[Botulinum toxin type A (Relatox) in transition from medication overuse to non-overuse status in patients with chronic migraine: a subgroup analysis of phase IIIb randomized single-blind multicenter active-controlled parallel-group trial]. / Botulinicheskii toksin tipa A (Relatoks) v preodolenii lekarstvennogo zloupotrebleniya u patsientov s khronicheskoi migren'yu: podgruppovoi analiz rezul'tatov mnogotsentrovogo prostogo slepogo randomizirovannogo sravnitel'nogo issledovaniya IIIb fazy.

OBJECTIVE: To access the effect of Relatox, the first Russian botulinum toxin type A, in patients with chronic migraine (CM) and medication overuse (MO). MATERIAL AND METHODS: In phase IIIb single-blind randomized multicenter active-controlled parallel-group study, patients with CM were randomized to once intramuscular injections of Relatox (n=101) or onabotulinumtoxin A injections - Botox (n=108). This subgroup analysis evaluated the percentage of patients who transition from medication overuse to non overuse status from baseline; mean changes in the number of headache days, migraine headache days, acute headache medication intakes days, headache intensity, proportion of patients who had a ≥50% reduction in headache days, proportion of the patients with severe (≥60) Headache Impact Test-6 score and with a severe (≥21) MIDAS score in a 28-day periods in each treatment among patients with baseline acute medication overuse via repeated measures. RESULTS: Of 209 patients with CM, 100% met medication overuse criteria. Relatox and Botox demonstrated significant improvement for overall least squares mean change in headache days, migraine headache days, headache intensity; and headache-related disability and quality of life in CM patients with baseline MO, without differences between the groups. 75% and 70% patients in the Relatox and Botox groups, respectively, achieved ≥50% reduction in headache days from baseline (OR 1.58, CI 95% 0.84; 3.02, p=0.155). Furthermore, Relatox and Botox significant reduced average medication overuse rates in patient with CM and MO at baseline. 62% of patients in the Relatox group and 48% of patients in the Botox group transitioned from medication overuse to non overuse status compared from baseline (OR 2.07, CI 95% 0.91; 4.62, p=0.044). Relatox group had greater reductions than the Botox group in the percentage of patients with acute migraine-specific medication (triptan) overuse (p=0.050). CONCLUSION: The results demonstrate highly prevalent of medication overuse among individuals with CM. This analysis provides evidence that the Russian botulinum toxin type A Relatox significantly improves measures of headache symptoms, quality of life and headache-related disability, and also significantly greater, compared to Botox, reduces migraine-specific medication consumption in patients with chronic migraine who overuse acute medications.

[Experience of using rhythmic transcranial magnetic stimulation, extracorporeal shock wave therapy and botulinotherapy in individual motor recovery programs in patients with spastic paresis of the lower limb]. / Opyt ispol'zovaniya v individual'nykh programmakh dvigatel'nogo vosstanovleniya ritmicheskoi transkranial'noi magnitnoi stimulyatsii, ekstrakorporal'noi udarno-volnovoi terapii i botulinoterapii u patsientov so spasticheskim parezom nizhnei konechnosti.

Walking disorder is one of the most frequent consequences of stroke and traumatic brain injury, occurring in 80% of cases. Spastic paresis of the muscles of the lower extremity is the cause formed in 20-40% of patients within a few weeks after brain damage. In this case, a complex of symptoms occurs: motor deficiency (muscle paresis), increased muscle tone (spasticity), biomechanical changes in muscles, joints and surrounding tissues, contractures. Recovery of walking is a difficult task due to the peculiarities of its organization in the norm. At the same time, changes occurring in the muscles of the lower limb after a stroke, their modular reorganization, the formation of various pathological patterns, violation of the regulation of movements by the central nervous system, rapidly occurring changes in muscles, ligaments, complicate this process. Improving walking is one of the most important priorities of rehabilitation. Already at the second (stationary) stage of rehabilitation, patients have a lack of proper support on the lower limb, which inevitably leads to excessive load on the second limb, a change in the body scheme, incorrect foot placement, violation of the mechanics of walking (moving from heel to toe) due to plantar flexion / turn of the foot, etc. All this makes patients dependent on outside help, and walking unsafe, increases the risk of falls and complications (arthropathy, contracture, etc.). In this regard, it is important to timely diagnose the totality of changes in the lower limb and create optimal comprehensive rehabilitation programs using highly effective treatment methods aimed at reducing the severity of the motor defect, reducing spasticity and preventing complications. The article discusses the place of rhythmic transcranial magnetic stimulation, extracorporeal shock wave therapy and botulinum therapy during rehabilitation in patients with spastic paresis of the lower limb after a stroke. The results of the protocol of clinical approbation «Complex rehabilitation of patients with lower limb spasticity after focal brain damage at the second stage of medical rehabilitation¼ are presented.

[Botulinum toxin type A (Relatox) in the treatment of chronic migraine in adults: results of phase IIIb, randomized, one-blind, multicenter, active-controlled, parallel-group trial]. / Botulinicheskii toksin tipa A (Relatoks) v lechenii khronicheskoi migreni u vzroslykh: rezul'taty mul'titsentrovogo prostogo slepogo randomizirovannogo sravnitel'nogo issledovaniya IIIb fazy.

OBJECTIVE: To access the efficacy and safety of the first Russian botulinum toxin type A (Relatox) as a headache prophylaxis in adult with chronic migraine (CM). MATERIAL AND METHODS: The randomized, one-blind, multicenter, active-controlled, parallel-group trial study involved 209 patients with CM aged from 19 to 65 years. The patients were randomized to injections of the Russian botulinum toxin type A - Relatox (n=101) or onabotulinumtoxinA injections - Botox (n=108). The duration of the study was 16 weeks, which included five visits of patients every 4 weeks. Relatox and Botox were injected once into seven muscle groups of the head and neck at a dose of 155-195 units. Primary efficacy variable was mean change from baseline in frequency of headache days after 12 weeks. Secondary efficacy variables were mean changes from the baseline to week 12 in frequency of migraine days, acute headache pain medication intakes days; headache intensity; proportion of patients achieving ≥50% reduction from baseline in headache days, the proportion of the patients with medication overuse, the proportion of the patients with severe (≥60) Headache Impact Test-6 score and with a severe (≥21) MIDAS score. RESULTS: Analyses demonstrated a large mean decrease from baseline in frequency of headache days, without statistically significant between-group differences Relatox vs Botox at week 12 (-10.89 vs -10.06; p=0.365) and at other time points. Significant differences from baseline were also observed for all secondary efficacy variables at all time points without differences between the groups. The proportion of patients achieving ≥50% reduction from baseline in headache days was 75.0% and 70% in the Relatox and Botox groups, respectively (OR, CI 95% 1.58 [0.84; 3.02], p=0.155). Adverse events (AE) occurred in 15.8% of Relatox patients and 15.7% of Botox patients (p=1.000). No unexpected AE were identified. CONCLUSION: The results demonstrate that the first Russian botulinum toxin type A (Relatox) is an effective prophylactic treatment for CM in adult patients. Relatox led to significant improvements from baseline in multiple measures of headache symptoms, headache-related disability and quality of life. For the first time, a comparative analysis of two botulinum toxin type A products in parallel groups showed no less (not inferior) efficacy and safety of Relatox relative to Botox in the treatment of CM in adults.

[Safety and efficacy of the Relatox in the treatment of patients with cervical dystonia (results of a multicenter simple blind comparative randomized study)]. / Bezopasnost' i effektivnost' preparata Relatoks v lechenii patsientov s tservikal'noi distoniei (rezul'taty mul'titsentrovogo prostogo slepogo sravnitel'nogo randomizirovannogo issledovaniya).

OBJECTIVE: The analysis of evaluation of the efficacy and safety of Relatox in patients with cervical dystonia (CD). MATERIAL AND METHODS: Russian multicenter simple comparative randomized clinical trial. The study involved 180 patients of both sexes aged 18-65 years from 3 research centers of the Russian Federation. All patients had previously established diagnosis of CD and were randomized to one of two groups at 1 visit after the inclusion procedure and signing of informed consent. Patients in group 1 (n=90) got injections of Relatox, in group 2 (n=90) - injections of Botox for the first time or no earlier than 4 months after the previous injection of Dysport 500 units, Botox 200 units or Xeomin 200 units. The assessment of changes in cervical dystonia followed, including of determination of changes in the severity of CD, assessed on the TWSTRS scale by the total score and by the defining values of the blocks, as well as on the scales: the Patient Global Impression of Improvement (PGI-I) and of adverse events (local and systemic reactions). Based on the form of cervical dystonia (torticollis, laterocollis, etc.), the drug was injected under electromyographic control into the target muscles: sternocleidomastoid, belt, trapezoidal, shoulder-lifting muscle. RESULTS: Equal efficacy, good tolerability and safety comparable to the comparison drug Botox was demonstrated in 12 weeks after injection of Relatox. The number of registered local and systemic reactions in both groups was insignificant and did not differ significantly (p>0.05). There were no significant differences in the results of laboratory parameters in patients of both groups (p>0.05). Serious adverse events were also not detected during the study. CONCLUSION: Obtained results indicate the safety, good tolerability and efficacy of Relatox in patients with CD comparable to Botox and can be recomemded for using by practitioners.

[Formation of immunity and tolerance to the cell membrane components in primary and secondary (postimplantation) cardiac immunopathies].

The role of humoral constituents of the innate immunity in altering of tolerance and formation of immune response to autoreactive cell membrane components during both primary endocardithis and atherosclerosis processes and secondary ones, following reconstructive implantation on heart was investigated. The ways of restoration of the tolerance to membrane components and elimination of immune deficiency during the treatment of primary and secondary immunopathy of the cardiovascular system before and after implantation were considered.

[Xenogenic formation of anodic autoprecipitins before and during cardiopulmonary bypass]. / Ksenohenne utvorennia anodnykh autopretsypityniv do ta pid chas shtuchnoho krovoobihu.

The peculiarities of an inductive phase in an immune response to xenobiotics were studied before and during cardiopulmonary bypass at surgical implantations on heart. It has been determined that an early xenogenic induction of the forming the humoral innate immune receptors-namely the anodic (anionic) autoprecipitins-to the surface component of the cellular membrane, depended on the xenobiotic properties, as well as on the initial immunopathogenic: immunocomplex and immuno adsorptive-processes in the cardiovascurlar system. The intensity of this reaction correlated with both subsequent acute disorders in the blood circulation and reducing the resistance to exogeneous (inter-current) infection in the patients with atherosclerosis and endocardits.

[Regulation of innate immunity during xenogenic changes in blood circulation]. / Rehuliatsia pryrodnoho imunitetu pry ksenohennykh porushenniakh krovobihy.

Calcium-dependent innate immune response with participation of the superfamily of immunoglobulins to several intra- and extracorporal xenobiotics were studied at 216 recipients during synthetic cardiac valves implantation or veins transplantation in coronary arteries. It was shown that immediate immune response to xenobiotics was manifested by generation of the antitissue anodical autoprecipitin with specificity to the surface cell membrane component. This reaction initiated and regulated the subsequent dynamics of the two different fibrinogen autoimmune complexes formation, resulting in development of the immunogenic damages of blood circulation. Correction of these rapid innate immune responses is important for prevention and normalisation of the xenogenic damages of blood circulation during trans- and implantation on the heart impaired with endocarditis or aterosclerosis.

[Treatment of purulent-inflammatory complications of the soft tissues wounds in elderly and senile patients]. / Likuvannia hniino-zapal'nykh uskladnen' ran m'iakykh tkanyn u khvorykh pokhyloho ta starechoho viku.

Experience of treatment of elderly and senile patients with purulent infection of the soft tissues wounds was summarized. For raising of the therapeutic effect of the local treatment the introduction of new combined medicinal forms, composition of which was scientifically substantiated according to the wound process pathogenesis with special attention to its phase and character of microflora (kind of microorganism and its sensitivity to antimicrobic agents), is perspective.

[Autoimmune processes and biocompatibility in local damage of endothelium of the heart and its vessels]. / Autoimunni protsesy ta biosumisnist' pry vohnyshchevykh urazhenniakh endoteliiu sertsia ta ioho sudyn.

At immunoproductive processes in endothelium of patients with coronary atherosclerosis and endocarditis a phase dynamics of innate immunity represented by polytypic Ca(2+)-dependent autoprecipitating proteins of nonclonal recognition of surface cell membrane components (CMC) have been revealed. In case of coronary atherosclerosis the organism reaction to expressed CMC is manifested basically by intensified synthesis of cathodic complement-C3-similar autoprecipitin, but in case of endocarditis--by consumption of one with formation of anodic autoprecipitin and by intensified synthesis of autoprecipitating immunoglobulin G. These membranotropic autoimmune reactions are identical with the organism reactions to alien (heterologous) agents and differentially participate in development both of basic disease and perioperational complications after cardiac operations using trans- and implants, hence, they should be taken into account during membrane-stabilising and immunocorrecting therapy of recipients.

[The formation of autoimmune complexes as an index of bioincompatibility in reconstructive heart operations]. / Utvorennia autoimunnykh kompleksiv iak pokaznyk bionesumisnosti pry vidnovnykh operatsiiakh na sertsi.

The manifestation of bioincompatibility in the shape of complement-dependent changes: solubilisation and inhibition--of immune complexed formation was investigated in patients at the prosthetic cardiac operations with using artificial blood circulation, artificial cardiac valves and heterotopic vascular grafts. It was established, that the solubilisation of the precipitate, preformed by plasmic fibrinogen with antifibrinogenic immunoglobulin, and inhibition of hemagglutinating activity of normal autoantibodies in plasma appeared in several minutes after the contact of alien mains with own blood circulation system. These changes of formation of immune complexes in plasma, caused by complement activation, had a selective and reversible nature and were followed breaches of blood circulation. Estimation of early, functional indexes of bioincompatibility, displaying by changes of immune complex formation, may be helpful in prognostic relation in patients with immunocomplex diseases at prosthetic cardiac operations.

[The humoral reactions of bioincompatibility in the early period after the heterotopic autograft of veins into the coronary bed and the implantation of synthetic heart valves]. / Humoral'ni reaktsiï bionesumisnosti u rann'omu periodi pislia heterotopichnoi autotransplantatsiï ven u koronarne ruslo ta implantatsiï syntetychnykh klapaniv sertsia.

Humoral manifestations of bioincompatibility were studied at early stages (during several hours and days) after operations using non-peculiar to heart trans- and implants: aortocoronary bypass at 102 patients with coronarosclerosis and implantation of artificial cardiac valves at 145 patients with endocarditis. In the various postoperation stages the formation of the structurally and functionally different types of the nonclonal specific autoprecipitins to autological membranocellular components was revealed at recipients by methods of double immunodiffusion and immunoelectrophoresis. These autoprecipitins such as: early, activated and tardly, synthesized under effect of alien agent--may be useful as diagnostic and prognostic indicators of bioincompatibility and its clinical consequences at the earliest period after cardiac operations using trans- and implants.

[The manifestations of the immediate bioincompatibility reaction in patients undergoing restorative heart operations]. / Proiavy nehainoï reaktsiï bionesumisnosti u khvorykh pry vidnovnykh operatsiiakh na sertsi.

The generation in plasma the anodic autoprecipitating protein, or autoprecipitin (AAP), as the bioincompatibility reaction under influence of a number of alien components during cardiac operations with using cardiopulmonary bypass, heterotopic vascular autotransplants and artificial valve implants was studied in 257 patients. Selective formation of the AAPs in result of their inductors effect was discovered by the methods of immunodiffusion and immunoelectrophoresis in blood of patients within operation periods and early postoperation hours. Repeated and reiterated generation of the AAPs due to bioincompatibility in patients with coronarosclerosis and endocarditis, undergoing prosthetic cardiac operations may favour developing reaction of immediate hypersensitivity with complications and has prognostic value.