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Biomedical subjects

D Ledoux

Publications and source records attributed to D Ledoux.

At least 19 recordsLinked to original sources
PubMed2007

RGTA OTR4120, a heparan sulfate mimetic, is a possible long-term active agent to heal burned skin.

Burn-related skin fibrosis leads to loss of tissue function and hypertrophic scar formation with damaging consequences for the patient. There is therefore a great need for an efficient agent to treat burned skin. We report that ReGeneraTing Agent (RGTA) reduces burn-induced skin alteration. The tissue-regenerating effect of RGTA OTR4120 was evaluated after 1-6 days and after 10 months in a rat skin burn model. This effect was also examined in vitro using fibroblasts isolated from control and 6-day-old burned skins. We measured production of dermal collagen I, III, and V and activities of metalloproteinases 2 and 9 (MMP-2 and MMP-9). Ratio of collagen III over collagen I production increased 6 days after the burn, because of a decrease in collagen I production. After 10 months, ratio of collagen III over collagen I in burn sites was still increased compared with control skin, because of an increase in collagen III production. Both abnormalities were corrected by OTR4120. OTR4120 increased pro- and active MMP-2 and MMP-9, compared with healthy and burned controls and therefore accelerated remodeling. Similar data were obtained with cultured fibroblasts from healthy and burned skins. OTR4120 enhanced healing in short- and long-term after burns, reducing the formation of fibrotic tissue, and then represents a potential agent to improve burned skin healing.

Animals↗
PubMed2005

Impact of operator expertise on collection of the APACHE II score and on the derived risk of death and standardized mortality ratio.

We assessed the impact of operator expertise on collection of the APACHE II score, the derived risk of death and standardized mortality ratio in 465 consecutive patients admitted to a multi-disciplinary tertiary hospital ICU. Research coordinators and junior clinical staff independently collected the APACHE II variables; experts (senior clinical staff) rescored 20% of the records. Agreement was moderate between junior clinical staff and research coordinators or senior clinical staff for most variables of the acute physiology score (weighted kappa<0.6); agreement between research coordinators and senior clinical staff data collectors was good (weighted kappa >0.75). The APACHE II score and its derived risk of death (ROD) were significantly lower using the junior clinical staff dataset compared to research coordinators and senior clinical staff (APACHE II score: 13.4+/-9.2 vs 16.8+/-8.5 vs 17.1+/-7 7, P<0.001; ROD: 14.7%+/-22.4% vs 21.6%+/-22.6% vs 20.8%+/-22.4%, P<0.01 respectively). The discriminative capacity was not altered by the lack of agreement (area under Receiver Operator Characteristic curve >0.8) but calibration of ROD from the junior clinical staff dataset was poor (Goodness-of-fit: P= 0.001). The standardized mortality ratio (SMR) was higher with the junior clinical staff dataset (SMR: 1.22, 95% CI: 0.96-1.52 vs 0.87, 95% CI: 0.70-1.06 vs 0.76, 95% CI: 0.40-1.3 calculated from junior clinical staff research coordinators and senior clinical staff datasets respectively). We conclude that the expertise of data collectors significantly influences the APACHE II score, the derived risk of death and the standardized mortality ratio. Given the importance of such scores, ICUs should be provided with sufficient resources to train and employ dedicated data collectors.

APACHE↗
PubMed2005

Effect of hydroxyethylstarch on renal function in cardiac surgery: a large scale retrospective study.

BACKGROUND: Recent reports indicated negative effects of hydroxyethylstarch (HES) on renal function. The goal of this large scale retrospective study was to detect whether there was an association between postoperative deterioration of renal function and the use of HES 200 kD, 0.5 DS in the cardiac surgery setting. METHODS: Retrospective analysis of daily collected data in 3124 patients who underwent coronary artery bypass and/or valvular surgery. Three groups were compared according to differences in fluid therapy: --GEL: gelatin was used as priming fluid of extracorporeal circulation (ECC) and for postoperative filling (n = 1276). --MIX: HES was used as priming fluid of ECC an gelatin was used for postoperative filling (n = 1008). --HES: HES was used as priming fluid of ECC and for postoperative filling (n = 840). MAIN RESULTS: There were no significant differences in postoperative serum creatinine concentrations between the 3 groups: GEL: 12,2 +/- 0,5 mg/l; MIX: 12,3 +/- 0.5 mg/l; HES: 12,3 +/- 0.6 mg/l. The need for postoperative extrarenal epuration was not significantly different between the 3 periods: GEL: 2,9%; MIX: 3,1%; HES: 3,8%. CONCLUSION: The use of HES 200 kD, 0.5 DS in cardiac surgery does not seem to be associated with a clinically significant deterioration of postoperative renal function.

Acute Kidney Injury↗
PubMed2005

["Fulminant" endocarditis due to Staphyloccocus aureus].

We report two cases of "fulminant" endocarditis due to Staphyloccoccus aureus. In both cases, the echocardiographic and bacteriologic diagnosis was esthablished in a clinical picture of severe sepsis and thrombocytopenia evolving after a fever of less than 3 days duration.

Adult↗
PubMed2003

Bronchoalveolar lavage fluids of ventilated patients with acute lung injury activate NF-kappaB in alveolar epithelial cell line: role of reactive oxygen/nitrogen species and cytokines.

In human alveolar epithelial cell line, we investigated the binding activity of NF-kappaB induced by the bronchoalveolar lavage fluids (BALs) from ventilated patients with acute lung injury (ALI), in correlation with the concentrations of inflammatory cytokines, RNOS, and the severity of the ALI. In BALs obtained in 67 patients (16 bronchopneumonia, 14 infected ARDS, 20 ARDS, and 17 ALI patients without bronchopneumonia and no ARDS), we measured endotoxin, IL-1beta, IL-8, and nitrated proteins (NTP), the activity of myeloperoxidase, and the capacity to activate the NF-kappaB in alveolar A549 cells by electrophoretic mobility shift and supershift assays. The neutrophil counts and mean IL-1beta, IL-8, myeloperoxidase, and NTP values were increased in bronchopneumonia and infected ARDS groups compared to ARDS and ALI without bronchopneumonia and no ARDS groups (P<0.001). The number of neutrophils was correlated to those of IL-1beta, IL-8, myeloperoxidase, NTP, and endotoxin in all groups (P<0.0001). NF-kappaB activity was induced in alveolar like cells by BALs in all groups, was higher in bronchopneumonia and infected ARDS groups (P<0.02), and was correlated to IL-1beta (P=0.0002), IL-8 (P=0.02), NTP (P=0.014), myeloperoxidase (P=0.016), and neutrophil counts (P=0.003). BALs of bronchopneumonia and infected ARDS patients had increased inflammatory mediators (compared to ARDS and ALI without bronchopneumonia and no ARDS patients) that correlated to neutrophil counts and to the NF-kappaB-binding activity. These mediators and NF-kappaB activation may induce an amplification of inflammatory phenomena. By in vitro studies, we confirmed that NO-derived species (10(-6) to 10(-5)M peroxynitrite and 10(-5)M nitrites) and myeloperoxidase (at concentration equivalent to that found in BALs) can participate in the NF-kappaB activation.

Acute Disease↗
PubMed2002

Bronchoalveolar lavage fluids of patients with lung injury activate the transcription factor nuclear factor-kappaB in an alveolar cell line.

In bronchoalveolar lavage (BAL) fluid from ventilated patients, cytotoxic oxidant activity is correlated with neutrophil activation. The aim of the present study was to investigate the hypothesis that BAL fluid induces activation of the transcription nuclear factor-kappaB (NF-kappaB) in human alveolar cells, in correlation with inflammatory mediators. We measured endotoxin, inflammatory cytokines [interleukin-1beta (IL-1beta), IL-8], nitrated proteins and the activity of myeloperoxidase (MPO) in BAL fluid from ventilated patients developing bronchopneumonia ( n =19 samples) or with acute respiratory distress syndrome (ARDS) ( n =14), and from ARDS/infection-free patients ( n =11). We also exposed alveolar cells to the BAL fluid or to human MPO, H(2)O(2) or HOCl, and tested nuclear extracts for the activation of NF-kappaB. IL-1beta, IL-8, nitrated protein, MPO and endotoxin levels were significantly higher in BAL fluid from patients with bronchopneumonia than in that from the ARDS and ARDS/infection-free groups. A correlation was observed between IL-8 and MPO values ( r =0.82). The level of NF-kappaB activity induced by the BAL fluid was correlated with levels of IL-1beta ( P <0.001), IL-8 ( P <0.005) and MPO ( P <0.002), and with the neutrophil count ( P <0.002), and was higher for BAL fluid from the bronchopneumonia group. NF-kappaB activation by MPO was also demonstrated. The activation of NF-kappaB by BAL fluid, especially that from bronchopneumonia patients, suggests that a similar phenomenon may occur in vivo, leading to potential amplification of the inflammatory reaction.

Adolescent↗
PubMed2001

[Cutaneous infections contracted during sports and recreational activities].

Going in for sports is at increased risk for cutaneous infections that can be viral, bacterial, mycotic and parasitic in nature. The specific conditions of sports practice have a major influence on their occurrence. Other factors such as age, gender and genetic predisposition can also play a role. The cutaneous infections should be the target of preventive measures. To assume the worse, they should be recognized and treated without delay in order to avoid the more or less prolonged arrest of the sports activity and the disease transmission to partners.

Adolescent↗
PubMed2001

[Severity scoring systems in the the ICU. Description, utilization, and potential].

Severity scoring systems are of great interest for the intensive care physicians. They provide major objective information regarding their patients and their medical practice. Scoring systems have been regularly improved over the two last decades. The different existing systems present advantages and disadvantages which influence their use in the intensive care. These scoring systems offer a wide range of analysis, however they are often underused. In this paper we suggest recommendations that could help to maximise the information provided by these systems.

Humans↗
PubMed2000

Human plasmin enzymatic activity is inhibited by chemically modified dextrans.

Some synthetic dextran derivatives that mimic the action of heparin/heparan sulfate were shown to promote in vivo tissue repair when added alone to wounds. These biofunctional mimetics were therefore designated as "regenerating agents" in regard to their in vivo properties. In vitro, these biopolymers were able to protect various heparin-binding growth factors against proteolytic degradation as well as to inhibit the enzymatic activity of neutrophil elastase. In the present work, different dextran derivatives were tested for their capacity to inhibit the enzymatic activity of human plasmin. We show that dextran containing carboxymethyl, sulfate as well as benzylamide groups (RG1192 compound), was the most efficient inhibitor of plasmin amidolytic activity. The inhibition of plasmin by RG1192 can be classified as tight binding hyperbolic noncompetitive. One molecule of RG1192 bound 20 molecules of plasmin with a K(i) of 2.8 x 10(-8) m. Analysis with an optical biosensor confirmed the high affinity of RG1192 for plasmin and revealed that this polymer equally binds plasminogen with a similar affinity (K(d) = 3 x 10(-8) m). Competitive experiments carried out with 6-aminohexanoic acid and kringle proteolytic fragments identified the lysine-binding site domains of plasmin as the RG1192 binding sites. In addition, RG1192 blocked the generation of plasmin from Glu-plasminogen and inhibited the plasmin-mediated proteolysis of fibronectin and laminin. Data from the present in vitro investigation thus indicated that specific dextran derivatives can contribute to the regulation of plasmin activity by impeding the plasmin generation, as a result of their binding to plasminogen and also by directly affecting the catalytic activity of the enzyme.

Dextrans↗
PubMed2000

Nitrated proteins in bronchoalveolar lavage fluid of patients at risk of ventilator-associated bronchopneumonia.

The study was designed to identify markers of oxidative injury, related to the nitric oxide derived cascade, in bronchoalveolar lavage (BAL) fluid from intensive care patients suspected of ventilator-associated pneumonia (VAP) and/or acute respiratory distress syndrome (ARDS). Thirty-eight patients developing VAP and/or ARDS (VAP/ARDS group) were compared to 20 ventilated patients without VAP/ARDS (control group). Myeloperoxidase (MPO) and elastase, taken as markers of neutrophil activation were measured by enzymatic techniques, and nitrated proteins (NTPs) by an immunological method. The cytotoxicity of the BAL fluid was tested using cultured human epithelial alveolar cells by the release of pre-incorporated 51Cr. Mean NTP concentration and, MPO and elastase activities were different between the VAP/ARDS and control groups (p<0.05 for NTPs; p<0.005 for MPO; p<0.005 for elastase). NTP concentration correlated with MPO and elastase activity and neutrophil number (r=0.93, 0.91 and 0.87, respectively), but not to protein concentration and arterial oxygen tension/inspiratory oxygen fraction. The cytotoxicity of BAL correlated with NTP concentration (r=0.92) and MPO activity (r=0.89). It was concluded that the concentrations of nitrated proteins in bronchoalveolar lavage fluid correlated with the oxidant activity of neutrophils and that, bronchoalveolar lavage fluid cytotoxicity was correlated with the nitrated protein concentration and may be mediated by oxidants.

Adolescent↗
PubMed2000

Correlation between endotoxin level and bacterial count in bronchoalveolar lavage fluid of ventilated patients.

OBJECTIVE: To assess the predictive value of the endotoxin level in the bronchoalveolar lavage (BAL) and to propose to the clinician a guide in the diagnosis of gram-negative bacterial (GNB) pneumonia. DESIGN: Retrospective and prospective studies to investigate the relation between endotoxin level and quantitative bacterial culture of BAL and to test the predictive value of a defined threshold. SETTING: University hospital general intensive care unit. PATIENTS: In the first part of the study, 77 consecutive ventilated patients with clinical suspicion of nosocomial pneumonia between January 1995 and January 1996. In the second part of the study, 93 consecutive ventilated patients studied prospectively between February 1996 and April 1997. MEASUREMENTS AND MAIN RESULTS: Quantitative cultures for aerobic bacteria were performed directly from the fluid. Bacterial species were determined with standard techniques. The detection of endotoxin in BAL was made using a quantitative chromogenic Limulus assay. In the retrospective analysis, a significant correlation between quantitative GNB cultures and BAL endotoxin levels was observed (r2 = 0.60, p < .0001). An endotoxin level > or = 4 endotoxin units/mL (EU/mL) distinguishes patients with a significant GNB count from colonized patients with a sensitivity of 92.6%, a specificity of 81.4% and a correct classification rate of 84.9%. In the prospective analysis, the 4 EU/mL threshold permits identification of infected patients with a sensitivity of 82.2%, a specificity of 95.6%, and a correct classification rate of 90.3%. The receiver operating characteristic curve analysis showed that the Limulus assay still had a good discrimination power in the prediction of significant bacterial count in BAL fluid. CONCLUSIONS: Endotoxin detection immediately after bronchoscopy is a distinct advantage to the clinician because antimicrobial gram-negative therapy may be immediately justified according to the results.

Adolescent↗
PubMed2000

[Transverse fracture of the upper sacrum with major displacement. CT reconstruction: case report].

PURPOSE OF THE STUDY: Transverse fractures of the upper sacrum are rare. We report a case with major displacement and neurological impairment. The use of 3D computed tomography (CT) reconstruction to facilitate preoperative planning and surgical procedure is discussed. MATERIALS AND METHODS: A 49-year-old depressive woman jumped from the second floor in an attemp to commit suicide. She presented an absence of motor reponse in L5 region on both sides, hypoesthesia of S1 dermatome, perineal problems including saddle hypoesthesia and a hypotonic anal sphincter. Radiologic investigation showed a transverse fracture of the upper sacrum with major displacement. CT with 3D reconstruction visualized the course of the different fracture lines on the different levels of the sacrum. Open reduction, extensive laminectomy and internal fixation were performed 6 days following the injury. RESULTS: After a 1-year post-operative follow up, complete neurological recovery with normal walking and full perineal sphincter control was observed. DISCUSSION AND CONCLUSION: Fractures of the upper sacrum with major displacement are exceptional. They require well prepared surgical management. CT series with 3D reconstruction allow an analysis of the course of the different sagittal fracture lines to facilitate surgical planning.

Female↗
PubMed1999

Total elbow arthroplasty in rheumatoid arthritis: 20 GSBIII prostheses followed 2-5 years.

From 1993 to 1996, we implanted 20 primary GSB IlI prostheses in 17 patients with rheumatoid arthritis. The Mayo Clinic performance index for the elbow was used for the evaluation. The average follow-up was 3 (2-5) years. At the follow-up examination, 12 elbows had an excellent result and 8 a good result. The median performance index increased from 30 (15-53) points to 95 (80-100) points. The subjective assessment was excellent for 11 elbows, good for 8 and poor for 1.2 elbows had radiographic loosening with a progressive radiolucent line and a change in the orientation of the prosthesis.

Aged↗
PubMed1998

Fibroblast growth factor-2 has opposite effects on human breast cancer MCF-7 cell growth depending on the activation level of the mitogen-activated protein kinase pathway.

In human breast cancer MCF-7 and MCF-7ras cells, we demonstrated that whereas insulin had a mitogenic effect on both cell lines, fibroblast growth factor-2 (FGF-2) had opposite effects, stimulating MCF-7 and inhibiting MCF-7ras cell proliferation. The inhibitory signal induced by FGF-2 was related to sustained mitogen-activated protein kinase (MAPK) activation in MCF-7ras cells, while transient MAPK activation was associated with MCF-7 cell proliferation. FGF-2 was further used in combination with insulin or cAMP. In MCF-7 cells, insulin and cAMP reversed the mitogenic effect of FGF-2. In MCF-7ras cells, insulin did not modify the inhibitory effect of FGF-2, but cAMP markedly enhanced it. These effects were also associated with an increased level and duration of MAPK activation. PD98056 abolished the effect of FGF-2 on DNA synthesis in both cell lines, demonstrating that the dual effect of FGF-2 on cell proliferation is dependent on the activity of the extracellular-signal-regulated kinase 1 and 2 (ERK1/2) signalling pathway.

Breast Neoplasms↗
PubMed1998

Biometry of the capsular ligaments of the wrist.

The aim of our study was to measure the length, width and inclination in the coronal plane of the capsular ligaments, and to express these measurements as a ratio in order to determine the correlation between these parameters and the bone index. The capsular ligaments were studied from 15 cadaveric upper limbs. We identified 11 volar and 2 dorsal intracapsular ligaments. For each ligament, we measured the length to its middle and to its proximal and distal edge, the width at its average portion, and the inclination in the frontal plane. There was a difference between the proximal or distal length and the middle length for four ligaments. In these cases, however, there was a significant correlation between the proximal or distal length and the middle length. The length of capitate, the length of the third metacarpal bone, and the carpal height were significantly correlated with four ligaments. There were correlations between the length of one ligament and that of all others. There was no correlation between the inclination of the radius and the inclination of ligaments in the coronal plane. Nevertheless, there were six significant correlations between the inclination of one ligament and that of all others.

Aged↗
PubMed1998

Hemodynamic effects of epinephrine associated to an epidural clonidine-bupivacaïne mixture during combined lumbar epidural and general anesthesia.

Clonidine or epinephrine are frequently combined to epidural local anesthetics to strengthen sensory block and prolong analgesia. Both drugs impair the hemodynamic profile of central neural blockade but the effects of their combination on arterial pressure and heart rate are not known and were examined in this double-blind prospective randomised study. Forty four patients scheduled for lumbar disc surgery were allocated to two groups. Epidural anesthesia was obtained by administration of 150 micrograms clonidine in 15 ml bupivacaine 0.25% solution without (group C) or with (group C + E) 37.5 micrograms epinephrine. Systolic, mean, diastolic arterial pressure and heart rate were measured throughout the study. Combined epidural and general anesthesia induced a significant decrease in arterial pressure and heart rate in both groups. SAP and MAP decreased significantly less in the patients receiving epinephrine. Low dose epidural epinephrine decreases arterial pressure instability during combined epidural and general anesthesia.

Adolescent↗