一例Fechtner综合征临床与分子缺陷研究——附文献复习

目的对1例Fechtner综合征先证者及其家系进行临床与实验室研究并检测非肌性肌球蛋白重链9基因（MYH9）突变。方法采用瑞特染色观察先证者及其家系患者的外周血涂片血小板和中性粒细胞的特殊形态；透射电镜观察先证者血小板及中性粒细胞的超微结构。从先证者及其家系成员外周血白细胞中提取基因组DNA，PCR扩增MYH9的40个外显子及侧翼内含子序列，检测其基因突变。结果该家系中Fechtner综合征患者表现为血小板减少、巨大血小板、中性粒细胞包涵体，伴或不伴遗传性肾炎。先证者及其家系患病成员的MYH9改变为外显子40第5981位核苷酸C-T杂合改变，使第1933位密码子CGA（编码Arg）突变为终止密码TGA。结论国内首次报道Fechtner综合征家系。MYH9（外显子40）R1933X杂合改变是导致Fechtner综合征的原因。     

遗传性血小板减少症分子机制研究进展

遗传性血小板减少症是一组少见的血小板异常疾病,临床表现为血小板减少,多数病例出现血小板巨大,常有不同程度出血症状.本文主要就MYH9相关疾病、先天性无巨核细胞(减少)性血小板减少、Wiskott-Aldrich综合征、植物固醇代谢异常等疾病的分子机制研究进展作一综述,以减少漏诊或误诊为ITP,避免大剂量激素或脾切手术等治疗给患者带来的负担与痛苦.     

遗传性巨大血小板病的研究进展

遗传性巨大血小板病是一组异质性疾病,表现为巨大血小板,多数有血小板减少,患者有不同程度的出血症状。目前已发现的遗传性巨大血小板病有十余种,本文主要介绍Bernard-Soulier综合征, MYH9相关性疾病,血小板颗粒异常性巨血小板病和具有自发性聚集特点的大血小板病的临床与分子机理的研究进展。     

遗传性血小板减少症分子机制研究进展

遗传性血小板减少症是一组少见的血小板异常疾病,临床表现为血小板减少,多数病例出现血小板巨大,常有不同程度出血症状.本文主要就MYH9相关疾病、先天性无巨核细胞(减少)性血小板减少、Wiskott-Aldrich综合征、植物固醇代谢异常等疾病的分子机制研究进展作一综述,以减少漏诊或误诊为ITP,避免大剂量激素或脾切手术等治疗给患者带来的负担与痛苦.     

遗传性巨大血小板病的研究进展

遗传性巨大血小板病是一组异质性疾病，表现为巨大血小板，多数有血小板减少，患者有不同程度的出血症状。目前已发现的遗传性巨大血小板病有十余种，本文主要介绍Bernard—Soulie，综合征，MYH9相关性疾病，血小板颗粒异常性巨血小板病和具有自发性聚集特点的大血小板病的临床与分子机理的研究进展。     

1例非肌性肌球蛋白重链9基因相关疾病家系并文献复习

目的鉴定1例非肌性肌球蛋白重链9(MYH9)基因相关疾病家系的致病突变。方法调查收集先证者和家系成员病史资料,观察其临床特征和实验室检查指标。采用芯片捕获高通量测序方法检测先证者MYH9基因,确定突变位点后,对先证者和家系成员进行Sanger验证。结果该家系三代4名患者均有鼻衄、瘀斑紫癜、外伤血肿或月经量增多病史,长期存在镜下血尿和蛋白尿。血涂片镜检均有血小板减少、巨大血小板和粒细胞异常包涵体"三联征"。所有患者MYH9基因第40内含子供体剪接位点存在错义突变c.5765+2TA(p.R1922Rfs*43),且该基因突变与疾病表型共分离。结论该家系存在MYH9基因c.5765+2TA(p.R1922Rfs*43)剪接突变,是MYH9基因相关疾病的致病突变,为国内首次报道。     

血小板计数、血小板抗体、骨髓细胞学对血小板减少鉴别诊断的意义

目的 探讨血小板计数、血小板抗体测定、骨髓细胞学检查对血小板减少鉴别诊断的临床意义.方法 对147例血小板减少患者的临床及实验室资料进行回顾性分析,应用SPSS11.5软件进行方差分析.结果 在血小板计数的比较中,特发性血小板减少性紫瘢(ITP)组与骨髓增生异常综合征(MDS)组、ITP组与系统性红斑狼疮(SLE)组、...     

一MYH9-RD家系患者血小板中NMMHC-ⅡA检测与分析

非肌性肌球蛋白重链9基因相关疾病(non-muscle myosin heavy chain 9 related disease,MYH9-RD)是一类罕见的常染色体显性遗传性血液性疾病,典型病例具有巨大血小板、血小板减少和粒细胞包涵体三大特点及不同的临床表型,是遗传性大血小板症的一个类型[1]。有研究[2,3]认为MYH9-RD是由于非肌性肌动蛋白重链ⅡA     

六例非肌性肌球蛋白重链9基因相关疾病患者的临床特征与基因分析

目的 分析6例非肌性肌球蛋白重链9(MYH9)基因相关疾病患者临床特征和基因.方法 取患者外周血,光镜下计数血小板数目、涂片并瑞氏染色后观察血小板形态以及有无中性粒细胞包涵体;抽提患者外周血基因组DNA,PCR扩增MYH9基因的40个外显子及两端侧翼序列,DNA测序并与基因库序列进行比对以确定基因异常,用限制性核酸内切酶和聚丙烯酰胺凝胶电泳法分析排除多态性.结果 6例患者血小板计数下降、体积增大,中性粒细胞内可见淡蓝色包涵体.基因分析发现在1号、30号和40号外显子中存在T97C(W33R)、4335InsCAGAAGAAG(1445InsQKK)、G4269A(D1424N)和G5833T(E1945Stop)4种基因突变,其中前2种突变为首次发现,并排除基因多态性的可能.结论 6例MYH9相关疾病患者的基因突变中T97C(W33R)和4335InsCAGAAGAAG(1445InsQKK)是国际上首次发现的新突变.病史较长且治疗反应不佳的原发免疫性血小板减少症患者应考虑MYH9基因相关疾病的可能性.     

Fechtner综合征异常家系的临床与分子缺陷

  目的  分析一先天性血小板减少症家系的临床、实验室特点, 并探讨其分子发病机制。  方法  收集该家系成员的临床资料, 采集先证者及其家系成员的静脉血, 分别进行全自动及人工血小板计数; 显微镜下观察血小板形态; 流式细胞术分析血小板膜蛋白; 透射电镜观察中性粒细胞胞浆包涵体。聚合酶链反应扩增非肌性肌球蛋白重链9基因(non-muscle myosin heavy chain9gene, MYH9)的40个外显子, 分析PCR产物的核苷酸序列, 并直接测序确定突变位点。  结果  镜下观察外周血涂片巨大血小板占90%以上, 血小板膜糖蛋白(CD41、CD61、CD42a、CD42b)均在正常范围内, 血小板功能正常; 中性粒细胞胞浆透射电镜可见无包膜分隔的包涵体, MYH9基因38号外显子第5521位核苷酸存在G→A杂合突变(GAG→AAG), 从而导致其编码的非肌性肌球蛋白重链A(NMMHC2A)第1841位谷氨酸变为赖氨酸, 正常对照及该家系正常者未见此突变。  结论  MYH9基因点突变并伴有血小板减少及巨大血小板是Fechtner综合征的主要特征。     

Determination of creatine kinase isoenzyme MB activity in serum using immunological inhibition of creatine kinase M subunit activity. Activity kinetics and diagnostic significance in myocardial infarction.

This is a new method for the determination of creatine kinase isoenzyme MB activity in serum. The method uses direct activity measurement of creatine kinase B subunit activity after blocking of CK-M subunit activity by inhibiting antibodies. The test takes no longer than 15 min. The method yields an intra-serial C.V. of 2.0-12.9%, and a C.V. from day to day of 5.5%. The detection limit is 3.4 U/l creatine kinase MB. In the 95 cases with proven myocardial infarction several types of creatine kinase MB activity kinetics could be determined. The percentage of creatine kinase MB of peak CK-total is 6-25%, with a mean of 11.1%. The amount of creatine kinase MB with respect to total CK activity after reinfarction is higher than the amount after initial infarction.     

Dissociable correlates of two classes of retrieval processing in prefrontal cortex

Although substantial evidence suggests that the prefrontal cortex (PFC) implements processes that are critical for accurate episodic memory judgments, the specific roles of different PFC subregions remain unclear. Here, we used event-related functional magnetic resonance imaging to distinguish between prefrontal activity related to operations that (1) influence processing of retrieval cues based on current task demands, or (2) are involved in monitoring the outputs of retrieval. Fourteen participants studied auditory words spoken by a male or female speaker and completed memory tests in which the stimuli were unstudied foil words and studied words spoken by either the same speaker at study, or the alternate speaker. On "general" test trials, participants were to determine whether each word was studied, regardless of the voice of the speaker, whereas on "specific" test trials, participants were to additionally distinguish between studied words that were spoken in the same voice or a different voice at study. Thus, on specific test trials, participants were explicitly required to attend to voice information in order to evaluate each test item. Anterior (right BA 10), dorsolateral prefrontal (right BA 46), and inferior frontal (bilateral BA 47/12) regions were more active during specific than during general trials. Activation in anterior and dorsolateral PFC was enhanced during specific test trials even in response to unstudied items, suggesting that activation in these regions was related to the differential processing of retrieval cues in the two tasks. In contrast, differences between specific and general test trials in inferior frontal regions (bilateral BA 47/12) were seen only for studied items, suggesting a role for these regions in post-retrieval monitoring processes. Results from this study are consistent with the idea that different PFC subregions implement distinct, but complementary processes that collectively support accurate episodic memory judgments.     

俯卧位通气对高海拔地区肺复张治疗无效急性呼吸窘迫综合征患者氧合的影响

目的 探讨俯卧位通气对高海拔地区肺复张术(RM)治疗无效急性呼吸窘迫综合征(ARDS)患者的治疗作用.方法 从海拔2260m的地区医院筛选RM治疗无效的41例ARDS患者[平均氧合指数( PaO2/FiO2)较RM前升高＜20％视为RM无效],依不同病因分为肺内源性ARDS组(ARDSp组)和肺外源性ARDS组(ARDSexp组),每组再按信封法随机分为俯卧位组和仰卧位组,即ARDSp俯卧位组(11例)、ARDSp仰卧位组(9例)、ARDSexp俯卧位组(10例)、ARDSexp仰卧位组(11例).在通气前及通气1、2、3、4h监测动脉血氧分压( PaO2)、PaO2/FiO2、静态顺应性(Cst)、气道阻力(Raw)的变化.结果 通气lh时,ARDSexp俯卧位组PaO2/FiO2( mm Hg,l mm Hg=0.133 kPa)即较通气前显著升高(157.4±40.6比129.3±48.7,P＜0.05),并随通气时间延长呈持续增高趋势,4h达峰值(219.1 ±41.1);且ARDSexp俯卧位组通气3h内PaO2/FiO2较其他3组显著增高,另3组间则差异无统计学意义.ARDSp俯卧位组、ARDSexp俯卧位组通气4h时PaO2/FiO2均较相应仰卧位组显著增高(208.8±39.7比127.4±47.1,219.1±41.1比124.9±50.8,均P＜0.05).4组通气前后Cst无显著改变,各组间差异也无统计学意义.ARDSp俯卧位组通气4h时Raw(cmH2O·L-1·s-1)较通气前显著降低(6.8±1.7比10.7±1.8,P＜0.05),且明显低于其他3组;其他3组各时间点Raw组内及组间比较差异均无统计学意义.结论 俯卧位通气作为ARDS机械通气重要策略之一,可以改善RM无效高原ARDS患者的氧合,为抢救患者赢得宝贵的时间.     

Digital imaging among medical facilities

The Department of Veterans Affairs (VA) in the USA operates a network of 172 medical centres which all utilize a hospital information system (HIS) which has been developed and is currently maintained by the VA. During the past several years, an image management and communication module has been developed, installed and clinically utilized at the Washington DC and Maryland VA Medical Centres. This image management and communication system, referred to as the decentralized hospital computer program (DHCP) imaging system, is fully integrated with a commercial picture archiving and communication system (PACS). The system is utilized to capture, archive, and display all images generated within the hospital including radiology, nuclear medicine, pathology, endoscopy, bronchoscopy, and dermatology, intraoperative photographs, ECG data, and a limited number of paper documents. The ultimate goal of the project is to have all patient text and image data available at any clinical workstation to any authorized user anywhere within the network of medical centres. Clinical requirements for an imaging workstation include ease of use, rapid and reliable access to the complete set of patient information, and images which are of acceptable quality to meet the requirements of the user and the subspecialty. Patient confidentiality and data security must be safeguarded at all times. Integration of the images with the remainder of the patient's database was found to be critical to the success of the project. The experience at the Washington and Maryland facilities suggests that an imaging system that is successfully integrated with a hospital information system can provide substantial clinical and economic benefits both within and among medical centres. Clinical acceptance and utilization of the system has been excellent, particularly in diagnostic radiology where DHCP Imaging has been interfaced to a commercial PAC system. Based upon this initial experience, the VA has begun to deploy the system throughout its large network of medical centres.     

Myocardial elastography at both high temporal and spatial resolution for the detection of infarcts

Myocardial elastography is a novel method for noninvasively assessing regional myocardial function, with the advantages of high spatial and temporal resolution and high signal-to-noise ratio (SNR). In this paper, in-vivo experiments were performed in anesthetized normal and infarcted mice (one day after left anterior descending coronary artery [LAD] ligation) using a high-resolution (30 MHz) ultrasound system (Vevo 770, VisualSonics Inc., Toronto, ON, Canada). Radiofrequency (RF) signals of the left ventricle (LV) in longitudinal (long-axis) view and the associated electrocardiogram (ECG) were simultaneously acquired. Using a retrospective ECG gating technique, 2-D full field-of-view RF frames were acquired at an extremely high frame rate (8 kHz) that resulted in high-quality incremental displacement and strain estimation of the myocardium. The incremental results were further accumulated to obtain the cumulative displacements and strains. Two-dimensional and M-mode displacement images and strain images (elastograms), as well as displacement and strain profiles as a function of time, were compared between normal and infarcted mice. Incremental results clearly depicted cardiac events including LV contraction, LV relaxation and isovolumetric phases in both normal and infarcted mice, and also evidently indicated reduced motion and deformation in the infarcted myocardium. The elastograms indicated that the infarcted regions underwent thinning during systole rather than thickening, as in the normal case. The cumulative elastograms were found to have higher elastographic SNR (SNR(e)) than the incremental elastograms (e.g., 10.6 vs. 4.7 in a normal myocardium, and 6.0 vs. 2.4 in an infarcted myocardium). Finally, preliminary statistical results from nine normal (m = 9) and seven infarcted (n = 7) mice indicated the capability of the cumulative strain in differentiating infracted from normal myocardia. In conclusion, myocardial elastography could provide regional strain information at simultaneously high temporal (>/=0.125 ms) and spatial ( approximately 55 microm) resolution as well as high precision ( approximately 0.05 microm displacement). This technique was thus capable of accurately characterizing normal myocardial function throughout an entire cardiac cycle, at the same high resolution, and detecting and localizing myocardial infarction in vivo.     

Clinical Pharmacokinetics of Morphine

Morphine, the most widely used mu-opioid analgesic for acute and chronic pain, is the standard against which new analgesics are measured. A thorough understanding of the pharmacokinetics of morphine is required in order to safely and effectively use this analgesic in a wide variety of patients with different levels of organ function. A MEDLINE search was conducted to identify literature published between 1966 and January 2002 relevant to the pharmacokinetics of morphine. These publications were reviewed and the literature summarized regarding unique and clinically important elements of morphine disposition relative to its parenteral administration (including intravenous, intramuscular, subcutaneous, epidural and intrathecal administration), absorption profile (immediate release, controlled release, and sublingual/buccal, and rectal administration), distribution, and its metabolism/ excretion. Special populations, including infants, elderly, and those with renal/liver failure, have a unique morphine pharmacokinetic profile that must be taken into account in order to maximize analgesic efficacy and reduce the risk of adverse events.