Abstract:
BACKGROUND:One form of sepsis, or endotoxic shock, is a hyperactivated systemic response caused by excessive expression of proinflammatory mediators, which results from Gram-negative bacterial lipopolysaccharide-stimulated Toll-like receptor-4 signaling. This lipopolysaccharide signaling is known to consist of a MyD88-dependent nuclear factor-κB-mediated pathway that results in production of proinflammatory mediators (tumor necrosis factor-α, interleukin-6, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, inducible nitric oxide synthase, cyclooxygenase-2) and a MyD88-independent interferon regulatory factor-mediated pathway that regulates production of Type 1 interferon-inducible proteins (interferon γ-induced protein-10, monocyte chemotactic protein-1). In prior studies, phenylmethimazole markedly decreased virally induced Toll-like receptor-3 expression and signaling and significantly suppressed murine colitis in an experimental model wherein lipopolysaccharide is known to play an important role. OBJECTIVE:In this study, we probed the hypothesis that phenylmethimazole inhibits lipopolysaccharide-mediated Toll-like receptor-4 signaling and is efficacious in attenuating inflammatory changes and improving survival in an in vivo murine model of endotoxic shock. DESIGN:Experimental animal model. SETTING:University laboratory. SUBJECTS:Male C57BL/6J mice weighing 18-22 g. INTERVENTIONS:Phenylmethimazole (1 mg/kg) was administered intraperitoneally to mice before a lethal lipopolysaccharide challenge (25 mg/kg). RAW264.7 mouse macrophage cells were pretreated with phenylmethimazole followed by lipopolysaccharide stimulation. MEASUREMENTS AND MAIN RESULTS:: Macroscopic observations revealed that phenylmethimazole was significantly protective in controlling clinical manifestations of endotoxic shock and death under conditions wherein flunixin of meglumine and prednisolone were marginally effective. A combination of enzyme-linked immunosorbent assay, Northern blot, reverse transcriptase-polymerase chain reaction, immunohistochemistry, and Western blot analyses showed that phenylmethimazole attenuated lipopolysaccharide-induced increases in production of proinflammatory cytokines (tumor necrosis factor-α, interleukin-6, interferon-γ), endothelial cell adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1), inducible nitric oxide synthase and cyclooxygenase-2, interferon regulatory factor-1, interferon-inducible proteins (interferon γ-induced protein-10, monocyte chemotactic protein-1), and signal transducer and activator of transcription-1 phosphorylation in multiple tissues in mice. Consistent with these observations, electrophoretic mobility shift assay demonstrated that phenylmethimazole inhibited in vitro lipopolysaccharide-induced nuclear factor-κB and interferon regulatory factor-1 activation in RAW 264.7 mouse macrophages. CONCLUSIONS:Collectively, these results provide direct evidence that phenylmethimazole diminishes lipopolysaccharide-induced MyD88-dependent as well as MyD88-independent signaling pathways and is protective in an experimental model of endotoxic shock.
journal_name
Crit Care Medjournal_title
Critical care medicineauthors
Benavides U,Gonzalez-Murguiondo M,Harii N,Lewis CJ,Schwartz AL,Giuliani C,Napolitano G,Dagia NM,Malgor R,McCall KD,Kohn LDdoi
10.1097/CCM.0b013e318236ef8bsubject
Has Abstractpub_date
2012-03-01 00:00:00pages
886-94issue
3eissn
0090-3493issn
1530-0293journal_volume
40pub_type
杂志文章abstract:OBJECTIVE:To review trial design issues related to control groups. DESIGN:Review of the literature with specific reference to critical care trials. MAIN RESULTS AND CONCLUSIONS:Performing randomized controlled trials in the critical care setting presents specific problems: studies include patients with rapidly lethal...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0b013e3181922bf4
更新日期:2009-01-01 00:00:00
abstract:OBJECTIVE:To determine whether plasma lipid hydroperoxides may be a useful marker for sepsis. DESIGN:Exploratory, open-label study. SETTING:Critical care unit at a university medical center. PATIENTS:Twelve patients with sepsis syndrome requiring hemodynamic monitoring with pulmonary artery catheters. Seven patients...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199109000-00004
更新日期:1991-09-01 00:00:00
abstract:OBJECTIVE:The Acute Respiratory Distress Syndrome Network protocol recommends limiting tidal volume and plateau pressure; it also recommends increasing respiratory rate to prevent hypercapnia. We tested a strategy that combines the low tidal volume with lower respiratory rates and minimally invasive CO2 removal. SUBJE...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000000312
更新日期:2014-06-01 00:00:00
abstract:OBJECTIVE:To determine the specific effect of peak volume history pressure on the inflation limb of the pressure-volume curve and peak pressure-volume curve pressure on the deflation limb of the pressure-volume curve. DESIGN:Prospective assessment of pressure-volume curves in saline, lung lavage injured sheep. SETTIN...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/01.ccm.0000128573.28173.2e
更新日期:2004-06-01 00:00:00
abstract:OBJECTIVE:Procalcitonin may be associated with reduced antibiotic usage compared to usual care. However, individual randomized controlled trials testing this hypothesis were too small to rule out harm, and the full cost-benefit of this strategy has not been evaluated. The purpose of this analysis was to evaluate the ef...
journal_title:Critical care medicine
pub_type: 杂志文章,meta分析,评审
doi:10.1097/CCM.0b013e31821201a5
更新日期:2011-07-01 00:00:00
abstract:OBJECTIVE:To provide a meta-analysis of current literature concerning the validation of thoracic impedance cardiography (TIC) and to explain the variations in the reported results from the differences in the studies. DATA SOURCES:A computer-assisted search of English-language, German, and Dutch literature was performe...
journal_title:Critical care medicine
pub_type: 杂志文章,meta分析
doi:10.1097/00003246-199906000-00053
更新日期:1999-06-01 00:00:00
abstract::Total parenteral nutrition (TPN) increases CO2 production (VCO2) in patients on intermittent positive-pressure ventilation who cannot match their CO2 excretion to the CO2 load, leading to an increase in PaCO2. We studied gas exchange and blood gas values in six patients with chronic respiratory failure, who were venti...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198507000-00005
更新日期:1985-07-01 00:00:00
abstract:BACKGROUND:Noninvasive positive-pressure ventilation (NPPV) has been shown to be effective in select patients enrolled in clinical trials. However, few data are available on the use of NPPV as routine standard medical care for patients with respiratory failure outside of controlled trials. MEASUREMENTS AND MAIN RESULT...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/01.CCM.0000300084.67277.90
更新日期:2008-02-01 00:00:00
abstract:OBJECTIVE:Nitric oxide regulates epithelial permeability and other properties of the intestinal mucosal barrier. It previously has been shown in animals that intestinal mucosal nitric oxide production is impaired during gut hypoperfusion. The study was performed to confirm the presence of intestinal mucosal nitric oxid...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/01.CCM.0000080489.67211.1F
更新日期:2003-08-01 00:00:00
abstract:OBJECTIVES:Regional tidal lung strain may trigger local inflammation during mechanical ventilation, particularly when additional inflammatory stimuli are present. However, it is unclear whether inflammation develops proportionally to tidal strain or only above a threshold. We aimed to 1) assess the relationship between...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000000346
更新日期:2014-07-01 00:00:00
abstract:OBJECTIVES:Acute renal failure is a complication in critically ill patients that has been associated with an excess risk of hospital mortality. Whether this reflects the severity of the disease or whether acute renal failure is an independent risk factor is unknown. The aim of this study was to analyze severity of illn...
journal_title:Critical care medicine
pub_type: 杂志文章,多中心研究
doi:10.1097/00003246-200209000-00016
更新日期:2002-09-01 00:00:00
abstract:OBJECTIVE:Acute renal failure can be treated with continuous renal replacement therapy (CRRT) or intermittent hemodialysis. There is no difference in mortality, although patients treated with CRRT may have a higher rate of renal recovery. Given these considerations, an estimate of the costs by modality may help in choo...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/01.CCM.0000045182.90302.B3
更新日期:2003-02-01 00:00:00
abstract:OBJECTIVE:Clinical predictors for acute respiratory distress syndrome (ARDS) have been studied in few prospective studies. Although transfusions are common in the intensive care unit, the role of submassive transfusion in non-trauma-related ARDS has not been studied. We describe here the clinical predictors of ARDS ris...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/01.ccm.0000165566.82925.14
更新日期:2005-06-01 00:00:00
abstract:OBJECTIVES:To create a novel tool to predict favorable neurologic outcomes during ICU stay among children with critical illness. DESIGN:Logistic regression models using adaptive lasso methodology were used to identify independent factors associated with favorable neurologic outcomes. A mixed effects logistic regressio...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000002753
更新日期:2018-01-01 00:00:00
abstract:OBJECTIVE:Initial success with chimeric antigen receptor-modified T cell therapy for relapsed/refractory acute lymphoblastic leukemia is leading to expanded use through multicenter trials. Cytokine release syndrome, the most severe toxicity, presents a novel critical illness syndrome with limited data regarding diagnos...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000002053
更新日期:2017-02-01 00:00:00
abstract:OBJECTIVES:To identify and appraise articles describing criteria used to prioritize or withhold a critical care admission. DATA SOURCES:PubMed, Embase, Medline, EBM Reviews, and CINAHL Complete databases. Gray literature searches and a manual review of references were also performed. Preferred Reporting Items for Syst...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000004624
更新日期:2020-11-01 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:To prospectively evaluate the oxygenation effect of inhaled nitric oxide (INO) delivered during high-frequency oscillatory ventilation in adult patients with the acute respiratory distress syndrome and oxygenation failure. DESIGN Prospective, clinical study. SETTING:Intensive care unit of a university teachi...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/01.CCM.0000049953.86613.02
更新日期:2003-02-01 00:00:00
abstract:OBJECTIVE:To review recent advances in the use of transforming growth factor (TGF)-beta in acute lung injury and to apply this knowledge to understanding the pathophysiology of this syndrome. DATA SOURCES AND STUDY SELECTION:Published research and review articles in the English language related to the role of TGF-beta...
journal_title:Critical care medicine
pub_type: 杂志文章,评审
doi:10.1097/01.CCM.0000057901.92381.75
更新日期:2003-04-01 00:00:00
abstract::offstudied hemodynamic and renal effects of increasing the dosage of dopamine (DP) by 5 micrograms/kg X min, in 7 patients with peritonitis and clinical findings of septic shock, all of whom were already receiving variable dosages of DP. Stroke index (SI) (p less than .01), except in 3 cases, and mean arterial pressur...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198401000-00006
更新日期:1984-01-01 00:00:00
abstract:BACKGROUND:Remarkable progress has been made during the last decade in defining the molecular mechanisms that underlie septic shock. This rapidly expanding field is leading to new therapeutic opportunities in the management of severe sepsis. AIM:To provide the clinician with a timely summary of the molecular biology o...
journal_title:Critical care medicine
pub_type: 杂志文章,评审
doi:10.1097/CCM.0b013e31819267fb
更新日期:2009-01-01 00:00:00
abstract:OBJECTIVE AND DESIGN:To review and discuss selected literature, expert opinion, and conventional care of the hyperglycemic perioperative or critically ill patient. MAIN POINTS:Diabetes mellitus, the most commonly encountered perioperative endocrinopathy, continues to increase dramatically in prevalence. Diabetes is th...
journal_title:Critical care medicine
pub_type: 杂志文章,评审
doi:10.1097/01.ccm.0000115623.52021.c0
更新日期:2004-04-01 00:00:00
abstract::Intralipid elimination patterns were compared in 25 healthy controls, 12 patients recovering from uncomplicated cholecystectomy, and 25 critically ill patients. The intravenous fat tolerance test revealed a similar fractional removal rate (k2) in healthy controls and critically ill patients, but k2 was increased in ch...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198605000-00009
更新日期:1986-05-01 00:00:00
abstract:OBJECTIVE:To characterize the withholding or withdrawing of life support from patients with severe head injury. SETTING:San Francisco General Hospital, a city and county hospital with a Level I trauma center. DESIGN:A standardized questionnaire was used to collect data on demographics and functional outcome of severe...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199509000-00018
更新日期:1995-09-01 00:00:00
abstract:OBJECTIVES:Acinetobacter baumannii complex bacteremia has been identified increasingly in critical patients admitted in ICUs. Notably, A. baumannii complex bacteremia has a high mortality rate, yet the risk factors associated with mortality remain unclear and controversial. DESIGN:Retrospective study. SETTING:All adu...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000000125
更新日期:2014-05-01 00:00:00
abstract::Two new catecholamines, dopamine and dobutamine, have found widespread use for cardiovascular support. The relative efficacy of these drugs in aiding resuscitation from cardiopulmonary arrest is unknown. Dogs were subjected to either asphyxial or fibrillatory cardiac arrest. Resuscitation was attempted with artificial...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198109000-00005
更新日期:1981-09-01 00:00:00
abstract:OBJECTIVE:To determine the frequency, etiology, and risk factors of ventilator-associated pneumonia (VAP) and purulent tracheobronchitis (TBX) in patients who have undergone heart surgery. To study the predictive role of systematic surveillance cultures. DESIGN:Prospective study. SETTING:Heart surgery intensive care ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/01.ccm.0000084807.15352.93
更新日期:2003-07-01 00:00:00
abstract::Critically ill patients who fear impending death may die suddenly. We studied prospectively the incidence of death in critically ill surgical patients who articulated the fear that they were about to die. Physiologic, environmental, and behavioral correlates which might influence perceptions of impending death were ex...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198607000-00005
更新日期:1986-07-01 00:00:00
abstract:OBJECTIVE:To determine the blood discard volume, as a multiple of deadspace, that is required for accurate arterial blood gas and electrolyte testing from arterial catheters. DESIGN:Prospective, controlled, crossover trial. SETTING:Eighteen-bed intensive care unit of a metropolitan teaching hospital. PATIENTS:A tota...
journal_title:Critical care medicine
pub_type: 临床试验,杂志文章
doi:10.1097/01.CCM.0000063448.98777.EF
更新日期:2003-06-01 00:00:00
abstract:OBJECTIVE:To compare the effects of continuous negative extrathoracic pressure (CNEP) and positive end-expiratory pressure (PEEP) at the same level of transpulmonary pressure. DESIGN:Prospective analysis. SETTING:Medical intensive care unit of a university hospital. PATIENTS:Nine consecutive acute lung injury patien...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199806000-00021
更新日期:1998-06-01 00:00:00