低强度脉冲超声对兔膝骨性关节炎软骨细胞整合素-局部粘着斑激酶-促分裂原活化蛋白激酶力化学转导通路相关蛋白表达的影响

目的观察低强度脉冲超声（LIPUS）对兔膝骨性关节炎（OA）软骨细胞中整合素-局部粘着斑激酶（FAK）-促分裂原活化蛋白激酶（MAPK）力化学信号转导通路相关蛋白表达的影响。 方法共选取18只新西兰大白兔,其中12只进行膝OA造模,其余6只作为正常对照。于制模后第4周处死实验兔,提取软骨细胞进行体外培养并鉴定。将所培养细胞分为正常对照组、OA模型组及OA超声组。待细胞传至第2代时,正常对照组及OA模型组细胞不给予任何处理,OA超声组细胞则给予LIPUS辐射。于LIPUS持续作用1周后收集各组细胞,应用Western blot技术检测各组细胞中Ⅱ型胶原、蛋白多糖、基质金属蛋白酶(MMPs)-13、整合素β1、FAK、MAPK（如p38、ERK1/2、JNK）蛋白表达以及磷酸化蛋白表达情况。 结果①OA模型组及OA超声组Ⅱ型胶原、蛋白多糖含量均较正常对照组明显降低（P<0.05）,并以OA模型组下降幅度较显著,与OA超声组间差异具有统计学意义（P<0.05）。②OA模型组及OA超声组MMP-13含量均较正常对照组明显增高（P<0.05）,并以OA模型组增高幅度较显著,与OA超声组间差异具有统计学意义（P<0.05）。③OA模型组及OA超声组整合素β1、磷酸化FAK含量均较正常对照组明显增高,且以OA超声组增高幅度较显著,与OA模型组间差异具有统计学意义（P<0.05）。④OA模型组磷酸化p38、ERK1/2及JNK含量均较正常对照组明显增加（P<0.05）,OA超声组上述指标则较OA模型组显著降低（P<0.05）。 结论LIPUS体外辐射可抑制OA软骨细胞Ⅱ型胶原、蛋白多糖降解及MMP-13表达,同时还能促进整合素β1表达以及FAK磷酸化,抑制p38、ERK1/2、JNK磷酸化,提示LIPUS辐射可能通过启动整合素-FAK-MAPK力学信号转导通路诱导软骨细胞外基质发生改变。     

低强度脉冲超声波对早中期兔膝骨性关节炎软骨细胞外基质及MAPKs信号通路的影响

目的:研究低强度脉冲超声波(LIPUS)对早中期兔膝骨性关节炎(OA)软骨细胞外基质(ECM)、丝裂原活化蛋白激酶(MAPKs)信号通路的影响,探讨LIPUS对关节软骨损伤修复和延缓退变的作用机制。方法:36只健康新西兰兔随机分成6组,早期对照组(EC组)、早期OA组(EO组)、早期治疗组(ET组)、中期对照组(MC组)、中期OA组(MO组)和中期治疗组(MT组),6只/组。EO、ET、MO及MT组均接受左后肢前交叉韧带切断术(ACLT),对照组仅接受左侧膝关节囊切开术。ET组和MT组分别于术后第3天和第5周起接受LIPUS治疗。超声频率3MHz,强度40mW/cm2,作用时间20min,1次/d,6d/周,持续6周。EO与MO组的LIPUS方案与治疗组相同,但无超声输出。LIDUS6周后,采用甲苯胺蓝染色进行关节软骨的组织学观察,并进行Mankin评分。采用免疫印迹法检测蛋白多糖、Ⅱ型胶原、磷酸化的细胞外信号调节激酶1/2(p-ERK1/2)及p38(p-p38)的变化。结果:③组织学观察及Mankin评分:EO组关节软骨表面不规则、甲苯胺蓝染色变浅、软骨细胞减少,与EC组相比,Mankin评分显著升高(P<0.01);MO组关节软骨损伤明显,Mankin评分较MC组显著升高(P<0.01)。与EO组相比,ET组病理学改变程度轻,Mankin评分显著降低(P<0.01);但MT组Mankin评分较MO组无显著降低(P>0.05)。③Ⅱ型胶原、蛋白多糖检测:与EC组比较,EO组和ET组均下降,但EO组较ET组明显下降(P<0.05);与MC组相比,MO和MT组均显著降低(P<0.05),MO组与MT组间无显著差异(P>0.05)。③p-ERK1/2、p-p38检测:与EC组相比,EO组表达量显著升高(P<0.05),但与EO组相比,ET组显著降低(P<0.05);与MC组相比,MO组和MT组表达显著升高(P<0.05),MT组与MO组间无明显差异(P>0.05)。结论:LIPUS可以减轻关节软骨ECM的损伤程度,其作用与LIPUS治疗后关节软骨中p38、ERK1/2表达下调有关,这种作用与OA的病变阶段密切相关,即在OA早期进行LIPUS作用更明显。     

低强度脉冲超声对兔膝骨性关节炎骨软骨连接血管形成与侵袭的影响

目的观察低强度脉冲超声(LIPUS)对早期兔膝骨性关节炎骨软骨连接血管形成与侵袭的影响。 方法18只新西兰大白兔按随机数字表法分为对照组、模型组和治疗组,每组6只,模型组和治疗组接受前交叉韧带切断法手术,4周后建立早期骨性关节炎疾病模型,而对照组仅接受假手术处理。治疗组接受LIPUS辐射治疗4周,模型组和对照组仅接受LIPUS假辐射。采用番红O 固绿染色比较各组膝关节骨软骨连接血管形成与侵袭情况;采用免疫印迹(Western blot)技术检测各组的整合素β1、磷酸化黏着斑激酶(p FAK)、磷酸化p38、磷酸化c Jun氨基末端激酶(p JNK)、血管内皮生长因子(VEGF)及软骨调节素(CHM) 1蛋白表达水平。 结果模型组和治疗组与对照组比较,骨软骨连接血管形成明显增多,潮线出现漂移、重复,结构紊乱,甚至消失,部分血管突破潮线,侵入非钙化软骨层,而治疗组较模型组病理改变明显减轻。模型组的整合素β1、p FAK和VEGF表达水平［（0.92±0.07）、（0.83±0.09）和（1.02±0.10）］较对照组［（0.45±0.04）、（0.18±0.03）和（0.35±0.02）］明显增高,且组间差异有统计学意义(P<0.05);模型组的p38和JNK磷酸化水平［（0.99±0.11）和（1.86±0.06）］亦较对照组［（0.31±0.04）和（0.38±0.03）］明显增高(P<0.05);而模型组的ChM 1表达（0.61±0.04）较对照组（1.91±0.08）下降,且差异有统计学意义(P<0.05)。治疗组与模型组比较,治疗组的整合素β1和p FAK表达［（1.10±0.09）和（1.09±0.08）］亦较模型组明显增高,组间差异有统计学意义(P<0.05);但治疗组的VEGF表达（0.58±0.06）较模型组明显降低(P<0.05),治疗组的p38和JNK磷酸化水平［（0.54±0.09）和（1.29±0.08）］亦较模型组降低,且差异有统计学意义(P<0.05);但治疗组的ChM 1表达（1.09±0.12）较模型组明显升高,差异有统计学意义(P<0.05)。 结论LIPUS可以抑制骨性关节炎骨软骨连接血管形成与侵袭,其作用机制可能与LIPUS通过整合素β1 FAK p38/JNK VEGF/ChM 1通路调控血管形成相关因子VEGF和ChM 1的表达有关。     

低强度脉冲超声经PI3K/Akt通路调控兔膝骨性关节炎软骨细胞凋亡的作用机制研究

目的:探讨低强度脉冲超声(LIPUS)对兔膝骨性关节炎(OA)软骨细胞凋亡的影响及有关作用机制。方法:共选取30只新西兰大白兔,随机分为正常对照组(A组)、OA模型组(B组)、OA+LIPUS组(C组)、OA+LY294002(PI3K/Akt抑制剂)组(D组)、OA+LY294002+LIPUS组(E组),每组各6只。采用右后膝前交叉韧带切断术(ACLT)造模。于造模后第6周时采用空气栓塞法处死实验兔,切取软骨组织进行组织学观察,并进行Mankin评分;提取软骨细胞进行体外培养并采用免疫组化染色法鉴定;应用western blot检测各组软骨细胞中Ⅱ型胶原(COL2)、MMP-13、Akt、pAkt、P53、Bcl-2蛋白表达情况。结果:B组COL2、pAkt、Bcl-2蛋白含量较A组降低,MMP-13、P53蛋白含量较A组增高(P<0.05)。与B组相比,C组COL2、pAkt、Bcl-2蛋白含量增高,MMP-13、P53蛋白含量下降(P<0.05);D组COL2、Bcl-2、pAkt蛋白含量下降,MMP-13、P53蛋白含量升高(P<0.05),E组COL2、MMP-13、P53、Bcl-2、pAkt蛋白含量无明显变化,但与C组、D组相比差异显著(P<0.05)。各组Akt蛋白表达无明显差异。结论:LIPUS能通过PI3K/Akt通路降低兔膝骨性关节炎软骨细胞凋亡率,促进抗凋亡基因Bcl-2表达,下调促凋亡基因P53水平,促进关节软骨损伤修复。     

IS201对GL15神经胶质瘤细胞FAK、ERK1/2蛋白表达量及其磷酸化的影响

目的:通过检测整合素αvβ3拮抗剂IS201对人GL15神经胶质瘤细胞FAK、ERK1/2蛋白表达量及其磷酸化的影响,探讨其意义.方法:采用western-blotting法检测不同浓度的整合素αvβ3拮抗剂IS201对GL15细胞黏着斑激酶(FAK)、细胞外调节蛋白激酶(ERK1/2)表达量以及对FAK、ERK1/2的磷酸化有无明显抑制作用.结果:各实验组不同浓度的IS201均能明显降低FAK、ERK1/2的表达,对FAK、ERK1/2的磷酸化有明显的抑制作用.各实验组差异均具有统计学意义(P ＜ 0.05).结论:IS201对人GL15神经胶质瘤细胞FAK、ERK1/2蛋白表达量及其磷酸化均起负性调节作用,对胶质瘤的细胞增殖和侵袭性生长等恶性生物学行为起抑制作用.     

IL-1β，MMP-1在兔膝关节骨性关节炎模型软骨中的表达

目的建立兔膝关节骨性关节炎（OA）模型并观察白细胞介素1β（IL-1β）和基质金属蛋白酶（MMP-1）在其软骨中的表达，从而探讨与OA间的关系。 方法采用木瓜蛋白酶注射法建立兔膝OA模型（木瓜蛋白酶组），同时采用向兔膝关节注射生理盐水的方法建立兔膝对照模型（生理盐水组）。通过比较大体评分、Mankin评分、IL-1β及MMP-1表达强度间的差异，观察关节软骨退变情况及探讨IL-1β、MMP-1与软骨退变间的关系。 结果肉眼及电镜观察发现木瓜蛋白酶组软骨退变程度明显重于生理盐水组，木瓜蛋白酶组软骨大体评分及Mankin评分均明显高于生理盐水组，差异有统计学意义（P<0.01），木瓜蛋白酶组软骨细胞IL-1β、MMP-1的表达强度亦明显高于生理盐水组,差异有统计学意义（P<0.05）。 结论向实验兔膝关节腔内注射木瓜蛋白酶及L-半胱氨酸可成功建立兔膝OA模型；IL-1β、MMP-1表达水平与软骨退变严重程度有密切联系。     

5-氟脲嘧啶关节腔注射治疗兔膝骨性关节炎的实验研究

目的：评价5-氟脲嘧啶（5-fluorouracil，5-Fu）关节腔注射治疗兔膝骨性关节炎（osteoarthritis，OA）的疗效。方法：24只兔子制成骨关节炎模型后随机分成OA组、5-Fu组和对照组，OA组立即处死，5-Fu组按5-Fu 2mg／kg关节腔注射．每周1次连续4次，对照组注射等量生理盐水，最后一次治疗后1周处死。观察3组滑膜组织的光镜、电镜改变及软骨的光镜、基质金属蛋白酶-1（MMP-1）免疫组化改变，比较软骨Mankin’s评分及关节液中IL-1的浓度。结果：5-Fu组可见软骨破坏减轻。滑膜炎症明显抑制，Mankin’s评分明显改善（P〈0．01）；关节液IL-1浓度降低（P〈0．05）．关节软骨中MMP-1表达减弱。结论：5-Fu关节腔内注射能抑制滑膜炎症，缓解软骨的破坏。     

低强度脉冲超声通过初级纤毛调控软骨细胞

目的 探讨低强度脉冲超声（low-intensity pulsed ultrasound, LIPUS）对白细胞介素（interleukin,IL）-1β干预后的C57小鼠软骨细胞的合成代谢、细胞凋亡、纤毛内转运蛋白88(intraflagellar transport 88, IFT88)表达的影响，以及LIPUS修复软骨与初级纤毛的相关性。方法 分别对小鼠软骨细胞进行IL-1β干预、LIPUS干预、携带IFT88短发卡RNA的慢病毒转染，分组包括正常软骨细胞组（N组）、IL-1β干预软骨细胞组（OA组）、IL-1β干预软骨细胞+LIPUS组（OA+U组）、慢病毒沉默IFT88+IL-1β干预软骨细胞组（KO+OA组）、慢病毒沉默IFT88+LIPUS+IL-1β处理软骨细胞组（KO+OA+U组）。利用实时聚合酶链反应和免疫荧光实验检测各组软骨合成基质Ⅱ型胶原、蛋白聚糖、初级纤毛的表达，利用流式细胞术检测细胞凋亡。所有实验数据采用GraphPad Prism 9.5软件进行统计分析。结果 OA+U组较OA组的小鼠软骨细胞Ⅱ型胶原、蛋白聚糖表达上升，凋亡降低，初级纤毛发生率上升，差异有...     

类风湿关节炎患者自身反应性B细胞异常表达相关分子的检测和分析

目的:分析类风湿关节炎(rheumatoid arthritis,RA)患者自身反应性B细胞及与之功能相关的自身抗体和信号分子的表达。方法:采用流式细胞仪分析22例RA患者及10例正常对照者的外周血自身反应性B细胞比率及RA和骨关节炎(OA)患者(n=10)外周血单个核细胞(PBMC)Th2的表达。用荧光定量PCR(FQ-PCR)检测RA患者及正常对照者PBMC细胞外信号调节激酶(ERK)、黏着斑激酶(FAK)基因的相对表达量,并采用蛋白印迹法检测NF-κB信号通路的磷酸化格局;用ELISA法检测和分析RA及OA患者血清及关节滑膜液抗Ⅱ型胶原抗体水平,同时检测RA患者血清及关节滑膜液中基质金属蛋白酶-3(MMP-3)、基质金属蛋白酶组织抑制因子-1(TIMP-1)的表达状况。结果:相对于正常对照者,RA患者外周血中存在高表达CD19+的自身反应性B细胞;同时其PBMC中ERK基因相对表达量提高、NF-κB信号通路磷酸化活跃。相对于OA患者,RA患者关节滑膜液中抗Ⅱ型胶原抗体水平显著升高。RA患者关节滑膜液中MMP-3及TIMP-1等水平较其自身血清中升高。结论:RA患者自身反应性B细胞及相关分子的异常表达可能是介导RA发病的又一重要因素。     

低强度脉冲超声经整合素-FAK-p38 MAPK通路对膝关节脂肪垫共培养下软骨细胞的影响

目的观察低强度脉冲超声(LIPUS)通过整合素-黏着斑激酶(FAK)-p38丝裂原活化蛋白激酶(MAPK)通路对膝关节脂肪垫共培养下软骨细胞的影响。 方法24例女性膝脂肪垫及膝关节软骨均由骨科手术室提供,年龄25～35岁,均为膝关节急性外伤手术患者,排除其他膝关节病史。切取脂肪垫行苏木精-伊红染色(HE);制作脂肪垫培养液(FCM);于表面完好部分提取正常软骨细胞进行体外培养,按随机数字表法分成对照组、模型组（正常软骨细胞+FCM）、治疗组（正常软骨细胞＋FCM＋LIPUS干预）和抑制剂组（正常软骨细胞＋FCM＋LIPUS＋整合素抑制剂GRGDSP干预）。采用Ⅱ型胶原(COL2)免疫细胞化学染色法比较并鉴定对照组与模型组的软骨细胞。治疗组和抑制剂组接受LIPUS辐射,LIPUS辐射强度为40mW/cm2,每次辐射20min,每日1次,每周6d;其余各组接受LIPUS假辐射。第6天收集各组细胞,应用免疫印迹(Western blot)技术检测软骨细胞中Ⅱ型胶原、蛋白多糖(Acan)、基质金属蛋白酶(MMP)-13、整合素β1、磷酸化FAK(p-FAK)、磷酸化p38(p-p38)的蛋白含量。 结果免疫细胞化学染色显示,模型组软骨细胞表达的COL2免疫反应物显著少于对照组。Western blot检测显示,模型组COL2、Acan蛋白含量［(0.16±0.04)、(0.12±0.02)］较对照组［(0.55±0.03)、(0.62±0.03)］降低,MMP-13、整合素β1、p-FAK和p-p38蛋白含量［(0.49±0.04)、(0.34±0.04)、(0.33±0.05)和(0.51±0.04)］较对照组［(0.07±0.02)、(0.13±0.03)、(0.16±0.04)和(0.10±0.03)］增高,且组间差异均有统计学意义(P<0.05)。与模型组相比,治疗组COL2、Acan、整合素β1和p-FAK蛋白含量［(0.42±0.07)、(0.50±0.07)、(0.74±0.06)和(0.64±0.07)］增高,而MMP-13、p-p38蛋白含量［(0.37±0.06)、(0.37±0.08)］下降,差异有统计学意义(P<0.05);而抑制剂组COL2、Acan、MMP-13、整合素β1、p-FAK和p-p38蛋白含量［(0.19±0.04)、(0.09±0.03)、(0.51±0.03)、(0.33±0.02)、(0.30±0.05)和(0.53±0.04)］无明显变化,差异无统计学意义(P>0.05),但与对照组和治疗组相比,差异有统计学意义(P<0.05)。 结论LIPUS可通过整合素β1-FAK-p38 MAPK通路抑制脂肪因子诱导的软骨细胞MMP-13增高,减少COL2、Acan降解,从而对膝关节脂肪垫共培养下的软骨细胞起一定的保护作用。     

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.