红细胞生成素受体mRNA在慢性肾功能衰竭大鼠骨髓细胞中表达减少

采用RT-PCR方法观察次全肾切除大鼠的骨髓细胞中红细胞生成素(EPO)受体mRNA表达的变化,结果发现急性贫血可使骨髓细胞中EPO受体mRNA表达显著增多,而次全肾切除大鼠的骨髓细胞中EPO受体mRNA表达显著减少。结论表明,慢性肾功能衰竭能明显抑制EPO受体基因表达,提示这一作用参与慢性肾功能衰竭贫血的发生。     

益比奥治疗肾性贫血90例临床观察

慢性肾功能衰竭多伴严重贫血，原因是肾实质受损使其生成促红细胞生成素减少，致机体内EPO水平降低，以往均采用重组促红细胞生成素(rHuEPO)治疗肾性贫血价格昂贵，近年应用国产促红细胞生成索治疗肾性贫血，取得了初步疗效。我院自1997年以来，应用国产促红细胞生成素(益比奥)治疗90例慢性肾功能衰竭合并肾性贫血的患者，现报道如下：     

苯那普利和氯莎坦延缓慢性肾功能衰竭进展的实验研究

目的：探讨血管紧张素转换酶报制剂苯那普利和血管紧张素Ⅱ受体阻断剂氯莎坦对慢性肾功能衰竭的延缓作用。方法：雄性SD大鼠40只，随机分成下列4组。A组：假手术组（n=8）；B组：慢性肾功能衰竭组(n=12)；C组：慢性肾功能衰竭氯莎坦（Losartan）治疗组（n=10)；D组：慢性肾功能衰竭苯那普利（Benazepril)治疗组（n=10)。B、C、D三组大鼠实验前元首地肾大部切除术（切除右肾并结扎左肾下极2支肾动脉分支）。C、D两组大鼠分别灌服Losartan和Benazepril溶液10mg.kg^-1.d^-1,A、B两组大鼠则灌服同等量的生理盐水。实验期为12周。观察大鼠血压（BP）、肾功能（尿素氮BUN、肌酐Scr)、24h尿蛋白（Upro）和肾病理变化。结果：实验12周后，⑴两治疗组大鼠BP、BUN、Scr、Upro均显著低于慢性肾功能衰竭未治疗组；⑵与未治疗组相比，两治疗组大鼠肾小球硬化和肾间质纤维化程度明显减轻，肾小球硬化积分值明显减少。结论：⑴血管紧张素Ⅱ是引起肾小球硬化和肾间质纤维化的重要因子；⑵苯那普利和氯莎坦可明显改善肾脏病理损害，保护肾功能，延缓慢性肾功能衰竭进展。     

同种肾组织移植改善肾性贫血的基因水平检测

背景:促红细胞生成素分泌不足使慢性肾衰所引起的贫血(肾性贫血)难以改善。目的:观察肾组织移植对肾性贫血大鼠促红细胞生成素基因表达的影响。方法:80只Wistar大白鼠随机均正常对照组,病例对照组、重组人类促红细胞生成素组和肾组织移植组,后3组建立慢性肾功能衰竭动物模型。结果与结论:60d时移植组血红蛋白水平及血清促红细胞生成素高于病例对照组(P<0.05),与重组人类促红细胞生成素组比较,差异无显著性意义(P>0.05)。移植组肾组织EPO mRNA表达显著高于病例对照组,差异有显著性意义(P<0.05)。提示肾组织移植改善肾性贫血的作用机制是促进肾组织EPO mRNA的基因表达,使肾脏合成促红细胞生成素增多,从而提高血红蛋白水平。     

重组人红细胞生成素治疗肾性贫血对网织红细胞指数的影响

目的研究重组人红细胞生成素(rHuEPO,简称EPO)治疗慢性肾功能衰竭对未成熟网织红细胞指数水平的影响。方法采用SYSMEXXE2100型血细胞分析仪测定网织红细胞百分率(Ret)、未成熟网织红细胞指数(IRF)、红细胞压积(HCT)。结果与对照组比较,慢性肾功能衰竭(CRF)患者组用药前HCT显著降低(P<0.01),Ret、IRF显著增高(P<0.01)。与用药前比较,CRF患者用药48h后,HCT未发生显著改变(P>0.05),Ret、IRF显著增高(P<0.01);与48h水平比较,CRF患者用药1周后,HCT水平略增高,无统计学意义(P>0.05),Ret、IRF水平进一步增高(P<0.01)。结论由于IRF比HCT更为敏感,对监测CRF患者EPO疗效更具有实用价值。     

间歇低氧对大鼠内皮素及其受体基因表达的影响

目的观察慢性间歇低氧诱发大鼠高血压发病过程中内皮素(ET)及其受体的动态变化,探讨慢性间歇低氧诱发高血压的发病机制。方法将Wistar大鼠(n=72)随机均分为间歇低氧组(IH组)、实验对照组(SC组)和空白对照组(UC组)。IH组大鼠循环给予氮气和压缩空气(每一循环60s,使舱内最低氧浓度达4%~6%,然后恢复至21%,8h/d),SC组大鼠循环给予压缩空气,UC组大鼠不给予任何处理。观察第7、21、42天时各组大鼠的血压、血浆ET-1水平及不同组织ET-1和内皮素A型受体(ETAR)mRNA的表达。结果第42天时IH组大鼠平均动脉压(MAP)较实验前升高约8mmHg(P<0·01),而两对照组大鼠MAP无显著变化。IH组大鼠血浆ET-1水平随间歇低氧时间的延长逐渐升高,从第7天[(157±35)ng/L]开始显著高于SC组[(123±29)ng/L]和UC组[(119±28)ng/L]水平(P<0·05),并且与MAP呈正相关(r=0·605,P=0·002);其心脏和肾皮质ET-1mRNA的表达随间歇低氧时间的延长也逐渐增加,从第21天开始显著高于两对照组水平(P<0·05);其主动脉、心脏和肾皮质ETARmRNA的表达与两对照组比较,差异无显著性(P>0·05)。SC组与UC组比较,各项观察指标差异均无显著性(P>0·05)。结论慢性间歇低氧可导致ET-1表达增加,使血循环ET-1水平升高,而对ETAR的表达没有影响,提示ET-1的过度表达可能是慢性间歇低氧诱发高血压的重要原因之一。     

波生坦对DOCA-盐型高血压大鼠肾脏的保护作用

目的观察内皮素受体阻断剂波生坦(bosentan)对DOCA-盐型高血压大鼠(DHR)的肾脏保护作用.方法采用10周龄雄性SD大鼠,切除左侧肾脏,术后予抗感染,1周后存活大鼠随机分成4组.对照组给予饮自来水.其他组予DOCA皮下注射,饮盐水.其中2组分别给予波生坦及氨氯地平,安慰剂组给予等量自来水灌胃共5周.留取血、尿送生化检测;摘取肾脏,石蜡包埋卮作组织学和免疫组化检测.结果与对照组相比,安慰剂组血压、单肾/体重值、24h尿蛋白排出量增加,肾脏有较明显的组织学改变(如肾小球硬化;肾小管扩张、肥厚;蛋白管型;肾间质细胞浸润;小动脉壁增厚等),肾内转化生长因子β1(TGF-β1)和Smad7的蛋白表达明显上调.波生坦能较显著地缓解上述异常(P＜0.05).结论波生坦对DHR肾脏有明显的保护作用,其机制可能与它能阻断内皮素系统以及下调TGF-β1和Smad7有关.     

同种肾组织移植改善慢性肾功能衰竭贫血:红细胞质量和数量验证(英文)

背景:既往通常采用的反复输血和重组人类促红细胞生成素纠正慢性肾功能衰竭后贫血,但由于多种副作用使其临床应用受到很大限制。目的:通过动物实验,以现代医学公认的治疗慢性肾功能衰竭后贫血的药物重组人类促红细胞生成素作为阳性对照,从红细胞数量、质量方面验证同种肾组织移植的治疗效果。设计、时间及地点:混合模型重复测量资料的方差分析,随机分组动物实验于2004-06/2005-03在山西医科大学生理实验室完成。材料:选用成年健康雄性Wistar大白鼠80只作为受体,成年受体大鼠尾静脉每天一次注射盐酸阿霉素6.5mg/kg,每周3次,共6周。然后切除右肾建立慢性肾功能衰竭模型。供肾组织移植用Wistar新生鼠20只,出生三四天,雌雄不拘。实验用主要试剂重组人类促红细胞生成素:2×106U/L,由山东阿华医药公司提供(批号99435)。方法:取20只大鼠为正常对照组,无特殊干预;其余60只大鼠制备慢性肾功能衰竭模型后,随机分为3组,每组20只:肾组织移植组,将取处新生鼠的肾组织块多点植入受体肾包膜下;促红细胞生成素治疗组,每次按30U/kg剂量腹腔注射重组人促红细胞生成素,每周3次,连续6周;模型组,不给予其他干预。主要观察指标:以SABC法检测促红细胞生成素在肾组织和移植物的表达及分布。取大鼠内眦静脉血,以ELISA法直接测定血清促红细胞生成素水平,常规方法测定血红蛋白水平,以相应的试剂盒测定红细胞膜Na+-K+ATP酶、超氧化物歧化酶活力,以及丙二醛水平。结果:①促红细胞生成素抗原阳性反应在正常对照组内表达呈强阳性。而在模型组呈弱阳性或不表达,在移植组中呈强阳性,模型组与其他两组比较,差异有显著性意义(P<0.01)。②实验30,45,60d时促红细胞生成素治疗组、肾组织移植组血清促红细胞生成素水平和血红蛋白和红细胞计数比模型组显著升高(P<0.05～0.01),实验60d时促红细胞生成素治疗组血清促红细胞生成素水平高于肾组织移植组(P<0.05)。③实验30,45,60d时促红细胞生成素治疗组、肾组织移植组红细胞膜丙二醛含量低于模型组(P<0.05),促红细胞生成素治疗组与肾组织移植组比较,差异无显著性意义(P>0.05)。红细胞膜超氧化物歧化酶和Na+-K+ATP酶活力组间差异与丙二醛相反。结论:肾组织移植可提高慢性肾功能衰竭贫血大鼠红细胞数量和质量,作用与重组人类促红细胞生成素基本相当。     

同种肾组织移植改善肾性贫血的基因水平检测

背景：促红细胞生成素分泌不足使慢性肾衰所引起的贫血（肾性贫血）难以改善。目的：观察肾组织移植对肾性贫血大鼠促红细胞生成素基因表达的影响。方法：80只Wistar大白鼠随机均正常对照组,病例对照组、重组人类促红细胞生成素组和肾组织移植组,后3组建立慢性肾功能衰竭动物模型。结果与结论：60d时移植组血红蛋白水平及血清促红细胞生成素高于病例对照组（P〈0.05）,与重组人类促红细胞生成素组比较,差异无显著性意义（P〉0.05）。移植组肾组织EPO mRNA表达显著高于病例对照组,差异有显著性意义（P〈0.05）。提示肾组织移植改善肾性贫血的作用机制是促进肾组织EPO mRNA的基因表达,使肾脏合成促红细胞生成素增多,从而提高血红蛋白水平。     

重组人类红细胞生成素治疗透析前慢性肾衰性贫血的护理

贫血是慢性肾功能衰竭(CRF)常见的并发症之一.1997年1月至2001年1月我们应用重组人类红细胞生成素(rHuEPO,EPO),治疗透析前CRF贫血32例,疗效显著.现将护理体会报告如下.     

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.