ISSN:0090-3493    

出版商:OVID    

年代:1995

数据来源: OVID

ISSN:0090-3493    

出版商:OVID    

年代:1995

数据来源: OVID

ISSN:0090-3493    

出版商:OVID    

年代:1995

数据来源: OVID

ISSN:0090-3493    

出版商:OVID    

年代:1995

数据来源: OVID

ISSN:0090-3493    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectivesEndotoxin is one of the principal mediators of Gram-negative septic shock. Pretreatment with monophosphoryl lipid A, a hydrolyzed derivative of endotoxin from Salmonella minnesota R595, induces endotoxin tolerance and nonspecific resistance to infection in experimental animals. The present clinical trial was undertaken to test the response to monophosphoryl lipid A in humans and the ability of monophosphoryl lipid A to attenuate the response of normal human volunteers to U.S. Reference Ec-5 endotoxin.DesignProspective, double-blind, randomized, controlled trial.SettingClinical research center.PatientsForty-four healthy volunteers.InterventionsIn part 1 of the study, 29 volunteers were randomized in varying ratios to receive vehicle control or monophosphoryl lipid A intravenously in a double-blind dose escalation trial. In part 2 of the study, 12 volunteers were randomized to receive either monophosphoryl lipid A (20 micro gram/kg) or vehicle control and, 24 hrs later, all 12 volunteers were challenged with U.S. Reference Ec-5 endotoxin (20 units/kg intravenous, bolus injection). Systemic response to endotoxin challenge was evaluated and compared between the monophosphoryl lipid A and vehicle control-pretreated subjects.Measurements and Main ResultsIn part 1 of the study, subjective effects and increases in cytokine levels were not observed until a dose of 10 micro gram/kg of monophosphoryl lipid A was administered. Six volunteers receiving a maximum dose of 20 micro gram/kg experienced mild-to-moderate symptoms that did not require therapy. Moderate increases in temperature, heart rate, and tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8 release were observed. IL-1 alpha and IL-1 beta were not detected but a significant increase in IL-1 receptor antagonist was observed.In part 2 of the study, monophosphoryl lipid A pretreatment reduced the number of volunteers who experienced one or more subjective complaints after endotoxin administration (3/6 vs.6/6; p equals .09). The febrile response and tachycardic response to endotoxin were significantly reduced by pretreatment with monophosphoryl lipid A. Monophosphoryl lipid A-pretreated volunteers demonstrated significantly reduced concentrations of TNF-alpha after endotoxin challenge, as compared with subjects treated with vehicle control (84 plus minus 76 vs. 244 plus minus 128 pg/mL; p less than .05). IL-6 concentrations (100 plus minus 91 vs. 268 plus minus 171 pg/mL; p less than .05) and IL-8 concentrations (136 plus minus 86 vs. 632 plus minus 323 pg/mL; p less than .05) elicited by endotoxin challenge were also significantly reduced by monophosphoryl lipid A pretreatment.ConclusionsData indicate that monophosphoryl lipid A, in a dose 10,000 times that of endotoxin, used in experimental pyrogenicity trials, is well tolerated in human volunteers. Pretreatment of normal human volunteers with monophosphoryl lipid A attenuated the systemic response to bacterial endotoxin. These data support further clinical testing of monophosphoryl lipid A for the prevention or amelioration of the severe sequelae of sepsis.(Crit Care Med 1995; 23:9-17)

ISSN:0090-3493    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectiveTo assess survival after cardiac arrest and to determine whether age is an independent determinant of late mortality or poor neurologic outcome.DesignAnalyses using results of Brain Resuscitation Clinical Trial I (1979 to 1984) and Brain Resuscitation Clinical Trial II (1984 to 1989), two randomized, double-blind studies of outcome following cardiac arrest.SettingA multicenter study in 12 acute care hospitals in nine countries (Brain Resuscitation Clinical Trial I), and 24 hospitals in eight countries (Brain Resuscitation Clinical Trial II).PatientsA total of 774 patients who were initially comatose after successful resuscitation from cardiac arrest. The analyses include both in- and out-of-hospital cardiac arrests.ResultsThe 6-month mortality rate for the entire group was 81%. Mortality rate was 94% for the oldest group (more than 80 yrs) compared with 68% for the youngest group (less than equals 45 yrs) (p less than .01). Other independent predictors of mortality were history of diabetes mellitus, inhospital arrests, arrest time of more than 5 mins, history of congestive heart failure, a noncardiac cause of arrest, and cardiopulmonary resuscitation time of more than 20 mins. Of the 774 patients, 27% recovered good neurologic function. There was no statistically significant difference in neurologic recovery rates by age. Multivariate analysis showed that independent predictors of good neurologic recovery were: no history of diabetes mellitus, a cardiac cause of arrest, short arrest time, and short cardiopulmonary resuscitation time.ConclusionIncreasing age was a factor in postresuscitation mortality, but was not an independent predictor of poor neurologic outcome.(Crit Care Med 1995; 23:18-25)

ISSN:0090-3493    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectiveTo investigate the balance between circulating concentrations of interleukin (IL)-1 and its natural inhibitor interleukin-1 receptor antagonist (IL-1Ra) in human inflammation.DesignProspective case-control study.SettingUniversity hospital burn care unit.PatientsFifteen patients with second- or third-degree thermal injuries of 7% to 78% of total body surface and 15 healthy age- and sex-matched control subjects.InterventionsNone.Measurements and Main ResultsMedian plasma IL-1Ra, but not IL-1 beta or tumor necrosis factor-alpha (TNF-alpha) concentrations were markedly increased on the day of admission in patients with thermal injuries compared with controls (1615 [range 426 to 23,800] vs. 494 [range 196 to 1093] pg/mL; p less than .001). In survivors, the median IL-1Ra concentration normalized 12 to 21 days after admission. The concentration of IL-1Ra on the day of admission was weakly positively correlated to the extent and degree of thermal injury (r2equals .46; p less than .05). IL-1Ra on days 1 to 3 was highest in three nonsurvivors with inhalation injuries compared with survivors (2166 [range 1362 to 36,624] vs. 1344 [range 665 to 13,085] pg/mL; p less than .05). IL-1Ra increased significantly after debridement and skin transplantation (preoperatively 742 [range 488 to 1506] vs. postoperatively 1431 [range 1286 to 2107] pg/mL; p less than .01). In nonsurvivors, median IL-1Ra was 3.6-fold higher than IL-1 beta on days 1 to 2 and 36-fold higher than IL-1 beta in three patients with bacteremia. IL-1Ra was studied for its relationship to previously reported parameters of the acute-phase response determined in the same samples from these patients. The increased concentrations of IL-1Ra coincided with a decrease in serum albumin concentration and increases in rectal temperature. However, IL-1Ra did not correlate with rectal temperature, plasma concentrations of endotoxin, IL-1 beta, or TNF-alpha either at admission or in follow-up samples.ConclusionsThermal injury causes an increase of circulating IL-1Ra, especially in patients with inhalation injuries. With the current plasma assays for IL-1 beta, IL-1Ra may be a more sensitive marker of human inflammation than IL-1 beta or TNF-alpha.(Crit Care Med 1995; 23:26-33)

ISSN:0090-3493    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectiveTo define whether endothelin-1, a peptide produced by injured/ischemic endothelium, has any effect on monocyte intracellular calcium and the production of interleukin (IL)-1 and IL-6.DesignProspective controlled laboratory study. Human monocytes from healthy donors were assayed for intracellular calcium by fluorometry and were stimulated for 24 hrs in tissue culture with purified endotoxin or endothelin.SettingVeterans Affairs Medical Center surgical critical care basic science laboratory.Measurements and Main ResultsEndothelin-1 increased the intracellular calcium concentration in fura-2 loaded human monocytes to a mean value of 37 plus minus 4 nmol. Phytohemagglutinin increased intracellular calcium in control monocytes to a mean value of 97 plus minus 12 nmol (n equals 15; p less than .001). Endothelin had no effect on neutrophil or lymphocyte intracellular calcium. Monocytes incubated with 10minus9 M endothelin significantly increased IL-6 production to values nearly as high as the lipopolysaccharide controls, but did not increase IL-1 production (n equals 8; p less than .01).ConclusionEndothelin-1 increased intracellular calcium in monocytes and caused production of IL-6.(Crit Care Med 1995; 23:34-40)

ISSN:0090-3493    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectiveTo test if serially sampled determinations of the contact system proteins and factor V have prognostic value for death in patients who develop the systemic inflammatory response syndrome.DesignProspective, observational study with sequential measurements in an inception cohort.SettingMedical intensive care unit (ICU) in a community hospital.PatientsOver a 1-yr period, a population base sample of 23 patients was selected from all ICU admissions who met established criteria for the systemic inflammatory response syndrome.InterventionsNone.Measurements and Main ResultsComponents of the contact system, factor XII, prekallikrein, high-molecular-weight kininogen, factor XI, alpha2-macroglobulin-kallikrein complexes and factor V values were measured in plasma samples collected serially (day of admission, and at 2, 12, 24, 48 and/or 72 hrs or at discharge). Data were analyzed to determine if admission values or serially obtained values within 48 hrs were useful in predicting outcome. Fourteen patients survived and nine died.At admission, in all patients, assay values indicated that prekallikrein, high-molecular-weight kininogen, and factor V were significantly lower than normal (as observed in a range of 20 to 23 healthy adults), alpha2-macroglobulin-kallikrein complexes were higher than normal, while concentrations of factor XII and factor XI were in the normal range. No differences were detected in the admission values between survivors and nonsurvivors, nor between patients with positive or negative blood cultures. However, subsequent values demonstrated a difference in values between survivors and nonsurvivors. Survivors showed improvement in high molecular weight kininogen values and higher than normal factor V values, as compared with nonsurvivors.ConclusionsLow or persistently low serial factor XII, high-molecular-weight kininogen and factor V values are associated with a poor prognosis, whereas high or increasing values of factor XII, high-molecular-weight kininogen, prekallikrein, and factor V all correlate with a favorable outcome.(Crit Care Med 1995; 23:41-51)

ISSN:0090-3493    

出版商:OVID    

年代:1995

数据来源: OVID