Maureen O. Meade, MD, MSc; Deborah J. Cook, MD, MSc; Gordon H. Guyatt, MD, MSc; Arthur S. Slutsky, MD; Yaseen M. Arabi, MD; D. James Cooper, MD; Andrew R. Davies, MD; Lori E. Hand, RRT, CCRA; Qi Zhou, PhD; Lehana Thabane, PhD; Peggy Austin, CCRA; Stephen Lapinsky, MD; Alan Baxter, MD; James Russell, MD; Yoanna Skrobik, MD; Juan J. Ronco, MD; Thomas E. Stewart, MD; for the Lung Open Ventilation Study Investigators
JAMA. 2008;299(6):637-645.
Context Low-tidal-volume ventilation reduces mortalityin critically ill patients with acute lung injury and acuterespiratory distress syndrome. Instituting additional strategiesto open collapsed lung tissue may further reduce mortality.
Objective To compare an established low-tidal-volume ventilationstrategy with an experimental strategy based on the original"open-lung approach," combining low tidal volume, lung recruitmentmaneuvers, and high positive-end–expiratory pressure.
Design and Setting Randomized controlled trial with concealedallocation and blinded data analysis conducted between August2000 and March 2006 in 30 intensive care units in Canada, Australia,and Saudi Arabia.
Patients Nine hundred eighty-three consecutive patientswith acute lung injury and a ratio of arterial oxygen tensionto inspired oxygen fraction not exceeding 250.
Interventions The control strategy included target tidalvolumes of 6 mL/kg of predicted body weight, plateau airwaypressures not exceeding 30 cm H2O, and conventional levelsof positive end-expiratory pressure (n = 508). Theexperimental strategy included target tidal volumes of 6 mL/kgof predicted body weight, plateau pressures not exceeding 40cm H2O, recruitment maneuvers, and higher positive end-expiratorypressures (n = 475).
Main Outcome Measure All-cause hospital mortality.
Results Eighty-five percent of the 983 study patientsmet criteria for acute respiratory distress syndrome at enrollment.Tidal volumes remained similar in the 2 groups, and mean positiveend-expiratory pressures were 14.6 (SD, 3.4) cm H2O in the experimentalgroup vs 9.8 (SD, 2.7) cm H2O among controls during the first72 hours (P < .001). All-cause hospital mortalityrates were 36.4% and 40.4%, respectively (relative risk [RR],0.90; 95% confidence interval [CI], 0.77-1.05; P = .19).Barotrauma rates were 11.2% and 9.1% (RR, 1.21; 95% CI, 0.83-1.75;P = .33). The experimental group had lower ratesof refractory hypoxemia (4.6% vs 10.2%; RR, 0.54; 95% CI, 0.34-0.86;P = .01), death with refractory hypoxemia (4.2% vs8.9%; RR, 0.56; 95% CI, 0.34-0.93; P = .03), and previouslydefined eligible use of rescue therapies (5.1% vs 9.3%; RR,0.61; 95% CI, 0.38-0.99; P = .045).
Conclusions For patients with acute lung injury and acuterespiratory distress syndrome, a multifaceted protocolized ventilationstrategy designed to recruit and open the lung resulted in nosignificant difference in all-cause hospital mortality or barotraumacompared with an established low-tidal-volume protocolized ventilationstrategy. This "open-lung" strategy did appear to improve secondaryend points related to hypoxemia and use of rescue therapies.
Background Recent studies indicate that S100P expression may be a biomarker that can predict the success of cancer chemotherapy. Whether it is relevant to chemotherapeutics in ovarian cancer is unknown. In this study, we investigated the association of S100P expression with paclitaxel sensitivity in ovarian cancer cell lines. Methods We measured S100P expression and paclitaxel resistance profiles in parent SKOV3 and OVCAR3 cell lines. Then, the two cell lines were transiently transfected with S100P siRNA. We also constructed an OVCAR3 cell clone that stably overexpressed S100P. The effect of S100P expression level on the survival of cells exposed to paclitaxel was measured using the MTT assay. S100P expression was evaluated by semi-quantitative RT-PCR and Western blotting. Significance of differences was calculated using independent samples t-test and one way analysis of variance (ANOVA). Results Lower S100P expression was associated with a survival advantage in OVCAR3 cells exposed to paclitaxel; the survival advantage in SKOV3 cells was smaller (P 〈0.05). The survival advantage associated with decreased S100P expression was even greater for SKOV3 and OVCAR3 cells that had been transfected with S100P siRNA before being exposed to paclitaxel (P 〈0.05). Consistent with this, the OVCAR3 cell clone that was transfected to overexpress S100P was more sensitive to paclitaxel (P 〈0.05). Conclusions Low S100P expression contributes to drug resistance to paclitaxel in ovarian cancer cell lines. S100P expression thus might be a marker that can predict the effectiveness of paclitaxel based chemotherapy. Such a marker could be helpful in improving individual medication regimens for ovarian cancer patients. 相似文献
目的观察兔急性脊髓损伤后经颅磁刺激运动诱发电位(transcranial magnetic stimulation motor evoked pontentials,TMS-MEP)的变化规律,并与脊髓病理变化相比较,探讨其相关性。方法将日本大耳兔32只随机分为4组,每组8只。A组为对照组,B、C、D组为实验组(脊髓损伤组)。然后对每组动物分别于麻醉后、暴露脊髓后、伤后5min、30min、1h、6h、1d、3d、7d检测TMS-MEP,对所得波形数据进行统计学分析。于伤后1d、3d、7d采用后肢的Tarlov分级行运动功能评分。以损伤部位为中心切取脊髓标本,行HE染色光镜、电镜观察。结果随着脊髓损伤的加重,MEP的潜伏期逐渐延长,波幅在逐渐减小,病理显示白质纤维脱髓鞘越重,神经细胞损伤数目越多,MEP的潜伏期延长和波幅降低越明显。结论经颅磁刺激运动诱发电位与脊髓病理变化有明显的相关性,TMS-MEP对脊髓损伤十分敏感,能客观地检测脊髓运动功能,反映脊髓损伤程度。 相似文献
The effect of targeted magnetic nanoparticles on hepatoma and the underlying mechanism were examined. Nude mice transplanted with a human hepatoma cell line (HepG2 cells) were randomized into 5 groups, including: (1) group A, receiving normal saline, (2) group B, receiving 5-fluorouracil (5-Fu), (3) group C, receiving magnetic nanoparticles containing 5-Fu, (4) group D, consisting of treatment with magnetic nanoparticles containing 5-Fu and inside magnetic field and (5) group E, receiving pure magnetic nanoparticles and inside magnetic field. Morphological features of transplanted tumors in mice in each group were observed under transmission electron microscope (TEM). The expression of bcl-2/bax protein was immunohistochemically detected by SABC method. The results showed that a large number of apoptotic tumor cells were found in group B and group D under TEM. The expression of bcl-2 protein was significantly decreased and the expression of bax protein increased significantly in both group B and D as compared with those in group A, C and E (P〈0.01 for all). The decrease in bcl-2 and the increase in bax were more in group D as compared with group B (P〈0.01). It is concluded that the targeted magnetic nanoparticles containing 5-Fu can improve the chemotherapeutic effect of 5-Fu by decreasing bcl-2 expression, increasing bax expres- sion and inducing apoptosis of the liver cancer cells. 相似文献