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Search Results: 1 - 10 of 3991 matches for " Jacques Creteur "
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Lactate concentration gradient from right atrium to pulmonary artery: a commentary
Jacques Creteur
Critical Care , 2005, DOI: 10.1186/cc3769
Abstract: In this issue, Gutierrez et al. [1] compared simultaneous measurements of blood lactate concentrations in the right atrium and pulmonary artery in critically ill patients. They found decreases in both blood lactate concentrations and venous blood oxygen saturation in gradients from the right atrium to the pulmonary artery. These gradients are presumably produced by mixing right atrial blood with coronary venous blood, which has lower lactate concentrations and blood oxygen saturation. More interestingly, in this study, the lactate gradient was inverted in three patients, suggesting myocardial ischemia, a condition associated with lactate release by the heart.Blood lactate levels are typically elevated in hypoperfusion states when pyruvate cannot enter the Krebs cycle as the cellular oxygen supply becomes insufficient. The pyruvate is shunted to lactate through the enzyme lactate dehydrogenase, producing only two molecules of energy-rich ATP for every two molecules of pyruvate (from one molecule of glucose), compared with 38 molecules of ATP for each glucose molecule through the aerobic mitochondrial process when sufficient oxygen is present. This causes the lactate to pyruvate ratio to increase (the normal value is around 10:1). Once molecular oxygen is again available, assuming that mitochondrial function is preserved, the excess lactate is rapidly metabolized back through pyruvate into carbon dioxide and water via the Krebs cycle. Lactate in the blood is metabolized mainly by the liver (50%) and kidney (20%). Liver function and liver blood flow can influence hepatic lactate clearance. Striated muscles, the heart and the brain can also metabolize lactate and, in some conditions, this clearance can be significant.Traditionally, elevated blood lactate levels in hemodynamically unstable patients have been interpreted as reflecting acute circulatory shock. Elevated blood lactate levels have been correlated with mortality in all types of shock [2,3]. The speed at which
The 32nd Annual Congress of the Society of Critical Care Medicine, 28 January – 2 February 2003, San Antonio, USA
Daniel De Backer, Jacques Creteur
Critical Care , 2002, DOI: 10.1186/cc2173
Abstract: Michael B Yaffe (Cambridge, MA, USA)In his lecture, Michael Yaffe alluded to how fundamental science may help in the development of new therapeutic agents. In the past, the search for new drugs was based on random selection of drugs of natural sources, which were secondary tested in all possible models. When the drug was proven to have efficacy, its chemical structure was isolated and the drug was then synthesized. Using this method, unfortunately, the rate of drug discovery has decreased. A more rational approach would be to take into account our understanding of the mechanism of diseases in order to identify target signalling pathways. Use of genomics to identify gene expression of cells in different conditions is unlikely to be helpful because the responses to several stimuli are often similar. For example, gene expression in macrophages is similar following stimulation by Gram-negative bacteria, Gram-positive cocci and mycobacteria. Proteomics may be more helpful in identifying regulatory pathways. Proteomics covers thousand of proteins acting in a changing environment, and hence it is important to identify how and why several proteins are interrelated and interplay in regulatory and/or pathophysiological processes. This leads to the possibility of identifying critical nodes in models and definition of where drugs are likely to act.Thierry Calandra (Lausanne, Switzerland)Thierry Calandra reviewed the mechanisms involved in innate immunity, with a special emphasis on the Toll-like receptor. He also stressed the important role played by the pituitary axis in the modulation of inflammation. In this context, the macrophage inhibitory factor (MIF) appears to be crucial. MIF is high in patients surviving sepsis, and the administration of MIF increases survival in experimental models. Interestingly, MIF is implicated in the hypothalamic–pituitary–adrenal axis, being present in the adrenal cortex, whereas dexamethasone induces MIF secretion.Mervyn Singer (London, Englan
Near-infrared spectroscopy technique to evaluate the effects of red blood cell transfusion on tissue oxygenation
Jacques Creteur, Ana Neves, Jean-Louis Vincent
Critical Care , 2009, DOI: 10.1186/cc8009
Abstract: This prospective, observational study included 44 consecutive patients hospitalized in the 31-bed, medical-surgical intensive care unit of a university hospital with anemia requiring red blood cell transfusion. Thenar tissue oxygen saturation (StO2) and muscle tissue hemoglobin index (THI) were measured using a tissue spectrometer (InSpectra? Model 325; Hutchinson Technology Inc., Hutchinson, MN, USA). A vaso-occlusive test was performed before and 1 hour after RBC transfusion by rapid inflation of a pneumatic cuff around the upper arm. The following variables were recorded: THI, the StO2 desaturation slope during the occlusion (%/minute) and the StO2 upslope of the reperfusion phase following the ischemic period (%/second). Muscle oxygen consumption (NIR VO2; arbitrary units) was calculated as the product of the inverse StO2 desaturation slope and the mean THI over the first minute of arterial occlusion.Blood transfusion resulted in increases in hemoglobin (from 7.1 (6.7 to 7.7) to 8.4 (7.1 to 9) g/dl; P < 0.01) and in oxygen delivery (from 306 (259 to 337) to 356 (332 to 422) ml/minute/m2; P < 0.001). However, systemic VO2 was unchanged. RBC transfusion did not globally affect NIRS-derived variables, but there was considerable interindividual variation. Changes in the StO2 upslope of the reperfusion phase after transfusion were negatively correlated with baseline StO2 upslope of the reperfusion phase (r2 = 0.42; P < 0.0001). Changes in NIR VO2 after transfusion were also negatively correlated with baseline NIR VO2 (r2 = 0.48; P = 0.0015). There were no correlations between RBC storage time and changes in StO2 slope or NIR VO2.Muscle tissue oxygenation, oxygen consumption and microvascular reactivity are globally unaltered by RBC transfusion in critically ill patients. However, muscle oxygen consumption and microvascular reactivity can improve following transfusion in patients with alterations of these variables at baseline.Critically ill patients often receive red
Perioperative optimization and right heart catheterization: what technique in which patient?
Daniel De Backer, Jacques Creteur, Jean-Louis Vincent
Critical Care , 2003, DOI: 10.1186/cc2177
Abstract: More than 20 years ago, Shoemaker and coworkers [1,2] observed that perioperative alterations in oxygen transport were closely related to the development of organ failure and death. Subsequently, several studies reported that perioperative hemodynamic optimization guided by the pulmonary artery catheter may decrease morbidity and mortality [3-6]. Nevertheless, the use of the pulmonary artery catheter has been challenged because of its invasiveness and possibly the unwarranted interventions that may result from its use [7].In a recent issue of the New England Journal of Medicine, Sandham and coworkers [8] reported the results of a multicenter Canadian study that investigated the effects of right heart catheterization on perioperative complications in high-risk patients undergoing noncardiac surgery. From 1990 to 1999, those authors randomly allocated 1994 American Society of Anesthesiologists class III and IV patients to conventional monitoring and therapy or to right heart catheterization and hemodynamic optimization. They observed that survival (up to 1 year of follow up) and hospital stay did not differ between the two groups. The incidence of perioperative complications was similar in both groups, except for an increased incidence of pulmonary embolism in the pulmonary artery catheter group.Although Sandham and coworkers [8] must be commended for their important undertaking, the study raises a number of important concerns. First, although the authors claimed that no patient selection was performed, the inclusion rate of a mean of only 22 patients/center per year was surprisingly low. For example, close to 1000 patients with American Society of Anesthesiologists class III and IV are operated on each year in our 760-bed institution. One of the inclusion criteria was the commitment of the surgeon and the anesthesiologist to adhere to the study concept; the most severely ill patients might therefore have been excluded, and this may explain the unexpectedly low mortal
Effects of changes in arterial pressure on organ perfusion during septic shock
Aurélie Thooft, Rapha?l Favory, Diamantino Salgado, Fabio S Taccone, Katia Donadello, Daniel De Backer, Jacques Creteur, Jean-Louis Vincent
Critical Care , 2011, DOI: 10.1186/cc10462
Abstract: This was a single center, prospective, interventional study conducted in the medico-surgical intensive care unit of a university hospital. Thirteen patients in septic shock for less than 48 hours who required NE administration were included. NE doses were adjusted to obtain MAPs of 65, 75, 85 and (back to) 65 mmHg. In addition to hemodynamic and metabolic variables, we measured thenar muscle oxygen saturation (StO2), using near infrared spectroscopy (NIRS), with serial vaso-occlusive tests (VOTs) on the upper arm. We also evaluated the sublingual microcirculation using sidestream dark field (SDF) imaging in 6 of the patients.Increasing NE dose was associated with an increase in cardiac output (from 6.1 to 6.7 l/min, P<0.05) and mixed venous oxygen saturation (SvO2, from 70.6 to 75.9%, P<0.05). Oxygen consumption (VO2) remained stable, but blood lactate levels decreased. There was a significant increase in the ascending slope of StO2 (from 111 to 177%/min, P<0.05) after VOTs. SDF imaging showed an increase in perfused vessel density (PVD, from 11.0 to 13.2 n/mm, P<0.05) and in microvascular flow index (MFI, from 2.4 to 2.9, P<0.05).In this series of patients with septic shock, increasing MAP above 65 mmHg with NE was associated with increased cardiac output, improved microvascular function, and decreased blood lactate concentrations. The microvascular response varied among patients suggesting that individualization of blood pressure targets may be warranted.Septic shock is characterized by an alteration in tissue perfusion associated with persistent arterial hypotension - generally defined as a systolic arterial pressure of less than 90 mm Hg [1] - despite adequate fluid resuscitation [2]. This leads to organ dysfunction and even death in around 50% of cases [3]. Evaluation of systemic hemodynamic variables can be inadequate to identify tissue perfusion, which is directly influenced by additional microvascular factors. De Backer and colleagues [4] showed that sepsis
Dark Energy as a Property of Dark Matter  [PDF]
Jacques Leibovitz
Journal of Modern Physics (JMP) , 2011, DOI: 10.4236/jmp.2011.212181
Abstract: A novel model of dark matter (DM), elastically compressible, can contribute to the acceleration of our Universe expansion. While each galaxy compresses its own DM within its gravitation field, the DM bordering neighboring galaxies, far from their centers, is pulled apart. It is shown that, although the DM pressure tends to zero at such locations, the DM compressibility tends to infinity. This allows the DM to expand between galaxies without gravitation hindrance. The model is consistent with the coupled distributions of baryonic and dark matters, with black hole formation at the centers of large galaxies, with galactic flat rotation curves, with a Tully-Fisher relation, and with Milgrom’s MOND relation. Results are discussed.
Mechanism and evolution of multidomain aminoacyl-tRNA synthetases revealed by their inhibition by analogues of a reaction intermediate, and by properties of truncated forms  [PDF]
Jacques Lapointe
Journal of Biomedical Science and Engineering (JBiSE) , 2013, DOI: 10.4236/jbise.2013.610115
Abstract: Many enzymes which catalyze the conversion of large substrates are made of several structural domains belonging to the same polypeptide chain. Transfer RNA (tRNA), one of the substrates of the multidomain aminoacyl-tRNA synthetases (aaRS), is an L-shaped molecule whose size in one dimension is similar to that of its cognate aaRS. Crystallographic structures of aaRS/tRNA complexes show that these enzymes use several of their structural domains to interact with their cognate tRNA. This mini review discusses first some aspects of the evolution and of the flexibility of the pentadomain bacterial glutamyl-tRNA synthetase (GluRS) revealed by kinetic and interaction studies of complementary truncated forms, and then illustrates how stable analogues of aminoacyl-AMP intermediates have been used to probe conformational changes in the active sites of Escherichia coli GluRS and of the nondiscriminating aspartyl-tRNA synthetase (ND-AspRS) of Pseudomonas aeruginosa.
A Review on Tectonic Record of Strain Buildup and Stress Release across the Andean Forearc along the Gulf of Guayaquil-Tumbes Basin (GGTB) near Ecuador-Peru Border  [PDF]
Jacques Bourgois
International Journal of Geosciences (IJG) , 2013, DOI: 10.4236/ijg.2013.43057

Gravimetric and geologic data show that the reactivation of the Neogene Interandean depression and/or the ~75 - 65 Ma ophiolite suture into the modern dynamic of the Andes controlled the Gulf of Guayaquil Tumbes basin (GGTB) location and evolution during the past 1.8 - 1.6 Myr at least. Depending on whether the remobilization occurred along the interandean depression or the ophiolite suture, the GGTB evolved trough pure or simple shear mechanisms, respectively. Because the GGTB exhibits an along strike tectonic asymmetry associated with a pervasive seismic gap, the simple shear solution is more likely. Tectonic inversion occurred along a mid-crust detachment (the Mid-Crust detachment hereafter) matching the ophiolite suture that accommodates the North Andean Block (NAB) northward drift. The so-called Decoupling Strip located at the shelf slope break accommodated the tensional stress rotation from N-S along the shelf area i.e. NAB-drift induced to E-W along the continental margin i.e. subduction-erosion-induced. The landward dipping Woollard detachment system located at the Upper-Lower slope boundary connects the subduction channel at depth, allowing the Upper slope to evolve independently from the Lower slope wedge. The long-term recurrence interval between earthquakes, the strong interplate coupling, and the aseismic creeping deformation acting along the main low-angle detachments i.e. the Woollard and the Mid-Crust detachments may account for the pervasive seismic gap at the GGTB area. Because the subduction channel exhibits no record of significant seismic activity, no evidence exists to establish a link between the GGTB sustained subsidence and a basin-centered asperity. Because the

Mind-Language, the Expanding Heart of Cognition  [PDF]
Jacques Coulardeau
Open Journal of Social Sciences (JSS) , 2018, DOI: 10.4236/jss.2018.66004
On the basis of already published research on the phylogeny of language during the emergence of Homo Sapiens starting around 300,000 years ago, and on still-to-be-published research in its final phase on the psychogenesis of language starting in the 24th week of gestation, I will present my work on the central role of two virtual human constructs of man’s nervous system and brain confronted to their real environment, both natural and social. These two constructs, the mind and language, are the results of the development of the general pattern-capturing potential of the brain’s architecture. The mind and language develop simultaneously, reciprocally and in close coordination transforming the pattern-capturing potential of the brain into the mental and linguistic conceptualizing power of men and women. This long process of development can be captured in six stages: to sense; to perceive; to discriminate (or recognize) patterns; to experiment; to speculate, and to conceptualize spatial items and temporal processes. In psychogenetics, these six stages are essential for education. Lev Vygotsky, among others, has proposed the best approach to this conceptualizing competence in children and young adults, and expanding in our whole life.
Cell-type specific regulation of MARCH1 E3 ubiquitin ligase by the anti-inflammatory cytokine IL-10  [PDF]
Tristan Galbas, Jacques Thibodeau
Open Journal of Immunology (OJI) , 2012, DOI: 10.4236/oji.2012.24020
Abstract: Membrane-associated RING-CH-1 (MARCH1) is an E3 ubiquitin ligase which targets MHC-II, CD86 and various other molecules for degradation. It is one of the most efficient post-translational regulators of antigen presentation. MARCH1 is expressed in resting immature dendritic cells and B cells but can be induced in other cell types. While activation of most immune cells results in a reduction in MARCH1 gene expression, its anti-inflammatory properties are highlighted by its induction in response to IL-10. Here, we review what is known about the regulation of MARCH1 gene expression in response to IL-10 by various immune cells. We speculate on the role of MARCH1 ininfection, its differential expression pattern and the promise that this E3 ubiquitin ligase holds to influence immune responses and mitigate immune pathologies.
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