and MBT infections in children incur a large proportion of errors therefore they should be used in the assessment of the tuberculosis epidemic situation with great caution.

[Criteria for evaluating the efficiency of chemotherapy in tuberculosis hospital].

The use of developed additional criteria for efficiency in the performed analysis has demonstrated that the most optimal duration of inpatient treatment regime I is 90 and 120 doses. Only the administration of 120 doses substantially reduces the number of caverns in multiple destructions and causes positive X-ray changes in complicated tuberculosis, which justifies the planning of inpatient treatment regimen I in patients with multiple lung tissue decay and complicated tuberculosis until 120 doses are used. The employment of additional criteria makes it possible to show the results of inpatient treatment in patients with drug resistance and justifies the leng of hospital stay until 120-150 doses are administered.

[Intranuclear development of the macrogametes of the coccidian, Tyzzeria parvula]. / Vnutriiadernoe razvitie makrogamet koktsidii Tyzzeria parvula.

The fine structure of macrogametes of a goose coccidium Tyzzeria parvula has been studied, intranuclear localization of these being discovered. Unlike other coccidia, macrogametes of T. parvula display only one type of wall-forming bodies. Deep invaginations are formed on the surface of macrogametes, in which fragments of host cell nucleoplasm, separated with the membrane of parasitophorous vacuole, are invaginating. They may be connected with process of parasite's feeding.

[Some clinical and immunological aspects of female pulmonary tuberculosis]. / Nekotorye kliniko-immunologicheskie osobennosti tuberkuleza legkikh u zhenshchin.

Expression of activation markers, such as CD25, HLA-DR), Fas-AG, CD16), on the lymphocytes was studied in female patients with tuberculosis (n = 40) and healthy donors. The level of antituberculous antibodies was measured in parallel in the sera of these patients. The above parameters were examined in relation to the nature of the microflora detected in these patients. Nonspecific co-infection in patients with active tuberculosis is an additional factor of activation of the immune system and simultaneously a factor that enhances the involvement of cells in apoptosis.

[Production of gamma-interferon by blood mononuclear cells in patients with various types of a tuberculous process]. / Produktsiia interferona-gamma mononuklearnymi kletkami krovi bol'nykh pri raznykh tipakh techeniia tuberkuleznogo protsessa.

To elucidate the diagnostic value of gamma-interferon (gamma-IFN) in the human body, the gamma-IFN production that was spontaneous and induced by BCG Mycobacterium bovis in the supernatants of short-term cultures of peripheral mononuclear cell from 31 patients with active tuberculosis was studied. The sandwich method of enzyme immunoassay was used, by employing two monoclonal antibodies in the avidin-biotin system. The studies have established the low spontaneous production of gamma-IFN in patients with the severe progressive course of a tuberculous process (22.5 +/- 2.5 pg/ml in Group 1 versus 41.5 +/- 8.6 pg/ml in patients with the favorable course of a tuberculous process (Group 2) and 34.0 +/- 3.5 pg/ml in healthy individuals (Group 3); p(1-2) < 0.05 and p(1-3) < 0.05)). Moreover, there was a reduction in the induced production of gamma-IFH in response to BGC (37.7 +/- 33.4 pg/ml in Group 1 versus 214.9 +/- 81.9 pg/ml in Group 2 and 206.0 +/- 31.1 pg/ml in healthy individuals; p < 0.05 and p(1-3) < 0.001), which is of diagnostic and prognostic values.

[Interferon-gamma and IgG antibodies to M. tuberculosis in the serum of patients with active pulmonary tuberculosis]. / Inteferon-gamma i IGG-antitela k M. tuberkulosis v syvorotke krovi bol'nykh aktivnym tuberkulezom legkikh.

The above parameters in the sera from patients with active tuberculosis (n = 20) and healthy individuals (n = 16) were studied in parallel to examine the relationship and mutual effects of interferon-gamma (IFN-gamma) and IgG antibodies to Mycobacterium tuberculosis, as well as their relationship with some clinical and immunological features of tuberculous infection. The relative and absolute counts of CD4 and CD16 cells were additionally measured in these patients' peripheral blood. Patients with active tuberculosis were found to have significantly elevated serum levels of IFN-gamma, IgG antibodies and CD16 cells with the decreased count of CD4 cells as compared with the similar parameters in healthy individuals. There was no relationship of the serum level of IFN-gamma to the clinical features of tuberculosis. The serum level of IFN-gamma is likely to determine the interferonogenic activity of the causative agent itself.

[Enzyme immunoassay and immunochromatographic assay in the differential diagnosis of tuberculosis and cancer of the respiratory organs]. / Immunofermentnyi i immunokhromatograficheskii analizy v differentsial'noi diagnostike tuberkuleza i onkologicheskikh zabolevanii organov dykhaniia.

The informative value of immunodiagnostic assays aimed at identifying specific antibodies in the peripheral blood was studied. Indirect solid-phase enzyme immunoassay (Antitub test system, Moscow) and rapid immunochromatographic assay (TB-CHECK, France) were used. Fifty-six diagnostic patients and 18 healthy individuals were examined. The diagnosis of active tuberculosis was verified in 29 patients (Group 1) and that of lung cancer was in 27 patients (Group 2). The detection rate of and the level of antituberculosis antibodies in patients with active tuberculosis greatly differed from those in patients with lung cancer (p < 0.01). In the diagnostic patients, the sensitivity of enzyme immunoassay was 79.3%, its specificity was 88.9; the sensitivity and specificity of the rapid assay were 72.4 and 96.3%, respectively. The high specificity of the immunochromatographic assay in patients with lung cancer may reduce the number of false-positive results of the enzyme immunoassay. The concurrent use of both methods is an essential adjunct to the clinical examination of diagnostic patients, it makes it possible to reduce the time of pre-examination of cancer patients and to restrict a group of patients who need for invasive studies to specify a diagnosis.

[Experience with using anti-TB preparations (rifabutin)]. / Opyt monitoringa ispol'zovaniia protivotuberkuleznykh preparatov (na primere rifabutina).

The study deals with the first experience of practically using a computer program designed to monitor the treatment process with a subsequent analysis of the efficiency of an anti-TB therapy with regard for different characteristics of patients. The efficiency of chemotherapy was compared (by using the clinical, microbiological and laboratory criteria) in two patients' groups, i.e. a control group (standard chemotherapy regimens) and a group, whose patients received rifabutin. Subgroups were isolated from among the last mentioned patients according to the below factors: primary and secondary therapy courses, completed and interrupted chemotherapy courses, and patients with multidrug resistance who discharged M. tuberculosis. Statistically reliable advantages of rifabutin were shown in respect to the arrest of bacterial discharge during a sufficiently prolonged (at leas 4 months) treatment course applicable to primarily diagnosed patients including those with multidrug resistance and M. tuberculosis. Disadvantages related with the application of rifabutin (a lack of clear-cut indications and abuse of treatment terms virtually in 50% of cases), which reduces the efficiency of its prescription, were equally detected.

[Analysis of reasons for late recognition of tuberculosis and cancer of the lung and the ways of enhancing the efficiency of their differential diagnosis].

Difficulties in the differential diagnosis of tuberculosis and cancer of the lung were analyzed in 272 patients from a regional tuberculosis dispensary. The efficiency of using the real-time polymerase chain reaction (PCR) to detect Mycobacterium tuberculosis DNA molecule fragments in the sputum specimens from 111 patients of this category was studied to improve the differential diagnosis of these diseases. The real-time PCR was ascertained to be a rather highly sensitive (78.3%) and highly specific (96.1%) technique for tuberculosis diagnosis, which considerably improves the etiological recognition of the pathological process. Examinations of patients with peripheral lung cancer and benign round shadow formations in the lung yielded encouraging results. The specificity of the technique in this pathology is as high as 100%.

[Effects of natural protease inhibitors on hemostasis and serum proteolysis blockers in patients with pulmonary tuberculosis]. / Vliianie prirodnykh ingibitorov proteaz na gemostaz i syvorotochnye blokatory proteoliza u bol'nykh tuberkulezom legkikh.

Changes in hemostasis and basic serum antiproteases (alpha 1 protease inhibitor--alpha 1-PI and alpha 2-macroglobulin--alpha 2-MG) were followed up in patients with infiltrative pulmonary tuberculosis in the destruction phase. 65 patients received chemotherapy in combination with contrykal inhalations, 63 patients were given glucocorticoid hormones and prodectin. It was found that natural protease inhibitors produced a marked clinical response, abated more rapidly thrombohemorrhagic syndrome, promoted normalization of coagulation and fibrinolysis. Replacement aerosol therapy with antiprotease agents reestablished the concentration of alpha 1-PI, but had no effect on that of alpha 2-MG. This may contribute to reparative processes in pulmonary tissue which ran without significant signs of sclerosis. The results obtained may be used by clinicians choosing methods of pathogenetic therapy.

[Complex evaluation of the defense systems in patients with infiltrative pulmonary tuberculosis]. / Kompleksnaia otsenka zashchitnykh sistem u bol'nykh infil'trativnym tuberkulezom legkikh.

Patients with infiltrative pulmonary tuberculosis at its degenerative stage were examined for parameters of hemostasis, serum proteolytic inhibitors, immunity status and complement. In doing so, the following changes were detected: simultaneous intensification of plasma coagulability and fibrinolytic properties, sputum-induced increase in fibrinolysis; disproportion in the content of the main protease blockers (higher alpha 1-protease inhibitor and lower alpha 2-macroglobulin); T-lymphocyte deficiency; stimulation of the immunity humoral link; rise in the count of O-lymphocytes and higher concentration of the complement component C3. The correlation between the indices of the examined systems was observed, thus indicating the interdependence of the body defensive factors. The findings can be used in the clinical practice when pathogenetic drugs are chosen.