Aim.
To identify predictors of heart failure in patients with dilated cardiomyopathy (DCM) and ischemic myocardial dilatation (IMD).
Material and methods.
In total, we examined 221 patients with ...cardiomyopathies: DCM and IMD. The mean age of the patients was 55,30±9,69 years (minimum — 20 years, maximum — 77 years). From the total number of patients, a group of patients with DCM (idiopathic origin) (group 1) was identified in the amount of 111 people, of which 99 were men (89,2%) and 12 women (10,8%). The mean age of patients with DCM was 51,73±9,74 years, for men — 51,00±8,96 years, for women — 57,75±3,71 years. The median age in DCM patients was 53,00 48,00; 58,00, for men — 53,00 46,00; 57,00, in women — 59,50 49,00; 68,75. Patients with IMD (ischemic origin) consisted of 110 people (group 2), of which 100 were men (91,5%) and 10 women (8,5%). The mean age of patients with IMD was 58,68±8,38 years, for men — 58,29±8,46 years, for women — 62,90±6,29 years. The median age in patients with IMD was 58,00 53,50; 63,50, in men — 58,00 52,00; 63,00, in women — 61,50 59,25; 66,00. Biological material (venous blood) was taken from all patients for molecular genetic analysis. To isolate the DNA structure, the phenol-chloroform extraction was used. Using the polymerase chain reaction, genotyping of gene polymorphisms was carried out, followed by analysis of restriction fragment length polymorphisms.
Results.
To assess the left ventricular systolic function, the ejection fraction was assessed. Heart failure and its severity are most often associated with a decrease in left ventricular (LV) systolic function. In our study, in the group of patients with DCM, the mean LV ejection fraction (EF) was 25,105±6,76, while in IMD group — 20,255±4,49 (p=0,0001). This confirms that these two groups have severe heart failure associated with impaired LV systolic function — a decrease in EF <30%. In patients with NYHA class III heart failure with IMD, there was a significant predominance of the heterozygous genotype (6a/5a) of the
MMP3
gene polymorphism compared to the control group (66,7% vs 12,5%, p=0,023).
Conclusion.
The heterozygous genotype of the
MMP3
gene polymorphism can be considered as a predictor of the development of HF in patients with IMD for the purpose of early diagnosis and prevention of heart failure. In the group of patients with DCM, no differences were found during a comparative analysis with gene polymorphism.
A highly effective method consisting of two affinity chromatography steps and ion-exchange and gel-filtration chromatography steps was developed for purification of autoantibodies from human sera ...with DNA-hydrolyzing activity. Antibody Fab fragment, which had been purified 130-fold, was shown to catalyze plasmid DNA cleavage. The flow linear dichroism technique was used for quantitative and qualitative studying of supercoiled plasmid DNA cleavage by these autoantibodies in comparison with DNase I and EcoRI restriction endonuclease. The DNA autoantibody Fab fragment was shown to hydrolyze plasmid DNA by Mg2+-dependent single-strand multiple nicking of the substrate. Kinetic properties of the DNA autoantibody Fab fragment were evaluated from the flow linear dichroism and agarose gel electrophoresis data and revealed a high affinity (Kobs
m= 43 nM) and considerable catalytic efficiency (Kapp
cat/Kobs
m= 0.32 min-1·nM-1) of the reaction.
The aim of the study is to present a successful case in treating primary cutaneous anaplastic large cell lymphoma (PCALCL) occurring with common lesions of the skin and lung tissue.Materials and ...methods. For the verification of the diagnosis in a patient with three types of skin elements (spot, thin plaque with and without ulceration), differential diagnosis was performed between ulcerative pyoderma gangrenosum, PCALCL, large-cell transformation of mycosis fungoides, and secondary skin lesions under the nodal ALK-negtaive ALCL. A complex of studies, including histological, immunohisto - chemical, cytogenetic studies of skin tumor biopsy, allowed the verification of the PCALCL diagnosis. For the treatment of the patient, intensive induction chemotherapy was used followed by high-dose consolidation and autologous transplantation of hematopoietic stem cells.Results. The selected treatment tactics allowed a long-term complete remission of the disease to be achieved in a patient from the poor prognosis group.Conclusion. An algorithm for the differential diagnosis and tactics of treating is presented for a patient with primary anaplastic large cell lymphoma with a widespread skin lesion and extradermal foci.
Introduction
Trimetazidine (TMZ) has been shown to be efficacious for angina treatment. The TMZ 80-mg formulation allows one-daily (od) dosage, which could improve symptom control and adherence.
...Methods
The 3-month, observational, multicenter, prospective ODA (antianginal effectiveness and tolerability of trimetazidine modified release 80 mg Once Daily in stable Angina patients in real-world practice) study assessed TMZ 80 mg od effectiveness in stable angina patients with persistent symptoms despite therapy. Two clinical situations were compared: patients who initiated treatment with TMZ 80 mg od (initiation group) and patients who were previously treated with TMZ 20 mg thrice daily (tid) or TMZ 35 mg MR twice daily (bid) and switched to TMZ 80 mg od (switch group). Number of angina attacks, short-acting nitrate (SAN) consumption, self-reported patient daily activity, Canadian Cardiovascular Society (CCS) class, adherence to antianginal therapy, overall efficacy and tolerability were assessed.
Results
A significant decrease in weekly number of angina attacks was observed for both the initiation group (
n
= 1841 patients) from 4.8 ± 3.5 at baseline to 0.9 ± 1.4 at 3 months (M3) (
P
< 0.001), and the switch group (
n
= 1216 patients) from 4.4 ± 1.3 at baseline to 0.9 ± 1.3 at M3 (
P
< 0.001). Significant reduction in SAN consumption and improvement in CCS class were observed for both groups. Adherence to antianginal therapy improved in both groups at 1 month (M1) and M3. Overall effectiveness of TMZ 80 mg od was rated by physicians as “very good” (68% initiation group, 70% switch group), “good” (31% initiation group, 29% switch group), “moderate” (1%, both groups) or “poor” (< 1%, both groups). Overall tolerability of TMZ 80 mg od was rated by physicians as “very good” (75%), “good” (25%) or “moderate” (< 1%) in both groups.
Conclusions
TMZ 80 mg od, in association with other antianginal therapy, effectively reduced angina attacks and SAN consumption and improved physical activity and adherence to antianginal therapy both in patients initiating TMZ treatment and those switching from a bid or tid formulation.
Trial Registration
ISRCTN registry Identifier, ISRCTN97780949.
Funding
Servier.
Plain Language Summary
Plain language summary available for this article.
Background. The discovery of new genetic predictors of cardiovascular diseases can be used in predicting and diagnosing latent forms of the disease. Wolff-Parkinson-White syndrome (WPW) occurs in all ...age groups and detected in 1-30 people per 10000, it manifests mainly in young age (on average 20 years), and the risk of sudden cardiac death is higher than in general population.Aim. To study the relationship of WPW syndrome with the polymorphism of endothelial nitric synthase gene (NOS3), and to identify genetic predictors of this syndrome.Material and methods. The study included 51 people with ECG proven WPW syndrome and 153 people with no cardiovascular disease. The patients were divided into subgroups according to sex: 21 women, 30 men. All patients underwent a standard cardiac examination (anamnesis, electrocardiography, echocardiography, bicycle ergometry, transesophageal electrical stimulation of the atria, Holter monitoring) and blood was taken for molecular genetic testing of DNA.Results. The results showed a statistically significant prevalence of rare genotype 4b\4b NOS3 gene in the control group of women (16.3%; р<0.05) compared with women from the main group, who did not have this genotype, while there was significant prevalence of genotype 4a\4a in the main group of women (81.0%; р<0.05) compared with women from the control group. In men this prevalence was not found.Conclusion. The presence of genotype 4b\4b NOS3 gene reduces the likelihood of WPW syndrome and its symptoms in females. In men, this prevalence is not found, presumably, in connection with some mechanisms of hormonal regulation. The results can be used in the genetic prediction of the course of the disease.
Background. Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disease that manifests by the accumulation of tumor monoclonal B-lymphocytes in the bone marrow, peripheral blood and secondary ...lymphoid organs. Recently it was found that CLL cells are able to form immunological synapses with microenvironment cells, directly and indirectly affecting their function. Therefore, it became clear that the pathogenesis of CLL is not only escape of apoptosis but also the ability of CLL cells to cause T-lymphocyte anergy, thereby avoiding immune surveillance.Objective: to study the expression of FAS, co-stimulatory molecules CD80 and CD86, PD-1, PD-L1 on CLL cells, and also to study the basic subpopulations of T-cells (naїve, memory, effector cells).Materials and methods. The study included 46 CLL patients: 16 patients with disease progression after chemotherapy and 30 patients with newly diagnosed CLL. “Primary” patients are categorized according to J. Binet’s CLL stages. Stage A was established in 14 patients, B – 10, C – 6. The control group included 29 healthy donors. Peripheral blood was used as a material for analysis. The study was performed on a 6-color flow cytometer BD FACS Canto II (BD Biosciences, USA).Results. In CLL patients, the proportion of CD80+, CD86+, FAS+ B-cells was significantly lower than in donors. In “primary” patients the proportion of CD80 + CLL cells was higher than in patients with CLL progression. Among “primary” patients the proportion of CD80+ and CD86+ was lower in advanced stages of the disease. In patients with CLL progression the proportion of FAS+ B cells was higher than in “primary” patients. The proportion of PD-1+ B cells in CLL patients was higher than in donors and “primary” patients. The proportion of PD-1+ tumor cells was significantly lower in advanced stages of the disease. The proportion of PD-L1+ B cells in CLL patients was lower than in donors. Among the “primary” patients, the proportion of PD-L1+ B-lymphocytes was higher in stage A. The proportion of PD-1+ Thelpers was higher in CLL patients than in donors, and among “primary” patients it was higher in advanced stages of the disease. The proportion of PDL1+ T-helpers and cytotoxic T-cells in CLL patients was lower than in donors. The proportion of naїve cells (CD95-CD28+) in patients compared with donors was lower and the proportion of effector cells (CD95+ CD28–), memory cells (CD95 + CD28 +) was higher, a proportion of CD8+ memory T-cells was higher among patients in the advanced stage of CLL.Conclusion. Therefore, a decline the CD80/CD86+ B-cells in CLL can cause ineffectiveness of an immunological synapse between tumor cells and T-cells, which leads to anergy of T-lymphocytes. Decline expression of the FAS receptor allows tumor CLL cells to avoid FAS-mediated apoptosis. A change in the T-cell pool toward memory cells and effectors, the acquisition of a CD4+PD-1+ (“exhausted”) phenotype impaired antitumor immunity and possible leads to disease progression.
A technique for preparing enriched glauconite on the basis of a natural mineral from the Beloozyorskoe field of Saratov oblast has been developed. The results of a study of the chemical composition, ...surface structure, and certain physicochemical properties of the samples of the sorbent are presented. The sorption of ambroxol hydrochloride ions from aqueous solutions has been studied using natural and enriched glauconite. The sorption isotherms, are approximated by the Langmuir equation, have been obtained, and the values of the maximum sorptive capacities have been calculated. Based on the obtained data, conclusions have been drawn on using the studied natural mineral sorbents to extract the above-mentioned substance from aqueous solutions.
The possibility of increasing the reactivity of low grade Kansk-Achinsk brown coal 2 BR from the Irsha-Borodino deposit due to mechanically activated micronizing by means of special mill ...disintegrators has been shown on the 5-MW experimental firing stand at the Institute of Thermophysics SB RAS (IT). This coal is used in the coal-fired PK-38 boiler of station 2B of the Krasnoyarsk State District Power Station-2 (SDPS-2). The experimental studies to ensure ignition and achievement of stable autothermal coal combustion have yielded the minimum operation time of the gas ignition device; to determine the effect of temperature on the ignition and combustion, the temperature of the burner muffle wall was controlled. In accordance with the experimental data on burning the coal with increased reactivity and the economic efficiency evaluation, the coal can be recommended for replacement of highly reactive fuel oil for ignition and lighting of the boiler considered.
Liparidae from stomachs of Antarctic toothfish
Dissostichus mawsoni
Norman, 1937 (Nototheniidae) caught in the Ross Sea (Pacific sector of Antarctica) have been identified. Two new species of ...deep-water liparids of the genus
Paraliparis
Collett, 1879—
P. caninus
sp. nov. (at a depth of 1182–1651 m) and
P. vipera
sp. nov. (1700 m)—were described. Both species that turned out to be most similar to
P. neelovi
Andriashev, 1982, from the Kerguelen area (the Indo-Oceanic sector of the South Ocean) are combined with it into a species group “
P. neelovi
.” According to meristic characters, pattern of dentition, and the size of gill opening, species of “
P. neelovi
” are close to the species group “
P. copei
.” In collections from a depth of 1700 m, also two individuals of
P. andriashevi
Stein et Tompkins, 1989, known previously from only two types from the northern boundary of the Ross Sea were found. The new finding supports species validity and extends the known limits of its range. The wide distribution of bathybenthal
Paraliparis
having low fecundity and leading a near-bottom mode of life can be explained by the presence of mesopelagic juveniles and their dispersal via currents.
Extranodal NK/T-cell lymphoma – a rare lymphoproliferative disease characterized predominantly by extranodal localization, aggressive course and low efficiency of conventional chemotherapy. Clinical ...presentation is diverse and depends on tumor lesion localization. In this article, a literature review and case report of patient with generalized extranodal NK/T-cell lymphoma with bone marrow involvement, unusual intracranial tumor localization, tumor leukemization and central nervous system-leukemia were presented. Adequate treatment strategy made it possible to achieve long-term complete remission in a patient with poor prognosis.