新英格兰医学杂志刘全

Diabetes Treatment Disappoints in New Study 细胞移植法治疗糖尿病遭遇尴尬 The cell transplants did free patients from insulin shots, but only temporarily: within two years, 86 percent needed insulin again, according to a report to be published Thursday in The New England Journal of Medicine. 星期四刊登在《新英格兰医学杂志》上的报告显示，细胞移植的确免除了患者注射胰岛素之苦，但是作用却只是暂时的：86%的患者在2年以内再次需要新的胰岛素。 The patients had severe Type 1 diabetes, also called juvenile diabetes, in which the body lacks insulin and people must inject it several times a day to control blood sugar. They were given islet cells from the pancreas of a dead organ donor. 患有严重的I型糖尿病，也称为青少年糖尿病的患者体内缺少胰岛素，为了控制血糖必须每天多次注射胰岛素。他们被移植了死亡的器官捐献者的胰脏细胞。 The transplants do not require major surgery, just a tube inserted into a vein in the abdomen so that the cells can be dripped into the liver, where they take up residence in tiny blood vessels. Because the transplanted cells come from someone else, recipients must take immune-suppressing drugs for life to prevent rejection. 移植手术不需要动大手术，只需要在患者腹部的血管中插入一个导管把细胞倒入患者的肝脏，细胞就依附在肝脏细小的血管上。因为细胞来自于别人体内，接受移植的患者必须终生服用免疫抑制药物，预防产生排异现象。 The study, involving 36 patients at nine centers in the United States, Canada and Europe, was inspired by a smaller trial published in 2000 that sparked excitement about a transplant technique called the Edmonton protocol, developed at the University of Alberta. In that initial test, none of the patients needed insulin shots-but when the report was published, none had been followed for more than 14 months. Later, many did need the shots again. 这项研究是在来自于美国、加拿大和欧洲9个中心的36名患者身上进行的。研究受到2000年发布的一项小规模的试验结果的启发，那一试验提出了让人兴奋的移植技术，即在埃尔伯塔大学发展起来的埃德蒙顿方案。在起初的试验中，没有一个患者需要注射胰岛素。但是到试验报告发布的时候，所有的病人跟踪观察还不到14个月。后来，许多患者还是需要接着注射胰岛素。 In the newer study, the transplants failed completely within a year in 10 of the 36 patients; but 16 others were off insulin completely, and the remaining 10 needed less insulin than before. By two years, only five were still free of insulin shots. A quarter of the patients had to switch immune-suppressing drugs because of side effects, which sometimes included a drop in kidney function. 在新近的研究中，在细胞移植的36例患者中，1年以内有10例移植完全失败；但是另外16例患者完全不在需要胰岛素注射，另外10例需要的胰岛素的量也比以前减少了。到2年的时候，仅有5例依然不需要注射胰岛素。由于副作用的原因，包括出现肾功能下降的情况，四分之一的患者不得不停止使用免疫抑制药物。 For now, the cell transplants are not recommended for most patients. 所以现在绝大部分患者都没有建议采用细胞移植法。 "I don't think this is ready for prime time," said Dr. Jonathan S. Bromberg, director of transplantation at Mount Sinai Hospital in Manhattan. He was not involved in the research, but wrote an editorial about it in the same journal. “我认为时机还不成熟，” 曼哈顿西奈山医院器官移植主任乔纳森·S·布隆伯格博士说。他没有参与这次研究，但是他在同一期刊上撰写了关于研究报告的社评。 But he also said the field was advancing so fast that the transplants may actually become a viable option in the not-so-distant future. 但是他说，这一领域发展很快，实际上移植可能在不远的将来成为可靠的治疗方法。 "I think we've got every reason to believe there will be significant progress," Dr. Bromberg said. 他表示：“我认为我们有足够的理由相信这一技术将会取得重大的进步。” In the meantime, even in their present form, the cell transplants may still help some people - approximately 10 percent of those with Type 1 diabetes, who frequently suffer from severe episodes of low blood sugar, or hypoglycemia, that strike without warning and can cause confusion, fainting or even seizures. 同时，即便是在他们现在的情形下，细胞移植对于大约10%的患有I型糖尿病的患者可能依然有用。这些患者经常受到严重的低血糖症状或者低血糖症的折磨，这些疾病会在没有任何征兆的情况下发生，并能诱发神志不清、昏迷甚至惊厥。 This kind of hypoglycemia can be so severe that patients "can't function in society," said Dr. . James Shapiro, who led the study and is director of the islet transplant program at the University of Alberta. His team developed the Edmonton protocol. 这种低血糖症会非常严重，可以导致患者“不能正常活动”，领导这项研究的埃尔伯塔胰岛移植项目主任. 詹姆斯·夏皮罗博士表示。他领导的团队开创了埃德蒙顿方案。 Patients in the study had the condition, but the transplants diminished their hypoglycemic attacks, even when the cells were only partly effective. 研究中的患者都有上述情况，但在细胞移植后，甚至即便在这些细胞只有部分发挥作用时，他们都免受了低血糖症的困扰。 In the United States, the cell transplants are considered experimental and are available only in studies. They are more widely available in Canada, Dr. Shapiro said. 在美国，细胞移植还在试验阶段，只有在研究中可以使用。夏普罗博士介绍说，但在加拿大，细胞移植应用更加广泛。 Transplanting the entire pancreas can reverse Type 1 diabetes, but it is a major operation and in this country is usually done only when the diabetes is so severe that the patient needs a kidney transplant as well. About 1,500 pancreas transplants a year are performed in the United States. The transplants tend to work for 5 to 10 years, Dr. Bromberg said. Eventually most patients need insulin again. 完全移植整个胰脏可以彻底治疗I型糖尿病，但是这是一项大手术，而且在美国只有糖尿病已经严重到需要肾移植的时候才通常会被采用。布隆伯格博士说，移植往往可以保证5到10年，但大多数患者最后还是需要注射胰岛素。 But people with Type 1 do not really need a whole pancreas: they need just the islet cells, which make up only about 3 percent of the organ. I型糖尿病患者并不是一定需要整个胰脏的移植，他们只需要相当于整个器官3%的胰岛细胞。 Researchers have been experimenting with islet transplants since the 1970's. But the cells never survived for long in humans - not until the study reported in 2000 by Dr. Shapiro and his colleagues. His team succeeded because they suspected that the immune-suppressing drugs were killing off the islet cells, and they switched to a less toxic regimen. It worked. 研究人员从20世纪70年就开始试验胰岛细胞移植。但是直到2000年夏普罗博士和他的同事发表的研究报告，这些细胞在人体内从来就没有存活过。他的研究小组的成功是由于他们怀疑抑制免疫的药物同时也杀死了胰岛细胞，所以他们成功地使用了一种毒性更小的疗法。 Even so, too many cells die - half to three quarters, Dr. Shapiro said. If more could survive, patients might be able to go much longer without insulin. Researchers are testing different drug combinations and other refinements to improve their results. 夏普罗博士说，即便如此，太多的细胞-大约有一半岛3/4，还是死亡了。如果更多的细胞能够存活，患者不需要使用胰岛素的时间就可能会延长。研究人员正在试验不同的药物组合和其他的更加精细的方法来提高细胞的成活率。 "I would be first to admit that it has a long way to go before it matches whole pancreas transplantation," Dr. Shapiro said, but he added that he still expected the cell infusions to catch up with whole organ transplants in a few years. The shortage of organ donors will be a limiting factor, however. “首先我得承认，要达到整个胰脏移植的效果还有很长的路要走，”夏普罗博士承认，但是他接着说，他依然期待在几年的时间里细胞灌输可以赶上整个胰脏器官移植的效果。然而，缺少胰脏捐献者将是一个不利因素。 Dr. Bromberg said that for most diabetics, new forms of insulin, insulin pumps and glucose monitors were improving control of the disease so much that it would be hard to justify the risks of a transplant and lifelong immune-suppressing drugs. 布隆伯格博士说，对于大多数糖尿病患者，新的合成胰岛素、胰岛素泵和血糖监测仪大量使用，用来改善对疾病的监控，但这也使得判断细胞移植和终生使用免疫抑制药物的风险变得困难。 Cell transplants are being studied primarily in people with Type 1 diabetes, which affects about a million people in the United States. It occurs when a person's immune system, for unknown reasons, attacks the pancreas cells that make insulin. 细胞移植的研究首先是在I型糖尿病患者身上进行的，患这种疾病的人在美国大约有100万人。这一疾病是由于某种不确知的原因致使免疫系统损害产生胰岛素的胰岛细胞所致。 Type 2 diabetes is different, and far more common, affecting about 20 million in the United States. Patients produce insulin, but their bodies cannot use it properly. The disease is genetic, but often develops only when someone who has the genes for it also becomes overweight. Type 2 is increasing in many countries as obesity rises. （Type 1 is not linked to obesity.） II型糖尿病则不同，也更加普遍，在美国大约有2000万患者。患者能够分泌胰岛素，但却不能正常地使用这些胰岛素。这种疾病是遗传所致，但是通常只在带有致病遗传基因同时也体重超标的人才会患这种疾病。II型糖尿病随着肥胖症的增加在很多国家也有所增加。I型糖尿病与肥胖症无关。 Both forms of the disease can have devastating consequences, including blindness, kidney failure and circulatory problems that can lead to amputations. 两种疾病都可能导致灾难性的后果，包括失明、肾衰竭和导致的截肢的循环系统疾病。

根据BBC的消息，来自英国的医生在血友病A的治疗上取得了令人振奋的成果，有望帮助患者们摆脱这一疾病的困扰。 血友病患者天生就有遗传缺陷，这意味着他们不能产生止血所需的蛋白质。试验中的十三例患者接受了基因治疗，他们目前能够生产11种正常水平的相关蛋白质。来自埃塞克斯郡的杰克今年29岁，是接受治疗的患者之一，在采访中他表示自己就像拥有了一具全新的身体。和在英国各地分布的其他2000个血友病患者一样，杰克的身体无法制造凝血因子VIII。轻微的伤害就能导致他的严重出血。他记得小时候自己不小心碰掉了两颗门牙，而这使他流了好几天的血。对他来说没有什么是安全的，甚至走路也会导致关节出血，最终形成关节炎。 没接受治疗前杰克每周至少需要注射三次凝血因子VIII，但现在的他告诉记者：“我现在感觉自己像一个全新的人，我觉得自己就像一个润滑良好的机器人。我能做得更多，而我的身体也允许我做更多的事情。如果我的关节有问题的话，我连500米都走不了，而步行两、三、四英里对我来说不是问题——我可以很容易地做到这一点。” 这种疗法是一种基因工程病毒。这种病毒就像邮递员一样，向肝脏传递遗传指令，然后接到指令的肝脏开始生产凝血因子VIII。在第一次试验中，由于剂量比较低，所以结果并不让人满意。但当医生给13名患者注射更高剂量的该病毒后，所有患者在一年内都停止服用血友病药物，在这一年中他们体内的相关因子仍能保持正常水平。 约翰教授在在巴特和玛丽女王伦敦大学领导了该项试验，他认为：“这是一个巨大的突破，因为这项研究为患病的人们提供正常生活的能力，而以前他们必须每隔一天注射一次凝血因子VIII以防止出血。” 对第一批九名患者的分析发表在《新英格兰医学杂志》上。现在他们正在进行更大规模的试验，看看这种疗法是否能真正改变病人的生活。 血友病协会的首席执行官丽斯·卡罗尔说认为基因疗法是一种很有潜力的治疗方法。尽管英国有世界领先的治疗手段，但仍有许多人因为血友病遭受流血的痛苦，并导致他们的慢性关节损伤。 然而，她警告说，不同的人对这种治疗的看法可能有很大的差异，因为基因疗法可能会十分的昂贵。尽管如此，目前治疗血友病的常规方法——注射凝血因子VIII的费用约为每年100000英镑，与其相比基因疗法将会很大的市场。