[The effectiveness and safety of sparfloxacine in combined therapy for tuberculosis].

The effectiveness and safety of the difluoroquinolone sparflo (sparfloxacine) used in combined therapy for drug-sensitive and drug-resistant pulmonary tuberculosis were studied. Clinical trials were carried out in 60 patients with severe pulmonary tuberculosis. The more effective combinations of sparfo and other antituberculous drugs were determined. Data on the satisfactory tolerability of sparfo used in various combinations of first- and second-line agents are presented.

[Thiopoeitins in the treatment of tuberculosis].

Drug resistance in Mycobacterium tuberculosis, adverse reactions, caused by antituberculous drugs, as well as suppressed cellular immunity are responsible for lower efficiency of treatment. To improve the results of treatment in patients with tuberculosis in the intensive phase, the authors used glutoxim, a representative of thiopoeitins. Glutoxim treatment was performed in 73 patients with pulmonary tuberculosis (a study group). A control group comprised 45 patients. The course of therapy with glutoxim, 60 mg/day, was 52 days. The study group was characterized by a rapider cessation of intoxication symptoms, the higher rates of bacterial isolation cessation, and decay cavity-closure. At the end of an intensive treatment, there was abacillarity in 64 (86.7%) patients from the study group and in 32 (71.1%) control patients; decay cavity closure was observed in 60 (88.3%) and 29 (70.8%) patients, respectively (p < 0.05).

[Glutoxim in the surgical treatment of patients with pulmonary tuberculosis].

Surgery results in the development of secondary immunodeficiency associated with inhibition of the phagocytic bactericidal systems, leading to postoperative complications. Glutoxim, a representative of thiopoietins, was used to reduce the number of postoperative complications. Twenty-nine patients with pulmonary tuberculosis received glutoxim therapy (a study group). A control group comprised 25 patients. A course of glutoxim therapy was 35 days; the daily dose was 60 mg. Postoperative complications (tuberculous pleural empyema with bronchopleural fistula, progressive tuberculosis, nonspecific pneumonias) developed in 2 (6.9%) study group patients and in 8 (32%) control ones (p < 0.05). The inclusion ofglutoxim into complex preoperative preparation and its postoperative use cause a significant reduction in postoperative complications.

[Clinical, X-ray, and bacteriological features of drug-resistant tuberculosis].

The data on 1400 patients with first diagnosed drug-resistant tuberculosis, who were followed up in 2000-2005, have been used to analyze the causes of and factors predisposing to the development of clinical, X-ray, and bacteriological features of drug-resistant tuberculosis. The prevalence of its clinical forms with a rapid progression of the process, with complications, comorbidity, the high frequency of multidrug resistance, total resistance, and massiveness and duration of bacterial isolation, which are commonly observed in socially dysadapted patients in incompliance of appropriate treatment regimens, is shown to determine a great epidemic danger. These features should be taken into account on developing and implementing the appropriate measures in both tuberculosis facilities and general hospitals.

[The use of discrete characters in discriminant analysis for diagnosis of pulmonary tuberculosis and for classification of patients differing in treatment efficiency based on polymorphisms at nine codominant loci-HP, GC, TF, PI, PGM1, GLO1, C3, ACP1 and ESD]. / Ispol'zovanie diskretnykh priznakov v diskriminantnom analize pri diagnostike tuberkuleza legkikh i pri klassifikatsii bol'nykh s razlichnoi éffektivnost'iu lecheniia po raspredeleniiu polimorfizmov v deviati kodominantnykh lokusakh-HP, GC, TF, PI, PGM1, GLO1, C3, ACP1 i ESD.

Discriminant analysis was used to differentiate patients with pulmonary tuberculosis (N = 106) from healthy individuals (N = 328) and patients whose treatment was efficient (N = 71) from those whose treatment was inefficient (N = 35). The analysis involved the data on nine polymorphic codominant loci: HP, GC, TF, PI, PGM1, GLO1, C3, ACP1, and ESD. The loci were selected by significance of differences in genotype frequencies between tuberculosis patients and healthy controls (GC, TF, PI, C3, ACP1) or between the two groups of patients differing in treatment efficiency (HP, GC, PI, PGM1, C3, ESD). Discrimination was based on a graphic method of Bayes classification procedure with a single-variate nomograph allowing easy estimation of the a posteriori probabilities for an individual to be classified. The two groups of patients proved to be discriminated sufficiently well (probability of misclassification Perr = 0.24), whereas discrimination between tuberculosis patients and healthy individuals was less efficient (Perr = 0.33). The method was proposed as a means of predicting the efficiency of treatment in pulmonary tuberculosis. Along with clinical, roentgenological, and laboratory examination, discriminant analysis may be employed as an accessory test in diagnostics of pulmonary tuberculosis, especially when the diagnosis is questionable.

[Effect of levofloxacine on cell elements of the lung tissue and on the growth of drug resistant Mycobacteria tuberculosis]. / Deistvie levofloksatsina na kletochnye élementy kul'tury legochnoi tkani i na rost v nei lekarstvennorezistentnykh mikobakterii tuberkuleza.

Levofloxacin effect on morphokinetic parameters of the murine lung tissue culture was investigated. This model allowed also to evaluate the levofloxacin activity against drug-resistant intracellular and extracellular Mycobacterium tuberculosis: MBC was 0.5-1.0 mg/l. Bactericidal effect started on the 3d day of incubation and was maximal on 7th day. Tissue cells vitality was not changed. Combination of levofloxacin with antimycobacterial drugs of first choice was investigated: isoniazid demonstrated synergistic effect, pyrazinamide also demonstrated synergistic effect. Combination of levofloxacin with rifampicin was antagonistic.

[Myrin P in the combined treatment of tuberculosis]. / Mairin-P v kompleksnoi terapii tuberkuleza.

Experimental and clinical evaluation of the new antimycobacterial quadrocomposition Myrin P was performed. The composition consists of isoniazid, rifampicin, pyrazinamide and ethambutol in fixed doses. The results of the formulation application at 474 patients with primary pulmonary tuberculosis caused by drug-susceptible and drug-resistant mycobacteria are presented. High efficacy and good tolerability of the formulation was demonstrated.

[Heterozygosity in patients with pulmonary tuberculosis showing varying responses to therapy]. / Issledovanie urovnei geterozigotnosti u bol'nykh tuberkulezom legkikh s razlichnoi éffektivnost'iu lecheniia.

The distribution of the levels of heterozygosity was analyzed by 9 loci of genetic markers: PI, TF, PGM1, ACPI, HP, GC, GLO1 C3, and ESD in two groups of patients with pulmonary tuberculosis who had improvements (Group 1, n = 71) and failures (Group 2, n = 35). The heterozygosity observed in the groups was compared with that calculated by the Hardy-Weinberg law by using data on healthy controls (n = 328; the locus ESD was investigated in 78 healthy individuals). The analysis indicated that there were statistically significant deviations of the observed heterozygosities, g1, at 4 loci (GC, PI, C3, and ACPI) from the expected ones; h1 calculated from the data in the control group. The observed heterozygisities were higher than the expected ones at 3 loci (PI, C3, and ACPI), and at the GC locus. the observed heterozygosity being lower than the expected one. Comparing the observed heterozygosities. g1, within the loci, by using Fisher's exact test revealed significant differences between the groups of patients and healthy controls at the same loci, which showed significant differences between the observed and expected heterozygosities. There were no differences between the groups of patients by the observed heterozygosities. The mean expected heterozygosity were h = 0.386 +/- 0.056. The mean observed heterozygosity, were g = 0.415 +/- 0.037, 0.402 +/- 0.061, 0.371 +/- 0.055 in Groups 1 and 2 and in the controls, respectively. There were no differences between the mean expected and obsorved heterozygosities or between the mean observed heterozygosities in the three groups under study. It is proposed that a single locus rather than the mean heterozygosities should be used as a generalized nonspecific measure of genetic control over diseases while the former can show the involvement of a specific marker locus to develop a disease, the latter can simply veil the effects of each of the loci alone. Thus, the findings produce strong evidence for that there is a genetic control in the development of pulmonary tuberculosis.

[Analysis of heterozygosity levels at P1,TF, PGM1, ACP1, HP, GC, GLO, C3, and ESD loci in pulmonary tuberculosis patients with different treatment outcomes]. / Analiz urovnei geterozigotnosti po lokusam PI, TF, PGM1, ACP1, HP, GC, GLO1, C3 i ESD u bol'nykh tuberkulezom legkikh s razlichnoi éffektivnost'iu lecheniia.

Heterozygosity at nine genetic loci (PI, TF, PGM1, ACP1, HP, GC, GLO1, C3, and ESD) was analyzed in pulmonary tuberculosis patients with good (group 1, N = 71) and poor (group 2, N = 35) response to treatment. The observed heterozygosities were compared with the expected values, which were calculated from allele frequencies in a control sample of healthy individuals (N = 328 with all but one locus and 78 with ESD) according to Hardy-Weinberg expectations. The analysis showed that the observed heterozygosities gl of patients significantly differed from the expected values hl in the case of four loci (GC, PI, C3, and ACP1). The observed heterozygosity was higher than expected in three cases (PI, C3, and ACP1) and lower then expected (GC) in one case. When data on each individual locus were compared using Fisher's exact test, both groups of patients proved to significantly differ (PF < 0.05) from the control group in the same four loci. No difference in observed heterozygosity was detected between the two groups of patients. The mean expected heterozygosity was h = 0.386 +/- 0.00674; the mean observed heterozygosity was g = 0.415 +/- 0.02 in group 1, g = 0.402 +/- 0.026 in group 2, and g = 0.371 +/- 0.00955 in the control group. The t test did not reveal a significant difference between the mean values of expected observed heterozygosities. Heterozygosity at individual loci, rather than mean heterozygosity, was proposed as an integral nonspecific indicator of the genetic control of a disease, because the former directly implicates individual marker loci in the development of a disorder, whereas effects of individual loci may eliminate each other when mean heterozygosity is computed. Based on the results obtained, a genetic control was assumed for the development of the tuberculosis process in the lungs.

[The efficacy of the ambulatory treatment of patients with newly detected pulmonary tuberculosis]. / Effektivnost' ambulatornogo lecheniia bol'nykh s vpervye vyiavlennym tuberkulezom legkikh.

Scientific rationale has been provided for the fact that new cases of pulmonary tuberculosis can be successfully treated in the outpatient setting. The paper suggests that the pattern of a tuberculous process and the patient's socioeconomic status and education level should be taken into account while choosing a treatment regimen. Indications, contraindications, necessary conditions for outpatient treatment are defined. General recommendations how to use an antibacterial treatment regimen and its methods are given. The efficiency of outpatient and inpatient treatment regimens is compared in the matched groups of patients and the advantages of treatment in the outpatient setting are noted. Treatment in the outpatient setting shows a 2-fold decrease in the likelihood of preschedule discontinuation of the basic course of antibacterial therapy as compared to that in a 24-o'clock hospital, a 2.4-fold reduction in the length of temporary disability and it can also decrease the basic course of antibacterial therapy by 1.5-2.5 months. With this, its therapeutical efficiency does not drop.

[Blood protein phenotypes and effectiveness of the treatment of patients with pulmonary tuberculosis]. / Fenotipy belkov krovi i éffektivnost' lecheniia bol'nykh tuberkulezom legkikh.

Genetic polymorphism at 9 independent loci (HP, GC, TF, PI, PGM1, GLO1, C3, ACP1, and ESD) was studied in two groups of patients with pulmonary tuberculosis and healthy controls. The patients were subdivided into two subgroups depending on their response to chemotherapy: 1) responsive and 2) unresponsive to adequate chemotherapy. The control (Group 3) comprised 327-329 healthy persons; only 78 of them were phenotyped for ESD-locus. A pairwise comparison of arcsinus-transformed both phenotypic and allelic frequencies using t-test revealed significant differences between Groups 1 and 3 in phenotypes--GC 1F-1S, (P = 3.73 x 10(-4), C3 F-S (P = 4.10 x 10(-5), C3 S-S (P = 1.9 x 10(-6) and in alleles--C3*F (P = 4.2 x 10(-6), C3*S (P = 1.7 x 10(-6). These differences are reliable at the levels of significance, Pc corrected by all numbers of times, k, of independent pairwise comparisons (k = 126 for phenotypes, Pc = 0.00041; k = 60 for alleles, Pc = 0.000855). Differences between Groups 2 and 3 were significant as well: there were 8 P values both for phenotypes and alleles, which rejected the null-hypothesis at 5% significance while the expected numbers of times, kch, to reject the null-hypothesis by chance, were kch = 6.3 for phenotypes and kch = 3 for alleles. Differences between the two subgroups of patients were found to be insignificant because the P values were obtained, that rejected the null-hypothesis only 6 and 3 times for phenotypes and alleles, respectively. Principal component analysis showed that the GLO1 locus was not informative for the differences in the groups studied. The perspectives of further analysis of the data presented using the remaining 8 loci are discussed.

[Mental evaluation of new cases of pulmonary tuberculosis in different treatment settings]. / Psikhicheskaia otsenka bol'nykh s vpervye vyiavlennym tuberkulezom legkikh pri razlichnykh organizatsionnykh formakh lechebnogo protsessa.

New one hundred and five cases of pulmonary tuberculosis were examined to evaluate the mental status in different treatment settings: a day hospital, a polyclinic, and a hospital. The Aizenok questionnaire. Shihan's test, and a clinical and symptomatological questionnaire and interviews with patients were used for psychological studies. In the day hospital and polyclinic, therapy improved the mental status of the patients at discharge. They showed their adequate attitude towards their disease, felt well and had great visas for their future social and familial life. They all were eager to resume their former work, attempted to preserve their social and working status and 16 (72.7%) patients treated at the day hospital and 18 (75%) outpatients continued working.

[Discriminant analysis of clinical laboratory data for diagnosis and treatment of tuberculosis and lung cancer]. / Diskriminantnyi analiz laboratornykh pokazatelei pri diagnostike i lechenii tuberkuleza i raka legkogo.

The study is based on the clinical observation and examination of 33 patients with stages 1 or 2 lung cancer (Group 1), 53 with stage 3 lung cancer (Group 2), and 44 patients with pulmonary tuberculosis (Group 3). All the patients underwent surgical treatment. A control group comprised 50 apparently healthy individuals. The clinical laboratory studies included general peripheral blood analysis of ESR, the levels of hemoglobin, leukocytes, lymphocytes, total protein and albumin. ANOVA revealed a highly significant (p < 0.00004) differences in 5 of the 6 study laboratory parameters, variations in the level of total protein between the groups did not differ from that in the groups (p = 0.25). ANOVA revealed significant covariation of the levels of protein with ESR (p < 0.00004) and those of albumin (p < 0.00004). When variations in the latter were eliminated, the effect of the groups on total protein variation was highly significant (p = 0.0018). Discriminant analysis showed that the parameters studied were of diagnostic value in the differential diagnosis: probabilities of correct subdivision of patients ranged 72.6 to 78%, those of erroneous classification being 27.4 and 22%, respectively. The actual probabilities of misclassification were twofold lower. The problems in the employment of the discriminant procedure in the differential diagnosis of the study diseases using the specific contingent principle are discussed and a specific clinical observation is cited as an example.

[Inpatient treatment of pulmonary tuberculosis: present day status and prospects]. / Statsionarnyi étap lecheniia bol'nykh tuberkulezom legkikh: sovremennoe sostoianie i perspektivy.

Analyzing the duration and efficiency of treatment of 95 inpatients with first detected pulmonary tuberculosis indicated that the mean hospital stay of patients without and with decay was 205 and 291 days, respectively. Medical and social aspects should be considered while defining indications and hospital stay periods in patients with tuberculosis. Long-term hospitalization of the patients is justifiable only in complicated tuberculosis and special circumstances which require direct continuous follow-up.

[Heterogeneity of pulmonary fibroblasts in tuberculosis]. / Geterogennost' legochnykh fibroblastov pri tuberkuleze.

Chronic inflammation and pneumofibrosis are the central events in tuberculosis morphogenesis. It was suggested that a certain type of fibroblasts may play a role in chronization of the inflammation and development of sclerosis in tuberculosis. Fibrous tissue from the foci of secondary tuberculosis (fibrous-cavernous tuberculosis and tuberculomas) of 35 patients were studied light- and electron-microscopically and immunohistochemically. (THY 1-)fibroblasts non-containing lipids and producing insulin-like growth factor 2 (ILGF 2), binding proteins 2 and 4 and epidermal growth factor receptors were found in the foci of secondary tuberculosis close to the granulomatous inflammation and in the new and scarrous fibrous connective tissue of the tuberculoma capsule and caverna walls. These fibroblasts are able for auto- and paracrine regulation of the proliferation of fibroblasts, epithelium and other cells in the inflammatory foci. (THY 1+) fibroblasts containing lipids were observed in the foci of old sclerotic changes among the rough collagen fibres. Thus, (THY 1-) fibroblasts probably play a key role in chronization of inflammation, proliferation and pretumorous dysplasia of pulmonary epithelium in secondary tuberculosis. (THY 1+) fibroblasts containing lipids may show more pronounced collagenesis and may persist under hypoxia condition in the collagenous scars for a long time.

[Body's responsiveness and postoperative course in patients with pulmonary tuberculosis]. / Reaktivnost' organizma i techenie posleoperatsionnogo perioda u bol'nykh tuberkulezom legkikh.

The purpose of the study was to reveal a package of criteria for the body's responsiveness in order to predict the course of a postoperative period in 25 patients with short-term pulmonary tuberculosis. The indices of the responsiveness were comparable with the specific features of a postoperative course. The study of the body's responsiveness prior to surgery and in the first days after it was found to be of value in the prediction of a postoperative course. The determination of the intensity of free radical processes may more accurately estimate the impact of surgical interventions on the body's responsiveness. The drastic rise in the activation of free radical oxidation after surgery suggests its unfavourable influence on immune mechanisms.