甲状腺肿瘤原位细胞凋亡检测与PPARγ表达的研究

目的：研究原位细胞凋亡指数（apoptosis index，AI）及核转录因子过氧化物酶体增殖物激活受体γ（peroxisome proliferator-activated receptor γ，PPARγ）在原发性甲状腺肿瘤中的表达及其与病变的关系。方法：对87例原发性甲状腺肿瘤组织（乳头状腺癌38例，滤泡性腺癌21例，未分化癌5例，腺瘤23例）分别应用原位细胞凋亡检测（TuNEL）试剂盒测定AI及应用免疫组化方法检测PPARγ表达情况。结果：AI及PPARγ,蛋白在各甲状腺肿瘤组织均有表达，AI在腺癌表达高于腺瘤（P〈0．01），PPARγ在滤泡性腺癌及腺瘤表达显著高于乳头状腺癌及未分化癌（P〈0．01）；AI及PPARγ有正相关性（r=0．554，P〈0．01）。结论：AI及PPARγ的表达与甲状腺肿瘤显著相关，检测AI及PPARγ水平对于鉴别原发性甲状腺滤泡癌具有重要参考意义。     

分化性甲状腺肿瘤中脆性组氨酸三联体和垂体肿瘤转化基因-1表达与临床意义

目的 研究脆性组氨酸三联体(FHIT)、垂体肿瘤转化基因-1(PTTG-1)在分化性甲状腺肿瘤中表达及其与病变的关系.方法应用免疫组化方法检测96例原发性甲状腺肿瘤[腺癌56例(腺癌组),腺瘤40例(腺瘤组)]标本中FHIT、PTTG-1表达.结果FHIT蛋白在腺癌表达显著低于腺瘤(P<0.01),PTTG-1在腺癌表达高于腺瘤(P<0.01).分化性甲状腺癌中癌转移23例与非转移33例、高预后指数(≥65)与低预后指数(<65)中FHIT(P<0.01,P<0.05)、FITG-1蛋白(P<0.05,P<0.01)表达均有统计学意义.结论检测FHIT及PTTG-1水平对于鉴别原发性甲状腺肿瘤良恶性具有重要参考意义,其表达水平可能是判断甲状腺癌预后的观测指标.     

原发性甲状腺肿瘤中C-myc和垂体肿瘤转化基因-1的表达与临床意义

目的：研究原癌蛋白C-myc、垂体肿瘤转化基因-1（pituitary tumor-transforming gene 1,PTTG-1）在原发性甲状腺肿瘤中的表达及其与病变的关系.方法：应用免疫组化方法检测85例原发性甲状腺肿瘤（腺癌42例,腺瘤43例）标本中C-myc、PTTG-1的表达.结果：C-myc及PTTG-1在甲状腺癌表达均高于腺瘤（P＜0.01）.C-myc及PTTG-1蛋白表达与腺癌转移（P＜0.05及P＜0.05）、预后指数（P ＜0.05及P＜0.01）具有相关性.C-myc蛋白表达水平与PTTG-1呈显著正相关（r=0.602 8,P＜0.01）.结论：检测C-myc及PTTG-1水平对于鉴别原发性甲状腺肿瘤良恶性具有重要参考意义,其表达水平可能是判断甲状腺癌预后的观测指标.     

结、直肠癌中FHIT和p53蛋白表达及其临床病理学意义

目的探讨脆性组氨酸三联体（FHIT）和p53蛋白在结、直肠癌中的表达及临床病理学意义。方法采用EnVision两步法检测76例结、直肠癌和癌周黏膜组织及30例腺瘤标本中的FHIT和p53蛋白表达。结果FHIT在结、直肠腺癌中表达降低或缺失占51.3%,在癌组织学分级中高分化占10%,与中分化56%或低分化62.5%相比差异显著（P〈0.05）;癌组织中FHIT表达降低或缺失明显高于腺瘤组（P〈0.01）。结、直肠癌中p53的阳性率为51.3%,明显高于腺瘤组的10%（P〈0.01）。中、晚期组（Dukes分期C＋D）结、直肠癌组织p53的表达率61.7%,高于早期组（Dukes分期A＋B）的34.5%（P〈0.05）。结、直肠癌组织中FHIT表达降低或缺失与p53表达之间无明显相关性。结论部分结、直肠癌和少数腺瘤FHIT表达降低或缺失,提示可能在结、直肠癌的发生、发展过程中起重要作用。     

PLK1在甲状腺乳头状癌中的表达及临床意义

目的探讨甲状腺乳头状癌中PLK1（polo-likekinase1）的表达及临床意义。方法用免疫组织化学EnVision法检测54例甲状腺乳头状癌及18例甲状腺腺瘤中的PLK1表达。结果甲状腺乳头状癌PLK1表达阳性率57．4％（31／54）显著高于甲状腺腺瘤5,6％（1／18）（P〈0.01）；甲状腺乳头状微灶癌（直径≤10mm）PLK1表达阳性率68．9％（31／54）显著高于癌灶直径〉10mm者（44.0％）（P〈0.05）；PLKI表达与淋巴结转移无关（P〉0．05）。结论PLK1在早期甲状腺乳头状癌的发生、发展中起重要作用，PLK1的检测有望成为甲状腺乳头状癌早期诊断指标。     

C-Met和脆性组氨酸三联体在卵巢癌中的表达及临床意义

目的:探讨C-Met和脆性组氨酸三联体蛋白在卵巢肿瘤中的表达及意义.方法:采用免疫组化SP法检测51例卵巢癌、16例卵巢交界性肿瘤、18例卵巢良性肿瘤、10例正常卵巢组织中脆性组氨酸三联体和C-Met蛋白表达.结果:C-Met蛋白在正常卵巢组织中无表达,在卵巢良性肿瘤、卵巢交界性肿瘤及卵巢癌组织中的阳性表达率分别为22.2%,37.5%,66.7%,卵巢癌与正常卵巢组织、卵巢良性肿瘤、卵巢交界性肿瘤比较差异有统计学意义(P<0.05).脆性组氨酸三联体在卵巢癌组织的阳性率低于正常卵巢组织和卵巢良性肿瘤,差异有统计学意义(P<0.05).在卵巢癌组织中,随组织学分级的增加和淋巴结的转移,C-Met表达阳性率逐渐上升,脆性组氨酸三联体表达阳性率逐渐下降,差异有统计学意义(P<0.05);C-Met和脆性组氨酸三联体表达呈负相关性(r=-0.382,P=0.006).结论:C-Met和脆性组氨酸三联体基因突变或缺失在卵巢癌的发生、侵袭和转移中可能起重要作用,C-Met和脆性组氨酸三联体联合栓测有助于卵巢肿瘤的早期诊断、早期治疗及生物学行为的评估.     

甲状腺滤泡性肿瘤中核转录因子过氧化物酶体增殖物激活受体γ表达与临床意义

目的 研究核转录因子过氧化物酶体增殖物激活受体7(peroxisome proliferator-activated receptor γ,PPAR γ)在甲状腺滤泡性肿瘤中表达及其与病变的关系.方法 分别应用免疫组化方法及原位杂交方法检测42例原发性甲状腺滤泡性肿瘤(滤泡性腺癌19例,腺瘤23例)标本中PPAR 7蛋白及tuRNA表达.结果 PPAR γ蛋白及PPAR TmRNA在甲状腺滤泡性腺癌表达与甲状腺滤泡性腺瘤的表达差异无统计学意义,11例vs 8例(P＞0.05).PPAR γ蛋白在无肿瘤转移、低预后指数的甲状腺滤泡性腺癌表达阳性率升高,7例vs 4例,6例vs 5例(均P＜0.05),PPAR γmRNA在无转移甲状腺滤泡性腺癌表达阳性率增高,7例vs 5例(P＜0.05).PPARγ蛋白和PPARγmRNA表达水平呈显著正相关(rs=0.771,P=0.000).结论 检测PPAR γ蛋白及PPAR TmRNA水平可能是判断甲状腺癌预后的观测指标.     

Survivin和Caspase-3在人类大肠腺瘤及大肠癌中的表达以及与凋亡的关系

目的 评价大肠腺瘤及大肠癌组织中Survivin和Caspase-3的表达情况以及与细胞凋亡的关系。方法 采用免疫组化二步法，对48例无术前放、化疗史的大肠癌患者的手术标本，20例正常大肠黏膜和25例腺瘤标本。进行Survivin和Caspase-3检测，并用TUNEL法检测凋亡细胞。结果 Survivin在正常大肠黏膜中无表达，在管状腺瘤、绒毛状和混合型腺瘤及腺癌中的阳性表达分别为10％、33．3％、70．8％。Caspase-3在正常粘膜、管状腺熘、绒毛状和混合型腺瘤及腺癌中的阳性表达分别为95％、60％、53．3％、45．8％。正常黏膜组织Caspase-3的表达高于大肠腺瘤和大肠癌（P〈0．05）。Survivin和Caspaso-3在大肠癌中的表达强度随组织分化程度增高而增强；而在不同的Dukes分期间无显著差异（P〉0．05）。大肠癌组织中Survivin与Caspase-3的表达无直线相关关系，Survivin阳性组凋亡指数明显低于阴性组（P〈0．005）。结论 Survivin在大肠癌发生早期过程中表达上调，有望成为大肠癌新的早期诊断标志物。Survivin作为凋亡抑制蛋白显著抑制癌组织的细胞凋亡，但不能完全抑制Caspase-3的表达。     

肾上腺皮质肿瘤增殖抗原和脆性组氨酸三联体表达的相关性及意义

目的 研究肿瘤增殖抗原(Ki67)和脆性组氨酸三联体(FHIT)在肾上腺皮质肿瘤中的表达及其与肾上腺皮质肿瘤的关系.方法应用免疫组化方法检测75例肾上腺皮质肿瘤(腺瘤61例、腺癌14例)及10例瘤旁正常组织标本中Ki67及FHIT的表达情况.结果Ki67在正常肾上腺组织不表达,在腺癌表达最高,腺瘤次之;FHIT表达的情况相反.Ki67和FHIT在肾上腺皮质组织的表达呈负相关关系(r=-0.721,P<0.005).结论Ki67及FHIT的表达与肾上腺肿瘤显著相关,联合检测Ki67和FHIT在肾上腺皮质肿瘤的表达,为难以判断良、恶性的肾上腺皮质肿瘤提供较为客观、简捷的诊断方法.     

彩色血管能量成像检测甲状腺癌血流及其与凋亡抑制因子的关系

目的应用彩色血管能量成像（CPA）技术检测甲状腺癌内的血流及其与凋亡抑制因子（survivin）的相关性。方法应用CPA技术检测50例甲状腺癌患者及30例甲状腺腺瘤患者的血流信号,及其阻力指数（RI）,采用免疫组化法检测该组织中survivin的表达。结果甲状腺癌survivin的阳性表达率（68%）显著高于甲状腺腺瘤组（33.3%,P〈0.05）,甲状腺癌中survivin的阳性表达率与病理的高分期和淋巴结转移密切相关（P均〈0.05）。甲状腺癌中的survivin表达强度与CPA血流分级及RI值均呈正相关（r1=0.827,r2=0.809,P〈0.05）。结论应用CPA技术与免疫组化技术二者的有机结合可对甲状腺癌进行术前、术后多方面评估,从而为评价其临床应用提供参考。     

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.