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Myasthenia Gravis 重症肌无力
Pub Date : 2020-06-03 DOI: 10.1201/9780138719128-73
Curtis Wells Dewey
Background: Myasthenia gravis (MG) is an autoimmune disorder targeting skeletal muscle acetylcholine receptor. Thymoma is associated with MG in some patients, the majority of whom present with symptoms of MG before detection of underlying thymoma. This study aimed to study clinical and serological characteristics of Chinese thymomatous MG patients. Methods: Autoimmune MG patients with thymomectomy and histologically confirmed thymoma followed up in our hospital for at least 12 months were studied. Results: A total of 37 Chinese MG patients with histology-proven thymoma were retrospectively studied. The mean MG symptom onset age was 48.5 (range, 25-81) years; 25 (68%) were female. The mean follow-up duration was 4.9 (range, 1-15) years. Symptoms of MG preceded detection of thymoma in the majority (31 patients, 84%), in six patients thymoma detection preceded MG symptoms onset by 1 to 8 years. Nineteen (51%) patients had early-onset MG (before 50 years of age). All patients were seropositive for acetylcholine receptor antibodies and 30 (81%) patients seropositive for striated muscle antibodies. Eleven (30%) patients had experienced myasthenic crisis and the worst MGFA clinical severity grade were class I (6 patients), class II (3), class III (8), class IV (9), and class V (11); hence 31 (84%) had generalised MG and six (16%) had ocular MG. Twenty-seven (73%) patients had a history of corticosteroid therapy, 22 (60%) required azathioprine, two required other immunosuppressant (1 mycophenolate mofetil, 1 cyclosporin A). All 37 patients had good or satisfactory MG clinical outcome measured by MGFA post-intervention status (2 pharmacological remission, 23 minimal manifestation, 12 improved) though one patient died from metastatic thymoma. Conclusion: Thymoma MG was clinically severe with frequent myasthenic crises, but responses to conventional immunosuppressive therapies are satisfactory. Parkinson’s disease (PD) is the second most common neurodegenerative movement disorder, characterised by slow movement, resting tremor, and postural instability. Lrrk2 has been added to the list of genes that are implicated in PD. LRRK2 is a very large gene, which has over 2527 amino acid and 51 exons. LRRK2 is a complex protein consisting of five domains, which is expressed throughout the brain and the whole body. More than 20 mutations have been reported in LRRK2 in PD patients in different races. More importantly, 5 to 6% of familial PD patients have these mutations. Some in these mutations, R1441C, R1441G, Y1699C and G2019S, are amino acids conserved across vertebrates. Some patients with LRRK2 mutations have loss dopamine neuron in substantia nigra and Lewy body, which are typical features of PD. Initial studies proved these mutations increased LRRK2 kinase activity with autophosphorylation. Tauopathy and hyperphosphorylated tau are also found in Lrrk2 in vitro models. All these indicated its important role in PD pathogenesis. The importance of the R1441 residue
背景:重症肌无力(MG)是一种以骨骼肌乙酰胆碱受体为靶点的自身免疫性疾病。胸腺瘤在一些患者中与MG相关,其中大多数患者在发现潜在的胸腺瘤之前就有MG的症状。本研究旨在探讨中国胸腺瘤性MG患者的临床及血清学特点。方法:对经胸腺瘤切除术并组织学证实为胸腺瘤的自身免疫性MG患者进行至少12个月的随访。结果:回顾性研究了37例组织学证实的胸腺瘤MG患者。MG症状的平均发病年龄为48.5岁(范围25 ~ 81岁);25例(68%)为女性。平均随访时间为4.9年(1-15年)。MG症状先于胸腺瘤的患者占多数(31例,84%),在6例患者中,胸腺瘤先于MG症状出现1至8年。19例(51%)患者为早发性MG(50岁前)。所有患者乙酰胆碱受体抗体血清阳性,横纹肌抗体血清阳性30例(81%)。11例(30%)患者经历过肌无力危象,最严重的MGFA临床严重程度等级为I级(6例)、II级(3例)、III级(8例)、IV级(9例)和V级(11例);因此,31例(84%)为全身性MG, 6例(16%)为眼部MG。27例(73%)患者有皮质类固醇治疗史,22例(60%)患者需要硫唑嘌呤,2例需要其他免疫抑制剂(1例霉酚酸酯,1例环孢素a)。37例患者均有良好或满意的MG临床结果(2例药物缓解,23例症状轻微,12例改善),尽管1例患者死于转移性胸腺瘤。结论:MG型胸腺瘤临床严重,经常出现肌无力危象,但对常规免疫抑制治疗的反应令人满意。帕金森病(PD)是第二常见的神经退行性运动障碍,其特征是运动缓慢、静止性震颤和姿势不稳定。Lrrk2已被添加到与帕金森病有关的基因列表中。LRRK2是一个非常大的基因,有超过2527个氨基酸和51个外显子。LRRK2是一种复杂的蛋白质,由五个结构域组成,在整个大脑和全身表达。在不同种族的PD患者中,LRRK2有超过20个突变。更重要的是,5%到6%的家族性PD患者有这些突变。这些突变中的一些,R1441C、R1441G、Y1699C和G2019S,是在脊椎动物中保守的氨基酸。部分LRRK2突变患者黑质和路易体多巴胺神经元丢失,这是PD的典型特征。最初的研究证明这些突变通过自磷酸化增加了LRRK2激酶的活性。在Lrrk2的体外模型中也发现tau病变和tau过度磷酸化。提示其在帕金森病发病中起重要作用。通过鉴定出三种不同的错义突变,突出了R1441残基在发病机制中的重要性。我们制作了R1441G KI小鼠,对其进行了分子表征,并分析了注射MPTP后R1441G KI小鼠正常DA神经元的变化。此外,我们比较了野生型和单突变蛋白(R1441G、R1441C和G2019S)在HEK293和Sh-Sy5y细胞系中线粒体参数的差异。
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引用次数: 0
Radiology of the Critical Care Patient 危重病人放射学
Pub Date : 2020-06-03 DOI: 10.1201/9780138719128-26
R. O’Brien
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引用次数: 0
Transfusion Medicine 输血医学
Pub Date : 2020-06-03 DOI: 10.1201/9780138719128-16
M. T. Green
This well-known handbook presents the experience of a world leader in the field of blood banking and transfusion therapy. Transfusion Medicine offers complete guidance on the full range of topics from donor recruitment, blood collection and storage, to testing and transfusing blood components, complications and transmissible diseases, as well as cellular engineering, therapeutic apheresis, and the role of hematopoietic growth factors.
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引用次数: 0
Respiratory System 呼吸系统
Pub Date : 2020-06-03 DOI: 10.1201/9780138719128-24
E. Orton
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引用次数: 0
Smoke Inhalation 烟雾吸入
Pub Date : 2020-06-03 DOI: 10.1201/9780138719128-81
K. Drobatz
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引用次数: 0
Acute Respiratory Distress Syndrome 急性呼吸窘迫综合征
Pub Date : 2020-06-03 DOI: 10.1201/9780138719128-41
L. King, L. Waddell
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引用次数: 0
Adrenal Dysfunction 肾上腺功能障碍
Pub Date : 2016-04-26 DOI: 10.1201/9780138719128-66
Douglass K. MacIntyre
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引用次数: 0
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