白蛋白微球颈外动脉灌注后经动—静脉短路溢出量及主要脏器分布的分析

目的　了解平均粒径 53 6μm的白蛋白微球 (AMS)经颈外动脉灌注后 ,经动 -静脉短路 (AVA)溢出部分微球的量和在重要脏器的分布。方法　经家兔颈外动脉灌注1 2 5I标记的微球后抽取颈外静脉血 ,测定放射剂量和静脉血中所含微球的比例 ;观察微球经家兔颈外静脉推注后全身各重要脏器组织中微球的分布情况。结果　经颈外动脉注入微球后仅有 0 51 %的放射剂量出现在静脉血中。微球经静脉推注后 ,主要聚集于肺 ,其它各重要脏器未见分布。结论　以平均粒径 53 6μm的白蛋白微球作为口腔颌面部肿瘤栓塞化疗药物的载体 ,全身副作用轻微 ,是安全可行的     

经皮穴位电刺激对咪达唑仑镇静作用的影响

目的:探讨经皮穴位电刺激对咪达唑仑镇静作用的影响。方法:选择在我院择期椎管内麻醉行骨科下肢手术患者80例,随机分为两组:经皮穴位电刺激组和对照组,每组均40例。经皮穴位电刺激组在完成椎管内麻醉后开始给予经皮穴位电刺激,刺激参数频率2/100 Hz,波宽0.2~0.6 ms,调节刺激电流至患者可耐受的最大强度,穴位选择双侧合谷穴、内关穴,20 min后靶控输注咪达唑仑。对照组患者在相应穴位贴电极片,并连接刺激器,不予电刺激。对患者进行警觉/镇静(OAA/S)评分,依据脑电双频指数(BIS)调整咪达唑仑靶控输注浓度。观察并记录OAA/S评分首次为3分时的目标靶浓度(Ce)、BIS、咪达唑仑用量、平均动脉压(MAP)、血氧饱和度(SpO2)、心率(HR)及氟马西尼使用和不良反应发生情况。结果:经皮穴位电刺激组在OAA/S评分首次为3分时咪达唑仑效应室靶浓度较对照组低[(60.3±8.0)ng/mL vs.(66.8±8.5)ng/mL],经皮穴位电刺激组的咪达唑仑用量少于对照组[(4.9±0.6)mg vs.(5.3±0.5)mg],差异均有统计学意义(P<0.05);经皮穴位电刺激组术后应用氟马西尼12例,低于对照组的28例,差异有统计学意义(P<0.05);2组间BIS、SpO2、MAP、HR差异无统计学意义。结论:经皮穴位电刺激能够增强咪达唑仑的镇静作用,减少咪达唑仑用量。     

硬膜外间歇脉冲注入技术用于分娩镇痛的效果

目的 探讨硬膜外间歇脉冲注入技术（PIEB）在产妇自控硬膜外分娩镇痛中的效果及对分娩结局的影响。
方法 选择行硬膜外分娩镇痛的单胎、头位、足月妊娠产妇100例,年龄18～38岁,BMI 20～32 kg/m²,ASA Ⅰ或Ⅱ级,采用随机数字表法分为两组：PIEB组和连续硬膜外输注组（CEI组）,每组50例。两组镇痛药配方均为0.08％罗哌卡因＋0.4 μg/ml舒芬太尼。PIEB组参数设置：脉冲频率每小时1次,剂量10 ml,注药速率400 ml/h,单次剂量10 ml,间隔20 min。CEI组参数设置：背景输注速率10 ml/h,单次剂量10 ml,间隔20 min。记录产妇分娩镇痛前、镇痛后1、2、3、5 h、宫口开全和分娩时的VAS疼痛评分;产妇首次按压时间、按压次数、镇痛泵用药总量、镇痛时间;总产程时间、产后出血量、新生儿Apgar评分、产妇对分娩镇痛效果满意度评分;感觉阻滞平面达T4的例数、改良Bromage评分;以及低血压、恶心呕吐等不良反应发生情况。
结果 与分娩镇痛前比较,分娩镇痛后两组产妇VAS疼痛评分明显降低（P<0.05）。与CEI组比较,PIEB组镇痛后2、3、5 h、宫口开全、分娩时VAS疼痛评分均明显降低（P<0.05）,首次按压时间明显延迟（P<0.01）,按压次数、镇痛泵用药总量明显减少（P<0.01）。与CEI组比较,PIEB组产妇满意度评分明显增高（P<0.01）,感觉阻滞平面达T4的产妇比例明显升高（P<0.05）。两组总产程时间、产后出血量、新生儿Apgar评分差异无统计学意义。两组低血压和恶心呕吐等不良反应发生率差异无统计学意义。
结论 PIEB可安全有效地用于产妇自控硬膜外分娩镇痛,其效果优于连续硬膜外输注,产妇满意度高,且不影响分娩结局。     

Long-Term Results of Prophylactic Donor Lymphocyte Infusions for Patients with Multiple Myeloma after Allogeneic Stem Cell Transplantation

The major reason for treatment failure after allografting in multiple myeloma (MM) is relapse. Donor lymphocyte infusions (DLIs) are considered a valuable post-transplant strategy mainly for relapsed patients but using them to prevent relapse in MM has been reported rarely. In the present study, we examined the efficacy of prophylactic DLIs after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in myeloma patients with a long-term follow-up of more than 5 years. A total of 61 patients with MM who did not relapse or develop disease progression after allo-HSCT were treated with prophylactic DLI in an escalating fashion (overall 132 DLI procedures) to deepen remission status and prevent relapse. Overall response rate to DLI was 77%. Thirty-three patients (54%) upgraded their remission status, 41 patients (67%) achieved or maintained complete remission, and 26% achieved a molecular remission. Incidence of acute graft-versus-host disease (GVHD) grade II to IV was 33% and no DLI-related mortality was noted. After a median follow-up of 68.7 months from first DLI the estimated 8-year progression-free survival (PFS), and overall survival (OS) in a landmark analysis was 43% (95% confidence interval [CI], 28% to 57%) and 67% (95% CI, 53% to 82%), respectively, with best outcome for patients who acquired molecular remission (8-year PFS was 62% and 8-year OS was 83%). Prophylactic escalating DLI in a selected cohort of MM patients to prevent relapse after allograft resulted in a low incidence of severe GVHD and encouraging long-term results, especially if molecular remission is achieved.     

GAP,an aequorin-based fluorescent indicator for imaging Ca2+ in organelles

Genetically encoded calcium indicators allow monitoring subcellular Ca²⁺ signals inside organelles. Most genetically encoded calcium indicators are fusions of endogenous calcium-binding proteins whose functionality in vivo may be perturbed by competition with cellular partners. We describe here a novel family of fluorescent Ca²⁺ sensors based on the fusion of two Aequorea victoria proteins, GFP and apo-aequorin (GAP). GAP exhibited a unique combination of features: dual-excitation ratiometric imaging, high dynamic range, good signal-to-noise ratio, insensitivity to pH and Mg²⁺, tunable Ca²⁺ affinity, uncomplicated calibration, and targetability to five distinct organelles. Moreover, transgenic mice for endoplasmic reticulum-targeted GAP exhibited a robust long-term expression that correlated well with its reproducible performance in various neural tissues. This biosensor fills a gap in the actual repertoire of Ca²⁺ indicators for organelles and becomes a valuable tool for in vivo Ca²⁺ imaging applications.Ca²⁺ is involved in the regulation of many intracellular processes that take place both in the cytosol and inside organelles (1–3). Therefore, accurate measurement of the calcium concentration ([Ca²⁺]) inside organelles is essential to discriminate discrete Ca²⁺ signals between the different compartments. Although synthetic Ca²⁺ indicators can be loaded into organelles, the signal has poor selectivity, as the dye is also present in the cytosol and must be carefully removed before measurements (4). The main advantage of Genetically Encoded Ca²⁺ Indicators (GECIs) is their ability to be targeted to specific intracellular locations. Both bioluminescent and fluorescent proteins have been successfully used to measure subcellular [Ca²⁺]. The photoprotein aequorin (5), purified from the jellyfish Aequorea victoria, was the first protein-based Ca²⁺ indicator, injected into cells in the early 1970s (6). After cloning of its cDNA (7), recombinant aequorin became the most frequently used probe to measure Ca²⁺ in organelles, including mitochondria (8), the endoplasmic reticulum (ER) (9), the nucleus (10), the Golgi apparatus (11), or secretory vesicles (12).Fluorescent GECIs achieve a better spatial resolution than bioluminescent sensors. They are generally composed of one or two fluorescent proteins, most of them variants of GFP, fused to a Ca²⁺-binding protein (13). Recently, a single EF-hand motif has been inserted in the GFP moiety to generate a Ca²⁺ fluorescent probe (14). Since the first cameleon based on FRET (15), the number of GECIs has exponentially increased, attempting optimization of critical features such as adequate expression, signal strength, or dynamic range. However, the in vivo use in mammals, one of the main applications of GECIs, has grown more slowly and has disclosed severe limitations (16, 17). Transgenic sensors usually showed a low expression, often resulting in its inactivation or reduced dynamic range. With the exception of troponin derivatives, most of the available GECIs, namely cameleons, camgaroos, pericams, or GCaMPs (circularly permutated EGFP-based Ca²⁺ sensors), are based on calmodulin, a highly regulated ubiquitous protein that binds a large number of targets (13). Although the interference with endogenous calmodulin has been reduced in the improved cameleons (18), the interaction with other cellular proteins cannot be ruled out. Thus, the loss of Ca²⁺ sensitivity observed in vivo may reflect the interaction of the probe with endogenous partners, which may disturb cellular functions.The jellyfish aequorin exhibits a number of advantages over mammalian EF-hand proteins. It is not toxic and appears not to interfere with other intracellular Ca²⁺-binding molecules, even when microinjected at high concentrations in mammalian cells. Moreover, the use of aequorin as a bioluminescence sensor has been extensively reported, ranging from subcellular Ca²⁺ measurements in many different cell types up to whole organisms, including transgenic animals (19–21).Here we describe a family of fluorescent Ca²⁺ sensors based on the fusion of two jellyfish proteins, GFP and apoaequorin. This Ca²⁺ probe shows a larger dynamic range compared with other GECIs and a robust photonic and thermal stability. It can be targeted to distinct compartments such as the nucleus, cytosol, or mitochondria, where it selectively and accurately monitors dynamic Ca²⁺ changes. In addition, we have generated a variant with a lower Ca²⁺ affinity suited for imaging Ca²⁺ changes in organelles with high resting [Ca²⁺] such as the ER or the Golgi apparatus. Finally, we demonstrate its in vivo applicability by generating transgenic mice where the Ca²⁺ biosensor maintained its in vitro features.     

口腔科常用医疗器械清洗消毒效果的评价

目的评价口腔科医疗器械常规清洗消毒的效果。方法选择2013年7月～12月口腔科使用过的非一次性医疗器械（拔牙钳、车针）共36669件,消毒供应室清洗消毒处理前后,对物体表面口腔常见的变形链球菌、白色念珠菌、金黄色葡萄球菌以及乙肝病毒进行检测,并用目测法分析清洗的质量,测评临床的满意度。结果（1）器械清洗消毒质量的合格数为35395件,合格率达到96．52％;（2）细菌和病毒检测结果显示,除了工作室桌子有10次细菌不达标以外,其余均未检出细菌和病毒;（3）紫外照射与高压的消毒效果差距较大,未高压的灭菌消毒效果低于高压的灭菌消毒效果;（4）临床使用满意度达到95．83％。结论经规范化清洗消毒与管理,基本能确保口腔器械的卫生安全,所采用的清洗消毒措施,在一定程度上能有效控制医院感染的发生。     

持续颅内压监测下观察甘露醇不同输注速度的降压效果

目的了解不同速度静脉滴注甘露醇降压效果及作用维持时间。方法将需要定时使用甘露醇的患者随机分为3组，观察1组：10min内输完，观察2组：11～20min输完，观察3组：21～30min输完，分别在输注甘露醇前和输完甘露醇时、输完甘露醇后30min、输完甘露醇后6h记录颅内压（ICP）值，观察不同速度输注甘露醇患者ICP的变化。结果3组输完甘露醇后30min内患者的ICP都有下降，以观察1组变化的幅度最大。6h后患者ICP恢复至使用甘露醇前的水平。结论使用甘露醇降压时，输注速度越快，其降压效果越好，建议甘露醇使用的间隔时间以6h为宜。     

液氮冷冻治疗仪辅助建立兔股骨头缺血性坏死模型

目的:为股骨头缺血性坏死(avascular necrosis of the femoral head,ANFH)的治疗研究建立动物模型。方法:40只健康大白兔建立双侧股骨头骨缺损模型,并用液氮冷冻治疗仪将股骨头冷冻坏死,术后2、4、6、8周处死兔子各4只,对兔子股骨头进行大体标本观察及取股骨头摄X线片。结果:(1)大体标本观察显示,术后2周时可见头部规整、光滑,未见明显塌陷;术后4~6周可见软骨面剥离;术后8周可见骨修复与骨吸收同时存在,股骨头有变小,有轻度塌陷改变,软骨呈苍白色,骨质脆。(2)X线检查示,术后2周可见骨密度有所增加,骨小梁结构完整;术后4~6周可见骨密度增加,骨小梁结构出现紊乱;术后8周可见骨小梁结构紊乱,软骨下囊性变。结论:液氮冷冻建立的兔ANFH模型适合模拟临床治疗的研究。     

Subanesthetic,Subcutaneous Ketamine Infusion Therapy in the Treatment of Chronic Nonmalignant Pain

This study was designed to describe the efficacy and toxicity of subcutaneous ketamine infusions and sublingual ketamine lozenges for the treatment of chronic nonmalignant pain. Data were collected prospectively on 70 subjects managed in an academic, tertiary care hospital between 2007 and 2012 who received between 3 and 7 days of subanesthetic, subcutaneous ketamine infusion. Data were analyzed for efficacy, adverse effects, and reduction in use of opioid medication. We also analyzed whether subsequent treatment with sublingual ketamine lozenges resulted in longer-term efficacy of the beneficial effects of the initial ketamine infusion. There was a significant reduction in pain intensity measured by numerical rating scale (NRS) from mean of 6.38 before ketamine to 4.60 after ketamine (P < .005) that was sustained for between 3 months and 6 years. In subjects on opioids, there was a significant reduction in opioid use at the end of the ketamine infusion from a mean morphine equivalent dose (MMED) of 216 mg/day before ketamine to 89 mg/day after ketamine (P < .005). The overall reduction in opioid use after ketamine infusion was 59%. No subjects increased their use of opioids during their hospitalization for the ketamine infusion. A small proportion of subjects who responded to the infusion were continued on ketamine lozenges. This group was followed for between 3 months and 2 years. The use of ketamine lozenges after the infusion resulted in 31% of these subjects being able to cease their use of opioids compared with only 6% who did not receive ketamine lozenges. Eleven percent of subjects who received lozenges subsequently increased their opioid usage. Adverse effects were fairly common, but only mild, with 46% of patients experiencing light-headedness and dizziness, 25% tiredness and sedation, 12% headaches, 12% hallucinations, and 8% vivid dreams. Adverse effects were easily managed by reducing the rate of the ketamine infusion. The administration of subanesthetic, subcutaneous ketamine infusion was well tolerated, with mostly mild adverse effects and no serious adverse effects. The infusion provided significant pain relief in subjects who had failed a wide range of pharmacological and cognitive behavioral therapies. In addition, the results indicate that sublingual ketamine lozenges offer a promising therapeutic option for longer-term relief of chronic nonmalignant pain. The ketamine lozenges have been shown to have acceptable storage stability, and the sublingual bioavailability is sufficiently high and reproducible to support its use in this context.     

Continuous paravertebral block for pain relief in unilateral multiple rib fracture: A case series

Rib fracture secondary to blunt chest trauma is an indicator of the severity of injury. It is one of the factors associated with morbidity and mortality in blunt chest trauma. Current management of such patients stresses on provision of adequate analgesia and early institution of aggressive physiotherapy. The current study evaluates the analgesic efficacy of continuous thoracic paravertebral infusion of Bupivacaine in unilateral multiple rib fracture (MRF).

Study design

Retrospective, non-randomized case series of 11 patients with unilateral MRF.

Method

Thoracic paravertebral (TPV) space on the side of fractured ribs was catheterized with an epidural catheter. TPV block was initiated with 0.3 ml/kg body weight of 0.25% Bupivacaine with adrenaline. The block was maintained with a continuous infusion of 0.2% Bupivacaine 30 min later, at 0.1–0.2 ml/(kg/h) for a total of 4 days or for the length of admission, which ever was earlier.

Patients were monitored for pain scores at rest and when asked to cough and vital capacity manoeuvre, respiratory rate, oxygen saturation, oxygen index (PaO₂/FiO₂) and percentage change in incentive spirometry.

There were significant improvements in pain scores at rest (p = 0.0097), on cough (p = 0.0039) and vital capacity manoeuvre (p = 0.0078). Other respiratory parameters like respiratory rate, PaO₂ and oxygen index showed persistent improvement from baseline. None of the patients had any complications or side effect related to procedure and technique.

Conclusion

Our study confirms that continuous TPV block is a safe and effective technique for analgesia in patients with unilateral MRF.