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Biomedical subjects

J L Vincent

Publications and source records attributed to J L Vincent.

At least 73 records · Page 4Linked to original sources
PubMed2000

Localized expression of cathepsin B-like sequences from root nodules of pea (Pisum sativum).

Cathepsin B is an ancient family of eukaryotic cysteine proteases. We describe PsCat1, a plant cathepsin B-like transcript, identified as an expressed sequence in Rhizobium-induced, nitrogen-fixing root nodules of pea. In situ hybridization studies in root nodules showed strong, extremely localized expression of PsCat1 in individual cells associated with the central infected tissue. Restriction fragment polymorphism mapping of the PsCat1 locus in pea shows no correlation with existing mutant lines defective in symbiosis.

Cathepsin B↗
PubMed2000

Consensus conference definitions for sepsis, septic shock, acute lung injury, and acute respiratory distress syndrome: time for a reevaluation.

Definitions for sepsis, septic shock, acute lung injury (ALI), and acute respiratory distress syndrome (ARDS) were developed by consensus conferences with the goal of achieving standardization of terminology and improved homogeneity of patient populations in clinical studies. Although such definitions have been useful in epidemiologic investigations, the criteria specified by the consensus conferences are broad and insufficiently specific to address the problem of heterogeneous mechanisms leading to clinical syndromes. An important challenge is to progress from clinical syndromes, as presently defined, to more specific entities that are delineated by alterations in specific immunologic or biochemical pathways. Such mechanistic definitions will provide more homogeneous groups of patients who can be identified at early stages of their clinical course. This approach encourages focused investigation of pathways leading to organ system dysfunction and death and, also, provides an efficient framework for the development of new therapies useful in critically ill patients.

Animals↗
PubMed2000

Phase II multicenter clinical study of the platelet-activating factor receptor antagonist BB-882 in the treatment of sepsis.

OBJECTIVE: To evaluate the safety and efficacy of the platelet-activating factor receptor antagonist BB-882 in the treatment of patients with sepsis. DESIGN: Double-blind, placebo-controlled, randomized, multi-centered study. SETTING: Thirty-four European intensive care units. PATIENTS: One hundred fifty-two patients with clinical suspicion of infection and a mean APACHE II score between 15 and 35 in the 24 hrs before entry into the trial. INTERVENTIONS: Patients received either a loading dose of 4 mg of BB-882 on the first day, followed by an intravenous infusion of 96 mg/24 hrs for up to 120 hrs, or placebo. MEASUREMENTS: Hemodynamic, respiratory and oxygen transport variables, blood lactate concentrations, interleukin-6, interleukin-8, tumor necrosis factor (TNF)-alpha, soluble TNF receptor concentrations, organ failure score, 28-day mortality rate, Acute Physiology And Chronic Health Evaluation (APACHE) II score within 24 hrs of entry. RESULTS: Sixty-nine patients (42 male, 27 female) received placebo and 83 (59 male, 24 female) received BB-882. Patients ranged in age from 16 to 89 yrs (mean, 60 yrs). No important differences existed between the two groups in terms of gender distribution, age, or initial APACHE II score. Sepsis was identified as Gram-positive in 49 patients, Gram-negative in 40, mixed in 37, and unknown in 26. No important differences were shown in hemodynamic, respiratory, or oxygen transport variables between groups during the study. Organ failure scores were similar in the two groups throughout the study. Cytokine concentrations were not significantly different in the two groups. Within 28 days of entering the study, 75 patients died, including 31 (45%) in the placebo group and 44 (53%) in the treatment group, p = .32. The median time to death in the placebo group was 6.0 days, and in the treatment group, it was 4.5 days (p = .30). CONCLUSION: Treatment of sepsis with the platelet-activating factor antagonist BB-882 offers no advantage over placebo on survival, hemodynamic status, respiratory function, or organ failure scores.

APACHE↗
PubMed2000

Strong vasopressor support may be futile in the intensive care unit patient with multiple organ failure.

OBJECTIVE: The aim of the study was to determine the prognosis in patients who needed norepinephrine treatment in our institution in relation to the degree of organ failure and the evolution of the disease process. DESIGN: Retrospective case note analysis of outcome of those patients who needed norepinephrine according to our institutional regimen. PATIENTS: A total of 100 consecutive patients admitted to our 31-bed medical-surgical intensive care unit (ICU) who were treated with norepinephrine for severe hypotension and evidence of end-organ hypoperfusion unresponsive to both fluid resuscitation and dopamine treatment at 20 microg/kg/min. MEASUREMENTS: The degree of organ dysfunction at the time of starting norepinephrine treatment was assessed by the sequential organ failure assessment (SOFA) score. The time before starting norepinephrine treatment was defined as the time elapsed between ICU admission and that of starting norepinephrine administration. The patients were defined as survivors or nonsurvivors according to their ICU outcome. RESULTS: There were relationships between mortality and the degree of organ dysfunction and mortality and the duration of ICU stay before starting norepinephrine treatment. The mortality rate was 100% in the 30 patients with a total SOFA score of >12 and a delay before starting norepinephrine treatment of >1 day. The mortality rate of the other patients was 63%. The lowest mortality was seen in patients with lower SOFA scores and early norepinephrine administration after admission. CONCLUSIONS: Both the time of starting norepinephrine treatment after admission to the ICU and the degree of organ dysfunction have an important bearing on subsequent outcome. Although norepinephrine may be a lifesaving catecholamine in some cases, its administration to patients who have already developed multiple organ failure during their stay in the ICU is associated with a poor outcome.

Adolescent↗
PubMed2000

Which therapeutic interventions in critical care medicine have been shown to reduce mortality in prospective, randomized, clinical trials? A survey of candidates for the Belgian Board Examination in Intensive Care Medicine.

OBJECTIVE: To highlight the lack of randomized controlled trial (RCT) evidence in support of accepted therapeutic interventions in the intensive care unit by assessing the ability of Intensive Care Board Examination candidates to cite relevant studies. DESIGN: As part of the Board Examination for Intensive Care Medicine in Belgium, candidates were asked to name accepted therapeutic interventions that have been shown to reduce mortality in RCTs. SETTING: Survey of doctors. SUBJECTS: Candidates for the 1998 Board Examination for Intensive Care Medicine in Belgium. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: Of the 46 candidates, 25 (54%) gave no response and 3 (7%) stated that no such study exists; 16 responses from 13 doctors were considered acceptable answers. CONCLUSIONS: Candidates for the Board Examination of Intensive Care in Belgium were unable to list many accepted interventions in critical care medicine that are supported by RCT evidence. The RCT may not be the most appropriate tool for assessing the value of an intervention in the intensive care environment.

Belgium↗
PubMed2000

Effects of propofol, etomidate, and pentobarbital on critical oxygen delivery.

OBJECTIVE: To test the hypothesis that propofol, etomidate, and pentobarbital increase critical oxygen delivery in a dose-dependent manner during progressive hemorrhage. DESIGN: Prospective, randomized laboratory investigation. SETTING: University laboratory. SUBJECTS: A total of 40 anesthetized, paralyzed, and mechanically ventilated dogs weighing 29.2+/-4.6 kg. INTERVENTIONS: Dogs were randomly assigned to be anesthetized with propofol (n = 13), etomidate (n = 13), or pentobarbital (n = 14) at either low or high dosages. At 30 mins after splenectomy, the dogs underwent progressive hemorrhage by successive withdrawals of 3-5 mL/kg arterial blood. MEASUREMENTS AND MAIN RESULTS: At each step of hemorrhage, oxygen consumption and oxygen delivery were determined. Oxygen consumption was obtained from expired gas analysis, and oxygen delivery was determined from thermodilution cardiac output and calculated arterial oxygen content. In each animal, critical oxygen delivery and critical oxygen consumption were obtained from a plot of oxygen consumption vs. oxygen delivery as the point of intersection of the two best-fit regression lines determined by a least sum of squares method. Critical oxygen extraction was obtained by dividing critical oxygen consumption by critical oxygen delivery. In the three groups, animals receiving the higher anesthetic infusion had a significantly higher critical oxygen delivery (propofol: 10.5+/-0.8 vs. 13.9+/-2.5 mL/min/m2, p < .05; etomidate: 10.1+/-0.7 vs. 13.4+/-3.0 mL/min/m2, p < .05; pentobarbital: 7.8+/-1.0 vs. 12.3+/-2.5 mL/min/m2, p < .01) attributable to a lower critical oxygen extraction ratio (propofol: 41.1+/-6.4% vs. 54.2+/-2.5%, p < .01; etomidate: 42.7+/-10.2% vs. 60.6+/-7.1%, p < .01; pentobarbital: 42.2+/-7.2% vs. 64.3+/-8.8%, p < .01). CONCLUSIONS: This study indicates that propofol, etomidate, and pentobarbital increased critical oxygen delivery in a dose-dependent manner. This effect was mainly related to a decrease in tissue oxygen extraction capabilities.

Anesthetics, Intravenous↗
PubMed2000

Power spectral analysis of cardiovascular variability in critically ill neurosurgical patients.

OBJECTIVE: Patients with brain damage exhibit a number of changes in heart rate and cardiovascular control. The aim of this study was to relate changes in autonomic cardiovascular control seen in critically ill neurosurgical patients to the quality of subsequent outcome and survival. DESIGN: Prospective, longitudinal, outcome study. SETTING: Intensive care department of a university teaching hospital. PATIENTS: A total of 29 consecutive neurosurgical patients admitted for > or =2 days to the intensive care department with a Glasgow Coma Scale score < 13 who needed electrocardiographic and invasive arterial monitoring. INTERVENTIONS: Sampling of the electrocardiogram, respiratory rate, and arterial pressure into a personal computer was carried out for > or =60 mins. Power spectral analysis was then applied to the data by using a fast Fourier transformation. Arterial baroreflex sensitivity was determined as the gain of the transfer function between systolic arterial blood pressure and electrocardiograph R-R interval (RRI) variability. All surviving patients were followed up at 3 months postadmission to measure quality of outcome. MEASUREMENTS AND MAIN RESULTS: There were reductions in the total power (p < .01) of RRI variability in those who subsequently died compared with those who survived. This was significant for very low frequency (p < .001) and low-frequency (LF) (p < .05) but not high-frequency (HF) bands (p = .11). Blood pressure variability, however, did not change between groups. Baroreflex sensitivity was 8.7+/-2.2 msecs/mm Hg for patients with a good later outcome and 4.4+/-1.5 msecs/mm Hg for patients who subsequently died (p = .03). Patients who recovered to a good quality outcome also had a raised LF/HF ratio in RRI (p = .05). CONCLUSION: A reduction in the total power variability of RRI and a lowered LF/HF ratio of the RRI are associated with a poor quality recovery or death after neurosurgical illness. A reduction in the baroreflex was specifically associated with death in this patient group.

Adult↗
PubMed2000

Hemoglobin solutions--not just red blood cell substitutes.

OBJECTIVE: To review current knowledge about cell-free hemoglobin solutions. DATA SOURCES: All studies involving cell-free hemoglobin were retrieved from a computerized MEDLINE search from 1980 to 1998. We also reviewed the reference lists of all available review articles and primary studies to identify references not found in the computerized search. STUDY SELECTION: Clinical and experimental studies in which cell-free hemoglobin solutions were studied. DATA EXTRACTION: From the selected studies, information was obtained regarding the experimental model or the study population in which cell-free hemoglobin solutions were investigated, the type of cell-free hemoglobin solution, their deleterious or beneficial effects, and their possible indications. DATA SYNTHESIS: In many studies, hemoglobin solutions were considered as efficient resuscitative agents and good alternatives to red blood cell transfusion, because of their marked vasopressor effect coupled with their capacity to improve the microcirculation and quickly restore metabolic parameters. Nevertheless, potential problems include an increased susceptibility to infection, immunosuppression, oxidative damage, excessive pulmonary and systemic vasoconstriction, and platelet activation. CONCLUSIONS: Hemoglobin solutions are more than mere blood substitutes. Promising effects on oxygen transport and the microcirculation need to be confirmed, and the results of continuing research are eagerly awaited.

Blood Substitutes↗
PubMed2000

New therapeutic implications of anticoagulation mediator replacement in sepsis and acute respiratory distress syndrome.

OBJECTIVE: To examine the relationship between the coagulation and immune systems in sepsis and acute respiratory distress syndrome and to review published experimental and clinical studies that use anticoagulation mediator replacement strategies in these conditions. DATA SOURCES: MEDLINE database and bibliographies of relevant articles. STUDY SELECTION: Articles (both original and review) relating to coagulation abnormalities and anticoagulation mediator replacement therapy in sepsis and acute respiratory distress syndrome. DATA EXTRACTION: All applicable data were extracted. CONCLUSIONS: Coagulation abnormalities are common in the critically ill. Early studies using anticoagulation mediator replacement in patients with sepsis have suggested beneficial effects on organ function and outcome. The results from larger, randomized controlled trials are eagerly anticipated.

Animals↗
PubMed2000

Enteral feeding with a solution enriched with antioxidant vitamins A, C, and E enhances the resistance to oxidative stress.

OBJECTIVE: To assess whether dietary supplementation with the antioxidant vitamins A, C, and E enhances parameters of oxidative stress and influences the course of critically ill patients. DESIGN: Prospective, randomized, double-blinded, placebo-controlled study. SETTING: Department of medicosurgical intensive care of an academic hospital. PATIENTS: Fifty-one patients expected to require at least 7 days of enteral feeding. Thirty-seven of these patients (age, 57 +/- 7 yrs; Simplified Acute Physiology Score II, 33 +/- 6 points) completed the study. INTERVENTIONS: Twenty patients were randomized to receive the formula supplemented with vitamins A (67 microg/dL), C (13.3 mg/ dL), and E (4.94 mg/dL), and 17 patients received an isocaloric and isonitrogenous control solution. MEASUREMENTS AND MAIN RESULTS: Plasma levels of antioxidant vitamins, lipid peroxidation (estimated by the malonyldialdehyde assay), and low-density lipoprotein (LDL), and erythrocyte resistance to experimental oxidative stress were determined on samples drawn two consecutive days before the initiation of feeding and at the end of the 7-day period. Clinical outcome measures included documented infection and intensive care unit and 28-day survival. Administration of the supplemented solution increased significantly the concentration of plasma beta-carotene (from 0.2 +/- 0.0 microg/mL to 0.6 +/- 0.1 microg/mL; p < 0.01) and plasma and LDL-bound alpha-tocopherol (from 6.0 +/- 0.4 microg/mL and 2.9 +/- 0.9 microg/mL to 9.7 +/- 0.5 microg/mL and 4.3 +/- 1.2 microg/mL, respectively; p < 0.05), and improved LDL resistance to oxidative stress by 21 +/- 4% (p < 0.05). No such change was observed in the control group. There was no significant difference in clinical outcome between the two groups. CONCLUSIONS: Supplemental antioxidant vitamins added to enteral feeding solutions are well absorbed. Dietary supplementation with vitamins A, C, and E is associated with an improvement in antioxidant defenses, as assessed by ex vivo tests.

APACHE↗
PubMed2000

Immunolocalization of a cysteine protease in vacuoles, vesicles, and symbiosomes of pea nodule cells.

PsCYP15A is a cysteine protease from pea (Pisum sativum L.). It was first recognized as an up-regulated transcript in wilted shoots and subsequently in root nodules containing Rhizobium. Proteolytic activity of PsCYP15A in nodule extracts is now reported following immunopurification with polyclonal antiserum raised against recombinant antigen. Western-blot analysis indicated two forms of PsCYP15A, a pro-form (approximately 38 kD) and a mature form (approximately 30 kD). Both forms were present in most tissue samples, but only the mature form was isolated from cell-fractionated symbiosomes containing nitrogen-fixing bacteroids. Immunolabeling of nodule sections showed localization of PsCYP15A antigen in large vacuolar bodies, cytoplasmic vesicles, and the perisymbiont space. Immunolabeling of tissue sections from wilted shoots also indicated the presence of PsCYP15A in vacuoles and cytoplasmic vesicles. This protease may be involved in the adaptation to changes in cell turgor, both in wilted shoots and in nodule tissue. Additionally, the protease may be involved in protein turnover in the symbiosome compartment.

Base Sequence↗
PubMed2000

Diaspirin cross-linked hemoglobin improves oxygen extraction capabilities in endotoxic shock.

We studied the effects of diaspirin cross-linked hemoglobin (DCLHb), a cell-free hemoglobin derived from human erythrocytes, on blood flow distribution and tissue oxygen extraction capabilities in endotoxic shock. Eighteen pentobarbital sodium-anesthetized, mechanically ventilated dogs received 2 mg/kg of E. coli endotoxin, followed by saline resuscitation to restore cardiac filling pressures to baseline levels. The animals were randomly divided into three groups: six served as control, six received DCLHb at a dose of 500 mg/kg (group 1) and six DCLHb at a dose of 1,000 mg/kg (group 2). Cardiac tamponade was then induced by saline injection in the pericardial sac to progressively reduce cardiac index and thereby allow study of tissue oxygen extraction capabilities. DCLHb had a dose-dependent vasopressor effect but did not significantly alter cardiac index or regional blood flow. During cardiac tamponade, critical oxygen delivery was 12.8 +/- 0.7 ml. kg(-1). min(-1) in the control group, but 8.6 +/- 0.9 and 8.2 +/- 0.7 ml. kg(-1). min(-1) in groups 1 and 2, respectively (both P < 0.05 vs. control group). The critical oxygen extraction ratio was 39.1 +/- 3.1% in the control group but 58.7 +/- 12.8% and 60.2 +/- 9.0% in groups 1 and 2, respectively. We conclude that DCLHb can improve whole body oxygen extraction capabilities during endotoxic shock in dogs.

Animals↗
PubMed2000

Effect of ibuprofen and diethylcarbamazine on the hemodynamic and inflammatory response to endotoxin in the dog.

We studied the effects of pretreatment with either ibuprofen (15 mg/kg), diethylcarbamazine (DEC, 15 mg/kg), or vehicle, on the hemodynamic, hematologic, and serum tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 responses to a bolus Escherichia coli endotoxin infusion (2 mg/kg) in 21 pentobarbital-anesthetized dogs (n = 7 each group). Hematologic and cytokine data were collected before and 0.5, 1, and 3 h after endotoxin infusion. Endotoxin decreased arterial pressure (P(a)), cardiac output (CO), total leukocyte (WBC) and platelet counts, and increased lactate, TNF-alpha, and IL-6. TNF-alpha levels peaked at 1 h and decreased by 3 h, whereas IL-6 remained elevated. Ibuprofen abolished the endotoxin-induced changes in P(a) and lactate, but did not alter the initial decrease in CO, WBC, and platelets or the increase in TNF-alpha and IL-6. DEC did not alter the response to endotoxin, although the DEC group had higher TNF-alpha and IL-6 levels before endotoxin infusion compared to controls. We conclude that the cardiovascular effects of ibuprofen in the canine model of acute endotoxemia are not due to suppression of the systemic inflammatory response.

Animals↗