Estimation of mutagenic effect and modifications of mitosis by silver nanoparticles.

We analyzed mutagenic and mitosis-modifying effects of silver nanoparticles (Allium test). Chromosome aberrations and laggings and micronuclei were simultaneously registered in the same sample. Mitotic and phase indexes were calculated. No mutagenic effects were detected after treatment with silver nanoparticles in doses of 1.0, 2.5, 5.0, and 50 mg/liter. Silver nanoparticles in a concentration of 50 mg/liter significantly increased the mitotic index. Nanoparticles in a dose of 5 mg/liter induced slight, but significant increase in mitotic index, but did not affect the ratio of phase indexes. Exposure to silver nanoparticles in concentrations of 1.0 and 2.5 mg/liter was not followed by modification of mitosis.

[Bacteriological substantiation of the antituberculosis effect of immunotropic drug tubosan].

The antituberculosis effect of tubosan registered in the Russian Federation as an immunostimulant drug has been studied on a series of 53 clinical strains of Mycobacterium tuberculosis (MBT). It is established that tubosan produces a bactericidal effect on drug-sensitive MBT strains and a bacteriostatic effect on resistant MBT strains. Use of tubosan for the treatment of 102 patients with drug-resistant destructive tuberculosis showed evident clinical-radiological involution process, with prospects of clinical recovery for 75% of patients. Results of this study show that tubosan possesses both antituberculosis and immunostimulant properties. It is recommended to use tubosan for complex treatment of patients with drug-resistant tuberculosis.

[Multiple drug resistance of Mycobacterium tuberculosis isolated from new cases of respiratory tract tuberculosis].

Resistance of Mycobacterium tuberculosis isolated from new cases registered during a period from 2007 to 2012 was estimated. High rate of the M.tuberculosis multiple drug resistance increase was observed: from 28% in 2007 to 64% in 2012. Low efficacy of the treatment of such patients requires revision of the tuberculosis control strategy and search for new pharmacological agents groups.

[Antituberculosis properties of methyldioxotetrahydropyrimidine sulfonisonicotinoyl hydrazide].

Antituberculosis properties of methyldioxotetrahydropyrimidine sulfonisonicotinoyl hydrazide (MSH) registered in Russia under the name of tubosan of the class of immunotropic agents were investigated with the use of 78 clinical isolates of Mycobacterium tuberculosis (MBT). In concentration of 60 or 80 mcg/ml the drug showed significant antituberculosis activity. The effect of MSH on drug susceptible MBT was bactericidal. The effect of MSH on the drug resistant MBT (with the isoniazid MIC of 1 mcg/ml) was bactericidal in 75% of the cases and bacteriostatic in 25% of the cases. With the use of MBT resistant to isoniazid in a concentration of 10 mcg/ml the antituberculosis effect was observed in 47% of the cases. The complex treatment of 102 patients with destructive forms of tuberculosis in a daily dose of 800-1200 mg for 2-5 months provided significant clinicoroentgenologic positive dynamics of the process in 75% of the patients. The destructive cavities closed up in 30% of the patients and reduction of the destruction dimentions up to 0.5-2 cm was stated in 45% of the patients. In the control group of 40 patients insignificant dynamics of the destructive processes was observed only in 40% of the patients. Satisfactory tolerability of the drug was registered. The immunity status parameters improved with increase of the total number of T-lymphocytes and phagocytosis indices. The study showed that MSH was efficient in complex therapy of tuberculosis patients allow for increased number of cases with drug resistant tuberculosis.

[Overcoming resistance of tuberculosis infectious agent by isoniazid-silver nanocomposite].

The antituberculous activity of a nanocomposite based on nanoparticulate silver and isoniazid has been studied on the model of drug-resistant tuberculosis in a group of 65 white mice. The possibility of overcoming the resistance of the tuberculosis activator by the proposed nanocomposite of isoniazid and nanoparticulate silver is demonstrated in terms of the survival index, biometric data, bacteriological and pathomorphological parameters. Dose-dependent parameters of the presence of nanoparticulate silver in the composite structure are established. The results of preclinical research scientifically prove good prospects for using nanoparticulate silver in the treatment of drug-resistant tuberculosis.

[Retrosternal lymphotropic chemotherapy and pneumoperitoneum in the treatment of drug-resistant destructive pulmonary tuberculosis].

The efficiency of combined treatment with retrosternal lymphotropic administration of drugs and pneumoperitoneum was comparatively analyzed in 148 new cases of destructive pulmonary tuberculosis. Both methods were applied during combined chemotherapy in a study group of 48 patients. In Group 2 (n = 54), lymphotropic procedure was employed alone during standard chemotherapy; in Group 3 (n = 46), only pneumoperitoneum was used in combination of chemotherapy. In 40 patients, pulmonary tuberculosis was acutely progressive. Drug resistance was identified in 81.7%, including multidrug resistance in 27.7%. With the combined use of retrosternal lymphotropic therapy and pneumoperitoneum, bacterial excretion ceased in 96.2% of new cases of drug-resistant tuberculosis; decay cavity resolved in 80.8%. The proposed therapeutic technology used in patients with persistent bacterial excretion and decay cavities after ineffective 4-9-month treatment could achieve abacillation in 90.9% of patients and resolve decay cavities in 77.3%. Retrosternal drug injection reduces a risk for complications due to bronchial tuberculosis involvement when pneumoperitoneum is applied.

[Efficiency of retrosternal lymphotropic chemotherapy in the treatment of new cases of destructive pulmonary tuberculosis].

The efficiency of treatment was evaluated in 2 groups of new tuberculosis cases discharging drug-resistant Mycobacterium tuberculosis. The authors' method of retrosternal lymphotropic administration of drugs was used in the complex of treatment in a study group of 96 patients; a control group (n = 93) received only combined chemotherapy. The treatment method showed a high efficiency in the treatment of new cases of destructive pulmonary tuberculosis, including acutely progressive forms and caseous pneumonia. Bacterial discharge cessation and decay cavity closure were increased by 26.9% and 27.2%, respectively. The abacillation rate increment was 32.9% for acutely progressive processes and 41.2% for caseous pneumonia. The authors show the efficiency of the method in treating bronchial or laryngeal tuberculosis and the expediency of applying the retrosternal procedure during preoperative preparation.

[The diagnosis and course of progressive disseminated pulmonary tuberculosis].

A hundred and forty-six patients with disseminated pulmonary tuberculosis were examined. Hematogenous disseminated tuberculosis at this stage was ascertained to run more frequently as acute and acutely progressive. The proportion of lymphogenous tuberculosis was shown to increase among all the types of disseminated pulmonary tuberculosis. Identification of the lymphobronchogenic type of disseminated pulmonary tuberculosis is recommended.

[Extracorporeal antiaggregant pharmacotherapy in the treatment of acutely progressive forms of tuberculosis].

The investigation was undertaken to study whether extracorporeal pharmacotherapy with the antiaggregant pentoxiphylline (trental) might be used to correct blood rheological disorders in the early combined treatment of 32 patients with acutely progressive destructive tuberculosis, including 15 patients with caseous pneumonia. The method is based on the administration of in vitro drug-treated autologous blood cells. Two-three-week extracorporeal pharmacotherapy with the antiaggregant pentoxiphylline substantially improved pulmonary microcirculation and made the laboratory values of hypercoagulation and endotoxicosis better. The method promoted accelerated regression of the clinical and X-ray manifestations of the disease in 27 of the 32 patients. Few observations lead to a preliminary conclusion that this method positively affects the results of treatment for acutely progressive forms of tuberculosis, including those of treatment for caseous pneumonia.

[Diagnostic and treatment policy errors in caseous pneumonia].

Analysis of diagnostic and treatment policy in 314 patients with caseous pneumonia has identified a complex of factors that considerably affect the outcome of the disease. The most significant diagnostic errors are a considerable delay of out- and inpatient diagnosis, untimely determination of caseous pneumonia as a form of tuberculosis under the conditions of tuberculosis institutions. Drug treatment errors involve the wrong determination of the goal of treatment to hopefully eliminate destructions, as well as inadequate etiopathogenetic therapy. The points are long-term preparation for surgical treatment and a low proportion of caseous pneumonia patients operated on. Strategic and tactical errors have been ascertained to be of great importance in defining a place of surgical treatment in the general plan of treatment for patients with caseous pneumonia.

[Diagnostic features for the early variant of caseous pneumonia].

Examination of clinical, X-ray, and laboratory data of 312 patients with caseous pneumonia identified an early variant of this disease in 35%. The early variant was the initial stage of caseous pneumonia, characterized by the comparable restricted extent of alterative lesion and by the absence of signs of severe multiple organ dysfunction. The application of a package of intensive methods of etiotropic and pathogenetic therapy, including regional lymphotropic therapy and extracorporeal immune pharmacotherapy led to bacterial isolation cessation in 81% of patients. Clinical recovery was achieved in 63% of the patients with the detected early variant of caseous pneumonia. There were no fatal cases in patients with the early variant of caseous pneumonia. The study demonstrated the value of the clinical X-ray variants of caseous pneumonia for its early diagnosis and initiation of therapy.

[Pathogenetic therapy for caseous pneumonia]. / Patogeneticheskaia terapiia pri kazeoznoi pnevmonii.

The efficiency of treatment was studied in 79 patients with caseous pneumonia, including 37 patients (a study group) in whom pathogenetic therapy was performed in accordance with the proposed scheme and 42 patients (a control group) used routine treatment regimens. A study of clinical and X-ray picture of caseous pneumonia identified its three variants requiring a differential approach to its treatment, such as an early stage of caseous pneumonia; an infiltrative and necrotic stage; and a caseous and destructive stage. Analysis of the course of the disease showed it necessary to make a timely correction of complex etiotropic and pathogenetic therapy, to determine the optimal time of surgical treatment. The use of a programme for stepwise pathogenetic therapy for caseous pneumonia by taking into account the identified variants decreased the number of fatal outcomes by 2.8 times in the study group of patients as compared with this parameter in the control group.

[Diagnostic features of newly diagnosed tuberculosis on different accounts of consulting with a physician]. / Nekotorye osobennosti vyiavleniia tuberkuleza organov dykhaniia.

The specific features of diagnosis were studied in 209 patients with tuberculosis at 9 phthisiological stations of the Yaroslavl Region in 1998-2002. In 96.2% of the patients, tuberculosis was found to have been newly diagnosed in general polyclinics and polyclinics. Only in 3.8% of the patients, the diagnosis of tuberculosis was made at prophylactic fluorography performed on the patients' initiative. A retrospective assessment of outpatient records indicated a significant delay in establishing tuberculosis, by using adequate diagnostic criteria if a physician had professional skills. The authors arrive at the conclusion that dispensary should assume the functions of phthisiopulmonological centers that will secure the continuity of early diagnosis of tuberculosis and its early treatment.

[Problems of the epidemiology, diagnosis, and treatment of caseous pneumonia]. / Problemy épidemiologii, diagnostiki i lecheniia kazeoznoi pnevmonii.

The pace on increases in new cases of caseous pneumonia in 1992-2001 is 50% ahead of that in the total number of new cases of pulmonary tuberculosis. Examination of the specific features and the course of caseous pneumonia in 128 new cases identified the criteria for diagnosing this form of tuberculosis. The leading criteria are the X-ray signs of caseous and necrotic lung tissue damage and the clinical and laboratory signs of significant endotoxicosis and immunodeficiency. The use of extracorporeal immune pharmacotherapy with diucifon in 53 patients and the retrosternal administration of isoniazid with hydrocortisone in 43 patients showed the efficiency of these methods in the treatment of patients with caseous pneumonia.

[Use of isofon in combined treatment of patients with acutely progressive forms of tuberculosis]. / Primenenie izofona v kompleksnom lechenii bol'nykh s ostroprogressiruiushchimi formami tuberkuleza.

Isofon given in a dose of 800 mg daily for 1.5-2 months contributed to clinical and X-ray involution of a process in 16 of the 19 patients with acutely progressive destructive forms of tuberculosis. The drug proved to be effective in patients who isolated drug-resistant Mycobacteria tuberculosis, including those to a combination of isoniazide and rifampicin. When used in patients with significant immunodeficiency, isofon provided an immunomodulating effect. It caused relatively a great deal of adverse reactions as fever in 11 patients, weakness, dizziness in 5, and cardiac arrhythmia in 1. The findings show it necessary to perform further clinical trials of the drug.

[Some specific features of drug resistance of Mycobacteria tuberculosis in patients with acutely progressive destructive forms of pulmonary tuberculosis]. / Nekotorye osobennosti lekarstvennoi rezistentnosti mikobakterii tuberkuleza u bol'nykh s ostroprogressiruiushchimi destruktivnymi formami tuberkuleza legkikh.

A clear correlation has been found between the drug resistance of Mycobacterium tuberculosis (MBT) and the degree of immunodeficiency in 127 patients with acute destructive tuberculosis. The findings indicate that it is possible to use significant immunodeficiency as an early marker of the multidrug resistance of MBT and as a predictor of cheesy pneumonia. The fact that there was X-ray involution in one lung and concomitantly progression in the other suggests the presence of MBT strains showing different drug resistance. The efficiency of treatment for acute tuberculosis has been ascertained to be determined by MBT drug resistance.

[Extracorporeal immunopharmacological therapy in the treatment of patients with acutely progressing froms of pulmonary tuberculosis]. / Ekstrakorporal'naia immunofarmakoterapiia v lechenii bol'nykh s ostroprogressiruiushchim tuberkulezom legkikh.

Extracorporeal immune-pharmacological therapy, involving Diuciphonium, was added to the complex treatment of 46 patients primarily diagnosed as having acutely progressing destructive pulmonary tuberculosis. Investigations showed that this method sped up the regression of clinical and X-ray signs, during 1 to 2 months, and recovered the immune reactivity in 89% of patients. The clinical changes were dynamically compared with those of 50 other patients in another group (including 39 patients with caseous pneumonia), who were treated by small-volume plasmapheresis. Advantages of applying the extracorporeal immune-pharmacological therapy were demonstrated; they comprise: a shorter time needed to arrest the endotoxicosis, a fuller and faster recovery of the main populations and sub-populations of lymphocytes and a less number of fatal outcomes.

[Errors in diagnosing pulmonary tuberculosis in general hospitals and results of treating the disease]. / Oshibki v diagnostike kazeoznoi pnevmonii v obshchesomaticheskikh statsionarakh i rezul'taty lecheniia zabolevaniia.

AIM: To specify diagnostic approaches to rapidly progressive destructive pulmonary tuberculosis (RPDPT) in general hospitals and effects of the time of the diagnosis on treatment results. MATERIALS AND METHODS: History, diagnostic techniques and treatment of 162 patients with RPDPT (98 cases with cheesy pneumonia, 37 cases with rapidly progressive infiltrative tuberculosis, 27 cases with rapidly progressive disseminated tuberculosis) were studied. RESULTS: The diagnosis of tuberculosis was verified for 7 days in 56% patients, in 33% of them the diagnosis took more than 14 days. Tuberculosis was hidden under the mask of inflammatory pulmonary diseases in 60% patients, concomitant pathology--in 19%. Masks were also due to severe intoxication, multiorgan insufficiency, complications, tuberculosis of other organs. RPDPT was diagnosed primarily by x-ray examination, bacteriological test for M. tuberculosis was used in 14%. Lethal outcomes in the group of patients diagnosed for 14 days and longer occurred 2.6 times more frequently than in those diagnosed within 7 days. CONCLUSION: The analysis of the diagnostic errors resulted in design of the scheme of the diagnosis of RPDPT including cheesy pneumonia intended for use in general practice with account for possible "masks" of the disease. Basic criteria of the diagnosis are stepwise development of the disease and infiltrative-alterative changes on x-ray picture. Phthisiological alertness of general practitioners in relation to RPDPT must direct the physicians to active detection of M. tuberculosis in the sputum and close cooperation with phthisiologist in complicated diagnostic cases.

[Problems of epidemiology, diagnosis and treatment of caseous pneumonia]. / Problemy épidemiologii, diagnostiki i lecheniia kazeoznoi pnevmonii.

In 1992-2001, the growth rates of new cases of caseous pneumonia were 50% greater than those of the total new cases of respiratory tuberculosis. Examining the specific features of the diagnosis and treatment of 128 new cases of caseous pneumonia has identified diagnostic criteria for this form of tuberculosis. The leading criteria are X-ray signs of caseous and necrotic lung tissue lesion; clinical and laboratory signs of significant endotoxicosis and immunodeficiency. The use of extracorporeal immunopharmacotherapy with diucifon in 53 patients and the retrosternal injection of isoniazid in combination with hydrocortisone in 43 patients have shown their efficiencies in the treatment of patients with caseous pneumonia.