2007年5月25日星期五
单纯的图片不好看。
yeah,it's not nice to post only photos on blogger,it's simple,monotonous as a whole.it's better to post photos with words together than only images present in blogger.ok,today is friday,another weekend.Hope that I could complete professional article reading and well slide-making in this weekend,it's hard work since molecular ecology is not my speciality.
2007年5月23日星期三
FDA approves ‘ethnic’ drug
The US Food and Drug Administration (FDA) has approved the first ever drug marketed for use solely in a specific ethnic group. BiDil, produced by US company NitroMed, has been approved for the treatment of heart failure in self-identified black patients, having been through clinical trials for the treatment of African Americans (see November 2004 newsletter item). This decision has been made amid considerable controversy; critics say that using race or ethnicity as a marker for genetic differences is crude and inaccurate, and fear that approval of BiDil lends weight to notions of race as a distinct biological marker. Others, such as the Association of Black Cardiologists, who sponsored the Nitromed trials, welcomed the decision.
FDA Associate Director of Medical Policy Dr Robert Temple said the drug was "a striking example of how a treatment can benefit some patients even if it does not help all patients”, adding that they hoped in the future “to discover characteristics that identify people of any race who might be helped by Bidil" (see FDA press release). However, some fear that marketing of a race-specific drugs is likely to be driven by financial motives irrespective of the validity of using ethnicity as a marker for genetic variation between individuals; BiDil is a combination of two pre-existing drugs, isosorbide dinitrate硝酸异山梨酯 and hydralazine肼屈嗪, for which the patent covering general use will expire in 2007; patent protection for the use of BiDil in black patients will extend until 2020
GENOMIC ANALYSIS
While BiDil® (isosorbide dinitrate/hydralazine hydrochloride) provides an effective treatment that has been shown in the African American Heart Failure Trial (A-HeFT) to save lives and improve the symptoms of self-identified black patients with heart failure, NitroMed regards this study as a first step in refining the understanding of why these patients may respond differently to BiDil than non-blacks.
Ongoing analysis of the genetic data from A-HeFT may help researchers identify other patient populations in whom BiDil can be studied, potentially leading to a new generation of personalized medicine.
NitroMed has presented preliminary results from ongoing analyses of data collected during A-HeFT that may determine whether specific variations of genes important in cardiovascular diseases can act as genetic markers for heart failure patients who best respond to treatment with BiDil.
NitroMed collected data from 358 patients who participated in A-HeFT in order to conduct the Genetic Risk Assessment in Heart Failure Trial (GRAHF), a prospectively defined genetic analysis of these A-HeFT patients developed to help identify specific, shared biomarkers within patient cohorts to delineate additional subsets where BiDil may also be effective.
In the GRAHF study, the frequency of genotypes important for cardiovascular diseases were determined amongst self-identified black patients who participated in both GRAHF and A-HeFT, and compared with the frequency of those same genotypes amongst white heart failure subjects who participated in the Genetic Risk Assessment of Cardiac Events (GRACE) study at the University of Pittsburgh.
To date, preliminary results from the GRAHF study on three gene variations (endothelial nitric oxide synthase, aldosterone synthase, and beta-1 adrenergic receptor) have been presented, offering the first preliminary data on genetic factors that may affect BiDil response.
Endothelial nitric oxide synthase (NOS3) gene researchers found that a majority of black patients in A-HeFT possess a specific gene variation that was observed in less than half of the white cohort from GRACE. NOS3, which encodes the nitric oxide synthesizing enzyme in the heart and vasculature, is important in hypertension and heart failure. The benefit of BiDil therapy on the primary composite score from A-HeFT - combining mortality, first heart failure hospitalization and patient functional status - was seen in those possessing the specific NOS3 gene variation.
Aldosterone synthase gene researchers examined a common genetic variation existing in the region of the gene at position -344 (C/T). Abnormally high levels of aldosterone, a hormone important in the control of salt and water balance in the body, can cause sodium retention and high blood pressure. Researchers discovered a racial difference in the frequency of -344 C/T variations. It was found in GRAHF that 62 percent of black patients with heart failure possessed the genotype TT, while 38 percent were either TC or CC. Comparatively, in GRACE, about one-third of white patients with heart failure possessed the TT variation. A-HeFT patients participating in GRAHF with the -344 C allele, which has been linked to increased aldosterone production, were found to have the greatest event-free survival (risk for death or hospitalization for heart failure). A-HeFT patients, participating GRAHF, with the TT variation were found to have the lowest risk for death or hospitalization for heart failure. In addition, BiDil-treated patients with the TT variation had statistically better primary composite scores compared to patients who received placebo, driven primarily by improvement in functional status. Composite scores include all-cause mortality, first heart failure hospitalization and changes in functional status at six months.
An additional analysis in GRAHF examined variations in the beta-1 adrenergic receptor represented by Gly389Arg polymorphism. The beta-1 adrenergic receptor is involved in the regulation of cardiac rhythm and fluency. The Arg389 gene varation is associated with increased receptor activity and has previously been linked to greater beta-blocker impact. In GRAHF, 32 percent of black heart failure patients, and in GRACE, 49 percent of white heart failure patients, possessed an Arg389Arg variation. The Arg389Arg patients treated with BiDil in A-HeFT experienced significantly better primary composite scores compared to Arg389Arg patients treated with placebo and standard therapy (composite score of 0.40 for BiDil vs. -0.25 for placebo, p=0.047).
BiDil®
In July 2005, NitroMed introduced a prescription medicine named BiDil® (isosorbide dinitrate and hydralazine hydrochloride) to the market. During previous years, BiDil underwent a carefully controlled clinical study referred to as A-HeFT (The African American Heart Failure Trial). A-HeFT demonstrated the drug's effectiveness in improving symptoms in African American patients, when taken as an add-on to their standard heart failure medicines. BiDil was also shown to significantly improve survival and decrease time to first hospitalization for heart failure, compared to patients treated with standard therapy alone. Based on this clinical evidence, BiDil was approved by the U.S. Food and Drug Administration (FDA) in June 2005.
BiDil is indicated for the treatment of heart failure as an adjunct to standard therapy in self-identified black patients to improve survival, to prolong time to hospitalization for heart failure, and to improve patient –reported functional status. There is little experience in patients with NYHA class IV heart failure. Most patients in the clinical trial supporting effectiveness (A-HeFT) received a loop diuretic, an angiotensin converting enzyme inhibitor or an angiotensin II receptor blocker, and a beta blocker, and many also received a cardiac glycoside or an aldosterone antagonist.
What is BiDil?
BiDil is a fixed-dose combination of hydralazine hydrochloride and isosorbide dinitrate (ISDN). Hydralazine is an arterial vasodilator; it relaxes the arteries so the heart doesn’t have to work as hard to push blood through them. Isosorbide dinitrate is also a vasodilator, with effects on both the veins and the arteries. ISDN releases nitric oxide at the blood vessel wall, but its effect wears off rapidly 1. Hydralazine is thought to prevent the loss of ISDN’s effect 2, however the exact mechanism of how the two drugs work together is not fully understood.
1. Preik M, Kelm M, Feelisch M, Strauer BE. Impaired effectiveness of nitric oxide-donors in resistance arteries of patients with arterial hypertension. J Hypertens. 1996;14:903-8.
2. Munzel T, Kurz S, Rajagopalan S, et al. Hydralazine prevents nitroglycerin tolerance by inhibiting activation of a membrane-bound NADH oxidase. A new action for an old drug. J Clin Invest 1996;98:1465-70.
BiDil® PUBLICATIONS
Angus, D.C., Linde-Zwirble, W.C., Tam, S,W., Ghali, J.K, Sabolinski, M.L.,Villagra,V.G., Winkelmayer, W.C., Worcel, M. Cost-Effectiveness of Fixed-Dose Combination of Isosorbide Dinitrate and Hydralazine Therapy for Blacks with Heart Failure. Circulation 112: 3745-3753 (2005)
Taylor, A.L., Ziesche, S., Yancy, C., Carson, P., D’Agostino, R. Jr., , Ferdinand, K, Taylor, M., Adams, K., Sabolinski, M., Worcel, M., Cohn, J.N. and the A-HeFT Investigators. Combination of Isosorbide Dinitrate and Hydralazine in African Americans with Heart Failure. N. Engl. J. Med., 351: 2049-2057 (2004)
Taylor, A.L., Cohn, J.N., Worcel, M., Franciosa, J.A. A-HeFT Investigators, African-American Heart Failure Trial. The African-American Heart Failure Trial: background, rationale and significance. J Natl. Med. Assoc. 94: 762-769 (2002)
FDA Associate Director of Medical Policy Dr Robert Temple said the drug was "a striking example of how a treatment can benefit some patients even if it does not help all patients”, adding that they hoped in the future “to discover characteristics that identify people of any race who might be helped by Bidil" (see FDA press release). However, some fear that marketing of a race-specific drugs is likely to be driven by financial motives irrespective of the validity of using ethnicity as a marker for genetic variation between individuals; BiDil is a combination of two pre-existing drugs, isosorbide dinitrate硝酸异山梨酯 and hydralazine肼屈嗪, for which the patent covering general use will expire in 2007; patent protection for the use of BiDil in black patients will extend until 2020
GENOMIC ANALYSIS
While BiDil® (isosorbide dinitrate/hydralazine hydrochloride) provides an effective treatment that has been shown in the African American Heart Failure Trial (A-HeFT) to save lives and improve the symptoms of self-identified black patients with heart failure, NitroMed regards this study as a first step in refining the understanding of why these patients may respond differently to BiDil than non-blacks.
Ongoing analysis of the genetic data from A-HeFT may help researchers identify other patient populations in whom BiDil can be studied, potentially leading to a new generation of personalized medicine.
NitroMed has presented preliminary results from ongoing analyses of data collected during A-HeFT that may determine whether specific variations of genes important in cardiovascular diseases can act as genetic markers for heart failure patients who best respond to treatment with BiDil.
NitroMed collected data from 358 patients who participated in A-HeFT in order to conduct the Genetic Risk Assessment in Heart Failure Trial (GRAHF), a prospectively defined genetic analysis of these A-HeFT patients developed to help identify specific, shared biomarkers within patient cohorts to delineate additional subsets where BiDil may also be effective.
In the GRAHF study, the frequency of genotypes important for cardiovascular diseases were determined amongst self-identified black patients who participated in both GRAHF and A-HeFT, and compared with the frequency of those same genotypes amongst white heart failure subjects who participated in the Genetic Risk Assessment of Cardiac Events (GRACE) study at the University of Pittsburgh.
To date, preliminary results from the GRAHF study on three gene variations (endothelial nitric oxide synthase, aldosterone synthase, and beta-1 adrenergic receptor) have been presented, offering the first preliminary data on genetic factors that may affect BiDil response.
Endothelial nitric oxide synthase (NOS3) gene researchers found that a majority of black patients in A-HeFT possess a specific gene variation that was observed in less than half of the white cohort from GRACE. NOS3, which encodes the nitric oxide synthesizing enzyme in the heart and vasculature, is important in hypertension and heart failure. The benefit of BiDil therapy on the primary composite score from A-HeFT - combining mortality, first heart failure hospitalization and patient functional status - was seen in those possessing the specific NOS3 gene variation.
Aldosterone synthase gene researchers examined a common genetic variation existing in the region of the gene at position -344 (C/T). Abnormally high levels of aldosterone, a hormone important in the control of salt and water balance in the body, can cause sodium retention and high blood pressure. Researchers discovered a racial difference in the frequency of -344 C/T variations. It was found in GRAHF that 62 percent of black patients with heart failure possessed the genotype TT, while 38 percent were either TC or CC. Comparatively, in GRACE, about one-third of white patients with heart failure possessed the TT variation. A-HeFT patients participating in GRAHF with the -344 C allele, which has been linked to increased aldosterone production, were found to have the greatest event-free survival (risk for death or hospitalization for heart failure). A-HeFT patients, participating GRAHF, with the TT variation were found to have the lowest risk for death or hospitalization for heart failure. In addition, BiDil-treated patients with the TT variation had statistically better primary composite scores compared to patients who received placebo, driven primarily by improvement in functional status. Composite scores include all-cause mortality, first heart failure hospitalization and changes in functional status at six months.
An additional analysis in GRAHF examined variations in the beta-1 adrenergic receptor represented by Gly389Arg polymorphism. The beta-1 adrenergic receptor is involved in the regulation of cardiac rhythm and fluency. The Arg389 gene varation is associated with increased receptor activity and has previously been linked to greater beta-blocker impact. In GRAHF, 32 percent of black heart failure patients, and in GRACE, 49 percent of white heart failure patients, possessed an Arg389Arg variation. The Arg389Arg patients treated with BiDil in A-HeFT experienced significantly better primary composite scores compared to Arg389Arg patients treated with placebo and standard therapy (composite score of 0.40 for BiDil vs. -0.25 for placebo, p=0.047).
BiDil®
In July 2005, NitroMed introduced a prescription medicine named BiDil® (isosorbide dinitrate and hydralazine hydrochloride) to the market. During previous years, BiDil underwent a carefully controlled clinical study referred to as A-HeFT (The African American Heart Failure Trial). A-HeFT demonstrated the drug's effectiveness in improving symptoms in African American patients, when taken as an add-on to their standard heart failure medicines. BiDil was also shown to significantly improve survival and decrease time to first hospitalization for heart failure, compared to patients treated with standard therapy alone. Based on this clinical evidence, BiDil was approved by the U.S. Food and Drug Administration (FDA) in June 2005.
BiDil is indicated for the treatment of heart failure as an adjunct to standard therapy in self-identified black patients to improve survival, to prolong time to hospitalization for heart failure, and to improve patient –reported functional status. There is little experience in patients with NYHA class IV heart failure. Most patients in the clinical trial supporting effectiveness (A-HeFT) received a loop diuretic, an angiotensin converting enzyme inhibitor or an angiotensin II receptor blocker, and a beta blocker, and many also received a cardiac glycoside or an aldosterone antagonist.
What is BiDil?
BiDil is a fixed-dose combination of hydralazine hydrochloride and isosorbide dinitrate (ISDN). Hydralazine is an arterial vasodilator; it relaxes the arteries so the heart doesn’t have to work as hard to push blood through them. Isosorbide dinitrate is also a vasodilator, with effects on both the veins and the arteries. ISDN releases nitric oxide at the blood vessel wall, but its effect wears off rapidly 1. Hydralazine is thought to prevent the loss of ISDN’s effect 2, however the exact mechanism of how the two drugs work together is not fully understood.
1. Preik M, Kelm M, Feelisch M, Strauer BE. Impaired effectiveness of nitric oxide-donors in resistance arteries of patients with arterial hypertension. J Hypertens. 1996;14:903-8.
2. Munzel T, Kurz S, Rajagopalan S, et al. Hydralazine prevents nitroglycerin tolerance by inhibiting activation of a membrane-bound NADH oxidase. A new action for an old drug. J Clin Invest 1996;98:1465-70.
BiDil® PUBLICATIONS
Angus, D.C., Linde-Zwirble, W.C., Tam, S,W., Ghali, J.K, Sabolinski, M.L.,Villagra,V.G., Winkelmayer, W.C., Worcel, M. Cost-Effectiveness of Fixed-Dose Combination of Isosorbide Dinitrate and Hydralazine Therapy for Blacks with Heart Failure. Circulation 112: 3745-3753 (2005)
Taylor, A.L., Ziesche, S., Yancy, C., Carson, P., D’Agostino, R. Jr., , Ferdinand, K, Taylor, M., Adams, K., Sabolinski, M., Worcel, M., Cohn, J.N. and the A-HeFT Investigators. Combination of Isosorbide Dinitrate and Hydralazine in African Americans with Heart Failure. N. Engl. J. Med., 351: 2049-2057 (2004)
Taylor, A.L., Cohn, J.N., Worcel, M., Franciosa, J.A. A-HeFT Investigators, African-American Heart Failure Trial. The African-American Heart Failure Trial: background, rationale and significance. J Natl. Med. Assoc. 94: 762-769 (2002)
2007年5月22日星期二
病理科的地位
今天下午在科里研三的同学在答辨了，下午又要做外检，但还是抽空去听了一个科里的博士做的答辨，她讲的内容倒没听进去多少，却由此想到了病理科的发展和未来。她做的课题是甲状腺癌的一些相关研究，血管淋巴管生成因子，以前一些基因方面的东西，因为没听进去多少，也不好在此多说。因为病理工作做的是临床外检，也就是要给美人做出病理诊断，这个工作的重复性很强，因为大多数在临床外检中碰到的都是简单易诊断的病例，虽然这需要的相关专业知识相当强，实际上做临床病理的，大多数时间都在做外检，，对病理学的另一项重要功能，那就是研究疾病的发病机制，很少涉及，现在病理科做的课题，多为对形态学的一种研究，而我认为在当今，对疾病的发病机制研究应该更多的深入到分子水平。
病理为医之本，不是体现在做外检能够给医学做出重要贡献，而是体现在病理要去研究疾病之理，而我觉得病理科越来越淡化观念，疾病之理的研究更多的发生 在生物专业，各个医学临床专业，病理学特别是医院病理科越来越成为检验科性质的科室。
另外，越来越觉得现在的病理学是一门医学工具学科，就像学工学理的要学数学一样，各临床专业做课题时都要用病理学提供的方法是HE，IHC，电镜来研究形态学，但是过了二十以后这种现象还会发生吗？如果病理科对分子生物学，对基因工程一窍不通，以后的工具学科的地位将被新兴科室取代，二十院庆时巴德年院士提出了Prediction, Prevention and Personalized 三P医学，疾病重在发病前期，要能从基因水平推测可能会性的疾病，做出预防，等到了那个时代，我们病理科也应该处在举足轻重的地位。
也许病理科以后会有个新的子科室，分子病理科，对于我们现在天天埋头看片子的人来说，希望能多学点分子方面的知识，以备无患。
病理为医之本，不是体现在做外检能够给医学做出重要贡献，而是体现在病理要去研究疾病之理，而我觉得病理科越来越淡化观念，疾病之理的研究更多的发生 在生物专业，各个医学临床专业，病理学特别是医院病理科越来越成为检验科性质的科室。
另外，越来越觉得现在的病理学是一门医学工具学科，就像学工学理的要学数学一样，各临床专业做课题时都要用病理学提供的方法是HE，IHC，电镜来研究形态学，但是过了二十以后这种现象还会发生吗？如果病理科对分子生物学，对基因工程一窍不通，以后的工具学科的地位将被新兴科室取代，二十院庆时巴德年院士提出了Prediction, Prevention and Personalized 三P医学，疾病重在发病前期，要能从基因水平推测可能会性的疾病，做出预防，等到了那个时代，我们病理科也应该处在举足轻重的地位。
也许病理科以后会有个新的子科室，分子病理科，对于我们现在天天埋头看片子的人来说，希望能多学点分子方面的知识，以备无患。
2007年5月21日星期一
blog this song.
这仅仅是个测试，blogger中很难嵌入音频，除了google video外，但到目前为止，googlevideo还不在中国开放。于是在网上插索了一下，发现了这个http://www.blogthissong.com/index.php，它能提供代码将音乐播放器嵌入到博客中，好啊。但是好像只支持mp3格式音频，用tingroom上的rm格式试了下，不行。
新装IE7
新装了ie7，以前多半用的还是FIREFOX，挺好用的，不过最近IE7炒的火热，我也不免落了俗，总想趁热打铁，把自己的IE6升级到了IE7，发现在各方面IE7都比IE6有较大的改善，IE7通过IE pro, 一款对其优化的软件，能将IE7古板的浏览方式变的有趣，浏览网页时能得到很大的方便，和我以前用的 maxthon越来越像，可以说，到目前为主，主流的浏览器都已经支持多标签式浏览，能有效对广告进行过滤，能快速切换代理，超级拖曳功能，支持rss功能，内嵌搜索引擎工具栏，对网页进行放大和缩小。值得称道的是，IE7 PRO有一项功能，是我用firefox时没有的，那就是能对所在页面进行截图，这项功能挺实用的。在浏览速度方面，没有做正规的测试，初步感觉IE7速度还挺快的。总的来说，ie7给我的有一点惊喜，喜欢他的那种简洁的界面。
有关更多浏览器的对比，可以链接到我的爱爱医博客上，曾经对浏览器做过专门的论述。
2007年5月20日星期日
忽然发现速度其实也蛮快的啦。
医改，医改，越改越乱，改的人越来越看不起病，一个现代化的国家连自己的公民看病都难，再大的发展也不能不能称社会全面发展，相比社会主义国家古巴，人家在几十年的美国经济制裁下，其卫生事业的发展，简直是难以置信，古巴1000多万人口，拥有6.9万名医生，8.2万张病床；每千人拥有6.2名医生， 7.9张病床，婴儿死亡率仅为6.9%，人均寿命75岁。这些数字在世界上也是名列上游的。古巴的全民免费医疗制度，是任何一个国家也比不上的，甚至一些超级富国也做不到的。
中国的官本位太强，我想说的第一点，中国自古到今都是这样，文化上的东西已经深入到精髓，一代两代很难改变的事实，一个贫穷的小镇，贫穷的孩子还要背着篓框去捡煤渣，镇办公大楼却做的像个宫殿一样，真不知道住在里面心能安吗？很难想象只想把钱花在自己身上的人，会尽心去做好医改，做起来可能也是想捞点政治资本吧。中央这几年确实做了不少事，可政策一下来，做的和说的却是另外一幅结果，不能说当地zhengfu或部门没有责任。
病人一方面在喊着没有钱看病，医生这边呢，照样在哭穷，乡镇医院的医生早就没活干了，全出去打工了，嘿，又是一个矛盾的问题，为什么那么多人要往大医院跑，为什么不能去社区医院呢，即使他们很穷也是这样。国家早就提倡要建设社区医院，能解决的小病就要在当地解决，可事实不是如此。
另外一个问题，医生间的贫富差距也在加大，这不是好事，只会加剧医院间以及医院内部利益的争夺，不说大医院和小医院的医生收入差别，就说同一级别医院不同科室医生的差别，据我所知，一个外科医生，和一个病理科医生，同年资，同学历，业务同样出色的情况下，收入水平相关在五倍以上，这不是个小数目，长此以往只会让人才单向流动，造成整个医学发展的恶性循环。
医疗队伍莨萎不齐，医生间的业务水平相差大，但收入奖励制度又没有很好体现这种业务水平差距，关键是没有一个很好的体制来遏制。
速度有点慢
和YAHOO的博客比起来，速度有点慢，但我的原则是，作为google的一个成员，相信BLOGGER会越做越好的，不能在BLOOGER上留下我的空白呀。以后的时间慢慢开始吧。在雅虎上我也说了一些使用博客的感受，雅虎和BLOOGER都是今天开张了，可能以后来的更多一点的还是这里呀。
其实博客对我来讲并不陌生，耳闻那是n年前的事了，使用最早的是用国外的一个博客，blogger.com，注册过，但没怎么写，后来在用163邮箱的时候，发现里面有个个人记事本，写写心情日记什么的还是挺好的，而且内嵌在邮箱里面的，别人也不会看到，怪好的。再到后来注册了一个医学论坛，爱爱医，里面也提供免费的博客，用了几天，也挺好。
写博客主要有几点要考虑，我认为，第一是提供博客的提供商的资历，因为博客写了不是玩儿，我只是 想把自己的一些日子感受都记下来，很像个日记形式，老了也好看看。不希望写了一年博客就倒了。另外一个就是眼下的博客都 是公开化的，而我更需要一个私人空间来书写自己。
其实博客对我来讲并不陌生，耳闻那是n年前的事了，使用最早的是用国外的一个博客，blogger.com，注册过，但没怎么写，后来在用163邮箱的时候，发现里面有个个人记事本，写写心情日记什么的还是挺好的，而且内嵌在邮箱里面的，别人也不会看到，怪好的。再到后来注册了一个医学论坛，爱爱医，里面也提供免费的博客，用了几天，也挺好。
写博客主要有几点要考虑，我认为，第一是提供博客的提供商的资历，因为博客写了不是玩儿，我只是 想把自己的一些日子感受都记下来，很像个日记形式，老了也好看看。不希望写了一年博客就倒了。另外一个就是眼下的博客都 是公开化的，而我更需要一个私人空间来书写自己。
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