吲哚布芬在抗血小板治疗中的临床应用

血栓栓塞性疾病严重威胁着人类的生命健康和生活质量,而抗血小板治疗是治疗血栓栓塞性疾病的重要手段,其中吲哚布芬作为一种抗血小板药物,对于治疗及预防血栓栓塞性疾病有一定的疗效。现就吲哚布芬对高危患者血栓栓塞事件的二级预防作用及其他血栓栓塞性疾病的治疗价值,对移植血管或介入术后冠状动脉通畅性的维持作用方面做一综述,以期指导临床。     

PET显像在阿尔茨海默病的应用进展

阿尔茨海默病是老年期痴呆之临床常见类型,随着发病率的逐年升高,受到社会各界更多的关注。PET功能显像可通过各种显像剂敏感、特异性地反映阿尔茨海默病的病理生理学改变,笔者将重点介绍18F-FDG显像剂、淀粉样蛋白和神经原纤维缠结tau蛋白显像剂在阿尔茨海默病中的应用,详细阐述PET显像在阿尔茨海默病病因学研究、早期诊断、鉴别诊断、疾病转归和药物治疗中的作用。     

中枢神经系统Rosai-Dorfman病的诊断

目的:探讨中枢神经系统窦组织细胞增生症的诊断及治疗。方法:对我院收治的2例颅内窦组织细胞增生症病例的临床资料进行回顾性分析。结果:2例患者病灶分别位于左侧大脑镰旁和左侧中颅窝。术前CT,MRI诊断为脑膜瘤。手术全切肿块。术后病理和免疫组化发现病变组织由大量淋巴细胞、浆细胞及S100和CD68标记阳性的组织细胞构成,并呈“明暗”相间的组织学特征,部分组织细胞内有吞噬淋巴细胞现象。结论:原发颅内窦组织细胞增生症少见,易被误诊,免疫组化检查有助于鉴别诊断。手术是治疗本病的主要手段。     

The effect of onset age on the clinical features of Parkinson's disease

Many clinicians view age at onset as an important determinant of clinical phenotype in Parkinson's disease (PD) and this has been reinforced by the identification of Mendelian genes that account for some cases of younger onset PD. A systematic review of OVID Medline for articles relevant to the relationship between clinical features and age at onset in PD published in English between 1950–2007 was performed. There are very few prospective community based studies which focus on the relationship between age at onset and the features of PD and a variety of case definitions are used in the literature. Most studies of young onset PD are based on specialist clinic referral series. The available evidence suggests that PD patients with a younger age at onset have: (i) a slower disease progression, (ii) an increased rate of dystonia at onset and during treatment, (iii) a lower rate of dementia and (iv) an increased rate of dyskinesias in response to l -DOPA treatment. The majority of the available studies do not report patient genotype data, but it is probably that the clinical heterogeneity of PD will be further refined with detailed clinico-genetic studies.     

Pharmacotherapy of Alzheimer's disease: is there a need to redefine treatment success?

The traditional aim of Alzheimer's disease treatment in clinical trials has been to improve cognitive abilities. It has become increasingly clear, however, that other aspects are important in assessing treatment responses. A group of 10 physicians recently gathered to review the current criteria for assessing treatment success in Alzheimer's disease. While cognition has been previously viewed as the primary measure of efficacy, areas such as functional abilities, behaviour, caregiver burden, quality of life and resource utilization all need to be comprehensively assessed to fully evaluate treatment effects in patients with Alzheimer's disease, as well as their impacts on caregivers and society. Postponing or slowing decline in any of these areas may represent an important benefit and should be considered as an outcome measure in clinical trials, clinical practice and decision-making about healthcare budgets. Accepted instruments are available for assessing outcomes in each aspect of Alzheimer's disease, but they need to be selected carefully to provide valid, meaningful data. Some of the most frequently used outcome measures in Alzheimer's disease are reviewed. Using expanded criteria for treatment success and clinically relevant outcome measures, data from currently available studies show that cholinesterase inhibitors produce clinically meaningful long-term benefits in multiple domains in patients with Alzheimer's disease.     

出血型烟雾病的研究进展

【摘要】 烟雾病是一种以颈内动脉末端狭窄、闭塞并伴有颅底异常血管网形成为特征的脑血管病,出血型烟雾病是其中的一个重要类型,也是目前的研究热点,本文就出血型烟雾病的流行病学特征、病因及发病机制、影像学特征及预测出血的指标、治疗和疗效评价等做一综述。     

Absence of protease-resistant prion protein in dementia characterized by neuronal loss and status spongiosus

Dementia characterized by neuronal loss and status spongiosus (DNLS) is a non-Alzheimer degenerative process which is characterized by Pick-like lobar atrophy with neuronal depletion and gliosis of the cerebral cortex, corpus striatum, medial thalamus, and substantia nigra and the absence of neuronal inclusions. To further investigate the cause and pathogenesis of DNLS, we probed cerebral homogenates from three cases of DNLS for protease-resistant prion protein to determine if DNLS could be a variant of a human prion disease. Limited proteolysis of prion proteins and guanidine thiocyanate treatment of cortical homogenates was used to enrich potential abnormal prion protein immunoreactivity. Although protease-resistant prion protein was detected in a case of sporadic Creutzfeldt-Jakob disease no abnormal prion protein was found in the cases of DNLS. We conclude that DNLS is not a human prion disease and remains an important dementia of uncertain eitology.     

Problems associated with long-term levodopa treatment of Parkinson's disease

ABSTRACT — Levodopa treatment improves significantly not only the parkinsonian disability but also the mortality rate. However, during long-term levodopa treatment the therapeutic benefit gradually declines. Furthermore, most cognitive skills improve initially, but long-term levodopa treatment is associated with declining intellectual capacity and dementia.
In patients on long-term levodopa treatment there seems to be a low threshold for certain clinical side-effects, especially postural hypotension, psychiatric disturbances and various types of fluctuations in disability. Low age at onset of Parkinson's disease, and at the commencement of levodopa therapy, the duration of levodopa treatment and a high dose of levodopa seem to be significant risk factors for the development of response fluctuations, but not the pretreatment duration of Parkinson's disease nor the disability of the patients.
A readjustment of the levodopa dosage, and as an adjuvant drug treatment, deprenyl, a specific inhibitor of MAO type B, or a direct-acting dopamine agonist may prove helpful in the management of fluctuations in disability. It is important, moreover, to try to prevent these phenomena by taking into account the predictive risk factors of response fluctuations in the treatment strategy of Parkinson's disease.     

Can directed activity improve mobility in Huntington's disease?

Huntington's disease is an inherited disorder of the CNS that results in progressive deterioration of mobility and cognition and also affects behaviour. There are no disease-modifying interventions available to date, although there has been considerable progress in research directed at understanding the pathological basis of the disease with a view to identifying potential treatments. It is however important not to overlook currently available treatment strategies, including rehabilitation approaches. There has been little work to date to explore the potential of such approaches and here we highlight the need for more systematic studies in this area as well as the need for good objective assessment tools and the potential role that rehabilitation and training may have in the application of novel treatment options.     

The basis for day and night-time control of symptoms of Parkinson's disease

While optimal treatment strategies are widely established for daytime treatment of Parkinson's disease (PD), nighttime problems of PD are often not adequately addressed in clinical practice. Nocturnal/sleep disturbance is common in PD and occurs due to a combination of the disease process and effect of dopaminergic and other treatments. The role of dopamine and other neuropeptides such as hypocretin is being investigated in the causation of sleep problems in PD. The impact of sleep dysfunction in PD on daytime fatigue and sleepiness is also being explored as such issues have important implications. The recently described Parkinson's disease sleep scale aims to measure the causes of sleep dysfunction in PD in a semi-quantitative manner and using this scale we have shown that sustained dopaminergic stimulation initiated at bedtime may help with improving motor symptoms at night and secondarily improve sleep and daytime functioning in PD.     

Cerebral ischemia combined with beta-amyloid impairs spatial memory in the eight-arm radial maze task in rats

beta-Amyloid (Abeta), a major component of senile plaques in Alzheimer's disease, has been implicated in neuronal cell death, a characteristic feature of this condition. In our previous experiments using primary cultures of hippocampal neurons, Abeta treatment induced neuronal cell death, displaying morphological characteristics of apoptosis that was significantly enhanced by hypoxia. Based on these results, we developed a simple in vivo rat model of Alzheimer's disease using cerebral ischemia, instead of hypoxia, combined with continuous intracerebroventricular administration of Abeta. The combination of cerebral ischemia and Abeta administration, but not either treatment alone, significantly impaired spatial memory in an eight-arm radial maze. A microdialysis study showed that spontaneous release of acetylcholine (ACh) from the dorsal hippocampus had a tendency to decrease in response to Abeta treatment alone or the combination of ischemia and Abeta. High K(+)-evoked increase in ACh release had a tendency to be inhibited by either ischemia or Abeta treatment alone and was significantly inhibited by the combination of both. Moreover, combination of ischemia and Abeta induced apoptosis of pyramidal neurons in the CA1 region of the hippocampus. Donepezil, a drug currently in clinical use for Alzheimer's disease, improved the impairment of spatial memory induced by cerebral ischemia combined with Abeta. These findings suggest that ischemia is an important factor facilitating the symptoms of Alzheimer's disease, and this model may be useful for developing new drugs for the treatment of Alzheimer's disease.     

Anatomical and biochemical basis of the extrapyramidal disorders

1. Degeneration of various components of the extrapyramidal system has been correlated with specific clinical syndromes. 2. In Parkinson's disease, loss of ascending nigrostriatal fibers is associated with reduction of presynaptic dopamine binding and increase of postsynaptic dopamine binding. The latter is reversed by treatment with dopamine agonists. 3. In Huntington's disease, multiple types of striatal neurons are lost, with their corresponding enzymes and receptors. 4. In tardive dyskinesias, there are no specific neuropathological findings, but increased amounts of striatal dopamine receptors. 5. Knowledge of the chemical nature of the pallidal outflow to the thalamus may be the next most important step in the pharmacological control of extrapyramidal function.     

Effects of medicinal plants on Alzheimer's disease and memory deficits

Alzheimer's disease is an age-related neurodegenerative disorder characterized by memory deficits. Various studies have been carried out to find therapeutic approaches for Alzheimer's disease. However, the proper treatment option is still not available. There is no cure for Alzheimer's disease, but symptomatic treatment may improve the memory and other dementia related problems. Traditional medicine is practiced worldwide as memory enhancer since ancient times. Natural therapy including herbs and medicinal plants has been used in the treatment of memory deficits such as dementia, amnesia, as well as Alzheimer s disease since a long time. Medicinal plants have been used in different systems of medicine, particularly Unani system of medicines and exhibited their powerful roles in the management and cure of memory disorders. Most of herbs and plants have been chemically evaluated and their efficacy has also been proven in clinical trials. However, the underlying mechanisms of actions are still on the way. In this paper, we have reviewed the role of different medicinal plants that play an important role in the treatment of Alzheimer s disease and memory deficits using conventional herbal therapy.     

Promoting remyelination for the treatment of multiple sclerosis: opportunities and challenges

Multiple sclerosis (MS) is a chronic and devastating autoimmune demyelinating disease of the central nervous system. With the increased understanding of the pathophysiology of this disease in the past two decades, many disease-modifying therapies that primarily target adaptive immunity have been shown to prevent exacerbations and new lesions in patients with relapsing-remitting MS. However, these therapies only have limited efficacy on the progression of disability. Increasing evidence has pointed to innate immunity, axonal damage and neuronal loss as important contributors to disease progression. Remyelination of denuded axons is considered an effective way to protect neurons from damage and to restore neuronal function. The identification of several key molecules and pathways controlling the differentiation of oligodendrocyte progenitor cells and myelination has yielded clues for the development of drug candidates that directly target remyelination and neuroprotection. The long-term efficacy of this strategy remains to be evaluated in clinical trials. Here, we provide an overview of current and emerging therapeutic concepts, with a focus on the opportunities and challenges for the remyelination approach to the treatment of MS.     

左旋多巴在帕金森病治疗中的地位及进展

数十年来,左旋多巴曾为帕金森病(PD)治疗带来革命性的改变,并始终作为PD治疗的金标准享有及其重要的地位。然而,伴随其治疗产生的运动并发症却成为困扰医患的一大难题。近年来,随着对运动并发症机制的研究,越来越多的证据表明持续性多巴胺能刺激(CDS)可在产生良好疗效的同时降低运动并发症的风险,故其被作为PD治疗的新理念备受关注。为此,大量研究致力于开发能形成CDS状态的左旋多巴新制剂,从而探寻出提高疗效与降低运动并发症之间的平衡点。文中就左旋多巴治疗PD的回顾及进展予以介绍。     

A randomized,double‐blind,placebo‐controlled,delayed start study to assess rasagiline as a disease modifying therapy in Parkinson's disease (the ADAGIO study): Rationale,design, and baseline characteristics

A neuroprotective therapy is the single most important unmet medical need in Parkinson's disease. Several promising agents in the laboratory have been tested in the clinic, but none has been established in clinical trials to have a disease modifying effect despite positive results because of potential confounding symptomatic or pharmacologic effects. The delayed start design was developed to try to avoid a symptomatic confound when testing a putative neuroprotective therapy. In this study design, patients are randomly assigned to study drug or placebo in the first phase of the study, and both groups receive the active drug in the second phase. If benefits seen at the end of phase I persist through the end of phase II, they cannot be readily explained by a symptomatic effect (as patients in both groups are receiving the same medication) and benefits in the early start group must relate to the early initiation of the treatment. Although the precise mechanism responsible for such an effect can be debated, positive results in a delayed start study indicate that patients who receive early treatment have a better outcome than those where the treatment is delayed. We are using the delayed start design to assess the potential disease modifying effects of rasagiline in a prospective double blind controlled trial (the ADAGIO study). We here describe the rationale for the study and baseline characteristics of the 1,176 patients who have been enrolled into the trial. © 2008 Movement Disorder Society     

针刺联合美多巴治疗帕金森病的疗效观察

目的探索帕金森病患者应用针刺联合美多巴治疗的效果与特点。方法选取2012-03—2015-04我院接收并治疗的帕金森病患者中随机抽取120例,并行回顾性分析,将患者分为对照组和研究组各60例。对照组应用传统治疗,研究组应用针刺联合美多巴治疗,探究其效果。结果研究组帕金森病总有效率(95.00%)明显高于对照组(76.67%),差异有统计学意义(P0.05),研究组患者口干、便秘、失眠、恶心、心悸、异动、剂末现象、开关现象、烦躁、精神障碍等不良反应均明显低于对照组,差异有统计学意义(P0.05)。结论对帕金森病患者给予针刺联合美多巴治疗效果较佳,可明显改善患者的临床病症,提高临床疗效,且不良反应较少,具有重要临床价值和意义。     

Von Hippel—Lindau病5例分析并文献复习

目的：探讨VonHippel-Lindau病（VHL病）的临床特点。方法：回顾性分析5例VHL病患者的病史、影像学资料和病理检查,并结合文献进行分析。结果：VHL病多以小脑血管母细胞瘤为首发症状。5例患者均接受小脑或脊髓血管母细胞瘤切除术,其中2例小脑血管母细胞瘤术后复发,1例小脑血管母细胞瘤术后11年后出现脊髓血管母细胞瘤;余3例未见肿瘤复发,无新病灶出现。结论：VHL病可涉及多个系统,应该早期、全面诊断,采用联合治疗。对于VHL患者及家族成员应长期随访,及早发现新病灶并予治疗。     

Changing epidemiology of Parkinson's disease: Predicted effects of levodopa treatment

Recent studies suggest that levodopa treatment reduces the excess mortality due to Parkinson's disease, found to be three times that expected in the general population. This will affect the equilibrium state of the epidemiology of Parkinson's disease. The predicted increase in prevalence of Parkinson's disease was calculated according to two mortality patterns, one the same as expected in the general population and the other 1.5 times that expected; the proportional increase in prevalence is 1.8 and 1.4, respectively. The predicted increase in the duration of the disease is 6.3 or 3.2 years. As a consequence, there will be an increase of patients with longterm levodopa treatment difficulties and with Parkinson's disease symptoms not treatable with levodopa, e. g. dementia. This seriously warrants the research of new approaches in the treatment of Parkinson's disease.     

肿瘤坏死因子基因多态性与脑血管病的关系研究进展

脑血管病的发生受环境和遗传等多方面因素影响,与炎性反应密切相关。肿瘤坏死因子 （tumor necrosis factor,TNF）作为一种促炎性因子,其基因多态性与脑血管病的关系受到人们的关注。 TNF不同基因型作为基因背景有可能决定了不同人群对疾病不同的易感性。TNF基因多态性在脑血管 发病中所起的作用,可能与其基因突变有关,但也可能存在多个位点相互协同或与其他炎症细胞因子 共同作用。本文对近年来有关TNF基因多态性与脑血管的关系研究进展进行综述,以便对脑血管病进 行风险预测、诊断及个体化治疗等方面的研究提供线索。