12 research outputs found
Complement-Inhibiting Therapy of Atypical Haemolytic Uremic Syndrome in a Patient With Factor H Mutation
No full textAtypical haemolytic uremic syndrome (aHUS) is an extremely rare pathology with the development of complement-mediated thrombotic microangiopathy (TMA). Before eculizumab, a humanized IgG monoclonal antibody to the complement component C5, the prognosis of total and renal survival with aHUS was unfavourable due to the high probability of death and the development of end-stage chronic renal failure in surviving patients. This article presents a clinical observation of a patient with aHUS who had an identified heterozygous factor H (CFH) mutation — c.3653G>A(p.Cys1218Tyr), and two heterozygous variants of polymorphism in the same gene — c.2016A>G; c.2808G>T. Despite the achievement of haematological remission of TMA against the background of plasma therapy, the child developed dialysis-dependent renal failure. Treatment with eculizumab in a patient with chronic kidney damage provided a significant improvement in their function, maintaining a stable remission and improving the quality of life of the patient with aHUS.Kh. М. Emirova, Е. S. Stolyarevich take part in educational events for doctors as lecturers with the support of Alexion Pharma. The other contributors confirmed the absence of a reportable conflict of interest
Dose–response of an extrafine dry powder inhaler formulation of glycopyrronium bromide: randomized, double-blind, placebo-controlled, dose-ranging study (GlycoNEXT)
No full textKai M Beeh,1 Aida Emirova,2 Hélène Prunier,2 Debora Santoro,3 Marie Anna Nandeuil2 1Insaf Respiratory Research Institute, Wiesbaden, Germany; 2Global Clinical Development, Chiesi S.A.S, Bois-Colombes, France; 3Global Clinical Development, Chiesi Farmaceutici SpA, Parma, Italy Introduction: An extrafine formulation of the long-acting muscarinic antagonist, glycopyrronium bromide (GB), has been developed for delivery via the NEXThaler dry powder inhaler (DPI). This study assessed the bronchodilator efficacy and safety of different doses of this formulation in patients with COPD to identify the optimal dose for further development.Patients and methods: This was a multicenter, randomized, double-blind, placebo-controlled, incomplete block, three-way crossover study, including three 28-day treatment periods, each separated by a 21-day washout period. Eligible patients had a diagnosis of COPD and post-bronchodilator forced expiratory volume in 1 s (FEV1) 40%–70% predicted. Treatments administered were GB 6.25, 12.5, 25 and 50 µg or matched placebo; all were given twice daily (BID) via DPI, with spirometry assessed on Days 1 and 28 of each treatment period. The primary end point was FEV1 area under the curve from 0 to 12 h (AUC0–12 h) on Day 28.Results: A total of 202 patients were randomized (61% male, mean age 62.6 years), with 178 (88%) completing all the three treatment periods. For the primary end point, all the four GB doses were superior to placebo (p<0.001) with mean differences (95% CI) of 114 (74, 154), 125 (85, 166), 143 (104, 183) and 187 (147, 228) mL for GB 6.25, 12.5, 25 and 50 µg BID, respectively. All four GB doses were also statistically superior to placebo for all secondary efficacy end points, showing clear dose–response relationships for most of the endpoints. Accordingly, GB 25 µg BID met the criteria for the minimally acceptable dose. Adverse events were reported by 15.5, 16.2, 10.9 and 14.3% of patients receiving GB 6.25, 12.5, 25 and 50 µg BID, respectively, and 14.8% receiving placebo.Conclusion: This study supports the selection of GB 25 µg BID as the minimal effective dose for patients with COPD when delivered with this extrafine DPI formulation. Keywords: pulmonary disease, chronic obstructive, muscarinic antagonists, pulmonary function tests, dose–response relationship, drug, metered-dose inhaler
Government regulation of foreign economic activity in Russia: Legal and economic aspects
No full textThe paper assesses the fact that in the current conditions of globalization, any national economy is becoming more open, and therefore the state should take into account in its trade and economic policy the consistent relationship between the processes occurring within the economy and in the sphere of foreign economic relations. The state also acts as the organizer of the system of servicing foreign economic relations and achieving internal economic equilibrium, and finances this activity from budgetary funds. This system is branched in its nature, covering such areas of activity as the provision of information and consulting services, and organization of advertising and exhibition work; it also helps to increase the efficiency of foreign economic activity, introducing new participants to it. The authors conclude that in order to maintain domestic economic balance, the state should strengthen its influence on imports in order to maintain domestic producers and without depriving them of competition from foreign goods at the same time
Комплементингибирующая терапия атипичного гемолитико-уремического синдрома у пациентки с мутацией гена, кодирующего фактор Н
No full textAtypical haemolytic uremic syndrome (aHUS) is an extremely rare pathology with the development of complement-mediated thrombotic microangiopathy (TMA). Before eculizumab, a humanized IgG monoclonal antibody to the complement component C5, the prognosis of total and renal survival with aHUS was unfavourable due to the high probability of death and the development of end-stage chronic renal failure in surviving patients. This article presents a clinical observation of a patient with aHUS who had an identified heterozygous factor H (CFH) mutation — c.3653G>A(p.Cys1218Tyr), and two heterozygous variants of polymorphism in the same gene — c.2016A>G; c.2808G>T. Despite the achievement of haematological remission of TMA against the background of plasma therapy, the child developed dialysis-dependent renal failure. Treatment with eculizumab in a patient with chronic kidney damage provided a significant improvement in their function, maintaining a stable remission and improving the quality of life of the patient with aHUS.Kh. М. Emirova, Е. S. Stolyarevich take part in educational events for doctors as lecturers with the support of Alexion Pharma. The other contributors confirmed the absence of a reportable conflict of interest.Атипичный гемолитико-уремический синдром (аГУС) — ультраредкая патология с развитием комплементопосредованной тромботической микроангиопатии (ТМА). До появления экулизумаба — гуманизированного моноклонального антитела класса IgG к C5-компоненту комплемента — прогноз общей и почечной выживаемости при аГУС был неблагоприятным вследствие высокой вероятности летального исхода и развития терминальной хронической почечной недостаточности у выживших пациентов. В этой статье представлено клиническое наблюдение пациентки с аГУС, у которой были идентифицированы гетерозиготная мутация гена, кодирующего фактор Н (CFH) — c.3653G>A(p.Cys1218Tyr) и два гетерозиготных варианта полиморфизма в том же гене — c.2016A>G; c.2808G>T. Несмотря на достижение гематологической ремиссии ТМА на фоне плазмотерапии, у ребенка развилась диализзависимая почечная недостаточность. Лечение экулизумабом при уже имеющемся хроническом повреждении почек обеспечило существенное улучшение их функции, поддержание стойкой ремиссии и повышение качества жизни пациентки с аГУС.Х.М. Эмирова, Е.С. Столяревич принимают участие в образовательных мероприятиях для врачей в качестве лекторов при поддержке компании «Алексион Фарма». Другие соавторы статьи подтвердили отсутствие конфликта интересов, о котором необходимо сообщить
The Role of the Complement System in the Pathogenesis of Infectious Forms of Hemolytic Uremic Syndrome
No full textHemolytic uremic syndrome (HUS) is an acute disease and the most common cause of childhood acute renal failure. HUS is characterized by a triad of symptoms: microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. In most of the cases, HUS occurs as a result of infection caused by Shiga toxin-producing microbes: hemorrhagic Escherichia coli and Shigella dysenteriae type 1. They account for up to 90% of all cases of HUS. The remaining 10% of cases grouped under the general term atypical HUS represent a heterogeneous group of diseases with similar clinical signs. Emerging evidence suggests that in addition to E. coli and S. dysenteriae type 1, a variety of bacterial and viral infections can cause the development of HUS. In particular, infectious diseases act as the main cause of aHUS recurrence. The pathogenesis of most cases of atypical HUS is based on congenital or acquired defects of complement system. This review presents summarized data from recent studies, suggesting that complement dysregulation is a key pathogenetic factor in various types of infection-induced HUS. Separate links in the complement system are considered, the damage of which during bacterial and viral infections can lead to complement hyperactivation following by microvascular endothelial injury and development of acute renal failure
Efficacy and Safety of CHF6001, A Novel Inhaled PDE4 Inhibitor in COPD: The Pioneer Dose Finding Study
No full textТромбоцитаферез в комплексной терапии больных различными формами бронхиальной астмы
No full textBasing on the active role of platelets (Pt’s) in bronchial asthma (BA) pathogenesis, the influence of plateletapheresis (PtA) on bronchial asthma and Pt’s functional activity was investigated. PtA was used in 88 patients with various asthma forms. 41 patients with atopic BA, 28 patients with “mixed” asthma, and 19 ones with aspirin BA were treated. The clinical state and the Pt’s functional parameters (aggregation, intracellular Ca2+, Pt’s secretion, levels of Pt’s-binding IgE) were evaluated. The therapy was efficient in 86% of patients with atopic BA, in 62% of ones with aspirin-sensitive BA, in 46% of patients with “mixed” BA. The results of the study demonstrated that PtA restores normal platelet functional status parameters, especially in atopic patients with dramatic clinical course of the disease.На основе предположения об активной роли тромбоцитов в патогенезе бронхиальной астмы (БА) решили исследовать влияние тромбоцитафереза (ТА) на течение заболевания и тромбоцитарную функциональную активность. Тромбоцитафсрез выполнялся у 88 пациентов с различными формами бронхиальной астмы: 41 больной — с атопической БА, 28 — со “смешанной формой” и 19 — с аспириновой формой БА. Исследовалось клиническое состояние больных и параметров, отражающих функциональный статус тромбоцитов: агрегация, внутриклеточный кальций, тромбоцитарная секреция, уровень связывания IgE тромбоцитами. Терапия ТА оказалась эффективной у 88% больных с атопической БА, у 62% больных с аспиринчувствительной БА и 46% — со “смешанной” БА. Результаты исследования показали, что ТА восстанавливает нормальный функциональный стстус тромбоцитов, особенно у больных с атопией с неблагоприятным клиническим течением
Моноклональная анти-LgЕ-плазмоиммуносорбция в комплексном лечении больных атопической бронхиальной астмой
No full textWc have studied the efficacy of monoclonal extracorporeal anti-IgE-plasmoimmunosoibtion (EPIA) in treatment of 16 atopic asthma patients. We used new immunosorbent with immobilized anti-IgE-antibodies. The first group (9 patients) was treated by EPIA, the second group (7 patients) was treated only by placebo procedures. The investigation was done by double blind method. After EPIA in first the group good clinical results were obtained in 8 patients, in the second group we have seen clinical improvement only for a short time. It was not possible to decrease the number o f broncholitics and corticosteroids in patients of the second group. We have seen specific changes of the IgE serum levels after EPIA, but not after placebo procedures. Thus, EPIA is effective extracorporeal method for treatment of atopic asthma patients with high serum levels of IgE and plural hypersensitivity.Исследовалась эффективность применения моноклональной анти-LgЕ-плазмоиммуносорбции в лечении больных атопической бронхиальной астмой. Процедура проводилась с новым синтезированным иммуносорбентом с иммобилизованными моноклональными антителами к LgЕ . Обследовано 16 больных: 1-й группе (9 больных) проводились истинные процедуры, 2-й группе (7 больных) — ложные процедуры. Исследование проведено двойным слепым методом. После проведения процедур в 1-й группе эффективным лечение оказалось у 8 больных, во 2-й группе отмечено улучшение состояния и прекращение приступов удушья на короткое время, этим больным не удалось снизить объем лечения, отменить гормональную терапию. Выявлена определенная закономерность в изменении уровня общего LgЕ после истинных процедур, плацебо таких изменений не вызывало. Таким образом, иммуносорбция является безопасной эффективной процедурой в лечении больных атопической бронхиальной астмой с высокими уровнями общего LgЕ, поливалентной аллергией. Метод имеет большие перспективы и требует дальнейшего изучения
Effects of the Novel Inhaled Phosphodiesterase-4 (PDE4) Inhibitor CHF6001 in Targeting Markers of Inflammation in Patients with Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) and Chronic Bronchitis
No full textModern Approaches to the Management of Children with Atypical Hemolytic Uremic Syndrome
No full textExperts of the Union of Pediatricians of Russia have developed modern guidelines on management of children with atypical hemolytic uremic syndrome (aHUS). aHUS is ultra-rare (orphan) disease with progressive and relapsing course during the life with potentially life-threatening state. This article covers issues of disease etiology, pathogenesis, and classification. Specific attention is paid to the diagnosis, differential diagnosis, and therapy of aHUS according to the evidence-based approaches
