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Issue. Articles

1(16) // 2014



1. Original research


The causes of thyroid dysfunction in patients with tuberculosis/HIV co-infection

S.A. Cherenko, S.L. Matveyeva

The state of thyroid homeostasis influences on the outcomes of antituberculosis treatment. Thyroid dysfunction in HIV infection is well known. As the data of homeostasis in patients with tuberculosis/HIV co-infection is absolutely absent the objective of the research is to study the changes of thyroid homeostasis in the patients with tuberculosis/HIV co-infection in comparison to the HIV-negative tuberculosis patients.
Materials and methods. 90 patients with newly diagnosed cavitary tuberculosis and 30 patients with tuberculosis/HIV co-infection were studied to assess thyroid state: echostructure of thyroid gland was examined; the levels of free thyroxin, thyroid stimulating hormone, antibodies to thyroglobulin and thyroid peroxides in the serum were defined by immune-enzyme method.
Results and discussion. Different changes of thyroid volume and structure were specified in 51.11 % of tuberculosis patients and in 60.33 % of patients with co-infection. Subclinical hypothyroidism was diagnosed when the level of thyroid stimulating hormone was higher than 4.2 mg IU/l and was present in 13.33 % of tuberculosis patients and in 17.64 % of patients with co-infection. Autoimmune thyroiditis was diagnosed with heterogeneity of structure and increased level of antibodies to thyroid peroxides more than 30 U/ml and was present in 13.33 % of tuberculosis patients and in 33.33 % of patients with co-infection.
The causes of changes of thyroid homeostasis in patients with co-infection include decrease of index of body weight, protein insufficiency, wasting, increase of CD4+ cells and influence of highly active antiretroviral therapy (HAART), antituberculosis therapy, development of immunity reconstitution syndrome, involvement of hypothalamic structure of brain.
Conclusions. High frequency of subclinical hypothyroidism in patient with co-infection suggests providing screening of thyroid function and its correction in these patients during the period of combined HAART and antituberculosis treatment.

Keywords: tuberculosis, tuberculosis/HIV co-infection, thyroid homeostasis, subclinical hypothyroidism, autoimmune thyroiditis.

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2. Original research


Morphological features of tuberculous meningoencephalitis in HIV-infected persons

E.V. Korzh, T.V. Tlustova, T.V. Dgedgeia, E.E. Sadovnik

Objective — to study the morphological features of tuberculous meningoencephalitis (TM) in the HIV-in­fected patients.
Materials and methods. The study included 45 patients who died of TM, 36 of them were HIV-infected: 27 persons with the CD4-lymphocytes count less than 100 cells/ml (median — 32.0 cells/ml) and 9 — with the CD4-lymphocytes count more 100 cells/ml (median — 126.0 cells/ml). 9 HIV-negative TM patients were the comparison group.
Results and discussion. Autopsy revealed generalized tuberculosis in 100.0 % HIV-infected patients regardless of the HIV-status. At the level CD4 < 100 cells/ml fibrinous-purulent masses were present on the soft tunics of brain foundation in 92.6 % patients; in 77.8 % we found the miliary eruptions as characteristic of acute miliary tuberculosis. In the group of patients with CD4 > 100 cells/ml fibrinous-purulent masses were present in 100.0 % cases, miliary eruptions on the brain foundation — in 44.4 % cases. Among HIV-negative patients miliary tuberculosis was determined in 44.4 % cases, miliary eruptions on the brain foundation — in 33.3 %. In the 85.2 % HIV-infected patients with the CD4 level < 100 cells/ml the basic morphological feature of TM was zones of caseous necrosis without the peripheral cellular reaction, tuberculous granulomas were found in 22.2 % cases and all patients had vasculitis and thrombovasculitis. 77.8 % persons with the CD4 level > 100 cells/ml had tubercular granulomas and zones of caseous necrosis, 88.9 % — widespread vasculitis and thrombovasculitis. Regardless of the HIV-status and state of the immune system plethora and edema of cerebrum, perivascular lymphoid infiltration and considerable dystrophy of nervous cells were observed at all patients. No tuberculous granulomas were found in the brain of the HIV-infected patients; in the HIV-negative persons granulomas were revealed rarely (11.1 %). The areas of demyelinization and softening of the cerebral tissue were 4.5—3.5 times frequently determined in the HIV-infected patients, that we explained by development of thrombovasculitis.
Conclusions. Fibrinous-purulent masses on the brain-tunics and numerous vasculitis and thrombovasculitis on the soft brain-tunics and cerebrum were the main morphological features of TM in the HIV-in­fected patients. At the CD4 level < 100 cells/ml organism loses a possibility for cellular reactions, and zones of caseous necrosis were the main morphological changes of brain-tunics, however at CD4 > 100 cells/ml majority of patients developed tuberculous granulomas. Frequent vasculitis, thrombovasculitis and, as a result, areas of demyelinization and softening of the cerebral tissue were the original feature of TM in the HIV-infected patients.

Keywords: morphological features, tuberculous meningoencephalitis, HIV infection.

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3. Original research


Interferon inducer effect on clinical indices in patients with newly diagnosed infiltrative pulmonary tuberculosis

V.I. Petrenko, Yu.A. Varchenko, S.S. Gritsay, T.V. Malinovska, V.V. Kovalenko, O.G. Matskov, .Ye. Kharlamov

Objective of the research was to estimate interferon inducer cagocel effect on the dynamics of smear conversion, blood biochemical indices and roentgenologic dynamics in patients with newly diagnosed infiltrative pulmonary tuberculosis (NDPTB).
Materials and methods. The dynamics of cavities closure, biochemical indices and smear conversion were evaluated in 58 patients with NDPTB. The basic group of NDPTB patients, who recieved interferon inducer, included 28 persons. The control group of patients, who were treated using the standard regimen, consisted of 30 persons.
Results and discussion. The study revealed positive effect of interferon inducer resulted in 32.2 % higher cavities closure after four months of treatment and 29.8 % higher cavities closure on the moment of treatment completion in comparison to control group patients. Frequency of smear conversion in basic group of patients was 21.15 % higher on the second month of treatment in comparison to the control group ofpatients. Cagocel administration improves the indices of liver functional activity that presents with sighnificant lowering of ALT and bilirubin levels.
Conclusions. Use of interferon inducer (cagocel) during 4 weeks of the first month of treatment in patients with newly diagnosed pulmonary tuberculosis favors improving of cavities closure on the 4th month of treatment, promotes more frequent smear conversion after two months of treatment, improves the indices of functional activity of liver.

Keywords: tuberculosis, interferon inducer, clinical efficacy.

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4. Original research


L-arginine efficiency in the correction of primary kidney impairment in patients with newly diagnosed pulmonary tuberculosis

.K. Asmolov, S.. Polyakova, Ya.V. Beseda

Objective — to estimate the efficiency of L-arginine use for the correction of primary kidney impairment in patients with newly diagnosed pulmonary tuberculosis.
Materials and methods. All patients with the newly diagnosed pulmonary tuberculosis (30 persons) were divided into 2 groups: the main group (n = 20) included patients who received L-arginine solution 4.2 % — 100 ml once a day N 5 simultaneously with antituberculosis therapy; control group (n = 10) — patients who received only antituberculosis therapy.
Results and discussion. Including L-arginine into the therapy resulted in the decline of level of microalbuminuria in patients of the 1-st group to the mean values — 18.0 ±  0.8 mg/l, that sighnificantly differs from the analogical index in the initial state — 40.0 ± 0.8 mg/l ( < 0.05). Patients of the 2-nd group didn’t show the positive dynamics for level of microalbuminuria, that was even elevated in two patients. Two patients of the 2-nd group had marked increase of level of day’s proteinuria on the second week of antituberculosis therapy, while this index remained within normal limits in the patients of the 1-st group.
Conclusions. L-arginine 4.2 % — 100 ml solution administration once a day N 5 in the complex therapy of patients with the newly diagnosed pulmonary tuberculosis allows to prevent development of sighnificant kidney impairment and has favorable tolerability.

Keywords: newly diagnosed pulmonary tuberculosis, primary kidney impairment, microalbuminuria, L-arginine.

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5. Original research


Retabolil effect on the haematological and biochemical indices in tuberculosis/HIV patients

U.B. Zaguta

Objective — study the retabolil effect on haematological and biochemical indices in tuberculosis/HIV patients.
Materials and methods. The study included 51 patients with different clinical forms of newly diagnosed pulmonary tuberculosis associated with HIV-infection. Patients were divided into two groups: 20 patients (the 1st group) received standardized antituberculosis therapy, 31 patients (the 2nd group) received adjuvant Retabolil according to the following schedule: 50 mg intramuscular once in 2 weeks from the beginning of the initial phase during 2 months. The assessment of clinical symptoms, data of general blood count and biochemical indices was conducted and whole blood protein, bilirubin, AST, ALT, glucose, urea, creatinine, thymol test were analyzed.
Results and discussion. Significant increase of haemoglobin level and erythrocytes count has occurred in patients of the second group after treatment. The patients of the first group after treatment had signifi­cant increase of bilirubin level and almost normal AST and ALT level that can be explained by negative influence of antimycobacterial therapy on liver function. Patients of the second group had increased bilirubin level in comparison to indices before treatment, although AST level decreased and the significant decrease of urea and creatinine level showed up. Toxic adverse TB-drug reactions were 2 times less often in patients of the 2nd group. Cytoprotective action of retabolil at toxic adverse TB-drug reaction can be explained by increase of liver protein-synthesis function, the antioxidation activity, energy state of the cells, improvement of membrane transport and membrane structure presented with liver-protective effect, particularly raising antytoxic ability of liver.
Conclusions. Significant haematological and biochemical disorders, such as anaemia, general plasma protein level reduction, increased transaminase level, as well as thymol test indices are present in tuberculosis/HIV patients. That reflects the unsatisfactory functional condition of the liver, increased urea and creatinine levels, being indicative of intensification of the protein disinteration. Inclusion of retabolil in standardized antimycobacterial therapy promotes the significant reduction of anaemia, significant increase of general protein level with simultaneous reduction of the urea and creatinine level that reflects the reinforcement of the protein-synthesis. Retabolil also favours improvement of the certain liver function indices (AST level decrease) against the background of the reduction of toxic adverse TB-drug reactions.

Keywords: tuberculosis, HIV, retabolil.

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6. Original research


Pecularities of tuberculosis course according to NAT2 genotype

P.B. Antonenko

Objective — to detect peculiarities of pulmonary tuberculosis (TB) course during hospital-stage of treatment according to N-acetyltransferase 2 (NAT2) genotype.
Materials and methods. Analysis of medical cards of 84 patients with newly diagnosed pulmonary tuberculosis at the end of in-patient treatment in Odessa Regional Tuberculosis Dispensary was conducted in 2012 year with consideration of NAT2 genotype.
Results and discussions. At the beginning of treatment TB-patients that are rapid acetylators (RA) 3 times more often had dissemination signs than slow acetylators (SA), however the last ones had more commonly focal TB-process.  During in-patient treatment of SAs the destructive process has been aborted 1,3 times more quickly, sputum smear conversion by culture was 1,2 times more often in comparison to the RAs. At the discharge from the hospital RAs 2,2 times more often were reported as 4 category and had multidrug-resistant TB in comparison to the SAs.  
Conclusions. Detection of NAT2 genotype in TB patients could be a predictor of treatment course and outcome.

Keywords: tuberculosis, N-acetyltransferase 2, treatment outcome.

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7. Original research


On the pathogenesis of hemodynamic pulmonary edema

V.I. Korgov, I.V. Liskina, .V. Loza, .. lexynskaya, N.G. Palivoda

Objective — examine the level of malondialdehyde (MDA) in erythrocytes and main structural and morphological changes in the lungs in the dynamics of hemodynamic pulmonary edema.
Materials and methods. Research work was made on 75 white rats with weight ranged from 180 to 200 gram. Hemodynamic pulmonary edema was reproduced by a single intramuscular injection of adrena­line tartrate solution to animals in doses: 2.5 mg/kg, 1.5 mg/kg, 1 mg/kg and 0.5 mg/kg. Rats were taken out of the experiment by decapitation under light ether anesthesia after 1 and 11 days.
The concentration of MDA in red blood cells was determined. Sampling of lung tissue was made for histological studies.
Results and discussion. Study results indicate that the edemogenic action of adrenaline depends on the dose and time after administration. Injection to animals of the lethal dose of epinephrine (2.5 mg/kg) leads to their death in average 15 minutes. At a dose of epinephrine 1.5 mg/kg survival rate was 40 %. After 1 and 11 days after drug administration to animals at a dose of 1.5 mg/kg, 1 mg/kg and 0.5 mg/kg MDA content in the erythrocytes was significantly increased. Temporal changes in lung morphology were revealed, with characteristics depending on the initial dose of the drug. It should be noted that structural damage of the lung tissue due to pulmonary edema, although are preferably reversible, but completely recovery doesn’t occur. Most likely this is related with destabilization of the lipid peroxidation.
Conclusions. Edemogenic process in lungs after 1 day and 11 days after the injection of adrenaline to animals in a dose of 1.5 mg/kg, 1 mg/kg and 0.5 mg/kg is followed by a reliable increase of MDA in erythrocytes and morphological changes in the lungs, the severity and nature of which is dependent to epinephrine dose and the time period after administration.

Keywords: pulmonary edema, malondialdehyde, erythrocytes, morphological changes.

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8. Original research


The use of anterior upper extrapleural thoracoplasty for the purpose of liquidation of residual pleural cavity

I.D. Duzhyi, O.V. Kravec, N.I. Glazunova

Objective — to study the possibilities of applying own method of anterior upper extrapleural thoracoplasty in the short-term postoperative period.
Materials and methods. 7 (3.9 %) of 170 operated patients in the early postoperative period had residual pleural cavity. In order to eradicate residual cavities anterior upper extrapleural thoracoplasty in modification of the authors was applied [6].
Results and discussion. Operation was performed on the 12—18 day with good early and distant results. Operation on the right side was performed in five cases, left — in two cases.
Conclusions. Being not traumatic surgical intervention and performed in the physiological position, the operation is recommended to perform in any short-term postoperative period.

Keywords: time-lapse lung expansion, residual pleural cavity, anterior upper extrapleural thoracoplasty.

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9. Original research


The efficiency of psychological follow-up to tuberculosis treatment on inpatient phase

D.A. Yasinov, I.. Polovinko, L.. Smagina

Adherence of patient to treatment has the significant meaning in the problem of morbidity decreasing. Improvement of the adherence system is the key point to fight tuberculosis epidemic. The experience of implementation of psychological follow-up model for tuberculosis patients’ adherence to treatment on inpatient phase with involvement of psychologists is presented in the paper.
Objective — to compare indicators of treatment failure for patients with pulmonary TB for the period preceding psychologists work in in-patient departments of TB dispensary with indicators for the similar period of their work with patients.
Materials and methods. The study is based on the case histories of 321 adult patients with pulmonary TB, who underwent treatment in in-patient departments of TB dispensary within 9 months of 2011 and without psychologists follow-up; case histories of 550 adult patients with pulmonary TB, who underwent treatment in in-patient departments of TB dispensary within 9 months of 2012 and with psychologists follow-up.
Results and discussion. Comparative survey showed credibility of patients treatment failure indicators to decrease for the period of psychological follow-up p < 0.001.
Conclusion. Study data indicate significant decrease of treatment failure when the described model of psychological follow-up for TB treatment adherence at in-patient department is used.

Keywords: newly diagnosed tuberculosis, multidrug-resistant tuberculosis, tuberculosis relapse, adherence to tuberculosis treatment, treatment failure, dynamic process, psychological follow-up, in-patient phase of treatment.

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10. Reviews


Resistance of Mycobacterium tuberculosis: myths and reality

L.D. Todoriko, V.I. Petrenko, M.M. Grishin

Analysis of the most advanced research on molecular genetic aspects of the development of resistance in tuberculosis patients is reviewed in order to avoid its emergence in application of contemporary treatment programs. Issues of genetic aspects of the M. tuberculosis drug resistance development and study of the role of polymorphic genes variants of xenobiotics system metabolism for understanding the mechanisms of interaction in hereditary information realization at the organismal level aiming improve the efficiency of tuberculosis treatment are emphasized.

Keywords: Mycobacterium tuberculosis, molecular genetic aspects, drug resistance, multidrug resistance.

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11. Reviews


Antiretrovirus therapy: what, when, and why?

A.G. Dyachenko, S.L. Grabovyi, P.A. Dyachenko, Ye.N. Gorobchenko

Advances in antiretroviral therapy (ART) have drastically improved the quality of life for people with HIV infection. But despite of potent combination therapy usually suppresses plasma viral loads in HIV-1 patients below the detection limit of conventional clinical assays, a low level of viremia frequently can be detected in plasma by more sensitive assays. Additionally, many patients experience transient episodes of viremia above the detection limit even after being on highly suppressive therapy for many years. Failure of HAART to eradicate HIV, even in patients with undetectable virus levels for many years, associates with the existence of persistent infection in certain cellular and anatomical reservoirs. The latent reservoirs appear to be the major hurdles in HIV eradication. Progress toward eradication of the infection will require novel approaches to target the latency that persist even when viral replication is completely halted. This review will discuss these strategies and their potential for clinical development.

Keywords: human immunodeficiency virus (HIV), antiretroviral therapy (ART), latency.

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12. Reviews


Current view on course and treatment of HIV and HCV co-infection

.S. Mamedova, O.A. Golubovska, Kh.O. Pronyuk

Common routes of transmission of HIV and hepatitis C virus (HCV), an increase in the number of injection drug users cause increase of number of patients with HIV/HCV co-infection. According to the WHO there are about 200 million chronic hepatitis C patients in the world. 4 to 5 billion are HIV co-infected. Prevalence of HCV in HIV-infected injection drug users is about 72—95 % in the U.S. and Western Europe. Co-infection is associated with higher mortality in comparison to the monoinfection with each of the viruses. Treatment of HCV infection in HIV-infected patients is a priority task due to the rapid progression to end-stage liver disease, worse tolerability of antiretroviral therapy and increased risk of hepatotoxicity.

Keywords: chronic hepatitis C, HIV-infection, antiretroviral therapy.

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13. epidemic situation


Tuberculosis in health care workers (literature review and own data)

O.P. Litvinyuk, M.A. Thorovskyy, N.. Gonchar, I.O. Paliy

Objective — to study the tuberculosis morbidity among medical workers of Vinnytsia region of Ukraine in the period 2007—2012 years.
Materials and methods. Analysis of published data on the incidence of TB among health workers around the world and official TB service surveillance in Vinnytsia region for the last 6 years were studied.
Results and discussion. TB remains a serious problem for society and health systems of most countries. TB among health care workers is an urgent problem for many countries, especially the countries of the CIS. The situation of the TB morbidity among health workers in Vinnytsia region is serious. In 2007—2012 the incidence of TB among health workers of Vinnytsia region increased from 50.5 to 51.5 per 100 thousand medical workers. The bulk of cases of TB among health workers accounted for nurses. We noted also high (18.8 %) prevalence of TB relapces. Over a fifth of tuberculosis cases (21.8 %) were found in health care workers of TB facilities. The bulk (78.2 %) workers are ill women due to the high TB morbidity of nursing staff. Among the 75 % of cases among physicians are presented by male workers. All these features can be attributed to TB among health care workers.
Conclusions. The highest incidence of TB is in Africa, Latin America and Southeast Asia. A significant number of TB cases is registered in Eastern Europe, especially in the CIS. In these countries there is also high tuberculosis morbidity among health care workers. Against the background of TB morbidity reduction among the general population and the population of Ukraine of Vinnytsia region for the past 6 years, TB incidence among medical workers of GMN and TB facilities increased. The highest incidence was observed among nurses. A significant proportion of all cases of TB among health care workers are relapses. The majority of all TB cases among health care workers are among employees of TB facilities and women.

Keywords: tuberculosis, health care workers, morbidity, Vinnytsia region, Ukraine.

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14. to help a general practitioner


Modern aspects of diagnosis and treatment of chronic obstructive pulmonary disease according to the new international recommendations GOLD

M.O. Kulynych-Miskiv, M.M. Ostrovskyy, O.I. Varunkiv, I.O. Savelikhina, G.Z. Korz, A.B. Zuban

The paper presents the literature review for the problems of treatment of chronic obstructive pulmonary disease. The review on recommendations «Global Strategy: diagnosis, treatment and prevention of COPD» (GOLD), European Respiratory Society (ERS) and a protocol of care for diagnosis and treatment of COPD is presented. The importance of using modern technologies in the treatment of chronic obstructive pulmonary disease is emphasized.

Keywords: chronic obstructive pulmonary disease, recommendations, treatment.

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15. Lectures


Spontaneous pneumothorax in tuberculosis of the respiratory system: athogenesis, pathological changes, clinical manifestations, diagnosis and emergency treatment

N.A. Gritsova, O.M. Raznatovska

The article presents the pathogenesis and pathological changes, clinical manifestations, diagnosis and emergency care for spontaneous pneumothorax with pulmonary tuberculosis. Algorithms are described in detail step by step diagnostic and emergency care for spontaneous pneumothorax.

Keywords: spontaneous pneumothorax, pulmonary tuberculosis.

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16. Lectures


Immunization of HIV-infected children

N.V. Kotova

The article presents data on the efficacy and safety of vaccination of HIV-infected children before treatment and during HAART, describes the causes of poor post-vaccination response in HIV-infected children and provides recommendations on the use of various vaccines and immunoglobulins in HIV-in­fected children.

Keywords: HIV infection in children, vaccination, immunization.

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17. education


Experience of implementation of the Stop-TB strategy for the tuberculosis control in the Autonomous Republic of Crimea

M.N. Grishin, Ye.A. Ochota, A.I. Hripunov, Ye.O. Korchagina, I.V. Polsky, A.V. Aukhadieva, N.N. Aukhadiev

Experience of Stop-TB strategy implementation in RC has shown that this process should be made in two stages. In the beginning, the public medical opinion should be formed proving necessity of reorganization of the antituberculous care, and elements of new system into the regional medical institutions should be further adopted. For the formation of public opinion, the most effective is carrying out trainings with phthisiologists, laboratory assistants, doctors and doctor's assistants of the general medical network. It is necessary to introduce teachers of the field-specific department, and expert phthisiologists of the region into the training group. During carrying out of training, it is expedient to organize a meeting with the leaders of region supervising Public Health and regional organs of the mass communication. Regular monitoring visits to regions should be carried out for implementation control. Monitoring groups should include the representative of the field-specific department — the participant of a training group. It allows employees of a department to be well informed about epidemiological situation, fruitfully participate in working up the programs and orders concerning the antituberculous care, carry out trainings and seminars with employees of funds and organizations, who are engaged in social care, carry out good teaching of phthisiology for students, interns and postgraduates, offer to the Ministry of Health Panel high-grade, scientifically based recomendations on enriching work of medical institutions.

Keywords: tuberculosis, strategy implementation, training.

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