左旋多巴和多巴胺对PC12细胞的毒性及其他抗帕金森病药物的神经保护作用

目的　研究左旋多巴和多巴胺对PC12细胞的毒性作用以及抗帕金森病 (PD)药物的神经保护作用。　方法　通过体外大鼠嗜铬细胞瘤PC12细胞培养 ,采用溴化 3(4 ,5 二甲基噻唑基 2 ) 2 ,5 二苯基四唑 (MTT)细胞活性检测和流式细胞仪观察不同剂量左旋多巴和多巴胺对PC12细胞的毒性作用 ,以及抗PD药物 (金刚烷胺、培高利特和司来吉兰 )能否拮抗左旋多巴和多巴胺的细胞毒性。　结果　MTT显示左旋多巴和多巴胺使PC12细胞活性降低 ,与剂量、时间相关 (P <0 0 1) ;流式细胞仪显示左旋多巴和多巴胺使PC12细胞发生凋亡 ,呈剂量依赖性 (P <0 0 1)。金刚烷胺、培高利特和司来吉兰均能保护PC12细胞活性 ,免受左旋多巴和多巴胺的影响 (P <0 0 1) ,并能抑制左旋多巴和多巴胺引起的PC12细胞凋亡 (P <0 0 5 )。　结论　大剂量左旋多巴和多巴胺对PC12细胞产生毒性损害 ,金刚烷胺、培高利特和司来吉兰能拮抗左旋多巴和多巴胺对PC12细胞的毒性效应 ,具有神经保护作用。     

培高利特和左旋多巴联合治疗帕金森病的疗效和安全性研究

目的　观察培高利特作为复方左旋多巴制剂的附加药物来治疗复方左旋多巴疗效减退、运动功能波动的帕金森病 (PD)患者的临床疗效及安全性。　方法　采用开放、为期 1年的临床研究 ,5 7例患者入组前服用不同剂量的复方左旋多巴制剂 ,培高利特采用剂量滴定法加服 ,临床疗效判断采用改良Webster评定量表 ,PD运动功能评定量表 (MDRSPD)和Hoehn Yahr分级评定进行治疗前后的比较。　结果　改良Webster评定结果显示 ,老年组 14例 (31 8%)有明显进步 ,15例 (34 1%)有进步 ;非老年组分别为 5例 (33 3%)有明显进步和 5例 (33 3%)有进步。PD运动功能量表评定结果显示 :老年组 14例 (31 8%)有明显进步 ,12例 (2 7 3%)有进步 ;非老年组 5例有明显进步 (33 3%)和 6例 (4 0 0 %)有进步。培高利特的平均日服用剂量老年组为 (0 4 0± 0 2 6 )mg ,非老年组为 (0 39± 0 2 0 )mg ,总副反应发生率为 2 3 7%。　结论　培高利特是一种有效的、耐受性良好副作用较小的治疗的附加药物。     

帕金森病患者认知功能障碍与同型半胱氨酸的相关性研究

目的探讨同型半胱氨酸(homocysteine,Hcy)与帕金森病患者认知功能的相关性及其影响因素。方法选择2013年1月~2016年5月烟台市烟台山医院神经内科住院的帕金森病患者81例,根据诊断分为非智能减退组25例、轻度智能减退组32例及帕金森病痴呆组24例。另选择健康体检者19例作为对照组。登记病史及详细体检,行Hoehn-Yahr分级,通过简易智能状态检查量表评分、临床痴呆评定量表筛查认知功能障碍。测定Hcy、叶酸、维生素B12,并进行相关性分析。结果非智能减退组、轻度智能减退组和帕金森病痴呆组Hcy水平明显高于对照组,差异有统计学意义(P0.05,P0.01);且帕金森病痴呆组Hcy水平明显高于非智能减退组[(14.8±3.9)μmol/L vs(12.5±3.3)μmol/L,P0.05]。所有帕金森病患者Hcy与口服左旋多巴-苄丝肼日剂量(r=0.298,P=0.000)、口服左旋多巴-苄丝肼时间(r=0.280,P=0.000)、病程(r=0.301,P=0.000)、年龄(r=0.184,P=0.019)相关,与疾病严重程度不相关。结论高Hcy很可能为帕金森病及帕金森病认知功能障碍的危险因素之一,控制多巴制剂口服剂量可能有助于帕金森病痴呆的防治。     

血管性帕金森综合征的多巴反应性研究

目的观察血管性帕金森综合征(VP)对复方多巴的反应性以及多巴反应性与病变部位的相关性。方法临床诊断VP的患者共61例(VP组)进行急性阶梯性左旋多巴治疗试验,计算服用左旋多巴-苄丝肼后统一帕金森病(PD)评分量表(UPDRS)运动部分评分最大改善率。同期146例PD患者(PD组)作为对照。根据头颅MRI所示缺血性病灶部位,将VP组再分组,第1种分组:基底节区病变组(25例);白质病变组(21例);黑质病变组(3例);混合病变组(12例)。第2种分组:黑质纹状体通路病变组(28例);白质病变组(21例)。经t检验比较各组间UPDRS运动部分最大改善率。结果VP组和PD组的UPDRS运动部分平均最大改善率依次为(10.4±7.4)%和(40.1±14.9)%,两组差异有显著性意义(P<0.01)。VP各分组:基底节区病变组UPDRS改善率(23.2±11.3)%,高于白质病变组的(6.5±4.3)%,低于PD组(P<0.01)。黑质病变组UPDRS改善率为(35.4±8.7)%,但例数少无法进行统计学分析。黑质纹状体通路病变组UPDRS改善率(26.3±10.6)%,高于白质病变组,但低于PD组(P<0.01)。结论VP组由于不同的病变部位,对复方多巴有不同的反应性;以累及黑质、基底节等黑质纹状体通路病变为主的VP对复方多巴有一定的反应性,而以白质病变为主的对复方多巴反应较差。可根据MRI提示的病变部位决定是否应用复方多巴治疗VP患者。     

帕金森病治疗药物对患者外周血单核红胞分泌细胞因子的影响

目的探讨治疗药物对帕金森病患者外周血单核细胞(PBMC)分泌白细胞介素-6(IL-6)和肿瘤环死因子-α(TNF-α)的影响.方法用酶联免疫吸附方法检测健康对照组、培高利特+美多芭组和美多芭组共25例受试者的外周血单核细胞,分别在无刺激、含刀豆蛋白A (ConA )或含培高利特的不同培养方式下,分泌IL-6和TNF-α的浓度. 结果 IL-6分泌水平在ConA刺激下, 培高利特+美多芭组和美多芭组均显著低于对照组(P<0.05,P<0.01),且培高利特+美多芭组显著高于美多芭组 (P<0.05);培高利特刺激下,3组差异无显著性(P>0.05).TNF-α浓度培高利特+美多芭组在ConA刺激下较无刺激和培高利特刺激均显著增高(P<0.01);且不同培养基培养后,3组间比较差异均无显著性(均为P>0.05). 结论药物治疗的PD患者PBMC分泌IL-6的能力显著低于健康对照者.培高利特可能通过改善和恢复帕金森病患者PBMC分泌 IL-6能力发挥治疗作用,同时不增加TNF-α的分泌,而后者可能对神经系统具有细胞毒作用.     

培高利特对大鼠纹状体神经营养活性的影响

目的　观察培高利特 (pergolide)对大鼠纹状体神经营养活性的影响。　 方法　取 1d的新生大鼠中脑腹侧细胞悬液 ,将其接种于 2 4孔培养板中进行培养。实验分 4组 :单纯培养组及 3个实验组 ,实验组为分别向培养液中加入经生理盐水、培高利特及培高利特 +氨黄酰基苯甲酰胺化合物 (sulpiride)腹膜内注射 7d后的大鼠纹状体提取液。培养 7d后 ,应用酪氨酸羟化酶免疫组化法检测并比较各组多巴胺 (DA)能神经元的生长状态。　结果　实验组的各培养孔内的酪氨酸羟化酶(TH)阳性神经元及其细胞突起的数量增多 ,长度增加 ,与单纯培养组〔TH阳性细胞数为 382 ,第 1级突起数为 0 8± 0 1,最长突起长度为 (11 7± 0 9) μm〕比较 ,差异均有显著性 (P <0 0 5 ) ,其中尤以培高利特组的变化更为明显 (TH阳性细胞数分别为 15 2 0 ,第 1级突起数为 2 7± 0 2 ,最长突起长度为〔92 1± 3 7) μm〕 ,而生理盐水组与培高利特 +Sulpiride组之间差异无显著性 (P >0 0 5 )。　 结论　培高利特能促进纹状体神经营养活性 ,其机制可能与刺激DAD2 受体有关。     

帕金森病治疗药物对患者外周血单核细胞分泌细胞因子的影响

目的　探讨治疗药物对帕金森病患者外周血单核细胞 (PBMC)分泌白细胞介素 6(IL 6 )和肿瘤坏死因子 α(TNF α)的影响。　方法　用酶联免疫吸附方法检测健康对照组、培高利特 美多芭组和美多芭组共 2 5例受试者的外周血单核细胞 ,分别在无刺激、含刀豆蛋白A (ConA )或含培高利特的不同培养方式下 ,分泌IL 6和TNF α的浓度。　结果　IL 6分泌水平 :在ConA刺激下 ,培高利特 美多芭组和美多芭组均显著低于对照组 (P <0 0 5 ,P <0 0 1) ,且培高利特 美多芭组显著高于美多芭组 (P <0 0 5 ) ;培高利特刺激下 ,3组差异无显著性 (P >0 0 5 )。TNF α浓度 :培高利特 美多芭组在ConA刺激下较无刺激和培高利特刺激均显著增高 (P <0 0 1) ;且不同培养基培养后 ,3组间比较差异均无显著性 (均为P >0 0 5 )。　结论　药物治疗的PD患者PBMC分泌IL 6的能力显著低于健康对照者。培高利特可能通过改善和恢复帕金森病患者PBMC分泌IL 6能力发挥治疗作用 ,同时不增加TNF α的分泌 ,而后者可能对神经系统具有细胞毒作用     

补肾中药对帕金森病模型小鼠黑质-纹状体神经元的保护作用

目的 探讨补肾中药对帕金森病(PD)模型小鼠黑质-纹状体神经元的保护作用.方法 取PD模型小鼠40只,随机分为淫羊藿组、女贞子组、黄精组、司来吉兰组及模型组5组,每组8只,另取同周龄C57BL/6J雄性小鼠8只作为正常对照组.正常对照组及模型组均给予蒸馏水,淫羊藿组、女贞子组、黄精组、司来吉兰组分别灌胃给予淫羊藿、女贞子、黄精、司来吉兰的水煎液及水溶液.每次灌胃0.5 ml,2次/d,连续给药4 w后冰浴中取黑质-纹状体,流式检测FasL、Fas、Caspase-3、Bcl-2,酶联免疫法检测神经生长因子(NGF)、脑源性神经因子(BDNF)、胶质源性GDNF,电镜下观察小鼠黑质中神经元的形态.结果 黄精组FasL的含量明显低于模型组(P＜0.05),与司来吉兰组及正常对照组无明显差异(P＞0.05);淫羊藿组、女贞子组及黄精组的Caspase-3的含量均低于模型组(P＜0.05),均与正常对照组和司来吉兰组无明显差异(P＞0.05);黄精组中NGF的含量明显高于模型组、司来吉兰组(P＜0.05),与正常对照组无明显差异(P＞0.05);淫羊藿组和黄精组中的BDNF的含量均高于模型组和正常对照组(P＜0.05),淫羊藿组与司来吉兰组无明显差异(P＞0.05),黄精组明显高于司来吉兰组(P＜0.05);淫羊藿组、女贞子组及黄精组小鼠黑质神经元凋亡程度较模型组有减轻.结论 补肾中药可能通过降低黑质-纹状体中相关凋亡因子的含量、增加NGF的含量来对DA能神经元起保护作用的.     

司来吉兰治疗帕金森病冻结步态病人的疗效观察

目的观察司来吉来治疗帕金森病(PD)冻结步态病人的临床疗效及安全性。方法采用开放性的自身治疗前后对照研究,纳入51例有冻结步态的PD病人,其中3例中途脱落,48例完成临床观察。15例初诊病人直接给予司来吉兰治疗,33例非初诊病人在原有左旋多巴治疗基础上加用司来吉兰治疗,疗程均为12周。所有入组病人于治疗前及治疗后4周、12周进行冻结步态问卷(FOGQ)、UPDRSⅢ、汉密尔顿焦虑量表(HAMA)、汉密尔顿抑郁量表(HAMD)、简易精神状态评价量表(MMSE)的评估。结果 48例病人经过司来吉兰治疗后能改善PD病人的冻结现象,降低UPDRS-Ⅲ评分及FOGQ评分,对PD非运动症状中的焦虑、抑郁及认知功能亦有改善,治疗前后比较差异有统计学意义(P 0.05)。治疗期间未见明显严重不良反应。结论盐酸司来吉兰能改善帕金森病病人的冻结步态及焦虑抑郁等非运动症状,是一种有效的抗帕金森病药物。     

蛋白激酶C抑制剂改善帕金森病大鼠异动症的研究

目的 探讨蛋白激酶C(PKC)抑制剂他莫昔芬对左旋多巴诱发异动症的细胞学与行为学效应. 方法将6-羟多巴胺立体定向注射于大鼠前脑内侧束建立帕金森病(PD)动物模型.模型成功的PD大鼠接受每天2次左旋多巴(50 mg/kg左旋多巴+12.5 mg/kg苄丝肼)腹腔注射,持续22 d.在第23天左旋多巴注射前,2组PD大鼠给予他莫昔芬或溶剂处理.评估旋转反应时间及剂峰旋转次数,采用蛋白印迹法检测纹状体区N-甲基-D-天冬氨酸受体NR1亚单位(NR1)和890、896位丝氨酸位点磷酸化的NR1(NR1S890、NR1S896)表达情况. 结果 PKC抑制剂他莫昔芬减轻少了左旋多巴诱导的PD大鼠剂峰旋转次数[(121.0±7.6)次与(161.5±22.1)次,t=2.6,P<0.05];此外,他莫昔芬能调节与异动症密切相关的NR1的亚细胞分布,使纹状体部位NR1在膜蛋白中的表达量减少至(82.4±5.1)%,与左旋多巴+溶剂组[(103.0±3.5)%]比较差异有统计学意义(t=6.7,P<0.05),同时使NR1S890、NR1S896的磷酸化水平明显降低,其表达量分别为(77.2±4.2)%与(98.4±6.4)%(t=5.9、3.6,均P<0.05). 结论长期左旋多巴作用激活了纹状体棘状神经元内丝氨酸激酶PKC,并导致谷氨酸受体磷酸化,从而出现了异动症;抑制丝氨酸激酶(如PKC)活性的药物可能是治疗及预防帕金森病异动症的一种新的治疗方式.     

帕金森病~(99m)TC-TRODAT-1多巴胺转运体单光子计算机断层摄影脑显像研究

目的应用~(99m)Tc-TRODAT-1多巴胺转运体(DAT)单光子计算机断层摄影(SPECT)脑显像,研究不同运动障碍亚型帕金森病(Parkinson's diseas e,PD)纹状体生化改变。方法选择不同运动障碍亚型PD患者68例,其中震颤为主型PD患者36例(震颤PD组),姿势异常步态障碍(PIGD)为主型PD患者32例(PIGD PD组),分别行~(99m)Tc-TRODAT-1 DAT SPECT脑显像,利用感兴趣区技术计算首发症状对侧纹状体与小脑的特异性放射性比值。结果 PIGD PD组患者首发症状对侧纹状体、小脑较震颤PD组患者明显降低(1.43±0.92) vs (1.49±0.10),P0.05]。纹状体、小脑下降与PIGD评分呈负相关(r=-0.73,P0.05),而与震颤评分无明显相关性(r=-0.21,P0.05)。结论不同运动障碍亚型PD患者~(99m)Tc-TRODAT-1 DAT SPECT脑显像存在明显的异质性,PIGD为主型PD患者纹状体DAT的功能降低更明显,提示不同运动障碍亚型PD有不同的生化病理基础。     

多巴胺受体激动剂普拉克索和单胺氧化酶B抑制剂司来吉兰治疗早期帕金森综合征的疗效对比

目的比较多巴胺受体激动剂普拉克索和单胺氧化酶B抑制剂司来吉兰治疗早期帕金森综合征的临床疗效。 方法选择自2012年5月至2015年10月收治于新疆维吾尔自治区人民医院神经外科的帕金森病患者90例,按照随机数字表法分为对照组（30例）、普拉克索组（30例）和司来吉兰组（30例）。对照组仅给予美多巴（初始剂量为62.5 mg/次,根据治疗效果逐渐增加至125 mg/次,3次/d）治疗,普拉克索组和司来吉兰组在对照组的基础上分别给予普拉克索（1.0 mg/d）和司来吉兰（2.5 mg/d）进行治疗。所有患者治疗6个月,期间观察并记录患者临床症状改善情况以及治疗过程中出现的不良反应。采用统一PD评分量表（UPDRS）对患者进行评估,计算患者用药前后的UPDRS得分。 结果普拉克索组与司来吉兰组治疗的总有效率分别为93.3%和90.0%,明显高于对照组（70.0%,P<0.05）。治疗前,普拉克索组、司来吉兰组和对照组的UPDRS评分差异无统计学意义（P>0.05）。在使用普拉克索和司来吉兰分别治疗后,患者的UPDRS评分显著下降,而对照组患者UPDRS评分下降不明显,普拉克索组、司来吉兰组与对照组的差异具有统计学意义（P<0.05）。普拉克索组的PD患者不良反应发生率（60.0%）明显多于司来吉兰组（6.7%,P<0.05）,但症状均能自行缓解。 结论普拉克索和司来吉兰均可有效改善早期帕金森症状,安全性好,但司来吉兰组的不良反应较少。     

血管性帕金森综合征与帕金森病的脑多巴胺转运体代谢比较

目的比较血管性帕金森综合征(vascular parkinsonism,VP)与帕金森病(Parkinson's disease,PD)患者在脑多巴胺转运体代谢方面的差异以及鉴别诊断价值。方法筛选临床诊断VP患者12例(VP组)和Hohen-Yahr分期匹配的PD患者12例(PD组)。分别应用多巴胺转运体示踪剂~(11)C-CFT正电子发射断层显像(PET)进行脑多巴胺转运体代谢的显像,并应用感兴趣区法测定和比较基底节多巴胺转运体示踪剂摄取指数。应用急性左旋多巴负荷试验测评和比较患者的急性多巴反应性,采用国际通用PD统一评分量表(UPDRS)运动分量表,计算最大改善率。结果 VP组患者两侧壳核后部~(11)C-CFT摄取信号轻度减低,~(11)C-CFT摄取信号降低范围小于壳核横断面的后1/4区域;壳核后部信号降低的范围基本对称,左侧与右侧壳核前部、壳核后部以及尾状核头部的示踪剂摄取指数比值为0.969、1.023、0.995,两侧比较差异无统计学意义(P0.05)。Hohen-Yahr分期匹配的PD组患者首发症状,肢体对侧的壳核前部、壳核后部~(11)C-CFT摄取信号强度明显低于首发症状肢体同侧(P0.01);首发症状肢体,对侧的壳核横断面后1/2区域~(11)C-CFT摄取信号缺损。在左旋多巴-苄丝肼200/50 mg剂量水平下,VP组患者的平均UPDRS运动评分最大改善率为(13.6±7.2)%,明显低于PD组患者的平均UPDRS运动评分最大改善率(42.6±13.9)%,差异有统计学意义(P0.05)。结论 VP和PD在脑多巴胺转运体代谢和急性多巴反应性方面存在显著差异。可应用脑多巴胺转运体代谢的PET作为这2种疾病鉴别诊断的生物学标记物。     

Is calculation of the dose in radioiodine therapy of hyperthyroidism worth while?

OBJECTIVE The persistent controversy as to the best approach to radioiodine dose selection in the treatment of hyperthyroldism led us to perform a study in order to compare a fixed dose regime comprising doses of 185, 370 or 555 MBq based on gland size assessment by palpation only, with a calculated ¹³¹I dose based on type of thyroid gland (diffuse, multinodular, solitary adenoma), an accurate thyroid volume measurement, and a 24-hour ¹³¹I uptake determination. DESIGN Prospective randomized study. PATIENTS Two hundred and twenty-one consecutive hyperthyroid patients referred for ¹³¹I treatment. Four patlents who dled for reasons unrelated to hyperthyroidism, 7 lost to follow-up and 47 who did not receive antithyroid drugs after treatment, were excluded. The remalnlng 163 patlents (143 women) were studied, dlvlded into subgroups accordlng to the type of gland. They all recelved antithyroid drugs prior to ¹³¹I treatment and this was resumed 7 days after treatment for a period of 3 weeks. MEASUREMENTS Thyroid function variables were determined approximately 2 weeks before ¹³¹I treatment, and again 1, 2, 3, 6, 9 and 12 months after treatment. Prior to ¹³¹I therapy the size of the thyroid gland was determined by ultrasound and a 24-hour uptake of ¹³¹I was carried out. Thyroid in 78 of the 163 patients. Twelve months after the initial ¹³¹I dose patients could be classified as euthyroid, hyperthyrold or hypothyroid. RESULT Neither in the group of 163 patients nor within the three subgroups of hyperthyroidism could any significant difference in outcome between the two treatment regimes be demonstrated. Thirty-two of 78 patients (41%) in the calculated dose group and 30 of 85 patients (35%, NS) in the fixed group were classified as hyperthroid. Seven of 78(9%) in the calculated dose group were classified as permanently hypothyroid. Finally, 39 of 78(50%) In the calculated dose group and 49 of 85(58%, NS) in the fixed group were enthyroid at 12 months after ¹³¹I treatment. One year after ¹³¹I therapy thyroid volume was deduced from 59.3 ± 9.2 (mean ± SEM) to 36.2 ± 6.6 ml (average reduction 39%) In the calculated dose group (P < 0.001). This reduction did not differ significantly from the fixed dose group where thyroid volume declined from 61.6 ± 6.1 to 41.17 ± 4.7 ml (average reduction 32%) (P < 0.001). CONCLUSIONS A semiquantitative approach is probably as good as the more elaborately calculated radiolodine dose for treatment of hyperthyroidism. It is clearly more cost effective and allows the use of predetermined standard doses.     

减重平板训练对老年帕金森病患者姿势和平衡能力的改善作用

目的探讨减重平板训练对老年帕金森病（parkinson's disease, PD）患者姿势和平衡能力的改善作用。 方法选取2018年1月至2019年6月浙江医院收治的74例老年PD患者,其中采用常规药物联合传统物理训练进行康复治疗38例（对照组）,在对照组治疗基础上给予减重平板训练进行康复治疗36例（观察组）。采用统一帕金森病评分量表（unified rating scale for Parkinson's disease, UPDRS）Ⅲ评估步态和姿势异常;采用Berg平衡量表（Berg balance scale, BBS）评估平衡能力;采用功能独立性评定量表（functional independence measure, FIM）评估运动能力。比较分析两组患者治疗前后UPDRSⅢ、BBS、FIM评分的差异。组间及组内比较均采用t检验。 结果与治疗前比较,观察组和对照组治疗后UPDRSⅢ评分、BBS评分、FIM评分均明显增高（t=2.815、3.016、4.281,2.035、2.049、2.234;均P<0.05）。两组患者治疗前UPDRSⅢ评分、BBS评分、FIM评分的差异均无统计学意义（t=0.975、0.784、0.539,P>0.05）;观察组治疗后UPDRSⅢ评分、BBS评分、FIM评分均明显高于对照组（t=2.346、2.035、3.014,P<0.05）。 结论减重平板训练能有效改善老年帕金森病患者的姿势和平衡能力。     

High doses of pergolide improve clinical global impression in advanced Parkinson's disease:- a preliminary open label study

We evaluated the efficacy and safety of high-dose pergolide treatment in patients with moderate to severe Parkinson's disease (PD) in an open-label multicenter clinical trial. The primary objective was to assess the amount of reduction in levodopa, the improvement in Unified Parkinson's Disease Rating Scale (UPDRS) and adverse reactions. We treated 32 patients with PD presenting with motor fluctuations. Pergolide treatment started with a dose escalation period of 12 weeks followed by a 12-week continuation period. Pergolide doses were increased up to a maximum of 12 mg/day in combination with a simultaneous decrease of levodopa doses in 100mg steps. Levodopa was reduced from 500 mg/day (median) to 250 mg/day. Mean UPDRS part III improved significantly (p=0.01). Clinical global impression improved significantly after 24 weeks (p<0.01). Most frequent adverse events were hallucinations, asthenia, anxiety, abdominal pain, and peripheral edema. Twenty-two patients finished the complete study according to protocol. A possible relationship to the study medication was assumed for two serious adverse events reporting psychosis. We conclude that high doses of pergolide are efficacious in advanced stages of PD if given in appropriate regimens.     

TRANSIENT THYROTOXICOSIS IN ENDEMIC GOITRE PATIENTS FOLLOWING EXPOSURE TO A NORMAL IODINE INTAKE

Twenty-three endemic goitrous subjects (goitre grade: III and IV) that were living in a chronic iodine-deficient area (iodine intake: less than 40 μg I/d) were submitted to clinical and laboratory evaluation within 3–8 weeks of arrival at the metropolitan area of São Paulo, where daily iodine intake is estimated to be 150–200 μg I/d. Eight patients developed a mild thyrotoxic state (T4 = 14.7 ± 2.3 μg/dl, T3 = 279 ± 55 ng/dl, no TSH response to TRH). Five additional subjects, although euthyroid, had a blunted TSH-response to TRH, and the remaining ten patients were euthyroid and had a normal TSH response to TRH. Thyrotoxicosis was associated with larger goitres (mean thyroid weight: 133 ± 46 g), with high thyroid uptake of RAI (mean 24 h ¹³¹ I uptake: 40 ± 15%) but not with increased urinary iodine excretion. Serum Tg levels were more elevated in the first two groups of patients (respectively, geometric means 68 and 72 ng/ml), than in the euthyroid, TRH-responsive group (52 ng/ml). Thyrotoxicosis resolved spontaneously after three to six months without the need for any specific medication. It was concluded that a relatively small and normal iodide intake due to regular consumption of iodized salt and industrialized foods may induce a transient form of thyrotoxicosis in endemic goitre patients arriving into urban areas.     

Effects of low-dose pergolide therapy on cardiac valves in patients with Parkinson's disease

BACKGROUND: Pergolide mesilate is widely used to treat Parkinson's disease in both the USA and Japan, but the maintenance dose is distinctly different between the USA (usually more than 1.5 mg/day) and Japan (usually less than 1.5 mg/day). Although several reports from the USA have suggested that mitral, aortic, and tricuspid valvular lesions were caused by pergolide, it is unclear whether low-dose pergolide therapy causes such valvular lesions. OBJECTIVES: The effects of low-dose pergolide therapy on cardiac valves were studied in Japanese patients with Parkinson's disease. METHODS: One hundred and five consecutive patients with Parkinson's disease approved for our protocol were enrolled in this study. Forty patients were treated with low-dose pergolide (0.05-1.5 mg/day for 2-115 months), and were included in the pergolide group (mean age 71 +/- 6 years). The other 44 patients received no ergot-derived dopamine receptor agonists, and 32 patients acted as age-matched controls (mean age 71 +/- 7 years). Both groups of patients underwent echocardiographic examination to detect organic lesions in cardiac valves such as thickening of the leaflet, annular calcification, restriction of valve motion and valvular tenting, and valvular regurgitation greater than 2 + on the 4-point scale. RESULTS: No significant difference was observed in the incidence of aortic, mitral and pulmonic valve lesions between the pergolide group and the control group. Although no organic lesions were detected in the tricuspid valve, the incidence of tricuspid regurgitation was significantly higher in the pergolide group than in the control group (p < 0.05). CONCLUSIONS: Although low-dose pergolide of less than 1.5 mg/day does not cause serious damage in the left-sided valves, it may induce tricuspid regurgitation.     

Modulation of Ventricular Repolarization and R‐R Interval Is Altered in Patients with Globally Impaired Cardiac 123I‐MIBG Uptake

Background: Cardiac ¹²³l‐metaiodobenzylguanidine (MIBG) imaging is widely used to assess cardiac sympathetic neuronal function. However, physiologic significance of impaired cardiac MIBG uptake is not fully elucidated. The purpose of the present study was to determine influences of abnormal cardiac sympathetic neuronal function on heart rate variability (HRV) and ventricular repolarization process. Methods: Twenty‐nine patients with prior myocardial infarction were divided into two groups by a heart‐to‐mediastinum ratio (H/M) of MIBG scintigraphy. Ten patients with globally decreased MIBG uptake (group I: H/M < 1.5), 19 patients with partially decreased MIBG uptake (group II: H/M < 1.5), and 17 control subjects with normal MIBG uptake (group III) were studied. Holler recording and a standard 12‐lead electrocardiography were used for evaluation of HRV, QT‐RR relation, and QT dispersion. Results. Low, high, and total frequency components decreased in groups I and II, as compared to that of group III. The reduction of these frequency domain measures was more severe in group I than in group II, but the differences did not reach statistical significance. Circadian variation of frequency domain measures disappeared in group I. The slope of QT‐RR relation was significantly greater in group I than in groups II and III. QT dispersion was also greater in group I (64 ± 25 msec) than in group 11(43 ± 19 msec) and group III (28 ± 9 msec). Conclusion. These results suggest that patients with sympathetic neuronal dysfunction inferred from globally impaired cardiac MIBG uptake have an altered modulation of ventricular repolarization process as well as decreased HRV.