调节血脂:来自心脏病学者的经验

本刊2009年第1期重点为:调脂治疗.目前以3-羟基-3-甲基戊二酰辅酶A(HMG-CoA)还原酶抑制药即他汀类药物为代表的调脂治疗,已被公认为心脑血管疾病的常规治疗方法;它们通过抑制体内胆固醇合成途径而降低血清胆固醇水平.     

他汀类药对脑梗死的临床疗效和作用机制

多项研究已经提示他汀类药可以降低缺血性脑卒中发生率，具有神经保护作用。他汀类药除降血脂作用外，还有改善血管内皮功能，减少氧化应激，抑制炎性反应等作用。缺血性脑卒中患者使用他汀类药治疗后恢复较好，这不仅归因于他汀类药的调脂作用，其还有各种非降脂作用，称他汀类药具有多效性。本文总结了有关他汀类药多效性作用的实验研究，以及他汀类药预防缺血性脑卒中的临床试验研究。     

抗3-羟基-3-甲基戊二酰辅酶A还原酶抗体实验室检测及临床意义

抗3-羟基-3-甲基戊二酰辅酶A还原酶抗体是新近发现的一种自身抗体,与他汀类调脂药密切相关,可以作为免疫性坏死性肌病的免疫学标志物。本文拟就该抗体的发现、检测方法和临床意义进行简要综述。     

长效安定剂哌(口普)嗪棕榈酸酯治疗精神病50例临床疗效观察

哌(口普)嗪(Pipothiazine)是一种新的酚噻嗪类强神经阻滞剂。其化学名称为2-dimethylsufamoyl-10-[3-(4-hydroxyethyl piperidino)-propyl]phenothia-zine。其化学结构式为本药系哌(口普)嗪和棕榈酸结合而成,故名哌(口普)嗪棕榈酸脂(Pipothiazinepalmitate)。由于其酯化物(酯     

血脂康与来适可的调脂疗效比较

目的 比较天然他汀药物与人工合成他汀药物的调脂效果。方法 取符合条件的患者62例,随机分为血脂康组和来适可组,疗程8周,服药前后各测血脂1次。结果 两组调脂疗效无显著差别(P>0.05)。结论 国产天然他汀类药物血脂康与国际上公认的人工合成他汀类药物来适可的调脂效果相似,且价格便宜,适合基层医院使用。     

他汀类药对蛛网膜下腔出血不良反应及病死率影响的Meta分析

目的探讨他汀类药对SAH不良反应及病死率的影响。方法使用MEDLINE、PUBMED、中国知网全面检索关于SAH后使用他汀类药物治疗的随机对照试验。检索语言为中、英文。结局指标为不良预后及病死率。使用ReVMan5.3进行统计学分析。结果共11篇文章入选,他汀治疗SAH后不良反应发生率(OR=0.98,95%CI=0.66~1.45),80mg辛伐他汀治疗后不良反应发生率(OR=1.06,95%CI=0.44~2.52)。他汀药治疗SAH病死率(OR=0.77,95%CI=0.52~1.12),高剂量辛伐他汀治疗后病死率(OR=0.31,95%CI=0.07~1.36)均与对照组无明显差异。结论尚未发现他汀药治疗SAH后有增加临床不良反应发生率或病死率的风险。     

静脉注射免疫球蛋白在免疫介导的神经肌肉疾病中的应用

目前,如何治疗免疫性神经肌肉疾病是神经科面临的一大问题。皮质类固醇是应用时间较久、范围最广、疗效最肯定的免疫抑制药物。但因其不良反应明显,造成治疗上的困惑。而静脉注射免疫球蛋白(IVIG)治疗免疫介导的神经肌肉疾病,已逐渐应用于临床,现就其免疫病理基础及其对照性临床试验进行综述如下。1免疫介导的神经肌肉疾病的免疫病理基础自身免疫性神经疾病是机体失免疫耐受的结果。免疫失衡的机制多种多样,从免疫病理的角度来说,Guillain-Barre综合征(GBS)可能是由于微生物的介入引起的,尤其是空肠弯曲菌,后者有部分结构与神经糖酯以及…     

钙调神经蛋白抑制剂引起的肾毒性：肾移植术后的早期预防和治疗

目的：就近年来国内外预防和治疗钙调神经蛋白抑制剂肾毒性的方法进行综述。 方法：应用PubMed检索及CNKI中国期刊全文数据库检索系统,以“环孢素A,他克莫司,钙调神经蛋白抑制剂肾毒性”和“Ciclosporine A,Tacrolimus,CNIS drug-induced chronic nephrotoxicity”为关键词检索相关文献。时间范围为1980-01/2010-01。选择文章主要内容与钙调神经蛋白抑制剂肾毒性直接相关、针对性强、代表性好、相关领域权威杂志的文章共44篇进行综述。 结果：环孢素A与他克莫司做为常用的免疫抑制剂,明显改善了器官移植者的生活质量和生存率,如果要取得移植肾的长期存活,必须考虑到导致移植物丧失功能的病因学问题。目前,已经证明慢性移植物肾病和钙调神经蛋白抑制剂的肾毒性是导致移植肾丧失功能的主要原因,而同时钙调神经蛋白抑制剂肾毒性在慢性移植物肾病的自然病程中又起到了重要的作用。 结论：目前没有有效预防和治疗钙调神经蛋白抑制剂肾毒性的手段。移植术后早期减少钙调神经蛋白抑制剂用量或撤除,或许是预防钙调神经蛋白抑制剂肾毒性更好的选择。     

阿托伐他汀对动脉粥样硬化性脑梗死患者的调脂效果及颈动脉粥样硬化斑块的影响

目的分析阿托伐他汀对动脉粥样硬化性脑梗死患者的调脂效果及对颈动脉粥样硬化斑块的影响。方法 92例动脉粥样硬化性脑梗死患者采用随机数字表法随机分为阿托伐他汀(20 mg/d)治疗组和非他汀类药物治疗组(对照组),评价两组患者治疗前后血脂水平和颈动脉斑块变化。结果经阿托伐他汀治疗后,阿托伐他汀组患者血清总胆固醇、甘油三酯、低密度脂蛋白胆固醇水平降低(均P0.05),高密度脂蛋白胆固醇水平升高(P0.05);颈动脉斑块面积、斑块厚度和颈动脉内-中膜厚度明显改善(均P0.05)。结论阿托伐他汀具有改善动脉粥样硬化性脑梗死患者血脂水平、软化甚至缩小颈动脉斑块作用,有利于脑梗死患者的二级预防且无明显不良反应。     

他汀类药物相关免疫介导坏死性肌病1例并文献复习

<正>他汀类药物是预防心脑血管事件最常用的药物之一,具有降脂、抗炎、稳定动脉粥样硬化斑块等作用,其药理学作用靶点为3-羟基-3-甲基戊二酰辅酶A还原酶(3-hydroxy-3-methylglutaryl-coenzyme A reductase,HMGCR)^[1,2]。通常情况下他汀类药物具有良好的安全性和耐受性,但部分患者在使用后可能出现横纹肌溶解、免疫介导的坏死性肌病(immunemediated necrotizing myopathy,IMNM)和其他肌肉相关的不良反应,除IMNM患者即使停用他汀类药物后病情仍继续进展外,其他大多数不良反应具有自限性^[3]。抗HMGCR抗体的产生被认为是他汀类药物相关IMNM的致病机制^[4,5]。本研究报道1例血清HMGCR抗体阴性的他汀类药物相关IMNM病例,通过免疫治疗后症状完全缓解,以期引起临床关注。     

Homozygous W748S mutation in the POLG1 gene in patients with juvenile-onset Alpers syndrome and status epilepticus

Purpose: Polymerase gamma (POLG) is the sole enzyme in the replication of mitochondrial DNA (mtDNA). Numerous mutations in the POLG1 gene have been detected recently in patients with various phenotypes including a classic infantile-onset Alpers-Huttenlocher syndrome (AHS). Here we studied the molecular etiology of juvenile-onset AHS manifesting with status epilepticus and liver disease in three teenagers.
Patients and Methods: We examined 14- and 17-year-old female siblings (patients 1 and 2) and an unrelated 15-year-old girl (patient 3) with juvenile-onset AHS, sequenced POLG1, and the entire mtDNA, examined mtDNA deletions by amplification of the full-length mtDNA with the long PCR method and used real-time PCR to quantify mtDNA in the tissue samples.
Results: The initial manifestations were migraine-like headache and epilepsy, and the terminal manifestations status epilepticus and hepatic failure. A homozygous W748S mutation in POLG1 was detected in the three patients. No deletions or pathogenic point mutations were found in mtDNA, but all three patients had mtDNA depletion.
Conclusions: POLG mutations should be considered in cases of teenagers and young adults with a sudden onset of intractable seizures or status epilepticus, and acute liver failure. The W748S POLG1 mutation seems to lead to tissue-specific, partial mtDNA depletion in patients with juvenile-onset Alpers syndrome. Valproic acid should be avoided in the treatment of epileptic seizures in these patients.     

Epidemiologic study of hepatolenticular degeneration (Wilson''s disease) in Sardinia (1902–1983)

From 1902 to 1983, 68 cases of hepatolenticular degeneration (HLD) were discovered in Sardinia, with a mean frequency, in reference to number of live births, of 27.7 and a sex ratio of 1.83. The prevalence of the disease was seen to be higher over the last few decades. With regard to the geographic distribution of the disease, 3 high-frequency areas were evident, in Barbagia, in Campidano, and in the area surrounding the city of Sassari. In 38.23% of cases, the clinical picture was of hepatoneurologic type; hepatic forms have become more frequent over the last decades. The first symptoms were observed at mean age of 15 years 8 months. The number of asymptomatic cases was fairly consistent (22.05%). The median survival rate in subjects who received inadequate therapy was 6 years 4 months. Only 3 patients of the 45 treated with adequate therapy died. The gene frequency, calculated by the application of Dahlberg's formula, was extremely high.     

Conjugal amyotrophic lateral sclerosis: a report on a couple from Sardinia, Italy

A conjugal case of amyotrophic lateral sclerosis (ALS) observed in Sardinia, Italy is reported. This is believed to be the ninth such observation described in the literature. The couple had lived together for 38 years in a house adjacent to the distillery they owned. No exogenous factors were revealed which could explain the genesis of the disease in either patients. Particularly, exposure to alcohol does not appear to have been involved in causing ALS. On the basis of statistical and epidemiological evaluations, the most likely explanation is that this association was purely coincidental.     

Increased Risk of Cardio-Cerebrovascular Diseases in Migraine Patients: A Nationwide Population-Based,Longitudinal Follow-Up Study in South Korea

Background and PurposeMigraine is reportedly associated with several cardio-cerebrovascular diseases (CCDs), but some of these diseases have not received sufficient attention. We thus attempted to determine the associations of migraine with peripheral arterial disease (PAD), ischemic heart disease (IHD), atrial fibrillation/flutter (AF), ischemic stroke (IS), and hemorrhagic stroke (HS).MethodsThe study population was recruited by applying International Classification of Diseases, Tenth Revision (ICD-10) codes to the database of the Korean National Health Insurance Service from 2002 to 2018. Cumulative incidence curves were plotted to compare the incidence rates of CCDs between the migraine (ICD-10 code G43; n=130,050) and nonmigraine (n=130,050) groups determined using 1:1 propensity-score matching. Cox proportional-hazards regression models were used to obtain adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for CCDs in patients with any migraine, migraine with aura (n=99,751), and migraine without aura (n=19,562) compared with nonmigraine controls.ResultsFor all CCDs, the cumulative incidence rates were higher in the migraine group than the nonmigraine group (p<0.001 in log-rank test). Any migraine, irrespective of the presence of aura, was associated with PAD (aHR 2.29, 95% CI 2.06–2.53), IHD (aHR 2.17, 95% CI 2.12–2.23), AF (aHR 1.84, 95% CI 1.70–1.99), IS (aHR 2.91, 95% CI 2.67–3.16), and HS (aHR 2.46, 95% CI 2.23–2.71). aHR was higher in female than in male migraineurs for all of the CCDs.ConclusionsAssociations of migraine with CCDs have been demonstrated, which are stronger in females than in males.     

Human brain receptor autoradiography using whole hemisphere sections: a general method that minimizes tissue artefacts

A general method for the preparation of high-quality, mostly ice-crystal-artefact-free whole human brain hemisphere sections is described. Upon receipt, hemispheres are divided; one is then fixed in buffered 10% formalin for neuropathological analysis while the other is cut in 8-10-mm-thick coronal slices that are then rapidly frozen in 2-methylbutane at -40 degrees C (10-15 sec) before being placed in the brain bank at -80 degrees C. Such rapid freezing markedly decreases the formation of ice-crystal artefacts. Whole-hemisphere 20-micron thick sections are then cut and mounted onto lantern-type gelatin-coated slides. These sections are subsequently used for both qualitative and quantitative in vitro receptor autoradiography. Examples of data obtained are given by using various radioligands labelling "classical" neutrotransmitter, neuropeptide, enzyme, and ion channel receptor binding sites. This method should be useful for the obtention of various receptor maps in human brain. Such information could be most useful for in vivo receptor visualization studies using positron emission tomography (PET) scanning. It could also indicate if a given receptor population is specifically and selectively altered in certain brain diseases, eventually leading to the development of new therapeutic approaches.     

A novel mutation in the mitochondrial tRNA for tryptophan causing a late‐onset mitochondrial encephalomyopathy

Sanaker PS, Nakkestad HL, Downham E, Bindoff LA. A novel mutation in the mitochondrial tRNA for tryptophan causing a late‐onset mitochondrial encephalomyopathy.
Acta Neurol Scand: 2010: 121: 109–113.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Background – Mitochondrial DNA (mtDNA) mutations are increasingly being recognized as causes of late‐onset disease. We report a patient with a late‐onset mitochondrial encephalomyopathy caused by a novel G > C transition in mtDNA at position 5556 in the gene encoding the tRNA for tryptophan (MTTW). Aims – To investigate the cause of disease and assess the pathogenicity of this new mutation. Methods – Clinical, histopathological and gene sequencing studies. Quantification of the mutation was performed in different tissues from the patient and two relatives and in single muscle fibres. Results – The mutation was heteroplasmic, segregated in biochemically affected muscle fibres and was absent in blood. The level of mutation in skeletal muscle was higher than in brain, although the brain was clinically the most affected tissue. Discussion – The 5556G > C mutation appears sporadic. It was not found in any of the family members tested, although some of them manifested disorders that can be associated with mtDNA disease. In addition to reporting the eighth mutation in MTTW, our case illustrates the challenges posed when assigning pathogenicity to mtDNA mutations.     

高血压合并无症状性大脑中动脉狭窄患者的药物干预研究

目的探讨在降血压治疗的同时联合应用辛伐他汀和阿司匹林对高血压合并无症状性大脑中动脉狭窄患者的干预作用和脑血管事件的预防效果。方法177例高血压合并大脑中动脉狭窄患者,其中90例应用辛伐他汀(每晚20mg)和阿司匹林肠溶片(75mg/d)进行治疗(干预组),通过经颅多普勒超声检查分别观察治疗前及治疗后1～3年大脑中动脉收缩期血流速度峰值、搏动指数、阻力指数、频谱形态,同时检测治疗前后血压、血脂等项生化指标的变化,并与87例对照者进行比较。结果治疗第1年,干预组患者大脑中动脉收缩期血流速度峰值、搏动指数、阻力指数及频谱形态等与治疗前差异无统计学意义(P>0.05);随访至第2,3年,上述各项指标均改善(P<0.01),频谱形态明显好转。随访结束时,两组患者大脑中动脉上述指标间差异有高度统计学意义(均P<0.01),干预组患者脑血管事件发生率为11.11%(10/90),低于对照组的24.14%(21/87)(P<0.01)。结论在有效降低血压的同时,联合应用辛伐他汀和阿司匹林可稳定并延缓高血压患者大脑中动脉狭窄的进程,对降低脑血管事件的发生率具有良好的作用。