新英格兰语料(1)摘要(修订版)

目 录 1.绝经后骨质疏松症妇女中 Strontium Ranelate 对椎体骨折的影响 5 2.渗出性缩窄性心包炎 6 3.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 8 4.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 .10 5.B 型钠尿肽在急性呼吸困难评估和处理中的应用 .11 6.血浆钠尿肽水平与心血管事件和死亡的危险 13 7.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 15 8.血循环中的血管生成因子与先兆子痫的发生危险 17 10.阿伦膦酸盐或骨化三醇预防心脏移植后的骨丢失 20 11.既往早产和小于胎龄儿产与以后死产的危险 22 12.儿童期体质指数连续改变与青年期糖耐量异常的相关性 24 13.有瘘道克罗恩病的 Infliximab 维持治疗 26 14.肺动脉高压是镰状细胞病病人的死亡危险因素 28 15.在瑞士使用灭活鼻内流感疫苗与面神经麻痹的发病危险 30 16.慢性阻塞性肺疾病的体质指数、气流阻塞、呼吸困难和运动能力指数 31 17.增殖性狼疮肾炎的序贯治疗 33 18.HIV 感染男性的持续 GB 病毒 C 感染和生存 .35 20.突破物种屏障 个人迈出一小步，人类跨越一大步（综述） 39 21.海分枝杆菌 45 22.克罗恩病中的炎性假息肉 46 23.患有原发性乳腺癌的绝经后妇女在他莫昔芬治疗 23 年后的依西美坦随机临床试验 47 24.男性中的富含嘌呤食物、牛奶和蛋白摄入量与痛风危险 49 25.降钙素基因相关肽受体的拮抗剂 BIBN 4096 BS 用于偏头痛的急性治疗 51 26.胰腺癌切除术后进行化放疗与化疗的随机临床试验 52 27.大剂量化疗和自体骨髓干细胞支持初治侵袭性淋巴瘤 54 28.致命性表面活性物质缺乏新生儿的 ABCA3 基因突变 55 29.患原发性乳腺癌的绝经后妇女在他莫昔芬治疗 23 年后改用依西美坦治疗的随机临床 试验 57 31.儿童期疫苗接种与 1 型糖尿病 61 32.手术切除和非整倍体对口腔白斑患者病死率的影响 63 33.急性冠脉综合征后采用他汀类药物进行强化降脂与中度降脂的比较 65 34.接受血液透析的病人采用 Cinacalcet 治疗继发性甲状旁腺功能亢进症 66 35.胆固醇脂转运蛋白抑制剂对 HDL 胆固醇的作用 68 36.在成人急性粒细胞性白血病中应用基因表达谱分析来鉴定预后不同的病人亚组 70 37.急性粒细胞性白血病中有预后作用的基因表达谱 72 38.危重病人中的血清游离皮质醇测定 74 39.早产儿的产后皮质类固醇治疗:是也,非也? 76 40.美国胚胎移植实践和辅助生殖技术应用转归的趋势 82 41.尿嘧啶-替加氟辅助化疗肺腺癌的随机临床试验 84 42.心脏停搏患儿采用大剂量与标准剂量肾上腺素治疗的比较 85 43.严重急性呼吸综合征病毒空气传播的证据 87 44.常规补片与腹腔镜补片修复术在腹股沟疝治疗中的比较 89 2 45.ATP 敏感钾通道亚单位 Kir6.2 的编码基因的活化突变和永久性新生儿糖尿病 .91 46.HIV 感染初始治疗中的核苷三联方案或含依法韦仑方案 .93 47.头颈部高危鳞状细胞癌的术后同步放疗和化疗 95 48.舒张期心力衰竭 左心室主动性舒张和被动性僵硬的异常 97 49.Hurler 综合征病人的非亲缘供体脐带血移植 .98 50.基于 6 种基因预测弥漫性大 B 细胞淋巴瘤患者的生存情况 100 51.高半胱氨酸水平和骨质疏松性骨折危险 101 52.高半胱氨酸是老年人髋部骨折的预测因素 103 53.腹腔镜辅助切除术与开腹切除术治疗结肠癌比较 105 54.表皮生长因子受体活化突变是 Gefitinib 对非小细胞肺癌有效的基础 107 55.慢性心力衰竭晚期病人中有或无可置入除颤器的心脏再同步治疗 109 56.加强监护病房中采用白蛋白与生理盐水输液急救比较 110 57.肺栓塞后的慢性血栓栓塞性肺动脉高压的发生率 112 58.聚乙二醇化干扰素 -2b 和利巴韦林治疗黑人和非西班牙语裔白人的慢性丙型肝炎 114 59.儿童和青少年中的肥胖症和代谢综合征 115 60.Bevacizumab 加伊立替康、氟尿嘧啶和亚叶酸治疗远处转移结直肠癌 .117 61.6 种预防术后恶心和呕吐干预措施的析因性临床试验 .119 62.吸脂术对胰岛素活性和冠心病危险因素没有作用 121 63.与骨骼肌组织同种异体移植相关的梭状芽胞杆菌感染 123 64.类风湿性关节炎病人中使用针对 B 细胞的利妥昔单抗的疗效 125 65.在多伦多严重急性呼吸综合征暴发期间控制传播的公共卫生措施 127 67.冠脉支架置入后的叶酸治疗与支架内再狭窄 130 68.慢性阻塞性肺疾病中小气道阻塞的性质 132 69.终末期肾病儿童的远期生存率 133 70.局部应用 乳白蛋白-油酸治疗皮肤乳头状瘤 135 71.伊拉克和阿富汗作战任务相关精神卫生问题和医疗服务的障碍 137 72.一项有关多种维生素补充剂与 HIV 疾病进展和死亡率的随机临床试验 139 73.非高血压个人的血清醛固酮与高血压发生率 141 74.术前 PSA 变化速度与根治性前列腺切除术后的前列腺癌死亡危险 143 75.内镜激光手术或连续减少羊水治疗严重双胎输血综合征 144 76.右雷佐生对多柔比星治疗的急性淋巴细胞性白血病儿童的心肌损伤的作用 146 77.在泰国采用围产期单剂量奈韦拉平加标准齐多夫定疗法预防 HIV-1 母婴传播 148 78.产中暴露于奈韦拉平与后来母亲对奈韦拉平为主的抗逆转录病毒疗法的疗效反应 150 79.B 细胞淋巴瘤中微血管内皮细胞的淋巴瘤特异遗传学畸变 .152 80.甲状旁腺功能减退症妇女在妊娠期间对左甲状腺素需要量增加的时间和幅度 153 81.系统性红斑狼疮中甘露糖结合凝集素变异性等位基因和动脉血栓形成的危险 155 82.急性呼吸窘迫综合征病人中较高与较低呼气末正压治疗的比较(论著) 157 83.在对伊立替康耐药的转移性结肠癌中的西妥昔单抗单药治疗与西妥昔单抗加伊立替康治 疗的比较 159 84.甲泼尼龙、伐昔洛韦或两者联合治疗前庭神经炎 161 85.Fibulin 5 基因的错义变异和与年龄相关的黄斑退行性变 .162 86.在有家族或遗传倾向的妇女中采用 MRI 和乳房 X 线照相术进行乳腺癌筛查的效果 164 87.聚乙二醇化干扰素 -2a 加利巴韦林或干扰素 -2a 加利巴韦林治疗伴有 HIV 感染者 的慢性丙型肝炎 166 3 88.与 Carney 综合征变异体相关的围产期肌球蛋白重链突变 168 89.耐药急性淋巴细胞白血病细胞的基因表达模式与对治疗的反应 170 90.急性 T 细胞性淋巴细胞白血病的 Smad3 缺失 172 91.随机螺内酯评估研究发表后的高钾血症发生率 173 92.哮喘支气管平滑肌细胞中 C/EBP 与糖皮质激素受体的异常功能相互作用 175 93.粒细胞-巨噬细胞系祖细胞是 CML 原始细胞危象时的候选白血病干细胞 177 94.院外心脏停搏后的公众除颤和生存率 179 95.院外心脏停搏的加强心脏生命支持 181 96.采用核酸扩增法检测抗体阴性献血者中 I 型人类免疫缺陷病毒和丙型肝炎病毒感染 182 97.用和未用毒液免疫治疗对儿童中昆虫叮咬所致变态反应转归的影响 184 98.美国组织供者中 HBV、HCV、HIV 和 HTLV 病毒血症的概率 186 99.干扰素调节因子 6(IRF6)基因变异与孤立性唇裂或腭裂危险 .188 100.转移性乳腺癌的循环肿瘤细胞、疾病进展与生存期 190 101.糖皮质激素敏感肾病综合征儿童中长期应用大剂量糖皮质激素和骨矿物质含量关系研 究 191 102.心脏移植过渡期全人工心脏的心脏替代 194 103.ZAP-70 与免疫球蛋白重链突变状态作为慢性淋巴细胞白血病疾病进展预测因子的比较 195 104.复发性外阴阴道念珠菌病的氟康唑维持治疗 197 105.以重组表面活性蛋白 C 为主的表面活性剂对急性呼吸窘迫综合征的作用 199 106.他莫昔芬加或不加乳腺照射治疗年龄50 岁的早期乳腺癌妇女 .200 107.肿块切除术+他莫昔芬加或不加照射治疗年龄70 岁的早期乳腺癌妇女 .202 108.妊娠 46 月期间母亲血清甲胎蛋白水平与随后的婴儿猝死综合征发生危险 203 109.重组人瘦素治疗下丘脑性闭经妇女 205 110.口服红霉素与心源性猝死危险 207 111.空气污染对 1018 岁期间肺发育的影响 209 112.以家庭为基础的环境干预措施对城市哮喘患儿的效果 211 113.血浆第因子和 D-二聚体水平升高作为血栓形成患儿不良转归的预测因子 .213 114.聚乙二醇干扰素 -2a 单药、拉米夫定单药和两药合治疗 HBeAg 阴性的慢性乙型肝炎 病人 215 115.与患严重恶性疾病儿童谈论死亡 217 116.采用自体口腔黏膜上皮的组织工程细胞片进行角膜重建 219 117.射频消融治疗儿童无症状的 Wolff-Parkinson-White 综合征 220 118.心肌梗死后肾功能障碍和心血管转归之间的关系 222 119.慢性肾病与死亡、心血管事件和住院危险 224 120.单剂口服地塞米松治疗轻度哮吼的随机试验 226 121.卡泊芬净与脂质体两性霉素 B 在持续发热和中性粒细胞减少病人中的经验性抗真菌治 疗比较 228 122纯红细胞再生障碍与红细胞生成素治疗 230 123.伴体细胞 Fas 突变的自身免疫性淋巴组织增生综合征 232 124.拉米夫定治疗慢性乙型肝炎和晚期肝脏疾病病人 233 125.高危病人中保护性颈动脉支架术与动脉内膜切除术的比较 235 126.多西紫杉醇+泼尼松或米托蒽醌+泼尼松治疗晚期前列腺癌疗效比较 237 127.多西紫杉醇+雌莫司汀与米托蒽醌+泼尼松治疗晚期难治性前列腺癌的比较 239 4 128.女性的生长特点与乳腺癌危险 241 129.比较腹主动脉瘤常规治疗与血管内修复的随机试验 243 130.女性的生长特点与乳腺癌危险 244 131.缺血性二尖瓣反流在急性肺水肿发病机制中的作用 246 132.在婴儿心脏手术中，使用新鲜全血与重建血进行泵预冲的比较 247 133.暴露于交通工具与心肌梗死发病 249 134.直肠癌的术前与术后化放疗 251 137.缩短实习医师的轮班时间对减少 ICU 中严重医疗差错的影响 256 138.预防 2 型糖尿病的微量白蛋白尿 257 139.在 2 型糖尿病和肾病中血管紧张素受体阻滞剂与转换酶抑制剂的比较 259 140.单剂阿奇霉素用于砂眼的集体治疗 261 141.德系犹太人的帕金森病与葡糖脑苷脂酶基因突变 263 142.心力衰竭黑人的硝酸异山梨酯加肼屈嗪联合治疗 265 143.在稳定型冠心病中抑制血管紧张素转换酶的效果 266 144.抗白介素 12 抗体治疗活动性克罗恩病 268 145.超声增强系统溶栓治疗急性缺血性卒中的随机临床试验 270 146.根据肿瘤浸润免疫细胞的分子特征预测滤泡性淋巴瘤的生存期 272 147.早产与出生后胰岛素抵抗 273 148.成年白血病病人移植非血缘供者脐血或骨髓后的转归 276 149.成人急性白血病患者无血缘关系供者的脐带血或骨髓移植 277 150.桡动脉与大隐静脉冠状动脉旁路移植术的随机比较 279 151.充血性心力衰竭病人房颤的导管射频消融治疗 281 152.体外受精中的单胚胎移植或双胚胎移植 283 153.急性心肌梗死后置入式心律转复除颤器的预防性应用 284 154.二次细胞减灭术治疗晚期卵巢癌 286 155.左旋多巴和帕金森病病情进展 288 156.利伐斯的明治疗与帕金森病相关的痴呆症 290 157.有剖宫产史妇女中，与试产相关的母亲及婴儿围生期转归 292 158.Palifermin 治疗血液系统癌症强化治疗后的口腔黏膜炎 .294 159.炎性标志物与男性和女性的冠心病危险的关系 296 160.急性感染或接种疫苗后的心肌梗死和卒中危险 298 161.减肥术后 10 年生活方式、糖尿病与心血管危险因素的研究 300 162.体脂过多与体力活动在预测妇女病死率方面的比较 301 163.在平均危险人群中,粪便 DNA 检测与粪便潜血试验筛查结直肠癌的比较 303 164.择期大血管手术之前的冠状动脉血运重建术 305 165.Pegaptanib 治疗新生血管性年龄相关的黄斑变性 .307 166.多基因检测预测接受他莫昔芬治疗的淋巴结阴性乳腺癌复发危险 309 167.病人随身带药门诊治疗新近发生的房颤 311 5 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 Osteoporosis Pierre J.Meunier,M.D.,等 法国里昂 Edouard Herriot 医院，风湿病和骨病科，等 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 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。 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(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。 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)。两组 之间的严重不良事件发生率没有显著差异。 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。 (N Engl J Med 2004;350:459-68.January 29,2004)王华 译 The Effects of Strontium Ranelate on the Risk of Vertebral Fracture in Women with Postmenopausal Osteoporosis 6 Pierre J. Meunier, M.D., Christian Roux, M.D., Ph.D., Ego Seeman, ABSTRACT 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 increasing bone formation and decreasing bone resorption, has been shown to reduce the risk of vertebral fractures and to increase bone mineral density. Methods To evaluate the efficacy of strontium ranelate in preventing vertebral fractures in a phase 3 trial, we randomly assigned 1649 postmenopausal women with 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 measurements of bone mineral density were performed every six months. 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 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 (P 2.5 g/dl)。 METHODS Base-line serum total cortisol, cosyntropin-stimulated serum total cortisol, aldosterone, and free cortisol concentrations were measured in 66 critically ill patients and 33 healthy volunteers in groups that were similar with regard to sex and age. Of the 66 patients, 36 had hypoproteinemia (albumin concentration, 2.5 g per deciliter or less), and 30 had near-normal serum albumin concentrations (above 2.5 g per deciliter). 结果 有低蛋白血症的病人与血清白蛋白浓度接近正常的病人相比,前者的 基线和替可克肽刺激后的血清总皮质醇浓度低于后者(P2.0 ng/ml 与前列腺癌所致死亡(P2.0 ng/ml 的病人，根治性前列腺切除术后 7 年由 前列腺癌所致死亡和所有原因所致死亡的危险估计值也受诊断时 PSA 水平、肿 瘤分期和 Gleason 评分的影响。 147 RESULTS As compared with an annual PSA velocity of 2.0 ng per milliliter or less， an annual PSA velocity of more than 2.0 ng per milliliter was associated with a significantly shorter time to death from prostate cancer （P0.01 ng/ml，为主要转归)或极度升高(0.025 ng/ml)。 METHODS To determine whether dexrazoxane decreases doxorubicin- associated injury of cardiomyocytes， we randomly assigned 101 children with ALL to receive doxorubicin alone (30 mg per square meter of body-surface area every three weeks for 10 doses) and 105 to receive dexrazoxane (300 mg per square meter) followed immediately by doxorubicin. Serial measurements of serum cardiac troponin T were obtained in 76 of 101 patients in the doxorubicin group and 82 of 105 patients in the group given dexrazoxane and doxorubicin. A total of 2377 serum samples (mean) 15.1 samples per patient) were obtained before， during， and after treatment with doxorubicin. Troponin T levels were evaluated in a blinded fashion to determine whether they were elevated ( 0.01 ng per milliliter) the primary end point or extremely elevated ( 0.025 ng per milliliter). 结果 35%的病人(158 例中有 55 例)发生肌钙蛋白 T 升高。接受单纯多柔比 星治疗的病人比接受右雷佐生和多柔比星治疗的病人更可能发生肌钙蛋白 T 水 平升高(50%对 21%，P18 个月,P18 个月,P18 months, P18 months; P1 cm 的晚期卵巢癌患者中,评估在 术后化疗的基础上加用二次细胞减灭术对无疾病进展生存期和总生存期的影响。 方法 患者在首次手术后 6 周内入组。在 3 个周期的术后紫杉醇+顺铂治疗 后,如果患者没有疾病进展的证据,将其随机分配接受二次细胞减灭术+随后再接 受 3 个周期的化疗,或仅再接受 3 个周期的化疗。 结果 我们纳入了 550 例患者。在完成 3 个周期的术后化疗后,216 例符合 入选标准的患者被随机分配接受二次细胞减灭术+随后的化疗,208 例患者被随 机分配为仅接受化疗。分入二次手术组的患者中,15 例患者(7%)拒绝接受手术 或医学上有手术禁忌证。到 2003 年 3 月为止,296 例患者死亡,82 例患者疾病进 展。被分配至接受二次细胞减灭术+化疗组的患者与仅接受化疗组的患者相比, 前者无疾病进展生存的相对危险为 1.07(95%可信区间为 0.871.31,P=0.54), 死亡的相对危险为 0.99(95%可信区间为 0.791.24,P=0.92)。 294 结论 首次细胞减灭术已使晚期卵巢癌患者获益最大化,在术后紫杉醇+顺铂 化疗的基础上再加用二次细胞减灭术不能改善无疾病进展生存期和总生存期。 (N Engl J Med 2004;351: 2489-97. December 2, 2004.)张萱译 Secondary Surgical Cytoreduction for Advanced Ovarian Carcinoma Peter G. Rose, M.D., Stacy Nerenstone, M.D., Mark F. Brady, Ph.D. ABSTRACT Background We evaluated the effect of adding secondary cytoreductive surgery to postoperative chemotherapy on progression-free survival and overall survival among patients who had advanced ovarian cancer and residual tumor exceeding 1 cm in diameter after primary surgery. Methods Women were enrolled within six weeks after primary surgery. If, after three cycles of postoperative paclitaxel plus cisplatin, a patient had no evidence of progressive disease, she was randomly assigned to undergo secondary cytoreductive surgery followed by three more cycles of chemotherapy or three more cycles of chemotherapy alone. Results We enrolled 550 women. After completing three cycles of postoperative chemotherapy, 216 eligible patients were randomly assigned to receive secondary surgical cytoreduction followed by chemotherapy and 208 to receive chemotherapy alone. Surgery was declined by or medically contraindicated in 15 patients who were assigned to secondary surgery (7 percent). As of March 2003, 296 patients had died and 82 had progressive disease. The likelihood of progression-free survival in the group assigned to secondary surgery plus chemotherapy, as compared with the chemotherapy- alone group, was 1.07 (95 percent confidence interval, 0.87 to 1.31; P=0.54), and the relative risk of death was 0.99 (95 percent confidence interval, 0.79 to 1.24; P=0.92). Conclusions For patients with advanced ovarian carcinoma in whom primary cytoreductive surgery was considered to be maximal, the addition of secondary cytoreductive surgery to postoperative chemotherapy with paclitaxel plus cisplatin does not improve progression-free survival or overall survival. 295 155.左旋多巴和帕金森病病情进展 Levodopa and the Progression of Parkinsons Disease The Parkinson Study Group 背景 尽管已知左旋多巴对减轻帕金森病症状有益,但人们仍然担忧使用该 药可能会加速神经变性。本研究评估了左旋多巴对帕金森病进展速度的影响。 BACKGROUND Despite the known benefit of levodopa in reducing the symptoms of Parkinsons disease, concern has been expressed that its use might hasten neurodegeneration. This study assessed the effect of levodopa on the rate of progression of Parkinsons disease. 方法 在这项随机、双盲、安慰剂对照的临床试验中,我们评估了 361 例早 期帕金森病患者,这些患者被分配接受卡比多巴-左旋多巴(每天剂量分别为 37.5 mg 和 150 mg、75 mg 和 300 mg 或 150 mg 和 600 mg)或匹配安慰剂治疗 40 周,然后停止治疗 2 周。主要转归是基线时与 42 周时相比的统一帕金森病分 级量表(UPDRS)得分的变化。142 例研究对象于基线和 40 周时采用 123I 标记 2- -羧甲氧基胺-3-(4-碘苯)托烷( 123I-CIT)摄取法进行了神经影像学研 究,以评估纹状体的多巴胺转运蛋白密度。 METHODS In this randomized, double-blind, placebo-controlled trial, we evaluated 361 patients with early Parkinsons disease who were assigned to receive carbidopa-levodopa at a daily dose of 37.5 and 150 mg, 75 and 300 mg, or 150 and 600 mg, respectively, or a matching placebo for a period of 40 weeks, and then to undergo withdrawal of treatment for 2 weeks. The primary outcome was a change in scores on the Unified Parkinsons Disease Rating Scale (UPDRS) between baseline and 42 weeks. Neuroimaging studies of 142 subjects were performed at baseline and at week 40 to assess striatal dopamine-transporter density with the use of iodine-123-labeled 2- -carboxymethoxy-3-(4-iodophenyl)tropane ( 123I-CIT) uptake. 296 结果 安慰剂组的帕金森综合征加重程度重于所有接受左旋多巴治疗组:基 线时与 42 周时相比的 UPDRS 总评分的平均差异是,安慰剂组为 7.8 单位,接受 150 mg/天左旋多巴组为 1.9 单位,300 mg/天组为 1.9 单位,600 mg/天组为 1.4 单位(P0.001)。相反,在 116 例病人的亚组研究中,左旋多巴治疗组 123I- CIT 摄取率下降的平均百分数显著大于安慰剂组(接受 150 mg/天左旋多巴组为- 6%,300 mg/天组为-4%,600 mg/天组为-7.2%,而安慰剂组为-1.4%;在基线扫描时 没有多巴胺能缺陷的 19 例病人从分析中排除)(P=0.036)。接受最大剂量左旋多 巴治疗者比接受安慰剂治疗者在出现运动障碍、张力亢进、感染、头痛和恶心 等方面显著增多。 RESULTS The severity of parkinsonism increased more in the placebo group than in all the groups receiving levodopa: the mean difference between the total score on the UPDRS at baseline and at 42 weeks was 7.8 units in the placebo group, 1.9 units in the group receiving levodopa at a dose of 150 mg daily, 1.9 in those receiving 300 mg daily, and 1.4 in those receiving 600 mg daily (P0.001). In contrast, in a substudy of 116 patients the mean percent decline in the 123I-CIT uptake was significantly greater with levodopa than placebo (-6 percent among those receiving levodopa at 150 mg daily, - 4 percent in those receiving it at 300 mg daily, and -7.2 percent among those receiving it at 600 mg daily, as compared with-1.4 percent among those receiving placebo; 19 patients with no dopaminergic deficits on the baseline scans were excluded from the analysis) (P=0.036). The subjects receiving the highest dose of levodopa had significantly more dyskinesia, hypertonia, infection, headache, and nausea than those receiving placebo. 结论 临床数据提示,左旋多巴可延缓帕金森病的进展或对疾病症状有持久 作用。相反,神经影像学数据提示,左旋多巴可加速黑质纹状体多巴胺神经末梢 的消失或其药理作用可改变多巴胺转运蛋白。左旋多巴对帕金森病的潜在远期 影响仍未确定。 297 CONCLUSIONS The clinical data suggest that levodopa either slows the progression of Parkinsons disease or has a prolonged effect on the symptoms of the disease. In contrast, the neuroimaging data suggest either that levodopa accelerates the loss of nigrostriatal dopamine nerve terminals or that its pharmacologic effects modify the dopamine transporter. The potential long-term effects of levodopa on Parkinsons disease remain uncertain.(N Engl J Med 2004;351: 2384-91. December 2, 2004.)王华译 156.利伐斯的明治疗与帕金森病相关的痴呆症 Rivastigmine for Dementia Associated with Parkinsons Disease Murat Emre, M.D., 土耳其伊斯坦布尔市 伊斯坦布尔大学医疗系,等 背景 与帕金森病相关的痴呆症患者有明显的胆碱能功能缺陷。我们研究了 双相胆碱酯酶抑制剂利伐斯的明在这类病人中的作用。 BACKGROUND Cholinergic deficits are prominent in patients who have dementia associated with Parkinsons disease. We investigated the effects of the dual cholinesterase inhibitor rivastigmine in such patients. 方法 在临床诊断为帕金森病后至少 2 年发生轻中度痴呆症的病人被随机分 配接受安慰剂或 312 mg/天利伐斯的明治疗 24 周。主要疗效指标是阿尔茨海 默病评估量表(ADAS)认知功能次级量表和阿尔茨海默病协作研究-临床医师对病 人病情变化全面印象(ADCS-CGIC)的评分。次要临床转归是阿尔茨海默病协作研 究-日常活动、10 项神经精神目录、简明精神状态量表、认知药物研究注意力 测试、语言流畅度测试和 10 分画钟测试。 METHODS Patients in whom mild-to-moderate dementia developed at least 2 years after they received a clinical diagnosis of Parkinsons disease were randomly assigned to receive placebo or 3 to 12 mg of rivastigmine per day for 24 weeks. Primary efficacy 298 variables were the scores for the cognitive subscale of the Alzheimers Disease Assessment Scale (ADAS-cog) and Alzheimers Disease Cooperative Study-Clinicians Global Impression of Change (ADCS-CGIC). Secondary clinical outcomes were the scores for the Alzheimers Disease Cooperative Study-Activities of Daily Living, the 10-item Neuropsychiatric Inventory, the Mini-Mental State Examination, Cognitive Drug Research power of attention tests, the Verbal Fluency test, and the Ten Point Clock-Drawing test. 结果 共纳入 541 例病人,其中 410 例完成研究。利伐斯的明治疗者的转归 好于安慰剂治疗者,但是,两组之间的差异程度为中等,并与利伐斯的明治疗阿尔 茨海默病临床试验报告的结果相似。利伐斯的明治疗者的 70 分 ADAS 认知功能 次级量表评分较基线的 23.8 分平均改善 2.1 分,而安慰剂组的评分较基线的 24.3 分恶化 0.7 分(P0.001)。研究观察到利伐斯的明治疗组中有 19.8%的病人,安 慰剂治疗组中有 14.5%的病人 ADCS-CGIC 得分获得有临床意义的改善,另外,分 别有 13.0%和 23.1%的病人获得有临床意义的恶化(在 24 周时平均得分分别为 3.8 分和 4.3 分,P=0.007)。就所有次要疗效指标而言,利伐斯的明治疗组的转归显 著较好。最常见的不良事件是恶心(累及 29.0%的利伐斯的明治疗组病人和 11.2%的 安慰剂治疗组病人,P0.001)、恶心(16.6%和 1.7%的病人,P0.001)和震颤 (10.2%和 3.9%的病人,P=0.01)。 RESULTS A total of 541 patients were enrolled, and 410 completed the study. The outcomes were better among patients treated with rivastigmine than among those who received placebo; however, the differences between these two groups were moderate and similar to those reported in trials of rivastigmine for Alzheimers disease. Rivastigmine-treated patients had a mean improvement of 2.1 points in the score for the 70-point ADAS-cog, from a baseline score of 23.8, as compared with a 0.7-point worsening in the placebo group, from a baseline score of 24.3 (P0.001). Clinically meaningful improvements in the scores for the ADCS-CGIC were observed in 19.8 percent of 299 patients in t