[Peculiarity modification mechanical property of a pulmonary tissue in the period of physiological pregnancy].

In the period of pregnancy are reduced elastic of property of a pulmonary tissue. More than in 2 times is enlarged an extensibility, as at the expense of participation of the surface active agents, and some factors of parenchyma. The conditions for augmentation of the size of alveolus's, delay in them of air and infringement of a bodily machinery of respiration are framed. Obviously, as a result of rising a hydrophilic nature the effective viscosity plasticity of system of a pulmonary tissue is reduced, that causes infringement of alveolar ventilation (close-effect) and hypercarbondioxide in respiratory ways. The combined influence of the factors of pregnancy at some women promotes formation dynamic hyperinflation mild, development of respiratory failure and hypoxia to complications on the part of a fetus.

Allelic polymorphism of cytokine genes during pulmonary tuberculosis.

Modern immunological and molecular genetic studies showed that tuberculosis is accompanied by an imbalance in the production of immunoregulatory cytokines by mononuclear leukocytes. T allele and homozygous TT genotype of T-330G polymorphism in the IL2 gene, T allele and TT genotype of C-590T polymorphism in the IL4 gene, and CC genotype of A-1188C polymorphism in the IL12B gene are immunogenetic factors that have protective activity against susceptibility to pulmonary tuberculosis. Susceptibility to tuberculous infection is associated with A1A2 genotype of the polymorphic region +3953 A1/A2 in the IL1B gene; G allele and TG and GG genotypes of T-330G polymorphism in the IL2 gene; C allele and CC and CT genotypes of C-590T polymorphism in the IL4 gene; and AC genotype of the polymorphic region A-1188C in the IL12 gene.

[Modulatory effect of isoniazid and rifampicin in vitro on cytokine secretion in pulmonary tuberculosis].

The effects of isoniazid and rifampicin on the peripheral mononuclear production of IL-2, IL-12, IL-10, IFN-gamma, and TGF-beta were evaluated in patients with infiltrative pulmonary tuberculosis. Irrespective of the susceptibility of the causative agent to the essential antituberculous drugs, rifampicin was ascertained to initiate increased IL-2 secretion and to reduce the generation of IL-12, IFN-gamma and TGF-beta. Isoniazid suppressed the mononuclear leukocytic production of IFN-gamma in drug-sensitive pulmonary tuberculosis, and conversely, stimulated it in the drug-resistant type. Rifampicin showed a more significant negative effect on mononuclear cytokine-producing activity. In drug-resistant pulmonary tuberculosis, the imbalance of spontaneous, protein- and drug-induced mononuclear secretion of cytokines was established to be more pronounced than in drug-sensitive tuberculosis.

[The molecular-genetic aspects of tubercular infection forecasting and immunotherapy].

In article is presented, the analysis of the data of the literature and own researches, concerning molecular-genetic mechanisms of antimycobacterial immunity infringements. The role of the factors defining features of a current and an outcome of a tubercular infection, namely of immunity system condition, feature of infecting microbic Mycobacterium tuberculosis strain biological properties (a genotype, a spectrum of drag sensitivity/resistance), influence of combined antitubercular chemotherapy is disc issed. The opinion is expressed that the given factors are necessary for taking into consideration for working out methodology the personalised preventive maintenance and correction of immunity infringements during pulmonary tuberculosis.

[Control of tuberculosis in Russia and other countries of the former Soviet Union]. / Die Kontrolle der Tuberkulose in den Nachfolgestaaten der Sowjetunion am Beispiel Russlands.

BACKGROUND: Tuberculosis (TB) remains a serious threat to public health in Russia and other former Soviet Union Countries. The purpose of this paper is to describe the current trends of TB and MDR-TB in Russia and identify the characteristics of the traditional Russian TB control model inherited from the Soviet Union. We discuss current challenges to TB control in the country. METHODS: WHO tuberculosis notification data were analysed for Russia and 14 other former Soviet Union countries. To investigate the characteristics of TB control in Russia, we performed a systematic literature review using MEDLINE/EMBASE databases. 136 articles were initially identified of which 66 fulfilled the inclusion criteria. Full texts were reviewed. Additionally, we reviewed non-systematically Russian state reports, guidelines and legislations. RESULTS: In 2006, nearly 125 000 TB cases and 28 000 TB deaths were notified in the Russian Federation. The TB notification rate was 13 times higher than in Germany. The characteristics of the traditional Russian TB control model include: a centralised disease-specific inpatient network for diagnosis and treatment of TB, countrywide population screenings using fluorography, a strong focus on X-ray for diagnosis and disease classification, individualised and lengthy inpatient care, high rates of drug resistance, and inefficient financing systems. CONCLUSIONS: Current challenges to TB control in Russia are: the implementation of a quality-assured laboratory network for sputum-smear microscopy, culture and drug susceptibility testing, ensuring MDR-TB treatment and control, prevention and management of TB/HIV, and reform of health care financing systems. For TB control to be successful in the Russian Federation, the characteristics of the traditional TB control model need to be taken into account.

[The specific features of diagnosis of latent small airway obstruction].

Latent obstruction of the small airway is a preclinical stage of chronic obstructive pulmonary disease (COPD), has no specific signs and it is a risk factor of respiratory failure. Its mechanism is unknown; it is likely to be caused by rearrangement of lung tissue, its increased hydrophicility due to the influence of various endogenous factors, which ultimately causes a change in the mechanical omechanics. The new sensitive functional integral index (the latent small airway obstruction coefficient) has been proposed for timely diagnosis. Body plethysmography was used to comparatively study the health status of 152 women during a gestational period by a special program; of them 66 suffered from COPD. It was found that 26 (16.1%) patients who considered themselves healthy had latent obstruction of the small airway and there was a considerable increase in the number of cases of fetal hypoxic complications.

[Apoptosis and micro- and macroelement composition of lymphocytes in patients with pulmonary tuberculosis].

The paper describes the results of comparatively analyzing the parameters of apoptosis, micro- and macroelement spectrum of peripheral blood lymphocytes in healthy donors and in patients with chronic obstructive pulmonary disease (COPD) and pulmonary tuberculosis. In drug-responsive and drug-resistant pulmonary tuberculosis, unidirectional pretreatment changes were generally recorded in the activity of apoptosis and the spectrum of chemical elements of peripheral blood lymphocytes, which were most pronounced after completion of a phase of intensive antituberculosis chemotherapy. After termination of a complete course of the therapy, apoptotic activity lowered with the cationic composition of cells being normalized. The parameters differentiating pulmonary tuberculosis from COPD were ascertained, these included increases in the count of apoptotic cells and the cell concentrations of Ca2+, Zn2+, and Mg2+.

[Multidrug pulmonary tuberculosis: sociomedical features and the efficiency of inpatient treatment].

Case histories of 147 patients with new-onset destructive pulmonary tuberculosis (PT) (infiltrative, disseminated, fibrocavernous) with the pathogen of the disease showing multidrug resistance (MDR) were analyzed, by evaluating the efficiency of treatment involving sputum abacillation after termination of the inpatient stage of treatment. A control group included 220 patients with PT of the similar lesion and clinical forms, who preserved drug resistance (DR) to antibacterial agents. Most patients with MDR disseminated destructive PT are young people aged 36.6 +/- 1.6 years, this disease-associated disabled individuals (65.3%), alcoholics (48.3%), opium addicts (11.5%), ex-prisoners (26.5%), single, homeless; more frequently suffer from gastrointestinal (40%) and chronic nonspecific lung (24.5%) diseases. The course of MDR PT is significantly more commonly complicated by the development of respiratory failure (48.9%) and hemoptysis (6.1%) (in DR PT 19.1 and 2.3%, respectively). In terms of negative smear tests and the results of sputum cultures, the abacillation rates were 70.1 and 67.3%, respectively (in DR PT, these were 88.18 and 86.34%, p = 0.01). A negative reaction of sputum occurred in 42.1% of patients at 2-3 months of treatment while its culture did in 46.2% at 4-5 months. In the control group wherein drug sensitivity of M. tuberculosis was preserved, sputum abacillation occurred in the larger proportion of the patients within the first 2 months (in 68.6 and 56.3% of cases with sputum smear and culture, respectively). The efficiency of inpatient therapy is greatly affected by short-term treatment caused by voluntary withdrawal and irregular uses of antituberculous drugs, mainly due to alcoholization.

[Evaluation of the effects of antituberculous drugs on the cytochemical status of lymphocytes in vitro].

The effects of basic drugs of chemotherapy for tuberclosis, such as isoniazid and rifampicin, on the activity of the most important mitochondrial enzymes of lymphocytic energy metabolism were studied in patients with infiltrative tuberculosis and healthy donors. The authors detected the significantly inhibited activity of succinate dehydrogenase and the redistribution of lymphocytic populations with the increased proportion of cells with the low and high activities of the enzyme. The more significant negative effect on the lymphocytes of patients with tuberculosis was observed when rifampicin was administered. In patients with pulmonary tuberculosis, the suppressed enzymatic activity of peripheral blood lymphocytes was shown to be more pronounced when the cells were incubated with rifampicin and isoniazid for 2 hours than for 1 hour.

[Role of cytokines in the modulation of lymphocytic subpopulational composition in patients with pulmonary tuberculosis].

The parameters of the lymphocytic CD-population composition and the production of cytokines in the cell cultures of peripheral blood mononuclear cells were studied in patients with infiltrative pulmonary tuberculosis. A marked reduction in the relative and absolute count of CD3+ and CD4+ lymphocytes and an increase in the level of CD8- and CD16-positive cells were established in both drug-sensitive and drug-resistant types of the disease. A significant increase in the production of IL-12 and a reduction in the spontaneous elaboration of interferon-gamma were observed in all the examinees. Addition of lipid and protein myobacterial antigens (Beijing strains) caused a notable decrease in the generation of the study cytokines as compared with the respective parameters in healthy donors and their basal secretion irrespective of the type of a tuberculous process.

[Immune pathology in pulmonary tuberculosis].

The data of modem literature and the results of original investigations on mechanisms of immunopathological alterations in tuberculosis infection are presented. The role of cellular and humoral parts of immunity in pathogenesis of pulmonary tuberculosis is discussed and cytokine-mediated mechanisms of disorders in a specific immune response are analysed.

[The superficial architectonics of peripheral blood lymphocytes in patients with pulmonary tuberculosis].

Peripheral blood lymphocytes were electron microscopically studied in patients with disseminated drug-sensitive and drug-resistant pulmonary tuberculosis before and during specific antituberculous chemotherapy. There was a tendency for an increase in the count of lymphocytes with membranous morphostructural changes during the therapy, which was more clearly defined in the drug-resistant type of the infectious process. It is suggested that antituberculous drugs have a damaging effect on the membrane of immunocompetent blood cells.

Adverse reactions among patients being treated for MDR-TB in Tomsk, Russia.

BACKGROUND AND SIGNIFICANCE: Treatment of multidrug-resistant tuberculosis (MDR-TB) is challenging because of the toxicity of second-line medications. Little is known about whether adverse events impact treatment outcome. METHODS: We conducted a retrospective case series of 244 MDR-TB patients enrolled in Tomsk between 10 September 2000 and 10 September 2002. Adverse reactions were determined by laboratory data and/or clinical criteria. A multiple logistic regression model was performed to determine whether the occurrence of adverse reactions was associated with poor treatment outcome. RESULTS: In this cohort, 76.0% were cured, 6.6% failed, 4.9% died and 11.5% defaulted. Adverse events were observed in 73.3% of patients, occurring in 74.8% of patients who were adherent (taking at least 80% of prescribed doses) and 59.1% of non-adherent individuals (P = 0.11). The impact of adverse events on outcome was modified by non-adherence; among adherent patients, the occurrence of any adverse reaction was associated with treatment cure (adjusted odds ratio 3.24, 95% confidence interval 1.56-6.70). CONCLUSION: Adverse reactions occurred frequently in MDR-TB patients in Tomsk, Russia, but did not negatively impact treatment outcome. The occurrence of adverse reactions among adherent patients was associated with treatment cure.

Barriers to successful tuberculosis treatment in Tomsk, Russian Federation: non-adherence, default and the acquisition of multidrug resistance.

OBJECTIVE: To identify barriers to successful tuberculosis (TB) treatment in Tomsk, Siberia, by analysing individual and programmatic risk factors for non-adherence, default and the acquisition of multidrug resistance in a TB treatment cohort in the Russian Federation. METHODS: We conducted a retrospective cohort study of consecutively enrolled, newly detected, smear and/or culture-positive adult TB patients initiating therapy in a DOTS programme in Tomsk between 1 January and 31 December 2001. FINDINGS: Substance abuse was strongly associated with non-adherence [adjusted odds ratio (OR): 7.3; 95% confidence interval (CI): 2.89-18.46] and with default (adjusted OR: 11.2; 95% CI: 2.55-49.17). Although non-adherence was associated with poor treatment outcomes (OR: 2.4; 95% CI: 1.1-5.5), it was not associated with the acquisition of multi-drug resistance during the course of therapy. Patients who began treatment in the hospital setting or who were hospitalized later during their treatment course had a substantially higher risk of developing multidrug-resistant TB than those who were treated as outpatients (adjusted HRs: 6.34; 95% CI: 1.35-29.72 and 6.26; 95% CI: 1.02-38.35 respectively). CONCLUSION: In this cohort of Russian TB patients, substance abuse was a strong predictor of non-adherence and default. DOTS programmes may benefit from incorporating measures to diagnose and treat alcohol misuse within the medical management of patients undergoing TB therapy. Multidrug-resistant TB occurred among adherent patients who had been hospitalized in the course of their therapy. This raises the possibility that treatment for drug-sensitive disease unmasked a pre-existing population of drug-resistant organisms, or that these patients were reinfected with a drug-resistant strain of TB.

[Evaluation of biochips for the rifampin resistance detection of M. tuberculosis in strains isolated at the Novosibirsk and Tomsk regions].

Recently in Russia biochips for rifampin resistance detection of M. tuberculosis were developed. To investigate the conformity between rifampin resistance results determined both by the routinely used absolute concentration method and USING the biochips, 272 DNA samples of M. tuberculosis isolated from TB patients at Novosibirsk and Tomsk regions in 2000-2005 were analyzed. The biochip can detect 30 mutations in rpoB gene. The mutations were also tested using the single stranded conformational polymorphism method (SSCP). In addition, 60 DNAs were randomly sampled and sequenced. The results of rifampin resistance detection using biochip and absolute concentration methods were congruent in 86% cases, and were different when analyzed samples consisted of the susceptible and resistant strains of M. tuberculosis mixture. The most frequent mutations in the rpoB gene were S531 (76.2%), H526 (7%), D516 (5.6%), and L511 (5.6%). In 94% of rifampin resistant strains, there was also resistance to isoniazid. Therefore, in Siberia the rifampin resistance is the reliable marker for MDR strains of M. tuberculosis, and biochips can be used also for their detection. To hybridize with biochip the fluorescent-labeled single-stranded DNAs were routinely synthesized by two PCR, and intermediary product after the first PCR should be transferred into another tube. The last stage included high risk of cross-contamination. To exclude the risk, primer concentrations and temperature-time profile of PCR reactions were improved, and both PCR were combined in one tube. The two methods were congruent in 100%. The one tube method would be especially attractive for the routine PCR laboratory.

Causes of death during tuberculosis treatment in Tomsk Oblast, Russia.

SETTING: Tuberculosis (TB) incidence and mortality in Russia have risen dramatically over the past 15 years. OBJECTIVE: To identify risk factors and causes of death among TB patients in Russia. DESIGN: A retrospective study conducted to determine the risk factors and causes of death in patients receiving TB therapy in Tomsk, Siberia. RESULTS: Of 1916 patients who initiated treatment between 1 January 2002 and 31 December 2003, 183 (9.6%) died during treatment, 38 (21%) in the first week of therapy. Twenty-five per cent of deaths were not directly attributable to TB. Risk factors for death included older age, previous treatment for TB, multidrug resistance and alcoholism. CONCLUSIONS: The high death rate during TB treatment observed in this cohort likely reflects an increased risk of dying not only from TB, but also from comorbid conditions, such as alcoholism and cardiovascular disease. Overall, alcoholism and late presentation both contributed substantially to the mortality in this cohort.

Treatment outcomes in an integrated civilian and prison MDR-TB treatment program in Russia.

SETTING: Multidrug-resistant tuberculosis (MDR-TB) is a major problem in countries of the former Soviet Union in both the civilian and prison sectors. OBJECTIVE: To evaluate outcomes of the MDR-TB treatment program (DOTS-Plus) in Tomsk, Russia. DESIGN: Retrospective case series of all patients enrolled in this program between 10 September 2000 and 10 September 2002. The program involves both the civilian and penitentiary TB services in Tomsk. Poor treatment outcome was defined as death, default and treatment failure. RESULTS: Among the 244 patients who received treatment, 77% were cured, 5% died, 7% failed, and 12% defaulted. In a multivariable analysis, alcohol consumption during treatment and the presence of both cavitary and bilateral disease were found to be the strongest predictors of poor treatment outcome. CONCLUSIONS: The integration of civilian and penitentiary TB services in the Tomsk MDR-TB treatment program has resulted in high cure rates and low rates of default. However, alcohol use among patients with MDR-TB is associated with poor treatment outcomes. Better understanding and programmatic alcohol interventions are needed if large-scale treatment of MDR-TB is to be successful in areas with high rates of alcohol use disorders.

[A comparative analysis of tuberculosis susceptibility genetic make-up in Tuvinians and Russians].

The results of the first Russian study of polymorphisms of tuberculosis (TB) susceptibility genes SLC11A1, VDR, IL12B, IL1B, IL1RN in Tuvinians from Tuva Republic and Russians from Tomsk city are presented. In Tuvinians, as compared with Russians, the significantly higher prevalence of potentially disease-associated alleles of the genes studied was shown: SLC11A1*543N (0.139 and 0.043, respectively, p = 4.6E-5), IL12B*1188C (0.378 and 0.174, respectively, p = 1.1E-8), VDR*b (0.825 and 0.532, respectively, p = 3.2E-16), IL1B*(+3953A1) (0.865 and 0.806, respectively, p = 0.035). However, no one of these alleles was associated with TB in Tuvinians, whereas, in Russians TB patients, in comparison with the controls, there was a higher prevalence of the following markers: IL1RN*A2 (0.258 and 0.186, respectively, p = 0.024), SLC11A1*274T (0.251 and 0.164, respectively, p = 0.009), IL12B*1188C (0.240 and 0.174, respectively, p = 0.044), ILIB*(+3953A2) (0.259 and 0.194, respectively, p = 0.044). Distinct patterns of linkage disequilibrium between pairs of the polymorphisms studied in Tuvinians and Russians were shown. At whole, the data obtained demonstrate the ethnic specificity of the distribution and pathogenetic significance of the alleles of the TB susceptibility genes.