Mutation spectrum of 260 dystrophinopathy patients from Turkey and important highlights for genetic counseling.

We genetically evaluated 260 dystrophinopathy patients from Turkey. Karyotyping as an initial test in female patients, followed stepwise by multiplex ligation-dependent probe amplification and by targeted next-generation sequencing of DMD revealed definitive genetic diagnoses in 214 patients (82%), with gross deletions/duplications in 153 (59%), pathogenic sequence variants in 60 (23%), and X-autosome translocation in one. Seven of the gross and 27 of the sequence variants found novel. In silico prediction, co-segregation and transcript assays supported the pathogenic nature of the novel silent (p.Lys534=) and the splice site (c.4345-12C>G) alterations. From a total of 189 singleton cases, 154 (82%) had pathogenic alterations. From 138 of those who had maternal carrier testing, 68 out of 103 (66%) showed gross and 11 out of 35 (31%) showed small pathogenic variants. This suggests that the de novo occurrences in DMD appear approximately 2.1 times more frequently in meiotic unequal crossing-over than in uncorrected replication errors. Our study also disclosed three mothers as obligate gonadal mosaic carriers. Family-based investigation of dystrophinopathy patients is crucial for the ascertainment of novel or rare variants and also for counseling and follow-up care of the families.

[Comparative analysis of effectiveness and safety of diclofenac and nimesulide in patients with early rheumatoid arthritis].

The aim of the work was to evaluate effectiveness and safety of diclofenac and nimesulide in patients with early RA. The open clinical study included 80 outpatients (mean age 49.0 +/- 11.1 years) within the first year after development RA (mean duration of the disease 4.9 +/- 3.1 months prior to the onset of basic therapy). The patients were divided into 2 groups of 40 persons each depending on the type of non-steroidal anti-inflammatory agents they received. Patients in group 1 were treated with 100 mg of diclofenac daily and in group 2 with 100 mg BID of generic nimesulide preparation (nais, Dr. Reddy Co.). Duration of therapy was 30 days in both cases. The two drugs were roughly identical in terms of therapeutic effect although nimesulide produced fewer side effects. Subjective complaints of gastrointestinal problems were recorded in 11 (27.5%) patients f group 1 and in 8 (20%) of group 2. It is concluded that timely prescription of proton pump inhibitors permits to avoid premature withdrawal of non-steroidal anti-inflammatory agents at patient discretion.

[Effect of protracted therapy with chondroprotectors and non-steroidal anti-inflammatory drugs on the quality of life in patients with osteoarthrosis].

Dynamics of clinical parameters and quality of life (QL) was evaluated in 281 patients with knee and hip osteoarthrosis (OA) during long-term treatment of different duration. The group was dominated by women (71%) aged 41-65 yr with grade I-III OA according to Kellgren. Patients of groups I and II received only non-steroidal anti-inflammatory drugs (diclofenac, nize), those of groups III-IV the same drugs in combination with structum, chondrolon, and zeel T respectively. Clinical parameters were assessed based on VAS at rest and in motion, Leken's indices, and WOMAC, QL from SF-36 questionnaire. Variable clinical course was recorded in patients treated with non-steroidal drugs alone that caused rapid improvement after the very first treatment sessions followed by deterioration of the patients' condition. Addition of structum resulted in marked optimization of clinical and QL parameters within 3 months after the onset of combined therapy. Similar effect was obtained using chondrolon and zeel T, but 2-3 clinical parameters and 3 QL parameters were not significantly different from the initial ones after 12 and 24 months of therapy. It is concluded that structum produced the best therapeutic effect followed by chondrolon and zeel T. Non-steroidal anti-inflammatory drugs had no beneficial action whatever in patients with OA.

[Pharmaco-economic efficiency of the treatment of patients with acute vertebrogenic lumbar pain syndrome].

The aim of the study was to evaluate pharmaco-economic efficiency of two therapeutic schemes for the treatment of acute vertebrogenic lumbar pain syndrome. One hundred patients (including 77 women) with this syndrome caused by vertebral osteochondrosis (VO) were examined. Mean age of the patients was 41.00 +/- 8.33, mean duration of exacerbation 6.92 +/- 4.55 days. The majority of the patients had roentgenologic stage II VO. Patients of one group (n=50) were given intramuscular injections of ketorol (1 ml twice daily for 5 days) and diclofenac-retard (100 mg per os twice daily for 10 days). The second group (n=50) received ketorol and nise (100 mg twice daily for 10 days). This treatment was followed by 10 seances of phonophoresis using 1% hydrocortisone ointment. The clinical efficiency of therapy was evaluated based on the visual analog scale and in terms of Lasagne symptom, muscular syndrome index, Schober test, Thomayer's symptom, vertebrogenic syndrome coefficient. Pharmaco-economic analysis included calculation of direct medical care expenses and cost index/efficiency. The efficiency of therapy in group 2 (restoration of lumbar vertebral column mobility and alleviation of pain) was higher than in group 1 while the number of adverse effects was lower and the periods of remission longer. Combined therapy with ketorol and nise per unit efficiency was more expensive but the total cost of the management of one case including all yearly relapses suggested its advantages over the alternative treatment with ketorol and diclofenacin terms of clinical and pharmaco-economic efficiency.

[Metabolic syndrome and a course of osteoarthrosis].

AIM: To compare osteoarthritis (OA) course in patients with metabolic syndrome (MS) and those free of MS. MATERIAL AND METHODS: The presence and completeness of MS according to 2005 criteria were studied in 1350 OA patients (mean age 52.65 +/- 11.31 years). Most of the patients were women (74%) and persons over 45 years of age (80%). RESULTS: MS was detected in 82.3% examinees with OA. MS was complete in 62.56%. MS-free OA was separately comorbid with arterial hypertension, obesity and diabetes mellitus. OA patients with MS had earlier clinical symptoms of OA, its longer duration, prevalence of generalized disease, more frequent development of knee joint synovitis and periarthritis, more intensive pain in the joints. OA patients with MS were more frequently affected with cardiovascular, gastrointestinal, renal and thyroid diseases, diabetes mellitus and complications of these diseases. This resulted in 2.5 times greater nosological load on the patients. 20% patients with OA were declared invalid, most of them (266, 90.17%) had MS. CONCLUSION: Relationship of OA symptoms with metabolic factors may point to participation of the latter in the development and progression of OA.

[Metabolic syndrome and rheumatic diseases].

AIM: To characterize prevalence and features of rheumatic diseases in patients with metabolic syndrome, metabolic disturbances in patients with rheumatic diseases (RD), to ascertain their most frequent variants and characteristics. MATERIAL AND METHODS: After examination of 1291 therapeutic patients 19 to 79 years of age for metabolic syndrome (MS), those with MS were screened for RD. In parallel, 1212 RD patients were studied for associated pathology: arterial hypertension, coronary heart disease, obesity, dyslipidemia, hyperuricemia and other components of MS. A separate electronic matrix was created for each of the two groups. Statistics were obtained using standard programs Statistica 6.0 and MS Excel 2000 for Windows XP 2000. RESULTS: MS was detected in 317 (24.6%) patients seeking medical advice (mean age 54.11 +/- 0.59 years). MS was complete in 272 (85.8%) patients, 287 (90.5%) had arthralgia, 131 (41.3%)--episodes of painful joints swelling in the presence of family history. RD were detected in 295 (93.1%) MS patients. Osteoarthrosis, osteochondrosis and systemic osteoporosis occurred most often. Various metabolic disorders occurred in all the examinees with RD. The disorders were most pronounced in patients with gout and osteoarthrosis. CONCLUSION: MS patients comprise a group of a high risk for RD, especially gout and osteoarthrosis.

[Functional indices in assessment of gonarthrosis treatment efficacy with structum and chondrolon].

MATERIAL AND METHODS: The trial included 50 patients aged from 40 to 67 years with osteoarthrosis (OA) stage I and II by Kellgren-Lawrence. Patients of group 1 (n=30) received chondrolon, of group 2 (n=20)--structum. Treatment efficacy was assessed by WOMAC scale, Leken's functional index, VAS pain at rest, walking, goniometry findings, time of 30 m walking. RESULTS: A positive clinical effect was achieved in both groups by all the indices. The improvement was significant in VAS pain, functional tests, Leken's index, WOMAC scale. A positive trend in clinical symptoms and tests developed more quickly in the treatment with chondrolon than with structum (in 8 vs. 12 months, respectively). Treatment with different chondroitin sulphate drugs raised quality of life in gonarthrosis patients assessed by WOMAC scale, the effect being comparable. CONCLUSION: Structum and chondrolon can be used for OA stage I-II with moderate dysfunction of knee joints. The treatment course should be long, at least 3 months, 3-6 months for structum.

[Comparison of quality of life and treatment efficacy in patients with chronic low back pain syndrome].

AIM: To test use of quality of life (QL) parameters for assessing treatment efficacy in patients with chronic low back pain syndrome (CLBPS). MATERIAL AND METHODS: Clinical, device examinations, questionnaire survey were made in 100 patients, most of them females (77%) with CLBPS due to spinal osteochondrosis. Mean age of the patients was 45.69 +/- 7.61 years, mean duration of the disease 10.20 +/- 6.01 years, duration of the exacerbation 4.04 +/- 1.75 months. Most of the examinees had CLBPS x-ray stage II. QL was evaluated by questionning (general SF-36, HAQ and special Oswestry low back pain disability (OLBPD) questionnaires). RESULTS: The patients were divided into two groups by clinical and device findings and responses to the questionnaires. Group I patients had significant improvement of all the parameters studied, patients of group 2 had no improvement. A strong correlation was found between OLBPD responses and the patients' appraisal of the treatment efficacy. The effect value, standardized significance rates and factors intensity reflected high informative value of the questionnaire by assessment of efficacy of CLBPS treatment. CONCLUSION: SF-36 and OLBPD are recommended as adequate general and special questionnaires respectively, to estimate QL in patients with CLBPS. The treatment is effective if total parameters of physical and mental health by SF-36 rise significantly while vital activity disorders by OLBPD reduce more than 2-fold.

[Diagnostic possibilities of ultrasonic scanning of the knee joints in osteoarthrosis].

AIM: To examine diagnostic potential of arthrosonography (ASG) in diagnosis of tendenitis in combination with synovitis in patients with gonarthrosis stage I-III by Kellgren's classification. MATERIAL AND METHODS: A total of 40 patients with gonarthrosis exacerbation were examined with x-ray and ultrasound scanning (80 joints). ASG was made on Aloka-SSD-630 device using two-dimentional scanning in 4 longitudinal and 4 transverse positions. RESULTS: Clinical symptoms of synovitis were predominant in patients with gonarthrosis x-ray stage II (68.3%). In ASG synovitis was detected in 41 (51.25%) of 48 knee joints with clinical picture of synovitis. Ultrasound detected such synovitis signs as increased amount of water in the knee joint cavity and b. suprapatellaris, thickening of the synovial membrane more than 0.3 cm and changes in its structure. Six (7.5%) joints were affected with subclinical synovitis diagnosed only in ASG. Ultrasound visualized Baker's cyst in 5 patients and in 5 knee joints. Periarthritis was detected in 77.5% joints, in 46.25% joints it combined with synovitis, ASG provided differential diagnosis of synovitis with periarthritis. Thinning of the cartilage was detected in most of the joints both in synovitis and in its absence but it was more significant in synovitis (62.5 and 40%, respectively). CONCLUSION: ASG is an informative diagnostic method in periarthritis and synovitis, including subclinical, and give additional information for x-ray diagnosis in gonarthrosis stage I-III.

[Day hospital: experience and efficacy].

AIM: To analyse efficacy of treatment in a day hospital (DH) of Avtotrans (Orenburg city) outpatient department. MATERIAL AND METHODS: The activity of the DH was assessed by case histories and annual records for 5 years. RESULTS: DH provides high-quality examination and treatment for patients with different diseases (efficacy of treatment 99.5%). Ulcer treatment analysis showed that 98.53% of DH ulcer patients achieve a complete healing of the ulcer defect and its decrease was observed in 1.47%. CONCLUSION: DH facilities are able to provide differential therapy of patients and active prophylaxis of chronic disease progression. Combined therapy under a close control of physicians results in a good therapeutic effect.

[Midocalm in complex therapy of chronic low back pain syndrome].

The aim of the study was to determine whether application of midocalm is appropriate in patients with chronic low back pain (LBP) from the point of view of quality of life (QL), efficacy and tolerance. The subjects were 50 patients with chronic LBP associated with spinal osteochondrosis, who underwent clinical examination and were questioned using four QL questionnaires: Health Assessment Questionnaire (HAQ), Womac osteoarthritis index Womac osteoarthritis index, Oswestry Low Back Pain Disability Questionnaire, and The 36-Item Short-Form Health Survey (SF-36). The subjects were divided into two groups. The 25 patients of Group I were administered nise in a dose of 100 mg twice a day during 10 days, the 25 patients of Group II--nise in a dose of 100 mg twice a day plus midocalm in a dose of 150 mg per day during the first two days and 450 mg per day from the third day through the tenth day. The study showed high efficacy of midocalm in complex therapy of patients with chronic LBP, as well as low rate of adverse reactions and high treatment tolerance. QL of the patients improved. Combining midocalm therapy with nise allows quicker positive effect in patients with chronic LBP and lowers need for long application of non-steroid antiinflammatory drugs.

[Prevalence and risk factors of the lower back syndrome in automobile drivers]. / Rasprostranennost' i faktory riska vozniknoveniia sindroma boli v nizhnem otdele spiny u rabotnikov avtotransporta.

AIM: To study epidemiology of low spine pain syndrome (LSPS) in drivers of municipal transport; to specify factors stimulating its onset. MATERIAL AND METHODS: 600 drivers from Orenburg were screened for LSPS. Risk factors were evaluated in two groups of patients: 130 drivers with LSPS and 130 matched controls free of LSPS. The data obtained were entered to a standard questionnaire, risk factors were considered according to working place attestation. RESULTS: Low spine pain complaints were registered in each 1-2 drivers of three. Those having the pain were as a rule 30-50-year-olds with service duration more than 10 years. They had pain for more than 5 years. 94.6% of them had acute pain. Spinal function was restricted in most of the examined LSPS drivers. Major risk factors of LSPS were the following: toxic substances, static loads, physical overstrain, draughts. A relationship was found between intensive smoking, alcohol abuse, low physical activity and LSPS onset. CONCLUSION: High prevalence of LSPS, frequent exacerbations, impaired spinal function cause a high disability rate. Thus, LSPS is an important medicosocial problem.

[Treatment of chronic heart failure in patients with mitral and aortic valve defects of rheumatic origin]. / Lechenie khronicheskoi serdechnoi nedostatochnosti u bol'nykh s mitral'nymi i aortal'nymi porokami serdtsa revmaticheskoi étiologii.

AIM: To evaluate efficiency of using ACE inhibitor (capoten) and beta-blocker (atenolol) in diverse mitral and aortic valve defects (MVD and AVD, respectively) of rheumatic etiology complicated by chronic cardiac failure (CCF) of the first and second stages. MATERIAL AND METHODS: The trial enrolled 41 patients with MVD and 21 patients with AVD of rheumatic etiology. 60 of them had CCF. In cross-over study 38 patients with MVD and 21 with AVD received capoten (6.25 mg/day) for 7 days while 33 patients with MVD were treated with atenolol. Exercise tolerance (ET) and hemodynamics (echo-CG) were examined before and after the treatment. RESULTS: Hemodynamic parameters and ET improved after capoten and atenolol treatment in patients with MVD or AVD and in complex disease (stenosis and insufficiency) with predominant insufficiency. No significant hemodynamic changes were induced by the above drugs in patients with isolated mitral and aortic stenoses. CONCLUSION: Capoten vs atenolol has more potent positive effect in CCF patients with MVD or AVD.

[Quality of life in rheumatoid arthritis patients]. / Otsenka kachestva zhizni bol'nykh revmatoidnym artritom.

AIM: To study quality of life (QL) in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: Questionnaire survey (MCA, BIPQ, AIMS, MHAQ) covered 190 RA patients (mean age 47.7 +/- 1.4 years). Many of them were group II invalids. All the patients had slow-progressive polyarthritis, articular and seronegative RA prevailed. Most of the patients had articular and seronegative RA with first-degree activity, x-ray stage II and third-degree deficiency of the articular function. RESULTS: It is shown that RA patients have subnormal quality of life. Its deterioration was related to clinical parameters: duration of the disease and its activity, invalidity, X-ray stage, articular and locomotor functions, psychological status. Hypochondriac, apathical and neurastenic reactions to the disease occurred most frequently. Euphoric reaction to the disease was a positive factor for QL. Changes in social status were essential for QL in RA patients. CONCLUSION: QL is an integral indicator of health status in RA patients. It can be estimated basing on only one questionnaire--AIMS as it includes all the necessary components.

[The organization of ambulatory services for patients with rheumatoid diseases at an industrial enterprise]. / Organizatsiia ambulatornogo obsluzhivaniia bol'nykh revmaticheskimi zabolevaniiami na promyshlennom predpriiatii.

The authors have elaborated a complex of economically profitable organizational and medical measures aimed at stabilization or reduction of temporary disability due to osteoarthrosis (OA) in workers of an industrial enterprise. As a result of epidemiological studies it has been established that at the enterprise under study the OA incidence exceeded the general populational one more than 5-fold, with the number of cases and days of temporary disability due to OA ranking the first among the leading causes of temporary disability. The complex of medico-organizational and treatment-and-prophylactic measures closely related to the industrial process and taking account of the patients' interests made it possible to stabilize, within a period of 6 months, the characteristics of temporary disability and to reduce economic losses due to OA.