2011年12月20日 星期二

治癒失智症 Alzheimer's disease 的新希望



[Baylor University的Maura Costa-Mattioli及Ottawa Hospital Research Institute的John
Bell等發現小老鼠和人的腦有很相似的地方。兩者的腦,都有一種基因稱為 PKR,是在有失智症Alzheimer’s
disease時腦內會釋放、出現的。而最近他們還發現腦內有可以抑制 PKR的基因。
Costa-Mattioli現在已發現可以抑制PKR的藥物。如果PKR被抑制,腦還會釋出gamma-interferon,可以增強神經細胞細胞間的溝通,增強記憶。他們的研究可能會導致治療失智症、加強記憶的藥物。]




“Super memory” pill–and possibly an
Alzheimer’s cure–could be around the corner


 (Damian
Dovarganes/AP)




Scientists have isolated a gene in mice that works to give
them "super memories" and reverses the course of several degenerative
mental illnesses like Alzheimer's. And because of the similarity of mice and
human brains, a powerful brain pill for humans may now not be far off.




The brains of both mice and humans release a gene known
as PKR, which is triggered by the onset of Alzheimer's.
But the newly discovered gene can apparently
block PKR's release
--a development that not only can reverse the course
of degenerative brain diseases such as Alzheimer's, but induces a state of
"super memory" in the mice it has been tested on.




"If we were to find an inhibitor, a molecule, a drug
that will specifically block PKR, we should be able to do the same [in humans]
,"
Maura Costa-Mattioli, who led the
research study at Baylor University
, told the Vancouver Sun. "And
we did."



"We recognize that PKR
plays a dual role
, one in regulating simple everyday processes like the
way neurons talk to each other [for] memory, but also has a stress
response," added John Bell, a
senior scientist at the Ottawa Hospital Research Institute
who also
contributed to the study.




More from the Sun:




A virus is one form of stress that triggers PKR, but
Alzheimer's patients' brains also experience PKR-releasing stress,
said
Bell, whose cancer research led him to create PKR-deficient mice which he
shared with Costa-Mattioli's lab. Researchers found that when PKR is
genetically suppressed in mice, another immune molecule, called gamma interferon,
increases communication between neurons, improving memory and making brain
function more efficient
, Costa-Mattioli said.




Reportedly, when
PKR is blocked, the gamma interferon can work more or less spontaneously to
improve brain functions--and can be activated via a simple PKR-inhibitor
injection
into a mouse's stomach rather than through more conventional
and drawn-out gene therapy. The possible application for humans would lead to
something like taking a "brain pill" to treat diseases like
Alzheimer's, or simply to give the memory a significant boost:




When the researchers tested the PKR-deficient mice in a
series of memory tests, those mice were able to pick up on patterns and
remember them on the first try, while the other mice needed days to figure out
how to solve the puzzle. The PKR-deficient mice consistently showed
significantly better memory and learning abilities than their counterparts
.




Of course, Costa-Mattioli said the goal is not to create a
new society of super-memory powered people.




"Let's say we'd compare with Viagra. People use Viagra
at whatever age, let's say 60, 65. But someone (who) is 40 goes to buy it, they
can get it," he said. "But this is not our goal . . . Our goal would
be to treat people who have a memory problem."





 





 








2011年12月19日 星期一

中國及美國經濟學家都說: 中國已經接近破產!



 台灣還要再向中國經濟靠攏嗎?  台灣人別再被馬先生騙啦!!


(參看中國的幽靈城市及商場: http://tw.myblog.yahoo.com/ccshsu-clement/article?mid=9047&prev=9049&next=9039 )


 




Chinese Economist Says Regime Nearly Bankrupt




What I’m about to say is
all true. But under




this system, we are not
allowed to speak




the truth.




– Larry Lang




 




China's
economy has a reputation for being strong




and
prosperous, but according to an economics




professor
who is also a well-known Chinese




television
personality, the country's Gross Domestic




Product
is going in reverse.




 




Larry
Lang, chair professor of finance at the




Chinese
University of Hong Kong, said in a lecture,




which
he did not think was being recorded, that




the
Chinese regime is in a serious economic crisis—




on
the brink of bankruptcy. In his memorable




formulation:
every province in China is Greece.




 




The
restrictions Lang placed on the Oct 22




speech
in Shenyang City, in northern China’s




Liaoning
Province, included no audio or video




recording,
and no media. He can be heard saying




that
people should not post his speech online, or




“everyone
will look bad”, in the audio that is now on




YouTube.




 




In
the unusual, closed-door lecture, Lang gave




a
frank analysis of the Chinese economy and the




censorship
that is placed on intellectuals and public




figures.
“What I’m about to say is all true. But under




this
system, we are not allowed to speak the truth,”




he
said.




 




Despite
Lang's polished, high-profile




appearances
on TV, he said: “Don’t think that we are




living
in a peaceful time now. Actually the media




cannot
report anything at all. Those of us who do TV




shows
are so miserable and frustrated, because we




cannot
do any programmes. As long as something is




related
to the government, we cannot report about




it.”




 




He
said that the regime does not listen to experts,




and
that Party officials are insufferably arrogant. "If




you
don’t agree with him, he thinks you are against




him,”
he said.




 




Lang's
assessment that the regime is bankrupt




was
based on five conjectures.




 




Firstly, the regime’s debt sits at about 36 trillion




yuan (S$7.35 trillion).
This calculation is arrived at by




adding
up Chinese local government debt (between




16
trillion and 19.5 trillion yuan, or S$3.27 trillion and




S$3.98
trillion), and the debt owed by state-owned




enterprises
(another 16 trillion, he said). But with




interest
of 2 trillion per year, he thinks things will




unravel
quickly.




 




Secondly, the regime’s officially published




inflation rate of 6.2 percent is fabricated. The real




inflation
rate is 16 percent, according to Lang.




 




Thirdly, there is serious excess capacity in




the economy, and private consumption is only




30 percent of economic activity. Lang said that




beginning
this July, the Purchasing Managers Index,




a
measure of the manufacturing industry, plunged




to
a new low of 50.7. This is an indication, in his view,




that
China’s economy is in recession.




 




Fourthly, the regime’s officially published GDP of




9 percent is also fabricated. According to Lang’s data,




China’s
GDP has decreased 10 percent. He said that




the
bloated figures come from the dramatic increase




in
infrastructure construction, including real estate




development,
railways, and highways each year




(accounting
for up to 70 percent of GDP in 2010).




 




Fifthly, taxes are too high. Last year, taxes on




Chinese
businesses (including direct and indirect




taxes)
were at 70 percent of earnings. The individual




tax
rate sits at 81.6 percent, Lang said.




Once
the "economic tsunami" starts, the regime




will
lose credibility, and China will become the




poorest
country in the world, Lang said.




Several
commentators have expressed broad




agreement
with Lang's analysis.




 




Professor
Frank Xie at the University of South




Carolina,
Aiken, said that the idea of China going




bankrupt
is not far fetched. Major construction




projects
have helped inflate the GDP, he says. “On




the
surface, it is a big number, but inflation is even




higher.
So in reality, China’s economy is in recession.”




 




Further,
Xie said that official figures should not




be
relied on. The regime’s vice premier, Li Keqiang,




for
example, admitted to a U.S. diplomat—as




mentioned
in a cable from 15 March 2007 obtained




by
a Wikileak—that he does not believe the statistics




produced
by lower-level officials, and when he was




the
governor of Liaoning Province, “had to personally




see
the hard data”.




 




Cheng
Xiaonong, an economist and former




aide
to ousted Party leader Zhao Ziyang, said that




high praise of the "China
model" is often made on




the basis of the high-visibility
construction projects,




a big GDP, and much money in foreign
reserves.




"They
pay little attention to things such as whether




people's basic rights are guaranteed, or their living




standard has improved or not," he said.




 




Behind
the control of the economy by fiat, which




can
have the appearance of being efficient, there




is
enormous waste and corruption, Cheng said. It




means
that little spending is done on education,




welfare,
the health system, and so on.




 




Cheng
says that for the last decade, the
Chinese




regime has accumulated its wealth
primarily by




promoting real estate development,
buying urban




and suburban residential properties at
low prices (or





simply taking them), and selling
them to developers




at high prices.




 




According
to Cheng, the goals of regime
officials




(to enrich themselves and increase their
power)
are




in
direct conflict with those of the people—so social




injustice
expands, and economic propaganda meant




to
portray the situation as otherwise prevails.




Few
scholars inside the country dare to speak as




Lang
has, Cheng said. And that is probably because




he has a
professorship in Hong Kong.


 


New York Times
December 18, 2011

Will China Break?

By PAUL KRUGMAN
Consider the following picture: Recent growth has relied on a huge construction boom fueled by surging real estate prices, and exhibiting all the classic signs of a bubble. There was rapid growth in credit — with much of that growth taking place not through traditional banking but rather through unregulated “shadow banking” neither subject to government supervision nor backed by government guarantees. Now the bubble is bursting — and there are real reasons to fear financial and economic crisis.
 
Am I describing Japan at the end of the 1980s? Or am I describing America in 2007? I could be. But right now I’m talking about China, which is emerging as another danger spot in a world economy that really, really doesn’t need this right now.
 
I’ve been reluctant to weigh in on the Chinese situation, in part because it’s so hard to know what’s really happening. All economic statistics are best seen as a peculiarly boring form of science fiction, but China’s numbers are more fictional than most. I’d turn to real China experts for guidance, but no two experts seem to be telling the same story.
Still, even the official data are troubling — and recent news is sufficiently dramatic to ring alarm bells.
 
The most striking thing about the Chinese economy over the past decade was the way household consumption, although rising, lagged behind overall growth. At this point consumer spending is only about 35 percent of G.D.P., about half the level in the United States.
 
So who’s buying the goods and services China produces? Part of the answer is, well, us: as the consumer share of the economy declined, China increasingly relied on trade surpluses to keep manufacturing afloat. But the bigger story from China’s point of view is investment spending, which has soared to almost half of G.D.P.
 
The obvious question is, with consumer demand relatively weak, what motivated all that investment? And the answer, to an important extent, is that it depended on an ever-inflating real estate bubble. Real estate investment has roughly doubled as a share of G.D.P. since 2000, accounting directly for more than half of the overall rise in investment. And surely much of the rest of the increase was from firms expanding to sell to the burgeoning construction industry.
 
Do we actually know that real estate was a bubble? It exhibited all the signs: not just rising prices, but also the kind of speculative fever all too familiar from our own experiences just a few years back — think coastal Florida.
 
And there was another parallel with U.S. experience: as credit boomed, much of it came not from banks but from an unsupervised, unprotected shadow banking system. There were huge differences in detail: shadow banking American style tended to involve prestigious Wall Street firms and complex financial instruments, while the Chinese version tends to run through underground banks and even pawnshops. Yet the consequences were similar: in China as in America a few years ago, the financial system may be much more vulnerable than data on conventional banking reveal.
Now the bubble is visibly bursting. How much damage will it do to the Chinese economy — and the world?
 
Some commentators say not to worry, that China has strong, smart leaders who will do whatever is necessary to cope with a downturn. Implied though not often stated is the thought that China can do what it takes because it doesn’t have to worry about democratic niceties.
To me, however, these sound like famous last words. After all, I remember very well getting similar assurances about Japan in the 1980s, where the brilliant bureaucrats at the Ministry of Finance supposedly had everything under control. And later, there were assurances that America would never, ever, repeat the mistakes that led to Japan’s lost decade — when we are, in reality, doing even worse than Japan did.
 
For what it’s worth, statements about economic policy from Chinese officials don’t strike me as being especially clear-headed. In particular, the way China has been lashing out at foreigners — among other things, imposing a punitive tariff on imports of U.S.-made autos that will do nothing to help its economy but will help poison trade relations — does not sound like a mature government that knows what it’s doing.
 
And anecdotal evidence suggests that while China’s government may not be constrained by rule of law, it is constrained by pervasive corruption, which means that what actually happens at the local level may bear little resemblance to what is ordered in Beijing.
 
I hope that I’m being needlessly alarmist here. But it’s impossible not to be worried: China’s story just sounds too much like the crack-ups we’ve already seen elsewhere. And a world economy already suffering from the mess in Europe really, really doesn’t need a new epicenter of crisis.



 




2011年12月18日 星期日

馬先生在全國人民面前再說謊!!

[這些紀錄都可看出馬先生 "清廉恭儉讓、、、" 甚麼甚麼XX,都是謊言!!


 


看馬先生在辯論會上,對全國人民說出這些謊話,都是臉不改色,一副好誠懇的樣子。   真是說謊慣了,這種謊言都不當一回事,很可能心中都不會感覺到不誠實是錯的、     不道德的   (這種人叫做 pathological liar)! 他的話還有甚麼可信的?


 


以前票選馬先生當市長、總統的選民,看了他的這幾則不實言論及一堆馬氏謊言錄  http://tw.myblog.yahoo.com/jw! GAJfq5CREwTFZ1gGiWhZt.zp/article?mid=9034,不知做如何感想?!]


 


[馬先生的誠信問題越討論越多,他在市長時是否賤賣台北銀行給富邦銀行,"魚翅宴"違法的情節越談越清楚! 回溯過去他的謊言,都是一開始 "誠懇地"否認,被拿出證據對質,曉得無法再否認,他才承認。


http://www.taiwanus.net/news/press/2011/201112190314301257.htm]


 


越揭發越多!現在又多了一筆劉文雄的 "兩億馬"!


 


還有別忘了,在2008年李遠哲院士曾透露有兩位科技大老說過,他們各曾捐給馬先生五億元,可是都沒有紀錄、沒人調查!  他們講這些可都不是開玩笑的哦!! 無私鐵漢的黃檢察總長在哪?? 調查了沒?


 
















劉文雄的「兩億馬」傳奇   作者:黑雨



可能被宇昌議題邊緣化的親民黨昨天出招了。



昨天晚上(12/19)的年代「新聞追追追」節目中,親民黨名嘴劉文雄突然爆了一個料。他說,馬英九曾經收過兩億政治獻金,而且歡迎國民黨去告他。此話一出,在場所有人都楞了,連主持人張啟楷也呆住。



 



在以下「新聞追追追」側錄影片一開始,就是劉文雄的爆料:



劉文雄:「(馬英九!) 2008 年時,我的好朋友說拿給你和你的助理有兩億耶!要不要出來告告我,我們來找人跟你對一下?馬英九,你沒那麼乾淨啦!現在大家談的是你的清廉問題嘛!」



主持人張啟楷:「等一下!這個更嚴重!這個 2008 年兩億… 」



劉文雄:「超過超過,他選市長有一次,他選總統一次,請各位看看在高雄不是有國宴對不對?就職的國宴,前四桌五桌是什麼人坐?大家去查一查,據說數字比我說的還多耶!」



張啟楷:「這要有證據,等一下… 」
劉文雄:「沒關係,我接受大家來提告,因為我的證人都在等,因為他們實在不滿,不滿這兩組候選人都在那邊耍可愛、耍清白、耍清廉,非常惡劣!」



接著,就是馬辦發言人賴素如氣急敗壞地要劉文雄拿出證據,劉文雄說他當場講的話就是證據,歡迎來告,結果賴素如居然愣住,不敢說要告他。




劉文雄在昨晚爆料時神定氣閒,一副老神在在的樣子,顯然胸有成竹,早就準備好了。這個爆料代表兩個意義:



1. 宋楚瑜跟親民黨決定加強批判馬英九的力道,而且一出手就是要命的死穴



2. 劉文雄的確點到一個重點:馬英九一再把自己裝扮成清廉、清白,但他上一次跟這一次競選總統的經費來源始終是個謎,多數的人們也不會相信馬英九有那麼像聖人。光是以連戰在 2000 年選總統為例,傳聞就花了一百億以上。



當馬英九集團拿著宇昌案對著蔡英文大聲叫罵追殺的時候,其實他犯了一個致命的錯誤:越是想把自己假扮成聖人的政客,就越是容易被拆穿,支持者們失望的程度也越大。親民黨出手了,馬英九跟聯合報、中國時報、TVBS 等藍色媒體所共同演出的「亂世聖人」大戲,到底是會越演越像?還是會變成「亂世爛人」?






富邦併北銀案 綠議員痛批市府成冤大頭 【11:41】


〔記者黃忠榮/台北報導〕台北市議員簡余晏、李建昌今天召開記者會表示,2003年8月時任台北市長的馬英九將北市金雞母台北銀行產權移轉給富邦金,卻只換來2席董事,結果富邦「蛇吞象」北銀後,8年來只繳市庫115億元,其中還有1年繳庫0元,市府成了冤大頭。

 簡余晏指出,當時不分藍綠的台北市議員可說一致反對市府將北銀賣給富邦,但馬市長還是不顧議會反對,更令人不可思議的是,賣掉北銀前竟未做資產重估,光以房地產來看,北銀資產至少低估60億元。

 簡余晏表示,北銀在官方自營時代,從1993年至1999年,這7年就繳庫100億元,而且當時北銀在台北市的44個黃金地段的分行房地產都在市府名下,都是市民財產,現在龐大房產全歸富邦,獲利又比不上官方自營時代,「馬市長難道不必對台北市民說清楚,為什麼會有這麼離譜的購併案﹖」


全國人民面前馬英九再度公然撒謊



◎ 陳新福



總統大選最後一場電視辯論會,馬騜在結論時,臉不紅氣不喘的說:「民進黨不敢成立的廉政署,我成立了。」這和二○○八年電視辯論會上承諾若六三三未達成則捐半薪一樣,再度在全國民眾面前公然撒謊。



眾所周知:在扁政府擔任法務部長長達約七年的陳定南,素有「包青天」之譽。他深知極大多數屬「深藍」的檢調政風系統,不太可能會聽他指揮徹底執行他的肅貪政策,所以上任之初就積極規劃籌備成立廉政署。



他首先嚴選解嚴後由考試院招考學歷特高的五百名「正牌」政風人員,擬轉任為廉政署成員(解嚴前政風人員皆由調查局招考、篩選國民黨員任用)。但在長達七年之間,陳定南向包括馬英九領導的中國國民黨掌控的立法院要求成立廉政署多達一六五次,卻全遭封殺,致使陳青天抑鬱以終。



由以上事實可以證明,沒有「完全執政」的執政黨,事實上是個執政的在野黨而已,能力再高強,也根本無法展現立法及預算的政績。反觀「完全執政」意氣風發的馬騜,如今由於無能致使民調下至「死亡交叉」,交不出政績,情急之下一而再再而三藉說謊來欺騙選民。這種沒有品格的國家領導人,讓他下台吧!



(作者為退休政風人員)



剽竊扁政府成果



◎ 鄭光倫



馬英九總統在上週六電視辯論會的結辯時間表示「民進黨不敢精簡的行政院,我精簡了!」根本是再次欺騙全民!



二○○一年,陳水扁總統在「經濟發展諮詢委員會」中組成「政府改造委員會」,更於二○○二年五月成立了「行政院組織改造推動委員會」,並陸續研擬「中央政府機關組織基準法草案」、「中央政府總員額法草案」、「行政院組織法修正草案」,以及「行政院功能與業務調整暫行條例草案」等所謂的「政府再造四法」。民進黨政府把「政府組織再造」視為重要的國家政策並且迅速落實,哪裡是「不敢精簡行政院」?



同樣是二○○二年,民進黨政府即將「政府再造四法」送至立法院審議。然而,當年在立法院佔有優勢席次的國民黨,卻一再杯葛,不願讓民進黨取得改革光環,遲至二○一○年才通過三讀。「政府再造」延宕多年,馬總統難道不是禍首?



馬總統從政多年素以「溫良恭儉讓」自居,卻為了選舉而收割前朝成果、甚至不惜浪費公帑、製造冗員,實在是令人感到唏噓與不齒。



(作者為政治大學法研所碩士生、台灣青年智庫法政中心副研究員)



 



他斷送了台灣醫療人權



◎ 張武修



馬先生於電視辯論中恥談WHA,我很痛心!



猶記得今年五月世界衛生大會召開前,曾有立委揭露世界衛生組織內部對台灣文件,將台灣參與大會觀察員視為中國一省。此事揭發後,外交部對這麼重要、殘害我們國際生存空間的大事宣稱不知情,隨後卻一下子由馬總統與行政院吳院長用最高規格召開國家安全會議,異口同聲、信誓旦旦要到日內瓦向世界衛生組織抗議;行前記者會慷慨激昂,到日內瓦後於公開場合卻噤若寒蟬,虛晃一招;不久,多位歐洲議員、美國國會議員與美國衛生部長Sebelius看不過去,幫忙問世衛,回函確認馬政府對國人宣稱的「觀察員」,根本是喪權辱國而已。一晃半年過去,馬政府沒為台灣要回任何一分公道。



我們醫界上下為爭取加入世界衛生組織,一九九七年起由李鎮源院士帶領,每年出錢出力動員到各國遊說拜訪,漸獲得世界醫師會等國際團體支持,歷經十餘年,將加入世衛組織推進成國際共識,美日歐盟等大國紛紛表態支持,目的為台灣醫療衛生界及民眾爭取全面實質參與世界衛生舞台的機會。



二○○八年馬先生上台後,與中國政府私下協商,與北京聯手換得每年僅參加五天世衛大會以欺騙國人,但馬政府於國際上默認並接受中國對台灣主權的宣示,完全搭配中國與世衛備忘錄中的路線,乖乖束手就擒;早先還曾宣稱會持續努力參加世衛的技術性會議,但最近我與世衛組織內多位資深官員朋友聯絡,驚訝悲憤得知,這三年來,台灣並未再持續嘗試參與世衛組織的活動,也沒聽說或看到台灣來詢問能否參加世衛組織的技術會議;以前常動員大國來遊說參加區域會議或到執委會旁聽,這些年卻沒接到任何正式來信或請求參與;簡單講,世衛組織不知道台灣要什麼,似乎一年參加一次五天的會議就滿足了。



馬先生為了討好中國政府,犧牲台灣人民基本醫療人權與國際參與權利,也糟蹋了台灣醫界優質水準與國際知名度;馬先生與北京聯手終結台灣醫界多年爭取實質參與國際衛生的努力,令人痛心!



(作者為前衛生署駐外衛生代表,醫師)


看下面報導,又是一個很可能的馬謊言:


「馬指定蔡國強當建百顧問」 胡永芬:盛治仁說的

盛撇清:我是說相關人事不是我決定的


〔記者凌美雪/台北報導〕上週四總統候選人接受文化元年基金會籌備處答詢時,馬英九總統公開表示,他的女兒的老闆蔡國強承攬建國百年活動,他事先並不知情。但藝術策展人胡永芬卻在臉書上指出,她曾在一年前與前文建會主委盛治仁同在一個飯局時,聽到盛治仁說,「是馬總統決定的。」但盛治仁隨即在臉書上反駁,雙方說法陷入羅生門。


胡永芬:盛確實回答當然是馬總統決定


昨天胡永芬透過越洋電話,還原去年她與盛治仁對話的過程,她說,事情源起於十一月下旬,陳文茜在電視上為盛治仁抱不平說夢想家都是馬總統決定的,所以胡永芬在臉書上寫了「終於,內爆了~原來,文茜姐姐就是大家期待已久的深喉嚨!」沒想到收藏家「劉先生」回文說,「一年前飯局您就聽到了啊!」引起盛治仁的關注。


「一年前飯局」指的是因為視覺藝術家不滿視覺藝術經費在文建會被大幅縮減,與視覺藝術家們及盛治仁都有交情的「劉先生」,好意做東請吃飯,讓雙方進行良性溝通,席間除聊到視覺藝術經費問題,正好胡永芬有問到盛治仁,「為甚麼建國百年活動顧問五位裡就有兩位是中國人?而且一位竟然是蔡國強以前的助理?憑甚麼?」


胡永芬說,「盛治仁確實是回答:這哪是我能決定的?當然是馬總統決定。」那個助理指的是蔡國強前助理馬文,但當時胡永芬並不知道另一個中國人就是蔡國強,更完全不知道日後還有《夢想家》這回事。


對此,盛治仁前天在臉書上反駁,「針對胡永芬小姐的說法,為求慎重起見,我剛剛跟當天安排餐會的劉先生求證,他聽到的跟胡小姐完全不一樣,並無馬英九決定蔡國強的說法。」盛治仁說,「跨年慶典所有的標案、經費支出和行政流程,都是由台北市政府執行而非中央。當北市府和文建會來洽談合辦事宜時,相關架構以及人事已經安排好了,市府找了林懷民老師,林老師邀了蔡國強。所以我當時說明的應該是相關人事不是我決定的,但是要跳躍到是馬總統決定的,實在跟事實差距太大。」


到底盛治仁有沒有說過是馬總統決定的?胡永芬說,她又特別打電話問了飯局當天坐在盛治仁左手邊的藝術家駱麗真,「她說,她不只記得盛治仁說了這句話,還記得很清楚,盛治仁說完的表情好像有些後悔自己失言的感覺。」




 



2011年12月17日 星期六

劉憶如的墮落









〈李筱峰專欄〉台灣人墮落的象徵



如果憶起劉憶如的父親劉慶瑞教授,真是不勝感慨。劉慶瑞是一九六○年代台大著名憲法學者,與彭明敏、李登輝是學生心中的鐵三角。劉慶瑞娶了彭明敏的表妹郭婉容,生下劉憶如,所以彭明敏是劉憶如的表舅。劉慶瑞很早就關心台灣國際地位問題,曾經完成一部《臺灣新憲法》草案,是台獨思想的先覺者;而彭明敏也於一九六四年與學生謝聰敏、魏廷朝提出〈台灣人民自救宣言〉,遭國民黨當局入罪。遺憾的是,劉憶如顯然沒有受到父親與表舅的精神感召,她不但不願意為台灣獨立建國努力,反而投身外來政客集團陣營中。更悲哀的是,這次竟然還淪為國民黨政治鬥爭的打手!不論是出於有意還是無心,當變造過的文件被拆穿後,她心不甘情不願地「道歉」,卻又順手再打民進黨一把,推諉說是由於民進黨執政時遺失公文所致。台灣人的德性,不該是這樣的!尤其是乃父及表舅那一輩的台灣知識份子,絕對不是這樣的德性!表舅彭明敏正在糾集國際學者組成「公平選舉國際委員會」,而外甥女劉憶如卻幫執政黨進行選戰抹黑,下一代墮落了?



至於林益世的言行,更不堪聞問!林益世用經過變造的公文污衊蔡英文,事後被問起要不要道歉,他理歪氣壯說:「沒什麼好道歉!我只是引用資料錯誤而已。」設想如果黑道殺手根據錯誤訊息殺錯人,是否也可說「殺錯人沒什麼好道歉,我只是根據訊息錯誤而已」?名譽是人的第二生命,林益世可以如此殺人第二生命,卻還如此囂張!殺人兇手被捕之後見了被害人家屬都知道下跪請求原諒,這位奪人第二生命的兇手,竟然還揚眉瞬目!台灣人幾時淪落到如此無羞恥心的地步!



小學公民道德課上教學生「錯怪別人要說對不起」,連基本公民道德都不懂的林益世,何以益世?全然害世!過去的台灣人被公認是敦厚、老實、淳樸的,林益世的言行,卻讓我們看到台灣人德性的墮落!殷海光教授告訴彭明敏教授的話真的沒錯─「台灣人敦厚老實的氣質,被國民黨破壞了!」



林益世的家世,沒有像劉憶如那樣擁有關心台灣前途的學者父親,而是投靠外來政權的政治世家。劉憶如有那樣有理想的父親和表舅,都無法耳濡目染,更遑論林益世「願同弱少鬥強權」(林秋梧語)而不趨炎附勢了。林益世讀北醫牙醫系時,正值野百合學運時代,但民主潮流對他毫無所動,他始終站在民主運動的對立面,畢業後不學以致用而效忠權貴集團,效忠到連基本公民道德都不顧。



這種政客是否還會當選,正是台灣社會向上或沉淪的指標。孔子說「其善者惡之,其不善者好之」,我正要看看選民是否還會把這種連公民基本道德都不懂的政客送進國會?答案若是肯定的,台灣沒救了!



(作者李筱峰現任國立台北教育大學台灣文化研究所教授,http://www.jimlee.org.tw)



 



絕不能讓變造文件栽贓得逞



◎ 畢笙



宇昌案的關鍵文件已證實是造假,如果一個政府,因政績乏善可陳而必須靠變造文件栽贓對手,以尋求連任,而竟能得逞,這是全民之福嗎?



在威權時代,人民沒有選擇權,對國民黨的抹黑迫害、白色恐怖,只能噤若寒蟬。但在人民有投票權的今天,若仍以選票為國民黨的卑劣作法背書, 那可以想見這個政權連任後會怎麼做:首次上台,換法官也要收押陳水扁,連任後是不是要接著收押蔡英文?台灣政壇未來是否就這樣陷入肅清政敵的鬥爭萬劫不復?政敵肅清完畢,接下來是不是同樣以假證據栽贓的方式,肅清反對政府的媒體?肅清反對政府的人民?台灣的民主還能維持下去嗎?和重返威權體制有何差別?



這已經不是支持藍或綠,或選擇要相信誰的問題。這一票的選擇,實際上已經是保衛台灣民主的最後關鍵,決定台灣的未來,要迎向光明,還是墮入黑暗。(作者為律師,高雄市左營區民



 



馬英九‧劉憶如‧特偵組



總統候選人的第二場辯論會,老實說無甚可觀,十二個公民團體的提問,支離破碎,沒有形成壓力。至於三個人的表現,蔡英文或許因為感冒而戰力不如首場,即使如此,還是三人中稱冠,尤其開場發言,以宏觀角度擘畫未來施政方針,鏗鏘有力也具說服力。結論最好的則推宋楚瑜,火力四射,力爭出線。馬英九卻了無新意,執政黨的候選人馬英九,在設語音現場投票的三台電子媒體中,幾乎居末,票數約只有蔡英文的六分之一。



不過還是明顯看到馬英九在辯論中揮起指揮棒,繼續打「宇昌案」。馬英九的表態,一則否定了《中國時報》日前所報導的「打宇昌停損,藍選戰回歸政績」,同時也否決了副手吳敦義所說因「宇昌案」的「得分不多」,提出戰略調整之議。



「宇昌案」有兩個轉折點:一個是經建會主委劉憶如拿出假造的公文,意欲證實蔡英文在副院長任內即出任TaiMed的負責人之一,結果被抓包而敗局;第二個轉折點是「特偵組」出手密查國發基金,而且透過媒體昭告天下。國民黨要製造的印象或說想像很明顯,就算公文是假,檢調出手是真,妄圖以司法替揭弊出包的劉憶如解套,也達到替藍營的指控做背書的作用。



劉憶如捅了不可彌補的樓子,民進黨揚言提告,劉關機神隱一整天,到十二日深夜接受《聯合報》獨家專訪,表示「我覺得此事到此已too much(過頭了),「我不想奉陪了,我要辭職!」要問的是,為什麼隔了一天她又態度趨強,認為「我有必要留下來釐清宇昌案方向,不會把該負的責任丟下」?其中的關鍵就是「特偵組」要接手,不然她憑什麼說要釐清云云。



可以合理的懷疑是,劉憶如已與馬英九密謀,雙方達成共識?她不必辭而「特偵組」將當門神。不然如何解釋從「辭職」丕變為「奉陪到底」?誰給她的力量與勇氣?



馬英九說,自己不介入司法?有誰相信!「特偵組」代表的是政府,政府可以指揮檢調,尤其在「法院是國民黨開的」情況下。「特偵組」沒有奉命而為?這是其一。在昨天辯論會中,馬英九又特別稱讚檢察總長黃世銘,這無異是公開鼓勵黃世銘,其中沒有玄機嗎?這是其二。



「宇昌案」的停損點在劉憶如下台。劉不下台,宇昌之火受命延燒,會燒到誰的眉毛,從眉毛燒到哪裡,等著瞧罷!


v






劉憶如的選擇,在一念之間

[轉載自:自由電子報 ]


[Linda]於2011-12-17 00:01:18上傳[ 1018]


 






劉憶如的選擇,在一念之間

經建會主委劉憶如提出「烏龍公文」,為國民黨政媒勢力藉揭發宇昌案打擊蔡英文增添柴火,連日來經中研院院長、院士等生化科學家澄清辯駁,一場「動用國家機器追殺對手」的醜劇被台灣人民看穿,連帶造成馬英九選情大逆轉,內部傳出「設停損點」的說法。不過,拿出烏龍公文的劉憶如,在自爆「不想奉陪,too much,我要辭職!」之後,不但拒絕向蔡英文道歉,不承認經建會擺烏龍,還決定好官我自為之。


當事人也許自我感覺良好,但是問問一般公眾,認為劉憶如充當馬吳棋子或打手的社會觀感卻顯然普遍存在。箇中道理不待法律程序,僅從常識出發,其實即可判明。


劉憶如十三日所出示的文件,如其為真,顯示二○○七年三月三十一日時任行政院副院長的蔡英文,已經名列宇昌生技公司發起人。政府官員兼任營利事業負責人,不但違法,法律出身的副閣揆列名宇昌生技,且當時又係朝小野大的時期,劉主委如具一般公民的常識,即可知事屬不可能;要以這樣的文件誣指蔡英文,尤其荒唐。


再從文件的英文內容看,蔡英文的抬頭之後註明她是「中華民國(台灣)副閣揆,二○○六—二○○七;國立政治大學教授」。任何稍具常識的人都可辨識,這顯示蔡英文已非行政院副院長,劉憶如卻故意在記者會上至少五度強調「三三一文件才是大關鍵」,甚至與立委一搭一唱,暗示蔡英文三月雖尚未接任宇昌生技董事長,但已知會離開行政院,似有事先安排出路之嫌。


事實從常識來看已經很清楚,烏龍文件如果只是劉憶如所說的幕僚「資料誤植」,理應於出手之前,即可查知。然而,她仍然以此示人,合理的解釋是她與背後的「影武魔頭」沒有想到,蔡英文陣營居然握有原件,兩相對照,其烏龍甚至加料變造的伎倆,立遭拆穿;原先打算以此文件讓蔡英文無以反擊的人格謀殺詭計,反而盡暴露於國人面前。


尤有甚者,劉憶如在捅出樓子之後,仍辯稱「宇昌案相關資料太多,很多帳目看不懂,公司名稱也變來變去,逐一核對,非常困難且費工夫,出了一點差錯。」這樣的說法,出自一位有經濟學博士學位,曾任教授、立委、金融機構首席經濟專家,現任經建會主委,且主持國發基金的大官,令人不敢置信。


不尋常的事背後必然有因。從表面看,當大官以後的劉憶如,經濟財務專業水準似乎大幅衰退,連基本財務資訊也無力理清,加上馬吳經濟政策的嚴重偏差,難怪台灣近年在亞洲四小龍經濟表現落居最後一名。然而,從她所出示的機密文件有媒體披露於先,她的閣揆長官出事後仍以「卷宗擺錯」、「三月跟八月沒有多大差別」硬拗,從而,更可能的事實應是劉主委不過奉命賣力演出,個別演員之上還有影武者。


誠然,大選關係重大,但為挽回艱困的選情,不擇手段,連最基本的「行政中立」、生技產業發展、政務官風骨、選舉格調都可以完全犧牲。加上黨國總動員,從媒體戰到立委、名嘴出動,連行政部門、特偵組也一起加入配合,如此惡形惡狀,台灣人民看在眼裡,當然要反映在民調之中。


在如此政治利益共同體的黨國結構之下,加入即難以退出。劉憶如在烏龍文件被拆穿的「不想奉陪」立即反應,可能最接近真心誠意。連日來有不少有識之士,引她專治公法學者父親劉慶瑞的典型,或以她學者轉任公職有成的母親郭婉容相比,感嘆、期待的都有。劉憶如在做錯事之後,究竟要繼承上一代的令名,還是繼續為了黨國勝選,做官做到連做人的格調也做掉了,選擇其實就在自己的一念之間。



2011年12月14日 星期三

對vancomycin有高MIC 的 MRSA 血流感染,要用Daptomycin治療!

Consider Daptomycin for MRSA With High Vancomycin MICs


NEW YORK (Reuters Health) Dec 05 - Daptomycin is best for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection when the vancomycin minimum inhibitory concentration (MIC) is high, researchers say.


Dr. Marcus J. Zervos and colleagues with Wayne State University and Henry Ford Hospital in Detroit, Michigan say that while the breakpoint for susceptibility of MRSA to vancomycin is supposedly an MIC of 2 mcg/mL, treatment failure has been reported in bloodstream infections with MICs below this threshold.


The researchers also say their findings support recent guidelines suggesting that doctors consider alternative agents when the isolate has a vancomycin MIC above 1 mcg/mL or when patients are not improving.


But, they point out, the guidelines don't have a lot of data behind them, which is why the team reviewed its own experience in patients hospitalized with a MRSA bloodstream infection and an MIC between 1 and 2 mcg/mL.


As reported online November 21 in Clinical Infectious Diseases, the authors compared 59 daptomycin-treated patients and 118 vancomycin-treated patients.


Rates of treatment failure (a composite of death, microbiologic failure or infection recurrence) were 17% in the daptomycin group and 31% in the vancomycin group, although this difference was not statistically significant (p=0.084).


The benefit was mainly driven by lower mortality with daptomycin vs vancomycin (9% vs 20%; p=0.048).


The results "provide the first clinical comparison of alternative therapy in patients with MRSA BSI (bloodstream infection) with a high vancomycin MIC and confirm that vancomycin-treated patients are at high risk for failure; however, this risk is mitigated by treatment with daptomycin," Dr. Zervos and colleagues conclude.


In an editorial, Drs. Adam Weston and Helen W. Boucher with Tufts University School of Medicine in Boston note that daptomycin is less successful in cases with moderate renal impairment.


That and other safety concerns, along with the cost of the drug, "preclude our recommending daptomycin for all patients with elevated vancomycin MICs," they write.


That said, they conclude, "We hope that future prospective studies will clarify the question of whether every patient with an elevated vancomycin MIC benefits from daptomycin therapy."


Clin Infect Dis 2011.



使用吸入抗生素的方法治療院內肺炎





Aerosolized Antibiotics for Treating Hospital-acquired and Ventilator-associated Pneumonia

G Christopher Wood

Abstract and Introduction






Abstract




Hospital-acquired pneumonia is a common complication that
continues to have a poor cure rate in some patients with intravenous therapy
alone. Aerosolized antibiotics are theoretically attractive in an attempt to
optimize lung concentrations of antibiotics. Limited data suggest that
aerosolized aminoglycosides or colistin in addition to intravenous therapy
results in good response rates in patients with multidrug-resistant organisms
or nonresponding pneumonia. Adverse events can occur, especially with colistin.
When used, care should be taken to properly compound and administer aerosolized
antibiotics to ensure tolerability and good drug delivery.




Introduction




Hospital-acquired pneumonia (HAP) continues to be a common
and often devastating complication of modern healthcare. Approximately 90% of
HAP patients are mechanically ventilated and may also be referred to as having
ventilator-associated pneumonia (VAP).[1]
Approximately 9–27% of mechanically ventilated patients in the intensive care
unit (ICU) develop HAP/VAP. This results in an increased attributable mortality
of up to 50%, an increased length of stay by 7–9 days, and increased healthcare
costs of up to US$40,000 per patient.[1] Despite
the availability of modern ICU care and modern antibiotics, the overall
clinical cure rate for HAP in randomized clinical trials is only 63%. The cure
rate for Pseudomonas aeruginosa is even lower.[1,2] It is
unclear why HAP/VAP cure rates are so low. A number of patient and
pathogen-related factors could be involved including patients' underlying
disease states, interpatient differences in the immuno-inflammatory response to
illness and bacterial colonization, and pathogenic differences among bacteria
including the potential to develop resistance during therapy. Compounding the
problem is the lack of novel Gram-negative antibiotics in a time of increasing
resistance from organisms such as P. aeruginosa, Acinetobacter
baumannii
and various Enterobacteriacae.




However, problems with antibiotic delivery may also be
important. Many antibiotics used to treat HAP, including β-lactams, aminoglycosides
and vancomycin, have poor penetration into the epithelial lining fluid (ELF) of
the lungs.[3]
The ELF concentrations for these antibiotics are usually less than 50% of the
concentrations achieved in the serum.[3]
Unfortunately, pharmacokinetic studies to determine optimal dosing of
antibiotics are normally done in normal volunteers and not critically ill
patients who can have markedly different pharmacokinetics.[4] Even
fewer formal pharmacokinetic studies are done to assess lung ELF penetration of
antibiotics in actual patients. As such, relatively little is known about the
optimal dosing of most antibiotics for HAP. Many antibiotics have doses
specific to treating HAP or life-threatening infections; however, correct doses
may not be used.[1]
It is clear that antibiotic therapy needs to be optimized in HAP.




One method of improving antibiotic delivery to the lung ELF,
and potentially improving outcomes, is aerosolized delivery into the lungs.
Since the 1960s there have been a number of reports using aminoglycosides,
colistin and β-lactams for treating HAP. However, there has been a sharp
increase in these reports over the last decade largely in an effort to treat
emerging multidrug-resistant (MDR) strains of Gram-negative bacilli such as P.
aeruginosa
and A. baumannii. This article will summarize the
available literature on the use of aerosolized antibiotics for treating HAP in
adult patients.






Aminoglycosides






Until the 2000s, aminoglycosides were the most widely
studied aerosolized agents for treating HAP (Table 1). Pines et al.
initially reported two observational case series with aerosolized gentamicin.[5,6] The
first series included patients that had not responded to intravenous therapy for
chronic bronchial infections.[5] The
clinical improvement rate after 4–8 weeks of therapy was rather dismal (18%)
regardless of whether systemic therapy was continued or not. However, in the
second series 12 patients undergoing initial treatment for HAP had aerosolized
therapy added to carbenicillin.[6] A more
typical response rate of 67% was reported after 7–10 days of therapy.




Subsequently, Klastersky et al. increased the rigor
of study design with two randomized trials.[7,8] It is
important to note that antibiotics were endotracheally instilled (ET) as a solution
in these two studies rather than aerosolized. In the first, 15 patients were
randomized to receive either ET or systemic gentamicin.[7] The cure
rate was significantly better in the patients in the ET group (100 vs 25%). In
the second study, 38 patients were randomized to receive either ET sisomicin or
placebo added to systemic β-lactam/aminoglycoside therapy.[8] Again, the
cure rate was significantly better in the ET group (77 vs 45%). Incredibly,
this study from 1979 remains the largest randomized, placebo-controlled trial
of aerosolized antibiotics for treating HAP.[8] In the
1980s, three case reports totaling eight patients showed a cure rate of 100%
with ET or aerosolized therapy for 7–16 days.[9–11] Seven
of the eight cases also received intravenous antibiotics. Importantly, five of
the patients had previously not responded well to intravenous antibiotics
alone.




After years without new data, since 2007 there have been
four new publications. All four reports used increased rigor in that they all
used aerosolization, included only patients with VAP, and required
bacteriologic confirmation of infection. A small trial randomized ten patients
to receive either aersosolized or intravenous tobramycin for P. aeruginosa
or A. baumannii.[12] The two
treatment failures were in the intravenous group. A retrospective observational
study of 22 patients receiving either aerosolized tobramycin or amikacin for a
mean of 7 days added to intravenous therapy reported a 41% recurrence rate
(i.e., 59% cure rate).[13] This
cure rate is not impressive; however, many of the treatment failures were in
patients with difficult-to-treat situations such as previous episodes of VAP or
MDR organisms. In the largest observational study to date, Czosnowski et al.
reported the outcomes of 53 trauma ICU patients treated with aerosolized
tobramycin or amikacin added to intravenous therapy for approximately 10 days.[14] The
clinical cure rate was a reasonable 73% despite a high rate of patients with
previous treatment failure with intravenous therapy alone or the presence of
MDR organisms. This study is also the only one with microbiologic confirmation
of outcomes in a large percentage of patients. Lastly, there was an observational
study in 16 cancer patients treated with aerosolized aminoglycosides and/or
aerosolized colistin. The overall clinical response rate was 100% compared with
55% in a matched group of patients who did not receive aerosolized therapy.
However, the outcomes for colistin and aminoglycosides were not reported
separately.[15]






Colistin






Similar to aminoglycosides, reports with aerosolized
colistin date from the 1960s (Table 2). Pines et al.
again reported poor outcomes (clinical improvement 24%) when adding aerosolized
colistin to intravenous colistin in 17 patients treated for 7–10 days.[5] However,
the use of systemic and aerosolized colistin has reemerged over the past decade
owing to the emergence of MDR P. aeruginosa and A. baumannii,
which are resistant to all other antibiotic choices such as carbapenems,
aminoglycosides and floroquinolones. Hamer reported a 100% cure rate in three
patients with MDR P. aeruginosa HAP treated for 11–14 days with
aerosolized colistin added to intravenous therapy.[16] Similarly,
16 patients with MDR A. baumannii VAP in another report also had a 100%
cure rate after 15 days of therapy.[17]
Interestingly, rifampicin was the systemic therapy used rather than intravenous
colistin.




Four other relatively small observational reports since 2004
involved a total of 46 patients with either MDR P. aeruginosa or A.
baumannii
HAP.[14,18–20]
Various systemic antibiotic regimens were used in all but one patient and the
mean treatment duration was 10–19 days. The clinical cure rates in these
reports were rather consistent (73–88%) and seem reasonable for treating MDR
organisms.




Fortunately, the most recent group of four studies had
better study designs and/or increased numbers of patients. All of the patients
in these studies were mechanically ventilated and higher quality culture
techniques were used. Michalopoulos et al. reported a prospective
observational study of 60 patients with P. aeruginosa, A. baumannii
or Klebsiella pneumoniae VAP treated for a mean of 16 days.[21] The
vast majority also received intravenous therapy (57 out of 60) and half of the
isolates were MDR. The clinical cure rate was 83% and the mortality rate
attributable to VAP was 17%. Similarly, Lin et al. reported a
retrospective observational study of 45 patients with MDR A. baumannii
VAP treated for a mean of 10 days.[22] All
patients also received intravenous therapy; however, the clinical cure rate was
lower than most other reports (58%). The overall mortality rate was high at
42%, but the VAP-related mortality was not reported. Pereira et al. also
reported an observational case series of 14 patients; mostly with P.
aeruginosa
. The combined cure or improvement rate was 93%.[23]




The largest and most well-designed study was a retrospective
matched case–control study of 43 VAP patients who received aerosolized and
intravenous colistin compared with 43 patients treated with intravenous
colistin monotherapy.[24]
Patients were matched based on age and APACHE II score and the mean treatment
duration was 10–13 days. Approximately 75% of patients had A. baumanii
and the remaining patients had K. pneumoniae or P. aeruginosa.
Unfortunately, there were no significant differences between the aerosolized
group and the control group in the combined clinical cure or improvement rate
(74 vs 60%) or VAP-related mortality (16 vs 26%). However, there was a
statistical trend towards decreased mortality in the aerosolized group (23 vs
42%; p = 0.066). Three important limitations of the study are the retrospective
design, the possibility of a type II error because of the small study size, and
a lack of reporting of antibiotic therapy prior to initiating colistin that
could have affected patient outcomes. Nonetheless, this is an important study
because of the case-matched design.




Three other reports deserve mention. A case series of five
patients with chronic P. aeruginosa pulmonary colonization were treated
with 4–8 days of aerosolized colistin alone.[25] All
patients had eradication of the organism. A larger observational study reported
on a mixed group of 71 patients with either HAP or pulmonary colonization with P.
aeruginosa
or A. baumannii.[26] Most
patients received intravenous therapy, and the mean duration was 11 days. The
eradication rate was 92%. These two reports are less important because it
wasn't clear which patients actually had HAP versus colonization. Last, a case
report showed successful treatment of Stenotrophomonas maltophilia VAP
with aerosolized colistin added to intravenous doxycycline in one patient who
failed trimethoprim/sulfamethoxazole therapy.[27]






β-lactams






Pines et al. again provided an early report, this
time with aerosolized carbenicillin added to intravenous in 15 patients with P.
aeruginosa
HAP (Box 1).[6] Only 47%
of patients responded well to 7–14 days of therapy. Other researchers in the
1980s added aerosolized cefotaxime or ceftazidime to the same antibiotic given
intravenous for HAP caused by various Gram-negative organisms.[28] The
cure rate was 96% in 25 patients.






Administration Considerations in
Mechanically Ventilated Patients






Because 90% of HAP patients have VAP, this article will
focus on administration issues only in mechanically ventilated patients. Also,
there are a number of unique issues in delivery of aerosolized medications in
mechanically ventilated patients. Outpatient administration of aerosolized
tobramycin results in delivery of approximately 10–20% of the dose to the lung.[29]
However, initial data examining the lung delivery of aerosolized medications in
mechanically ventilated patients showed that less than 3% of a dose reached the
lung.[30]
Not only was drug delivery poor, but it was highly variable with over a tenfold
difference in delivery depending on the administration techniques used.[31] It is
unclear why delivery is so poor during mechanical ventilation, but some
potential problems include deposition of drug in the tubing, the distance from
the site of aerosolization to the lung, the inability of patients to control
their breathing and the nonphysiologic nature of mechanical ventilation. Other
patient-related factors that may impair drug delivery include atelectasis,
mucus production, or possibly preexisting lung diseases such as asthma or
chronic obstructive pulmonary disease.




Thus, a series of laboratory and clinical studies were
performed to determine how to improve aerosol drug delivery during mechanical
ventilation.[29,32]
It has subsequently been shown that using optimal technique can increase lung
delivery by as much as 650%.[31] Factors
related to optimal aerosol delivery in mechanically ventilated patients are
listed in Box 1.
Ideally, hospitals would only use ventilators for which good aerosolized
delivery has been confirmed in studies. One study showed a high degree of
variability between four ventilators in aerosol delivery.[32]
However, very few comparative data are available. A reasonable alternative is
to ensure that ventilators used for antibiotic delivery should have a flow rate
greater than 6 l/min and that they only nebulize during inspiration rather than
continuously.[32]




The choice of nebulizer can also be important. One of the
primary determinants of lung deposition is the median mass aerodynamic diameter
(MMAD) of the particles generated. Lung deposition is optimized at a MMAD of
1–5 µm. Larger particles tend to deposit in the upper airways and smaller
particles tend to be exhaled.[29,32] Jet
nebulizers are the most widely used in ICUs. They are inexpensive, disposable
and generally produce acceptable particle size. The aforementioned studies
almost universally used jet nebulizers. Ultrasonic nebulizers can perform
better than jet nebulizers in producing better particle size and shorter
administration times. However, they require a specialized power supply at the
bedside, must be cleaned, and are more expensive.[32] Also,
some large drug molecules may be broken down during ultrasonic nebulization.[32] As
such, jet nebulizers are preferred for aerosolized antibiotic use in HAP. There
is no preferred model of jet nebulizer for HAP. Clinicians should ensure that
the nebulizer model being used creates a MMAD of 1–5 µm based on the
manufacturer's information.




Clinicians should also know the maximum fill volume for the
nebulizer being used. Starting administration with a full nebulizer results in
improved drug delivery.[32]
Aerosolized doses should be compounded to a total volume equivalent to the fill
volume.[29,32]
The placement of the nebulizer in the ventilator circuit also affects delivery.
The optimal site for placement is 30 cm from the endotracheal tube in the
inspiratory loop.[29,32] There
are also data showing that drug delivery is improved when the ventilator
humidification is turned off during nebulization.[29,32]
Obviously, it is important that humidification be resumed after the dose is
administered. Implementing this into practice will require more training and
vigilance than the other methods described here.






Safety & Tolerability






A number of pulmonary adverse events such as coughing and
bronchospasm can occur with outpatient use of aerosolized antibiotics. The only
adverse events reported in the aminoglycoside HAP studies were coughing and
dizziness in four patients.[5,10] No
other adverse events were reported. The vast majority of aminoglycoside HAP
reports used the intravenous formulation. A preservative-free formulation of
tobramycin for inhalation used in cystic fibrosis may theoretically provide a
better safety profile, but this has not been studied widely in HAP patients.
There are fewer data on the safety of aerosolized β-lactams; however, no
adverse events were reported in the HAP treatment studies or when ceftazidime
was used in trials of VAP prevention.[6,28,33,34]




Compared to aminoglycosides, aerosolized colistin may have a
worse adverse event profile. It was 'badly tolerated' in an earlier report but
a number of more recent studies reported that there were no adverse events.[14,17,19,24]
Hypotension was reported in one patient treated and cough or bronchospasm was
reported in four others.[23,33,35] This
did not occur with intravenous colistin in this patient. Another case report
showed hypersensitivity pneumonitis and fibrosis from aerosolized colistin used
to treat HAP.[36]
Most worrying is the report of death in a patient treated as an outpatient with
aerosolized colistin.[101] It is
thought that this patient suffered from a reaction to a toxic breakdown product
of colistin that occurred because the doses were prepared more than 24 h prior
to administration. Subsequently, the US FDA issued a public health advisory
that colistin be administered promptly after preparation.




Clinicians should be aware of several factors that can
improve tolerability of aerosolized antibiotics.[29,32]
Doses should be diluted in normal saline when dilution is needed to QS to the
maximum fill volume of the nebulizer being used. A sodium concentration of
77–154 mEq/l is associated with better tolerability. The pH of the dose should
also be roughly physiologic (4.0–8.0). There is a wide range of tolerable
osmolarity (150–1200 mOsm/l), but hypotonic solutions should be avoided. For patients
with chronic lung disease or who have had previous adverse events from an
aerosolized dose, pretreatment with albuterol should be considered (Box 1). Another option may
be to switch to the preservative-free tobramycin if the organism is sensitive
to it.




One of the potential benefits of aerosolized administration
is the potential for lower systemic concentrations and thus fewer adverse
events such as nephrotoxicity. It appears that aerosolized aminoglycosides do
not generate detectable serum concentrations in patients with normal renal
function.[29,32]
A recent study of nine critically ill HAP patients showed that the only patient
with a detectable tobramycin serum concentration (0.80 µg/ml) during
aerosolized therapy also had moderate renal dysfunction.[37]
Similarly, a lack of detectable serum concentrations was seen with aerosolized
ceftazidime.[33]
However, accumulation has been rarely reported, especially in patients with
renal dysfunction.[10,37]
Thus, assessing systemic accumulation in patients with renal dysfunction may be
prudent.






Expert
Commentary





Despite the fact that adjunctive aerosolized
antibiotics are commonly used in HAP, there is a disappointing amount of data
in the medical literature. Almost all of the studies were observational and did
not have control groups. Nonetheless, the relatively poor response rates seen
with intravenous therapy of HAP and the emergence of MDR organisms makes new
treatment options desirable. The ATS/IDSA HAP guidelines recommend that
"adjunctive therapy with an inhaled aminoglycoside or polymyxin (colistin)
for MDR Gram-negative pneumonia should be considered, especially in patients
who are not improving.[1] "
The recommendations by the Society of Infectious Diseases Pharmacists are
similar.[38]




However, is it still unclear from the literature if
aerosolized antibiotics provide an additional benefit in HAP. If one discounts
the universally poor results seen by the early studies by Pines et al., aminoglycoside cure rates
were 67–100% in a total of over 165 patients[6–14] and
colistin cure rates were 58–100% in a total of over 200 patients.[14,16–24]
Given than many of these patients had MDR organisms or had failed intravenous
therapy alone, these cure rates seem to compare favorably to the baseline cure
rate of 63% for VAP seen in clinical trials. The only randomized study did show
a benefit; but that study is from the 1970s.[8]
Unfortunately, the most recent and best designed study with colistin failed to
show a benefit.[24]




There are also questions regarding the quality of the
data. There could have been publication bias over time such that clinicians
only reported positive experiences. Obviously, there is a lack of controlled
studies and the numbers are low. Perhaps more concerning are the vast
differences in ICU care over the decades between the early reports and today in
any number of areas. Many of the early reports included nonmechanically
ventilated patients or did not report whether patients were mechanically
ventilated. It is also difficult to determine the severity of illness of those
patients. The culture techniques were also not well described in earlier
studies. Thus, it is not clear if those patients truly had HAP. Some patients
were treated with aminoglycoside monotherapy for HAP which is not acceptable in
the modern context based on poor cure rates.[1]
Fortunately, reports from the 2000s have generally become larger and more
rigorous in important aspects of HAP care. For instance, the recent reports
focused only on VAP patients, used far better microbiologic techniques for
diagnosis and were likely to have used better administration techniques.
Although most studies did a very poor job of describing drug administration in
detail.




Ultimately, the risk versus benefit analysis seems to
be somewhat in favor of using aerosolized antibiotics in selected patients.
Such patients might include those:





  • Not responding to
    intravenous therapy alone;

  • Who are being treated for
    a recurrence of the same organism;

  • Who have MDR organisms.



This recommendation is based on what seems to be good
cure rates in difficult-to-treat cases. This is balanced by a rather benign
adverse event profile based on limited data – at least for aminoglycosides.
Aminoglycosides should be the drug of choice when they can be used based on in vitro sensitivity. Colistin
should only be used for aminoglycoside-resistant isolates based on what seems
to be a higher risk of adverse events. Clinicians should also take care that
doses are optimally compounded and administered to ensure the best drug
delivery possible.




Regarding dosing, a wide range of doses were used
clinically in the reports described. The Society of Infectious Diseases
Pharmacists statement also provides dosing recommendations.[38] A
reasonable approach when using gentamicin or tobramycin is to use 300 mg every
12 h. This is the FDA-approved dose in cystic fibrosis. There are very few data
to guide amikacin dosing, but the drug is typically dosed approximately three
times higher than gentamicin and tobramycin when administered systemically, so
a dose of 500–1000 mg every 12 h seems reasonable. A colistin dose of 150 mg every
12 h is reasonable based on recent reports. Although the prescribing
information recommends 25–50 mg two to three times per day. Note that these
doses are based on the Coly-Mycin M product (Monarch Pharmaceuticals, TN, USA)
in the USA, which is dosed in mg of active colistin. The Colomycin product
(Forest Laboratories UK, Dartford, UK) has 30–33 mg of active colistin per 80
of colistimethate sodium (equivalent to 1 million units).






Five-year
View





Current
Research



In 5 years from now, the first large randomized,
placebo-controlled clinical trial of aerosolized antibiotics in HAP might have
been completed.[102]
This will be a clear landmark in this area for two reasons. First, this will be
by far the largest and most rigorous study to date. Second, the study will use
a new generation of nebulizer technology: vibrating mesh plate nebulizers.
These nebulizers seem to provide much better drug delivery than jet nebulizers.[38] A
pharmacokinetic trial of a new aerosolized amikacin product in VAP patients
showed excellent drug delivery to the lung.[39] If this
study is successful at showing that adding the aerosolized plus intravenous
therapy is superior to intravenous therapy alone, then it could potentially
create a dramatic shift in the treatment of HAP. One could also envision a
middle ground where aerosolized therapy only adds a benefit in certain
situations based on patient- or organism-related factors. Although such an
outcome would likely not result in FDA approval. If the study shows no benefit
for aerosolized therapy, then it will cast a very negative light on this
therapy.




Future
Research



With a lack of any other currently registered clinical
trials under development, it appears that clinician-investigators will have to
continue to report on their experiences with aerosolized antibiotics.
Hopefully, some will use the higher-level techniques, as seen in the recent
case-matched study, to better determine if there is a beneficial effect.
Ideally, more prospective, randomized, double-blinded trials will be performed.
However, the funding challenges for such a trial are clear. Funding would have
to come from the federal government or from a manufacturer developing an
aerosolized drug formulation. A welcome advance would be more data on the use
of β-lactams, which appear to be well tolerated. Data on aerosolized quinolones
may also be available in 5 years, although more likely in other indications
than HAP. Even more on the cutting edge are potential advances in drug
formulations using lipid-based products, or new-generation dry powder delivery
that could improve lung deposition.