BACKGROUND & AIMS: :Consonant identification was measured for a stationary and amplitude-modulated noise masker in four listeners with flat cochlear hearing loss, and four age-matched normal-hearing listeners. The masker modulation rate was systematically varied between 2 and 128 Hz. Masking release (MR), that is better identification performance in fluctuating, than in stationary noise, was highest in a masker fluctuating at 8-16 Hz in all normal-hearing listeners. In comparison, MR was only observed in two out of the four impaired listeners. In these listeners, MR was poorer than normal, and peaked at lower rates, that is 2 or 8 Hz. MR corresponded to increased reception of information for voicing, place, and manner between 2 and 64 Hz in all normal-hearing listeners. In impaired listeners, increased reception of information was mainly observed for manner, and mainly reduced for place, but these differences were not significant. For all phonetic features, MR was observed at lower masker fluctuation rates (< or =32 Hz) than in normal-hearing listeners. This study therefore shows that cochlear damage affects MR, both quantitatively and qualitatively.

背景与目标： ：在四个平直的人工耳聋听力下降的听众和四个年龄相匹配的正常听力的听众中，对平稳和调幅的噪声掩蔽器的辅音识别进行了测量。掩蔽调制率在2到128 Hz之间系统地变化。在所有正常听力的听众中，以8-16 Hz波动的掩蔽器中，掩蔽释放（MR）的波动性要好于平稳噪声，这在静态噪声中具有更好的识别性能。相比之下，只有四个受损听者中有两个观察到了MR。在这些听众中，MR比正常人差，并且以较低的频率（即2或8 Hz）达到峰值。 MR对应于在所有正常听力的收听者中2至64 Hz之间的声音，位置和方式信息接收的增加。在听力受损的听众中，主要是通过方式观察到了信息接收的增加，而对于场所则主要是观察到的减少，但是这些差异并不明显。对于所有的语音特征，与正常听力的听众相比，在较低的掩蔽者波动率（<或= 32 Hz）下观察到了MR。因此，这项研究表明，耳蜗损害在数量和质量上都影响MR。

BACKGROUND & AIMS: :Hepatic steatosis is defined by an increased content of hepatocellular lipids (HCLs) and is frequently observed in insulin-resistant states including type 2 diabetes mellitus. A dietary excess of saturated fat contributes significantly to HCL accumulation. Elevated HCL levels mainly account for hepatic insulin resistance, which is probably mediated by partitioning of free fatty acids to the liver (fat overflow) and by an imbalance of adipocytokines (decreased adiponectin and/or increased proinflammatory cytokines). Both free fatty acids and adipocytokines activate inflammatory pathways that include protein kinase C, the transcription factor nuclear factor kappaB, and c-Jun N-terminal kinase 1 and can thereby accelerate the progression of hepatic steatosis to nonalcoholic steatohepatitis and cirrhosis. Proton magnetic resonance spectroscopy has made it possible to quantify HCL concentrations and to detect even small changes in these concentrations in clinical settings. Moderately hypocaloric, fat-reduced diets can decrease HCL levels by approximately 40-80% in parallel with loss of up to 8% of body weight. Treatment with thiazolidinediones (e.g. pioglitazone and rosiglitazone) reduces HCL levels by 30-50% by modulating insulin sensitivity and endocrine function of adipose tissue in type 2 diabetes. Metformin improves hepatic insulin action without affecting HCL levels, whereas insulin infusion for 67 h increases HCL levels by approximately 18%; furthermore, HCL levels positively correlate with the insulin dosage in insulin-treated type 2 diabetes. In conclusion, liver fat is a critical determinant of metabolic fluxes and inflammatory processes, thereby representing an important therapeutic target in insulin resistance and type 2 diabetes mellitus.

背景与目标： 肝脂肪变性是由肝细胞脂质（HCL）含量增加所定义的，并且经常在包括2型糖尿病在内的胰岛素抵抗状态中观察到。饮食中饱和脂肪过多会大大增加HCL的积累。 HCL水平升高主要是肝脏胰岛素抵抗的原因，这可能是由游离脂肪酸在肝脏中的分配（脂肪溢出）和脂肪细胞因子的失衡（脂联素减少和/或促炎细胞因子增加）介导的。游离脂肪酸和脂肪细胞因子均激活包括蛋白激酶C，转录因子核因子kappaB和c-Jun N端激酶1在内的炎症途径，从而可以加速肝脂肪变性发展为非酒精性脂肪性肝炎和肝硬化。质子磁共振波谱使量化HCL浓度和检测临床环境中这些浓度的微小变化成为可能。适度低热量，低脂肪饮食可将HCL水平降低约40-80％，同时最多可减少8％的体重。噻唑烷二酮类药物（例如吡格列酮和罗格列酮）治疗可通过调节2型糖尿病的胰岛素敏感性和脂肪组织的内分泌功能将HCL水平降低30-50％。二甲双胍在不影响HCL水平的情况下改善了肝胰岛素的作用，而胰岛素输注67 h可使HCL水平增加约18％。此外，在用胰岛素治疗的2型糖尿病中，HCL水平与胰岛素剂量呈正相关。总之，肝脏脂肪是代谢通量和炎症过程的关键决定因素，因此代表胰岛素抵抗和2型糖尿病的重要治疗靶标。

BACKGROUND & AIMS: :In 4 experiments, the authors investigated the reversal of spatial congruency effects when participants concurrently practiced incompatible mapping rules (J. G. Marble & R. W. Proctor, 2000). The authors observed an effect of an explicit spatially incompatible mapping rule on the way numerical information was associated with spatial responses. The authors also observed an effect of an incompatible numerical mapping rule (if smaller than 5, press right; if larger than 5, press left) on the Simon effect. This effect was observed only when both tasks used the same effectors. The results point to a shared spatial representation for explicit spatial information (locations) and implicit spatial information (numbers).

背景与目标： ：在4个实验中，作者研究了参与者同时练习不兼容的映射规则时空间一致性效果的逆转（J. G. Marble和R. W. Proctor，2000）。作者观察到明确的空间不兼容映射规则对数字信息与空间响应相关联的方式的影响。作者还观察到不兼容的数字映射规则（如果小于5，请按向右；如果大于5，请按向左）对西蒙效果的影响。仅当两个任务使用相同的效应器时，才观察到这种效果。结果指向用于显式空间信息（位置）和隐式空间信息（数字）的共享空间表示。

BACKGROUND & AIMS: :In vitro experiments and expression patterns have long suggested important roles for the genetically related cytosolic fatty acid binding proteins (FABPs) in lipid metabolism. However, evidence for such roles in vivo has become available only recently from genetic manipulation of FABP expression in mice. Here, we summarize the fuel-metabolic phenotypes of mice lacking the genes encoding heart-type FABP (H-/- mice) or liver-type FABP (L-/- mice). Cytosolic extracts from H-/- heart and skeletal muscle and from L-/- liver showed massively reduced binding of long chain fatty acids (LCFA) and, in case of L-/- liver, also of LCFA-CoA. Uptake, oxidation, and esterification LCFA, when measured in vivo and/or ex vivo, were markedly reduced in H-/- heart and muscle and in L-/- liver. The reduced LCFA oxidation in H-/- heart and L-/- liver was not due to reduced activity of PPARa, a fatty acid-sensitive transcription factor that determines the lipid-oxidative capacity in these organs. In H-/- mice, mechanisms of compensation were partially studied and included a redistribution of muscle mitochondria as well as increases of cardiac and skeletal muscle glucose uptakes and of hepatic ketogenesis. In skeletal muscle, the altered glucose uptake included decreased basal but increased insulin-dependent components. Metabolic compensation was only partial, however, since the H-/- mice showed decreased exercise tolerance. In conclusion, the recent studies established H- and L-FABP as major determinants of regional LCFA utilization; therefore the H-/- and L-/- mice are attractive models for studying principles of fuel selection and metabolic homeostasis.

背景与目标： ：体外实验和表达模式长期以来一直表明遗传相关的胞质脂肪酸结合蛋白（FABPs）在脂质代谢中的重要作用。但是，体内这种作用的证据直到最近才从小鼠中FABP表达的基因操作中获得。在这里，我们总结了缺少编码心脏型FABP（H-/-小鼠）或肝型FABP（L-/-小鼠）的基因的小鼠的燃料代谢表型。 H-/-心脏和骨骼肌以及L-/-肝脏的胞质提取物显示长链脂肪酸（LCFA）的结合大大降低，对于L-/-肝脏，LCFA-CoA的结合也大大降低。当体内和/或离体测量时，LCFA的摄取，氧化和酯化作用在H-/-心脏和肌肉以及L-/-肝中显着降低。 H-/-心脏和L-/-肝脏中LCFA氧化的减少并不是由于PPARa的活性降低，PPARa是一种脂肪酸敏感的转录因子，决定了这些器官中脂质的氧化能力。在H-/-小鼠中，对补偿机制进行了部分研究，包括肌肉线粒体的重新分布以及心肌和骨骼肌葡萄糖摄取的增加以及肝脏生酮的发生。在骨骼肌中，葡萄糖摄取的改变包括基础减少，但胰岛素依赖性成分增加。但是，由于H-/-小鼠表现出降低的运动耐力，因此代谢补偿仅是部分的。总之，最近的研究确定了H-FABP和L-FABP是区域LCFA利用的主要决定因素。因此，H-/-和L-/-小鼠是用于研究燃料选择和代谢稳态的原理的有吸引力的模型。

BACKGROUND & AIMS: OBJECTIVE:The purpose of our study was to evaluate the effects of 0.3-second high-resolution CT (HRCT) of the lung using partial reconstruction on cardiac motion artifacts and image noise. SUBJECTS AND METHODS:Thirty-seven pairs of 0.3-second (partial reconstruction) and 0.75-second (full reconstruction) HRCT images were obtained for the lower lung zone during full-inspiration breath-holding. Imaging parameters other than temporal resolution were identical for each patient. Two radiologists visually graded motion artifacts of the cardiac border, bronchi, pulmonary vessels, and fissure in the left lung on a 4-point scale (with 4 indicating no artifacts). The maximum width of motion along the left cardiac border and the area percentage of motion artifacts in the left lung were calculated. Image noise in the air and lung was also determined. Cardiac motion artifacts and image noises were compared between the two sets of CT images. RESULTS:Visual grades for the cardiac border (4 +/- 0), bronchi (3.8 +/- 0.7), pulmonary vessels (3.6 +/- 0.8), and fissure (3.9 +/- 0.5) were higher for 0.3-second images than for 0.75-second images (1.7 +/- 0.7, 2.0 +/- 1.0, 1.6 +/- 0.7, and 2.4 +/- 0.9, respectively) (p < 0.001). The maximum width of motion along the left cardiac border (0.1 +/- 0.5 mm) and the area percentage of motion artifacts in the left lung (6.7% +/- 18.4%) were smaller for 0.3-second images than for 0.75-second images (4.5 +/- 1.7 mm and 36.2% +/- 20.9%, respectively) (p < 0.001). Image noises in the air (38.0 +/- 9.2) and the lung (86.0 +/- 23.1) were greater for 0.3-second images than for 0.75-second images (35.6 +/- 9.6 and 76.0 +/- 20.3, respectively) (p < 0.01). CONCLUSION:Compared with 0.75-second HRCT using full reconstruction, 0.3-second HRCT using partial reconstruction substantially reduces cardiac motion artifacts in the lung at the expense of increasing image noise.

背景与目标： 目的：本研究的目的是通过部分重建对心脏运动伪影和图像噪声的效果，评估0.3秒高分辨率肺部CT（HRCT）的影响。
研究对象和方法：在全屏吸气时，获得了37对0.3秒（部分重建）和0.75秒（完全重建）的HRCT图像，用于下肺区。对于每个患者，除时间分辨率以外的成像参数均相同。两位放射科医生对心脏边界，支气管，肺血管和左肺裂的运动伪影进行了4分制的视觉分级（其中4表示无伪影）。计算沿左心脏边界的最大运动宽度和左肺中运动伪影的面积百分比。还确定了空气和肺中的图像噪声。比较两组CT图像之间的心脏运动伪影和图像噪声。
结果：0.3秒图像的心脏边界（4 /-0），支气管（3.8 /-0.7），肺血管（3.6 /-0.8）和裂痕（3.9 /-0.5）的视觉等级高于0.75秒图像（分别为1.7 /-0.7、2.0 /-1.0、1.6 /-0.7和2.4 /-0.9）（p <0.001）。对于0.3秒的图像，沿左心脏边界的最大运动宽度（0.1 /-0.5 mm）和左肺中的运动伪影的面积百分比（6.7％/-18.4％）小于0.75秒的图像（分别为4.5±1.7毫米和36.2％±20.9％（p <0.001）。对于0.3秒的图像，空气（38.0 /-9.2）和肺（86.0 /-23.1）的图像噪声大于0.75秒的图像噪声（分别为35.6 /-9.6和76.0 /-20.3）（p <0.01 ）。
结论：与使用完全重建的0.75秒HRCT相比，使用部分重建的0.3秒HRCT可以显着减少肺部的心脏运动伪影，但会增加图像噪声。

BACKGROUND & AIMS: :Rhodopseudomonas palustris is a purple, facultatively phototrophic bacterium that uses hydrogen gas as an electron donor for carbon dioxide fixation during photoautotrophic growth or for ammonia synthesis during nitrogen fixation. It also uses hydrogen as an electron supplement to enable the complete assimilation of oxidized carbon compounds, such as malate, into cell material during photoheterotrophic growth. The R. palustris genome predicts a membrane-bound nickel-iron uptake hydrogenase and several regulatory proteins to control hydrogenase synthesis. There is also a novel sensor kinase gene (RPA0981) directly adjacent to the hydrogenase gene cluster. Here we show that the R. palustris regulatory sensor hydrogenase HupUV acts in conjunction with the sensor kinase-response regulator protein pair HoxJ-HoxA to activate hydrogenase expression in response to hydrogen gas. Transcriptome analysis indicated that the HupUV-HoxJA regulatory system also controls the expression of genes encoding a predicted dicarboxylic acid transport system, a putative formate transporter, and a glutamine synthetase. RPA0981 had a small effect in repressing hydrogenase synthesis. We also determined that the two-component system RegS-RegR repressed expression of the uptake hydrogenase, probably in response to changes in intracellular redox status. Transcriptome analysis indicated that about 30 genes were differentially expressed in R. palustris cells that utilized hydrogen when growing photoheterotrophically on malate under nitrogen-fixing conditions compared to a mutant strain that lacked uptake hydrogenase. From this it appears that the recycling of reductant in the form of hydrogen does not have extensive nonspecific effects on gene expression in R. palustris.

背景与目标： ：Rhodopseudomonas palustris是一种紫色的兼性光养细菌，它利用氢气作为电子供体，在光养植物生长过程中固定二氧化碳，或在固氮过程中合成氨气。它还使用氢作为电子补充剂，以在光异养生长期间将氧化的碳化合物（例如苹果酸）完全同化到细胞材料中。 R. palustris基因组预测膜结合的镍铁摄取氢化酶和几种调节蛋白来控制氢化酶的合成。与氢化酶基因簇直接相邻的还有一个新的传感器激酶基因（RPA0981）。在这里，我们显示帕氏疟原虫调节传感器氢化酶HupUV与传感器激酶响应调节蛋白对HoxJ-HoxA共同作用，以响应氢气激活氢化酶表达。转录组分析表明，HupUV-HoxJA调节系统还控制编码预测的二羧酸转运系统，推定的甲酸盐转运蛋白和谷氨酰胺合成酶的基因的表达。 RPA0981在抑制氢化酶合成方面作用很小。我们还确定了两组分系统RegS-RegR抑制摄取氢化酶的表达，可能是响应细胞内氧化还原状态的变化。转录组分析表明，与缺乏摄取氢酶的突变菌株相比，当在固氮条件下在苹果酸上光异养生长时，利用氢的pal.ris细胞中约有30个基因差异表达。由此看来，还原剂以氢的形式的循环利用对R. palustris的基因表达没有广泛的非特异性影响。

BACKGROUND & AIMS: :Statins are increasingly being used for the treatment of a variety of conditions beyond their original indication for cholesterol lowering. We previously reported that simvastatin increased dopamine receptors in the rat prefrontal cortex [Q. Wang, W.L. Ting, H. Yang, P.T. Wong, High doses of simvastatin upregulate dopamine D(1) and D(2) receptor expression in the rat prefrontal cortex: possible involvement of endothelial nitric oxide synthase, Br. J. Pharmacol. 144 (2005) 933-939] and restored its downregulation in a model of Parkinson's disease (PD) [Q. Wang, P.H. Wang, C. McLachlan, P.T. Wong, Simvastatin reverses the downregulation of dopamine D1 and D2 receptor expression in the prefrontal cortex of 6-hydroxydopamine-induced Parkinsonian rats, Brain Res. 1045 (2005) 229-233]. Here we explore the effects of simvastatin treatment on tissue dopamine content and reuptake. Sprague-Dawley rats were given simvastatin (1 and 10 mg kg(-1)day(-1), p.o.) for 4 weeks. Brain tissue from prefrontal cortex and striatum were taken out for dopamine content and its reuptake. Using high-performance liquid chromatographic-mass spectrometer (HPLC-MS), simvastatin (10 mg kg(-1)day(-1)) was found to increase dopamine content by 110% in the striatum but decreased by 76% in the prefrontal cortex compared with the saline treated group. Dopamine (DA) reuptake was unchanged in both brain regions. These results suggest that chronic treatment with high dose of simvastatin may affect DA tissue level in prefrontal cortex and striatum without changing on DA reuptake. This may have important clinical implications in psychiatric and striatal dopaminergic disorders.

背景与目标： 他汀类药物已被用于治疗多种疾病，这些症状超出了降低胆固醇的最初指标。我们先前曾报道辛伐他汀会增加大鼠前额叶皮层中的多巴胺受体[Q.王伟丁宏阳黄，辛伐他汀大剂量上调大鼠前额叶皮层中的多巴胺D（1）和D（2）受体表达：可能与内皮一氧化氮合酶Br有关。 J.Pharmacol。 144（2005）933-939]，并在帕金森氏病（PD）模型中恢复了其下调[Q.王凤华Wang C.McLachlan，P.T. Wong，辛伐他汀逆转了6-羟基多巴胺诱导的帕金森病大鼠Brain Res的前额叶皮层中多巴胺D1和D2受体表达的下调。 1045（2005）229-233]。在这里，我们探讨辛伐他汀治疗对组织多巴胺含量和再摄取的影响。 Sprague-Dawley大鼠接受辛伐他汀（1和10 mg kg（-1）day（-1），口服）4周。取出前额叶皮层和纹状体的脑组织中的多巴胺含量并重新摄取。使用高效液相色谱质谱仪（HPLC-MS），发现辛伐他汀（10 mg kg（-1）day（-1））在纹状体中可使多巴胺含量增加110％，但在前额叶中减少76％皮层与生理盐水处理组相比。在两个大脑区域中，多巴胺（DA）的再摄取均未改变。这些结果表明，高剂量辛伐他汀的长期治疗可能会影响额叶前额叶皮层和纹状体中的DA组织水平，而不会改变DA的再摄取。这在精神病和纹状体多巴胺能障碍中可能具有重要的临床意义。

BACKGROUND & AIMS: :Heat shock protein 90 (HSP90) is required for structural folding and maintenance of conformational integrity of various proteins, including several associated with cellular signaling. Recent studies utilizing 17-allylamino-17-demethoxygeldanamycin (17-AAG), an inhibitor of HSP90, demonstrated an antitumor effect in solid tumors. To test whether HSP90 could be targeted in multiple myeloma (MM) patients, we first investigated expression of HSP90 by immunofluorescence and flow cytometric analysis in a myeloma cell line (U266) and primary myeloma cells. Following demonstration of HSP90 expression in myeloma cells, archival samples of 32 MM patients were analysed by immunoperoxidase staining. Myeloma cells in all patients showed strong cytoplasmic expression of HSP90 in all samples and 55% also demonstrated concurrent nuclear immunopositivity. Treatment of U266 and primary MM cells with 17AAG resulted in significantly increased apoptosis compared to untreated control cells. Analysis of anti-apoptotic BCL2 family proteins and akt in MM cells incubated with 17-AAG revealed down-regulation of BCL-2, BCL-XL, MCL-1 and akt. Furthermore, although a low concentration of bortezomib resulted in no cell death, a combination of 17AAG and bortezomib treatment revealed a synergistic apoptotic effect on the U266 cell line. These data suggest that targeted inhibition of HSP90 may prove to be a valid and innovative strategy for the development of future therapeutic options for MM patients.

背景与目标： ：热休克蛋白90（HSP90）是结构折叠和维持各种蛋白质（包括与细胞信号相关的几种蛋白质）构象完整性的必需。利用HSP90抑制剂17-烯丙基氨基-17-去甲氧基格尔德霉素（17-AAG）的最新研究表明，在实体瘤中具有抗肿瘤作用。为了测试HSP90是否可以靶向于多发性骨髓瘤（MM）患者，我们首先通过免疫荧光和流式细胞术分析了骨髓瘤细胞系（U266）和原发性骨髓瘤细胞中HSP90的表达。在证明HSP90在骨髓瘤细胞中表达后，通过免疫过氧化物酶染色分析了32例MM患者的档案样本。在所有患者中，骨髓瘤细胞在所有样品中均表现出强烈的HSP90细胞质表达，并且55％的患者还表现出并发的核免疫阳性。与未处理的对照细胞相比，用17AAG处理U266细胞和原代MM细胞可导致凋亡明显增加。分析与17-AAG孵育的MM细胞中的抗凋亡BCL2家族蛋白和akt，表明BCL-2，BCL-XL，MCL-1和akt下调。此外，尽管低浓度的硼替佐米不会导致细胞死亡，但是17AAG和硼替佐米治疗的组合显示出对U266细胞系的协同凋亡作用。这些数据表明，针对HSP90的靶向抑制可能被证明是开发MM患者未来治疗选择的有效且创新的策略。

BACKGROUND & AIMS: :Fludarabine and alemtuzumab are routinely used for treatment of B-cell chronic lymphocytic leukemia (B-CLL). The present study aimed to compare the expression of signaling molecules and cytokine production by T cells of B-CLL patients in long-term unmaintained remission/plateau phase following fludarabine or alemtuzumab treatment with that of indolent/untreated B-CLL patients and healthy donors. The frequency and intensity of TCR-CD3zeta chain, p56lck, p59fyn, ZAP-70, PI3-kinase and interferon (IFN)-gamma/interleukin (IL)-4 production in CD4 and CD8 T cells was examined by flow cytometry. T-cell function was assessed by stimulation with purified protein derivative (PPD) and phytohemagglutinin (PHA). Despite a reduction in number, the expression of IFN-gamma/IL-4 in T-cells in patients was significantly higher than in healthy donors. The intensity of most signaling molecules in treated patients was relatively unaffected vs. healthy donors but lower than untreated-indolent patients. However, the total number of T cells which expressed each of the signaling molecules was decreased in patients, with no difference between fludarabine- and alemtuzumab-treated patients. The T-cell response to PHA but not PPD was reduced in treated patients. The results suggest that, despite some alterations in signaling molecules and a reduction in T-cell number, overall T-cell functions may be relatively well preserved long-term after treatment with fludarabine and alemtuzumab.

背景与目标： 氟达拉滨和阿仑单抗通常用于治疗B细胞慢性淋巴细胞性白血病（B-CLL）。本研究旨在比较氟达拉滨或alemtuzumab治疗后长期未维持的缓解/高原期的B-CLL患者的信号分子的表达和T细胞的细胞因子产生与惰性/未经治疗的B-CLL患者和健康供体的长期比较。通过流式细胞术检测TCR-CD3zeta链，p56lck，p59fyn，ZAP-70，PI3-激酶和干扰素（IFN）-γ/白介素（IL）-4在CD4和CD8 T细胞中的产生频率和强度。通过用纯化的蛋白质衍生物（PPD）和植物血凝素（PHA）刺激来评估T细胞功能。尽管数量减少，但患者T细胞中IFN-γ/ IL-4的表达明显高于健康供体。与健康供体相比，已治疗患者中大多数信号分子的强度相对未受影响，但低于未治疗的惰性患者。但是，表达每种信号分子的T细胞总数在患者中减少了，在氟达拉滨和阿仑单抗治疗的患者之间没有差异。在治疗的患者中，对PHA而非TPD的T细胞反应降低。结果表明，尽管在用氟达拉滨和阿仑单抗治疗后，长期而言，尽管信号分子发生了某些变化并且T细胞数量有所减少，但总体T细胞功能仍可以得到较好的保留。

BACKGROUND & AIMS: BACKGROUND:Despite the recent improvement in techniques and patient selection, post-ERCP pancreatitis remains the most frequent and dreaded complication of ERCP. Recent studies suggest that pretreatment with glyceryl trinitrate (GTN) may prevent post-ERCP pancreatitis and improve cannulation success. OBJECTIVE:To evaluate the effect of transdermal GTN on ERCP cannulation success and post-ERCP pancreatitis. DESIGN:Prospective, double-blind, placebo-controlled trial. SETTING:Tertiary referral university hospital. PATIENTS:A total of 318 patients (mean age 62 years, 61% women) were randomized to either active (n = 155) or placebo (n = 163) arms. INTERVENTIONS:Active patch (GTN) versus placebo patch. MAIN OUTCOME MEASUREMENTS:Cannulation time and success. Post-ERCP pancreatitis rates. RESULTS:There was no significant difference between the active or placebo arms for the following: successful initial cannulation (96.8% vs 98.8%), deep cannulation (96.1% vs 98.8%), time to successful cannulation, use of guidewire (27% vs 25%) or needle knife (13% vs 13%), and post-ERCP pancreatitis (7.4% of placebo patients and 7.7% active patients). Multivariate analysis identified women, younger patients, pancreatogram, number of attempts on papilla, and poor pancreatic-duct emptying after opacification as risk factors for post-ERCP pancreatitis. Transdermal GTN did not reduce post-ERCP pancreatitis in any of the identified high-risk groups. CONCLUSIONS:Transdermal GTN did not improve the rate of success in ERCP cannulation or prevent post-ERCP pancreatitis in either average or high-risk patient groups.

背景与目标： 背景：尽管最近在技术和患者选择方面已有改进，但ERCP后胰腺炎仍然是ERCP最常见和最可怕的并发症。最近的研究表明，用三硝酸甘油酯（GTN）进行预处理可以预防ERCP后胰腺炎并提高插管成功率。
目的：评价经皮GTN对ERCP插管成功和ERCP术后胰腺炎的影响。
设计：一项前瞻性，双盲，安慰剂对照试验。
单位：大专转诊大学医院。
患者：共有318例患者（平均年龄62岁，女性占61％）被随机分配到活动组（n = 155）或安慰剂组（n = 163）。
干预措施：主动贴片（GTN）与安慰剂贴片。
主要观察指标：排尿时间和成功率。 ERCP后胰腺炎发生率。
结果：主动或安慰剂组之间在以下方面没有显着差异：成功的初始插管（96.8％vs 98.8％），深层插管（96.1％vs 98.8％），成功插管的时间，使用导丝（27％vs 25％）或针刀（13％比13％）以及ERCP后胰腺炎（安慰剂患者为7.4％，活动患者为7.7％）。多变量分析确定女性，年轻患者，胰腺造影，乳头尝试次数以及混浊后胰管排空不良是ERCP后胰腺炎的危险因素。在任何已确定的高危人群中，经皮GTN均不能减轻ERCP后胰腺炎的发生。
结论：无论是普通患者还是高危患者，经皮GTN均不能提高ERCP插管成功率或预防ERCP术后胰腺炎。

BACKGROUND & AIMS: :Responses to [D-Ala2, MePhe4, Gly-ol5]enkephalin, a selective agonist for mu-receptors, were recorded intracellularly from 26 neurons in slices of guinea-pig hypothalamus. Of eight cells tested in the supraoptic nucleus, all of which had electrical properties characteristic of magnocellular neuroendocrine cells, four were sensitive to the agonist applied in the perfusion bath or with microdrops. The main effect was a decrease or suppression of spontaneous firing. In the paraventricular nucleus, seven of 18 cells tested also had electrophysiological characteristics similar to magnocellular neurons: two of them were sensitive to the mu-agonist and the effect was similar to that observed in the supraoptic nucleus. The remaining paraventricular neurons displayed low-threshold Ca2+ spikes, and thus had electrophysiological characteristics different from putative magnocellular neurons. Ten of 11 cells with low-threshold Ca2+ spikes were hyperpolarized by more than 10 mV by the mu-agonist, and showed a 33 +/- 1.9% (S.E.M.) decrease in input resistance. In both types of cells, when synaptic transmission was blocked with tetrodotoxin, the mu-agonist could still induce a hyperpolarization, suggesting that the effect was in part direct. Hyperpolarization was also obtained when the Cl- reversal potential was shifted to more positive values by using KCl electrodes, thus excluding a Cl- conductance mechanism. These results provide evidence that opioid peptides can directly inhibit hypothalamic neurons, that the mechanism is an increase in K+ conductance, and that two types of hypothalamic neurons appear to have different sensitivities to a mu-agonist.

背景与目标： ：对豚鼠下丘脑切片中26个神经元的细胞内记录了对[D-Ala2，MePhe4，Gly-ol5]脑啡肽（一种针对mu受体的选择性激动剂）的反应。在视上核中测试的8个细胞中，所有细胞均具有大细胞神经内分泌细胞的电特性，其中4个对灌注浴或微滴中使用的激动剂敏感。主要作用是减少或抑制自发放电。在脑室旁核中，测试的18个细胞中有7个也具有类似于大细胞神经元的电生理特性：其中两个对mu激动剂敏感，作用类似于在视上核中观察到的。其余的脑室旁神经元显示低阈值的Ca2尖峰，因此具有与假定的大细胞神经元不同的电生理特性。 mu激动剂将11个具有低阈值Ca2尖峰的细胞中的10个超极化了10 mV以上，显示输入电阻降低了33 /-1.9％（S.E.M.）。在两种类型的细胞中，当突触传递被河豚毒素阻断时，mu-激动剂仍可诱导超极化，这表明这种作用部分是直接的。当通过使用KCl电极将Cl-反转电位移动到更正值时，也获得了超极化，因此排除了Cl-电导机制。这些结果提供证据表明阿片样物质肽可以直接抑制下丘脑神经元，其机制是钾电导增加，并且两种类型的下丘脑神经元似乎对μ-激动剂具有不同的敏感性。

BACKGROUND & AIMS: OBJECTIVES:This prospective study was designed to assess the sensitivity and specificity of Doppler ultrasound parameters in the diagnosis of cirrhosis and portal hypertension. METHODS:Portal and hepatic arterial Doppler ultrasound was performed on 76 patients with cirrhosis and esophageal varices and on 73 age- and sex-matched controls. The parameters evaluated were portal venous velocity and hepatic arterial pulsatility index. The liver vascular index was calculated as the ratio of portal venous velocity to hepatic arterial pulsatility index. RESULTS:Portal venous velocity was significantly lower (11.0 +/- 2.4 vs 15.9 +/- 2.8 cm/s, p < 0.001) and hepatic arterial pulsatility index was significantly higher (1.28 +/- 0.18 vs 0.95 +/- 0.17,p < 0.001) in patients than in controls. Thus, the liver vascular index was significantly lower in patients than in controls (8.7 +/- 2.1 vs 17.2 +/- 4.3 cm/s, p < 0.001). The sensitivity and specificity of these parameters in the detection of cirrhosis and portal hypertension was then analyzed with the receiver operating characteristic curve. The best cut-off values were considered to be 13 cm/se of portal venous velocity and 1.1 of hepatic arterial pulsatility index, showing a sensitivity and specificity of 83, 85, 84, and 81%, respectively. The best cut-off value of the liver vascular index was 12 cm/s with a sensitivity and specificity of 97 and 93%, respectively. CONCLUSIONS:The liver vascular index is a high sensitive and specific Doppler ultrasound parameter in the diagnosis of cirrhosis and portal hypertension.

背景与目标： 目的：本前瞻性研究旨在评估多普勒超声参数在肝硬化和门静脉高压症诊断中的敏感性和特异性。
方法：对76例肝硬化和食管静脉曲张患者以及73例年龄和性别相匹配的对照者进行门静脉和肝动脉多普勒超声检查。评价的参数是门静脉速度和肝动脉搏动指数。肝血管指数计算为门静脉速度与肝动脉搏动指数之比。
结果：门静脉血流速度显着降低（11.0 /-2.4 vs 15.9 /-2.8 cm / s，p <0.001），肝动脉搏动指数显着升高（1.28 /-0.18 vs 0.95 /-0.17，p <0.001）患者比对照组。因此，患者的肝血管指数显着低于对照组（8.7 /-2.1对17.2 /-4.3 cm / s，p <0.001）。然后使用接收器工作特性曲线分析这些参数在检测肝硬化和门脉高压中的敏感性和特异性。最佳的临界值被认为是门静脉速度的13 cm / se和肝动脉搏动指数的1.1，分别显示出83％，85％，84％和81％的敏感性和特异性。肝血管指数的最佳临界值为12 cm / s，敏感性和特异性分别为97％和93％。
结论：肝血管指数是诊断肝硬化和门静脉高压症的高敏感度和特异性多普勒超声参数。

BACKGROUND & AIMS: BACKGROUND:Pulmonary surfactant dysfunction may contribute to the development of ventilator induced lung injury (VILI). Tracheal gas insufflation (TGI) is a technique in which fresh gas is introduced into the trachea and augment ventilation by reducing the dead space of ventilatory system, reducing ventilatory pressures and tidal volume (V(T)) while maintaining constant partial arterial CO2 pressure (PaCO(2)). We hypothesised that TGI limited peak inspiratory pressure (PIP) and V(T) and would minimize conventional mechanical ventilation (CMV) induced pulmonary surfactant dysfunction and thereby attenuate VILI in rabbits with acute lung injury (ALI). METHODS:ALI was induced by intratracheal administration of lipopolysaccharide in anaesthetized, ventilated healthy adult rabbits randomly assigned to continuous TGI at 0.5 L/min (TGI group) or CMV group (n = 8 for each group), and subsequently ventilated with limited PIP and V(T) to maintain PaCO(2) within 35 to 45 mmHg for 4 hours. Physiological dead space to V(T) ratio (V(D)/V(T)), dynamic respiratory compliance (Cdyn) and partial arterial O(2) pressure (PaO(2)) were monitored. After ventilation, lungs were analysed for total phospholipids (TPL), total proteins (TP), pulmonary surfactant small to large aggregates ratio (SA/LA) in bronchoalveolar lavage fluid (BALF) and for determination of alveolar volume density (V(V)), myeloperoxidase and interleukin (IL)-8. RESULTS:TGI resulted in significant (P < 0.05 or P < 0.01) decrease in PIP [(22.4 +/- 1.8) cmH2O vs (29.5 +/- 1.1) cmH2O], V(T) [(6.9 +/- 1.3) ml/kg vs (9.8 +/- 1.11) ml/kg], V(D)/V(T) [(32 +/- 5)% vs (46 +/- 2)%], TP [(109 +/- 22) mg/kg vs (187 +/- 25) mg/kg], SA/LA (2.5 +/- 0.4 vs 5.4 +/- 0.7), myeloperoxidase [(6.2 +/- 0.5) U/g tissue vs (12.3 +/- 0.8) U/g tissue] and IL-8 [(987 +/- 106) ng/g tissue vs (24 +/- 3) mN/m] of BALF, and significant (P < 0.05) increase in Cdyn [(0.47 +/- 0.02) ml.cmH2O(-1).kg(-1) vs (0.31 +/- 0.02) ml.cmH2O(-1).kg(-1)], PaO(2) [(175 +/- 24) mmHg vs (135 +/- 26) mmHg], TPL/TP (52 +/- 8 vs 33 +/- 11) and Vv (0.65 +/- 0.05 vs 0.44 +/- 0.07) as compared with CMV. CONCLUSIONS:In this animal model of ALI, TGI decreased ventilatory requirements (PIP, V(T) and V(D)/V(T)), resulted in more favourable alveolar pulmonary surfactant composition and function and less severity of lung injury than CMV. TGI in combination with pressure limited ventilation may be a lung protective strategy for ALI.

背景与目标： 背景：肺表面活性物质功能障碍可能导致呼吸机诱发的肺损伤（VILI）的发展。气管内注气（TGI）是一种将新鲜气体引入气管并通过减少通气系统的死腔，降低通气压力和潮气量（V（T））并保持恒定的局部动脉CO2压力来增强通气的技术（ PaCO（2））。我们假设TGI限制了峰值吸气压力（PIP）和V（T），并且将传统机械通气（CMV）引起的肺表面活性剂功能异常减至最小，从而减轻了急性肺损伤（ALI）兔的VILI。
方法：通过气管内脂多糖经气管内施用麻醉的，通气的健康成年兔，以0.5 L / min（TGI组）或CMV组（每组n = 8）随机分配为连续TGI，然后在有限的PIP和通气条件下通气，从而诱发ALI。 V（T）将PaCO（2）维持在35至45 mmHg的范围内4个小时。监测生理死区与V（T）的比率（V（D）/ V（T）），动态呼吸顺应性（Cdyn）和部分动脉O（2）压力（PaO（2））。通气后，对肺中的总磷脂（TPL），总蛋白（TP），支气管肺泡灌洗液（BALF）中的肺表面活性剂小到大聚集比（SA / LA）进行分析，并测定肺泡体积密度（V（V）） ），髓过氧化物酶和白介素（IL）-8。
结果：TGI导致PIP显着降低（P <0.05或P <0.01）[（22.4 /-1.8）cmH2O与（29.5 /-1.1）cmH2O]，V（T）[（6.9 /-1.3）ml / kg vs（9.8 /-1.11）ml / kg]，V（D）/ V（T）[（32 /-5）％vs（46 /-2）％]，TP [（109 /-22）mg / kg vs（187 /-25）mg / kg]，SA / LA（2.5 /-0.4 vs 5.4 /-0.7），髓过氧化物酶[（6.2 /-0.5）U / g组织vs（12.3 /-0.8）U / g组织]和IL-8 [（987 /-106）ng / g组织vs（24 /-3）mN / m] BALF，Cdyn [（0.47 /-0.02）ml.cmH2O显着（P <0.05）增加（-1）.kg（-1）vs（0.31 /-0.02）ml.cmH2O（-1）.kg（-1）]，PaO（2）[（175 /-24）mmHg vs（135 /-26 ）mmHg]，TPL / TP（52 /-8 vs 33 /-11）和Vv（0.65 /-0.05 vs 0.44 /-0.07）。
结论：在这种ALI动物模型中，TGI降低了通气需求（PIP，V（T）和V（D）/ V（T）），与CMV相比，肺泡表面活性剂的肺泡表面活性剂组成和功能更佳，肺部损伤的严重程度更低。 TGI结合限压通气可能是ALI的肺保护策略。

BACKGROUND & AIMS: :A major problem in the search for new cancer drug targets is that the drugs are often toxic to normal tissues and require high doses to kill tumor cells. Therefore cellular targets which appear to involve low dose responses to cancer therapy are especially interesting since they could selectively target normal tissues which are not targeted by the treatment and thus may be responsible for unpleasant side effects or may be amenable to exploitation in order to improve the therapeutic ratio. One such target, which is the subject of this review, is radiation-induced bystander effects [RIBE], which result in the observation of radiation like responses in cells which have not been irradiated. RIBE is a novel phenomenon which indicates that at low doses, cell signaling is more important than direct DNA damage. Historically, DNA has always been considered to be the target for radiation therapy. The growing realization that signaling is important opens up several important therapeutic strategies which will be discussed in this review. RIBE appears to be the result of a generalized stress response in tissues or cells which is expressed at the level of the tissue, organ or organism rather than at the level of the individual cell. The signals may be produced by all exposed cells, but the response may require a quorum of cells in order to be expressed. The major response involving low LET (x- or gamma-ray) radiation exposure discussed in the existing literature is a death response. This has many characteristics of apoptosis but may be detected in cell lines without p53 expression, although the death response is suppressed in many tumor cell lines. While a death response in unirradiated normal cells around a tumor might appear to be adverse, it can in fact be protective and remove damaged cells from the population. If harnessed correctly, it could lead to the development of new drugs aimed not at tissue destruction but at enabling homeostatic mechanisms to control tumor expansion. In this scenario, the level of harmful or beneficial response will be related to the background damage, carried by the cell population, and the genetic programme determining response to damage. This focus may be important when attempting to predict the consequences of mixed therapies involving radiation and other cytotoxic agents. In this review, our current knowledge of the mechanisms underlying the induction of bystander effects by ionizing radiation is reviewed, and the question of how bystander effects may be harnessed to produce a new generation of anti-cancer drugs aimed at stabilization of tissue homeostasis rather than tissue destruction is considered.

背景与目标： ：寻找新的癌症药物靶标的主要问题是该药物通常对正常组织有毒性，需要高剂量才能杀死肿瘤细胞。因此，细胞靶标似乎涉及对癌症治疗的低剂量反应，因此特别令人感兴趣，因为它们可以选择性地靶向未被治疗靶标的正常组织，因此可能引起令人不快的副作用，或者可能适合于剥削以改善治疗效果。治疗比率。辐射诱导的旁观者效应[RIBE]是本综述的主题之一，该效应导致在未辐射的细胞中观察到辐射样反应。 RIBE是一种新现象，表明在低剂量时，细胞信号传导比直接DNA损伤更为重要。从历史上看，DNA一直被认为是放射治疗的目标。人们日益认识到信号转导很重要，这开启了几种重要的治疗策略，本文将对此进行讨论。 RIBE似乎是组织或细胞中普遍的应激反应的结果，这种应激反应是在组织，器官或生物体的水平而不是单个细胞的水平表达的。信号可能由所有暴露的细胞产生，但响应可能需要一定数量的细胞才能表达。现有文献中讨论的涉及低LET（X射线或γ射线）辐射暴露的主要反应是死亡反应。这具有许多细胞凋亡特征，但尽管在许多肿瘤细胞系中死亡反应受到抑制，但在没有p53表达的细胞系中可能检测到。虽然在肿瘤周围未照射的正常细胞中的死亡反应似乎是不利的，但实际上可以起到保护作用，并从群体中清除受损的细胞。如果利用得当，它可能会导致开发新药物，其目的不是破坏组织，而是使稳态机制能够控制肿瘤的扩展。在这种情况下，有害或有益反应的水平将与细胞群所携带的背景损伤以及决定对损伤的反应的遗传程序有关。当试图预测涉及放射线和其他细胞毒剂的混合疗法的后果时，这一重点可能很重要。在这篇综述中，我们对电离辐射诱发旁观者效应的潜在机制的现有知识进行了综述，并探讨了如何利用旁观者效应来生产旨在稳定组织稳态而不是稳定组织的新一代抗癌药物的问题。考虑组织破坏。

BACKGROUND & AIMS: BACKGROUND:To determine the utility of contrast-enhanced ultrasonography (CEUS) in assessing hepatic tumors with central feeding arteries found by color/power Doppler ultrasonograophy (CDUS/PDUS). METHODS:We prospectively studied 37 hepatic tumors (34 patients), with a mean size of 2.9cm and each having a central feeding artery, by CDUS/PDUS. The CEUS was performed with a galactose-based microbubble contrast agent. The detection of a spoke-wheel sign was interpreted as evidence of focal nodular hyperplasia (FNH). All patients underwent tumor biopsies or surgical resection. RESULTS:CEUS showed a central feeding artery with a spoke-wheel sign in 36 tumors, including 34 FNHs and 2 hepatocellular carcinomas. The remaining tumor was demonstrated to be FNH despite the absence of a spoke-wheel sign as detected by CEUS. The sensitivity of the spoke-wheel sign or central scar for FNH was 97.1% (34/35), 40% (14/35), 28.6% (10/35), 50% (8/16) and 0% (0/15) for CEUS, CDUS/PDUS, dynamic computed tomography (CT) or magnetic resonance imaging (MRI), hepatic angiography and liver scintigraphy, respectively. The two hepatocellular carcinomas showed scirrhous changes histologically. CONCLUSIONS:CEUS is more sensitive than CDUS/PDUS, dynamic CT, MRI, hepatic angiography and liver scintigraphy in the detection of the spoke-wheel sign or central scar in FNH. Scirrhous hepatocellular carcinoma should be included in the differential diagnosis for liver tumors with spoke-wheel sign detected by CEUS.

背景与目标： 背景：为了确定造影增强超声（CEUS）在评估彩色/能量多普勒超声检查（CDUS / PDUS）发现的中央供血动脉肝肿瘤中的效用。
方法：我们通过CDUS / PDUS前瞻性研究了37例肝肿瘤（34例患者），平均大小为2.9cm，每个均具有中央供血动脉。 CEUS用半乳糖基微泡造影剂进行。轮辐迹象的检测被解释为局灶性结节性增生（FNH）的证据。所有患者均进行了肿瘤活检或手术切除。
结果：CEUS显示36个肿瘤（包括34个FNHs和2个肝细胞癌）中有一条带有轮辐迹象的中央进食动脉。尽管CEUS检测到没有轮辐迹象，但其余肿瘤仍被证明是FNH。轮辐迹象或中央疤痕对FNH的敏感度分别为97.1％（34/35），40％（14/35），28.6％（10/35），50％（8/16）和0％（0 / 15）分别用于CEUS，CDUS / PDUS，动态计算机断层扫描（CT）或磁共振成像（MRI），肝血管造影和肝闪烁显像。两种肝细胞癌在组织学上均显示出硬化性改变。
结论：CEUS在检测FNH的轮辐征象或中央疤痕方面比CDUS / PDUS，动态CT，MRI，肝血管造影和肝闪烁显像术更为敏感。 CEUS检测到轮辐征兆的肝肿瘤的鉴别诊断中应包括肝硬化性肝癌。