Genome-wide analysis identifies novel susceptibility loci for myocardial infarction

AIMS: While most patients with myocardial infarction (MI) have underlying coronary atherosclerosis, not all patients with coronary artery disease (CAD) develop MI. We sought to address the hypothesis that some of the genetic factors which establish atherosclerosis may be distinct from those that predispose to vulnerable plaques and thrombus formation. METHODS AND RESULTS: We carried out a genome-wide association study for MI in the UK Biobank (n∼472 000), followed by a meta-analysis with summary statistics from the CARDIoGRAMplusC4D Consortium (n∼167 000). Multiple independent replication analyses and functional approaches were used to prioritize loci and evaluate positional candidate genes. Eight novel regions were identified for MI at the genome wide significance level, of which effect sizes at six loci were more robust for MI than for CAD without the presence of MI. Confirmatory evidence for association of a locus on chromosome 1p21.3 harbouring choline-like transporter 3 (SLC44A3) with MI in the context of CAD, but not with coronary atherosclerosis itself, was obtained in Biobank Japan (n∼165 000) and 16 independent angiography-based cohorts (n∼27 000). Follow-up analyses did not reveal association of the SLC44A3 locus with CAD risk factors, biomarkers of coagulation, other thrombotic diseases, or plasma levels of a broad array of metabolites, including choline, trimethylamine N-oxide, and betaine. However, aortic expression of SLC44A3 was increased in carriers of the MI risk allele at chromosome 1p21.3, increased in ischaemic (vs. non-diseased) coronary arteries, up-regulated in human aortic endothelial cells treated with interleukin-1β (vs. vehicle), and associated with smooth muscle cell migration in vitro. CONCLUSIONS: A large-scale analysis comprising ∼831 000 subjects revealed novel genetic determinants of MI and implicated SLC44A3 in the pathophysiology of vulnerable plaques

THE EFFICACY AND SAFETY OF IMMARD (HYDROXYCHLOROQUINE) IN RHEUMATOID ARTHRITIS ACCORDING TO THE DATA OF AN OPEN-LABEL UNCONTROLLED TRIAL IN OUTPATIENT PRACTICE

Objective: to evaluate the efficacy and safety of immard in rheumatoid arthritis (RA) in outpatient practice. Subjects and methods. The open-labeled uncontrolled trial enrolled 30 patients with the reliable and valid diagnosis of RA of varying duration. Immard was used in patients with early RA or as an additive agent when a disease-modifying anti-rheumatic drug (mainly methotrexate) was ineffective. The effect of immard was evaluated 3 months of its intake of 400 mg from the number of swollen and tender joints, patients' and physicians' total ratings of disease activity on a visual analogue scale, from ESR values, C-reactive protein (CRP) levels, and DAS28 scores. Results. There was a significant decrease in the number of swollen joints and DAS28 scores in the patients receiving a combination of methotrexate and immard. No significant reduction in ERS and CRP levels was revealed during the follow-up period

Study of correlation between bone mineral density and clinical and laboratory indices of rheumatoid arthritis activity

Objective. To study association between bone mineral density (BMD) and clinical and laboratory indices of rheumatoid arthritis (RA) activity Material and methods. 60 women with RA who had not received glucocorticoid and anti-osteoporotic therapy were included. 30 had unchanged menstrual cycle and 30 were postmenopausal. Lumbar spine BMD and proximal femur was studied with double radiological absorptiometry (QDR 1000 Hologic apparatus). W.Wilke indices were used to characterize activity and severity of RA. CRP level was evaluated with quantitative immunoenzyme method. Results. Significant negative association was revealed between spine and femoral neck BMD and RA severity so as between femoral neck BMD and CRP level in pts with unchanged menstrual cycle and in postmenopausal pts

Balsam “Mercana-Artrovit warming” — efficacy and tolerability in knee osteoarthritis

Objective. To assess efficacy, local and systemic tolerability of balsam “Mercana-Artrovit warming” (BMAW) containing methylnicotinat, mint and eucalyptus ethereal oils, propylene glycol extracts of eucalyptus, linden, nettle, elecampane, common wormwood, tansy, terpentine oil in knee osteoarthritis (KOA) Material and methods. 60 pts were included in a two-week double blind placebo controlled randomized study. BMAW 5 ml was administered in 30 pts (the main group) twice a day (in the morning and in the evening) on the target knee joint. 30 pts of control group received placebo containing only components of stuff. Demographic and clinical parameters in the main and the control groups were comparable. Inclusion criteria: age from 40 to 70 years, pain intensity in the target joint at least 40 mm on VAS, I-III radiological stage according to Kellgren, Leqesne score 4-10, treatment with NSAIDs during the previous 3 months. Exclusion criteria: indications for intra-articular glucocorticoid injection, clinically significant disturbances of internal organs function and skin damages in the region of knee joint. Clinical efficacy was assessed by WOMAC index, pain at movement and at rest, time of 15 meters walking, general assessment of efficacy (separately by the pt and by the doctor). Frequency and character of adverse events was registered. Results. Local BMAW administration provided statistically significant decrease of WO MAC summated score (p=0,008), pain at movement (p<0,001) and at rest (p<0,005). So analgesic effect of the drug is sufficient for improvement of functional activity of pts with KOA. General efficacy assessment was significantly higher in the main group (Fisher exact test, p<0,005). Placebo did not significantly change efficacy measures. Adverse events were absent in both groups. Conclusion. The results of the study allows to recommend BMAW for local therapy of KO

Gas Flowmeter Based on Vibrating Wires

The paper proposes a new type of gas flowmeters based on measurements of the deformations of the thermal field of the heater in the presence of a flow using vibrating wires. The advantage of such flowmeters as compared with the known ones using a similar thermal principle of operation is the improved accuracy of temperature measurements compared to resistance thermometers or thermocouples. The use of thin wires can also increase the speed of flowmeters. The use of wires 20-30 mm long allows the creation of wide-aperture inlet holes for gas streams. A natural property of the developed flowmeters is also in their bidirectionality. A sample of a flowmeter based on vibrating wires was made and the calibration experiments were carried out. An experiment was carried out in which a flowmeter was used to measure the acceleration

4-WEEK OPEN-LABEL CONTROLLED RANDOMIZED COMPARATIVE STUDY OF THE INJECTABLE AND TABLETTED FORMULATIONS OF METHOTREXATE IN RHEUMATOID ARTHRITIS

Objective: to estimate the advantages and disadvantages of using the injectable formulation of methotrexate (MT) (Methoject (MTJ)) in rheumatoid arthritis (RA) in clinical practice. Subjects and methods. A 24-week open-label controlled randomized comparative study evaluated the therapeutic and side effects of MTJ and methotrexate tablets in RA and clarified whether MTJ treatment might be continued if its tabletted formulation was discontinued because of adverse reactions. Results and discussion. MTJ was found to be more effective than the tabletted formulation of MT and as a whole; and following 3-month therapy, more patients receiving MTJ achieved an ACR20 response. The advantage of MTJ was also retained 6 months after therapy. Higher transaminase levels were noted in 2 patients, one in each group. Switching from MT to MTJ noticeably reduced the number of adverse reactions in the majority of patients from an additional group. Conclusion. As compared to MT, MTJ used in RA patients is more effective when given in an equivalent dose, exerts a therapeutic effect more rapidly, and induces adverse gastrointestinal reactions less frequently

RHEUMATOID ARTHRITIS IN THE RUSSIAN FEDERATION ACCORDING TO RUSSIAN ARTHRITIS REGISTRY DATA (COMMUNICATION I)

The paper presents the materials of the Russian Arthritis Registry (OREL) that includes 3276 patients from 11 Russian Federation's largest research-and-practical centers situated in Moscow, Saint Petersburg, Novosibirsk, Kazan, Tula, Yaroslavl, Tyumen. It discusses the main goals of setting up registries, compares the results of an analysis of the data available in the Russian Registry OREL and registries of European countries and the USA. The findings suggest that there is non-uniform information on clinical, laboratory, and instrumental parameters in the national registers of a number of European countries and the USA. According to its basic characteristics, the Russian Registry OREL compares favorably with a number of other registries in the completeness of data collection, which allows a general idea of rheumatoidarthritis (RA) patients in Russia. For further development of the OREL Registry, it is necessary to concentrate our attention on the following main areas: to improve the quality of filling out documents; to follow-up patients receiving different RA therapy regimens according to the guidelines of the Association of Rheumatologists of Russia for the treatment of RA; to conduct in-depth studies of comorbidity, primarily depressive disorders; to analyze adverse reactions that make RA therapy difficult; to actively use modules for patients' self-rating of their condition; to develop nursing care, etc