網誌文章搜尋建議

給多發性硬化症MS病友和親友的建議:
如要搜尋站內相關文章可多利用
"搜尋此網誌的文章內容"的功能,這樣就可以快速的找到你想要得資訊而不需要從第一篇開始看了.
有關CCSVI(靜脈血管窄化及手術的資訊)可在相關連結以及相關MS blog內

推薦頻道:Gimmy a break

2011年10月20日 星期四

Meta分析支持 CCSVI和MS之間的關聯性

經過了兩年的研究, 該分析包括在意大利,德國,約旦,和美國數地的比較 CCSVI與非MS患者進行的8項研究。Conclusion;We found a strong association be tween chronic cerebrospinal venous insufficiency and multiple sclerosis.
另外, Dr. Robert J. Fox也提到體內脫水/缺水現象可能會影響血液的流量


ECTRIMS 2011大會上 Dr. Robert J. Fox的專訪

附上原文:

October 19, 2011 — A new meta analysis concludes there is a strong and statistically significant association between chronic cerebrospinal venous insufficiency (CCSVI) and multiple sclerosis (MS), although it raises questions about the blinding of the included studies and the protocol used by technicians evaluating ultrasound results.

However, marked heterogeneity among the studies prevents a definitive conclusion about the role of CCSVI in MS, the researchers add.

"If you're one of those who believes that CCVSI causes MS, I don't think this study tells us that, but conversely, if you're one of the skeptics who says that it's all a bunch of nonsense, this study suggests that maybe that's not the case," lead author Andreas Laupacis, MD, a general internist and executive director, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada, said to Medscape Medical News.

The study was published online October 3 in the Canadian Medical Association Journal.

Ultrasound Parameters

Dr. Andreas Laupacis

The analysis included 8 studies conducted in Italy, Germany, Jordan, and the United States that compared the frequency of CCSVI among patients both with and without MS. One of the studies, by Paolo Zamboni, MD, director of the Vascular Diseases Center at the University of Ferrara, Italy, who first described this potential relationship, found that patients with MS had more abnormalities in the internal jugular and other veins than those without MS, and renewed interest in the vascular theory of MS.

To be included, the studies had to have reported original data in a peer-reviewed publication, used Doppler ultrasonography to detect CCSVI, and included at least 1 control group. The studies enrolled a small number of patients with MS (ranging from 10 to 310), most with relapsing-remitting disease and taking disease-modifying agents, and a small number of control patients (ranging from 7 to 210). All studies included healthy control patients, and 4 also included control patients with a neurological disease other than MS.

All but 1 study described the assessment of the 5 ultrasound parameters for CCVI, one of which is reflux in the internal jugular veins or vertebral veins. The diagnosis of CCSVI requires that a patient have an abnormality in at least 2 of the 5 parameters.

Blinding of the ultrasound technician and the interpreters of images varied among the studies. The method of blinding was well described in only 1 study, poorly described in 2 studies, and "reasonably" well described in 2 others. Three studies were not blinded at all. The success of the blinding was not reported in any study.

"Incredible Variability"

Pooled analysis showed a statistically significant association between CCSVI and MS compared with healthy control patients (odds ratio, 13.5; 95% confidence interval, 2.6 - 71.4), but there was "incredible variability," said Dr. Laupacis. "The Zamboni study found a perfect correlation — everybody with MS had CCSVI, and nobody without MS had it — while 2 other studies found that nobody with MS had CCSVI."

Patients with MS had significantly higher odds than healthy control patients of having reflux in the internal jugular or vertebral veins (odds ratio, 13.7; 95% confidence interval, 2.0 - 93.8) although here, too, there was extensive heterogeneity among study results.

In the comparison with control patients with another neurological disease, CCSVI was more frequent among those patients with MS, but the association was not statistically significant, and heterogeneity among the study results was large. The only ultrasound parameter that was significantly more frequent among patients with MS was reflux in the internal jugular or vertebral veins.

Even when the Zamboni study was removed from the analysis, the odds of CCSVI being more frequent among patients with MS remained statistically significant, although the odds ratio decreased from 13.5 to 4.7.

In an analysis that excluded the Zamboni trial and added one that did not find CCSVI in any patient, the odds ratio was 3.7 and still remained significant.

The analysis highlighted the potential problems with lack of blinding in many of the included studies. "With a borderline test, if you really believed that CCSVI causes MS, you're more likely to call that test positive if you know the person has MS, and you're more likely not to if you know the person doesn't have MS," said Dr. Laupacis. "It's not that you're deliberately trying to cheat, but that's why we blind studies."

Ultrasound Interpretation

The studies varied in terms of the detail they provided about how ultrasounds were interpreted, with the best detail provided in a study published in the July issue of Neurology by Robert Zivadinov, MD, PhD, from the University of Buffalo, New York, and colleagues, said Dr. Laupacis. He added that ultrasound technicians may not use the same standardized technique to assess images.

The results do not mean that CCSVI causes MS; indeed, it could be a consequence of MS. "It could be that MS over a long period of time causes abnormalities in the veins," said Dr. Laupacis.

Ultimately, there just are not enough studies yet to draw firm conclusions, Dr. Laupacis added. "The reason we're convinced that cigarette smoking causes lung cancer is that study after study after study found the same thing; we're clearly not in that situation here with CCSVI and MS."

However, that is changing. Results of other studies being carried out in both Canada and the United States that are investigating the connection between MS and CCSVI are expected within the next year or so, said Dr. Laupacis.

Meanwhile, the meta-analysis will be regularly updated, he said. "Our plan is to update our systematic review about every 3 months, so as new data becomes available, it will be incorporated."

Association Validation

Approached for comment on these findings, Robert J. Fox, MD, neurologist and medical director, Mellen Center for MS, Cleveland Clinic, Ohio, who contributed a commentary that was also published online October 3 in the Canadian Medical Association Journal, said the study validates the association between CCSVI and MS but does not answer the question of why the association exists.

Dr. Robert J. Fox

"The analysis just tells us about the association; it does not tell us whether the association is specific for MS and the disease itself, or whether a therapeutic intervention will or will not improve the MS patient condition. Those are 2 very important issues," Dr. Fox told Medscape Medical News.

The CCSVI could be related to the disease itself, or it could merely indicate an injured brain that could lead to vascular changes in the blood flowing away from the brain, said Dr. Fox.

Interpreting ultrasound images of venous blood flow and anatomy is not as simple and straightforward as a chest X-ray, for example, he said. "There's a lot more finesse and nuance involved in performing these ultrasounds."

Dr. Fox also pointed out that there is potential for bias among people performing the ultrasound, who may use varying techniques, as well as among those reading the results. For example, how hard a technician presses down on the transducer can change the flow and diameter of the jugular vein, and adjusting the machine can make reflux completely resolve or create it where there was not any, said Dr. Fox.

Even something like hydration can affect ultrasound results, he added. Patients with MS tend to prefer to be a little dehydrated to avoid bladder accidents, which can affect venous blood flow.

Diagnostic Issues

In another recent report published in the September issue of Expert Reviews on Neurotherapeutics, Dr. Zivadinov's group also reviewed the evidence to date on CCSVI in the setting of MS. "The idea behind this paper was to provide what we believe is the current knowledge about this problem, to really contribute to the understanding of what the diagnostic issues are with CCSVI," Dr. Zivadinov told Medscape Medical News. "Also, to identify certain pathogenetic mechanisms that might be related to CCSVI in MS; whether they are true or not, the future is going to show."

Dr. Robert Zivadinov

In general, however, he agreed that the literature to date has been less than reliable, with many small observational studies, varied methodology, and what appears to be a bias for studies showing no relationship between CCSVI and MS being published in neurological journals, and those finding positive relationships being published in radiological journals.

The hope was that their article would summarize the current knowledge and point to ways that studies could be improved, as well as give an overview of "5-year" directions for future research, he said.

One of the issues requiring definition is the various venous abnormalities themselves, not just the blockage of venous outflow but also the precise abnormalities that are causing any blockage, he noted. Multimodal studies that use more than 1 imaging technique to examine these abnormalities appear to be more reliable. Intravenous Doppler, for example, is perhaps the most reliable of these modalities, Dr. Zivadinov noted, allowing direct visualization of the abnormalities in the pulsatile venous setting.

"I really think that one of the key messages of this review paper is that we are making clear the importance of a multimodal approach, of standardized guidelines, and of understanding what you are looking at," Dr. Zivadinov concluded. "While there is a common knowledge among radiologists about how to perform diagnostic imaging and intervention on the extracranial vessels, there are no guidelines for CCSVI, and before people begin to do research studies and say it's something or it's not, they should understand the arguments and understand how to do it, and follow some guidelines."

The authors are critical, however, of the so-called Zamboni criteria that outline 5 abnormalities, the presence of 2 or more of which constitute CCSVI. "I think the binary composite of these criteria is probably the major confusion at the moment in the literature," he said. "Basically, if you don't find that second criteria, you are classifying all of your subjects as negative, although the patient or subject may have important venous abnormalities."

Dr. Laupacis receives honoraria as a member of a data safety monitoring board for studies of 2 drugs for MS funded by Novartis Pharmaceuticals. Coauthor Jodie Burton, MD, has received unrestricted educational support and honoraria for speaking and educational engagements from Teva Neuroscience Canada, EMD Serono, and Biogen Idec Canada. The other authors of the Canadian Medical Association Journal article have disclosed no relevant financial relationships. Dr. Fox has served as a consultant for Avanir, Biogen Idec, Genentech, and Novartis; has served on clinical trial advisory committees for Biogen Idec; has received research support from the National Multiple Sclerosis Society, which includes funding to study CCSVI; and serves on the editorial boards of Neurology and Multiple Sclerosis Journal. The authors of the Expert Reviews on Neurotherapeutics article have declared that their CCSVI studies were supported with internal resources of the Buffalo Neuroimaging Analysis Center, Baird MS Center, and Jacobs Neurological Institute, University of Buffalo. In addition, they received support from the Direct MS Foundation, Kaleida-Health, Volcano, Ev3, Codman, the Jacquemin Foundation, the Bronfman Foundation, and smaller donors. Dr. Zivadinov received personal compensation from Teva Neuroscience, Biogen Idec, EMD Serono, and Questcor Pharmaceuticals for speaking and consultancy fees. He received financial support for research activities from Biogen Idec, Teva Neuroscience, Genzyme, Bracco, Questcor Pharmaceuticals, and EMD Serono. Disclosures for other coauthors appear in the paper.

CMAJ. Published online October 3, 2011. Full text, Editorial

Expert Rev Neurother. 2011;11:1277-1294. Abstract

Neurology. 2011;77:138-144. Abstract

再附上原始論文的連結:
http://www.cmaj.ca/content/early/2011/10/03/cmaj.111074.full.pdf

下載之後, 對於比較看不懂英文者, 可以看圖表, 圖2~4中 Increased likelihood
in MS patients(與Ms病人有強烈關聯性者)其Odds Ratio(勝算比), OR都大於1, 且多介於1~10之間
已經顯示出有其關聯性存在.

勝算比 (Odds Ratio, OR) (在病例對照研究中) 實驗組中發生疾病的勝算與控制組中發生疾病的勝算比值, 或罹患疾病的病患暴露於某變因的勝算除以控制組暴露的勝算
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未成年值夜班易罹多發性硬化症

(法新社斯德哥爾摩18日電) 今天發表的瑞典研究報告顯示,青少年值夜班不僅容易疲累,往後罹患多發性硬化症(MS)的風險也顯著增高。

領導卡洛林斯卡研究所(Karolinska Institute)研究團隊的海德斯特洛姆(Anna Hedstroem)發表聲明說:「我們的研究分析披露,在年輕時值夜班與罹患多發性硬化症之間有明顯關連。」

研究報告刊登在「神經學年報」(Annals of Neurology)。研究人員仔細調查兩項瑞典研究的資料,其中一項的研究對象包括自2004年起新診斷出罹患MS的1343人以及無此疾病的控制組 2900人;另一項研究的對象為先前已確診罹患MS的5129人以及控制組的4509人。

所有研究對象的年齡都介於16歲至70歲,且詢問他們有關工作生涯以及是否曾於不正常時段工作。

研究團隊比較不同年齡值夜班(定義為晚間9時至清晨7時的任何時段)研究對象與未值夜班者的MS罹患率。結果令人大感驚訝:研究人員發現,20歲前曾值夜班越長期間者,罹患MS的風險是從未值夜班者的兩倍。

研究人員指出,擾亂人體的畫夜節奏,加上喪失睡眠,可能與罹患MS有關

海德斯特洛姆告訴法新社:「擔任輪班工作,人體的生理時鐘會紊亂,且睡眠品質較差,這些都已證明會影響免疫系統。

她又說,他的研究團隊把其他已知風險因素列入考量,且研究的假設是輪值夜班可能會升高罹患MS的風險,但令研究人員大感驚訝的是,似乎只有在20歲以前值夜班才會影響到罹患MS的風險。

她還指出,其他研究同樣顯示,只有年輕時期的肥胖才會增加罹患MS的風險,如果是成年後肥胖,則根本毫無影響。

先前的研究顯示,值夜班或從事輪班工作,會增加罹患心血管疾患、甲狀腺毛病及癌症的風險,也是由於擾亂生理節奏和睡眠而影響到免疫系統。
------------------

總之 只要你的生活不正常, 沒有充分休息,
免疫系統都會受到影響, 進一步的罹病的機率就會升高.
當你容易覺得累的時候, 就要密切小心了!!



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2011年10月13日 星期四

自體免疫機轉露曙光 update

記者戴淑芳/台北報導 2011-10-11

自體免疫疾病與癌症都是目前可能致死的重大傷病,國衛院與台中榮總研究團隊歷經 2年研究,發現可調控致病機轉的關鍵酵素蛋白激酶,為治療與預防打開一扇窗。

包括紅斑性狼瘡、類風濕性關節炎、僵直性關節炎、乾燥症等自體免疫疾病,乃至癌症,都是一種人體內自己的免疫系統攻擊自己身體正常細胞的疾病,致病原因是遺傳、環境、感染及內分泌等多種因素共同造成,但致病機轉目前仍未完全明瞭,也造成治療上一直無法有所突破。

國衛院與台中榮總合作研究証實,人體 T淋巴細胞中存在一種調控自體反應的酵素蛋白激酶( MAP4K3/ GLK),在傳導途徑中扮演承上啟下 的角色,如能有效抑制活化,可降低自體免疫疾病與癌症的致病反應。譚澤華團隊的論文已發表在國際免疫學界第一名的「自然雜誌,免疫學期刊(Nature Immunology)」,是國內首度有論文發表在該權威期刊,並已向美國智慧財產專利局申請暫時性專利。

由國衛院特聘研究員譚澤華主任主持帶領的研究團隊,成員包括莊懷佳、楊佳郁與李如璧博士後研究員及黃慶裕助研究員偕同台中榮民總醫院藍忠亮副院長、風濕免疫科陳得源主任、陳一銘主治醫師

莊懷佳博士表示,研究團隊先利用自行創建的基因剔除小鼠,結合分子生物技術及轉譯醫學研究,進行自體免疫疾病模式研究,結果証實,抑 制 MAP4K3/ GLK可避免同時影響訊息傳遞路徑,達到降低產生大量發炎激素或促進 B淋巴細胞產生自體抗體,因而攻擊自體的健康組織及器官,造成 發炎性多重系統慢性疾病副作用。

經過與台中榮總合作收案,針對紅斑性狼瘡、類風濕性關節炎、僵直性關節炎、乾燥症等 14種自體免疫疾病患者 的血清檢體比對,也証實 MAP4K3/ GLK蛋白的活性的確較高,其中以紅斑性狼瘡、類風濕性關節炎、乾燥症、成人型史提爾氏症最明顯僅陣發性風濕 症患者較不明顯。
譚澤華表示,這項成果深具臨床應用的價值,也為未來在治療自體免疫疾病、癌症及 IL-17相關疾病,提供了一種具潛力的藥物發展新模式與方向。

 國衛院研究員莊懷佳(左起)、免疫醫學部譚澤華主任、台中榮民總醫院副院長藍忠亮、風濕免疫科陳一銘醫師等人組成的研究團隊,找到紅斑性狼瘡等自體免疫疾病的調控關鍵酵素蛋白激酶,可望研發標靶藥物。(記者戴淑芳攝)

台中榮總免疫風濕科醫師陳一銘表示,在自體免疫疾病患者體內T淋巴細胞球中,大多能看到大量MAPAK3/GLK蛋白激酶的表現。現有十四種人體自 體免疫疾病中有十三種有此現象,又以類風濕性關節炎、紅斑性狼瘡、乾燥症與成人型史迪威爾症等四種疾病最為顯著,粗估國內病患有十萬人。

國衛院與台中榮總合作兩年多以來,針對一百多名全身性紅斑性狼瘡病人進行研究,其中尚有超過八成病人飽受病痛折磨,亟待醫藥界研發出更新、更有效的治療方式。

所以看來目前國內應仍屬於動物實驗的結果? 是否有人體試驗呢? 應該可以詢問台中榮總風濕免疫科陳得源主任、陳一銘主治醫師


該報導指出有14種自體免疫疾病有關,也包含多發性硬化症, 其他可以再找出詳細的這14種.. !

給同時具有自體免疫疾病(紅斑性狼瘡、類風濕性關節炎)以及多發性硬化症的患者,這真是一個好消息!

譚澤華 特聘研究員/主任 分機37600 / ttan@nhri.org.tw

莊懷佳 分機37612 / cinth@nhri.org.tw

李如璧 分機37612 / d888203@nhri.org.tw

楊佳郁 分機37612 / chiayu@nhri.org.tw


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2011年10月7日 星期五

我的腦血管影像 更新My status update 3~


我的3D血管圖如下:

這裡 可看

點擊之後,在頁面右上角有 [ download 1MB] 請按下去

之後會跳出視窗問你 : 下載還是開啟?

不論哪一種,請用瀏覽器開啟該檔案即可瀏覽

附上2D版本(差異好明顯)


左圖主要標示出右邊IJV被阻斷的部份
(因為箭號下方並沒有對應的黑色血劉影像...)右圖主要標示出左邊IJV狹窄的部份(下方隱約還有稍淺灰色的血流影像)

目前看起來我顱內右側的靜脈較大, 可能導因於右側IJV上端的阻塞, 所以累積大量的血流,相對比較粗, 而右側背脊靜脈 Vertebral vein 較左側大,而且感覺似乎有靜脈區張的現象...



左圖為Sammy(國外病友的MRV圖) 右圖為我的MRV圖, 左右雖然都不同, 但是差異性似乎還是有某種程度上的差別....

由於自己的靜脈窄化處不同於大多國外MS病友(位於顱內),就手邊能夠找到的病友(我只能找到兩個例子)做一比對,並且異想天開的想了一些問題和方法,主要是因為左邊的Sammy裝了支架之後一年後, 安裝支架的部份都再度的窄化, 所以才會讓我有這樣的思考。因為內頸靜脈最上面的血管最小,到心臟部份比較大,所以在這裡所安裝的支架相對的可能比較容易滑落,一旦滑落,就會進入心臟。或許這是Dr.Dake採用折彎式的支架的原因吧。但是有了轉折又會容易再塞住。真是難解的問題....
能否先用氣球試試看呢? 或許先擴張,看看恢復情形,也能夠再次的確認這是能夠阻止這種慢性漸進病程的最安全有效的方式。

依稀還記得上一次做氣球擴張手術的感覺,左邊還能夠送上氣球到頸椎第一節C1的位置,但是到右邊的時候,在送氣球的過程當中,我發現會有些疼痛,那時候在手術台上直接反映給張醫師,為了保險起見,所以決定不冒險在更深入推進,難道說 這顯示著右邊的頸靜脈已經完全塞住了嗎? 要是塞住了,豈不是連擴張的機會都沒有?

祈禱著,右邊不要塞住,或許能夠再轉個角度,來回多試試幾次,找到不會讓我感到疼痛的角度深入,或許就能夠有機會了吧?Praying ...
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