1、1.绝经后骨质疏松症妇女中 Strontium Ranelate 对椎体骨折的影响The Effects of Strontium Ranelate on the Risk of Vertebral Fracture in Women with Postmenopausal Osteoporosissrontium: 锶 vertebral : 脊骨的,脊椎的,椎骨的ranelate:硬脂酸 osteoporosis: 骨质疏松症postmenopausal: 经绝后的,停经后 背景 骨质疏松性结构破坏和骨质脆弱是骨质形成减少而骨质吸收增加的结果。在一项 2 期临床试验中，strontium
2、ranelate,一种通过增加骨质形成和减少骨质吸收来解除骨质重塑的口服活性药物，已经显示可降低椎体骨折危险而增加骨矿密度。Background: Osteoporotic structural damage and bone fragility result from reduced bone formation and increased bone resorption. In a phase 2 clinical trial, strontium ranelate, an orally active drug that dissociates bone remodeling by inc
3、reasing bone formation and decreasing bone resorption, has been shown to reduce the risk of vertebral fractures and to increase bone mineral density. fragility: 脆弱,脆性,易碎性 resorption: 吸收dissociate: 分离,离解,分裂 orally: 经口的,口服的density: 密度方法 为了在一项 3 期临床试验中评估 strontium ranelate 对预防椎体骨折的疗效，我们将 1649 例患有骨质疏松症(
4、低骨矿密度)并至少有一个椎体骨折的绝经后妇女随机分成两组，使她们分别接受每天 2g 口服 strontium ranelate 或安慰剂治疗共 3 年。我们在研究前和研究期间给两组病人都补充钙质和维生素 D。每年 1 次进行椎体 X 线检查，每 6 个月 1 次进行骨矿密度测定。Methods To evaluate the efficacy of strontium ranelate in preventing vertebral fractures in a phase 3 trial, we randomly assigned 1649 postmenopausal women with
5、 osteoporosis (low bone mineral density) and at least one vertebral fracture to receive 2 g of oral strontium ranelate per day or placebo for three years. We gave calcium and vitamin D supplements to both groups before and during the study. Vertebral radiographs were obtained annually, and measureme
6、nts of bone mineral density were performed every six months. placebo： n. 安慰剂radiograph: x 射线照片 ,放射显影图,放射线照片,放射线照相片,射线照结果 Strontium ranelate 组比安慰剂组较少病人发生新的椎体骨折，骨折发生危险下降在治疗的第 1 年中为 49%，在 3 年研究期间为 41%(相对危险为 0.59，95%可信区间为0.480.73)。Strontium ranelate 使 36 个月时的腰椎骨矿密度增加 14.4%，股骨颈骨矿密度增加 8.3%(两项比较均 P0.001)。两
7、组之间的严重不良事件发生率没有显著差异。Results: New vertebral fractures occurred in fewer patients in the strontium ranelate group than in the placebo group, with a risk reduction of 49 percent in the first year of treatment and 41 percent during the three-year study period (relative risk, 0.59; 95 percent confidence
8、interval, 0.48 to 0.73). Strontium ranelate increased bone mineral density at month 36 by 14.4 percent at the lumbar spine and 8.3 percent at the femoral neck (P0.001 for both comparisons). There were no significant differences between the groups in the incidence of serious adverse events. spine: n.
9、 脊骨;脊柱 lumbar: 腰,腰部的,腰的,腰椎,腰椎;腰部femoral: 大腿的,大腿骨的 ,股的,股动脉,股骨的结论采用 strontium ranelate 治疗绝经后骨质疏松症可使椎体骨折危险早期出现持久下降Conclusions Treatment of postmenopausal osteoporosis with strontium ranelate leads to early and sustained reductions in the risk of vertebral fractures. 2.渗出性缩窄性心包炎 Effusive Constrictive Pe
10、ricarditis effusive a.流出的；溢出的；喷出的 ;喷发岩; 热情洋溢的；溢于言表的;constrictive 狭窄的,缩窄的 constrictionn n 狭窄pericarditis 心包炎背景 渗出性缩窄性心包炎是一种罕见心包综合征，其特征为伴有由紧张性心包渗出引起的心脏填塞和由脏层心包引起的缩窄。我们进行了一项有关该病的临床演变和处理的前瞻性研究。Background Effusiveconstrictive pericarditis is an uncommon pericardial syndrome characterized by concomitant t
11、amponade, caused by tense pericardial effusion, and constriction, caused by the visceral pericardium. We conducted a prospective study of its clinical evolution and management. concomitant 伴发的,伴行的,并发的,副,副的,附随的,相伴的tamponade 填塞 ,压塞effusion n.U(液体等)流出；溢出；喷出;C流出物；溢出物；喷出物;方法 从 1986 年至 2001 年，所有渗出性缩窄性心包炎病
12、人都接受前瞻性评估。对所有病人都联合进行心包穿刺和心脏导管插管，对持续缩窄病人进行心包切开。随访时间范围是从1 个月至 15 年(中位数为 7 年)。Methods From 1986 through 2001, all patients with effusiveconstrictive pericarditis were prospectively evaluated. Combined pericardiocentesis and cardiac catheterization were performed in all patients, and pericardiectomy was
13、 performed in those with persistent constriction. Follow-up ranged from 1 month to 15 years (median, 7 years). pericardiocentesis 心包穿刺术catheterization 插入导管术,导管插入术,导尿术pericardiectomy 心包切除术median adj. 中间的,n. (三角形) 中线结果 我们共对 1184 例心包炎病人进行了评估，其中 218 例有心脏填塞。在这 218 例病人中，190 例接受了联合心包穿刺和心脏导管插管。这些病人中有 15 例为渗
14、出性缩窄性心包炎，这 15 例病人被纳入研究。所有病人都有心脏填塞的临床表现，但是，只有 7 例病人确认伴发缩窄。在进行导管插管时，所有病人的心包内压都升高(中位数为 12mmHg，四分位数间距为 718mmHg)，右房压以及左室和右室舒张期末压也都升高。在心包穿刺后，心包内压力下降(中位数为5mmHg，四分位数间距为50mmHg)，而右房压及左室和右室舒张期末压虽然有轻微下降但仍然较高，形态上表现为倾角平台状。原因是多方面的，死亡与基础疾病相关。7 例病人需要心包切开，所有这些病人都累及了脏层心包。3 例病人自发缓解。Results A total of 1184 patients with
15、 pericarditis were evaluated, 218 of whom had tamponade. Of these 218, 190 underwent combined pericardiocentesis and catheterization. Fifteen of these patients had effusiveconstrictive pericarditis and were included in the study. All patients presented with clinical tamponade; however, concomitant c
16、onstriction was recognized in only seven patients. At catheterization, all patients had elevated intrapericardial pressure (median, 12 mm Hg; interquartile range, 7 to 18) and elevated right atrial and end-diastolic right and left ventricular pressures. After pericardiocentesis, the intrapericardial
17、 pressure decreased (median value, 5 mm Hg; interquartile range, 5 to 0), whereas right atrial and end-diastolic right and left ventricular pressures, although slightly reduced, remained elevated, with a dipplateau morphology. The causes were diverse, and death was mainly related to the underlying d
18、isease. Pericardiectomy was required in seven patients, all of whom had involvement of the visceral pericardium. Three patients had spontaneous resolution. intrapericardial 心包内的 interquartile 四分位atrial 房的,前房的 diastolic a.心脏舒张的ventricular 室的,心室的,腹的,胃的 visceral 内脏的morphology 形态；形态学，形态论 pericardium 心包u
19、nderlying 基础的；潜在的,根本的,下面的；结论 渗出性缩窄性心包炎是一种罕见心包综合征，在一些表现为心脏填塞的病人中可能被漏诊。虽然演变为持续性缩窄很常见，但一些特发性病例可能自发缓解。我们认为，广泛心外膜切除术是需要手术病人的首选治疗措施。Conclusions Effusiveconstrictive pericarditis is an uncommon pericardial syndrome that may be missed in some patients who present with tamponade. Although evolution to persis
20、tent constriction is frequent, idiopathic cases may resolve spontaneously. In our opinion, extensive epicardiectomy is the procedure of choice in patients requiring surgery. idiopathic 特发性的 ,原发性的,自发性的epicardiectomy 心外膜切除术3.Eculizumab 对阵发性夜间血红蛋白尿病人的溶血和输血需要的影响Effect of Eculizumab on Hemolysis and Tran
21、sfusion Requirements in Patients with Paroxysmal Nocturnal Hemoglobinuriahemolysis n.溶血 transfusion n.输血; 倾注；转移；nocturnal 夜间的;夜行的 paroxysmal 阵发的；突发性,hemoglobinuria n.血红蛋白尿背景 阵发性夜间血红蛋白尿(PNH)起源于造血干细胞 PIGA 基因的体细胞突变和随后生成了缺乏表面蛋白(能保护细胞免除补体系统攻击)的血细胞。我们在 PNH 病人中检验了eculizumab(一种抑制终末补体成分活化的人化抗体)的临床疗效。Backgrou
22、nd Paroxysmal nocturnal hemoglobinuria (PNH) arises from a somatic mutation of the PIG-A gene in a hematopoietic stem cell and the subsequent production of blood cells with a deficiency of surface proteins that protect the cells against attack by the complement system. We tested the clinical efficac
23、y of eculizumab, a humanized antibody that inhibits the activation of terminal complement components, in patients with PNH. somatic a. cell体细胞. 身体的，肉体的; 【生】体的;mutation n. 突变 ,变异hematopoietic 定向造血干细胞,血球生成的,造血的方法 11 例依赖输血的 PNH 病人连续 4 周每周接受 eculizumab(600mg)输注治疗，在 1 周后改为 900mg，然后每隔 1 周 900mg，连续 12 周。在整
24、个临床试验期间测定有关溶血的临床和生化指标。Methods Eleven transfusion-dependent patients with PNH received infusions of eculizumab (600 mg) every week for four weeks, followed one week later by a 900-mg dose and then by 900 mg every other week through week 12. Clinical and biochemical indicators of hemolysis were measur
25、ed throughout the trial. infusion n. 输注；灌输,激励结果 平均乳酸脱氢酶水平从治疗前的 3111IU/L 下降到治疗期间的 594IU/L(P0.002)。PNH型红细胞的平均百分数从占全部红细胞的 36.7%增加到占 59.2%(P0.005)。输血率的平均数和中位数分别从每例病人每月 2.1 个和 1.8 个单位下降到每例病人每月 0.6 个和0.0 个单位(输血率中位数的比较 P0.003)。血红蛋白尿的发作次数减少了 96%(P0.001)，生活质量指标发生了显著改善。Results Mean lactate dehydrogenase level
26、s decreased from 3111 IU per liter before treatment to 594 IU per liter during treatment (P=0.002). The mean percentage of PNH type III erythrocytes increased from 36.7 percent of the total erythrocyte population to 59.2 percent (P=0.005). The mean and median transfusion rates decreased from 2.1 and
27、 1.8 units per patient per month to 0.6 and 0.0 units per patient per month, respectively (P=0.003 for the comparison of the median rates). Episodes of hemoglobinuria were reduced by 96 percent (P0.001), and measurements of the quality of life improved significantly. lactate n.乳酸盐 v.分泌乳汁 , 授乳; dehyd
28、rogenase 脱氢酶erythrocyte 红细胞结论 在 PNH 的病人中，eculizumab 是安全的，并能被良好耐受。这种抗终末补体蛋白C5 的抗体可以减少 PNH 病人的血管内溶血、血红蛋白尿和对输血的需要，并伴有生活质量的相应改善。Conclusions Eculizumab is safe and well tolerated in patients with PNH. This antibody against terminal complement protein C5 reduces intravascular hemolysis, hemoglobinuria, an
29、d the need for transfusion, with an associated improvement in the quality of life in patients with PNH. intravascular 血管内的4.改变 HLA 配型优先级对少数民族病人肾脏移植率和转归的影响Effect of Changing the Priority for HLA Matching on the Rates and Outcomes of Kidney Transplantation in Minority Groups背景 HLA 分型和病人等待移植的时间，是美国在分配尸
30、体肾进行肾移植时所采用的主要标准。HLAA、B 和 DR 都匹配的等待移植病人享有最高优先级，然后是 HLAB 和 DR 位点最少不匹配的病人。这个政策使白人中的移植率高于非白人。我们假设，改变这种分配政策将影响移植物的生存率和移植受者中的种族平衡性。Background HLA typing and the time a patient has spent on the waiting list are the primary criteria used to allocate cadaveric kidneys for transplantation in the United State
31、s. Candidates with no HLA-A, B, and DR mismatches are given top priority, followed by candidates with the fewest mismatches at the HLA-B and DR loci; this policy contributes to a higher transplantation rate among whites than nonwhites. We hypothesized that changing this allocation policy would affec
32、t graft survival and the racial balance among transplant recipients. cadaveric 尸体的 graft n 移植物;locus 部位,部位、场所,场所,轨迹,基因座,位点,座位 loci 是 locus 的复数形式方法 我们采用 Cox 模型，针对从被列入等待名单到接受移植的时间，按照种族的情况计算了当前分配政策下的相对肾移植率和 HLA 抗原谱的种族差异。我们还采用另一个模型，在校正 HLAB 和 DR 抗原谱后，计算了在各民族和种族中这些抗原谱分布一致时将发生的相对肾移植率。我们还采用 Cox 模型，针对第一次移植到
33、移植物失败的时间，研究了 HLA 配型对移植物失败的影响。我们采用这两项分析的结果来估计，在取消 HLAB 配型或 HLAB 和 DR 配型作为分配优先级的方式后，移植种族平衡性和移植物失败率将发生的改变。Methods We estimated the relative rates of kidney transplantation according to race resulting from the current allocation policy and racial differences in HLA antigen profiles, using a Cox model fo
34、r the time from placement on the waiting list to transplantation. Another model, also adjusted for HLA-B and DR antigen profiles, estimated the relative rates of kidney transplantation that would result if the distribution of these antigen profiles were identical among the racial and ethnic groups.
35、We also investigated the effect of HLA matching on the risk of graft failure, using a Cox model for the time from the first transplantation to graft failure. The results of the two analyses were used to estimate the change in the racial balance of transplantation and graft-failure rates that would r
36、esult from the elimination of HLA-B matching or HLA-B and DR matching as a means of assigning priority. antigen n. 抗原 assign 分配,指定,赋予结果 取消 HLAB 配型作为优先级但保留 HLADR 配型作为优先级，使白人中的移植数减少 4.0%(在 1 年内移植数减少了 166 例)，而使非白人中的移植数增加 6.3%，并使移植物损失率增加 2.0%。Results Eliminating the HLA-B matching as a priority while ma
37、intaining HLA-DR matching as a priority would decrease the number of transplantations among whites by 4.0 percent (166 fewer transplantations over a one-year period), whereas it would increase the number among nonwhites by 6.3 percent and increase the rate of graft loss by 2.0 percent.结论 取消 HLAB 配型作
38、为尸体肾分配的优先级可以通过增加非白人中的移植数而减轻种族之间的分配失衡，而移植物损失的发生率只有轻微增加。 Conclusions Removing HLA-B matching as a priority for the allocation of cadaveric kidneys could reduce the existing racial imbalance by increasing the number of transplantations among nonwhites, with only a small increase in the rate of graft lo
39、ss. 5.在 2 型糖尿病病人的对胰岛素抵抗的后代中存在线粒体活性受损Impaired Mitochondrial Activity in the Insulin-Resistant Offspring of Patients with Type 2 Diabetes impair vt.削弱；损伤；损害; insulin 胰岛素mitochondrial 线粒体的 diabetes n. 糖尿病背景 在 2 型糖尿病病人的子女中,胰岛素抵抗似乎是发生糖尿病的最佳预测因素,但引起的机制尚不清楚。 Background Insulin resistance appears to be the
40、best predictor of the development of diabetes in the children of patients with type 2 diabetes, but the mechanism responsible is unknown.方法 我们在 2 型糖尿病病人的健康、年轻、体瘦、对胰岛素抵抗的后代中,以及在年龄、身高和体力活动相匹配的对胰岛素敏感的对照研究对象中,联合注射6，6- 2 H2葡萄糖进行了高胰岛素-正常血糖钳夹研究,来评估肝脏和肌肉对胰岛素的敏感性。我们进行质子 1H 磁共振波谱检查研究来测量肌细胞内脂质和肝细胞内甘油三酯的含量。我们通过
41、测定 2H5甘油周转率并联用微量渗析法测定的皮下脂肪释放甘油指标来评估全身和皮下脂肪的脂解率。我们采用 31P 磁共振波谱检查研究来评估肌肉内的线粒体氧化磷酸化活性。 Methods We performed hyperinsulinemiceuglycemic clamp studies in combination with infusions of 6,6-2H2glucose in healthy, young, lean, insulin-resistant offspring of patients with type 2 diabetes and insulin-sensitiv
42、e control subjects matched for age, height, weight, and physical activity to assess the sensitivity of liver and muscle to insulin. Proton (1H) magnetic resonance spectroscopy studies were performed to measure intramyocellular lipid and intrahepatic triglyceride content. Rates of whole-body and subc
43、utaneous fat lipolysis were assessed by measuring the rates of 2H5glycerol turnover in combination with microdialysis measurements of glycerol release from subcutaneous fat. We performed 31P magnetic resonance spectroscopy studies to assess the rates of mitochondrial oxidative-phosphorylation activi
44、ty in muscle. euglycemic 血糖正常的 clamp n.夹子 vt.夹住,夹紧glucose 葡萄糖 proton n.质子magnetic 磁的,有磁性的 spectroscopy 光谱学intramyocellular 肌蜂窝织炎内的 lipid n. 脂;脂质intrahepatic 肝内的 triglyceride 甘油三酯,subcutaneous adj. 皮下的 turnover 更新,周转glycerol 甘油 lipolysis n.脂解( 作用)microdialysis 微量透析 ,微透析 oxidative 氧化的phosphorylation 磷
45、酸化( 作用),磷酸化作用结果 对胰岛素抵抗的研究对象与对胰岛素敏感的对照研究对象相比,前者的肌肉在胰岛素刺激下的葡萄糖摄取率要比后者低大约 60%(P0.001),并且与肌细胞内脂质含量增加大约80%相关(P=0.005)。肌细胞内脂质含量的这种增加最可能由线粒体功能障碍所致,反映在线粒体的磷酸化大约下降了 30%(与对照者比较 P=0.01),而全身或局部脂解率或肿瘤坏死因子、白介素 6、抵抗素及脂联素都没有显著差异。 Results The insulin-stimulated rate of glucose uptake by muscle was approximately 60 p
46、ercent lower in the insulin-resistant subjects than in the insulin-sensitive control subjects (P0.001) and was associated with an increase of approximately 80 percent in the intramyocellular lipid content (P=0.005). This increase in intramyocellular lipid content was most likely attributable to mito
47、chondrial dysfunction, as reflected by a reduction of approximately 30 percent in mitochondrial phosphorylation (P=0.01 for the comparison with controls), since there were no significant differences in systemic or localized rates of lipolysis or plasma concentrations of tumor necrosis factor , inter
48、leukin-6, resistin, or adiponectin.necrosis 坏死interleukin 白细胞介素 resistin 抵抗素adiponectin 脂连素 plasma n.血浆, 乳浆concentrations 浓聚物结论 这些资料支持下列这种假设,即在 2 型糖尿病病人的对胰岛素抵抗的子女中,骨骼肌对胰岛素的抵抗与肌细胞内脂肪酸代谢的功能障碍相关,这种代谢障碍可能缘于线粒体氧化磷酸化的遗传性缺陷。 Conclusions These data support the hypothesis that insulin resistance in the skeletal muscle of insulin-resistant offspring of patients with type 2 diabetes is associated with dysregulation of intramyocellular fatty acid metabolism, possibly because of an inherited defect in mitochondrial oxidative phosphorylation. metabolism n. 新陈代
