两种HLA不全相合异基因造血干细胞移植治疗恶性血液病

目的:研究HLA配型不相合异基因造血干细胞移植联合亲缘单倍体相合骨髓输注,探讨降低急性移植物抗宿主病发生率的方法及其临床的意义。方法:亲缘半相合及非亲缘HLA不全相合造血干细胞移植联合亲缘单倍体相合骨髓输注共30例,其中急性髓系白血病(AML)8例(其中1例为骨髓增生异常综合征转化AML),急性淋巴细胞白血病(ALL)17例(其中合并BCR/ABL融合基因阳性者1例),骨髓增生异常综合征RAEB 2例,急性混合细胞白血病3例。第一供者来源亲缘单倍体相合移植20例,非血缘不全相合移植10例。预处理方案采用改良马利兰/环磷酰胺(马利兰、阿糖胞苷、司莫司汀、环磷酰胺/氟达拉滨)+抗人胸腺T细胞免疫球蛋白。移植物抗宿主病预防采用短程甲氨蝶呤+环孢素A或吗替麦考酚酯的方案。结果:30例患者均获得造血重建。中性粒细胞≥0.5×10~9/L及血小板≥20×10~9/L的时间分别为14(8-26)d及11.5(10-24)d,植入证据检测为100%第一供者造血,100 d内Ⅰ-Ⅱa GVHD的累计发生率是22.3%(95%CI 9.9%-34.7%),Ⅱ-Ⅳ和Ⅲ-Ⅳa GVHD累积发生率分别为22.7%(95%CI,10%-35.4%)和12.7%(95%CI 6.9%-15.5%)。11例1-2个位点不合移植患者中有4例发生Ⅱ-Ⅳ度a GVHD(13.3%),19例3-5个位点不合移植患者中有5例发生Ⅱ-Ⅳa GVHD(16.7%)。发生急性移植物抗宿主病组和无急性移植物抗宿主病组复发率、2年无病生存率差异无显著性意义(P0.05)。Ⅰ-Ⅱ和Ⅲ-Ⅳc GVHD累积发生率为13.3%(95%CI,1.4%-26.8%)和3.3%(95%CI,0%-12.2%),其中1例(3.3%)为广泛慢性GVHD。2年预计总生存率(OS)及2年无病生存率(DFS)分别为68.2%(95%CI 51.0%-85.4%)和81.1%(95%CI 66.0%-96.2%)。结论:两种HLA不全相合异基因造血干细胞a GVHD发生率低,在缺乏HLA相合供者时,联合亲缘单倍体相合骨髓移植治疗恶性血液病的方法安全有效。     

非血缘及HLA配型不合移植预防急性移植物抗宿主病13例

目的:探讨非血缘及人类白细胞抗原配型不合的异基因外周血造血干细胞移植时,环孢素A、麦考酚酸酯、抗胸腺细胞球蛋白、白细胞介素11及短程甲氨蝶呤联合预防急性移植物抗宿主病的疗效.方法:2004 09/2008-11海口市人民医院采用环孢素A等五联用药预防非血缘及血缘HLA配型不合异基因外周血造血干细胞移植患者13例.供受者HLA相合情况:非血缘供者7例,单倍型移植3例,人类白细胞抗原1个位点不合同胞供者3例.具体预处理方案为移植前7d开始,环孢素A5-10mg/(kg·d),12 h静滴1次,2次/d,无呕吐后改为口服维持:移植前7 d开始,麦考酚酸酯1次/d;移植前5 d～移植前2 d予抗胸腺细胞球蛋白2.5 mg/(kg·d);移植前2 d～移植后10 d予白细胞介素11,1.5 mg/d皮下注射;移植后1 d予甲氨蝶呤15 mg/m2,移植后3,6,11 d各予甲氨蝶呤10 mg/m2静脉滴注.临床若无移植物抗宿主病出现,3～6个月逐渐减量至停药,单倍型移植者适当延长.移植前3 d,供者行重组人粒细胞集落刺激因子皮下注射,于用药第4,5天采集外周血干细胞,并分别于当天由锁骨下静脉输入患者体内,回输单个核细胞数为(7.82～9.1 1)×108/kg,CD34+细胞数为(2.9～7.7)×106/kg.结果:13例患者均获得造血重建,急性移植物抗宿主病的发生率为46%(6/13),Ⅲ～Ⅳ度急性移植物抗宿主病发生率为8%(1/13).随访至2009-04,除1例患者尚未能到公共场所外,余12例目前均正常生活或工作.结论:环孢素A、麦考酚酸酯、抗胸腺细胞球蛋白、白细胞介素11及短程甲氨蝶呤联合预防急性移植物抗宿主病可获得较好的疗效.     

非亲缘异基因外周血干细胞移植重建白血病幼儿造血功能：1例报告

目的:分析非亲缘异基因外周血干细胞移植治疗幼儿急性非淋巴性白血病的可行性。方法:患儿,男,3岁,于2005-07-18为行造血干细胞移植入本院血液科骨髓移植病房,入院诊断为急性非淋巴细胞性白血病-M5b。经抗肿瘤药物治疗病情获得完全缓解。患儿首先接受清髓性预处理,然后接受同性别非亲缘异基因外周血造血干细胞移植。①移植预处理包括马利兰、阿糖胞苷和环磷酰胺。移植前依次用药为马利兰3.2mg/(kg·d)×4d,口服,于移植前6,7,8,9d给药;阿糖胞苷3.2g/(m2·d)×2d,于移植前4,5d给药;环磷酰胺54mg/(kg·d),于移植前2,3d给药。②急性移植物抗宿主病的预防用药包括环孢菌素A和氨甲蝶呤、抗胸腺细胞球蛋白及吗替麦考酚酯。供者接受粒细胞集落刺激因子动员4d后采集外周血造血干细胞,供、受者间HLA全相合,患者血型A,供者血型B,主次要均不合。结果:①患儿移植后早期获得造血重建,中性粒细胞>0.5×109L-1和血小板>50×109L-1的天数分别是12d和11d。②移植后1个月经DNA短串联重复序列多态性分析证明为供者型完全植入,移植后3个月查骨髓象正常。③移植后3,6个月定期行淋巴细胞亚群检查表明除CD19 ,CD4 细胞未恢复外,自然杀伤细胞在移植后3个月恢复正常,T淋巴细胞CD3 与CD8 、体液免疫球蛋白在移植后6个月中均获得重建。④整个移植过程顺利,未出现明显感染和重度急性移植物抗宿主病。移植后96d时出现Ⅰ度皮肤移植物抗宿主病,经加用激素治疗,皮疹消失。移植术后已随访观察12个月,患儿正常生活。结论:如果患儿有HLA完全相合的供者,非亲缘异基因外周血干细胞移植治疗儿童高危白血病是一种有效和安全的方法,对国内独生子女家庭拓宽供者来源有重要的实用价值。     

亲缘间单倍体造血干细胞移植治疗白血病4例

背景:建立及维持非血缘供者库需要大量投资,而亲属部分相合的供者则不需要特殊费用,有更强的可操作性.目的:评估亲缘间半相合造血干细胞移植治疗白血病的疗效.方法:选取2002-11/2008-03中南大学湘雅医学院附属海口市人民医院血液科住院患者4例,均进行HLA单倍体相合亲缘供者造血干细胞移植.采用改良的Bu/CY预处理方案:阿糖胞苷2.0～3.0g/(m2·d)×2 d,持续24 h静滴:马利兰4 mg/(kg·d)×3 d:环磷酰胺50 mg/(kg·d)×2 d:甲基环已亚硝脲25 mg/(m2.d)×1 d;抗胸腺细胞球蛋白25 mg/(kg·d)×4 d.在改良方案的基础上加大阿糖胞苷剂量1倍,且改为持续24 h静滴,使预处理强度增加,促进造血干细胞持久植入.移植物抗宿丰病预防:存经典的甲氨蝶呤方案基础上将环孢素A及霉酚酸酯提前至-7 d(同输干细胞前为-)使用.患者移植前后进行ABO血型发DNA检测.结果与结论:①移植后造血重建检测:4例患者均获得造血重建,未发生预处理相关死亡.造血于细胞移植后-3～+7 d白细胞降为0,片持续2-14 d,+12-+20 d白细胞>1.0×109L-1,+20～+51 d血小板>20×109L-1.②移植物抗宿土病的发病情况:4例患者移植物抗宿主病Ⅳ级(肠道)1例,出现急件移植物抗宿主病Ⅱ级(肠道)1例,急性移植物抗宿丰病Ⅱ级(皮肤)1例.提示随着预处理方案、移植物抗宿主病预防方案的优化,亲缘间单倍相合造血干细胞移植治疗白血病安全有效.     

2例急性淋巴细胞白血病行脐血移植患儿的护理

目的 :探讨和总结组织相容性抗原 (HLA)不全合非亲缘供者脐血移植 (UCBT)治疗儿童急性淋巴细胞白血病的护理。方法 :根据儿童患者的生理、病理及心理特点进行脐血移植前的准备和空气层流洁净病房 (LAFR)的建立 ,护理人员及患儿的准备 ,以及脐血回输时和回输后感染的预防 ,各种药物副反应和并发症的观察和护理。结果 :例 1和例 2分别于移植后 2 6d和2 1d出现Ⅱ度急性GVHD ,134d和 12 2d免疫功能恢复正常 ,4 4d和 4 2dHLA抗原检测为供者白细胞抗原表达。现 2例受者已无病生存 2 7个月和 2 4个月。结论 :针对性护理措施是HLA不全合非亲缘供者脐血移植治疗儿童急性淋巴细胞白血病成功与否的关键因素之一。     

非亲缘供者外周血造血干细胞移植治疗恶性血液病

为了探讨非亲缘供者外周血造血干细胞移植(UD-HSCT)治疗恶性血液病的可行治疗方案和疗效,应用高分辨HLA配型(HLA-A、-B、-DR)完全相合或1个位点不合的非亲缘供者外周血造血干细胞移植治疗恶性血液病10例,预处理方案采用马利兰、环磷酰胺、阿糖胞苷、甲基环己亚硝脲和抗胸腺细胞球蛋白,以霉酚酸酯、环孢素A加短疗程的甲氨喋呤、舒莱预防移植物抗宿主病(GVHD)。结果显示,中性粒细胞回升>0.5×109/L的中位时间为13天,血小板回升>20×109/L的中位时间为17.5天;28天STR-PCR检测显示,10例均为完全供者型;急性GVHD3例(Ⅰ度1例自行缓解,Ⅲ度1例治愈,Ⅵ度1例死亡)。结论:在非亲缘供者外周血造血干细胞移植治疗恶性血液病过程中采用上述预处理方案和GVHD预防措施是可行而且有效的。     

非去T细胞HLA单倍体外周血造血干细胞移植治疗难治性急性白血病

目的:探讨非去T细胞人类白细胞抗原(HLA)单倍体外周血造血干细胞移植对难治性急性白血病的有效性和安全性.方法:受者为1例难治性急性淋巴细胞白血病,供者为HLA单倍体相合的患者父亲.预处理方案主要由全身照射、阿糖胞苷、环磷酰胺和司莫司汀组成.移植物抗宿主病(GVHD)的预防采用环孢素A、甲氨蝶呤、霉酚酸酯和抗胸腺细胞球蛋白四联方案.结果:患者移植过程顺利,未出现严重感染、出血、间质性肺炎及GVHD等并发症.于移植后20天患者获得造血重建,第70天血型由B型转变为供者O型,第140天HLA完全转为供者型.结论:应用非去T细胞、增强预处理及免疫抑制强度的HLA单倍体相合外周血造血干细胞移植治疗急性白血病,简便安全,疗效较好,为无HLA相合供者的白血病患者提供了新的治疗手段.     

单倍体造血干细胞移植治疗儿童重型再生障碍性贫血

本研究分析非体外去T细胞亲缘单倍体造血干细胞移植(hi-HSCT)治疗儿童重型再生障碍性贫血(SAA)的疗效。我院于2010年10月-2013年3月对2例SAA/极重型再生障碍性贫血(VSAA)患儿进行了非体外去T淋巴细胞的父亲2个HLA位点不合的HSCT。2例在病程4个月内用环孢素A(CsA)+粒细胞集落刺激因子(G-CSF)治疗无效,有活动或重症感染,输血依赖,无HLA全合的同胞供者或非血缘供者。移植前预处理用福达拉滨(Flu)+环磷酰胺(Cy)+抗胸腺细胞球蛋白(ATG)。移植物为G-CSF动员的外周血造血干细胞(PBHSC)和骨髓(BM)。移植物抗宿主病(GVHD)预防用CsA+骁悉(MMF)+短程甲氨蝶呤(MTX)。结果2例患儿均达到100%供者植入,粒细胞植入时间分别为移植后12 d、18 d,血小板植入时间分别为移植后17 d、26 d。2例均出现I度急性GVHD(aGVHD),1例发展为可控制的局限性慢性GVHD(cGVHD)。2年随访期间,2例患儿保持稳定的100%供者植入并有免疫功能的重建。结论:小数量临床研究结果提示在没有同胞HLA全合供者或非血缘HLA全合供者时,亲缘单倍体造血干细胞移植对儿童SAA是适宜的选择,总体生存率(OS)的提高还有待大规模前瞻性临床研究的开展。     

HLA不全相合非亲缘供者脐血移植治疗二例儿童急性淋巴细胞白血病

目的　探讨HLA不全相合非亲缘供者脐血移植 (CBT)治疗血液系统恶性肿瘤造血及免疫重建情况及移植相关并发症。方法　对 2例儿童急性淋巴细胞白血病 (ALL)患儿进行HLA 1个位点不合非亲缘供者的CBT。预处理方案 :例 1采用白消安、环磷酰胺 (BU CTX)方案 ,例 2采用BU CTX+卡氮芥方案。移植物抗宿主病 (GVHD)的预防采用环孢菌素A(CsA) +霉酚酸酯 (MMF)方案。移植有核细胞数 (NC)例 1为 14.6× 10 7 kg ,例 2为 16 .2 4× 10 7 kg ,CD3 4+细胞例 1为 7.2 4× 10 5 kg ,例 2为2 1.11× 10 5 kg。结果　例 1和例 2中性粒细胞绝对计数 >0 .5× 10 9 L的时间分别为移植后第 5天和第7天 ;血小板计数 >5 0× 10 9 L的时间分别为移植后第 5 3天和第 46天 ;全血细胞恢复正常的时间分别为移植后第 6 0天和第 5 2天。例 1、例 2分别于移植后第 6 0天和第 30天免疫功能开始恢复 ,移植后第134天和第 12 2天免疫功能恢复正常。移植后第 19天和第 17天DNA指纹图提示供者型。例 1供者为男婴 ,移植后第 49天外周血及骨髓染色体检查均为供者型 :46 ,XY ,10 0 %嵌合。例 1和例 2分别于移植后第 2 6天和第 2 1天出现Ⅱ度急性GVHD。 2例受者已无病生存 2 1个月和 16个月余。结论　CBT造血重建与免疫重建快而稳定 ,移植相关并发症     

减低预处理剂量异基因造血干细胞移植后的白血病复发

目的:减低预处理剂量异基因造血干细胞移植预处理方案剂量强度弱于清髓性移植且又强于真正的非清髓移植,期望在降低毒副反应的同时能够减少复发.评价减低预处理剂量的异基因造血干细胞移植后白血病的复发情况及主要影响因素.＃方法:①对象:选取2003-03/2005-06厦门大学附属中山医院血液科收治的23例白血病患者,急性粒细胞白血病6例,急性淋巴细胞白血病7例,慢性粒细胞白血病10例.供者同胞HLA全相合10例,同胞或亲缘供者不全相合12例,非血缘1例.供受者对治疗均签署知情同意书,实验经医院医学伦理委员会批准.②实验方法:23例白血病患者均采用减低预处理剂量方案,马利兰4 mg/(kg·d),2～3 d;环磷酰胺50 mg/(kg·d),2 d.其中19例患者在上述方案的基础上加用氟达拉滨30 mg/(m2·d),3～5 d;10例患者同时加用阿糖胞苷(1.0～2.0)g/(m2·d),1～3 d.供受者HLA位点不合时用兔抗胸腺细胞球蛋白(3.0～5.0)mg/(kg·d),3～5 d.异基因造血干细胞移植前行供者外周血干细胞动员,4～5 d后连续采集2次,23例白血病患者输入CD34 细胞中位数为4.02×106/kg.采用骁悉 环孢素 短程甲氨喋呤方案预防移植物抗宿主病.③实验评估:采用STR-PCR方法检测异基因造血干细胞植入证据.结果:①造血功能重建检测:23例患者均顺利完成造血功能重建,无一例发生预处理相关死亡.经预处理后外周血白细胞最低值为(0.01～0.30)×109 L-1,血小板最低值为(5～20)×109 L-1;中性粒细胞恢复到0.5×109 L-1的中位时间为术后11 d,血小板恢复到30×109 L-1的中位时间为术后12 d.术后30 d经STR-PCR检测22例患者为完全供者型,骨髓象均完全缓解,剩余1例复发患者未行STR-PCR检测.②移植物抗宿主病发生情况:23例患者中,9例(39.1%)发生急性移植物抗宿主病,19例(82.6%)发生慢性移植物抗宿主病.③术后复发及生存情况:随访截止至2007-06-30,共5例患者复发,复发率21.7%,复发时间为移植后1～24个月;其中急性淋巴细胞白血病2例,急性粒细胞白血病2例,慢性粒细胞白血病1例,后3例移植前处于复发状态.移植前处于缓解期的患者其复发率为10%.结论:①急、慢性粒细胞白血病缓解期患者采用减低预处理剂量的异基因造血干细胞移植方式,其术后复发率并未高于清髓性异基因造血干细胞移植,且预处理相关死亡率低.②疾病类型的选择、移植时的疾病状态、适当的预处理强度以及移植物抗宿主病是影响术后复发的重要因素.     

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.     

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.     

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.