[Conservative treatment of chronic diseases of lower limb veins: major risks of poor patient compliance]. / Konservativnoe lechenie khronicheskikh zabolevanii ven nizhnikh konechnostei: osnovnye riski nizkoi priverzhennosti so storony patsienta.

Presented herein are the results of the Russian part of the International Research Programme 'VEIN ACT' aimed at studying approaches to conservative treatment of chronic vein diseases in the Russian Federation, assessing its efficacy and safety, as well as monitoring the patient compliance. Also discussed are the regimen and results of conservative therapy, depending on patients' gender, age and body mass index, as well as the level of adherence to various methods of treatment in the cohorts concerned. High efficacy of conservative therapy in all patients was confirmed. However, the regimen of drug therapy needs to be adjusted depending on the disease severity, especially in patients of a more advanced age and those with obesity. The lowest patient compliance was observed in relation to compression treatment. The existing situation may be improved by be means of appropriate recommendations and a possible decrease of the level and degree of compression. This should of course be done carefully and attentively, with obligatorily taking into consideration the patients' age and body mass index.

[Efficacy of sulodexide in treatment of chronic venous insufficiency. Results of the ACCORD trial]. / Éffektivnost' sulodeksida pri lechenii khronicheskoi venoznoi nedostatochnosti. Rezul'taty issledovaniia ACCORD.

OBJECTIVE: The purpose of our study was to evaluate both clinical and laboratory efficacy of sulodexide given at a daily dose of 500 lipasemic units (LSU) in patients presenting with class C3-C4 chronic venous insufficiency (CVI) according to the CEAP classification. PATIENTS AND METHODS: The study included a total of 25 patients diagnosed with C3-C4 CVI and prescribed to receive sulodexide at a daily dose of 500 LSU for 90 days. Efficacy was comprehensively controlled by the following tools: the disease-specific Chronic Venous Insufficiency Quality of Life Questionnaire (CIVIQ), visual-analogue methods of assessment separate symptoms; the Venous Clinical Severity Score (VCSS), as well as ultrasonographic determination of the thickness of subcutaneous fat and crural fascia. Amongst the key laboratory indices determined by means of the ELISA test were the levels of interleukin-1 alpha (IL-1α), interleukin-1 beta (IL-1ß), matrix metalloproteinases-2 and -9 (MMP-2, MMP-9), vascular endothelial growth factor A (VEGF-A), vasopressin and endothelin. RESULTS AND DISCUSSION: Of the initially enrolled 25 subjects, twenty-two patients completed the study and were taken as 100%. The 90-day treatment yielded favourable results manifesting themselves in complete disappearance of convulsions in the calf muscles detected at the first visit in 22.7% of patients (p=0.0485), a significant reduction in the frequency of complaints of decreased tolerance to static loads from 27.3 to 9.1% (p=0.2404). The volume of the crus of the control lower extremity decreased from 134.18±14. 92 to 128.42±12.46 cm3 (p=0.0006), subcutaneous fat thickness at the fixed point decreased from 1.50±0.53 to 1.32±0.46 cm (p=0.0007), and fascial thickness decreased from 0.14±0.7 to 0.11±0.04 (p=0.0359). Pain syndrome according to the visual analogue scale (VAS) decreased from 36.45±25.60 to 17.50±19.27 mm (p=0.0002). The global index of quality of life (GIQoL) according to the CIVIQ-20 increased by 27.7% compared with the baseline level (p = 0.0001), the VCSS index decreased from 6.00±1.83 to 4.86±2.05 points (p=0.0002). as for the laboratory markers of endothelial dysfunction, there was a significant decrease in the levels of MMP-2 - from 178.53±36.30 to 176.35±36.67 ng/ml (p=0.0152), MMP-9 - from 90.84±20.41 to 89.78±20.32 ng/ml (p=0.0394), and that of endothelin - from 0.42±0.10 to 0.39±0.10 fmol/ml. CONCLUSION: Sulodexide exerting a statistically significant clinical and endothelium-protecting effect turned out to be an effective drug for treatment of initial forms of chronic venous insufficiency of lower limbs.

[Peculiarities of treatment of chronic venous diseases in Russia. Preliminary results of the "VEIN ACT Program"].

Presented herein are the results of the Russian part of the International Research Program "VEIN ACT" aimed at studying the structure of variants of conservative treatment for chronic venous diseases in the Russian Federation, assessing its efficacy and safety, as well as monitoring of patient compliance. The obtained findings demonstrated high popularity, among both physicians and patients, of phlebotrophic drugs, determining high patient's adherence thereto. Recommendations on correction of the lifestyle were complied with by more than 80% of patients, however frequently not in the full scale. Noted was sufficiently low compliance to compression therapy, manifesting itself as a decrease in the class of compression and irregular use thereof in more than 30% of patients. Usefulness of conservative therapy was objectively proved, consisting in satisfaction with treatment and a statistically significant decrease in severity of symptoms of chronic venous diseases in the overwhelming majority of patients.

Electrical muscle stimulation with Veinoplus® device in the treatment of venous ulcers.

AIM: The aim of the study was to analyze the results of the electrical muscle stimulation (EMS) usage in patients with venous ulcers developed on top of a post-thrombotic syndrome (PTS). METHODS: Sixty patients (60 legs) with active venous ulcer (C6EsAsdpPr according to CEAP classification) were divided into two groups. In addition to the background therapy consisting of a standardized compression with ULCER X and intake of micronized purified flavonoid fraction (MPFF 1000 mg daily), all the patients in the main group underwent EMS with Veinoplus® V.I. for at least 3 times a day. Follow-up examinations were performed on days 30, 60 and 90. These included pain severity assessment with 100-mm Visual Analogue Scale (VAS), disease severity measurement with VCSS (Venous Clinical Severity Score) and ankle circumference above malleolus, as well as recording number of healed venous ulcers. RESULTS: At day 90 pain severity was reduced in both main and control groups. However, according to VAS pain reduction rates were significantly higher in patients of the main group (from 8.7 ± 0.6 to 1.9 ± 0.3 in the main group and 8.4 ± 0.6 to 3.9 ± 0.5 in the control group). At the end of the study, ankle circumference decreased from 270.9 ± 4.6 mm to 257.1 ± 4.2 mm in the main and from 269.7 ± 5.3 mm to 263.4 ± 5.2 in the control group. VCSS before treatment was 7.3 ± 0.6 in the main group and 6.8 ± 0.5 in the control group. By day 90 VCSS significantly decreased to 2.3 ± 0.4 and 4.6 ± 0.5 in the main and control groups respectively. Healing rates were significantly higher in the main group. On day 90, the number of open venous ulcers in the main group was 3 times lower than in the control group (4 vs. 12). CONCLUSION: EMS demonstrated high efficacy and good tolerability and provided significant reduction in pain severity, VCSS score and ankle edema, as well as a 3-fold increase in the number of healed venous ulcers.

[Chronic venous oedema (C3 according to CEAP): new international guidelines and consensuses].

The review based on analysing the results of epidemiological studies, as well as international guidelines and consensuses published in 2011-2012 reflects the present-day data concerning prevalence, principles of diagnosis and treatment of chronic venous oedema. This is followed by determining the role of compression and drug therapy in treatment thereof from the positions of evidence-based medicine.

[Bioflavonoids and their significance in angiology: focus on diosmin].

The article deals with historical information dedicated to the discovery of bioflavonoids and their effect on the human cardiovascular system, also considering the modern classification of phlebotrophic agents, followed by generalization and analysis of their mechanisms of action, as well as detailed discussion of different forms of diosmin. Summing up contains generalization of the Russian, European, and American guidelines on using phlebotrophic drugs for various forms and stages of chronic venous diseases.

[On advisability of perioperative phleboprotection in endovascular treatment of lower in varicose disease: first initial results of the decision study].

Presented in the article are the results of the DECISION multicenter study dedicated io assessment of efficacy and feasibility of using the phlebotropbic drug detralex in the perioperative period in patients undergoing endovascular treatment of lower limb varicose discase. The study comprised a total of 230 patients presenting with chronic venous disease. (CVD) C2-4s according the CEAP classification, each of these had not less than three CVD- related symptoms. All patients were randomly assigned to the Study Group (126 people) and the Control Group (104 subjects). The Study Group patients 2 weeks prior to endovascular treatment and during 4 weeks thereafter took the phlebotrophic drug detralex at a standard daily dose of 1,000 mg. The Control Group patients received conventional compression thernpy using compression bandages or medicinal knitted fabric. The findings of the statistically processed results in the both groups demonstrated a significant decrease in the CVD severity score according to the VCSS scale and an increase in the quality of life parameters according to the disease-specilic questionnaire CIVIQ-14. While so doing, more pronounced dynamics was observed in patients taking detralex during the perioperative period. Besides, there was synergism between the results of the endovascular intervention and therapeutic effects from detralex. Based on the findings obtained in the present study, the authors made a conclusion on feasibility of using the drug detralex as an agent for nonspecific pharmacological protection in endovascular treatment of varicose disease.

[Participation of leucocytes in pathogenesis of primary forms of lower limb chronic venous disease].

AIM: The purpose of the study was to test the hypothesis on participation of WBCs in damaging the venous wall in patients presenting with primary forms of lower limb chronic venous diseases LLCVD . MATERIAL AND METHODS: The study included a total of fifteen consecutively selected patients (13 women and 2 men) diagnosed as having grade C2-C-4 LLCVD according to the CEAP classification. Static loading (30 minutes in the sitting position) was followed by simultaneous sampling of blood from the varicose vein of the cms and ulnar vein. The total blood count including determination of both the absolute values and percentage of blood formed elements was performed using the automated haematological counter «Advia 7¼ («Bayer¼, USA). The obtained findings were statistically processed using the Microsoft Office Excel software by means of the pared two-sample τ-test for the average values. RESULTS: The number of leukocytes and their subpopulations in blood samples obtained from the crural varicose veins turned out to be significantly less as compared with that in blood sampled from the ulnar vein. Thus, blood sampled from the crural varicose veins demonstrated a decrease in the counts of WBC by 9.6% in fourteen (93.3%) patients, that of neutrophils by 4.9% in twelve (80%) patients, that of lymphocytes by 16,8% in fifteen (100%) patients, and that oi monocytes by 24% in twelve (80%) patients. The mentioned differences were statistically significant at a = 0.05. The eosinophilic counts in blood sampled from the upper and lower extremities appeared similar in 66.7% of the examined subjects. In 33.3% of cases the eosinophilic count in blood samples from crural varicose vein was by 16.7% lower than that for blood samples form the ulnar vein. No differences for the rest parameters of the clinical blood count were revealed. CONCLUSION: The absolute lymphocytic count in the blood samples taken after the 30-minute static loading from the crural varicose veins was significantly lower as compared with that in blood sampled form the cubital vein. The counts for RBCs and blood platelets, as well as other qualitative haematological indices (haemoglobin, haematocrit, average volume of the RBC, erythrocytic diameter, etc.) in blood sampled form crural and ulnar veins in the same patient were identical, thus strongly suggesting the lack of either haemodynamic or haemorheological phenomena capable of leading to redistribution of the blood formed elements in varicose veins. Hence a decrease in the counts of leukocytes and their subpopulations in blood sampled from crural varicose veins might be associated with the «leukocytic trap¼ phenomenon.

Electromuscular stimulation with VEINOPLUS® for the treatment of chronic venous edema.

AIM: Electromuscular stimulation (EMS) with VEINOPLUS® has recently emerged as a new technique to activate the calf muscle pump, improving the symptoms of venous disease. The aim of the study was to evaluate efficacy of EMS and its impact on evening edema, venous pain, venous outflow and patients quality of life. METHODS: Thirty patients (32 legs) aged 19-50 (mean 45.2±1.3) classified CEAP C3 with chronic evening venous edema took part in the study (22 limbs: C3, S, Ep, Asp, Pr and 10 limbs: C3, S, Es, Aspd, Pr). All patients were treated with CE-registered VEINOPLUS® neuromuscular stimulator for 30 days. 3 sessions per day (each session lasted for 20 minutes) for the first 10 days, the next 10 days 2 sessions per day and one session per day for the last 10 days. The main evaluated criteria for venous edema was the circumference of the supramaleoal shin segment, measured twice with a tape measure; in the evening the day before and then 5 days after the treatment. All measurements were taken during the interval between 6 and 8 o'clock P.M. All the patients were asked to evaluate venous pain using the Visual Analog Scale, and to fill in a CIVIQ questionnaire (validated for Russian patients) for the Quality Of Life (QOL) measurement. Also venous refilling time (RT) was measured by digital PPG. That was also made twice - before the treatment and in 35 days after the treatment. No other treatments were used. RESULTS: The EMS treatment was well tolerated by patients. There were no drop outs and patients had no need to change their lifestyles. After the treatment, total or partial reduction of evening edema was shown in 93.8% of limbs, the circumference of the lower leg diminished by 20.3mm (P<0.001), the number of painful legs reduced from 28 to 12 and the severity score of venous pain was cut from 8.3 ±1.1 to 3.8 points ±0.9 (P<0.001), QOL improved significantly as the score dropped from 34.5 ±7.8 to 17.2 points ±4.6 (P<0.001) and RT increased from 17.3 ±0.9 to 21.5 seconds ±1.1 (P<0.001). Three months after VEINOPLUS® treatment, total remission of symptoms was observed in 50% of legs, despite there being no other treatments. CONCLUSION: VEINOPLUS® stimulation is an effective and well-tolerated therapeutic method for the treatment of chronic venous disease. The introduced scheme of EMS application was shown to be useful for treatment of chronic edema, for reducing pain and improving quality of life. It can be used as an additional mean in treatment and to prevent symptoms of CVI. This study also reveals that stimulation of calf muscles with VEINOPLUS® can improve venous outflow and symptoms of CVI. This finding should be investigated and confirmed in further studies.

[Distribution of allelic variants of promotor sites of cytokine genes and endothelial growth factor gene among healthy subjects and patients with rheumatoid arthritis in a Russian Europeoid population].

The article reports results of the first study of cytokine gene polymorphic sites and analysis of distribution of their complexes among healthy subjects and patients with rheumatoid arthritis (RA) representative of the Russian Europeoid population; their possible prognostic significance is evaluated. Comprehensive analysis of the frequency of allelic variants of cytokine genes IL1B C-31T, IL6 G-174C, TNFA A-238G, TNFA A-308G, TNFA A-863C, IL4 C-590T, IL10 A-592C and VEGF C-2578A was performed for 513 residents of the Novosibirsk region showing no obvious signs of any diseases and 125 RA patients. The results suggest association of RA with certain alleles of pro- and anti-inflammatory cytokine genes. Complex indices reflecting combinations of genotypes of two, three, four, five, six and seven loci of the explored cytokine genes found in individual patient demonstrate their high specificity for RA. It is supposed that these findings can be used in further clinical studies for the development of algorithm designed to detect risk groups among clinically healthy subjects.

[Analysis of the gene polymorphism of matrix metalloproteinase-2 and -9 in patients with coronary heart disease].

AIM: To analyze the gene polymorphisms of matrix metalloproteinase-2 and -9 in patients with coronary heart disease (CHD). MATERIALS AND METHODS: The influence of single nucleotide polymorphism in the promoter region of the gene of matrix metalloproteinase (MMP)-2 at position -1306 and that of MMP-9 at position -1562 on the development of complications was studied in 181patients with atherosclerosis by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of amplification products. RESULTS: A significant genotype increase with enhanced MMP-9 gene transcriptional activity was found in the patients aged 55 years inclusively who had been diagnosed as having myocardial infarction as compared with an older age group and, on the contrary, a rise in the MMP-2 genotype with a high promoter activity in the older age group. CONCLUSION: The findings suggest that the functional polymorphism in the promoter region of the MMP-2 and MMP-9 genes plays a certain role in the development of acute coronary events.

[Analysis of polymorphism of three positions of promoter region of TNF- gene in patients with ischemic heart disease, unstable angina and myocardial infarction].

We studied polymorphism of three positions of promoter region of TNF alpha gene in patients with ischemic heart disease (IHD), development of unstable angina (UA) and acute myocardial infarction (MI). Analysis of frequencies of genotypes in position A308 showed that heterozygotness in patients with cardiovascular diseases significantly decreased. Lowering of risk of development of MI in carriers of heterozygous variant of the gene in position A308 was shown. In the group of patients with Q wave MI frequency of A308 AA genotype rose.

[Pharmacogenetic criteria for the efficacy of basic anti-inflammatory therapy for rheumatoid arthritis].

AIM: To analyze the prognostic value of detection of allelic variants of the promoter regions of cytokine genes in patients with rheumatoid arthritis (RA) with varying efficiency of basic anti-inflammatory therapy (BAIT). SUBJECTS AND METHODS: Eighty-nine patients with a valid diagnosis of RA, of them there were 79 females and 10 males (mean age 52.5 +/- 13.1 years), were examined. The patients received BAIT with methotrexate in a dose of 10.0-17.5 mg/week (77.5%) or with sulfasalazine in a dose of 2.0 g/day (22.5%) for 24 weeks. The efficiency of BAIT was evaluated using the European League Against Rheumatism (EULAR) criteria (DAS28) following 24 weeks. A high therapeutic effect was stated when DAS28 decreased by more than 1.2 scores. Changes in DAS28 by less than 0.6 scores were regarded as ineffective BAIT. Cytokine gene polymorphisms were studied by restriction analysis of amplification products. The following polymorphic sites in the interleukin genes: FNOA at positions C-863A, G-308A, G-238A, IL-1BT-31C, IL-4 C-590T, IL-6 G-174C, and IL-10 C-592A, were explored. RESULTS: The IL-6 G-174G genotype associated with the high production of this proinflammatory cytokine and the IL-IB C-31C genotype associated with the low production of interleukin-1beta (IL-1beta) were most frequently encountered in a group of patients with the high efficiency of BAIT (22 and 24.7%). At the same time the C allele associated with the low production of IL-6 and the IL1B T-31C genotype associated with the high production of this cytokine were most frequently detected at position of G-174C of the promoter regions in the IL-6 gene in patients unresponsive to BAIT (32 and 36%). CONCLUSION: The allelic variants of the promoter regions of the IL-6 G-174G, IL-1B C-31C, IL-4 C-590T, and IL-10 C-592A can be genetically prognostic factors of formation of the high efficiency of BAIT.

[Frequencies of the DRB1, DQA1, DQB1 and TNFA alleles in immigrant population of West Siberia].

Based on population analysis of the DRB1, DQA1, DQB1 and TNFA allele frequency distribution patterns, regional features of immunogenetic structure of the population of West Siberia were investigated. Statistically significant linkage disequilibrium within the HLA class II region, as well as between the TNFA and DRB1, DQA1, and DQB1 was demonstrated. Population frequency distribution patterns of two- and multilocus haplotypes were examined.

[Semisynthetic Diosmin (Phlebodia 600) for therapy of lower limb chronic venous insufficiency].

The study was held to assess clinical effectiveness of coaggregated semisynthetic Diosmin (Phlebodia 600) for patients with II-III CEAP classes of chronic venous insufficiency (CVI), caused by lower limb variceal diseases. In 30 cases Phlebodia 600 demonstrated positive effect on CVI symptoms, edematous and convulsive syndromes. The authors conclude that Phlebodia 600 is highly effective and safe for patients with CVI.

Chronic diseases of lower extremity veins in industrial workers of Moscow (results of the epidemiological survey).

This paper describes the results of the study into the prevalence of chronic venous diseases among industrial workers of Moscow. It has been established that chronic venous diseases are fairly prevalent among industrial workers. They affect the people of both sexes (67.5% of women and 50.4% of men), varying age and occupation. With age their incidence rises. The most significant risk factors of the onset of chronic venous diseases include hereditary predisposition, pregnancy and birth, overweight, and intake of hormonal contraceptives. The study has demonstrated that in most cases, such patients are not rendered medical assistance.

[Determination of ureaplasma DNA by the competitive and multiplex PCR]. / Opredelenie kolichestv DNK ureaplazm s pomoshch'iu konkurentnoi i multikompleksnoi PTsR.

Quantities of Ureaplasma spp DNA were determined by the methods of competitive and multiplex polymerase chain reactions (PCR). The results obtained by each of the methods were shown to be compatible. It was established that the number of Ureaplasma spp. cells per one epithelial cell in the female cervical canal varied from 0.05 to 10.

[Study of the most often encountered allele of the HLA-B27 gene in Tuvinian and Russian inhabitants of Western Siberia]. / Izuchenie naibolee chasto vstrechaiushchikhsia allelei gena HLA-B27 u tubintsev i russkikh zhitelei zapadnoi Sibiri.

HLA-B27 gene frequencies and allelic polymorphism were studied in two Siberian ethnic groups: Russians from Novosibirsk (western Siberia) and Tuvinians from Kyzyl (southern Siberia). The HLA-B27 frequencies were determined by means of serologic typing of HLA antigens in 198 Tuvinians and 288 Russians. Molecular typing was performed via hybridization of oligonucleotide probes with amplified DNAs obtained from 30 HLA-B27-positive Russians and 11 HLA-B27-positive Tuvinians. The HLA-B27 gene frequencies in Tuvinians and Russians were 5.5 and 10.4%, respectively. Molecular variants of the HLA-B27 gene were studied in Tuvinians for the first time. The proportions of the HLA-B2705 and HLA-B2704 alleles were found to be 64 and 36%, respectively, in the population studied. The presence of the HLA-B2704 allele indicates a Mongoloid origin of Tuvinians. In the Russian population of Novosibirsk, the HLA-B2704 allele was not found, whereas the proportions of the HLA-B2705 and HLA-B2702 alleles were 76.2 and 23.8%, respectively, which is characteristic of Caucasoid populations.

[The use of internal controls of different lengths in the detection of Chlamydia trachomatis DNA by the polymerase chain reaction method]. / Ispol'zovanie vnutrennikh kontrolei razlichnoi dliny pri detektsii DNK Chlamydia trachomatis metodom polimeraznoi tsepnoi reaktsii.

To detect C. trachomatis DNA, the polymerase chain reaction (PCR) with the use of primers corresponding to variable sites of rRNA gene 16S was carried out. As the positive control of the reaction, the amplification fragment of gene 16S of rRNA, cloned in the plasmid vector and having the length of 530 nucleotide pairs (n.p.), was used. On its basis 2 kinds of the internal control of the reaction were obtained with the deletion of 110 n.p. (pMOS-Chl420) and the insertion of 930 n.p. (pMOS-Chl1460) within the cloned amplification fragment. The study revealed that the addition of the DNA of pMOS-Chl420 or pMOS-Chl1460 into the reaction mixture did not affect the sensitivity of PCR (0.02 pg of bacterial DNA in the sample) in the detection of C. trachomatis DNA isolated both from the culture of bacterial cells and from clinical samples. But in some cases of the amplification of the DNA of internal control pMOS-Chl420, but not pMOS-Chl1460, was observed in the presence of DNA obtained from clinical samples. It was supposedly linked with a higher sensitivity of Taq DNA-polymerase to the action of inhibitors in the synthesis of high-molecular DNA fragments. The observed high frequency of the inhibition (17%) of PCR makes it expedient to carry out this reaction with the use of the internal control.