Thursday, November 15, 2018

Why Edward Gibbon is the historian of historians?

一個好的歷史家的來源(source/material) 最好是在事件發生的年代或離那年代不久的歷史學家所寫的.  Edward Gibbon 之所以是 the historian of historians 是因為他寫 The History of the Decline and Fall of the Roman Empire 時都根據 Roman historians (such as Tacitus, Suetonius) 所寫的歷史,Roman historians 是用拉丁文寫的。
Churchill  A history of English Speaking People 時有提到他是根據某某的 English translation of Tacitus’s works. (Churchill 有次提到為什麼他的英文特別好,他説當他的同學都在學 Latin and Greek 時,他只在學英文)Julius Caesar 兩度 進軍British Islands,大概是 Jesus 誕生的 50 年前。所以要寫英倫歷史是要牽涉到羅馬歷史的。

Gibbon  Latin, Greek, and French, 因為很多古老歷史的書都用這些語言寫的。當然一個好的歴史家還要知道如何 interpret data, 而且語言能力要好。Gibbon 擁有這些條件。當然也要有公正,not biased opinion and integrity of moral character, 這就比較困難,就我所知,Gibbon 有點反 organized religion, 這點我自己還沒讀出來。
The Great Books of the Western Word have 2 books of Gibbon's

我舉個例子來説明 Gibbon 如何利用 Tacitus and  Suetonius 的資料。在説明為什麼Roman Empire 想征服 British islands, 其中一個原因是謠言英倫有「pearl fishery」(珍珠),後來發現英倫的珍珠沒有想像的那麼好。

(以下是 來自 Gibbon  Roman Empire)

 The only accession which the Roman Empire received, during the first century of the Christian Aera, was the province of Britain.  In this single instance, the successors of Caesar and Augustus were persuaded to follow the example of the former, rather than the precept of the latter.  The proximity of its situation to the coast of Gaul 【歐洲大陸本土】seemed to invite their arms; the pleasing though doubtful intelligence of a pearl fishery, attracted their avarice; 6

6 (return) [Caesar himself conceals that ignoble motive; but is mentioned by Suetonius, c. 47.  The British Pearls proved, however, of little value, on account of their dark and livid color.  Tacitus observers, with reasons, (in Agricola, c. 12,) that it was an inherent defect. “Ego facility’s crediderim, natural margaritas deesee qualm nobis avaritiam.”]

Julius Caesar 自己都有寫下他進攻 Britain 的經過,但是都沒有提到 pearls fishery 之事,堂堂 Caesar emperor 一個,怎麼可以為了區區幾個珍珠 千軍萬馬 飃洋過海 進攻英倫呢,但是歴史學家不會放過他的。

Churchill, in his A History of English Speaking People 也提到 pearls fishery.
Churchill's A History of English Speaking People

To Caesar the Island now presented itself as an integral part of his task of subjugating the Northern barbarians 【只要不是 Romans, 其他的人都是 barbarians, 只要不是漢人,真他的人都是番人,古今中外皆然】to the rule and system of Rome.
The natives, though uncouth, had a certain value as slaves for rougher work on the land, in mines, even about the house.  There was talk of a pearl fishery, and also of gold.

由此可知 Gibbon  Churchill 都根據同資料只是 Gibbon 讀原文(Latin); Churchill 讀英文翻譯。

Friday, November 9, 2018

Using Cytosponge cell-collection technique in detecting Barrett's esophagus

(A friend 問我一個關於 cytosponge 的問題,食道逆流及 Barrett’s esophagus 是很常見的毛病,大家可能有興趣聽聽。)

The following is the link to the YouTube talking about “Cytosponge” cell-collection technique. (Cytosponge was developed at Cambridge U in UK, so the doctor is from Cambridge U. FDA approved it in 2014 or 2015)


食道逆流會引起食道發炎(esophagitis) 厲害的話叫 erosive esophagitis, 進而引起 Barrett’s esophagus.

What is the big deal for Barrett’s esophagus? 因為它會引起食道癌。食道的表面細胞跟腸胃的細胞構造不同。腸胃的表面細胞的設計是可以抗胃酸,而食道的表面細胞則不能抗胃酸。

開始有食道胃酸逆流,時間久了,食道的表面細胞 “get smart”, 它看到腸胃的表面細胞可以抗胃酸,它也"搖身一變",變成跟腸胃的表面細胞一樣 (change from squamous cell to columnar cell). (其 genetic alteration 非常複合雜,我這麼説比較容易了解,而且雖不中,亦不遠已)

新形成的食道表面細胞(現在跟腸胃的一様)因為不是上帝設計的原裝的 ,所以細胞分裂時比較容易發生問題, 而且 genetic repair 的功能較不好,所以有時候會引起癌症 (recall all cancers are genetic as some experts would say, when I say "genetic", do not confuse with "herediatry").

Barrett’s esophagus 變成癌症的機會有多少? 0.1% 5-6%,看情形而定.  (0.1% 1000 個有 Barrett’s esophagusv的人每年只有一個得食道癌。5% 100 個有 5 個得食道癌).  做胃鏡時對有 Barrett esophagus 的地方做切片檢查(biopsy) 若有 dysplasia  那得癌症的機會大大増加.

Barrett's esophagus
Barrett's esophagus can be see upon doing an endoscopy (esophago-gastro-duodenal endoscopy or EGD or 胃鏡) without doing a biopsy (切片檢查), but one has to do biopsy to know whether there is "dysplasia" or not (a very important information).

也是這個原因:有 Barrett’s esophagus 的人每兩,三年 或四,五年要做一次胃鏡(其實是 Esophago-gastro-duodenoscope or EGD, 檢查食道,胃及十二指腸)看看有沒有食道癌.


胄鏡是 invasive procedure, 也不是完全沒有危險性. 這是發明 cytosponge procedure 的原因. 吞下一粒膠囊(此膠囊接有一條線留在外頭 沒有吞下)膠囊在胃解, 內的一個 mesh sponge 就  burst open, 然後拉出來,經過食道時會把食道的表面細胞帶出來。檢查這些細胞若發現有一種東西(trefoilbfactor 3 TFF3) 就表示有 Barrett’s esophagus. (sensitivity is about 73%, specificity 93%)也就是說 TFF3 Barrett’s esophagus bio marker.

所以做 cytosponge, 不用做 invasive 的胃鏡就能知道有沒有  Barrett’s esophagus, 真是太好了。但是好處也是到此為止。

知道了有 Barrett’s esophagus, 以後就是要跟蹤是否有食道癌,胃鏡是很好的 tool, 但是 cytosponge 只告訴你是否有 Barrett’s esophagus, 但是不能告訴你是否變成食道癌了。The Youtube has a title saying "early detection of esophageal cancer", 其實就我所知 Cytosponge 只証明能診斷 Barrett’s esophagus, 目前還有 study 証明它能診斷食道癌,臨床上也沒有人這麼做。如果吞一粒膠囊就能知道有沒有食道癌 那真是太好了,The progress of medicine is inexorable (non-stoppable), hopefully that day will come.

而且要知道是否有 dysplasia (此時變成癌大大增加)一定要做 胄鏡及切片。

我的看法是: cytosponge 確有其可用之處,但不能取代胃鏡. 因為 cytosponge 確能知道是否有 Barrett’s esophagus (正確性是73%,不是100%)以前是一定要做胃鏡檢查才能知道.

但是做 cytosponge 而知道有 Barrett’s esophagusso whatwhat will be the next step?有了 Barrett’s esophagus 要跟蹤有沒有變成食道癌,但是每年繼續做 cytosponge 也沒有用(目前 cytosponge 的技術只能看出是否有 Barrett’s esophagus, 而不能看出是否有食道癌,or at least the technique is not reliable,希望技術能繼續改進)

有些專家也不認為所有 有 Barrett’s esophagus 的人都要常常做胃鏡,因為發現的比例很少,我的看法是若有 dysplasia 的話 (要做胃䭗切片檢查才能知道)那是一定要每隔幾年做一次胃鏡.



是不是每個有食道胃酸逆流的人都要做胃鏡(或 cytosponge) 看看有沒有 Barrett’s esophagus, 也是一個爭論的問題,一來變成癌症的機率很小. New England Journal of Medicine 一篇文章說 “Barrett’s esophagus is a strong risk factor for esophageal adenocarcinoma (cancer), but the absolute annual risk, 0.12%is much lower than the assumed risk of 0.5%, which is the basis for ongoing surveillance guideline.”

也就是說目前對有 Barrett’s esophagus 的人都定期(2 5 ) 做胃鏡, 是因為以前認為變癌症的機率是 0.5%, 現在認為 0.12%。該文章也認為有 dysplasia 的話還是要追蹤,因為厲害的(high grade) dysplasia 變癌症會增加到 5%或以上. 問題是不做胃鏡及切片檢查,就不知道有 dysplasia. 

有一個非常好的 study 發現被診斷有 esophageal adenocarcinoma ( Barrett‘s esophagus 引起的癌都是這一種),這以前被診斷有Barrett’s esophagus 的不到10%, 這表示我們在做胃鏡定期追蹤,其實效果非常不好。It looks like we doctors are not knowing what we are doing.  We can only do our best, constantly looking for new data, for without data, a doctor is only one with an opinion.

如果某人有輕微的 Barrett’s esophagus (沒有dysplasia), 一生得食道癌的機會可説是接近零,但是他一生將永遠有這個陰影. 如果這個陰影是醫生造成的, then we are not doing a service to the patients.  我若繼續談下去, 我將要談哲學,而不是醫學了. 最好就此打住.

Thursday, November 1, 2018

Reading science and medicine in nobel.com, I discover a captivating and beautiful musician


There was hardly a week went by without my looking into nobel.com site many times, rarely did I came back empty handed, I almost always discovered something, like today I found out the leukocyte (white blood cell) neutrophil eating the bacteria (invader) was the 1908 Nobel Prize in Medicine, that is to say the discovery was more than 110 years ago. We now know that was the initial step of the innate immunity.

Nobel laureate Frances Arnold of Caltech
I was trying to find out how Frances Arnold of Caltech uses evolutionary theory to design enzymes of medical uses or as she said “to copy nature's design process”, sort of tinkering the nature. She said “all this tremendous beauty and complexity of the biological world all comes about through this one simple, beautiful design algorithm, and what I do is use that algorithm to build new biological things.” It never escapes my notice that the first rated scientist always sees the the truth and beauty of the science involved, something beyond the reach of we mortals. George Smith of U. of Missouri and Sir Gregory Winter of Cambridge U. shared the award with her, they use the phage to display peptides and antibodies designed this way. I have been fascinated by how the phage (bacteriophae, the virus that invades the bacteria) contributed to the advance in science and medicine.

Violinist Lisa Batiashvili
But I have to wait for the answers until December 8 when they deliver their Nobel Lectures. But, I still didn't come back empty handed, as I discovered a captivating and beautiful musician, Lisa Batiashvili, the Georgia born violinist, who will be the soloist in the Nobel Prize Concert on December 8.

She grew up in Georgia until 11-years-old when the family left for Europe and eventually settled in Germany. Both parents are musicians. In one of the interviews she talked about how her family emigrated to Europe; they took the train to Moscow, where the policemen took all their money. An article in NY Times (1/31/2015) with a title of "Politics is Personal, and Professional" in which a story was told. She was once invited to perform with the Rotterdam Philharmonic Orchestra led by Valery Gergiev who has close ties to Russia’s president, Vladimir V. Putin. Ms. Batiashvili, who has vowed not to perform in Russia. She accepted the invitation, but prepared a gesture of protest. She commissioned an encore for solo violin from a Georgian composer, Igor Loboda, titled “Requiem for Ukraine,” which she performed after her concerto.

Lisa Batiashvili plays an encore for the people in the Ukraine at Philharmonie Berlin

Lisa Batiashvili performing with husband, an oboist
In the interview she reminisces the nature and the mountains of her native country, Georgia. She is not just a musician with a pretty face,

Classic Talk: Interview with Lisa Batiashvili: Part 1

playing Georgia "Lalem"
She was the artist in residence with the New York Philharmonic in 2015. Being an ignoramus in music, I am reluctant to introduce a musician to you. But if you watch the Youtube of Sibelius Violin Concerto in D minor, you may agree with me why she was chosen as the soloist in this year Nobel Prize Concert, as we all know only the best, in science or in humanity or in music, is associated with the Nobel Prize. There is an encore (at 36:05) of Traditional Georgia “Lalem”.

SIBELIUS Violin Concerto

performing with Philadelphia Orchestra