综合驱铜治疗对肝豆状核变性患者胆汁排铜及肝脾声像图的…

为了探讨综合驱铜治疗对具有不同肝脾声像图分型的肝豆状变性（ＨＬＤ）患者胆汁排铜及肝脾声像图指标的影响，我们采用二巯丁二酸和二巯丙磺钠治疗３０例ＨＬＤ，治疗前后用ＡｌｏｋａＳＳＤ２５６型声像图仪对患者进行声像图分型和测量，并施行１２指肠引流术留取胆汁Ｂ液检测铜，锌，铁含量。结果综合驱铜能有效地增加光点闪烁型，岩层征型和树枝状带型的胆汁铜排泄（Ｐ〈０．００１），且树肢状光带型的ＳＰＴ，ＳＰＬｂ，ＳＶ，     

凯西莱联合青霉胺治疗肝豆状核变性模型鼠的研究

目的探讨凯西莱(MPO)联合青霉胺(PCA)对肝豆状核变性(HLD)模型鼠铜代谢及肝功能的影响。方法采用铜负荷饮食法喂养大鼠制作HLD模型,并分为HLD对照组、MPO组、PCA组及MPO PCA组,予以相应的药物干预。观察各组大鼠肝铜、24h尿铜及谷氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总蛋白(TP)、白蛋白(ALB)水平变化情况。结果HLD对照组、各药物干预组肝铜、24h尿铜水平较正常对照组显著增高(均P<0.01);MPO PCA组、PCA组肝铜水平较HLD对照组、MPO组显著降低(均P<0.01),24h尿铜各药物干预组较HLD对照组显著增高(P<0.05～0.01)。ALB水平各药物干预组较HLD对照组显著增高(P<0.05～0.01),各药物干预组间差异无统计学意义。MPO PCA组ALT、AST水平较HLD对照组、PCA组、MPO组显著降低(均P<0.05),与正常对照组相比差异无统计学意义。结论MPO联合PCA能显著降低HLD模型鼠肝铜水平,促进尿铜排泄,升高血清ALB水平,保护肝功能,效果优于PCA或MPO单用。     

肝豆状核变性的腹部肌肉病理及铜染色研究

目的探讨肝豆状核变性(HLD)患者的腹部肌肉病理特点及铜染色技术在HLD的诊断价值。方法 21例HLD患者因脾脏功能亢进需行脾脏切除术为HLD组,其中肝型HLD 11例,脑-内脏型HLD 10例。另选择5例因外伤致脾破裂行急诊脾脏切除术的非HLD患者为对照组。两组患者均留取腹部手术切口处少许肌肉标本,经液氮-异戊烷处理后作厚度为10μm的冰冻切片,分别进行苏木精-伊红、改良Gomori(MGT)、还原型辅酶Ⅰ四氮唑还原酶(NADH-TR)、琥珀酸脱氢酶(SDH)、细胞色素C氧化酶(CCO)等组织病理染色,以及红氨酸、硫氧酸铜染色,光镜下观察病理表现。比较肝型和脑-内脏型患者的肌肉病理有无差异。结果肝型HLD患者腹部肌肉病理未见异常。脑-内脏型HLD患者腹部肌肉病理见肌纤维大小轻度不等,4例有明显的强反应性血管(SSVs),3例有破碎红纤维(RRF),2例CCO活性缺失纤维和S/C双染呈蓝纤维;其中2例颅脑MRI示额叶有软化灶者腹部肌肉均发现典型SSVs现象。21例HLD患者的腹部肌肉的铜染色均阴性。结论肝型HLD患者腹部肌肉未见线粒体功能异常,而脑-内脏型HLD患者腹部肌肉发现线粒体功能异常。肌肉铜染色对HLD诊断价值不大。     

青霉胺联合硫普罗宁治疗肝型肝豆状核变性的临床研究

目的 观察硫普罗宁(tiopronin,TPO)联合青霉胺(penicillamine,PCA)治疗肝型肝豆状核变性(hopatolenticular degeneration,HLD)的疗效和安全性.方法 将年龄大于12岁,首次住院的33例肝型HLD患者随机分为对照组(n=16)和治疗组(n=17).在低铜饮食和口服锌剂(150 mg/d)的基础上,对照组给予青霉胺250mg tid口服,治疗组在对照组基础上给予硫普罗宁200 mg tid口服,疗程均为12周.记录治疗前后24 h尿铜(u-Cu)、血清铜(p-Cu)和铜蓝蛋白(ceruloplasmin,CER)水平,估算游离铜(nCER-Cu)水平,观察肝功能、血常规和凝血常规指标.结果 两组u-Cu水平均较治疗前显著升高(P<0.01),与对照组比较,治疗组升高更为显著(P<0.05);两组nCER-Cu水平较治疗前显著降低(P<0.05),与对照组比较,治疗组降低更为显著(P<0.05).治疗组AST和TBIL水平较治疗前及对照组显著下降(P<0.01),而对照组无显著变化(P>0.05).治疗组Dhawan指数较治疗前显著降低(P<0.01),与对照组比较无统计学差异(P>0.05).结论 TPO联合PCA治疗肝型HLD能显著促进24 h尿铜排泄,降低游离铜毒性,并能改善肝功能,疗效优于PCA单用.     

肝豆状核变性患者肝细胞铜代谢的研究

肝豆状核变性(HLD)系常染色体隐性遗传性铜蓄积性疾病,是以肝脏和其他组织细胞内渐进性铜蓄积为发病基础。患者因肝铜蓄积,致急、慢性肝炎,肝硬化和暴发性肝功能衰竭等。在中枢神经系统,铜可致相应的损害,表现为多种神经、精神异常。此外,尚可致肾脏、心脏损害及多种内分泌紊乱等。资料和方法我们于2003年9月至2004年2月安徽中医学院神经病学研究所附属医院外科手术获取9例HLD患者和5例正常对照肝组织块,清洗、剪切并去除包膜、胶原酶温育消化、过筛、离心5min。接种于6孔培养板,37℃5%CO2培养箱中行细胞培养。定时换液,4～8d后,倾尽生…     

肝豆状核变性患者异常骨代谢机制研究

目的　探讨肝豆状核变性 (HLD)患者异常骨代谢机制。方法　对 3 5例HLD患者及 2 5例健康对照分别测定骨代谢相关的血清激素 :甲状旁腺激素 (PTH)、降钙素 (CT)、1,2 5二羟维生素D( 1,2 5 (OH) 2 vitD3)以及血清骨钙素 (BGP)水平 ;血、尿钙、磷及尿肌酐、脱氧吡啶啉 (DPD)等。其中 3 0例HLD患者驱铜治疗后重测上述指标。结果　HLD患者血PTH、1,2 5 (OH) 2 vitD3及血钙较正常对照明显减低 ;血CT、BGP较正常对照组明显升高。治疗后患者除骨痛症状基本消失外 ,尿钙、血CT较治疗前减低 ,血 1,2 5 (OH) 2 vitD3、尿DPD/肌酐较治疗前升高。结论　HLD患者存在异常骨骼代谢 ,驱铜治疗同时辅以补充钙剂、活性维生素D等有助于骨代谢改善。     

肝豆状核变性脾切除的探讨（附42例报告）

肝豆状核变性(HLD)并发脾功能亢进患者,于脾切除或/及分流术后极易招致神经症状迅速恶化而死亡,故长期以来大多数学者不主张手术。作者等对42例并发脾亢的HLD患者,于手术前采用中西医结合驱铜治疗,结果38例术后血细胞显著增高而神经症状基本未加重,术后死亡4例均为28岁以上的脑-肝型患者。     

驱铜药治疗后肝豆状核变性神经系统症状恶化机制探讨

肝豆状核变性(HLD)又称Wilson病,为一种遗传性铜代谢障碍所致的肝硬化和基底节为主的脑部变性疾病。研究证实,WD患者因ATP7B基因突变引起铜代谢障碍,使得游离的铜离子在肝、豆状核、角膜、肾脏等组织器官缓慢蓄     

口服二巯丁二酸对肝豆状核变性临床疗效及尿铜的影响

２０例肝豆状核性患者，男１１例，女９例。年龄１０－３７岁。口服二巯丁二酸７０ｍｇ．ｋｇ．ｄ观察８周，结果表明，１２例好转，１例无效，有效率达９５％。疗前与疗后１－８周２４ｈ尿铜比较，结果显示；疗后各周及疗后总平均尿铜值均显著高于疗前。其尿排铜增高与临床疗效相一致。治疗期６例出现齿龈出血、皮下瘀斑外，未见其他副反应。     

肝豆状核变性患者的人格特征及相关因素分析

目的　探讨肝豆状核变性 (HLD)患者的人格特征及相关因素。方法　对 83例住院HLD患者采用艾森克个性问卷 (EPQ)进行测查 ,并与 6 0名正常人进行对照。结果　HLD患者的精神质和掩饰程度两项粗分均显著高于正常对照组 (P <0 .0 5 ,P <0 .0 1) ;内外向维度分布较正常对照组有显著差异 (P <0 .0 5 ) ,且以外向型更多见。结论　HLD可改变自身人格特征 ,在药物驱铜治疗的同时应加强心理治疗 ,以提高临床疗效     

Observation on the changes of clinical symptoms,blood and brain copper deposition in Wilson disease patients treated with dimercaptosuccinic acid for 2 years

ObjectiveTo compare the clinical symptoms, brain copper deposition changes of Meso-2,3-dimercaptosuccinic acid (DMSA) and penicillamine therapy in patients with Wilson disease (WD) within 2 years.Methods68 drug-naive patients with WD were enrolled. 10 WD patients treated with zinc gluconate alone were used as the control group. Neurological symptoms were scored using the modified Young Scale. Liver function tests, copper indices and sensitive weighted imaging (SWI) examination were collected. The values of corrected phase (CP) were collected. WD patients were treated with DPA (group 1) or DMSA (group 2) for two years, and followed up every 2 months.ResultsThe ratio of neurological improvement in group 2 was higher than that in group 1 (P = 0.029). Higher rate of neurologic worsening was noticed in patients treated with DPA vs DMSA (P = 0.039). The post-treatment neurological score of DMSA group was lower than that of Zn group (P = 0.037). Hepatic function in 63.3% of patients was stable, while 16.7% was improved, and 20% was deteriorated, after DMSA therapy. Urinary copper levels were lower 1 month (p = 0.032), 4 months (p = 0.041), 12 months (p = 0.037) after initiation of treatment in group 2 than in group 1. At the first year of treatment, the CP values in globus pallidus and substantia nigra in group 2 were higher than those in group 1 (P = 0.034,0.039). At the second year of treatment, the CP values of substantia nigra in group 2 were higher (P = 0.041). Discontinuation was more common in patients on DPA therapy (P = 0 0.032).ConclusionsDMSA could remove metal from brain tissue faster than DPA. DMSA is effective for neurologic symptoms, while the outcome for hepatic symptoms is not entirely satisfactory. DMSA therapy is better tolerated than DPA.     

BAL modulates glutamate transport in synaptosomes and synaptic vesicles from rat brain

The therapeutic use of BAL (2,3-dimercaptopropanol) as treatment for poisoning has been halted by data suggesting serious neurotoxicity. This article is a report on the effects of BAL and other dithiols, DMSA (meso-2,3-dimercaptosuccinic acid) and DMPS (2,3-dimercaptopropane-1-sulfonic acid), on [3H]glutamate release and uptake by rat brain synaptosomes and [3H]glutamate uptake by synaptic vesicles. BAL (100 microM) inhibited glutamate uptake (30%) and stimulated its basal release (30%) in synaptosomes, without affecting K+-stimulated release. BAL also inhibited glutamate uptake by synaptic vesicles (up to 60%). DMPS and DMSA (100 microM) had no significant effects on these parameters. The data reported here provide some evidence of glutamate involvement in BAL-induced neurotoxicity by demonstrating direct effects of BAL on glutamatergic system modulation.     

Anticopper efficacy of captopril and sodium dimercaptosulphonate in patients with Wilson's disease

The aim of this study was to explore and compare initial treatment effects of captopril (Tensiomin) and sodium dimercaptosulphonate (DMPS) on a relatively large series of Wilson's disease inpatients. Two important markers of anticopper efficacy: serum sulphydryl and 24 h urinary copper levels in the patients were evaluated before and after treatment. The patients were randomly subdivided into 4 groups to allow statistical analysis (ANOVA) of the values recorded. The protocol was an open-label study of all the patients treated for 8 weeks (i.e., all the patients except those in the no-drug group), and a further six-month follow-up (post hospitalization) of the 14 patients administered captopril. Several copper-related variables were studied to evaluate the effect of the drugs on copper, and several biochemical and clinical variables were studied to evaluate potential toxic effects. Captopril was found to have a significant anticopper effect and did not markedly raise serum sulphydryl levels within this limited patient sample; the anticopper efficacy of captopril was, however, found to be markedly lower than that of DMPS; DMPS was found to raise the patients' serum sulphydryl and urinary copper levels. Evaluation of data from individual patients revealed evidence of a toxic side effect in only 1 patient, treated with DMPS, who exhibited transiently raised serum alanine aminotransferases, while no serious adverse events, upstanding syncope, irritating cough and leukopenia induced by captopril were noted. The results obtained in this four-group sample suggest that captopril might be a mild anticopper agent for Wilson's disease, possibly relieving the hepatic portal hypertension, but that DMPS has a greater field of anticopper efficiency than captopril. The authors also discuss recent experience of the overall treatment in China.     

小脑顶核电刺激合并高压氧治疗颅脑损伤

目的探讨小脑顶核电刺激合并高压氧治疗颅脑损伤恢复期患者的疗效。方法将颅脑损伤患者随机分为治疗组42例和对照组40例。治疗组接受小脑顶核电刺激并用高压氧治疗,对照组接受高压氧治疗,分别在治疗前后采用日常生活活动能力评分量表(ADL)进行功能评定,根据临床四级疗效标准进行疗效评定。结果治疗组治疗后ADL评分较前明显提高(P<0.01),且与对照组相比差异有统计学意义(P<0.05),治疗组总有效率80.95%明显高于对照组的52.22%(P<0.05)。结论小脑顶核电刺激合并高压氧能有效提高高压氧对颅脑损伤恢复期患者的疗效。     

扩容疗法应用于动脉瘤术后脑血管痉挛的效果观察

目的观察扩容疗法应用于动脉瘤术后脑血管痉挛的效果。方法将106例动脉瘤术后脑血管痉挛患者知情同意后分为观察组和对照组各53例。对照组给予尼莫地平治疗,观察组在此基础上给予胶体溶液静脉输注扩容治疗。对比2组经颅多普勒超声(TCD)检查结果、CT检查结果、GCS评分、血流动力学指标变化和不良反应发生率。结果观察组治疗后7d和14d的TCD值显著低于对照组(P0.01)。2组Fisher评分差异无统计学意义(P0.05)。观察组治疗后7d和14d的GCS评分显著高于对照组(P0.01)。观察组治疗后、灌注后的收缩压和舒张压显著低于对照组(P0.05)。2组不良反应发生率差异无统计学意义(P0.05)。结论扩容疗法应用于动脉瘤术后脑血管痉挛可有效改善患者脑部供血,但会降低血压,临床治疗中应予以重视。     

亚低温治疗急性脑出血的临床疗效及对自由基含量的影响

目的:本研究观察亚低温(MHT)技术治疗急性脑出血的临床疗效和对自由基含量的影响。方法:随机将52例急性脑出血病人分为治疗组和对照组各26例,治疗组在药物治疗脑出血的同时加用MHT治疗技术,并在治疗前及治疗后14天进行神经功能缺损评分及血清超氧化物歧化酶(SOD)、丙二醛(MDA)含量的测定。结果:治疗组较对照组神经功能缺损评分明显降低(P<0.05),血清SOD活性显著提高,MDA水平明显降低(P<0.01)。结论:MHT治疗技术可以明显改善急性脑出血患者的神经功能,与其清除自由基有一定关系。     

糖尿病合并脑梗死患者颈动脉超声46例分析

目的探讨糖尿病合并脑梗死惠者颈动脉超声的价值和意义。方法采用彩色多普勒显像仪对46例糖尿病合并脑梗死（DMCI）、40例非糖尿病脑梗死（CINDM）和42例非脑梗死糖尿病（DMNCI）患者进行颈动脉超声检测。结果DMCI组颈动脉内膜中层厚度（IMT）,颈动脉不稳定斑块率和颈动脉狭窄程度,分别与CINDM组和DMNCI组比较,均有明显差异（P〈0．01,P〈0.05,P〈0.01）。结论糖尿病合并脑梗死患者的颈动脉粥样硬化斑块形成,内膜增厚及颈动脉狭窄是造成脑梗死的主要原因,颈动脉超声为糖尿病患者可能造成脑梗死提供早期预测。     

脑梗死患者血清超敏C反应蛋白D-二聚体含量及颈动脉粥样硬化斑块的测定及分析

目的探讨颈内动脉系统急性脑梗死患者血清超敏C反应蛋白(hs-CRP)、D-二聚体(D-Dimer)含量及颈动脉粥样硬化斑块的变化及意义。方法测定85例首次颈内动脉系统急性脑梗死患者血清hs-CRP和血浆D-Dimer含量,并与正常对照组进行比较;颈动脉彩超测定颈动脉粥样硬化斑块情况。分析血清hs-CRP、血浆D-Dimer含量、颈动脉粥样硬化斑块情况与神经功能缺损程度评分的关系。结果脑梗死组血清hs-CRP和血浆D-Dimer含量、不稳定斑块率明显高于正常对照组(均P0.05),脑梗死中重度组明显高于轻度组(均P0.05),伴不稳定斑块患者血清hs-CRP和血浆D-Dimer含量明显高于不伴不稳定斑块患者(P0.05)。脑梗死组hs-CRP和D-Dimer含量与NIHSS评分呈正相关(r=0.57和0.38,均P0.05)。结论急性脑梗死患者血清hs-CRP及D-Dimer含量及不稳定斑块率明显增高,观察其情况对于预测脑梗死的发生和病情轻重具有重要意义。     

在体磁共振波谱及扩散张力成像观察肌萎缩性侧索硬化的病理变化的研究

目的结合磁共振波谱成像(MRSI)以及扩散张力成像(DTI)技术及磁共振影像(MRI)对肌萎缩性侧索硬化(ALS)进行对照研究,评价MRSI、DTI、MRI在ALS诊断中的作用。方法采用MRSI、DTI及MRI技术对ALS患者及对照组进行扫描,观察沿皮质脊髓束(CST)走行区域包括中央前回皮层下(SWM)、半卵圆中心(CS)、侧脑室旁白质(PV)、内囊后肢(PIC)、大脑脚(CP)的各向异性比(FA)以及平均扩散率(MD),以及SWM、PV、PIC平面氮乙酰门冬胺酸(NAA)与肌酸(Cr)比值在对照组及ALS患者的改变,并比较不同扫描序列在ALS诊断的作用。结果ALS的总FA较对照组明显降低(P<0.001),在CST走行区的SWM、CS、PV和PIC平面,ALS组的FA较对照组明显降低(P<0.05),MD在ALS组有升高的趋势,但无统计学差异。ALS组的NAA/Cr较对照组明显降低(P<0.05),在SWM和PV平面ALS组的NAA/Cr较对照组降低明显(P<0.05)。对T1WI、T2WI与FLAIR序列判断结果显示,对照组与ALS组间MRI的表现无明显差异。结论MRSI与DTI结合能够早期定量探测ALS患者CST的轴索损伤,SWM、CS、PV和PIC平面的FA,在SWM和PV的NAA/Cr为有效的指标。ALS与对照组MRI的表现则无明显差异。     

雌激素对阿尔茨海默病的干预作用

目的选择绝经期(65岁前)的轻中度AD(阿尔茨海默病)妇女,给予雌激素替代治疗(HRT),于治疗前、后分别测试其智力的变化;以双侧穹隆-海马伞切断制作AD大鼠模型,并给予雌激素治疗,观察穹隆-海马伞切断组、雌激素治疗组避暗实验的错误次数及潜伏期的变化,及脑内海马区(CA1区)烟碱型乙酰胆碱受体 (nAchR)表达的变化;从临床和基础两方面观察雌激素对AD的干预作用,探讨雌激素的作用及相关机制。方法选择21例绝经期(65岁前)的轻中度AD妇女,随机双盲比较治疗,用老年痴呆认知能力评价表,对治疗前、治疗后 16周分别进行智能评分。健康雌性Wistar大鼠,随机分为穹隆-海马伞切断组和雌激素治疗组;每组大鼠5只。在脑立体定位仪上切断双侧穹隆-海马伞,建立模拟AD的动物模型,对比穹隆-海马伞切断组和雌激素治疗组大鼠的智力变化;并应用免疫组织化学技术观察大鼠脑内CA1区nAchR细胞表达的变化。结果 21例患者行雌激素替代疗法后,修订长谷川量表(HDS-R)及精神认识能力(CCSE)评分比治疗前显著提高(P<0．001,P<0．01),社会活动功能调查(FAQ)评分比治疗前显著降低(P<0．05)。与穹隆-海马伞切断组大鼠比较,雌激素治疗组大鼠避暗实验的错误次数明显减少,潜伏期显著延长(P<0．05),脑内nAchR的表达显著增加(P<0．01)。结论临床和基础实验均证实雌激素能提高AD的智力,并认为其与脑内nAchR表达的增加有关。