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31. |
Role of ubiquitin-proteasome pathway in skeletal muscle wasting in rats with endotoxemia |
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Critical Care Medicine,
Volume 31,
Issue 6,
2003,
Page 1802-1807
Jiake,
Chai Yanqiu,
Wu Zhiyong,
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摘要:
ObjectiveTo investigate the mechanism of muscle protein breakdown under endotoxemia condition.DesignRandomized, controlled, animal experiment in a hospital institute.SettingExperimental laboratory.InterventionEither saline or endotoxin (Escherichia coliO55B5, 10 mg/kg) were administered into the peritoneal cavity in rats.Measurements and Main ResultsThe rate of total protein breakdown was increased by 29% and 61% in extensor digitorum longus muscle at 2 hrs and 6 hrs, whereas the myofibrillar proteolytic rate was increased by 155%, 222%, and 40% at 2 hrs, 6 hrs, and 12 hrs, respectively, in the endotoxin treatment group compared with that of the pair-fed normal control group. Meanwhile, compared with the normal control group, the level of 2.4-kilobase (kb) messenger RNA (mRNA) for ubiquitin in extensor digitorum longus muscle in rats was increased by 153% and 470% at 2 hrs and 6 hrs. There were 87% and 117% increases in 1.2-kb mRNA for E2-14K, and 89% and 168% increase in RC2 mRNA expression in extensor digitorum longus muscle in endotoxemic rats than normal control rats at 2 hrs and 6 hrs after injection of endotoxin peritoneally. The tumor necrosis factor-&agr; and interleukin-6 concentrations in rat plasma progressively increased after endotoxin treatment, but tumor necrosis factor-&agr; peaked at the 2-hr time point, whereas interleukin-6 peaked at 12 hrs. Endotoxin administration resulted in a marked increase in endotoxin level at 2 hrs and 6 hrs. No significant change was observed in soleus muscle after endotoxin injection. A significantly positive correlation was found between the net release of 3-methylhistidine and respective values of endotoxin, intensity of mRNA expression of 2.-kb ubiquitin, 1.2-kb E2-14K, and subunit RC2 in extensor digitorum longus muscle (r= .9882, .9731, .9653, .9814,p< .05). However, no significant correlation was seen between tumor necrosis factor-&agr; or interleukin-6 and respective values of 3-methylhistidine, mRNA expression of 2.4-kb ubiquitin, 1.2-kb E2-14K, and subunit RC2 (r= .3580, .4521, .5277, .4931,p> .05;r= .3950, .1767, .2136, .2519,p> .05, respectively.) in soleus muscle.ConclusionsEndotoxemia can induce enhancement of skeletal muscle protein breakdown, mainly involving myofibrillar protein and white, fast-twitch extensor digitorum longus muscle. Ubiquitin-proteasome proteolytic pathway plays an important and major role in skeletal muscle proteolysis. Endotoxin, tumor necrosis factor-&agr;, and interleukin-6 can directly or indirectly regulate muscle protein breakdown.
ISSN:0090-3493
出版商:OVID
年代:2003
数据来源: OVID
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32. |
Modulation of tissue Toll-like receptor 2 and 4 during the early phases of polymicrobial sepsis correlates with mortality* |
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Critical Care Medicine,
Volume 31,
Issue 6,
2003,
Page 1808-1818
David,
Williams Tuanzhu,
Ha Chuanfu,
Li John,
Kalbfleisch John,
Schweitzer William,
Vogt I.,
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摘要:
ObjectiveTo determine whether there was a correlation between induction of polymicrobial sepsis, modulation of tissue Toll-like receptor (TLR) gene, and protein expression and survival outcome.DesignProspective, randomized animal study.SettingUniversity medical school research laboratory.SubjectsAge- and weight-matched ICR/HSD mice.InterventionsSepsis was induced by cecal ligation and puncture (CLP). No-surgery and sham (laparotomy)-operated mice were controls. We also examined tissue TLR2 and TLR4 messenger RNA and TLR4 protein levels in mice treated with an immunomodulator that increases survival in polymicrobial sepsis. In the immunomodulator study, mice were treated with glucan phosphate (50 mg/kg, intraperitoneally) 1 hr before CLP. No-surgery, sham surgery, glucan + no-surgery, sham surgery + glucan, and CLP groups were employed as controls.Measurements and Main ResultsTotal RNA was isolated from liver, lung, and spleen at 0, 1, 3, 6, 8, and 24 hrs after CLP. TLR gene expression was assessed by reverse transcription-polymerase chain reaction. Tissue TLR4 protein levels were evaluated at 24 hrs by Western blot and immunohistochemistry. CLP sepsis increased (p< .05) liver and lung TLR2 and TLR4 gene expression compared with controls. TLR4 protein concentrations also were increased. Increased TLR2/4 gene and TLR4 protein expression correlated with mortality. Immunoprophylaxis with glucan phosphate increased (p< .001) long-term survival (20% vs. 70%) but inhibited (p< .05) CLP-induced increases in tissue TLR2 and TLR4 messenger RNA expression as well as TLR4 protein expression.ConclusionsEarly increases in TLR2/4 gene and TLR4 protein expression correlated with mortality, whereas blunting TLR gene and protein expression correlated with improved long-term survival. This suggests that early up-regulation of tissue TLR2/4 may play a role in the proinflammatory response and pathophysiology of polymicrobial sepsis.
ISSN:0090-3493
出版商:OVID
年代:2003
数据来源: OVID
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33. |
Stroke volumes and end-tidal carbon dioxide generated by precordial compression during ventricular fibrillation |
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Critical Care Medicine,
Volume 31,
Issue 6,
2003,
Page 1819-1823
Andrej,
Pernat Max,
Weil Shijie,
Sun Wanchun,
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摘要:
ObjectiveThe objective of this study was to measure stroke volumes produced by precordial compression during cardiopulmonary resuscitation and to quantitate relationships of stroke volume to measurements of end-tidal carbon dioxide.DesignA prospective, observational animal study.SettingMedical research laboratory in a university-affiliated research and educational foundation.SubjectsDomestic pigs.InterventionsEighteen anesthetized male, domestic pigs weighing between 40 and 45 kg were investigated. Ventricular fibrillation was electrically induced and continued for intervals ranging from 4 to 10 mins. Precordial compression was maintained at 80 per minute together with mechanical ventilation after endotracheal intubation.Measurements and Main ResultsStroke volumes were measured with the aid of transesophageal echocardiographic imaging. End-tidal carbon dioxide was quantitated with conventional capnography. Baseline values of thermodilution cardiac output were highly correlated with echocardiographic measurements (r = .92). The stroke volume index produced by precordial compression averaged 0.45 mL/kg or approximately 37% of the average prearrest value of 1.22 mL/kg. The end-tidal carbon dioxide was highly predictive of stroke volume index (r = .88,p< .001) with a mean bias of 0.003 mL/kg.ConclusionsWe confirmed that precordial compression produces approximately one third of prearrest stroke volumes during cardiopulmonary resuscitation and demonstrated that end-tidal carbon dioxide was quantitatively predictive of stroke volume index estimated by transesophageal echocardiographic imaging.
ISSN:0090-3493
出版商:OVID
年代:2003
数据来源: OVID
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34. |
Resuscitation with polyethylene glycol-modified human hemoglobin improves microcirculatory blood flow and tissue oxygenation after hemorrhagic shock in awake hamsters* |
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Critical Care Medicine,
Volume 31,
Issue 6,
2003,
Page 1824-1830
Reto,
Wettstein Amy,
Tsai Dominique,
Erni Robert,
Winslow Marcos,
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摘要:
ObjectiveTo determine whether resuscitation with polyethylene glycol-modified human hemoglobin (MalPEG-Hb), an oxygen-carrying blood replacement fluid with 4 g/dL Hb, viscosity of 2.5 cP, colloid osmotic pressure of 49 mm Hg, and p50 of 5.5 mm Hg, improves systemic and microvascular variables after hemorrhage compared with shed blood (SB) and 5% hydroxyethyl starch (HES).SettingLaboratory.SubjectsGolden Syrian hamsters.DesignProspective study.InterventionsHamsters implemented with a skin fold chamber were hemorrhaged 50% of blood volume and resuscitated with 50% shed blood volume (SB, HES, or MalPEG-Hb).Measurements and Main ResultsShock and resuscitation were monitored for 1 hr each. Microvascular events were characterized in terms of vessel diameter, flow velocity, functional capillary density, and Po2in arterioles, venules, and extravascular tissue. Systemic variables include mean arterial pressure, heart rate, Po2, Pco2, pH, and base excess. MalPEG-Hb resuscitation increased functional capillary density to 64% vs. 44% for SB and 32% for HES relative to baseline before shock. Microvascular flow increased 16% for MalPEG-Hb relative to baseline and remained decreased by 44% for SB and 80% for HES. Hemoglobin concentration was 10.4 g/dL with SB, 7.5 (6.8 g/dL in red blood cells and 0.9 g/dL in plasma) with MalPEG-Hb, and 7.5 g/dL with HES, leading to tissue Po2of 19, 8, and 5 mm Hg respectively. Calculations of oxygen extraction show that 0.9 g/dL of MalPEG-Hb increased oxygen extraction per gram of red cell hemoglobin in the tissue analyzed compared with SB. These measurements correlate well with a systemic indicator of recovery, base excess, 5.4 ± 4.7 (MalPEG-Hb), 1.7 ± 3.8 (SB), and −0.3 ± 5.7 (HES).ConclusionThe presence of 0.9 g/dL of high oxygen affinity MalPEG-Hb improves microvascular blood flow and oxygen transport during shock to a significantly greater extent than that attainable with blood or HES.
ISSN:0090-3493
出版商:OVID
年代:2003
数据来源: OVID
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35. |
Prone position in subarachnoid hemorrhage patients with acute respiratory distress syndrome: Effects on cerebral tissue oxygenation and intracranial pressure* |
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Critical Care Medicine,
Volume 31,
Issue 6,
2003,
Page 1831-1838
Andrea,
Reinprecht Manfred,
Greher Stefan,
Wolfsberger Wolfgang,
Dietrich Udo,
Illievich Andreas,
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摘要:
ObjectiveTo analyze the effect of prone position on cerebral perfusion pressure and brain tissue oxygen partial pressure in subarachnoid hemorrhage patients with acute respiratory distress syndrome (ARDS).DesignClinical study with retrospective data analysis.SettingNeurosurgical intensive care unit of a primary level university hospital.PatientsSixteen patients treated for intracranial aneurysm rupture with initial Hunt and Hess grade III or worse who developed ARDS within 2 wks after the bleeding.InterventionsRoutine neurosurgical intensive care treatment for subarachnoid hemorrhage and posthemorrhagic vasospasm including cerebral monitoring with continuous intracranial pressure and brain tissue oxygen partial pressure recordings.Measurements and Main ResultsHemodynamics, arterial oxygenation, ventilatory setting, intracranial pressure, cerebral perfusion pressure, and brain tissue oxygen partial pressure in the supine as well as in the prone position were analyzed and compared. A significant increase in Pao2from 97.3 ± 20.7 torr (mean ± sd) in the supine position to 126.6 ± 31.7 torr in the prone position was joined by a significant increase in brain tissue oxygen partial pressure from 26.8 ± 10.9 torr to 31.6 ± 12.2 torr (bothp< .0001), whereas intracranial pressure increased from 9.3 ± 5.2 mm Hg to 14.8 ± 6.7 mm Hg and cerebral perfusion pressure decreased from 73.0 ± 10.5 mm Hg to 67.7 ± 10.7 mm Hg (bothp< .0001).ConclusionsThe beneficial effect of prone positioning on cerebral tissue oxygenation by increasing arterial oxygenation appears to outweigh the expected adverse effect of prone positioning on cerebral tissue oxygenation by decreasing cerebral perfusion pressure in ARDS patients.
ISSN:0090-3493
出版商:OVID
年代:2003
数据来源: OVID
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36. |
Activation of protein C following infusion of protein C concentrate in children with severe meningococcal sepsis and purpura fulminans: A randomized, double-blinded, placebo-controlled, dose-finding study |
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Critical Care Medicine,
Volume 31,
Issue 6,
2003,
Page 1839-1847
Ester,
de Kleijn Ronald,
de Groot C.,
Hack Paul,
H. Mulder Werner,
Engl Berta,
Moritz Koen,
Joosten Jan,
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摘要:
BackgroundMeningococcal septic shock in children results in high mortality and morbidity, and decreased protein C levels in these patients are associated with a poor outcome. We carried out a randomized, double-blinded, placebo-controlled study by supplying protein C concentrate. This phase 2 study was designed to assess the activation process of protein C and to study the dosing regimen of protein C concentrate in children with purpura fulminans and meningococcal septic shock in the perspective of a possible phase 3 trial.MethodsForty children were randomized to receive placebo or protein C concentrate (200 IU/kg, 400 IU/kg, or 600 IU/kg), for a maximum of 7 days. Clinical and laboratory data, including plasma levels of protein C and activated protein C (APC), were collected at various time points. All patients received standard therapy for septic shock, including antibiotics, inotropic/vasoactive drugs, and blood products.ResultsIncreased APC levels relative to baseline were observed for the 27 of 28 patients treated with protein C concentrate, and the areas under the curve of protein C and APC were correlated with the dosage of protein C concentrate administered. Activation of coagulation, as evidenced by d-dimer levels, as well as the ratio of thrombin vs. APC normalized significantly faster with increasing dosages of protein C concentrate. No adverse reactions related to protein C concentrate were observed. Nine of the 40 (23%) patients died, and five survivors required amputations, with no differences in these rates among the randomized groups. Baseline APC levels were positively correlated with sequential organ failure assessment and pediatric risk of mortality scores and with d-dimers, tumor necrosis factor-&agr;, interleukin-1, interleukin-6, interleukin-8, plasminogen activator inhibitor-1, TAT complexes, and PAP complexes.ConclusionsTreatment with protein C concentrate is safe in children with purpura fulminans and meningococcal septic shock and leads to dose-related increases of plasma APC and resolution of coagulation imbalances.
ISSN:0090-3493
出版商:OVID
年代:2003
数据来源: OVID
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37. |
Effect of human immunodeficiency virus on intensive care unit outcome of patients with Guillain-Barré syndrome |
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Critical Care Medicine,
Volume 31,
Issue 6,
2003,
Page 1848-1850
Gunter,
Schleicher Andrew,
Black Andre,
Mochan Guy,
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摘要:
ObjectivesThe primary objective of this study was to investigate the effect of human immunodeficiency virus (HIV) infection on the outcome of patients admitted to the intensive care unit (ICU) with severe Guillain-Barré syndrome (GBS) requiring mechanical ventilation. A secondary objective was to compare the clinical and laboratory features of HIV-seronegative and HIV-seropositive patients admitted to the ICU with severe GBS.DesignRetrospective chart review.SettingTwo tertiary, academic hospitals in Johannesburg, South Africa.Materials and MethodsThe case records of all patients admitted to the ICU with GBS between January 1995 and June 2002 were reviewed. Patients were included if their HIV status was known and if they had clinical features, electrophysiologic studies, and cerebrospinal fluid analyses consistent with GBS. Demographic data, days in ICU, days ventilated, CD4 T-lymphocyte counts (in the HIV group), cerebrospinal studies, infection rate, and mortality data were analyzed.ResultsA total of 13 patients met the inclusion criteria: seven were HIV seronegative and six were HIV seropositive. The median age in the HIV group was 34.5 yrs, compared with 47 yrs in the non-HIV group. There was no significant difference between the two groups in days spent in the ICU or days ventilated. There were no significant differences in cerebrospinal studies, electrophysiologic studies, and blood culture–positive infections between the two groups. All patients received intravenous immunoglobulin (0.4 g/kg/day for 5 days). There was one death in the HIV-seropositive group and no deaths in the HIV-seronegative group. The median CD4 T-lymphocyte count in the HIV group was 322.5 × 106cells/L.ConclusionHIV is commonly associated with GBS in South Africa. The ICU outcome in patients with HIV-associated GBS is similar to HIV-seronegative patients, particularly if the CD4 T-lymphocyte count is greater than 200 × 106cells/L at admission.
ISSN:0090-3493
出版商:OVID
年代:2003
数据来源: OVID
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38. |
Cocaine and the critical care challenge |
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Critical Care Medicine,
Volume 31,
Issue 6,
2003,
Page 1851-1859
Christina,
Shanti Charles,
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摘要:
ObjectiveCocaine, which first made its appearance >1,000 yrs ago, is now widely used throughout the world. The physiologic responses to cocaine may cause severe pathologic effects. This review highlights the many critical care challenges resulting from these effects.DesignHistorical vignettes, epidemiologic factors, modes of preparation and delivery, and the physiologic and pharmacologic effects of these agents are presented.SettingCocaine causes intense vasoconstriction, which potentially causes damage to all organ systems. Examples of these toxicities are presented.PatientsThe adverse multisystem responses to cocaine exposure produce organ failure, which challenges diagnostic accuracy and therapeutic intervention. Organ system failure involves the brain, heart, lung, kidneys, gastrointestinal tract, musculature, and other organs. These harmful effects are additive to preexisting organ dysfunction.InterventionRecognition of associated cocaine injury alerts the physician that organ dysfunction is more likely to occur and to be more severe. Such anticipation helps plan for therapy in the critical care setting.Results and ConclusionsCocaine use is an expanding health hazard, despite intense governmental efforts to contain its distribution and use. Recognition of the signs and symptoms of cocaine toxicity help anticipate the subsequent organ dysfunction and implement earlier organ system support.
ISSN:0090-3493
出版商:OVID
年代:2003
数据来源: OVID
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39. |
Acute lung injury: Is the intensive care unit the tip of the iceberg?* |
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Critical Care Medicine,
Volume 31,
Issue 6,
2003,
Page 1860-1861
Andrew,
Quartin Roland,
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ISSN:0090-3493
出版商:OVID
年代:2003
数据来源: OVID
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40. |
Platelet activating factor inhibition in sepsis: The end?* |
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Critical Care Medicine,
Volume 31,
Issue 6,
2003,
Page 1861-1862
Reuven,
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ISSN:0090-3493
出版商:OVID
年代:2003
数据来源: OVID
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