[The efficacy and safety of intra-articular application of a combination of sodium hyaluronate and chondroitin sulfate for osteoarthritis of the knee: a multicenter prospective study].

in 3 mL on patients with knee osteoarthritis (OA) in a multicenter prospective study. MATERIALS AND METHODS: 79 outpatients (predominantly females 81.0%) from 5 RF constituent territories with primary tibiofemoral KellgrenLawrence score grade II or III knee OA, 40 mm pain intensity during walking on visual analogue scale (VAS), requiring NSAIDs intake (for at least 30 days during 3 months prior to enrollment) were included into the study after signing the informed consent form. Mean age was 60.38.7 years, mean BMI 29.24.7 kg/m2, disease duration 6 (310) years. Grade II OA was documented in 68.4% of patients, Grade III in 31.6%. The study lasted for 6 months. Efficacy and safety evaluations were made based on VAS pain assessment, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) [WOMAC pain (0500), WOMAC function (01700), WOMAC stiffness (0200)], VAS patients health status, EQ-5D-based assessment of patients quality of life, global physicians and patients efficacy assessment, and daily NSAIDs requirements. RESULTS: Obtained results demonstrate statistically significant VAS pain reduction during walking already in 1 week after intra-articular injection of the combination [respectively, 62 (5572) and 41 (3251) mm, р0.0001]. Moreover, pain continued to subside during all 3 months of follow up [in 1 month 28 (2042), in 3 month 22 (1437) mm]. A significant pan reduction achieved at Mo 3 persisted until Mo 6 20 (1442) mm, without documented pain increase. Similar trends were observed with total WOMAC score [1125 (8991540) at baseline, and 552 (309837) mm by the end of the study, p0.0001], and all WOMAC sub-scores [268 (189312) baseline WOMAC pain, 91 (48171) mm by the end of the study p0.0001; stiffness 101 (59130) and 40 (2061) mm, p0.0001; function 802 (6471095) and 402 (191638) mm, p0.0001, respectively]. Median time to the onset of therapeutic effect was 7 (518) days. Statistically significant improvement of patients quality of life by EQ-5D and general health status was observed during all follow up period [respectively, 0.52 (-0.020.59) and 0.69 (0.590.80), р0.0001; 48 (3060) and 72 (6080) mm, р0.0001]. One injection of the drug resulted in dose reduction or discontinuation of NSAIDs therapy: at baseline 76 patients (96.2%) were taking NSAIDs, in one week 31 (39.2%) patients discontinued NSAIDs, in 1 month 72.2%, in 3 months 73.4%, and by the end of the study at Mo 6 54.4% were not taking NSAIDs. These data were consistent with physicians and patients global assessment of the efficacy of treatment, who stated significant improvement and improvement in the majority of cases, with only few no effect or worsening cases documented in analyzed population. Adverse events, such as worsening of pain and/or swelling of the joint, were documented in 8 patients (10.1%); they resolved spontaneously or following NSAIDs intake. CONCLUSION: These results suggest that intra-articular injections of hyaluronic acid plus chondroitin sulfate in patients with knee OA are efficient and safe. A single injection of the drug resulted in statistically significant reduction of pain and stiffness, reduction in NSAIDs intake, as well as improvement in patients quality of life and function.

Factors affecting the results of analgesic therapy. Results of the Russian multicentre study of NOTE (NSAID: Open-label Trial of Efficacy).

AIM: To identify factors affecting the effectiveness of NSAIDs in patients with OA and LBP. MATERIALS AND METHODS: An observational study was conducted to evaluate the effectiveness of a 2-week course of NSAIDs in OA and LBP in real clinical practice. The study group consisted of 3604 patients with OA and LBP (60.6% women and 39.4% men, mean age 55.0±13.4 years). According to the study design, aceclofenac (Airtal) and other NSAIDs used in the ratio 1:1. The main criterion of effectiveness was the frequency of complete pain relief after 2 weeks of therapy. In addition, the decrease of pain and general health were determined on a 10-point numerical rating scale (NRS). We compared the frequency of complete pain relief in patients who had and did not have the studied factors. The value of the studied factors was determined using OR (95% CI). RESULTS: Most patients received aceclofenac (54.9%), as well as diclofenac (2.0%), ketoprofen (1.9%), lornoxicam (2.2%), meloxicam (13.7%), naproxen (2.1%), nimesulide (5.8%), celecoxib (5.9%), ethicoxib (7.1%) and other NSAIDs (4.4%); 56.2% of patients received muscle relaxants, mainly tolperisone (74.7%), vitamin B (10.4%), and proton pump inhibitors (42.8%). Complete pain relief was achieved in 54.8% of patients. The pain decrease and general health improvement were (for NRS) 63.9±13.4% and 61.7±14.8%, respectively. The efficacy of aceclofenac was slightly higher than in the whole group: complete pain relief was in 59.9% of patients. Adverse events in aceclofenac use were observed in 2.3% of patients, other NSAIDs-from 2.4 to 14.1%. The frequency of complete pain relief was higher in men: OR 1,239 (95% CI 1.08-1.418; p=0.002), who had the first episode of pain - OR 3.341 (95% CI 2.873-3.875; p=0.000), a good" response " to NSAIDs in history - OR 1.656 (95% CI 1.385-1.980; p=0.000) and received NSAIDs in combination with muscle relaxants - OR 1.218 (95% CI 1.067-1.390; p=0.004). The effect of therapy is lower in patients 65 years and older-OR 0,378 (95% CI 0.324-0.442; p=0,000), with body mass index >30 kg/m² - OR 0.619 (95% CI 0.529-0.723; p=0.000), with severe pain (≥7 points NRS) - OR 0.662 (95% CI 0.580-0.756; p=0.002), with pain at rest, - OR 0.515 (95% CI 0.450-0,589; p=0.000), pain at night - OR 0.581 (95% CI 0.501-0.672; p=0.000) and the presence of stiffness - OR 0.501 (95% CI 0.438-0,573; p=0.000). Treatment results are significantly worse in the cases of combination of LBP and joint pain, as well as pain in the trochanter major and pes anserinus area (p<0.001). CONCLUSION: NSAIDs are the first-line medications for the pain treatment in LBP and OA. Aceclofenac is effective and safe in this conditions. When carrying out analgesic therapy should take into account factors that affect the effectiveness of treatment: old age, overweight, insufficient effect of NSAIDs in history, severe pain, signs of "inflammatory" pain, multiple sources of pain.

[Cytokine gene polymorphism in type 2 diabetes mellitus in Russian women from eastern Europe].

AIM: To study the distribution of genotypes in the cytokine genes and their combinations with immunoregulatory activity in patients with type 2 diabetes mellitus (T2DM) and in healthy women. SUBJECTS AND METHODS: 586 Europeoid women from the eastern regions of Russia, including 374 healthy women aged 23-68 years and 212 women aged 28-69 years with T2DM complicated and uncomplicated by osteoporosis, were examined. Seven polymorphisms located in the promoter regions of the interleukin (IL) gene: TNF-alpha at positions C-863A, G-308A, G-238A, IL1B T-31C, IL6 G-174C, IL10 C-592A, VEGFA C-2578A were investigated. Restriction analysis of amplification products was applied. RESULTS: There were high associations of the predisposition and resistance to the development of T2DM with a number of polylocus cytokine genotype combinations having pro- and anti-inflammatory, angiogenic, and immunoregulatory activities. The association of the cytokine genes with T2DM was found to be mediated in nature through a relationship of the genotypes to the high or low production of regulatory cytokines and to different factors of regulation of lipid and carbohydrate metabolisms, inflammation, and bone remodeling. CONCLUSION: The high odds ratio and high specificity of the detected genetic combinations allow one to hope that they will be clinically used as predictors.

[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.

[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.

[Frequency distribution of HLA phenotypes, haplotypes and alleles in ethnic groups of Taimyr and Chukotka]. / Rasprostranenie chastot fenotipov, gaplotipov, allelei HLA v étnicheskikh gruppakh Taimyra i Chukotki.

HLA typing data of two little populations living in Tajmyr peninsula (Dolgans and Nganasans) and Chukotka peninsula (Chukchas and Chuvantses) were presented. Our data were compared with the International standard distribution of class I HLA antigens in orients and its distribution in orients who live in the Asian part of Russia. Indexes of genetic distribution and genetic likeness were calculated.

[Association of TAP1/TAP2 gene polymorphism with inflammatory urogenital diseases combined with joint diseases]. / Assotsiirovannost' polimorfizma genov TAP1/TAP2 s vospalitel'nymi zabolevaniiami urogenital'nogo trakta, sochetaiushchimisia s porazheniiami sustavov.

AIM: To study association of TAP1/TAP2 gene polymorphism with urogenital infections combined with joint lesions. MATERIALS AND METHODS: Of 139 patients examined 45 ones had inflammation caused by Chlamydia trachomatis (17 had joint disease), 42 had Mycoplasma hominis infection (joint lesions in 17 cases). Method of amplification was used on the basis of specific primers (ARMS). RESULTS: Patients infected with C. trachomatis significantly more frequently had allele TAP1-02011 and TAP2-0201 (RR = 18.5, p < 0.01 and RR = 4.61, p < 0.05, respectively). Joint lesion in patients with chlamydial infection was associated with allele TAP1-02011 (RR = 11.92, p < 0.05). In mycoplasmosis association with joint lesions there is a significant link of joint syndrome with heterogeneous combination threonine/alanine in gene TAP2 position 565 (RR = 4.22, p < 0.05). CONCLUSION: The findings can be used for predicting the joint syndrome development in patients with urogenital infection.

High-dose immunosuppression with autologous stem cell transplantation in severe refractory systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an immune-mediated disease that is responsive to suppression or modulation of the immune system. Patients with SLE who experience persistent multiorgan dysfunction, despite standard doses of intravenous cyclophosphamide (Cy), represent a subset of patients at high risk of early death. We investigated the efficacy and toxicity of high-dose immunosuppression and autologous hematopoietic stem cell transplantation (SCT) to treat such patients. Six patients (all female, age 15-29 years) with severe refractory SLE were enrolled in the clinic of our institution from 1998 to 2003. All patients were seriously ill, with SLE disease activity indices (SLEDAI) of 6-30, including two cases with central nervous system lupus, one case with lung vasculitis, and three cases with nephritis and nephrotic syndrome. All patients were registered in the European Group for Blood and Marrow Transplantation (EBMT)/European League Against Rheumatism (EULAR) database. Previous immunosuppression included pulse Cy intravenous, prednisolone (standard doses and pulse therapy), oral Cy and azathioprine, with little or no effect on disease progression. Autologous hemopoietic stem cells were collected from bone marrow (n = 4) or mobilized from peripheral blood with Cy and granulocyte colony-stimulating factor (G-CSF) (n = 2). Pre-transplant conditioning regimens included BEAM +/- ATG (n = 2), melphalan 140 mg/m2 + etoposid 1600 mg/m2 (n = 2) and Cy 200 mg/kg +/- ATG (n = 2). Median time to an absolute neutrophil count (ANC) greater than 0.5 x 10(9)/L and platelet count greater than 50 x 10(9)/L was 13 and 15 days, respectively. Three patients died on days 11, 22 and 63 due to transplant-related complications. The follow-up is now 60 and six months for two patients (complete remission), and 42 months for one other patient (partial response). All patients had experienced multiple and severe episodes of infections pre-SCT and long-term history of corticosteroid therapy (3-14 years). We conclude that achievement of prolonged, corticosteroid-free remissions is a reality. Judicious selection of patients earlier in disease or in remission, but with a high risk of relapse or further progression, will diminish transplantation-related mortality.