[Species composition and molecular-genetic characteristics of antibiotic-resistant strains of gram negative bacteria isolated from patients of a hospitals urology department].

AIM: To analyze the composition and molecular mechanisms of antibiotic resistance of Gram-negative bacteria - pathogens of urinary tract infections (UTIs) in adult patients living in the city of Almaty. MATERIALS AND METHODS: The study examined the etiological composition and antibiotic susceptibility of clinically significant isolates of bacteria and fungi ( more or equal 103) isolated from the urine of the patients of the Department of Urology of the Almaty city Central Clinical Hospital No. 12. The production of extended-spectrum beta-lactamases (ESBL) in antibiotic-resistant strains was determined using a phenotypic method with the double disk test. Detection of class A genes for cultures with confirmed ESBL phenotypes (TEM-1, CTX-M1, SHV, OXA) and carbapenemases of class B metallo--lactamases (VIM-2) genes was performed by PCR. RESULTS: Among the isolates obtained from patients, the species of Enterobacteriaceae family in the etiological composition of the UTI pathogens comprised 44.8% including E. coli (31%), K. pneumoniae (4.6%). The most effective drugs against all types of Enterobacteria were carbapenems (96.3-100%). E.coli showed highest sensitivity to nitrofurantoin (96.3%), amikacin (92.6%) and cefoxitin (81.5%). The high rate of resistance to III-IV generation cephalosporins among of E. coli (44.4%) and K. pneumoniae (50%) species was due to the production of ESBL types CTX-M1 and OXA. The proportion of non-fermenting Gram-negative bacteria in the etiological composition of UTI pathogens was 3.5%. Among them, there was a strain producing the metal -lactamase (VIM-2), characterized by absolute resistance to antibiotics of all classes, including carbapenems. CONCLUSION: The findings on sensitivity profiles and molecular genetic mechanisms of resistance of Gram-negative uropathogens are unique for the Almaty region provides the rationale for developing a local strategy for rational antibiotic therapy. Timely microbiological diagnosis and strict adherence to infection control in a specific hospital are the only way to contain the spread of ESBL and metal -lactamase.

[Prevention and control of HIV infection in the Osh region of the Kyrgyz Republic].

A total of 178 cases of HIV infection were diagnosed in the Osh region of the Kyrgyz Republic for January 1, 2003, the intensity of the prevalence of HIV infection being 14.5 per 100,000 of the population with this figure for the whole republic being equal to 5.9. In the dynamics of the HIV infection epidemic two periods were detected. During the first 3 years (1998-2000) a few individual imported cases of HIV infection were registered in the region. During the last 2 years (2001-2002) 98.8% of all cases of HIV infection registered in the region, as well as the presence of an epidemic outbreak among injection drug users (IDU), were detected. The risk factors of getting HIV infection were the intravenous use of drugs and a low level of information among young people concerning the routes of transmission of this infection and means of protection from HIV/AIDS: the promotion of healthy life style among young people, the introduction of the programs of "harm reduction" among IDU and the rules of safe sex.

[Effects of sodium nucleinate on immunological and nonspecific responsiveness in elderly and senile patients]. / Bliianie nukleinata natriia na immunologicheskuiu i nespetsificheskuiu reaktivnost' bol'nykh tuberkulezom pozhilogo i starcheskogo vozrasta.

Sixty-two elderly and senile patients with pulmonary tuberculosis were examined. Of them 32 had multimodality therapy involving sodium nucleinate. The inclusion of sodium nucleinate into a complex of therapeutical measures for the patients promotes improvement of T-cellular immunity. The patients taking sodium nucleinate were also found to have enhanced specific immunity against tuberculosis. In these patients, stimulation of immunity and nonspecific responsiveness is accompanied by the higher clinical benefits of treatment, as shown by shorter periods in abacillation, in the cessation of signs of intoxication, and in the resolution of infiltrative events and in the closure of decay cavities.

[Immunity of middle age and aged patients with tuberculosis and its changes during multimodality treatment by using T-activin]. / Immunologicheskii status bol'nykh tuberculezom pozhilogo i starcheskogo vozrasta i ego izmeneniia v protsesse kompleksnogo lecheniia s ispol'zovaniiem T-aktivina.

Fifty six patients with pulmonary tuberculosis were examined. Of them 30 had T-activin in multimodality treatment. To supplement the agent in elderly and old patients was found to elevate the counts of T lymphocytes and T helper cells, to normalize Tx/Tc ratios, to enhance T lymphocytic activity and IL-2 synthesis. At the same time there was an increase in nonspecific responsiveness: enhancement of NKC activity and IL-1 synthesis by macrophages. With this, stimulation of specific antituberculous immunity took place. Normalization of immunological responsiveness and stimulation of specific antituberculous immunity were associated with enhanced therapeutical efficiency.

[Specific antitubercular immunity in patients with tuberculosis and other pulmonary abnormality: diagnostic value of its study]. / Diagnosticheskoe znachenie izucheniia spetsificheskogo protivotuberkuleznogo immuniteta u bol'nykh pri tuberkuleze i drugoí legochnoí patologii.

A hundred and seventy one patients with revealed rounded lung formations of tuberculous and non-tuberculous origins were examined. Mycobacterial antigens, cellular antituberculosis immunity, and antituberculosis antigens were determined. Cellular sensitization to mycobacterial antigens was found to develop in about 50% of patients with round lung formations of tuberculous origin. This sensitization to PPD was more revealed by BTR rather than by TMR. At the same time, the latter is positive in healthy donors and in patients with non-tuberculous abnormality. Finally it can be concluded that cell tests are little suitable for immunodiagnosis of tuberculosis. It was also ascertained that determination of antituberculosis antigens and antigenemia might be a important component of examinations of patients with rounded lung formations in order to make a differential diagnosis of tuberculosis and non-tuberculous abnormality as with their determination, high sensitivity and specificity of appropriate tests can be achieved. These tests are more informative for the immunodiagnosis of tuberculosis than that of infiltrative tuberculosis.

[Tuberculin-provocation immunological tests in the diagnosis of pulmonary tuberculosis]. / Tuberkulinoprovokatsionnye immunologicheskie testy v diagnostike tuberkuleza legkikh.

Prior to and after administration of subcutaneous tuberculin (50 TU) 50 tuberculous and 84 patients with pulmonary tumors, pneumonia, cysts, echinococcosis were examined for immunologically active proteins (IgG, IgA, C3c) and individual serum proteins (alpha2-macroglobulin, alpha1-antitripsin, fibrinogen, acid alpha-glycoprotein). Blast-transformation and migration inhibition on PPI reactions were also conducted. It was established that the above tuberculin-provocative tests may be employed with different efficacy in different clinical situations. Tests for cell immunity are applicable in large well-equipped hospitals. Tests for immunologically active proteins and serum proteins of different functional groups are more suitable for wide practice.

[Immune status of middle-aged and aged patients with tuberculosis]. / Immunnyi status bol'nykh tuberkulezom u lits pozhilogo i starcheskogo vozrasta.

After examination of 165 tuberculous patient of presenile and senile age, 150 young patients, 65 healthy presenile and senile donors, 56 young healthy donors it was established that young and aged healthy donors differ by some parameters of T-cell immunity (inhibited blast-transformation response to PHA, reduced number of T-helpers, high suppressive activity of induced Con-A. Young tuberculous patients differ from their healthy counterparts by a variety of immunological parameters (low T-lymphocyte and helper count, poor blast-transformation, increased number of T-suppressors and induced ConA suppression, B-lymphocyte count and serum IgG level). Immunological reactivity is the least in aged tuberculous patients. Compared to aged healthy donors they have reduced number of T-lymphocytes, T-helpers, inhibited PHA response and IL-2 synthesis, greater count of T-suppressors, enhanced induced ConA suppression. B-cell immunity was similar in young and aged patients. Antituberculous immunity reactions were weaker than in young patients.

[Natural killer cells in middle-aged and elderly tuberculosis patients]. / Estestvennye kletki-killery u bol'nykh tuberkulezom pozhilogo i starcheskogo vozrasta.

The immunological study of 76 patients belonging to two age groups (group 1 consisting of 46 patients aged 60-85 years and group 2 consisting of 30 patients aged 20-40 years) was made. For control, healthy persons aged 60 years and older (30 subjects) and 20-40 years (28 subjects) were examined. The study revealed that, in contrast to the tuberculosis patients of the younger age group, the old-age patients exhibited a decrease in the activity of natural killer (NK) cells. The greatest decrease in the activity of NK cells was observed in patients with chronic fibrocavernous forms of tuberculosis (in comparison with other forms of tuberculosis).

[The tubercular process and antitubercular immunity in mice of different ages]. / Tuberkuleznyi protsess i protivotuberkuleznyi immunitet u myshei raznogo vozrasta.

Experiments on "young" and "old" mice (aged, respectively, 2-4 and 22-24 months) infected with Mycobacterium tuberculosis, strain Bovinus-8, have revealed that in old mice the tuberculous process progresses at a faster rate than in "young" mice, which is manifested in "old" mice by their earlier death, more pronounced lesion of their internal organs and by a greater number of Mycobacterium colonies harvested after the inoculation of samples taken from their organs (after equal periods of incubation). In the process of the development of tuberculosis most immunity parameters are progressively suppressed, this suppression being more pronounced in the old animals and leading to a decrease in antibody-dependent cell cytotoxicity, the number of natural killer cells, the reaction of lymphocyte blast-transformation on PPD, cytotoxic effect on PPD-coated red blood cells, the synthesis of interleukin-1 and interleukin-2 after incubation with PPD, the titer of antituberculosis antibodies.

[Immunologic shifts in inhabitants of the Tian'-Shan' lowlands and highlands, suffering from obesity and non-insulin-dependent diabetes mellitus]. / Immunologicheskie sdvigi u zhitelei nizkogor'ia i vysokogor'ia Tian'-Shania, bol'nykh ozhireniem i insulinnezavisimym sakharnym diabetom.

Cellular nonspecific immunity was found reduced in residents of the lowlands and highlands suffering from alimentary obesity and noninsulin-dependent diabetes mellitus (NIDM), this depression augmenting with the increment of obesity degree and age of NIDM patients (p < 0.01-0.001). Activities of antihypoxic enzymes in these patients are drastically depressed under conditions of the highlands and do not depend on the patient's age. Lymphocyte killer activity in both patient populations is increased, more so in the highlands; this activity functionally or organically impairs insulin in the body forming with it immune complexes.

[T-lymphocyte subpopulations in tuberculosis in middle aged and aged patients]. / Subpopuliatsiia T-limfotsitov pri tuberkuleze u lits pozhilogo i starcheskogo vozrasta.

The role of T-lymphocyte subpopulations in regulation of immunity was studied using monoclonal antibodies OKT-4 and OKT-8 in tuberculous patients and healthy subjects of different age. Basing on the examination of 174 patients, it was established that in older subjects pulmonary tuberculosis runs in the presence of aged-related changes in the immune system: an increase in the number of T-suppressors, a reduction in that of T-helpers, secondary immunodeficiency dependent on the process severity and forms. These shifts are suggested to be responsible for the inadequate immune response to M. tuberculosis in the elderly.

Interactions between heterochronic cells in the formation of delayed-type hypersensitivity.

The effect of ageing on lymphocyte and macrophage functional activity in the induction of tuberculin sensitivity was studied in experiments on 440 CBA mice of three age groups. The capacity of old animals to generate delayed-type hypersensitivity following administration of BCG cells was found to be diminished and their lymphocytes caused decreased hypersensitivity on transplantation. The capacity of recipients to reproduce delayed-type hypersensitivity after thymocyte and bone marrow cell transplantation was influenced by the age of transplanted thymocytes. This capacity was markedly suppressed on the recipients of old cells. The antigen presentation function of macrophage did not after significantly as a function of age.

[The macrophagal-lymphocytic interaction of heterochronic cells in the induction of delayed hypersensitivity]. / Makrofagal'no-limfotsitarnoe vzaimodeistvie geterokhronnykh kletok v induktsii zamedlennoi giperchuvstvitel'nosti.

The influence of senescence on the functional activity of lymphocytes and macrophages in the induction of sensitivity to tuberculosis has been studied in experiments on 226 CBA mice. The study has revealed that after the injection of BCG old animals exhibit decreased capacity for the formation of delayed hypersensitivity, and their lymphocytes, transplanted to recipients, induce a lower level of hypersensitivity. Joint incubation of lymphocytes and macrophages from animals of different ages has shown that immunological defect appearing with age is localized in lymphocytes, while the antigen-presenting function of macrophages remains basically unchanged.

[T-suppressors and their functional activity in tuberculosis in middle-aged and elderly subjects]. / T-supressory i ikh funktsional'naia aktivnost' pri tuberkuleze u lits pozhilogo i starcheskogo vozrasta.

The role of T-suppressor cells in regulation of the immune response in patients with pulmonary tuberculosis and in healthy persons in regard to their age was studied. 226 persons were examined. The findings showed that ageing was accompanied by an increase in the functional activity of T-suppressor cells. In the elderly and senile persons with active tuberculosis there were observed higher counts of T-suppressor cells and their increased specific and nonspecific activity. With aggravation of the tuberculosis process the lymphocyte activity increased. These shifts were likely to be the basis of incomplete immune responses to tubercle bacilli in elderly and senile patients with tuberculosis.

[A method of determining allergic changes in leukocytes]. / Sposob opredeleniia allergicheskoi al'teratsii leikotsitov.

The new technique for the detection of hypersensitivity to allergens is based on the fact that after 2 hrs incubation of citrate blood with the allergen the leukocytes are destroyed and K ions leave the cell. Potassium level in the supernatant is measured by flame photometry. This method has been tried in examinations of 81 patients with pulmonary tuberculosis and aspergillosis and 18 healthy donors. The method has proved to be specific and informative for the detection of tuberculin and fungal allergy. It is less labor-consuming than the determination of the neutrophil injury index and more objective, since its results are recorded instrumentally.

[Immunological diagnosis of aspergillosis in patients with pulmonary tuberculosis]. / Immunologicheskaia diagnostika aspergilleza u bol'nykh tuberkulezom legkikh.

The informative value of a number of immunological tests, such as the routine tests of lymphocyte blast cell transformation and indirect hemagglutination, and the original tests of cytotoxic effect and neutrophil damage was studied in diagnosis of aspergillosis. 94 patients with fibro-cavernous tuberculosis and 18 patients with lung aspergillosis along with tuberculosis were examined. It was shown that the tests provided diagnosis of aspergillosis in the tuberculosis patients. The diagnostic efficiency of the tests was studied. The test of neutrophil damage proved to be the most informative. Diagnostic tables for interpretation of the immunological examination results were developed.

Macrophage-lymphocyte interaction in the formation of delayed-type hypersensitivity.

Macrophage-lymphocyte interaction was studied on 121 CBA mice during a 2-hour contact of lymph-node cells of non-immune mice with a monolayer of peritoneal macrophages of BCG-immunized mice and subsequent intravenous administration of 4.10(7) pre-incubated lymphocytes to syngenic recipients. Sensitivity to tuberculin was demonstrated in the recipients by means of blast-transformation reaction of spleen cells (stimulation index was evaluated according to incorporation of 3H-thymidine--SI = 1.32 +/- 0.40) using administration of tuberculin into the paws (Mantoux reaction--MR = 0.11 +/- 0.02 mm) and the cytotoxic effect (CTE) of the lymphocytes on tuberculin-loaded sheep-cell erythrocytes whose disintegration was assessed according to discharge of iron from the target cells (CTE = 13.98 +/- 2.73%). At transfer of intact lymphocytes after contact with non-immune macrophages, SI = 1.046 +/- 0.019; MR = 0.014 +/- 0.002 mm; CTE = 0.214 +/- 0.048%. The treatment of lymphocytes with indomethacin during the contact with macrophages induced idvere changes in the indices of delayed-type hypersensitivity (DTHS). The conclusion has been drawn that the antigen-presenting ability of macrophages can materialize in vitro.