灯盏细辛对大鼠低氧性肺动脉高压的治疗效应

目的: 探讨灯盏细辛对大鼠低氧性肺动脉高压的治疗效应.方法: 将30只雄性Sprague-Dawley大鼠分为对照组、低氧组和灯盏细辛治疗组,以常压低氧复制肺动脉高压模型,分别测量平均肺动脉压(mPAP)、红细胞压积(HCT)及右心室肥厚指数[RV/(LV S)].对大鼠肺组织切片进行HE染色,用图像分析技术测定大鼠肺小动脉管壁厚度[管壁厚度占外径的百分比(WT%)和管壁面积占总面积的百分比(WA%)]的变化.结果: 低氧组大鼠mPAP、HCT、RV/(LV S)、肺小动脉管壁厚度指标均高于正常对照组[mPAP:(30.7±2.16)mmHg vs(17.6±1.85)mmHg;HCT:50.26%±2.49% vs 33.14%±3.34%;RV/(LV S):32.99%±2.29% vs 22.71%±1.17%;WT%:29.85%±4.27% vs 15.33%±3.15%;WA%:73.83%±8.92% vs 52.12%±7.63%,p均＜0.01];经灯盏细辛治疗的低氧大鼠其mPAP为20.3±1.95mmHg,HCT为42.59%±2.35%,RV/(LV S)为25.17%±1.42% ,WT%为17.67%±3.76%和WA%为54.39%±9.28%均低于低氧组(p＜0.01).结论: 灯盏细辛可降低红细胞压积,抑制肺血管重建和右心室肥厚,可有效减慢低氧性肺动脉高压的进程.     

间歇有氧训练激活自噬改善低氧肺动脉高压的肺动脉重构

目的 观察间歇有氧训练对低氧肺动脉高压(hypoxic pulmonary arterial hypertension,HPAH)大鼠的肺动脉压及肺小动脉结构的影响,探讨间歇有氧训练改善HPAH的机制。方法 30只雄性SD大鼠随机分为对照组、HPAH组、康复组,每组各10只。HPAH组及康复组给予低氧环境(氧浓度9%～11%,8 h/d,持续4周)建立大鼠HPAH模型。康复组在造模后给予间歇有氧训练4周。干预完成后测定各组大鼠的平均肺动脉压(MPAP)与右心室肥厚指数(RVHI);观察肺动脉病理学改变并测定肺小动脉管壁厚度/血管外径(MT%);检测自噬相关指标Beclin-1、LC3的蛋白表达。结果 HPAH大鼠MPAP、RVHI指标与对照组(12.52±2.60)mmHg (1 mm Hg=0.133 k Pa)、(21.37±3.75）%相比,HPAH组和康复组的MPAP、RVHI均升高,但康复组(26.14±4.21)mmHg、(28.09±4.43)%低于HPAH组(40.41±3.97)mmHg、(47.92±5.57)%,差异具有统计学意义(P<0.05)。HPAH组...     

缺氧性肺动脉高压大鼠肺血管转化生长因子β1的表达变化

目的：观察转化生长因子β1(TGF-β1)基因动态表达变化在大鼠缺氧性肺动脉高压中的作用。方法：40只成年雄性Wistar大鼠随机分成对照组、缺氧3、7、14和21d组,每组8只,测各组大鼠平均肺动脉压(mPAP)、血管形态学指标、右室肥大指数(RVHI);原位杂交和免疫组化检测TGF-β1基因表达。结果：缺氧7d后大鼠mRNA升高(18．4±0．37)mmHg,与对照组比较差异有显著性(P<0．05),缺氧14d达高峰并维持于高水平。缺氧性肺血管重塑(HPSR)、右心室肥大于缺氧14d后出现。TCF-β1 mPNA对照组中膜平滑肌细胞和外膜成纤维细胞呈弱阳性表达,缺氧3d、7d表达增高不明显,缺氧14d增高(0．385±0.028,P<0.01),并维持于高水平,TGF-β1 mRNA于肺动脉中膜和外膜表达;TGF-β1蛋白在对照组呈弱阳性,缺氧3d表达增强(0．198±0．031,P<0．01),缺氧7d组达高峰(0．267±0．035,P<0．01),随着缺氧时间进一步延长,TGF-β1水平逐渐向基线水平回降,TGF-β1蛋白于肺动脉中膜和外膜表达。结论：缺氧诱导TCF-β1表达变化可能在大鼠缺氧性肺动脉高压中起到重要作用。     

茶多酚对低氧肺动脉高压大鼠Smac表达的影响

目的:探讨茶多酚在预防肺动脉高压中的作用及可能机制.方法:24只雄性SD大鼠随机分为对照组、肺动脉高压组和茶多酚组,后两组置于低氧舱内4周,每组各8只.每日低氧前茶多酚组予茶多酚200 mg/(kg·d)灌胃,对照组、肺动脉高压组予等量生理盐水灌胃.比较各组平均肺动脉压(mPAP)、右心室肥厚程度、肺小动脉管壁厚度,及肺动脉平滑肌细胞(PASMC)凋亡、肺组织Smac mRNA表达水平.结果:茶多酚显著降低mPAP,减轻右心室肥厚、肺小动脉管壁厚度,上调Smac基因表达,促进PASMC凋亡(P＜ 0.01或P＜ 0.05).结论:茶多酚预防肺动脉高压可能是通过促进Smac基因表达,促进PASMC凋亡来实现的.     

低氧诱导因子-1α和血管内皮生长因子在玉树地震救援人员急性高原反应低氧性肺动脉高压发生中的作用

目的 观察低氧诱导因子-1α(HIF-1α)和血管内皮生长因子(VEGF)在急性高原反应(AHAR)低氧性肺动脉高压(HPH)发生中的作用及返回低海拔后的变化。方法 选择2010年4月14日青海玉树大地震后由低海拔(1 500m)快速进入高海拔地区(3 700m)并从事重体力劳动的18～35岁男性官兵96名,根据AHAR症状评分分为无AHAR组(25名)、轻中度AHAR组(47名)和重度AHAR组(24名);在高海拔地区停留50 d后下撤前及返回低海拔地区后12h、15d分别测定平均肺动脉压(mPAP)和血清HIF-1α、VEGF水平。同时选择低海拔地区50名健康官兵作为对照。结果 高海拔无AHAR组mPAP(mm Hg,1 mm Hg=0.133 kPa)和血清HIF-1α(pg/L)、VEGF(ng/L)水平（分别为24.23±1.56、68.80±7.52、82.56±6.32）明显高于低海拔对照组(18.50±1.30、50.95±3.33、65.78±4.03);且随AHAR加重,各指标进一步升高,高海拔轻中度AHAR组分别为28.42±1.32、88.10±9.20、104.82±10.36,重度AHAR组分别为34.70±2.94、117,93±13.46、136.77±12.03,组间两两比较差异均有统计学意义(均P＜0.01)。高海拔AHAR总计分与mPAP、血清HIF-1α、VEGF水平均呈显著正相关(r值分别为0.672、0.737、0.634,均P＜0．01);mPAP与血清HIF- 1α、VEGF水平呈显著正相关(r值分别为0.706、0.638,均P＜0.01)。与低海拔对照组比较,96名官兵进入高海拔地区50 d时mPAP (mm Hg)和血清HIF- 1α (pg/I)、VEGF (ng/L)水平（分别为29.08±4.22、91.16±20.58、107.11±10.32）显著升高(均P＜0.01),返回低海拔地区12 h(分别为23.05±3.18、70.99±8.22、78.65±6.47)、15 d（分别为18.96±1.75、52.31±4.92、63.08±4.55）时各指标显著下降,且15d明显低于12 d(均P＜0．01),15d时各指标与低海拔对照组比较差异均无统计学意义(均P＞0.05)。结论 人体在高海拔低氧地区并从事重体力劳动时,AHAR越重,mPAP和血清HIF-1α、VEGF水平就越高,说明HPH与HIF-1α、VEGF水平升高有密切关系;返回低海拔地区后12h上述指标有显著改善,15d可恢复到正常水平。     

胸交感神经阻滞降低大鼠低氧性肺动脉高压的机制

目的研究胸交感神经阻滞(TSB)降低大鼠低氧性肺动脉高压(HPH)的机制。方法选择健康雄性Wistar大鼠48只,随机分为常氧组、低氧组、低氧/罗哌卡因组、低氧/生理盐水组各12只。常氧组在常氧常压下饲养3周,其余3组大鼠在自制常压低氧(10±0.5)%舱内饲养3周,同时低氧/罗哌卡因组和低氧/生理盐水组给与胸段硬膜外腔置管分别注入0.2%罗哌卡因和0.9%生理盐水各50μl行胸段(胸1-5)交感神经阻滞术(TSB)。用放射免疫分析法测定大鼠血清环磷酸鸟苷(cGMP)和血清肿瘤坏死因子α(TNF-α)含量; RT-PCR和蛋白印迹法测定大鼠肺组织c AMP反应元件结合蛋白(CREB)的基因表达和蛋白质表达。结果①低氧/罗哌卡因组大鼠血浆cGMP水平增加和血清TNF-α水平降低,与低氧组、低氧/生理盐水组比较差异显著。②低氧/罗哌卡因组大鼠肺小动脉血管CREB的基因表达和蛋白质表达均降低,而低氧组、低氧/生理盐水组表达增加。结论 TSB可降低HPH大鼠血清TNF-α水平,升高血浆cGMP水平。同时能逆转肺小动脉CREB的基因和蛋白质过表达现象,这可能是TSB降低HPH和改善血管重构重要的分子学机制之一。     

肺动脉高压的病理生理

肺循环压力受肺血流、肺血管张力、肺血管容积和肺静脉压力的控制。肺血管收缩或肺血管床损伤引起了肺血管床的堵塞或破坏,肺血管床可灌注的容积严重减少时,则肺动脉高压出现。当可灌注的肺血管床容积减少至50%时,肺动脉压可升至4.0～4.7千帕和钙离子拮抗剂的使用即为通过本途径起作用的。对于平滑肌细胞内其他信号传递系统的研究也均在进行中。在慢性肺动脉高压时,肺小动脉平滑肌增生肥大形成中层肥厚,原来不存在平滑肌的细动脉有平滑肌出现是人所共知的肺动脉高压的典型标志。同时平滑肌细胞表型的转变也有重要的病理生理作用。平滑肌细胞在肺动脉高压时由收缩表型(细胞内主要充满肌纤维,其功能主要是收缩)为主变为有更多的分泌表型出现。分泌表型的平滑肌细胞内肌纤维减少而粗面内质网等细胞器增多,其合成及分泌功能增强。分泌表型的细胞合成及分泌的弹性蛋白与胶原蛋白明显增多。因此,慢性肺动脉高压时的动脉壁肥厚,除细胞外还有细胞外结缔组织蛋白含量的增加,特别是胶原蛋白的增加使管壁变硬阻力加大是慢性肺动脉高压的一个重要病理生理变化。已有实验证明,用抑制胶原生成的药物可减低缺氧引起的慢性肺动脉压升高的程度。此外,平滑肌也通过产生影响其他细胞的因子影响血管壁其他细胞的代谢而影响肺动脉高压。其生成的致弹性蛋白生成因子,能促使外膜成纤维细胞生成弹性蛋白和胶原蛋白,并能促使内皮细胞生成弹性蛋白和胶原蛋白。肺血管外膜成纤维细胞的变化肺动脉高压时内皮细胞释放因子引起成纤维细胞增生已有实验证实。当内皮细胞分别在5.3千帕(40毫米汞柱)和1.3千帕(10毫米汞柱)压力下生长时,5.3千帕压力下生长的内皮细胞培养液中有一种因子可使成纤维细胞增殖为1.3千帕者的9倍,成纤维细胞的增殖及其在平滑肌细胞产生的致弹性蛋白生成因子的影响下,产生的结缔组织蛋白增多均可使肺血管阻力增加。此外,肺动脉高压时成纤维细胞还通过向内皮下移行并转化为平滑肌细胞而起作用。吸入10%低氧气体24小时,可见成纤维细胞移至内皮下,并可见其细胞内出现肌纤维并逐渐转化为平滑肌细胞。由于肺血管壁中各种细胞在肺动脉高压的病理生理中有重要作用,因此,找出导致上述变化因子,自基因水平加以抑制,可为解决病理性肺动脉高压问题开辟一个新途径。     

白藜芦醇苷对大鼠慢性常压低氧性肺动脉高压的防治作用

目的 :观察白藜芦醇苷 (PD )对大鼠慢性常压低氧性肺动脉高压的防治作用并探讨其作用机制。方法 :2 9只健康SD大鼠随机分为正常对照组、单纯低氧组和低氧加白藜芦醇苷 (PD )组。右心导管法检测大鼠平均肺动脉压力 (mPAP) ,观察右室 /左室 室间隔比值 (R/L S) ,微量滴定法、免疫生化法及化学发光法检测血浆和肺匀浆中磷脂酶A2 (PLA2 )活性、血栓素B2 (TXB2 )、6 酮 前列腺素1α(6 k PGF1α)、丙二醛 (MDA)含量及超氧化物歧化酶 (SOD)活性的变化。结果 :与单纯低氧组比较 ,应用PD 2 1d后 ,mPAP从 (4 13± 0 44 )kPa降至 (3 48± 0 3 8)kPa (P <0 0 1) ,R/L S由 0 3 6± 0 0 5降至 0 3 1± 0 0 3 (P <0 0 1) ;血浆及肺匀浆中PLA2 活性、TXB2 和 6 k PGF1α含量、MDA浓度及SOD活性改变均有显著性差异。结论 :PD可有效防治慢性常压低氧性肺动脉高压 ,其机制与抑制PLA2 活性及其相关炎症介质和降低自由基的毒性等作用有关     

辛伐他汀对慢性低氧高二氧化碳所致大鼠肺动脉高压的干预作用

目的 探讨辛伐他汀对慢性低氧高二氧化碳致大鼠肺动脉高压的干预作用.方法 采用慢性低氧高二氧化碳肺动脉高压大鼠模型.30 只SD 大鼠随机分为常氧正常4 周组(NC)、低氧高二氧化碳4 周组(4WH)和低氧高二氧化碳4 周辛伐他汀干预组(Sim).HE 染色和电镜观察各组大鼠右肺病理和超微结构变化;实时定量逆转录-聚合酶链反应方法观察各组大鼠左肺组织碱性成纤维细胞生长因子(bFGF)和核因子κB mRNA 的转录情况,用ELISA 双抗体夹心法测定各组大鼠右肺组织匀浆血管内皮细胞生长因子(VEGF)和血清IL-6 含量.结果 4WH 大鼠平均肺动脉压力、右心肥厚指数高于NC 和Sim 组(P ＜0.01);光镜显示:4WH 组肺细小动脉血管壁平滑肌层明显增生,电镜下内皮细胞向管腔突起,胶原纤维增多,平滑肌细胞增生;而NC 组、Sim 组大鼠肺组织血管壁的改变明显减轻.与4WH 组相比,NC 组、Sim 组大鼠肺组织bFGF mRNA 和NF-κB mRNA 蛋白表达降低(P ＜0.05).Sim 组大鼠右肺组织匀浆中VEGF 和血清IL-6 含量较4WH 组低(P ＜0.01).结论 辛伐他汀可以降低慢性低氧高二氧化碳肺动脉高压大鼠肺动脉压力,其机制可能是减低肺组织bFGF mRNA 和NF-κB mRNA 蛋白表达,从而降低肺组织VEGF 和血清IL-6 的含量.     

高原慢性肺心病急性加重期血清碱性成纤维细胞生长因子水平与肺动脉压的关系及其干预的研究

目的:探讨碱性成纤维细胞生长因子(bFGF)在低氧性肺动脉高压发病中的作用及其干预治疗。方法:60例高原慢性肺心病急性加重期患者随机分为3组,每组20例。3组抗感染、祛痰、平喘治疗相同。氧疗组:给予持续吸氧,氧流量1.5~3.0L.min-1,使动脉血氧分压(PaO2)保持在55mmHg以上;红景天组:口服红景天胶囊每次2.0g,每天3次.d-1。常规治疗组:给予常规治疗。在治疗前、治疗3周后,采用酶联免疫吸附法检测血清bFGF水平,用超声心动仪测平均肺动脉压(mPAP)和用血气分析仪测PaO2。并以30例慢性阻塞性肺疾病(COPD)和30例当地健康人作对照。结果:肺心病组血清bFGF(87.25±12.10)pg·mL-1、mPAP(45.66±5.61)mmHg,显著高于COPD组[分别为(55.02±9.08)pg·mL-1、(22.98±2.41)mmHg,均P<0.01),COPD组显著高于健康人对照组[分别为(49.83±8.78)pg·ml-1、(20.34±2.23)mmHg,均P<0.01);肺心病组PaO2(38.68±4.46)mmHg显著低于COPD组(58.05±6.18)mmHg,COPD组显著低于健康人对照组(66.57±5.48mmHg,均P<0.01)。肺心病组和COPD组血清bFGF水平与mPAP均呈显著正相关(r=0.788、0.674,均P<0.01),与PaO2水平呈显著负相关(r=-0.735、-0.587,均P<0.01)。治疗后,肺心病3组患者血清bFGF、mPAP较治疗前显著降低、PaO2显著升高(均P<0.01),但氧疗组改善较红景天组显著、红景天组较常规治疗组显著,(均P<0.05)。结论:高原慢性肺心病患者血清bFGF水平明显升高,可能与其慢性低氧性肺动脉高压的形成有一定关系,氧疗和红景对其有显著治疗作用。     

Guns and Knives in New Mexico: Patterns of Penetrating Trauma, 1978–1993

Objective: To identify patterns of nonfatal and fatal penetrating trauma among children and adults in New Mexico using ED and medical examiner data.
Methods: The authors retrospectively sampled in 5-year intervals all victims of penetrating trauma who presented to either the state Level-1 trauma center or the state medical examiner from a 16-year period (1978–1993). Rates of nonfatal and fatal firearm and stabbing injury were compared for children and adults.
Results: Rates of nonfatal injury were similar (firearm, 34.3 per 100,000 person-years; stabbing, 35.1). However, rates of fatal injury were significantly different (firearm, 21.9; stabbing, 2.7; relative risk: 8.2; 95% confidence interval: 5.4, 12.5). From 1978 to 1993, nonfatal injury rates increased for children (p = 0.0043) and adults (p < 0.0001), while fatal penetrating injury remained constant. The increase in nonfatal injury in children resulted from increased firearm injury rates. In adults, both stabbing and firearm nonfatal injury rates increased.
Conclusions: Nonfatal injury data suggest that nonfatal violence has increased; fatal injury data suggest that violent death rates have remained constant. Injury patterns vary by age, mechanism of trauma, and data source. These results suggest that ED and medical examiner data differ and that both are needed to guide injury prevention programs.     

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.     

Systematic Reviews Published in the January 2011 Issue of The Cochrane Library

ABSTRACT

The Cochrane Library of Systematic Reviews is published quarterly as a DVD and monthly online. The January 2011 issue (first quarterly DVD for 2011) contains 4515 complete reviews, 1985 protocols for reviews in production, and 13,521 one-page summaries of systematic reviews published in the general medical literature. In addition, there are citations of 641,000 randomized controlled trials, and 14,018 cited papers in the Cochrane methodology register. The health technology assessment database contains over 9300 citations. One hundred and seven new reviews have been published in the last 3 months, of which five have potential relevance for practitioners in pain and palliative medicine.     

Interprofessional approaches to creating safe,high quality health care

Three supplementary perspectives are presented arguing that interprofessional collaboration is both necessary and desirable. Nonetheless, there are often too many serious intra-professional barriers and obstacles to interprofessional collaboration to make it successful. Some of these barriers, it is argued and illustrated, are found in the multiple ways in which professional identity is tacitly acquired and embodied in the practitioners' habitual, everyday practice. The paper then explores ways in which reflection, especially Second order reflection, can help to elucidate and overcome these obstacles, as well as increasing professional adaptability and competence.     

Modified micro-superior percutaneously-assisted total hip: early experiences & case reports

Because of the extensile nature and familiarity of the standard posterior-lateral approach to the hip, a family of "micro-posterior" approaches has been developed. This family includes the Percutaneously-Assisted Total Hip (PATH) approach, the Supercapsular (SuperCap) approach and a newer hybrid approach, the Supercapsular Percutaneously-Assisted Total Hip (SuperPATH) approach. Such approaches should ideally provide a continuum for the surgeon: from a "micro" (external rotator sparing) posterior approach, to a "mini" (external rotator sacrificing) posterior approach, to a standard posterior approach. This could keep a surgeon within his comfort zone during the learning curve of the procedure, while leaving options for complicated reconstructions for the more practiced micro-posterior surgeons. This paper details one author's experiences utilizing this combined approach, as well as permutations of this entire micro-posterior family of approaches as applied to more complex hip reconstructions.     

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.     

Prise en charge des entorses externes de cheville : étude clinique préliminaire sur l’efficacité du dispositif Myolux™

Ankle sprains are the most common injury of the musculoskeletal system and are associated with significant societal and economic impacts. It has been proven that classical therapeutic strategies may not be effective in preventing recurrent injuries: the recurrence rates reported in the literature can reach 73%. In order to provide an effective rehabilitation solution, a destabilizing orthosis was developed. This device is equipped with a mechanical articulator reproducing the subtalar mechanics and placed under the heel. In this paper, we present the main results of a preliminary clinical study conducted between 2004 and 2007. All subjects included in this study were treated with the abovementioned orthosis during 10 rehabilitation sessions of 30 minutes each. Data show a relatively low recurrence rate of 12% for the overall population. Moreover, it's of primary importance to note that this satisfactory ratio is largely reduced (3% of recurrence rate) for the 29 patients who performed one training session per month after the 10th initial rehabilitation sessions. Hence, the destabilizing orthosis appears to be an effective solution to prevent recurrent ankle sprains. However, joint protection requires long-term and regular training sessions. This result has motivated the development of a similar device allowing patients to perform training sessions at home. Finally, data obtained in this study are promising awaiting the final results of the comparative, multicentric and independent clinical trials currently managed by the Hospices Civils de Lyon.