高频超声对Duchenne型肌营养不良症的诊断价值

目的　探讨Duchenne进行性肌营养不良症肌肉声像图的特点及其诊断价值。方法　应用高频超声检测 81例Duchenne进行性肌营养不良症患者下肢肌肉。按照年龄分为 4组 :3～ <7岁 13例 ,7～ <10岁 3 0例 ,10～ <13岁 3 0例 ,13～ 14岁 8例。选择 1～ 11岁健康儿童 2 0例作为对照组。依次对臀部、大腿部、小腿部肌肉行纵横切位超声扫查。结果　患者 3岁时 ,臀肌萎缩 ,皮下脂肪增厚 ;随着年龄的增长 ,臀肌、大腿部位肌肉、小腿肌肉和背肌萎缩呈现进行性加重 ,皮下脂肪增厚 ,各年龄组差异有显著性意义 (P <0 .0 1)。结论　高频超声可为Duchenne进行性肌营养不良症的诊断、病情随访和临床病理活检提供客观依据。     

小剂量激素治疗Duchenne型肌营养不良的疗效

  目的  评估短期应用小剂量糖皮质激素是否具有提高Duchenne型肌营养不良(Duchenne muscular dystrophy, DMD)患儿肌力和运动功能的作用。  方法  纳入2005年9月至2008年12月北京协和医院明确诊断的5~10岁DMD患儿。试验采取随机、双盲、对照的原则, 分为治疗组和对照组。治疗组患儿给予泼尼松0.75 mg/(kg·d), 对照组给予维生素C 0.3 mg/d。治疗时间为3个月, 每隔1个月随访1次, 随访3个月, 评估4次就诊时的肌力、运动功能、肺功能和肌酸激酶。  结果  共31例DMD患儿纳入研究, 其中治疗组17例, 对照组14例。对照组患儿4次就诊的平均肌力评分依次为38.2±7.5、37.0±8.0、36.2±7.6、36.6±7.7, 治疗组为37.7±6.1、39.1±6.4、40.3±5.9、40.0±5.6, 两组治疗1、2、3个月后与治疗前肌力的差值比较, 差异均有统计学意义(P=0.024, P=0.000, P=0.002)。对照组4次就诊行走9 m的平均时间依次为(7.7±2.5)、(7.6±2.8)、(8.1±2.4)、(7.6±2.8)s, 治疗组为(8.5±3.4)、(7.2±3.3)、(7.6±3.1)、(7.1±2.8)s, 两组治疗2、3个月后与治疗前行走9 m所用时间的差值比较, 差异均有统计学意义(P=0.013, P=0.003)。对照组4次就诊的平均用力肺活量(forced vital capacity, FVC)依次为(1.24±0.28)、(1.13±0.26)、(1.21±0.31)、(1.16±0.26)L, 治疗组为(1.14±0.37)、(1.40±0.35)、(1.42±0.36)、(1.52±0.37)L, 两组治疗1、2、3个月后与治疗前FVC的差值比较, 差异均有统计学意义(P=0.000, P=0.006, P=0.000)。两组治疗1个月后与治疗前的肌酸激酶的差值比较, 差异亦有统计学意义(P=0.035)。3个月后治疗组激素不良反应仅表现为体重增加, 无其他严重不良反应。  结论  短期应用小剂量泼尼松治疗DMD可以增加患儿肌力, 改善患儿运动及肺功能。     

Duchenne型肌营养不良的康复评估及治疗研究进展

Duchenne型肌营养不良(DMD)又称假肥大型进行性肌营养不良,是儿童最常见的X连锁隐性遗传性肌肉病,表现为对称性、进行性肌无力,运动功能的丧失是其核心症状。本病目前尚无有效治愈的方法,康复治疗对改善患儿生活质量、延缓病情进展至关重要。本文对近年来DMD的康复评估及治疗研究进展作一综述。     

Duchenne型肌营养不良认知障碍机制研究进展

Duchenne 型肌营养不良是一种常见的X染色体连锁隐性遗传神经肌肉病,并常伴有认知障碍。目前关于其认知障碍机制研究较多,主要集中在抗肌萎缩蛋白亚型缺乏、中枢神经系统发育异常、突触功能改变、血脑屏障改变、大脑代谢改变及小脑功能异常等。     

Duchenne型肌营养不良症的治疗

Duchenne型肌营养不良症(Duchenne muscular dystrophy,DMD)是一种X连锁致死性遗传性肌病,由Dystrophin基因突变导致抗肌萎缩蛋白缺失所致.DMD尚缺乏有效的治疗方法,但随着对该病发病机制和病理变化过程的认识不断深入,其治疗选择越来越多.这些治疗方法旨在恢复Dystrophin...     

血清VEGF的表达与肌营养不良症的关系

目的检测肌营养不良症患者的血清血管生长因子（VEGF）水平,鉴定其是否与肌营养不良症的疾病发展有关。方法对46例肌营养不良患者,其中32例Duchenne肌营养不良症（DMD）、9例Becker肌营养不良症（BMD）、5例强直性肌营养不良症（DM）患者的血清VEGF水平进行检测。15例健康人和8例疾病患者为对照组。结果DMD患者血清VEGF为（274．7±2．52）pg／ml,BMD患者的为（358．8±9．64）pg／ml,DM患者为（165．0±6．34）pg／ml,而健康对照组为（148．3±2．91）pg/ml,疾病对照组为（153．7±5．42）pg／ml。与DM组和对照组相比,BMD的VEGF水平显著提高。而DMD组中卧床的患者相对于坐轮椅的DMD、DM组和对照组则VEGF水平显著升高。结论VEGF可以反映肌肉组织低氧和／或缺血状况,并且与DMD和BMD患者的疾病发展过程有关。     

肌营养不良蛋白表达在萎缩性肌病鉴别诊断中的意义

目的探讨肌营养不良蛋白(Dystrophin蛋白)在萎缩性肌病中的表达及其临床意义。方法对均表现为双下肢近端肌肉萎缩的43例肌营养不良患者、3例其他神经肌肉疾病患者(包括1例脂质沉积性肌病、2例运动神经元病)及5例正常对照者的骨骼肌标本进行Dystrophin蛋白免疫组化染色。结果 Duchenne型肌营养不良(DMD)患者肌细胞膜上无显色,Becker型肌营养不良(BMD)患者全部为弱阳性,BMD/LGMD(肢带型肌营养不良)患者中6例肌细胞膜上显色浅淡、不连续或呈斑片状,其余15例患者肌细胞膜上染色正常;2例运动神经元病患者中1例肌细胞膜显色浅淡、呈斑片状,另1例染色正常。脂质沉积性肌病患者和正常对照肌细胞膜上染色均正常。结论对于存在双下肢近端肌肉萎缩的临床表现相似的肌病患者,Dystrophin免疫组化染色可以将其大致区分,对早期预测肢体功能影响程度及正确地进行遗传咨询具有重要意义。     

血清VEGF的表达与肌营养不良症的关系

Objective To detect serum levels of vascular endothelial growth factor (VEGF) in patients with muscular dystrophy and further to examine whether VEGF is associated with muscular dystrophy development. Methods We measured serum levels of VEGF in 32 patients with DMD,9 with Becker muscular dystrophy (BMD),5 with myotonic dystrophy (DM),as well as in 15 healthy and eight disease controls. Results The serum level of VEGF in the DMD patients was (274.7±2.52)pg/ml,while it was(358.8±9.64) pg/ml in the BMD patients, (165.0±6.34) pg/ml in the DM patients, (1 48.3±2.91) pg/ml in the healthy controls,and (153.7±5.42) pg/ml in the disease controls. The level of VEGF in BMD was significantly elevated, as compared with DM and control groups. Further, the level of VEGF in the bedridden sub-group of DMD patients was significantly elevated as compared with chair-bound DMD, DM, and control groups. Conclusion We concluded that VEGF may reflect hypoxic and/or ischemic conditions in muscle tissue, and have a relationship with the process of disease progression in DMD and BMD patients.     

中国西北地区102例儿童Duchenne型肌营养不良基因突变及家系分析研究

目的　了解西北地区Duchenne型肌营养不良症(DMD)患者基因突变特点。方法　收集2014年7月～2020年6月的102例DMD患者作为研究对象,采用多重连接依赖探针扩增（multiplex ligationdependent probe amplification, MLPA）技术、二代基因测序（next-generation sepuencing, NGS)技术及Sanger测序方法进行基因检测,分析西北地区DMD患者基因缺失突变、重复突变、点突变的分布区域特点,且对2个DMD家系基因特点进行分析。结果　102例DMD患者,72.5%来源于遗传,27.5%为新发突变。基因突变类型中,85.3%为片段缺失,6.9%为片段重复,7.8%为点突变。片段缺失突变中,≤5个数目的外显子缺失最为常见,占比为66.6%;外显子44~54是最常见的缺失区域,外显子2是最常见的重复区域。2个家系研究,家系1中突变位点为缺失突变的热点区域,外显子45~51区域;家系2中主要是重复突变,集中在外显子2和17~18区域。结论　大样本对西北地区DMD患者及家系的基因分析,可以进一步了解DMD患者基因谱,为基因治疗建立基础。     

血清VEGF的表达与肌营养不良症的关系

Objective To detect serum levels of vascular endothelial growth factor (VEGF) in patients with muscular dystrophy and further to examine whether VEGF is associated with muscular dystrophy development. Methods We measured serum levels of VEGF in 32 patients with DMD,9 with Becker muscular dystrophy (BMD),5 with myotonic dystrophy (DM),as well as in 15 healthy and eight disease controls. Results The serum level of VEGF in the DMD patients was (274.7±2.52)pg/ml,while it was(358.8±9.64) pg/ml in the BMD patients, (165.0±6.34) pg/ml in the DM patients, (1 48.3±2.91) pg/ml in the healthy controls,and (153.7±5.42) pg/ml in the disease controls. The level of VEGF in BMD was significantly elevated, as compared with DM and control groups. Further, the level of VEGF in the bedridden sub-group of DMD patients was significantly elevated as compared with chair-bound DMD, DM, and control groups. Conclusion We concluded that VEGF may reflect hypoxic and/or ischemic conditions in muscle tissue, and have a relationship with the process of disease progression in DMD and BMD patients.     

Sodium Channel and Sodium Pump in Normal and Pathological Muscles from Patients with Myotonic Muscular Dystrophy and Lower Motor Neuron Impairment

TWO SODIUM TRANSPORT SYSTEMS HAVE BEEN ANALYZED IN THIS WORK: the voltage-sensitive sodium channel and the (Na(+), K(+)) ATPase pump. The sodium channel has been studied using a tritiated derivative of tetrodotoxin; the sodium pump has been studied using tritiated ouabain. Properties of interaction of tritiated tetrodotoxin and of tritiated ouabain with their respective receptors were observed in normal human skeletal muscle and in muscles of patients with myotonic muscular dystrophy and with lower motor neuron impairment.Levels of sodium pump and of sodium channels were measured at different stages of membrane purification. Microsomal fractions of normal human muscle have maximal binding capacities for tetrodotoxin of 230 fmol/mg of protein and of 7.4 pmol/mg of protein for ouabain.Dissociation constant for the complexes formed by the tetrodotoxin derivative and by ouabain with their respective receptors were 0.52 nM and 0.55 muM, respectively.In muscles from patients with myotonic muscular dystrophy, the maximal binding capacity for tetrodotoxin, i.e., the number of Na(+) channels was found to be very similar to that found for normal muscle. The maximal binding capacity for ouabain, i.e., the number of Na(+) pumps was three- to sixfold lower than in normal muscle. Dissociation constants for the complexes formed with the tetrodotoxin derivative and with ouabain were the same as for normal muscle.In muscles from patients with lower motor nerve impairment, the maximal binding capacities for tetrodotoxin and for ouabain were twice as high as in normal muscle. Again, dissociation constants for the complexes formed with the tetrodotoxin derivative and with ouabain were nearly unchanged as compared with normal muscle.These results suggest that sodium transport systems involved in the generation of action potentials and/or in the regulation of the resting potential are altered both in myotonic muscular dystrophy and in lower motor neuron impairment.     

Cardiac and Respiratory Dysfunction in Duchenne Muscular Dystrophy and the Role of Second Messengers

Duchenne muscular dystrophy (DMD) affects young boys and is characterized by the absence of dystrophin, a large cytoskeletal protein present in skeletal and cardiac muscle cells and neurons. The heart and diaphragm become necrotic in DMD patients and animal models of DMD, resulting in cardiorespiratory failure as the leading cause of death. The major consequences of the absence of dystrophin are high levels of intracellular Ca²⁺ and the unbalanced production of NO that can finally trigger protein degradation and cell death. Cytoplasmic increase in Ca²⁺ concentration directly and indirectly triggers different processes such as necrosis, fibrosis, and activation of macrophages. The absence of the neuronal isoform of nitric oxide synthase (nNOS) and the overproduction of NO by the inducible isoform (iNOS) further increase the intracellular Ca²⁺ via a hypernitrosylation of the ryanodine receptor. NO overproduction, which further induces the expression of iNOS but decreases the expression of the endothelial isoform (eNOS), deregulates the muscle tissue blood flow creating an ischemic situation. The high levels of Ca²⁺ in dystrophic muscles and the ischemic state of the muscle tissue would culminate in a positive feedback loop. While efforts continue toward optimizing cardiac and respiratory care of DMD patients, both Ca²⁺ and NO in cardiac and respiratory muscle pathways have been shown to be important to the etiology of the disease. Understanding the mechanisms behind the fine regulation of Ca²⁺‐NO may be important for a noninterventional and noninvasive supportive approach to treat DMD patients, improving the quality of life and natural history of DMD patients.     

Metabolic Effects of Human Growth Hormone and of Estrogens in Boys with Duchenne Muscular Dystrophy

Metabolic balance studies were conducted in seven boys with Duchenne-type muscular dystrophy, and in six normal boys of similar age, during a 12 day control period and during a 12 day period of treatment with human growth hormone (HGH) at the following doses: 0.0168, 0.0532, and 0.168 U/kg body weight (BW)((3/4)) per day (doses A, B, and C, respectively). In five of the six normals, dose C caused positive balances in N, P, Na, and K; doses B and A had anabolic effects in two and one normal subjects, respectively. In six of the seven Duchenne cases, dose C caused negative balances of N and K, and sometimes of P. Negative balances were produced in three of the Duchenne subjects by dose B, and in one by dose A. None of the dystrophy cases exhibited an anabolic response to any dosage of HGH tested.The release of endogenous HGH in response to insulin, after 2 days' pretreatment with diethylstilbestrol, was similar in both groups of subjects. In the course of these tests, a marked anabolic effect of diethylstilbestrol in the Duchenne patients was apparent. Therefore metabolic balance studies were repeated, in both Duchenne and normal cases, during a 12 day control period and during 12 days of treatment with diethylstilbestrol (0.106 mg/kg BW((3/4)) per day). In three of the normal children, diethylstilbestrol had no effect on the elemental balances; in two cases, a retention of Na was observed. In all seven Duchenne cases, diethylstilbestrol caused positive balances in N, P, Na, and K. Ethinyl estradiol (0.0106 mg/kg BW((3/4)) per day) produced positive N, P, Na, and K balances in all three Duchenne cases tested with this agent.The data show that exogenous HGH causes a catabolic effect in boys with Duchenne dystrophy. These patients are hyperresponsive to the anabolic effect of diethylstilbestrol. The latter phenomenon may reflect the inhibitory effect of estrogen upon the peripheral actions of these boys' endogenous HGH.     

可塑纤维桩与预成纤维桩在口腔修复患者中的应用效果比较

目的探析可塑纤维桩和预成纤维桩在口腔修复患者中的应用效果。方法选择2016年2月～2018年7月本院收治的80例口腔修复患者,遵照随机数字表法分为对照组和观察组各40例,对照组患者采用可塑纤维桩修复、观察组患者采用预成纤维桩修复,比较两组患者的修复效果、牙周健康状况和口腔美学效果。结果观察组患者的修复成功率、口腔修复美学评分均高于对照组患者,牙周健康状况优于对照组患者,差异有统计学意义(P<0.05)。结论预成纤维桩应用在口腔修复患者中,能够改善牙周状况,提高修复成功率与修复美学效果,值得临床推荐使用。     

假肥大型肌营养不良患儿的肌肉病理及dystrophin免疫组化SP法检测的临床意义

目的探讨肌肉病理及抗肌萎缩蛋白（dystrophin）免疫组化SP法检测在假肥大型肌营养不良诊断中的临床价值。方法通过组织学观察和免疫组化SP法检测方法,对50例假肥大型肌营养不良患儿[40例Duchenne型营养不良（DMD组）,10例Becker型营养不良（BMD组）]肌纤维膜dystrophin的表达、肌肉病理改变及临床表现进行观察,并与30例其他疾病（多发性肌炎3例、皮肌炎6例、糖元累积病1例、脂质累积病15例、周围神经病2例、脊肌萎缩症3例）对照组患儿进行对比分析。结果肌肉病理显示：DMD组中有30例肌肉病理改变较重,10例较轻;BMD组的肌肉病理改变较轻,这些均与年龄有关。免疫组化显示：DMD组肌肌纤维膜均有严重的dystro-phin缺失,BMD组肌纤维膜有50%~70%的dystrophin缺失;对照组无dystrophin缺失。结论肌肉病理及dys-trophin SP免疫组化检测对假肥大型肌营养不良具有较大的临床意义。     

颅内肿瘤患者照顾者心理体验的现象学研究

目的深入了解颅内肿瘤患者照顾者的心理体验,以了解中国文化背景下颅内肿瘤患者照顾者的体验及需求,最终为提高颅内肿瘤患者的治疗提供帮助。方法目的抽样法选择20例肿瘤患者的照顾者,采用质性研究中的现象学研究方法对其进行半结构式访谈,并用现象学分析法进行资料分析。结果共得出3个主题:确诊初期有恐惧、悲伤、沮丧、不知所措和获取信息的强烈愿望,经短暂的治疗和适应后心情逐渐平稳;治疗过程中患者感到巨大的压力,包括对疾病的不确定感、护理知识缺乏、精神和体力不支等;社会适应能力改变。结论颅内肿瘤患者照顾者的心理体验迫切需要得到医护人员的专业支持,采取针对性的干预措施来减轻照顾者的身心压力应成为护理的重要任务之一。