BACKGROUND & AIMS: :Many aspects of ventilatory management in patients with ARDS are still controversial and one of the major controversies is should HFO or CMV ideally be used to manage this patients. As shown by David et al. when the two approaches to ventilatory support are applied using similar principles the physiologic outcomes appear to be similar. With both approaches the use of lung recruitment maneuvers early in ARDS (1 to 3 day) after hemodynamic stabilization in patients without baratrauma is promising. The key to managing ARDS regardless of mode is to use an open lung protective ventilatory strategy. It is not the mode that makes the difference, it is the approach used to apply the mode!

背景与目标： : ARDS患者通气管理的许多方面仍然存在争议，主要争议之一是是否应理想地使用HFO或CMV来管理该患者。如David等人所示。当使用相似的原理应用两种通气支持方法时，生理结果似乎是相似的。对于两种方法，在没有baratrauma的患者中，在血流动力学稳定后的ARDS早期 (1至3天) 使用肺募集动作是有希望的。无论哪种模式，管理ARDS的关键是使用开放的肺保护性通气策略。与众不同的不是模式，而是用于应用模式的方法!

BACKGROUND & AIMS: Inflammatory cell infiltration of the lung is a predominant histopathological change that occurs during radiation pneumonitis. Emigration of inflammatory cells from the circulation requires the interaction between cell adhesion molecules on the vascular endothelium and molecules on the surface of leukocytes. We studied the immunohistochemical pattern of expression of cell adhesion molecules in lungs from mice treated with thoracic irradiation. After X-irradiation, the endothelial leukocyte adhesion molecule 1 (ELAM-1; E-selectin) was primarily expressed in the pulmonary endothelium of larger vessels and minimally in the microvascular endothelium. Conversely, the intercellular adhesion molecule 1 (ICAM-1; CD54) was expressed in the pulmonary capillary endothelium and minimally in the endothelium of larger vessels. Radiation-mediated E-selectin expression was first observed at 6 h, whereas ICAM-1 expression initially increased at 24 h after irradiation. ICAM-1 and E-selectin expression persisted for several days. P-selectin is constitutively expressed in Weibel-Palade bodies in the endothelium, which moved to the vascular lumen within 30 min after irradiation. P-selectin was not detected in the pulmonary endothelium at 6 h after irradiation. The radiation dose required for increased cell adhesion molecule expression within the pulmonary vascular endothelium was 2 Gy, and expression increased in a dose-dependent manner. These data demonstrate that ICAM-1 and E-selectin expression is increased in the pulmonary endothelium following thoracic irradiation. The pattern of expression of E-selectin, P-selectin, and ICAM-1 is distinct from one another.

背景与目标： 肺炎性细胞浸润是放射性肺炎期间发生的主要组织病理学变化。炎症细胞从循环中迁移需要血管内皮上的细胞粘附分子与白细胞表面的分子之间的相互作用。我们研究了经胸部照射治疗的小鼠肺中细胞粘附分子表达的免疫组织化学模式。X射线照射后，内皮白细胞粘附分子1 (ELAM-1; E-选择素) 主要在较大血管的肺内皮中表达，而在微血管内皮中表达最少。相反，细胞间粘附分子1 (ICAM-1; CD54) 在肺毛细血管内皮中表达，而在较大血管的内皮中表达最少。首先在6小时观察到辐射介导的E-选择素表达，而ICAM-1表达最初在辐射后24小时增加。ICAM-1和E-选择素表达持续数天。P-选择素在内皮的Weibel-Palade体中组成性表达，在照射后30分钟内移至血管腔。照射后6小时，在肺内皮中未检测到P-选择素。肺血管内皮细胞粘附分子表达增加所需的辐射剂量为2 Gy，并且表达以剂量依赖性方式增加。这些数据表明，胸部照射后，肺内皮中ICAM-1和E-选择素的表达增加。E-选择素，P-选择素和ICAM-1的表达模式彼此不同。

BACKGROUND & AIMS: BACKGROUND:The purpose of this study was to investigate the fit of a hypothesized model of medical students' diagnostic or clinical reasoning skills based on their aptitude for medical school, basic science achievement, and clinical competency measures. METHOD:A total of 589 medical students who received their MD from 1994 to 2002 participated in this study. Confirmatory factor analysis was used to evaluate the fit of theoretical models of clinical reasoning using measures of basic science and clinical knowledge. RESULTS:The results provided support for a three-factor model of medical student performance (Bentler's Comparative Fit Index = .905, standardized root mean squared residual = .054, root mean squared error of approximation = .105). The clinical reasoning skills of medical students were influenced by an independent relationship between latent variables of basic science achievement and clinical competency. CONCLUSION:The findings support a theoretical model of diagnostic or clinical reasoning that treats the basic science and clinical knowledge of medical students as distinct domains.

背景与目标：

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：

BACKGROUND & AIMS: OBJECTIVE:The 24-hour creatinine clearance is the standard clinical technique for measuring kidney function; however, this measurement is cumbersome and inconvenient for patients. We hypothesized that a camera-based technetium-99m mercaptoacetyltriglycine (MAG3) clearance obtained simultaneously with a standard MAG3 scan would correlate well with the 24-hour creatinine clearance and could serve as a simple marker of kidney function. MATERIALS AND METHODS:Data were obtained from a retrospective analysis of 28 patients with varying degrees of kidney dysfunction and 85 subjects evaluated for kidney donation. The MAG3 clearance was calculated using a camera-based technique without blood or urine sampling. The creatinine clearance was measured using the plasma creatinine and a 24-hour urine collection. The MAG3 and creatinine clearances were corrected for body surface area, and clearance values in healthy subjects and patients were compared using the paired Student's t test. The linear association between the MAG3 and creatinine clearances was expressed by Pearson's correlation coefficient. RESULTS:The mean MAG3 clearance in the potential kidney donors was 321 +/- 95 mL/min/1.73 m2 (95% CI, 171-546 mL/min/1.73 m2), significantly higher than the mean creatinine clearance of 152 +/- 51 mL/min/1.73 m2 (79-278 mL/min/1.73 m2, p < 0.001). The mean MAG3 clearance in patients was 153 +/- 70 mL/min/1.73 m2 (32-316 mL/min/1.73 m2) and was also significantly higher than the mean creatinine clearance of 74 +/- 36 mL/min/1.73 m2 (21-138 mL/min/1.73 m2, p < 0.001). The ratio of the mean creatinine clearance to the mean MAG3 clearance was essentially the same for volunteers and patients, 0.47 and 0.48, respectively. The Pearson's correlation between the MAG3 and creatinine clearances was 0.80 (0.72-0.86). CONCLUSION:The camera-based 99mTc-MAG3 clearance correlates well with the 24-hour creatinine clearance and can provide a simple and convenient index of kidney function.

背景与目标：

BACKGROUND & AIMS: OBJECTIVE:To investigate renal preservation by a novel method of perfusion using an oxygenated perfluorocarbon (PFC) emulsion via retrograde access to the kidney, as preserving renal function during urological surgery has been elusive, and the recognized technique of nephron-sparing surgery has increased its application and practice in modern urology. MATERIALS AND METHODS:After institutional review and approval, 30 New Zealand White rabbits were studied. In a solitary kidney model, each rabbit had the ureter catheterized before 40 min of renal artery occlusion. Each rabbit was randomized to one retrograde perfusion group, i.e. sham, normothermic PFC, chilled PFC, normothermic saline, and chilled saline. The rabbits were maintained for 2 weeks, during which renal function, urine output, systemic blood gases, weight and serum creatinine level were measured. After death, the kidneys were individually examined and graded by one renal pathologist unaware of the treatment. RESULTS:The rabbits treated with retrograde PFC perfusion (normothermic and chilled) had less change in their creatinine clearance, at 3.6 and 4.0 mL/min per kg, than the sham group, at 7.8 mL/min per kg, while also having significantly higher systemic venous oxygenation, at 26.3 and 10.0 mmHg, than the sham group, at 0.2 mmHg. Normothermic and chilled perfusion with PFC was also associated with less histological evidence of ischaemic damage, with mean (sd) scores of 13.0 (13.5) and 8.7 (4.5), respectively, than in the sham group, at 33.3 (16.8), while favourably matching the contralateral control kidney group, at 5.5 (2.3). The rabbits treated with saline retrograde perfusion also had better outcomes than the sham cohort. There were no adverse effects in any of the study arms or with the use of PFC. CONCLUSION:Retrograde oxygen delivery to the kidney through the urinary collecting system was successful in this pilot study. Renal function, laboratory and histological data indicate a trend towards renal preservation and even systemic oxygenation in the experimental groups compared with the sham rabbits, with no adverse effects attributed to this technique.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Side-stream spirometry offers a non-invasive method to monitor continuously respiratory mechanics in intubated patients. We studied the effects of different positions on dynamic lung compliance during anaesthesia. METHODS:The study consisted of 56 patients, operated in supine, prone, kneeling or lateral park-bench position. Dynamic lung compliance and inspiratory peak pressure were recorded after induction of anaesthesia, 15 min and 1 h after posturing the patient. RESULTS:The first measured compliances were comparable in all groups. The compliance in the lateral and the prone positions was significantly lower than in the supine position at 15 min (P < 0.01) and 1 h (P < 0.001) after the posture change. The peak inspiratory pressure was significantly lower in the kneeling position than in the other groups (P < 0.01 at the first measurement, P < 0.001 at the later measurements). No correlation was found between body mass index and compliance. CONCLUSION:We found that dynamic lung compliance decreased significantly upon change of posture from supine to lateral or prone position, whereas in the kneeling position no change in compliance was observed. We suggest that the kneeling position might be preferable to the prone position.

背景与目标：

BACKGROUND & AIMS: :Related outer membrane proteins, termed secretins, participate in the secretion of macromolecules across the outer membrane of many Gram-negative bacteria. In the pullulanase-secretion system, PulS, an outer membrane-associated lipoprotein, is required both for the integrity and the proper outer membrane localization of the PulD secretin. Here we show that the PulS-binding site is located within the C-terminal 65 residues of PulD. Addition of this domain to the filamentous phage secretin, pIV, or to the unrelated maltose-binding protein rendered both proteins dependent on PulS for stability. A chimeric protein composed of bacteriophage f1 pIV and the C-terminal domain of PuID required properly localized PulS to support phage assembly. An in vivo complex formed between the pIV-PulD65 chimera and PulS was detected by co-immunoprecipitation and by affinity chromatography.

背景与目标： : 相关的外膜蛋白，称为分泌素，参与许多革兰氏阴性细菌外膜的大分子分泌。在支链淀粉酶分泌系统中，PulS (一种与外膜相关的脂蛋白) 对于PulD分泌素的完整性和适当的外膜定位都是必需的。在这里，我们显示了PulS结合位点位于PulD的C末端65个残基内。将该结构域添加到丝状噬菌体分泌素pIV或不相关的麦芽糖结合蛋白中，这两种蛋白质都依赖于PulS的稳定性。由噬菌体f1 pIV和PuID的C端结构域组成的嵌合蛋白需要适当定位的PulS来支持噬菌体组装。通过共免疫沉淀和亲和色谱法检测在pIV-PulD65嵌合体和PulS之间形成的体内复合物。

BACKGROUND & AIMS: :Foxp3 has been shown to be both necessary and sufficient for the development and function of naturally arising CD4+ CD25+ regulatory T cells in mice. Mutation of Foxp3 in Scurfy mice and FOXP3 in humans with IPEX results in fatal, early onset autoimmune disease and demonstrates the critical role of FOXP3 in maintaining immune homeostasis. The FOXP3 protein encodes several functional domains, including a C2H2 zinc finger, a leucine zipper, and a winged-helix/forkhead (FKH) domain. We have shown previously that FOXP3 functions as a transcriptional repressor and inhibits activation-induced IL-2 gene transcription. To characterize the role of each predicted functional domain on the in vivo activity of FOXP3, we have evaluated the location of point mutations identified in a large cohort of patients with the immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) and found them to cluster primarily within the FKH domain and the leucine zipper, but also present within the poorly defined N-terminal portion of the protein. The molecular functions of each of the IPEX-targeted domains were investigated. We show that FOXP3 is constitutively localized to the nucleus and this localization requires sequences at both the amino and C-terminal ends of its FKH domain. Moreover, FOXP3 was found to homodimerize through its leucine zipper. We also identify a novel functional domain within the N-terminal half of FOXP3, which is required for FOXP3-mediated repression of transcription from both a constitutively active and a NF-AT-inducible promoter. Furthermore, we demonstrate that IPEX mutations in these domains correlate with deficiencies in FOXP3 repressor function, corroborating their in vivo relevance.

背景与目标： : Foxp3已被证明对于小鼠中自然产生的CD4 CD25调节性T细胞的发育和功能既必要又充分。在患有pex的Scurfy小鼠中Foxp3和人类中FOXP3的突变会导致致命的，早发性自身免疫性疾病，并证明了FOXP3在维持免疫稳态中的关键作用。FOXP3蛋白编码几个功能结构域，包括C2H2锌指，亮氨酸拉链和有翼螺旋/叉头 (FKH) 结构域。我们先前已经证明FOXP3作为转录阻遏物起作用并抑制激活诱导的IL-2基因转录。为了表征每个预测的功能域对FOXP3体内活性的作用，我们评估了在免疫失调，多内分泌病，肠病，X连锁综合征 (IPEX)，发现它们主要聚集在FKH结构域和亮氨酸拉链内，但也存在于蛋白质定义不明确的N端部分。研究了每个pex靶向域的分子功能。我们证明FOXP3组成性地定位于细胞核，并且这种定位需要在其FKH结构域的氨基和C末端都具有序列。此外，发现FOXP3通过其亮氨酸拉链同向二聚。我们还在FOXP3的N末端一半内鉴定了一个新的功能结构域，这是FOXP3-mediated抑制组成型活性和NF-AT诱导启动子转录所必需的。此外，我们证明了这些域中的IPEX突变与FOXP3阻遏物功能的缺陷相关，从而证实了它们在体内的相关性。

BACKGROUND & AIMS: :We show that STAT5b is important for the in vivo accumulation of CD4+ CD25(high) T cells with regulatory cell function. A patient homozygous for a missense A630P STAT5b mutation displayed immune dysregulation and decreased numbers of CD4+ CD25(high) T cells. STAT5b(A630P/A630P) CD4+ CD25(high) T cells had low expression of forkhead box P3 and an impaired ability to suppress the proliferation of or to kill CD4+ CD25- T cells. Expression of CD25, a component of the high-affinity IL-2R, was also reduced in response to IL-2 or after in vitro propagation. The impact of the STAT5b mutation was selective in that IL-2-mediated up-regulation of the common gamma-chain cytokine receptor and perforin, and activation-induced expressions of CD154 and IFN-gamma were normal. These results indicate that STAT5b propagates an important IL-2-mediated signal for the in vivo accumulation of functional regulatory T cells.

背景与目标： : 我们显示STAT5b对于具有调节细胞功能的CD4 CD25 (高) T细胞的体内积累很重要。一名因错义A630P STAT5b突变而纯合的患者表现出免疫失调和CD4 CD25 (高) T细胞数量减少。STAT5b(A630P/A630P) CD4 CD25 (高) T细胞的叉头盒P3表达低，抑制或杀死CD4 cd25-t细胞的增殖能力受损。高亲和力IL-2R的组分CD25的表达也在响应IL-2或体外繁殖后降低。STAT5b突变的影响是选择性的，因为IL-2-mediated常见的 γ 链细胞因子受体和穿孔素的上调，并且激活诱导的CD154和IFN-γ 的表达正常。这些结果表明STAT5b传播了功能性调节性T细胞在体内积累的重要IL-2-mediated信号。

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：

BACKGROUND & AIMS: :Activating mutations in the tyrosine kinase domain of the HER2 gene have recently been reported in lung adenocarcinomas, mainly in East Asian patients. Our study was devised to evaluate the prevalence and nature of HER2 mutations in lung adenocarcinomas from Caucasian patients. The mutational status of the HER2 gene was evaluated in 403 lung adenocarcinomas by PCR-single strand conformation polymorphism analysis and direct sequencing of Exons 19 and 20. We found HER2 mutations in 9 (2.2%) cases. Seven (78%) of the mutations were in frame duplications/insertions at codons 776-779 (YVMA), the other 2 were base substitutions resulting in aminoacid changes. The hotspot mutation at bases 776-779 was previously found to be the most frequent HER2 mutation in Asiatic patients. The distribution of mutations was significantly different between conventional lung adenocarcinomas (CLAs) and lung adenocarcinomas with bronchioloalveolar features (ABAFs). Seven (6.2%) of 113 ABAFs and 2 (0.7%) of 290 CLA were mutated (p = 0.0025). In addition, the frequency of HER2 mutations was slightly higher in females (4.1%) than in males (1.8%) and in never smokers (3.1%) than in smokers (1.9%), but differences were not statistically significant. This series of tumors was also investigated for EGFR and K-ras mutations. EGFR mutations were observed in 43 (10.7%) cases, and K-ras mutations in 110 (27.3%) cases. EGFR, HER2 and K-ras mutations were found to be mutually exclusive events. The presence of HER2 mutations in a subset of patients with lung adenocarcinoma raise hope to treat these patients with HER2 specific kinase inhibitors.

背景与目标： : 最近在肺腺癌 (主要是东亚患者) 中报道了HER2基因酪氨酸激酶结构域的激活突变。我们的研究旨在评估白种人肺腺癌中HER2突变的患病率和性质。通过PCR-单链构象多态性分析和外显子19和20的直接测序，评估了403例肺腺癌中HER2基因的突变状态。我们在9 (2.2%) 例病例中发现HER2突变。7 (78%) 个突变在密码子776-779 (YVMA) 的帧重复/插入中，另外2个是导致氨基酸变化的碱基取代。先前发现776-779碱基的热点突变是亚洲患者中最常见的HER2突变。在常规肺腺癌 (cras) 和具有细支气管肺泡特征的肺腺癌 (ABAFs) 之间，突变的分布显着不同。113 ABAFs中的7个 (6.2%) 和290 CLA中的2个 (0.7%) 发生突变 (p = 0.0025)。此外，女性 (4.1%) 的HER2突变频率略高于男性 (1.8%)，从不吸烟者 (3.1%) 高于吸烟者 (1.9%)，但差异无统计学意义。还研究了这一系列肿瘤的EGFR和K-ras突变。在43 (10.7%) 例中观察到EGFR突变，在110 (27.3%) 例中观察到K-ras突变。发现EGFR，HER2和K-ras突变是相互排斥的事件。在一部分肺腺癌患者中存在HER2突变，这使人们希望用HER2特异性激酶抑制剂治疗这些患者。

BACKGROUND & AIMS: :The oncoprotein LMP1 mimics an activated CD40 receptor, yet it is not known whether constitutive CD40 signaling, like LMP1, is sufficient to transform cells. Here we demonstrate that constitutive activation of the CD40 pathway by a chimeric LMP1CD40 molecule resembles the transforming function of LMP1 in inducing loss of contact inhibition and anchorage independent growth of Rat1 fibroblasts. Rat1 transformation correlates with the expression level of LMP1CD40 and depends on its ability to oligomerize. Our data provide direct evidence for the oncogenic potential of the CD40 signaling pathway, which is also established as a model-mechanism for LMP1-induced transformation.

背景与目标： : 癌蛋白LMP1模仿活化的CD40受体，但尚不清楚组成型CD40信号传导 (如LMP1) 是否足以转化细胞。在这里，我们证明了嵌合LMP1CD40分子对CD40途径的组成型激活类似于LMP1在诱导Rat1成纤维细胞的接触抑制丧失和锚定独立生长方面的转化功能。Rat1转化与LMP1CD40的表达水平相关，并取决于其寡聚能力。我们的数据为CD40信号通路的致癌潜力提供了直接证据，CD40信号通路也被确立为LMP1-induced转化的模型机制。

BACKGROUND & AIMS: BACKGROUND:The combination of inhaled corticosteroids (ICS) and long-acting beta2-agonists (LABA) is recommended by treatment guidelines for the treatment of persistent asthma. Two such combination products, salmeterol/fluticasone propionate (SFC, Seretide GSK, UK) and formoterol/budesonide (FBC, Symbicort, AstraZeneca, UK) are commercially available. OBJECTIVES:The purpose of these studies was to evaluate and compare the duration of bronchodilation of both combination products up to 24 hours after a single dose. METHODS:Two randomised, double blind, placebo-controlled, crossover studies were performed. Study A was conducted in 33 asthmatic adults receiving 400-1200 mcg of budesonide or equivalent. Serial forced expiratory volume in one second (FEV1) was measured over 24 hours to determine the duration of effect of both SFC (50/100 mcg) and FBC (4.5/160 mcg). Study B was conducted in 75 asthmatic adults receiving 800-1200 mcg of budesonide or equivalent and comprised a 4 week run-in of 400 mcg bd Becotide followed by 4 weeks treatment with either SFC 50/100 mcg bd or FBC 4.5/160 mcg bd taken in a cross-over manner. Serial 24-hour FEV1 was measured after the first dose and the last dose after each 4-weeks treatment period to determine the offset of action of each treatment. RESULTS:In study A, a single inhalation of SFC and FBC produced a sustained bronchodilation at 16 hours with an adjusted mean increase in FEV1 from pre-dose of 0.22 L (95% CI 0.19, 0.35 L) for SFC and 0.25 L (95% CI 0.21, 0.37 L) for FBC, which was significantly greater than placebo for both treatments (-0.05 L; p < 0.001). In study B, the slope of decline in FEV1 from 2-24 hours post dose was -16.0 ml/hr for SFC and -14.2 ml/hr for FBC. The weighted mean AUC over 24 hours was 0.21 Lxmin and 0.22 Lxmin and mean change from pre-dose FEV1 at 12 hours was 0.21 L for SFC and 0.20 L for FBC respectively CONCLUSION:Both SFC and FBC produced a similar sustained bronchodilator effect which was prolonged beyond 12 hours post dose and was clearly measurable at 24 h.

背景与目标：

BACKGROUND & AIMS: :The National Radiological Protection Board's advisory Group on Non-ionising Radiation has recommended further study on the effects of electric charge on the deposition of 0.005-1 microm particles in the lung. Estimates have been made regarding the integrated ion exposure within the corona plume generated by a power line and by ionisers in an intensive care unit. Changes in the charge state of particles with sizes in the range 0.02-13 mum have been calculated for these exposures. The corona plume increases the charge per particle of 0.02 and 0.1 microm particles by the order of 0.1. The ionisers in the intensive care unit produced negative ions-as do power lines under most conditions. Bacteria can carry in the order of 1000 charges (of either sign) and it is shown that the repulsion between such a negatively charged bacterium and negative ions prevents further ion deposition by diffusion charging. Positively charged bacteria can, however, be discharged by the ions which are attracted to them. The data provide no support for the hypothesis that ion exposure, at the levels considered, can increase deposition in the lung.

背景与目标： : 国家放射防护委员会的非电离辐射咨询小组建议进一步研究电荷对肺中0.005-1微米颗粒沉积的影响。已经对由电力线和重症监护病房中的离子发生器产生的电晕羽流中的综合离子暴露进行了估计。对于这些暴露，已经计算了尺寸在0.02-13微米范围内的颗粒的电荷状态变化。电晕羽流使0.02和0.1微米颗粒的每个颗粒的电荷增加0.1数量级。重症监护病房中的离子发生器会产生负离子-在大多数情况下，电源线也是如此。细菌可以以1000电荷的顺序携带 (任一符号)，并且显示出这种带负电荷的细菌与负离子之间的排斥防止通过扩散电荷进一步的离子沉积。但是，带正电的细菌可以被吸引到它们的离子排出。这些数据没有支持这样的假设，即离子暴露在所考虑的水平上会增加肺中的沉积。