Duchenne型肌营养不良症患者营养干预策略研究进展

Duchenne型肌营养不良症（Duchenne muscular dystrophy,DMD）是一种相对常见的致死性X连锁隐性遗传病。近年研究发现,早期多学科综合治疗能够明显延长患者生存时间和提高生活质量,而膳食营养干预和营养支持疗法已成为DMD综合治疗中非常重要的环节。在该疾病的不同阶段,体重管理、营养状况评价、肠...     

反义寡核苷酸治疗Duchenne型肌营养不良的研究进展

Duchenne型肌营养不良(DMD)是由抗肌萎缩蛋白基因Dystrophin发生移码突变导致的儿童遗传性致死性肌病。反义寡核苷酸(AON)靶向外显子中的剪接调控序列可以诱导Dystrophin基因的相应外显子跳读,以恢复dystrophin mRNA阅读框,是目前新的DMD治疗方法。该治疗方法的有效性已在患者来源的肌细胞及动物模型中得到证实。目前,AON靶向治疗DMD已经进入药物临床试验阶段。笔者拟对DMD的分子致病机制、AON治疗DMD的作用机制及其临床试验新进展进行综述,为AON在DMD治疗中的临床应用提供理论依据。     

用限制性内切酶TaqI检测DMD基因缺失

本文应用限制性内切酶 TaqI 及 DMD 的2种探针(cDNA2b-3和 cDNA8),采用 Southern 印迹法对 DMD 患者、患者母亲及正常人的 DMD 基因进行研究。确定了 TaqI/cDNA2b-3和 TaqI/cDNA8的杂交带型,并用探针 cDNA2b-3检测出一名缺失型 DMD 患者。实验结果表明,TaqI 可与 cDNA 探针一起用于 DMD 基因缺失的检测。     

23例假肥大型肌营养不良患者家系中女性生育情况的调查与分析

目的:调查假肥大型肌营养不良(DMD)患者家系中女性携带者生育情况,探讨影响DMD家系生育的因素。方法:对23名DMD患者家系中132名女性携带者的生育情况进行调查,分析患者家系中女性的遗传风险度、对疾病的理解力、家族史、个人史、文化水平及对选择性流产的观点等几个因素与生育的关系。结果:遗传风险度与生育结果和要求检测DNA的愿望无明显关系;对该病有较好的理解力与生育结果有明显关系;文化水平高和有该病家族史者对疾病的理解力好,选择性流产者较多;家族中有DMD患者和死于该病的人数越多,则要求检测DNA的愿望越强,对疾病的理解力也越好。结论:开展DMD遗传咨询,提高人口文化素质,对降低DMD患者和携带者的出生非常重要。     

70例假肥大型肌营养不良患者的心电图Q波改变

目的观察假肥大型肌营养不良(Duhenne muscular dystrophy,DMD)患者的心电图Q波改变。方法分析70例DMD患者心电图的Q波表现,以71例正常人作为对照组,比较两组Ⅰ、Ⅱ、Ⅲ、avL、avF、V4、V5、V6导联的Q波改变。结果DMD组与正常对照组心电图的Q波时限均<0.03s。DMD组Ⅰ、Ⅱ、avL、V4、V5、V6导联Q波振幅的平均值分别为0.1756、0.1996、0.3846、0.4844、0.4087、0.3573mV,与正常对照组比较明显加深(P<0.05)。结论DMD患者心电图Q波振幅明显加深。     

Duchenne肌营养不良的基因诊断和治疗

Duchenne肌营养不良(Duchenne muscu-ler dystrophy DMD)是一种较常见的X连锁性致死性肌肉变性疾病,其发病率为1/3 500性活婴。DMD患者常于2～5岁时出现肌无11岁失去行走能力,20岁左右死亡。该病迄今尚无有效的治疗方法。为了优生优育,产前诊断是防止DMD患儿出生的重要途径。目前,多根据羊水中的肌酸激酶(creatine phosphate ki-nase CPK)和肌红蛋白值、胎儿肌组织活检对胎儿进行产前诊断。近年来,随着分子生物学技术的迅速发展,不仅查明了DMD的致病基因,     

Duchenne肌营养不良的基因诊断和治疗

Duehenne肌营养不良(Duchenne muscu—lar dystrophy DMD)是一种较常见的X连锁隐性致死性肌肉变性疾病，其发病率为1／3500男性活婴。DMD患者常于2～5岁时出现肌无力，11岁失去行走能力，20岁左右死亡。该病迄今尚无有效的治疗方法。为了优生优育，产前诊断是防止DMD患儿出生的重要途径。目前，多根据羊水中的肌酸激酶(creatine phosphate kinase CPK)和肌红蛋白值、胎儿肌组织活检对胎儿进行产前诊断。近年来，随着分子生物学技术的迅速发展，不仅查明了DMD的致病基因，同时开展了基因诊断、携带者检出和产前基因诊断，另外，不久将实现对DMD的基因治疗给病人带来了希望。本文就这些方面的新进展加以归纳如下。     

肌营养不良蛋白在假肥大肌营养不良双生子肌组织中的表达

[目的]假肥大肌营养不良是男性最常见的X-连锁隐性遗传病,而肌营养不良蛋白(dystrophin)在DMD患者肌细胞上的表达异常是导致该病发生的最根本的病理生理机制。[方法]应用兔抗Anti5-7多克隆抗血清及免疫组化技术检测dystrophin在两对DMD孪生子肌组织中的表达。[结果]显示dystrophin在无症状的孪生子肌组织中存在着阳性表达,而在DMD患儿肌组织中则表达缺失。[结论]检测肌细胞膜上dystrophin蛋白的表达对DMD患者的诊断及预后判定有着重要的应用价值。     

Utrophin与Duchenne肌营养不良

duchenne肌营养不良(duchennemusclaldystrophy,DMD)是神经肌肉系统最常见的一种X连锁隐性遗传病,发病率占活产男婴的13500,儿童早期发病,以进行性近端肌无力、萎缩为特征,血清肌酸激酶(CK)水平很高,患儿在13～14岁前即运动受限,需依赖轮椅,通常在20岁左右死于呼吸及循环衰竭[1,2]。自duchenne于1868年首次描述此病以来,人们就对该病进行了不懈的研究。1987年DMD基因的cDNA被克隆和鉴定,此后抗DMD基因产物———抗肌营养不良蛋白(dys trophin)被发现。随着PCR技术的发展,DMD的基因诊断和产前基因诊断取得了突破性进展[3～5]。但是,…     

MLPA技术用于产前DMD基因诊断的应用探讨

<正>假肥大性肌营养不良症是一种严重的神经肌肉疾病,分为杜氏肌营养不良症(DMD)和贝氏进行性肌营养不良症(BMD),均是由于DMD基因(Xp21.2)突变所致[1]。由于本病目前无有效的治疗方法,产前诊断成为控制致病基因传递、防止患儿出生及降低发病率的主要措施。本研究对DMD产前诊断家系中具有高患病风险的2个胎儿,提取其羊水基因组DNA,采用多重连接探针扩增技术(ML-PA)进行产前基因诊断的探索。1资料与方法11一般资料2例均为进行DMD基因诊断,经MLPA技术确诊为DMD基因外显子缺失者,其母亲再次妊娠,经     

Hepatic Steatosis Assessment as a New Strategy for the Metabolic and Nutritional Management of Duchenne Muscular Dystrophy

Growing evidence suggests that patients with Duchenne muscular dystrophy (DMD) have an increased risk of obesity and metabolic syndrome (MetS). The aim of this study was to investigate the potential risk factors for MetS and hepatic steatosis in patients with different stages of DMD. A total of 48 patients with DMD were enrolled and classified into three stages according to ambulatory status. Body mass index (BMI), serum fasting glucose, insulin, and lipid profiles including triglycerides (TG) and high-density lipoprotein were measured, and the homeostatic model assessment for insulin resistance (HOMA-IR) index was evaluated. Ultrasound examinations of the liver were performed to assess hepatic steatosis using the Nakagami parameter index (NPI). The results showed that BMI, TG, HOMA-IR, and ultrasound NPI differed significantly among DMD stages (p < 0.05). In contrast to the low rates of conventional MetS indices, including disturbed glucose metabolism (0%), dyslipidemia (14.28%), and insulin resistance (4.76%), a high proportion (40.48%) of the patients had significant hepatic steatosis. The ultrasound NPI increased with DMD progression, and two thirds of the non-ambulatory patients had moderate to severe hepatic steatosis. Steroid treatment was a risk factor for hepatic steatosis in ambulatory patients (p < 0.05). We recommend that DMD patients should undergo ultrasound evaluations for hepatic steatosis for better metabolic and nutritional management.     

6～11岁杜氏进行性肌营养不良儿童与正常儿童下肢肌力对照分析

目的 比较6～11岁杜氏进行性肌营养不良(DMD)患儿与正常儿童下肢肌力差异,为开展DMD患儿的肌力训练提供科学依据。方法 2015年4月-2017年4月选择DMD患儿和正常儿童各20例,其中DMD患儿男19例,女1例;正常组男18例,女2例,两组儿童平均年龄均为(9.0±1.7)岁。采用手持式肌力测定仪(HHD)测定下肢髋、膝、踝等部位肌群肌力,比较DMD与正常儿童下肢肌群间及不同年龄间的肌力差异。结果 DMD组下肢肌力除足跖屈肌群以外均明显弱于正常组(P＜0.05);DMD组中6岁～组和9～11岁组各组肌群肌力差异无统计学意义(P＞0.05);在6岁～组中DMD患儿双侧髋外展和足趾屈肌力与正常组差异无统计学意义(P＞0.05),DMD组足趾屈肌力甚至高于正常儿童; 9～11岁组中DMD患儿除足趾屈肌群外髋屈曲、髋伸展、髋外展、膝屈曲、膝伸展和踝背屈肌群肌力都已经显著落后于正常儿童(P＜0.05)。结论 DMD患儿下肢肌群除足跖屈肌外均明显低于正常组儿童。开展DMD患儿下肢力量训练应关注所有肌群,在较大年龄组尤其需要重视髋膝伸展肌群。     

Protein and energy metabolism in patients with progressive muscular dystrophy.

Studies were made on whether body weight loss in patients with muscular dystrophy is due to reduced intake and/or abnormal expenditure of energy. For this, food intakes and various physiological variables were surveyed in totals of 310 patients with Duchenne muscular dystrophy (DMD) of 11 to 29 years old and 28 patients with limb-girdle muscular dystrophy (LGMD) of 30 to 47 years old. Energy and protein intakes, expressed on a unit body weight basis, in DMD patients were comparable to, or higher than the allowances for age-matched healthy controls, whereas those in LGMD patients were 92 and 94% respectively of these allowances. The basal metabolic rate (BMR), expressed as kcal/kg/day, of DMD patients of all ages was higher than that of controls, the difference increasing with age, and being about 20 to 30% higher than that of controls in older patients with DMD. The BMR of LGMD patients was nearly normal. The maintenance requirements of conventional dietary protein in DMD and LGMD patients were 1.26 and 0.84 g/kg/day, respectively. These values were about 68 and 12% higher than the normal adult value (0.75 g/kg/day), indicating decreased protein utilization and increased protein catabolism. Daily excretion of urinary 3-methylhistidine (3MH) per unit muscle mass (micrograms/mg creatinine) by MD patients was significantly higher than that by controls, indicating increased degradation of muscle protein. The BMR, maintenance protein requirement and 3MH excretion of DMD patients suggest that DMD is a hypercatabolic disease. Comparison of the energy and protein intakes with the allowances estimated in consideration of increased requirements showed deficiencies of energy and protein in DMD patients. Thus, we conclude that the underweight of the DMD patients resulted from nutrient deficiencies due to hypercatabolism, despite their considerably high intakes of energy and protein, expressed as per kg body weight. These deficiencies were confirmed by demonstrating decreased concentrations of free essential amino acids, particularly branched chain amino acids, in their serum. The values of variables of LGMD patients were intermediate between those of DMD patients and control subjects.     

生物电阻抗法与体重指数在杜氏肌营养不良患儿营养评估中的比较研究

目的 应用生物电阻抗分析(BIA)检测杜氏肌营养不良(DMD)患儿体成分, 并比较体重指数(BMI)与体脂百分比(PBF)判定患儿超重的一致性。方法 收集2015年8月-2017年2月在河北医科大学第三医院神经肌肉病科就诊的39例男性DMD患者作为患儿组, 同期随机选取46例健康男童作为对照组。应用BIA对两组儿童进行人体成分检测。结果 两组儿童的脂肪含量、BMI差异均无统计学意义(P＞0.05)。患儿组的身高、体重、身体水分、蛋白质、无机盐、肌肉质量和基础代谢率(BMR)均低于对照组(P<0.05), 但患儿组的PBF高于对照组(P<0.05)。患儿组中PBF与年龄呈正相关关系(r=0.546, P<0.05), BMI与PBF在判定DMD患儿超重时的一致性较差(Kappa=0.352, P<0.05)。结论 相比于同年龄段同性别的健康少儿, DMD患儿的整体营养状况较差, 应用BIA比使用BMI能更加准确地评估患儿的营养状况。     

MLPA技术在假肥大型肌营养不良症基因检测和产前诊断中的应用

目的 评价多重连接依赖式探针扩增 (Multiplex ligation-dependent probe amplification,MLPA) 技术对假肥大型肌营养不良症(DMD)患者进行基因诊断和产前诊断的应用价值。方法 应用MLPA技术对具有典型表型的22例患者进行DMD基因79个外显子拷贝数变异(缺失/重复突变)检测,同时对部分家系中孕妇携带者进行产前诊断,STR毛细管电泳连锁分析方法进行辅助诊断及验证。结果 22例患者中15例为缺失突变,4例为重复突变,3例未见拷贝数变异。14例MLPA检测结果为阳性的患者母亲中有9例为携带者。产前诊断的7例胎儿中,3例为女性胎儿携带者,3例男性正常胎儿和1例女性正常胎儿。结论 MLPA技术能准确、快速、可靠地检测DMD基因拷贝数变异(缺失或重复突变)。     

Designated Medical Directors for Emergency Medical Services: Recruitment and Roles

ABSTRACT:  Context: Emergency medical services (EMS) agencies rely on medical oversight to support Emergency Medical Technicians (EMTs) in the provision of prehospital care. Most states require EMS agencies to have a designated medical director (DMD), who typically is responsible for the many activities of medical oversight. Purpose: To assess rural-urban differences in obtaining a DMD and in their responsibilities. Methods: A national survey of 1,425 local EMS directors, conducted in 2007. Findings: Rural EMS directors were more likely than urban ones to report DMD recruitment problems, but recruitment barriers were similar, with the most commonly reported barrier being an unwillingness of local physicians to serve. Rural EMS directors reported that their DMDs were less likely to be trained in Emergency Medicine, and were less likely to provide educational support functions such as continuing education. Rural agencies were more likely to get on-line medical direction from their DMD, but were less likely to always get the on-line support they needed. Common barriers to on-line support were typical of rural communication barriers. Conclusions: Existing recommendations for DMD qualifications may be difficult to attain in rural communities. To develop programs that will support medical direction for rural EMS agencies, it is important to learn what physicians identify as the barriers to serving as DMDs, and whether there are alternative and innovative ways to provide an optimal level of medical oversight. Solutions will likely be multi-faceted, as EMS activities and organizational structures are diverse and the responsibilities of the DMD are broad.     

A review of quality of life themes in Duchenne muscular dystrophy for patients and carers

Duchenne Muscular Dystrophy (DMD) is a severe, life-limiting and incurable condition. However, studies estimating quality of life and those measuring actual quality of life in people living with DMD vary considerably. This discrepancy indicates potential difficulties with assessing quality of life using common generic quality of life instruments in this rare and unique population. This study sought to document the range of themes relevant to quality of life for people with DMD by examining the published literature and additionally to investigate the themes that are relevant to quality of life for carers and the wider family. Eligible studies for the review were primary studies of any study design that reported outcomes or themes relevant to quality of life for either people with DMD, their families, or both. A review of studies identified from searching medical bibliographic sources between 2010 and 2016 found 45 relevant published studies. A thematic framework is proposed to categorise the themes identified into: i. physical; ii. psychological; iii. Social; iv. well-being domains. A final “other” domain was included to encompass themes identified from the literature that are not covered by commonly used quality of life instruments. The rich variety of themes identified from the review highlights that DMD has a complex quality of life profile which is not currently captured by standard quality of life tools that are commonly employed in the healthcare setting. The findings also highlight that the resulting impact on the quality of life of carers and wider family of people with DMD requires consideration.     

From gene to disease; the dystrophin gene involved in Duchenne and Becker muscular dystrophy

Duchenne and Becker muscular dystrophy (DMD and BMD) are progressive disorders, which almost exclusively affect males. DMD is the more severe type with an onset at 2-3 years of age. Patients become wheelchair-bound before the age of 13 and often die due to cardiac arrest or respiratory insufficiency. BMD, a more varying phenotype which may overlap with limb girdle muscular dystrophy (LGMD), has a less severe muscle weakness which starts later than in DMD patients. DMD carriers may show some muscle weakness. The dystrophin gene (2.4 Mb), known to be involved in DMD/BMD, codes for a 427 kilodalton muscle-specific protein named dystrophin as well as several tissue-specific isoforms. Dystrophin, as part of a membrane-bound complex of proteins, connects the cytoskeleton of the muscle cell to the extracellular matrix. Since 1985, when highly reliable carrier detection and prenatal diagnosis at the DNA level became possible, over 250 prenatal tests have been performed. Molecular genetic analysis, highlighted a phenomenon called germinal mosaicism, which explains the recurrence of de novo mutations and led to the discovery of the so-called reading-frame rule, which helps to discriminate between DMD and BMD. Fifteen years after the discovery of the dystrophin gene, mutations can be detected in 95% of the patients, while the remaining 5% are still hiding within this very large gene.