Abstract:
OBJECTIVES:Delirium occurs in approximately 30% of critically ill patients, and the risk of dying during admission doubles in those patients. Molecular mechanisms causing delirium are largely unknown. However, critical illness and the ICU environment consistently disrupt circadian rhythms, and circadian disruptions are strongly associated with delirium. Exposure to benzodiazepines and constant light are suspected risk factors for the development of delirium. Thus, we tested the functional role of the circadian rhythm protein Period 2 (PER2) in different mouse models resembling delirium. DESIGN:Animal study. SETTING:University experimental laboratory. SUBJECTS:Wildtype, Per2 mice. INTERVENTIONS:Midazolam, lipopolysaccharide (lipopolysaccharide), constant light, nobiletin, or sham-treated animals. MEASUREMENTS AND MAIN RESULTS:Midazolam significantly reduced the expression of PER2 in the suprachiasmatic nucleus and the hippocampus of wild-type mice. Behavioral tests following midazolam exposure revealed a robust phenotype including executive dysfunction and memory impairment suggestive of delirium. These findings indicated a critical role of hippocampal expressed PER2. Similar results were obtained in mice exposed to lipopolysaccharide or constant light. Subsequent studies in Per2 mice confirmed a functional role of PER2 in a midazolam-induced delirium-like phenotype. Using the small molecule nobiletin to enhance PER2 function, the cognitive deficits induced by midazolam or constant light were attenuated in wild-type mice. CONCLUSIONS:These experiments identify a novel role for PER2 during a midazolam- or constant light-induced delirium-like state, highlight the importance of hippocampal PER2 expression for cognitive function, and suggest the PER2 enhancer nobiletin as potential therapy in delirium-like conditions associated with circadian disruption.
journal_name
Crit Care Medjournal_title
Critical care medicineauthors
Gile J,Scott B,Eckle Tdoi
10.1097/CCM.0000000000003077subject
Has Abstractpub_date
2018-06-01 00:00:00pages
e600-e608issue
6eissn
0090-3493issn
1530-0293journal_volume
46pub_type
杂志文章abstract:OBJECTIVE:To determine whether a correlation exists between concentrations of intracellular and extracellular potassium and to determine the frequency of ventricular ectopy in patients after cardiac operations. DESIGN:Prospective, observational clinical evaluation. SETTING:Surgical-respiratory intensive care unit of ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199911000-00018
更新日期:1999-11-01 00:00:00
abstract:OBJECTIVE:To appraise the literature on the effect of initial renal replacement therapy (RRT) modality on clinical outcomes. DESIGN:Systematic review and meta-analysis. SETTING:Academic medical center. PATIENTS AND PARTICIPANTS:Adult critically ill patients with acute kidney injury. INTERVENTIONS:Continuous vs. int...
journal_title:Critical care medicine
pub_type: 杂志文章,meta分析,评审
doi:10.1097/01.CCM.0B013E3181611F552
更新日期:2008-02-01 00:00:00
abstract:OBJECTIVE:The purpose of this study was to evaluate the long-term cardiopulmonary outcome at ages 10-15 yrs following neonatal extracorporeal membrane oxygenation (ECMO). The specific aims of the study were to assess baseline aerobic capacity, cardiac function, and pulmonary function in neonatal ECMO survivors using gr...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/01.CCM.0000084856.00372.CE
更新日期:2003-09-01 00:00:00
abstract:OBJECTIVES:Increases in exhaled nitric oxide have been demonstrated to originate from the lungs of rats after septic lung injury. The aim of this study was to investigate whether treatment with the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) would prevent lipopolysaccharide (LPS)-induced in...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199802000-00033
更新日期:1998-02-01 00:00:00
abstract:OBJECTIVE:To assess hemodynamic, tissue oxygenation, and tissue perfusion changes by comparing traditional therapy (fluid resuscitation followed by vasopressor treatment) and alternative therapy (early vasopressor treatment) in a hyperkinetic and sedated model of endotoxic shock. DESIGN:Prospective controlled experime...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/01.CCM.0000269028.28521.08
更新日期:2007-07-01 00:00:00
abstract::Nine ventilator-dependent patients were successfully weaned from mechanical ventilatory support by high-frequency jet ventilation. All patients had been on ventilatory support for at least 2 wk, and had not responded to attempts at weaning by intermittent mandatory ventilation. ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198409000-00021
更新日期:1984-09-01 00:00:00
abstract::A high rate of death from septic shock persists despite general improvements in care. The relative failure of mechanistically based therapies in various clinical trials should also trigger a reconsideration of such mechanistic approaches. Despite reversion of shock by hydrocortisone, the similar death rate compared wi...
journal_title:Critical care medicine
pub_type: 杂志文章,评审
doi:10.1097/CCM.0b013e3181f23dc4
更新日期:2010-10-01 00:00:00
abstract::In a prospective randomized study to determine whether prevention of colonization of Gram-negative bacteria results in prevention of Gram-negative bacterial infections, 96 intensive care patients were randomly allocated into a control group and a study group. The study group received oral nonabsorbable antimicrobial a...
journal_title:Critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00003246-198811000-00001
更新日期:1988-11-01 00:00:00
abstract:OBJECTIVE:The mortality of critically ill patients associated with intestinal ischemia/reperfusion remains very high, which results from multiorgan dysfunction or failure due to intestinal injury induced by intestinal ischemia/reperfusion. This study was carried out to investigate whether intestinal ischemia/reperfusio...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0b013e3182546855
更新日期:2012-08-01 00:00:00
abstract:OBJECTIVES:Visual assessment of the electroencephalogram by experienced clinical neurophysiologists allows reliable outcome prediction of approximately half of all comatose patients after cardiac arrest. Deep neural networks hold promise to achieve similar or even better performance, being more objective and consistent...
journal_title:Critical care medicine
pub_type: 杂志文章,多中心研究
doi:10.1097/CCM.0000000000003854
更新日期:2019-10-01 00:00:00
abstract:OBJECTIVE:Antioxidant therapy has shown some promise in critical care medicine in which glutathione depletion and heart failure are often seen in critically ill patients. This study was designed to examine the impact of glutathione depletion and the free radical scavenger, metallothionein (MT), on cardiac function. DE...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0b013e31817bf925
更新日期:2008-07-01 00:00:00
abstract:OBJECTIVES:To evaluate the ability of central venous-to-arterial carbon dioxide pressure difference, central venous oxygen saturation, and the combination of these two parameters to detect extubation failure in critically ill patients. DESIGN:Multicentric, prospective, observational study. SETTING:Three ICUs. PATIEN...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000004446
更新日期:2020-10-01 00:00:00
abstract::The EEGs of 40 infants paralyzed with D-tubocurarine or pancuronium during the neonatal period were reviewed retrospectively. The 23 infants who survived were re-examined at 1-3 yr of age. Sixteen infants had normal or mildly abnormal EEGs in the neonatal period; 3 died of nonneurologic causes; the remainder were norm...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198312000-00004
更新日期:1983-12-01 00:00:00
abstract:OBJECTIVE:Acute renal tubular injury is a serious complication in the postoperative period, which is associated with high mortality and increased ICU stay. We aimed to demonstrate the protective effect of rhEPO against acute tubular injury induced by ischemia-reperfusion and to explore the mechanism of canonical transi...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000000542
更新日期:2014-10-01 00:00:00
abstract:OBJECTIVE:To investigate the role of regulatory T cells in the modulation of long-term immune dysfunction during experimental sepsis. It is well established that sepsis predisposes to development of a pronounced immunosuppression. Nevertheless, the mechanisms underlying the immune dysfunction after sepsis are still not...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0b013e3181e78ad0
更新日期:2010-08-01 00:00:00
abstract:OBJECTIVE:To determine the number of adult or pediatric intensive care unit patients without documented invasive fungal infection who receive systemic antifungal therapy. DESIGN:A 1-day cross-sectional cohort study. SETTING:One hundred sixty-nine intensive care units in France and Belgium. PATIENTS:All patients stay...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0b013e318236f297
更新日期:2012-03-01 00:00:00
abstract:OBJECTIVES:To validate scoring algorithm criteria established by the Japanese Association for Acute Medicine (JAAM) for disseminated intravascular coagulation (DIC) and to evaluate its diagnostic property by comparing the two leading scoring systems for DIC, from the Japanese Ministry of Health and Welfare (JMHW) and I...
journal_title:Critical care medicine
pub_type: 杂志文章,多中心研究
doi:10.1097/01.ccm.0000202209.42491.38
更新日期:2006-03-01 00:00:00
abstract::Serum ionized calcium (Ca+2), creatinine, magnesium, phosphate, and arterial pH were measured in patients on admission to the medical ICU (MICU). Patients were classified into three groups: a) hypotensive (n = 38), those who received vasopressor support for frank hypotension; b) hypertensive (n = 21), those who requir...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198806000-00002
更新日期:1988-06-01 00:00:00
abstract::With the thermodilution technique, repeated determination of cardiac index (CI) has become a rapid, easily accomplished, safe procedure. We paired 77 CI determinations measured by direct Fick and thermodilution techniques in 21 patients who underwent myocardial revascularization. Commercially available thermistor-tipp...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-197509000-00002
更新日期:1975-09-01 00:00:00
abstract:OBJECTIVE:Effective therapies are needed to reverse the increased vascular permeability that characterizes acute inflammatory diseases such as acute lung injury. FTY720 is a pharmaceutical analog of the potent barrier-enhancing phospholipid, sphingosine 1-phosphate. Because both FTY720 and sphingosine 1-phosphate have ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000000097
更新日期:2014-03-01 00:00:00
abstract:BACKGROUND:Pneumonia accounts for almost half of intensive care unit (ICU) infections and nearly 60% of deaths from nosocomial infections. It increases hospital stay by 7-9 days, crude mortality by 70% and attributable mortality by 30%. OBJECTIVE:Our purpose was to assess the impact of standard operating procedures ad...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0b013e3181934f1b
更新日期:2009-01-01 00:00:00
abstract:OBJECTIVE:To validate performance characteristics of the intensive care unit (ICU) admission mortality probability model, version III (MPM0-III) on Project IMPACT data submitted in 2004 and 2005. This data set was external from the MPM0-III developmental and internal validation data collected between 2001 and 2004. DE...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0b013e31819ded31
更新日期:2009-05-01 00:00:00
abstract::Quality improvement (QI) activities have been done as long as medicine has been practiced and are integral to safety and efficacy of patient care. The 20th century witnessed sophisticated advances of QI methods, with concurrent advances in research ethics. The suggestion that some interventional QI activities resemble...
journal_title:Critical care medicine
pub_type: 杂志文章,评审
doi:10.1097/01.CCM.0000054902.85329.50
更新日期:2003-03-01 00:00:00
abstract:OBJECTIVE:The pathogenesis of acute gastric stress ulceration in the seriously ill is uncertain, and any role of Helicobacter pylori infection is unknown. We aimed to assess the relationship between H. pylori serological status and stress ulceration in seriously ill patients, as well as H. pylori serological status in ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199907000-00010
更新日期:1999-07-01 00:00:00
abstract:OBJECTIVE:To evaluate if the up-regulation of vascular endothelial growth factor strengthens the protective effect of amniotic fluid stem cells in a renal ischemia-reperfusion injury model. DESIGN:Randomized animal study. SETTINGS:University research laboratory. SUBJECTS:A total of 40 males 12-week-old Wistar rats w...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000002020
更新日期:2017-01-01 00:00:00
abstract:OBJECTIVE:Quality of care for patients admitted with pneumonia varies across hospitals, but causes of this variation are poorly understood. Whether hospitals with high ICU utilization for patients with pneumonia provide better quality care is unknown. We sought to investigate the relationship between a hospital's ICU a...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000000925
更新日期:2015-06-01 00:00:00
abstract:OBJECTIVE:Recent in vivo studies of both septic humans and animals demonstrate that leukocyte delivery is attenuated to sites remote from the primary infection. The mechanisms for this are not entirely clear. L-selectin is integral to rolling, the first step in leukocyte recruitment to an inflammatory site. L-selectin ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-200101000-00024
更新日期:2001-01-01 00:00:00
abstract:OBJECTIVE:To determine whether partial liquid ventilation (PLV) affects the risk of nosocomial pneumonia. STUDY DESIGN:To assess in vitro bacterial adhesion and viability after liquid perfluorocarbon exposure and to assess bacterial recovery after partial liquid ventilation in vivo in rabbits. SETTING:University anim...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199912000-00023
更新日期:1999-12-01 00:00:00
abstract:OBJECTIVE:Gabexate mesilate is a synthetic protease inhibitor capable of inhibiting both coagulation and cytokine production by monocytes. To investigate whether gabexate mesilate is useful for the prevention of posttraumatic spinal cord injury, we examined its effect on compression trauma-induced spinal cord injury in...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199705000-00026
更新日期:1997-05-01 00:00:00
abstract:OBJECTIVES:In this study, we hypothesized that coronavirus disease 2019 patients exhibit sublingual microcirculatory alterations caused by inflammation, coagulopathy, and hypoxemia. DESIGN:Multicenter case-controlled study. SETTING:Two ICUs in The Netherlands and one in Switzerland. PATIENTS:Thirty-four critically i...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000004862
更新日期:2021-01-07 00:00:00