The effect of long-term danazol therapy on the serum levels of complement proteins and attack frequency in hereditary angioedema

2009 ◽  
Vol 46 (14) ◽  
pp. 2871 ◽  
Author(s):  
Lilian Varga ◽  
Dorottya Csuka ◽  
George Füst ◽  
Henriette Farkas
Author(s):  
Т.П. Ветлугина ◽  
Е.В. Матафонова ◽  
Н.А. Бохан ◽  
В.Б. Никитина ◽  
А.И. Мандель ◽  
...  

Цель исследования: изучение динамики показателей иммунитета и уровня кортизола у больных опийной наркоманией в процессе терапии синдрома отмены. Методика. В исследование включено 136 больных опийной наркоманией (инъекции экстракта опия) с сформировавшейся физической зависимостью. Пациенты получали в стационаре стандартную терапию с полной отменой наркотика. Исследование проводилось на следующих этапах: при поступлении в стационар (опийный абстинентный синдром - ОАС); на 5-7-е сут. терапии (переход в постабстинентное состояние - ПАС); на 25-28-е сут. лечения (становление терапевтической ремиссии - СТР). Лабораторные методы включали определение количества лимфоцитов с рецепторами CD3, CD4, CD8, СD16, с рецепторами к дофамину (D-RFC); содержание иммуноглобулинов М, G, А, уровня кортизола и циркулирующих иммунных комплексов (ЦИК) в сыворотке крови. Результаты. Основной иммуноэндокринный паттерн на всех этапах терапии синдрома отмены характеризуется дефицитом субпопуляций Т-лимфоцитов CD3, CD4, СD8; увеличением числа лимфоцитов с рецепторами к дофамину (D-RFC); активацией гуморальных факторов иммунитета (IgM, IgG, ЦИК); высокой концентрацией кортизола. На этапе ОАС и ПАС эти изменения были наиболее выражены; на 25-28-е сут. лечения отмечена позитивная динамика Т-лимфоцитов СD3 и цитотоксических Т-лимфоцитов (СD8); хелперы/индукторы CD4 оставались устойчиво сниженными; D-RFC лимфоциты, параметры гуморального иммунитета и концентрация кортизола - повышенными. Длительный срок наркотизации при употреблении высоких доз наркотика связан с большей выраженностью нарушений. Заключение. Установленная дизрегуляция параметров иммуноэндокринной системы у больных опийной наркоманией на всех этапах терапии синдрома отмены в наблюдаемые сроки (25-28 сут.) свидетельствует о неустойчивости достигнутой терапевтической ремиссии и необходимости проведения дальнейших реабилитационных мероприятий. The purpose: investigate changes in immunity parameters and cortisol level in subjects with opiate addiction during the treatment of opiate withdrawal syndrome. Methods. The study enrolled 136 subjects with opiate addiction with physical dependence receiving injections of opium extract. Patients received conventional therapy with complete opiate withdrawal. The study was performed at the following stages: at admission to the hospital (acute withdrawal syndrome (AWS); on days 5-7 of therapy (transition into post-withdrawal state - PWS); on days 25-28 of therapy (formation of therapeutic remission - FTR). Laboratory methods included determination count of lymphocytes with receptors CD3, CD4, CD8, СD16, with receptors to dopamine (D-RFC); the serum levels of IgМ, IgG, IgА, cortisol, circulating immune complexes (CIC). Results. The principal immunoendocrine pattern for all stages of withdrawal syndrome therapy is characterized in comparison to the reference normal values quantitative deficit of CD3, CD4, СD8 Т-lymphocyte subpopulations, increased count of lymphocytes with receptors to dopamine, activation of humoral immunity factors (IgM, IgG, CIC), high cortisol level. At AWS and PAS stages such changes are most pronounced; on days 25-28 of therapy positive changes in cytotoxic Т-lymphocytes (СD8) and Т-lymphocytes СD3 was revealed. CD4 count remained steadily reduced, count of lymphocytes with receptors to dopamine and cortisol level were elevated. Clinical and immunological analysis demonstrated that consumption of high opiate doses, long-term narcotization are associated with higher intensity of disorders detected. Conclusion. Dysregulation of immunoendocrine parameters was revealed in subjects with opiate addiction at all stages of withdrawal syndrome therapy within the term observed evidencing instability of therapeutic remission achieved and necessity in further rehabilitation events.


2021 ◽  
Vol 11 (4) ◽  
Author(s):  
Henriette Farkas ◽  
Marcin Stobiecki ◽  
Jonny Peter ◽  
Tamar Kinaciyan ◽  
Marcus Maurer ◽  
...  

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Konrad Bork ◽  
John T. Anderson ◽  
Teresa Caballero ◽  
Timothy Craig ◽  
Douglas T. Johnston ◽  
...  

Abstract Background Hereditary angioedema (HAE) is a rare disease characterized by unpredictable, potentially life-threatening attacks, resulting in significant physical and emotional burdens for patients and families. To optimize care for patients with HAE, an individualized management plan should be considered in partnership with the physician, requiring comprehensive assessment of the patient’s frequency and severity of attacks, disease burden, and therapeutic control. Although several guidelines and consensus papers have been published concerning the diagnosis and treatment of HAE, there has been limited specific clinical guidance on the assessment of disease burden and quality of life (QoL) in this patient population. Practical guidance is critical in supporting effective long-term clinical management of HAE and improving patient outcomes. The objective of this review is to provide evidence-based guidelines for an individualized assessment of disease burden and QoL in patients with HAE. Methods A consensus meeting was held on February 29, 2020, consisting of 9 HAE experts from the United States and Europe with extensive clinical experience in the treatment of HAE. Consensus statements were developed based on a preliminary literature review and discussions from the consensus meeting. Results Final statements reflect the consensus of the expert panel and include the assessment of attack severity, evaluation of disease burden, and long-term clinical management of HAE caused by C1-esterase inhibitor deficiency. Patient-reported outcome measures for assessing HAE attack severity and frequency are available and valuable tools; however, attack frequency and severity are insufficient markers of disease severity unless they are evaluated in the broader context of the effect on an individual patient’s QoL. QoL assessments should be individualized for each patient and minimally, they should address the interference of HAE with work, school, social, family, and physical activity, along with access to and burden of HAE treatment. Advances in HAE therapies offer the opportunity for comprehensive, individualized treatment plans, allowing patients to achieve minimal attack burden with reduced disease and treatment burden. Conclusion This consensus report builds on existing guidelines by expanding the assessment of disease burden and QoL measures for patients with HAE.


Diagnostics ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 900
Author(s):  
Krasimir Kostov ◽  
Alexander Blazhev

Thickening of the vascular basement membrane (BM) is a fundamental structural change in the small blood vessels in diabetes. Collagen type IV (CIV) is a major component of the BMs, and monitoring the turnover of this protein in type 2 diabetes (T2D) can provide important information about the mechanisms of vascular damage. The aim of the study was through the use of non-invasive biomarkers of CIV (autoantibodies, derivative peptides, and immune complexes) to investigate vascular turnover of CIV in patients with long-term complications of T2D. We measured serum levels of these biomarkers in 59 T2D patients with micro- and/or macrovascular complications and 20 healthy controls using an ELISA. Matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9) were also tested. In the T2D group, significantly lower levels of CIV markers and significantly higher levels of MMP-2 and MMP-9 were found compared to controls. A significant positive correlation was found between IgM antibody levels against CIV and MMP-2. These findings suggest that vascular metabolism of CIV is decreased in T2D with long-term complications and show that a positive linear relationship exists between MMP-2 levels and CIV turnover in the vascular wall.


Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3702
Author(s):  
Anna Siemiątkowska ◽  
Maciej Bryl ◽  
Katarzyna Kosicka-Noworzyń ◽  
Jakub Tvrdoň ◽  
Iwona Gołda-Gocka ◽  
...  

Prognosis of advanced non-small cell lung carcinoma (NSCLC) is poor. Even though it can improve with anti-PD-1/PD-L1 agents, most patients do not respond to treatment. We hypothesized that the serum soluble form of the unit α of the interleukin-2 receptor (sCD25) could be used as a biomarker of successful immunotherapy in NSCLC. We recruited patients dosed with atezolizumab (n = 42) or pembrolizumab (n = 20) and collected samples at baseline and during the treatment. Levels of sCD25 were quantified with the ELISA kits. Patients with a high sCD25 at baseline (sCD25.0 ≥ 5.99 ng/mL) or/and at the end of the fourth treatment cycle (sCD25.4 ≥ 7.73 ng/mL) progressed faster and lived shorter without the disease progression and serious toxicity. None of the patients with high sCD25 at both time points continued therapy longer than 9.3 months, while almost 40% of patients with low sCD25 were treated for ≥12.3 months. There was a 6.3-times higher incidence of treatment failure (HR = 6.33, 95% CI: 2.10–19.06, p = 0.001) and a 6.5-times higher incidence of progression (HR = 6.50, 95% CI: 2.04–20.73, p = 0.002) in patients with high compared with low sCD25.0 and sCD25.4. Serum levels of sCD25 may serve as a non-invasive biomarker of long-term benefits from the anti-PD-1/PD-L1s in NSCLC.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Francesco Santoro ◽  
Tecla Zimotti ◽  
Adriana Mallardi ◽  
Alessandra Leopizzi ◽  
Enrica Vitale ◽  
...  

AbstractTakotsubo syndrome (TTS) is an acute heart failure syndrome with significant rates of in and out-of-hospital mayor cardiac adverse events (MACE). To evaluate the possible role of neoplastic biomarkers [CA-15.3, CA-19.9 and Carcinoembryonic Antigen (CEA)] as prognostic marker at short- and long-term follow-up in subjects with TTS. Ninety consecutive subjects with TTS were enrolled and followed for a median of 3 years. Circulating levels of CA-15.3, CA-19.9 and CEA were evaluated at admission, after 72 h and at discharge. Incidence of MACE during hospitalization and follow-up were recorded. Forty-three (46%) patients experienced MACE during hospitalization. These patients had increased admission levels of CEA (4.3 ± 6.2 vs. 2.2 ± 1.5 ng/mL, p = 0.03). CEA levels were higher in subjects with in-hospital MACE. At long term follow-up, CEA and CA-19.9 levels were associated with increased risk of death (log rank p < 0.01, HR = 5.3, 95% CI 1.9–14.8, HR = 7.8 95% CI 2.4–25.1, respectively, p < 0.01). At multivariable analysis levels higher than median of CEA, CA-19.9 or both were independent predictors of death at long term (Log-Rank p < 0.01). Having both CEA and CA-19.9 levels above median (> 2 ng/mL, > 8 UI/mL respectively) was associated with an increased risk of mortality of 11.8 (95% CI 2.6–52.5, p = 0.001) at follow up. Increased CEA and CA-19.9 serum levels are associated with higher risk of death at long-term follow up in patients with TTS. CEA serum levels are correlated with in-hospital MACE.


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