Distribution of human gene polymorphisms allele frequencies associated with viral infections.

INTRODUCTION: The design of studies aimed at finding the association between the genetic factor and the studied feature (disease) involves a comparison of the ratio of genotypes or allelic proportions in the study group with those in the control group. At the stage of determining the ratio of genotypes of the studied polymorphisms in the reference group, researchers meet a number of problems, which are the subject of the present work. Aim of the work is to provide scientific rationale for the feasibility of creating a national information system comprising genetic data of the relatively healthy population of Russia, incorporating its ethnic diversity. MATERIALS AND METHODS: The study group, total 1020 people, was genotyped for a number of single nucleotide polymorphisms of human genes. A comparative characteristic of the frequency distribution of the studied polymorphisms with those presented in international databases as reference data was carried out using χ2 index. RESULTS: The frequency of SNP rs4986790 of the TLR4 gene significantly differs from the EUR population (p = 0.032) and the CEU subpopulation (p = 0.047). The allele frequencies of the rs1800795 (IL6) and rs1800896 (IL10) polymorphisms in the study population differ from the CEU subgroup (p = 0.030 and 0.012, respectively). The frequency of SNP rs2295119 (HLA-DPA2) in the study group is significantly different from the EUR population (p = 0.034). CONCLUSION: The analysis carried out in this work confirms the need to create a domestic information system containing data on the occurrence of SNP alleles and genotypes for a conditionally healthy population and in subgroups with various pathological conditions.

[Generation of Antibiotic Tolerant Bacterial Persisters in Immunocompromized Patients with Hematologic and Malignant Diseases: A New Problem of Health-Care Associated Infections].

Background: Antibiotic tolerance (AT) represents one of the causes of the phenomenon of antibiotic resistance that allows escape of non-replicating metabolically inert microorganisms (persisters) from any antibiotics attack because molecular targets of antibiotics are lacking thereby creating the potential for chronic infections. Aims: Determine the heterogeneity of the strains of opportunistic pathogens E. coli and P. aeruginosa isolates from children with hematologic malignancies containing bacterial persisters that cause the AT phenomenon. Methods: Children with hematological malignancies were divided into 2 groups according to the intensity of antibiotic treatment of infectious complications. Ciprofloxacin-induced persisters were quantitatively determined in the biological materials obtained from sick children. Results: Within the clinical isolates of E. coli and P. aeruginosa, about a third of the strains belong to high-persisting. The numbers of persistent forms of bacteria did not correlate with a minimal inhibitory concentration values ciprofloxacin (r=0.148, n=25, p>0.05). Interestingly, higher level of formation of persistent E. coli and P. aeruginosa, is associated with higher frequencies of infection attacks, massive antibiotic use and unfavorable course of the disease in children. Conclusions: Therefore, detecting the persistent forms of bacterial pathogens including those associated with the health-care associated infection, specifically, in immunocompromised patients, should be included into the contemporary algorithms of microbiological observation and monitoring of patients and intrahospital environment.

[Results of hematopoietic cell transplantation in the first complete remission in children with acute myeloid leukemia from an intermediate risk group].

AIM: To analyze the results of allogeneic and autologous hemopoietic cell transplantations (allo- and auto-HCT) in children with acute myeloid leukemia (AML) from an intermediate risk group, most of which were performed using lower-intensity conditioning modes. SUBJECTS AND METHODS. The study enrolled 36 children from an intermediate risk group, who had undergone auto-HCT (n = 22) or allo-HCT (n = 14) in December 1994 to December 2008. The patients' age was 0.7 to 16.6 years (median 12.8 years). Chemotherapeutic conditioning regimens were applied to all the patients. Melphalan was a basic myeloablative agent in 83.3% of cases. RESULTS: With a median follow-up of 4.6 years (1.1-13.8 years), three-year relapse-free survival (RFS) was 80.4%; overall survival (OS) was 65.6%. Recurrences were documented only in 6 (16.6%) patients from the auto-HCT. Transplantation-associated mortality (TAM) was 13.8% (five patients died). After allo-HCT versus auto-HCT, RFS, OS, and TAM were 100 and 68.7% (p = 0.03), 93.2 and 55.5% (p = 0.02), and 7.1 and 18.2%, respectively. Acute and chronic graft-versus-host reactions developed in 57.1 and 23.1%, respectively. CONCLUSION: Transplantation of allogeneic hemopoietic cells from a compatible related donor in the intermediate risk group children with AML, by using melphalan-based conditioning regimen, demonstrates a high survival rate with the minimum toxicity.

[Transplantation of the bone marrow from a HLA-compatible unrelated donor after immunoablative conditioning in children with acquired aplastic anemia unresponsive to combined immunosuppressive therapy: preliminary results].

AIM: To analyze the efficiency of transplantation of the bone marrow from a HLA-compatible unrelated donor and continued immunosuppressive therapy (IST) in children with aplastic anemia (AA) unresponsive to 2 courses of IST. SUBJECTS AND METHODS: The study enrolled 14 children aged 2-16 years (median 9 years). A control group comprised 26 patients in whom IST was continued. The median interval between the diagnosis of AA and transplantation was 26 months (9-156 months). The conditioning regimen consisted of thoracoabdominal irradiation in a dose of 2 Gy, fludarabin (Flu) 100-150 mg/m2, cyclophosphamide (Cy) 100-200 mg/kg, antithymocyte globulin (ATG) in 11 patients and Flu, Cy, and ATG in 3. A graft-versus-host reaction was prevented with mycophenolate mefetil in all the patients, tacrolimus in 11, and cyclosporin A in 3. Donors were compatible for high-resolution typing of 10/10 and 9/10 alleles in 8 and 6 patients, respectively; the source of a transplant was bone marrow in 13 patients and granulocyte colony-stimulating factor-mobilized peripheral blood precursors in one case. RESULTS: Thirteen patients achieved primary engraftment after single transplantation; one patient did after repeat transplantation. Grades I to II graft-versus-host reaction (GVHR) developed in 9 patients; postengraftment life-threatening infections in 3, extensive chronic GVHR in 2, circumscribed GVHR in 7. All fourteen hemopoietic cell transplant recipients followed for a median 17.5 months (range 1-71 months) were survivors. CONCLUSION: The likelihood of good survival after unrelated transplantations in AA is much higher than that after continued IST: 100% versus 15 +/- 11%.

[Clinico-laboratory variants of the course and results of therapy of hepatitis-associated aplastic anemias in children].

AIM: To study clinical and laboratory characteristics of hepatitides and evaluate efficacy of immunosuppressive therapy and transplantation of the bone marrow in hepatitis-associated aplastic anemia (HAAA). MATERIAL AND METHODS: A retrospective analysis of case histories of children with HAAA was made. For all the patients standard tests for detection of aquired aplastic anemia and hepatitis were conducted. Transplantation of hemopoietic stem cells (THSC) from HLA-identical donors was made in 4 patients, 25 patients were treated with combined immunosuppressive therapy (antithymocytic globulin--ATG plus cyclosporin A -CsA), one patients received monotherapy with CsA, two--prednisolone and a short course of CsA, one child was untreated. RESULTS: Of 260 children admitted to hospital from April 1989 to July 2005 for aquired aplastic anemia, 33 (12.7%) met diagnostic criteria of HAAA. Boys to girls ratio was 267. Hepatitides were severe: median of alaninaminotransferase concentration was 1215 IU/l, aspartataminotransferase--789 IU/l, bilirubin--152.5 mcmol/l. Median of the interval from hepatitis symptoms to documentation of pancytopenia was 66 days (0-204 days). All four patients after THSC are alive for 30-72 months. Probability of complete remission after the first course of ATG+CsA is 0.72 +/- 0.09, probability of survival 0.81 +/- 0.07, median of the interval to transfusion independence--50 days. CONCLUSION: HAAA prognosis is good only in administration of up-to-date therapy. After seronegative hepatitis it is necessary to control hemogram parameters and in the presence of minimal cytopenia patients should be directed to hematological hospital.