• 【CCSVI-A。在互联网时代呼吁临床医生和科学家发声。】 复制标题 收藏 收藏
    DOI:10.1016/j.msard.2013.10.005 复制DOI
    作者列表:Gafson AR,Giovannoni G
    BACKGROUND & AIMS: :In 2008, Paulo Zamboni pioneered the 'liberation procedure' for treating multiple sclerosis (MS), claiming that MS is caused by an abnormality of venous drainage which he called chronic cerebrospinal venous insufficiency (CCSVI). CCSVI has been very controversial, both socio-politically and scientifically after going 'viral' via social media. In late 2012, only 56 original scientific research papers had been published on the 'CCSVI syndrome'; however, over 1,150,000 hits on Google existed when searching for the term 'chronic cerebrospinal venous insufficiency' or CCSVI. It is unclear whether the scientific community's response to CCSVI was influenced by Zamboni's original articles, a reactionary response to the 'social phenomenon' of CCSVI or indeed a complex interplay between both these factors. Furthermore, the epidemiology of this 'social phenomenon' remains un-investigated. A PubMed literature search revealed that the greatest level of public interest in CCSVI, as measured by Google Trends, occurred after only 30% of primary articles and 11% of negative studies were submitted for publication. The epicentre of social epidemic has been divided between Italy and Canada. Whilst Canadian scientists had yet to publish a primary article on CCSVI, it had a relative 76% search volume on Google Trends. It is likely that this public interest was sparked by media and political opportunism and fuelled by social media that was disconnected from the scientific community. Our findings call for a concerted effort for clinicians and scientists to engage with the public to ensure that uptake and spread of scientific discoveries via social media are viewed and interpreted in an appropriate context. Examples of how this may be achieved will also be discussed.
    背景与目标: :Paulo Zamboni于2008年率先提出了用于治疗多发性硬化症(MS)的“解放程序”,声称MS是由静脉引流异常引起的,他将其称为慢性脑脊髓静脉功能不全(CCSVI)。通过社交媒体“病毒式传播”后,CCSVI在社会政治和科学方面都引起了很大争议。 2012年底,关于“ CCSVI综合征”的科研论文仅发表了56篇;但是,在搜索“慢性脑脊髓静脉功能不全”或CCSVI一词时,在Google上的点击量超过1,150,000。目前尚不清楚科学界对CCSVI的反应是否受到Zamboni原始文章的影响,对CCSVI的“社会现象”的反应性反应,还是受这两个因素之间复杂的相互作用影响。此外,尚未对这种“社会现象”的流行病学进行调查。 PubMed文献搜索显示,按Google趋势衡量,对CCSVI的最大公众兴趣是在只有30%的主要文章和11%的负面研究提交发表后才发生的。社会流行病的重心已经在意大利和加拿大之间划分。尽管加拿大科学家尚未在CCSVI上发表主要文章,但其在Google趋势中的搜索量却占76%。这种公共利益很可能是由媒体和政治机会主义引发的,而与科学界脱节的社交媒体也推动了这种公共利益。我们的发现要求临床医生和科学家齐心协力,与公众互动,以确保在适当的情况下查看和解释通过社交媒体进行的科学发现的吸收和传播。还将讨论如何实现此目的的示例。
  • 【病人报告的颅外静脉治疗益处:不列颠哥伦比亚省CCSVI注册中心。】 复制标题 收藏 收藏
    DOI:10.1017/cjn.2017.27 复制DOI
    作者列表:Sadovnick AD,Yee IM,Attwell-Pope K,Keyes G,Kipp L,Traboulsee AL
    BACKGROUND & AIMS: :Objective Chronic cerebrospinal venous insufficiency (CCSVI) has been hypothesized to be a risk factor for multiple sclerosis (MS). Venoplasty has been proposed as a treatment for CCSVI. The aim of our study was to gain a better understanding of the "real-world" safety and longitudinal effectiveness of venoplasty Methods: British Columbia residents who self-reported having had venoplasty and consented to participate in the study were interviewed and followed for up to 24 months post-therapy using standardized structured questionnaires Results: Participants reported procedure-related complications (11.5%) and complications within the first month after the procedure (17.3%). Initially, more than 40% of participants perceived that the venoplasty had had positive effects on their health conditions, such as fatigue, numbness, balance, concentration/memory and mobility. However, this improvement was not maintained over time Conclusions: Follow-up patient-reported outcomes indicated that the initial perception of the positive impact of venoplasty on the health conditions of MS patients was not sustained over time. In addition, venoplasty was not without associated morbidity.
    背景与目标: :客观性慢性脑脊髓静脉功能不全(CCSVI)被认为是多发性硬化症(MS)的危险因素。静脉成形术已被提议作为CCSVI的治疗方法。我们的研究目的是为了更好地了解静脉成形术的“现实世界”安全性和纵向有效性。方法:对自我报告患有静脉成形术并同意参加该研究的不列颠哥伦比亚省居民进行了采访,并进行了随访。治疗后24个月,使用标准化结构化问卷调查结果:参与者报告了与手术相关的并发症(11.5%)和手术后第一个月内的并发症(17.3%)。最初,超过40%的参与者认为静脉成形术对他们的健康状况产生了积极的影响,例如疲劳,麻木,平衡,注意力/记忆力和活动能力。但是,随着时间的推移,这种改善并未保持。结论:随访患者报告的结果表明,随着时间的流逝,对静脉成形术对MS患者健康状况的积极影响的最初认识并没有持续。此外,静脉成形术并非没有相关的发病率。
  • 【后CCSVI时代的复原力,信任和公民参与。】 复制标题 收藏 收藏
    DOI:10.1186/s12913-018-3130-x 复制DOI
    作者列表:Benjaminy S,Schepmyer A,Illes J,Traboulsee A
    BACKGROUND & AIMS: BACKGROUND:Scientific and financial investments in chronic cerebrospinal venous insufficiency (CCSVI) research have been made to address both the hope for and scepticism over this interventional strategy for MS. Despite limited evidence in support of the CCSVI hypothesis, the funding of clinical research was responsive to a demand by the public rarely seen in the history of medicine. We characterize patient perspectives about the CCSVI research trajectory, with particular attention to its impact on other non-pharmaceutical areas of MS research with a focus on stem cell interventions. METHODS:Semi-structured interviews with 20 MS patients across Canada who did not have CCSVI interventions. Interviews were analysed for recurring themes and individual variations using the constant comparative approach. RESULTS:Participants had a critical view of the divestment of funds from longstanding research to support CCSVI trials. They retain a sense of optimism, however, about emerging evidence for stem cell interventions for MS, and highlight the need for greater caution and conscientious communication of advances in medicine and science. CONCLUSIONS:The unrealized hopes for CCSVI challenged but did not undermine the resilience of patient communities. The narrative that unfolded highlights the importance of drawing a socially-minded space for public participation in science.
    背景与目标: 背景:在慢性脑脊髓静脉功能不全(CCSVI)研究中进行了科学和财政投资,以解决对MS的这种干预策略的希望和怀疑态度。尽管支持CCSVI假说的证据有限,但临床研究的资金还是对公众的需求做出了回应,而公众的需求在医学史上很少见。我们刻画了患者对CCSVI研究轨迹的观点,特别关注了它对MS研究的其他非药物领域的影响,重点是干细胞干预。
    方法:对加拿大20例未接受CCSVI干预的MS患者进行半结构式访谈。使用不变的比较方法,对访谈进行了主题重复和个体变化的分析。
    结果:参与者对从长期研究中撤资以支持CCSVI试验的观点持批判性看法。然而,他们对MS的干细胞干预的新证据仍保持乐观的态度,并强调需要对医学和科学的进步给予更多的谨慎和认真的沟通。
    结论:对CCSVI的未实现的希望挑战了,但并未破坏患者社区的复原力。展开的叙述突出了为公众参与科学绘制具有社会意识的空间的重要性。
  • 【多发性硬化症患者CCSVI程序的医疗旅游:一项观察性研究。】 复制标题 收藏 收藏
    DOI:10.1017/cjn.2015.350 复制DOI
    作者列表:Metz LM,Greenfield J,Marrie RA,Jette N,Blevins G,Svenson LW,Alikhani K,Wall W,Dhaliwal R,Suchowersky O
    BACKGROUND & AIMS: BACKGROUND:Many Canadians with multiple sclerosis (MS) have recently travelled internationally to have procedures for a putative condition called chronic cerebrospinal venous insufficiency (CCSVI). Here, we describe where and when they went and describe the baseline characteristics of persons with MS who participated in this non-evidence-based medical tourism for CCSVI procedures. METHODS:We conducted a longitudinal observational study that used online questionnaires to collect patient-reported information about the safety, experiences, and outcomes following procedures for CCSVI. A convenience sample of all Albertans with MS was recruited between July 2011 and March 2013. RESULTS:In total, 868 individuals enrolled; 704 were included in this cross-sectional, baseline analysis. Of these, 128 (18.2%) participants retrospectively reported having procedures for CCSVI between April 2010 and September 2012. The proportion of participants reporting CCSVI procedures declined from 80 (62.5%) in 2010, to 40 (31.1%) in 2011, and 8 (6.3%) in 2012. In multivariable logistic regression analysis, CCSVI procedures were independently associated with longer disease duration, secondary progressive clinical course, and greater disability status. CONCLUSIONS:Although all types of people with MS pursued procedures for CCSVI, a major driver of participation was greater disability. This highlights that those with the greatest disability are the most vulnerable to unproven experimental procedures. Participation in CCSVI procedures waned over time possibly reflecting unmet expectations of treated patients, decreased media attention, or that individuals who wanted procedures had them soon after the CCSVI hypothesis was widely publicized.
    背景与目标: 背景:许多多发性硬化症(MS)的加拿大人最近已出国旅行,寻求一种称为慢性脑脊髓静脉功能不全(CCSVI)的推定性疾病的治疗程序。在这里,我们描述了他们去哪儿,什么时候去,并描述了参加这种非循证医学旅行的CCSVI程序的MS患者的基线特征。
    方法:我们进行了一项纵向观察性研究,该研究使用在线问卷收集了患者报告的有关CCSVI程序的安全性,经验和结果的信息。我们在2011年7月至2013年3月期间收集了所有艾伯塔省MS患者的便利样本。
    结果:共计868人入组; 704个样本包含在此横断面基线分析中。在这些参与者中,有128名(18.2%)回顾性地报告了在2010年4月至2012年9月之间进行CCSVI程序的参与者。报告CCSVI程序的参与者的比例从2010年的80(62.5%)下降到2011年的40(31.1%)和8 (6.3%)在2012年。在多变量Logistic回归分析中,CCSVI程序与疾病持续时间较长,继发性进行性临床病程以及更高的残疾状况独立相关。
    结论:尽管所有类型的MS患者都遵循CCSVI程序,但参与的主要动力是更大的残疾。这突出表明,残障最大的人最容易受到未经证实的实验程序的伤害。随着时间的流逝,参与CCSVI程序的人数逐渐减少,这可能反映出对治疗患者的期望未得到满足,媒体关注度降低,或者在广泛宣传CCSVI假设后,想要进行该程序的人很快就接受了该程序。
  • 5 Regarding CCSVI: is blinding the key? 复制标题 收藏 收藏

    【关于CCSVI:是盲目的钥匙吗?】 复制标题 收藏 收藏
    DOI:10.1016/j.ejvs.2011.10.012 复制DOI
    作者列表:Zamboni P,Weinstock-Guttman B,Zivadinov R
    BACKGROUND & AIMS: -2
    背景与目标: -2
  • 【使用超声筛查慢性脑脊髓静脉功能不全(CCSVI):方案建议。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Nicolaides AN,Morovic S,Menegatti E,Viselner G,Zamboni P
    BACKGROUND & AIMS: :Chronic cerebrospinal venous insufficiency (CCSVI) is a syndrome characterized by stenoses or obstructions of the internal jugular and/or azygos veins with disturbed flow and formation of collateral venous channels. Ultrasound and venographic studies of the internal jugular and azygos venous systems in patients with multiple sclerosis (MS) have demonstrated a high prevalence of CCSVI (mean 71%, range 0-100%; n=1336) associated with activation of collaterals. By contrast, ultrasound and venographic examinations of normal controls and patients without MS have demonstrated a much lower prevalence (mean 7.1%, range 0-22%; n=505). Ultrasound in the form of duplex scanning uses a combination of physiological measurements as well as anatomical imaging and has been used for the detection of CCSVI by different centers with variable results. A high prevalence of obstructive lesions, ranging from 62% to 100%, has been found by some teams in patients with MS compared with a low prevalence (0-25%) in controls. However, others have reported absence of these lesions or a lower prevalence (16-52%). This variability could be the result of differences in technique, training, experience or criteria used. In order to ensure a high reproducibility of duplex scanning with comparable accuracy between centers a detailed protocol with standard methodology and criteria is needed. Also, standardization of the method of reporting of duplex measurements and other findings will facilitate validation of the proposed criteria by different centers. The aim of this document is to produce recommendations for such a protocol and indicate what future research is needed in order to address areas of uncertainty.
    背景与目标: :慢性脑脊髓静脉功能不全(CCSVI)是一种综合征,其特征是颈内和/或合子静脉狭窄或阻塞,血流不畅,并形成侧支静脉通道。患有多发性硬化症(MS)的患者的颈内静脉和合子静脉系统的超声和静脉造影研究表明,CCSVI的患病率很高(平均值为71%,范围为0-100%; n = 1336),与侧支的激活相关。相比之下,正常对照和无MS患者的超声和静脉造影检查显示患病率要低得多(平均7.1%,范围为0-22%; n = 505)。双工扫描形式的超声结合了生理学测量和解剖学成像,已被不同中心用于检测CCSVI,结果各不相同。一些研究小组发现,MS患者阻塞性病变的患病率较高,范围从62%到100%,而对照组的患病率较低(0-25%)。但是,其他人则报告没有这些病变或患病率较低(16-52%)。这种差异可能是所使用的技术,培训,经验或标准不同的结果。为了确保在各个中心之间具有相当的准确性的双面扫描具有很高的重现性,需要使用标准方法和标准的详细协议。同样,双相测量和其他发现的报告方法的标准化将有助于不同中心对提议标准的验证。本文档旨在为此类协议提供建议,并指出需要进行哪些进一步的研究以解决不确定性领域。
  • 【经皮腔内血管成形术治疗多发性硬化症患者的慢性脑脊髓静脉功能不全(CCSVI)。】 复制标题 收藏 收藏
    DOI:10.1002/14651858.CD009903.pub3 复制DOI
    作者列表:Jagannath VA,Pucci E,Asokan GV,Robak EW
    BACKGROUND & AIMS: BACKGROUND:Multiple sclerosis (MS) is a leading cause of neurological disability in young adults. The most widely accepted hypothesis regarding its pathogenesis is that it is an immune-mediated disease. It has been hypothesised that intraluminal defects, compression, or hypoplasia in the internal jugular or azygos veins may be important factors in the pathogenesis of MS. This condition has been named 'chronic cerebrospinal venous insufficiency' (CCSVI). It has been suggested that these intraluminal defects restrict the normal blood flow from the brain and spinal cord, causing the deposition of iron in the brain and the eventual triggering of an auto-immune response. The proposed treatment for CCSVI is venous percutaneous transluminal angioplasty (PTA), which is claimed to improve the blood flow in the brain thereby alleviating some of the symptoms of MS. This is an update of a review first published in 2012. OBJECTIVES:To assess the benefit and safety of venous PTA in people with MS and CCSVI. SEARCH METHODS:We searched the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group's Specialised Register up to 30 August 2018, CENTRAL (in the Cochrane Library 2018, issue 8), MEDLINE up to 30 August 2018, Embase up to 30 August 2018, metaRegister of Controlled Trials, ClinicalTrials.gov., the Australian New Zealand Clinical Trials Registry, and the World Health Organization (WHO) International Clinical Trials Registry platform. We examined the bibliographies of the included and excluded studies. SELECTION CRITERIA:We included randomised controlled trials (RCTs) in which PTA and sham interventions were compared in adults with MS and CCSVI. DATA COLLECTION AND ANALYSIS:Two authors independently assessed study eligibility and risk of bias, and extracted data. We reported results as risk ratios (RR) with 95% confidence intervals (CI). We performed statistical analyses using the random-effects model; and we assessed the certainty of the evidence using GRADE. MAIN RESULTS:We included three RCTs (238 participants) in this update. One hundred and thirty-four participants were randomised to PTA and 104 to sham treatment. We attributed low risk of bias to two (67%) studies for sequence generation and two (67%) studies for performance bias. All studies were at a low risk of detection bias, attrition bias, reporting bias and other potential sources of bias.There was moderate-quality evidence to suggest that venous PTA did not increase the proportion of patients who had operative or post-operative serious adverse events compared with the sham procedure (RR 3.33, 95% CI 0.36 to 30.44; 3 studies, 238 participants); nor did it increase the proportion of patients who improved on a functional composite measure including walking control, balance, manual dexterity, postvoid residual urine volume, and visual acuity over 12-month follow-up (RR 0.84, 95% CI 0.55 to 1.30; 1 study, 110 participants); nor did it reduce the proportion of patients who experienced new relapses at six- or 12-month follow-up (RR 0.87, 95% CI 0.51 to 1.49; 3 studies, 235 participants). There was no effect of venous PTA on disability worsening measured by the Expanded Disability Status Scale, which was reported at follow-up intervals of six months (one study), 11 months (one study) and 12 months (one study). Quality of life was reported in two studies with no difference between treatment groups. Moderate or severe pain during or post venography was reported in both PTA and sham-procedure participants in all included studies. Venous PTA was not effective in restoring blood flow assessed at one-month (one study) or 12-month follow-up (one study). AUTHORS' CONCLUSIONS:This systematic review identified moderate-quality evidence that, compared with sham procedure, venous PTA intervention did not provide benefit on patient-centred outcomes (disability, physical or cognitive functions, relapses, quality of life) in people with MS. Venous PTA has proven to be a safe technique but in view of the available evidence of its ineffectiveness, this intervention cannot be recommended in people with MS. All ongoing trials were withdrawn or terminated and hence this updated review is conclusive. No further randomised clinical studies are needed.
    背景与目标: 背景:多发性硬化症(MS)是年轻人神经系统残疾的主要原因。关于其发病机理的最广泛接受的假设是它是一种免疫介导的疾病。已经假设颈内静脉或合子静脉内腔内缺损,压迫或发育不全可能是MS发病机理中的重要因素。这种情况被称为“慢性脑脊髓静脉功能不全”(CCSVI)。已经提出这些管腔内缺陷限制了来自脑和脊髓的正常血流,导致铁在脑中的沉积并最终触发了自身免疫反应。提议的CCSVI治疗方法是静脉经皮腔内血管成形术(PTA),据称可改善大脑中的血流,从而减轻MS的某些症状。这是2012年首次发布的评论的更新。
    目的:评估静脉PTA对MS和CCSVI患者的益处和安全性。
    搜索方法:我们搜索了截至2018年8月30日的中枢神经系统小组专业注册的Cochrane多发性硬化症和罕见病,CENTRAL(位于Cochrane图书馆2018年第8期),MEDLINE截至2018年8月30日,Embase截至8月30日2018年,对照试验的metaRegister,ClinicalTrials.gov。,澳大利亚新西兰临床试验注册中心和世界卫生组织(WHO)国际临床试验注册平台。我们检查了包括和排除研究的参考书目。
    选择标准:我们纳入了随机对照试验(RCT),其中比较了患有MS和CCSVI的成年人的PTA和假手术。
    数据收集与分析:两位作者独立评估了研究的资格和偏倚风险,并提取了数据。我们将结果报告为具有95%置信区间(CI)的风险比(RR)。我们使用随机效应模型进行了统计分析;我们使用GRADE评估了证据的确定性。
    主要结果:我们在此更新中包括了三个RCT(238名参与者)。一百三十四名参与者被随机分配到PTA,104名被随机分配到假治疗。我们将偏倚的低风险归因于两项(67%)的序列生成研究和两项(67%)的性能偏向研究。所有研究的检测偏倚,损耗偏倚,报告偏倚和其他潜在偏倚的风险均较低。有中等质量的证据表明静脉PTA不会增加手术或术后严重不良反应患者的比例与假手术相比的事件(RR 3.33,95%CI 0.36至30.44; 3个研究,238名参与者);在12个月的随访中,使用步行控制,平衡,手部敏捷度,术后剩余尿量和视敏度等功能性综合指标改善的患者比例也没有增加(RR 0.84,95%CI 0.55至1.30; 1个研究,110个参与者);也没有减少在6或12个月的随访中出现新复发的患者比例(RR 0.87,95%CI 0.51至1.49; 3个研究,235名参与者)。用扩展的残疾状况量表衡量,静脉PTA对残疾恶化没有影响,据报道,随访间隔为六个月(一项研究),11个月(一项研究)和12个月(一项研究)。两项研究报告了生活质量,治疗组之间无差异。在所有纳入研究中,PTA和假手术参与者均报告了静脉造影期间或之后的中度或重度疼痛。在一个月(一项研究)或12个月随访(一项研究)中评估的静脉PTA不能有效恢复血流。
    作者的结论:该系统评价确定了中等质量的证据,与假手术相比,静脉PTA干预对以MS为中心的以患者为中心的结果(残疾,身体或认知功能,复发,生活质量)没有好处。静脉PTA已被证明是一种安全的技术,但鉴于现有证据表明其无效,因此不建议在MS患者中推荐这种干预措施。所有正在进行的试验都已撤回或终止,因此本次更新的审查是结论性的。无需进一步的随机临床研究。
  • 【经皮腔内血管成形术治疗多发性硬化症患者的慢性脑脊髓静脉功能不全(CCSVI)。】 复制标题 收藏 收藏
    DOI:10.1002/14651858.CD009903.pub2 复制DOI
    作者列表:van Zuuren EJ,Fedorowicz Z,Pucci E,Jagannath VA,Robak EW
    BACKGROUND & AIMS: :Does accelerated cortical atrophy in aging, especially in areas vulnerable to early Alzheimer's disease (AD), unequivocally signify neurodegenerative disease or can it be part of normal aging? We addressed this in 3 ways. First, age trajectories of cortical thickness were delineated cross-sectionally (n = 1100) and longitudinally (n = 207). Second, effects of undetected AD on the age trajectories were simulated by mixing the sample with a sample of patients with very mild to moderate AD. Third, atrophy in AD-vulnerable regions was examined in older adults with very low probability of incipient AD based on 2-year neuropsychological stability, CSF Aβ(1-42) levels, and apolipoprotein ε4 negativity. Steady decline was seen in most regions, but accelerated cortical thinning in entorhinal cortex was observed across groups. Very low-risk older adults had longitudinal entorhinal atrophy rates similar to other healthy older adults, and this atrophy was predictive of memory change. While steady decline in cortical thickness is the norm in aging, acceleration in AD-prone regions does not uniquely signify neurodegenerative illness but can be part of healthy aging. The relationship between the entorhinal changes and changes in memory performance suggests that non-AD mechanisms in AD-prone areas may still be causative for cognitive reductions.
    背景与目标: :衰老中的皮质萎缩加速,特别是在容易患早老性阿尔茨海默氏病(AD)的地区,是否明确表示神经退行性疾病或它是否可以成为正常衰老的一部分?我们通过3种方式解决了这个问题。首先,在横截面(n = 1100)和纵向(n = 207)上划定了皮质厚度的年龄轨迹。其次,通过将样本与患有轻度至中度AD的患者样本混合来模拟未检测到的AD对年龄轨迹的影响。第三,根据2年的神经心理学稳定性,脑脊液Aβ(1-42)水平和载脂蛋白ε4阴性,检查了成年人AD弱势地区的萎缩,其发生AD的可能性非常低。在大多数地区都观察到稳定的下降,但是在各组中观察到内嗅皮层的皮层加速变薄。非常低风险的老年人的纵向内脏萎缩率与其他健康的老年人相似,并且该萎缩可预测记忆力的改变。尽管皮层厚度的持续下降是衰老的常态,但AD易发地区的加速并不唯一表示神经退行性疾病,而是健康衰老的一部分。内嗅变化与记忆性能变化之间的关系表明,AD易发地区的非AD机制可能仍然是导致认知能力下降的原因。
  • 【MS患者中CCSVI的发生及其与铁代谢和静脉曲张的关系。】 复制标题 收藏 收藏
    DOI:10.1111/ene.12010 复制DOI
    作者列表:Van den Berg PJ,Van den Berg GB,Westerhuis LW,Visser LH
    BACKGROUND & AIMS: :We have previously demonstrated that the concentration of normal prion proteins (PrP(C)) is increased in the serum and cerebrospinal fluid (CSF) of rats deficient in vitamin B(12) (cobalamin, Cbl). In this study, we investigated whether similar increases also occur in the serum and CSF of patients deficient in Cbl (Cbl-D), and whether the increase in serum levels can be corrected by Cbl therapy. The study involved two sample populations. The first consisted of 45 patients (13 patients with pernicious anemia [PA], 19 with other forms of anemia, and 13 healthy controls); and the second, 68 patients (five with subacute combined degeneration [SCD], 18 with amyotrophic lateral sclerosis, 22 with multiple sclerosis [MS], and 23 neurological controls). Serum PrP(C) levels were measured using an enzyme-linked-immunosorbent-assay before as well as after Cbl therapy. The mean serum PrP(C) levels in patients with PA were significantly higher than those of the controls (p=0.0017) but normalized after Cbl therapy; there was no significant change in the patients with other forms of anemia. Mean CSF PrP(C) levels in the patients with SCD were significantly higher than in the neurological controls (p<0.03). The serum and CSF PrP(C) levels of patients with PA and those with SCD were correlated significantly with serum (p=0.004) and CSF (p=0.0018) Cbl levels. In patients with MS, CSF PrP(C) concentrations were significantly lower than those of the controls regardless of their CSF Cbl levels. We found a correlation between Cbl and PrP(C) levels in the serum and CSF of Cbl-D patients, which suggests that Cbl may regulate the PrP(C) levels in the serum and CSF in humans.
    背景与目标: :我们先前已经证明,缺乏维生素B(12)(钴胺素,Cbl)的大鼠的血清和脑脊液(CSF)中正常病毒蛋白(PrP(C))的浓度会增加。在这项研究中,我们调查了Cbl缺乏症患者(Cbl-D)的血清和CSF是否也发生了类似的增加,以及是否可以通过Cbl治疗来纠正血清水平的增加。该研究涉及两个样本人群。第一名包括45例患者(13例恶性贫血[PA],19例其他形式的贫血和13例健康对照者);其次是68例患者(其中5例患有亚急性合并变性[SCD],18例患有肌萎缩性侧索硬化症,22例患有多发性硬化症[MS]和23例神经系统控制)。在Cbl治疗之前和之后,使用酶联免疫吸附测定法测量血清PrP(C)水平。 PA患者的平均血清PrP(C)水平显着高于对照组(p = 0.0017),但在Cbl治疗后恢复正常;其他形式的贫血患者无明显变化。 SCD患者的平均CSF PrP(C)水平显着高于神经系统对照(p <0.03)。 PA患者和SCD患者的血清和CSF PrP(C)水平与血清​​(p = 0.004)和CSF(p = 0.0018)Cbl水平显着相关。在MS患者中,无论其CSF Cbl水平如何,CSF PrP(C)浓度均显着低于对照组。我们发现Cbl-D患者的血清和CSF中Cbl和PrP(C)水平之间存在相关性,这表明Cbl可能调节人类血清和CSF中的PrP(C)水平。
  • 【认知障碍和“看不见的症状”与MS中的CCSVI不相关。】 复制标题 收藏 收藏
    DOI:10.1186/1471-2377-13-97 复制DOI
    作者列表:Leone C,D'Amico E,Cilia S,Nicoletti A,Di Pino L,Patti F
    BACKGROUND & AIMS: BACKGROUND & AIMS:Previous studies have shown that hepatitis B virus (HBV) interferes with host antiviral immunity via multiple pathways. In clinical practice, interferon resistance is a serious issue for treatment of HBV infection. Now, miRNAs have been reported to be widely involved in antiviral immunity and have become a novel tool to study virus-host interaction. We question whether miRNAs play a role in HBV-induced interferon resistance in hepatocytes. METHODS:MiRNAs levels in HepG2 and HepG2.2.15 cells were compared by qRT-PCR. The effects of miR146a on HBV infection were characterized by interference miR146a level, followed by the quantification of HBV mRNA, DNA and antigens. We employed qRT-PCR and western blot to study the effects of miR146a on the IFN-α signalling pathway. The miR146a promoter activity was validated by a luciferase reporter assay. RESULTS:HBV infection impaired IFN-α signalling pathway in hepatocytes. MiR146a was upregulated in HBV+ HepG2.2.15 cells, and the transcriptional activity of miR146a in HepG2.2.15 cells was increased compared with HepG2 cells. HBV infection, especially the introduction of HBx, induced miR146a expression in vitro. Moreover, miR146a attenuated the production of type I interferon-induced antiviral factors. Low STAT1 levels were noticed in HBV+ HCC cells, and the luciferase reporter assay showed that STAT1 was post-transcriptionally downregulated by miR146a. Furthermore, the silencing of miR146a by antisense inhibitors enhanced IFN-α-mediated anti-HBV efficiency. CONCLUSIONS:Our findings demonstrate that HBV infection promotes miR146a transcription, which represses STAT1 and results in interferon resistance. These observations reveal a novel role for miR146a in HBV immunopathogenesis, and provide a potential target for the therapeutic recovery of IFN-α-induced anti-HBV effects.
    背景与目标: 背景与目的:先前的研究表明,乙型肝炎病毒(HBV)通过多种途径干扰宿主的抗病毒免疫。在临床实践中,干扰素耐药性是治疗HBV感染的严重问题。现在,据报道,miRNA广泛参与抗病毒免疫,并已成为研究病毒-宿主相互作用的新工具。我们质疑miRNA是否在HBV诱导的肝细胞干扰素抗性中发挥作用。
    方法:采用qRT-PCR技术比较HepG2和HepG2.2.15细胞中的miRNA水平。 miR146a对HBV感染的作用以干扰miR146a水平为特征,然后对HBV mRNA,DNA和抗原进行定量。我们采用qRT-PCR和western blot研究miR146a对IFN-α信号通路的影响。 miR146a启动子活性已通过荧光素酶报告基因分析验证。
    结果:HBV感染损害了肝细胞中的IFN-α信号通路。 HBV HepG2.2.15细胞中MiR146a上调,与HepG2细胞相比,miR146a在HepG2.2.15细胞中的转录活性增加。 HBV感染(尤其是HBx的引入)在体外诱导miR146a表达。此外,miR146a减弱了I型干扰素诱导的抗病毒因子的产生。在HBV HCC细胞中发现STAT1水平较低,荧光素酶报告基因检测结果表明miR146a在转录后下调了STAT1。此外,反义抑制剂对miR146a的沉默增强了IFN-α介导的抗HBV效率。
    结论:我们的研究结果表明,HBV感染可促进miR146a转录,从而抑制STAT1并导致干扰素耐药。这些发现揭示了miR146a在HBV免疫发病机制中的新作用,并为IFN-α诱导的抗HBV作用的治疗性恢复提供了潜在的靶点。
  • 【CCSVI和铁在多发性硬化症中的争议:铁蛋白是关键吗?】 复制标题 收藏 收藏
    DOI:10.1212/WNL.0b013e3181fb44f0 复制DOI
    作者列表:van Rensburg SJ,van Toorn R
    BACKGROUND & AIMS:
    背景与目标:
  • 【多发性硬化症患者的CCSVI血管内治疗:462例临床结果。】 复制标题 收藏 收藏
    DOI:10.1007/s10072-013-1300-5 复制DOI
    作者列表:
    BACKGROUND & AIMS:
    背景与目标:
  • 【指示CCSVI的颅外静脉异常的多模式无创和有创成像:PREMiSe初步研究的结果。】 复制标题 收藏 收藏
    DOI:10.1186/1471-2377-13-151 复制DOI
    作者列表:Zivadinov R,Karmon Y,Dolic K,Hagemeier J,Marr K,Valnarov V,Kennedy CL,Hojnacki D,Carl EM,Hopkins LN,Levy EI,Weinstock-Guttman B,Siddiqui AH
    BACKGROUND & AIMS:
    背景与目标:
  • 【陷入双赢局面:多发性硬化症患者及其神经科医生之间有关CCSVI的讨论-定性研究。】 复制标题 收藏 收藏
    DOI:10.1186/s12883-017-0954-7 复制DOI
    作者列表:Driedger SM,Maier R,Marrie RA,Brouwers M
    BACKGROUND & AIMS: BACKGROUND:In recent years, shared decision making (SDM) has been promoted as a model to guide interactions between persons with MS and their neurologists to reach mutually satisfying decisions about disease management - generally about deciding treatment courses of prevailing disease modifying therapies. In 2009, Dr. Paolo Zamboni introduced the world to his hypothesis of Chronic Cerebrospinal Venous Insufficiency (CCSVI) as a cause of MS and proposed venous angioplasty ('liberation therapy') as a potential therapy. This study explores the discussions that took place between persons with MS (PwMS) and their neurologists about CCSVI against the backdrop of the recent calls for the use of SDM to guide clinical conversations. METHODS:In 2012, study researchers conducted focus groups with PwMS (n = 69) in Winnipeg, Canada. Interviews with key informants were also carried out with 15 participants across Canada who were stakeholders in the MS community: advocacy organizations, MS clinicians (i.e. neurologists, nurses), clinical researchers, and government health policy makers. RESULTS:PwMS reported a variety of experiences when attempting to discuss CCSVI with their neurologist. Some found that there was little effort to engage in desired discussions or were dissatisfied with critical or cautious stances of their neurologist. This led to communication breakdowns, broken relationships, and decisions to autonomously access alternative opinions or liberation therapy. Other participants were appreciative when clinicians engaged them in discussions and were more receptive to more critical appraisals of the evidence. Key informants reported that they too had heard of neurologists who refused to discuss CCSVI with patients and that neurology as a whole had been particularly vilified for their response to the hypothesis. Clinicians indicated that they had shared information as best they could but recommended against seeking liberation therapy. They noted that being respectful of patient emotions, values, and hope were also key to maintaining good relationships. CONCLUSIONS:While CCSVI proved a challenging context to carry out patient-physician discussions and brought numerous tensions to the surface, following the approach of SDM can minimize the potential for unfortunate outcomes as much as possible because it is based on principles of respect and more two-way communication.
    背景与目标: 背景:近年来,共享决策制定(SDM)已被提倡作为一种模型,以指导MS患者与其神经科医生之间的相互作用,以达成有关疾病管理的相互满意的决策-通常涉及确定流行的疾病改良疗法的治疗过程。在2009年,Paolo Zamboni博士向世界介绍了他的MS病因-慢性脑脊髓静脉功能不全(CCSVI)的假说,并提出了静脉血管成形术(“解放疗法”)作为一种潜在疗法。这项研究探索了在最近使用SDM指导临床对话的背景下,MS(PwMS)患者及其神经病学家之间关于CCSVI的讨论。
    方法:2012年,研究人员在加拿大温尼伯进行了PwMS(n = 69)焦点小组研究。还与加拿大全国15位参与者进行了访谈,他们是MS社区的利益相关者:倡导组织,MS临床医生(即神经病学家,护士),临床研究人员和政府卫生政策制定者。
    结果:PwMS尝试与神经科医生讨论CCSVI时报告了多种经验。一些人发现,他们很少努力进行期望的讨论,或者对神经科医生的批评或谨慎态度不满意。这导致沟通中断,关系破裂,并决定自主获取替代意见或解放疗法。当临床医生让他们参与讨论时,其他参与者会很感激,并且更愿意接受对证据进行更严格的评估。关键线人报告说,他们也听说过神经病学家拒绝与患者讨论CCSVI,并且整个神经病学因其对假说的反应而受到特别谴责。临床医生表示,他们已尽其所能地共享信息,但建议不要寻求解放疗法。他们指出,尊重患者的情感,价值观和希望也是保持良好关系的关键。
    结论:尽管CCSVI证明了进行患者-医师讨论的挑战性环境,并在表面上带来了许多压力,但遵循SDM的方法可以尽可能地将不幸结果的可能性降到最低,因为它基于尊重的原则,另外两个双向通信。
  • 15 A swan song for CCSVI. 复制标题 收藏 收藏

    【CCSVI的天鹅歌曲。】 复制标题 收藏 收藏
    DOI:10.1007/s00270-013-0833-6 复制DOI
    作者列表:Reekers J
    BACKGROUND & AIMS:
    背景与目标:

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