J Leclerc’s research while affiliated with University of Lille Nord de France and other places

To assess the effects of the angiotensin-converting enzyme (ACE) inhibitor (ACEI) perindopril on prolonged endothelial cell dysfunction in a rabbit endotoxic model. Randomized, controlled, interventional trial. University animal laboratory. A total of 65 male New Zealand White rabbits, randomly assigned to one of eight groups. Endotoxic shock was induced by a single lipopolysaccharide (LPS, serotype O55:B5) bolus (0.5 mg.kg(-1), i.v., Escherichia coli endotoxin). Coagulation factors and expression of monocyte tissue factor (TF) were determined by functional assay. Endothelium-dependent vascular relaxation was assessed by in vitro vascular reactivity. Immunohistochemical staining (CD31) was performed to assess endothelial injury of the abdominal aorta. These parameters were studied 5 days (D5) after the onset of endotoxic shock. Rabbits were randomized to receive perindopril (1 mg kg(-1) day(-1) orally) alone, or with N(G)-nitro-L-arginine methyl ester (L-NAME; 15 mg kg(-1) day(-1) orally), or L-NAME alone initiated 7 days before the onset of endotoxic shock and maintained for 5 days afterward. Perindopril prevented altered endothelium-dependent relaxation to acetylcholine induced by LPS injection (E(max)=75.6+/-3.7 vs 42.3+/-9.4% in LPS group, p<0.05). This effect was inhibited by co-treatment with L-NAME. Perindopril had no effect on either LPS-induced endothelial histological injury or monocyte TF expression. These data suggest that perindopril can prevent endothelial dysfunction in endotoxin-induced shock through an NO-dependent mechanism.

Las particularidades de la anestesia y reanimación en la cirugía de las glándulas suprarrenales se relacionan esencialmente con las alteraciones de la secreción endocrina y su brusca corrección por la exéresis (tumores secretantes); en ocasiones también pueden estar vinculadas con la amplitud de la disección quirúrgica (corticosuprarrenalomas). Los progresos realizados en el ámbito de las estrategias diagnósticas y terapéuticas han permitido reducir la mortalidad y la morbilidad perioperatorias, así como racionalizar y simplificar el tratamiento integral de los pacientes. La generalización del acceso laparoscópico en la mayoría de estos tumores es una de las modificaciones más importantes de los últimos diez años. En este capítulo se describen las principales características del tratamiento anestésico pre, intra y postoperatorio, en particular en presencia de hipercortisolismo, hiperaldosteronismo o secreción anormal de catecolaminas.

This study aimed at: i) stating what the routines are regarding ordering of preoperative coagulation test; ii) evaluating the impact on the use of pre-operative orders from the data obtained during the first and the second parts of the study. Descriptive and comparative epidemiologic study. This study was performed twice, and lasted for one day each during two consecutive years (1998 and 1999). It concerned 22 private clinics in the French region 'Nord-Pas-de-Calais'. The anaesthesiologists who took part in the project had to fill out an easy and brief questionnaire concerning each patient who had been admitted to the operating area. It dealt mainly with the presence or the absence, of a preoperative laboratory screening, and with who ordered the test and which tests. The results of the first part of the study (1998) have been evaluated several times with the involved anaesthesiologists. Before repeating the study in 1999, the results were first discussed and compared to the recommendations of the experts. In 1998, preoperative coagulation tests were ordered for 81% of the patients (n = 662), which in more than half the cases were ordered by an anaesthesiologists. In less than 5% of the cases, one or more abnormalities were detected out of which half were predictable because of the patients previous medical history. Only one of the patients in the study suffered from an haemorrhagical problem although he had a normal coagulation screening. A year after, the ordering of a preoperative coagulation check included 75% of the patients (n = 400), which represents a small but nonetheless significant decrease of the number of orders compared to 1998 (p < 0.05). The proportion of preoperative laboratory screening prescribed by an anaesthesiologist remained the same. There were one or more abnormalities in 1% of the screening tests that were obtained. A patient had a haemorrhagical problem while she had a normal coagulation screening. In this study, repeated feed-back to the writers of the preoperative orders in the time interval between the two parts of the study did not induce a noticeable decrease in the number of preoperative coagulation tests ordered. The results show the necessity of a different approach to present scientific knowledge in order to modify medical behaviour.

Objectives: This study aimed at: i) stating what the routines are regarding ordering of preoperative coagulation test; ii) evaluating the impact on the use of pre-operative orders from the data obtained during the first and the second parts of the study. Study design: Descriptive and comparative epidemiologic study Patients and methods: This study was performed twice, and lasted for one day each during two consecutive years (1998 and 1999). It concerned 22 private clinics in the French region 'Nord-Pas-de-Calais'. The anaesthesiologists who took part in the project had to fill out an easy and brief questionnaire concerning each patient who had been admitted to the operating area. It dealt mainly with the presence or the absence, of a preoperative laboratory screening, and with who ordered the test and which tests. The results of the first part of the study (1998) have been evaluated several times with the involved anaesthesiologists. Before repeating the study in 1999, the results were first discussed and compared to the recommendations of the experts. Results: In 1998, preoperative coagulation tests were ordered for 81% of the patients (n=662), which in more than half the cases were ordered by an anaesthesiologists. In less than 5% of the cases, one or more abnormalities were detected out of which half were predictable because of the patients previous medical history. Only one of the patients in the study suffered from an haemorrhagical problem although he had a normal coagulation screening. A year after, the ordering of a preoperative coagulation check included 75% of the patients (n=400), which represents a small but nonetheless significant decrease of the number of orders compared to 1998 (p < 0.05). The proportion of preoperative laboratory screening prescribed by an anaesthesiologist remained the same. There were one or more abnormalities in 1% of the screening tests that were obtained. A patient had a haemorrhagical problem while she had a normal coagulation screening. Conclusions: In this study, repeated feed-back to the writers of the preoperative orders in the time interval between the two parts of the study did not induce a noticeable decrease in the number of preoperative coagulation tests ordered. The results show the necessity of a different approach to present scientific knowledge in order to modify medical behaviour.

To analyze the current knowledge concerning xenon anaesthesia. References were obtained from computerized bibliographic research (Medline), recent review articles, the library of the service and personal files. All categories of articles on this topic have been selected. Articles have been analysed for history, biophysics, pharmacology, toxicity and environmental effects and using prospect. The noble gas xenon has anaesthetic properties that have been recognized 50 years ago. Xenon is receiving renewed interest because it has many characteristics of an ideal anaesthetic. In addition to its lack of effects on cardiovascular system, xenon has a low solubility enabling faster induction of and emergence from anaesthesia than with other inhalational agents. Nevertheless, at present, the cost and arety of xenon limit its widespread use in clinical practice. The developement of closed rebreathing system that allowed recycling of xenon and therefore reducing its waste has led to a recent interest in this gas. Reducing its cost will help xenon to find its place among anaesthetic agents. An European multicentric clinical trial under submission will contribute to the discussion of the opportunity for xenon introduction in anaesthesia.

Objective: To analyze the current knowledge concerning xenon anaesthesia.Data sources: References were obtained from computerized bibliographic research (Medline®), recent review articles, the library of the service and personal files.Study selection: All categories of articles on this topic have been selected.Data extraction: Articles have been analysed for history, biophysics, pharmacology, toxicity and environmental effects and using prospect.Data synthesis: The noble gas xenon has anaesthetic properties that have been recognized 50 years ago. Xenon is receiving renewed interest because it has many characteristics of an ideal anaesthetic. In addition to its lack of effects on cardiovascular system, xenon has a low solubility enabling faster induction of and emergence from anaesthesia than with other inhalational agents. Nevertheless, at present, the cost and rarety of xenon limit its widespread use in clinical practice. The developement of closed rebreathing system that allowed recycling of xenon and therefore reducing its waste has led to a recent interest in this gas. Reducing its cost will help xenon to find its place among anaesthetic agents. An European multicentric clinical trial under submission will contribute to the discussion of the opportunity for xenon introduction in anaesthesia.

Objectives: This study aimed at: i) stating what the routines are regarding ordering of preoperative coagulation test ; ii) evaluating the impact on the use of pre-operative orders from the data obtained during the first and the second parts of the study.Study design: Descriptive and comparative epidemiologic studyPatients and methods: This study was performed twice, and lasted for one day each during two consecutive years (1998 and 1999). It concerned 22 private clinics in the French region ‘Nord-Pas-de-Calais’. The anaesthesiologists who took part in the project had to fill out an easy and brief questionnaire concerning each patient who had been admitted to the operating area. It dealt mainly with the presence or the absence, of a preoperative laboratory screening, and with who ordered the test and which tests. The results of the first part of the study (1998) have been evaluated several times with the involved anaesthesiologists. Before repeating the study in 1999, the results were first discussed and compared to the recommendations of the experts.Results: In 1998, preoperative coagulation tests were ordered for 81% of the patients (n=662), which in more than half the cases were ordered by an anaesthesiologists. In less than 5% of the cases, one or more abnormalities were detected out of which half were predictable because of the patients previous medical history. Only one of the patients in the study suffered from an haemorrhagical problem although he had a normal coagulation screening. A year after, the ordering of a preoperative coagulation check included 75% of the patients (n=400), which represents a small but nonetheless significant decrease of the number of orders compared to 1998 (p

Objective: To analyze the current knowledge concerning xenon anaesthesia. Data sources: References were obtained from computerized bibliographic research (Medline(R)), recent review articles, the library of the service and personal files. Study selection: All categories of articles on this topic have been selected. Data extraction: Articles have been analysed for history, biophysics, pharmacology, toxicity and environmental effects and using prospect. Data synthesis: The noble gas xenon has anaesthetic properties that have been recognized 50 years ago. Xenon is receiving renewed interest because it has many characteristics of an ideal anaesthetic. In addition to its lack of effects on cardiovascular system, xenon has a low solubility enabling faster induction of and emergence from anaesthesia than with other inhalational agents. Nevertheless, at present, the cost and rarety of xenon limit its widespread use in clinical practice. The development of closed rebreathing system that allowed recycling of xenon and therefore reducing its waste has led to a recent interest in this gas. Reducing its cost will help xenon to find its place among anaesthetic agents. An European multicentric clinical trial under submission will contribute to the discussion of the opportunity for xenon introduction in anaesthesia. (C) 2001 Editions scientifiques et medicales Elsevier SAS.

Objectives: To determine the duration of vascular blood vessel dysfunction and coagulation abnormalities after administration of endotoxin in a nonlethal septic rabbit model. Design: Randomized, controlled, interventional trial. Setting: University animal laboratory. Subjects: A total of 30 male New Zealand White rabbits, randomly assigned to one of two groups. Interventions: Male New Zealand White rabbits were randomly divided into control or lipopolysaccharide (LPS) (0.5 mg/kg iv bolus Escherichia coli endotoxin)-treated groups. Metabolic acidosis and coagulation activation confirmed the presence of septic shock. The abdominal aorta was removed at 24 hrs (day 1), day 5, or day 21 after LPS injection. Immunohistochemical staining for an endothelial cell marker (PECAM-1/CD31) was performed to assess endothelial injury. Endothelium-dependent vascular relaxation was analyzed by in vitro vascular reactivity studies. Responses to acetylcholine, to calcium ionophore (A-23187), and to sodium nitroprusside were studied. In addition, arterial blood samples were collected on day 1, day 5, and day 21 for measurement of clotting factors and tissue factor activity. Measurements and Main Results: LPS injection resulted in endothelial injury, with loss of ∼25% of the endothelial area on day 5, which disappeared on day 21. LPS injection also caused a significantly reduced relaxation response to acetylcholine (44.9% ± 9.9% vs. 76.5% ± 5.4% for the control group;p < .005), which was restored on day 21. In contrast, vascular relaxation in response to A-23187 and sodium nitroprusside was not altered. A significant decrease in the platelet count was observed on day 1, associated with a decrease in factors II and V. On day 5, platelet count and factors II and V were corrected in conjunction with an elevated monocyte tissue factor activity in LPS-injected rabbits. On day 21, coagulation abnormalities were corrected. Conclusions: A single endotoxin injection in the rabbit was responsible for prolonged aortic endothelial cell dysfunction, as well as a prolonged procoagulant state. The latter is a potential trigger for disseminated intravascular coagulation. Importantly, these features are associated with normalization of conventional biological evidence of septic shock.

Septic shock is reported as the most common cause of death in intensive care units. Worldwide data indicate a 30 to 60% mortality rate. This death rate has not really changed since the early 1970s despite improved antibiotic therapy, cardiovascular support, and various advances in the management and treatment of sepsis. Septic shock pathophysiology may be related to several altered blood vessel functions associated or not with obvious anatomical injury. Normally, endothelial cells act as a signaling sensor for blood messages to vascular smooth muscle cells. They play a pivotal role in the regulation of local vascular tone. Endothelial injury due to systemic inflammation and induction of the coagulation cascade has been well recognized in the pathophysiology of septic shock. A better understanding of endothelial cell abnormalities occurring during septic shock might prove to be a good way to optimize septic shock therapy.