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Biomedical subjects

P Dabadie

Publications and source records attributed to P Dabadie.

At least 19 recordsLinked to original sources
PubMed2006

[Microparticles during sepsis and trauma. A link between inflammation and thrombotic processes].

Sepsis and trauma lead to a sustained activation of monocytes and endothelium. In the vascular compartment, stimulated cells release microparticles. Circulating MP provide an additional procoagulant phospholipid surface enabling the assembly of the clotting enzymes complexes and thrombin generation. Their procoagulant properties rely on the exposition of phosphatidylserine, made accessible after cell stimulation and on the possible presence of tissue factor, the main cellular initiator of blood coagulation. Microparticles constitute the main reservoir of blood-borne tissue factor activity. At sites of endothelium injury, enhanced release or recruitment of procoagulant MP through P-selectin-PSGL-1 pathway could concentrate TF activity above a threshold allowing blood coagulation to be triggered. Converging evidences from experimental or clinical data highlight a role for MP harboring tissue factor in the initiation of disseminated intravascular coagulopathy. In these settings, the pharmacological modulation of MP levels or biological functions through activated protein C or factor VIIa allows challenging issues.

Apoptosis↗
PubMed2006

[Use of activated recombinant FVII in the control of haemorrhage following trauma].

Uncontrolled haemorrhage is a major cause of death in trauma patients: sometimes inaccessible to surgery and often associated with coagulopathy. We report a case of severe blunt pelvic trauma associated with suicide. The conventional treatments were unsuccessful and embolization was impossible. The patient required massive blood product transfusion. A 100 microg/kg recombinant activated factor VII dose was infused, twice. After administration of the first dose, the blood requirement decreased dramatically. Further work and trials are required to assess the safety profile and dose regimen for this drug.

Coagulants↗
PubMed2004

[Protocol for advanced prehospital emergency care of severe head injury].

OBJECTIVES: To analyze the frequency of systemic factors leading to secondary brain insults in victims of serious head trauma in a prehospital setting and to evaluate a protocol for the advanced prehospital emergency care by mobile intensive care unit (i.e., the French Samu-Smur system). STUDY DESIGN: Prospective study, over a period of 24 months. PATIENTS AND METHODS: This prospective study involved 60 victims of severe head injuries (with the exception of polytrauma patients). Tracheal intubation was performed on each patient under direct laryngoscopy and after induction of anaesthesia (fentanyl-etomidate-rocuronium). Controlled ventilation and vascular loading (objectives: SpO(2) >or= 97%, PETCO(2) between 30 and 35 mmHg, SAP >or= 90 mmHg) were administered. RESULTS: Hypoxaemia was found to be the most frequent cause of secondary insults (57% of patients with SpO(2) < 97%). In the case involving an accident that occurred 17 km from the hospital (with extremes of 6-65 km), the speed of medical intervention was note-worthy: tracheal intubation was performed 50 min after the accident, and the patient was admitted into a trauma centre 101 min after impact (median). However, faster intervention could be obtained if the transmission of the alert was improved. The conditions under which the tracheal intubation was performed were found to be satisfactory (difficult intubation 1.6%) without deteriorating the haemodynamic status. This is probably related to the use of muscle relaxants and the choice of etomidate as the first line hypnotic in the prehospital emergency care.

Adolescent↗
PubMed2000

Pharmacological therapy of spinal cord injury during the acute phase.

STUDY DESIGN: Prospective, randomized clinical trial. SETTING: France. OBJECTIVES: To evaluate the safety and effect on neurological outcome of nimodipine, methylprednisolone, or both versus no medical treatment in spinal-cord injury during the acute phase. METHOD: One hundred and six patients who had spinal trauma (including 48 with paraplegia and 58 with tetraplegia) were randomly separated into four groups: M=methylprednisolone (30 mg x kg(-1) over 1 h, followed by 5.4 mg x kg(-1) x h(-1) for 23 h), N=nimodipine (0.015 mg x kg(-1) x h(-1) for 2 h followed by 0.03 mg x kg(-1)h(-1) for 7 days), MN (both agents) or P (neither medication). Neurological assessment (ASIA score) was performed by a blinded senior neurologist before treatment and at 1-year follow-up. Early spinal decompression and stabilization was performed as soon as possible after injury. RESULTS: One hundred patients were reassessed at 1 year. Neurological improvement was seen in each group (P<0.0001), however no additional neurological benefit from treatment was observed. Infectious complications occurred more often in patients treated with M. Early surgery (49 patients underwent surgery within 8 h of their accident) did not influence the neurological outcome. The only predictor of the latter was the extent of the spinal injury (complete or incomplete lesion). CONCLUSION: The present study confirms the absence of benefit of pharmacological therapy in this indication. Because of the paucity of clinical studies that demonstrate the efficacy of pharmacological treatment in spinal injury during the acute phase, systematic use of pharmaceutical agents should be reconsidered.

Acute Disease↗
PubMed2000

Spontaneous human combustion: a sometimes incomprehensible phenomenon.

Several cases of human combustion, the cause of which was not evident, have been described over the last few centuries. There are three intriguing elements to such cases. Firstly, although the body is destroyed, the immediate surroundings are left almost intact. Secondly, there is often no visible source of heat that might have started the fire. Thirdly, sometimes bodies are not completely destroyed, certain parts being perfectly preserved, adjacent to others that are reduced to a state of ashes.

Journal Article↗
PubMed2000

Absence of stereospecific effects of bupivacaine isomers on heart mitochondrial bioenergetics.

BACKGROUND: Highly lipophilic local anesthetics interfere with mitochondrial energy metabolism. These metabolic effects could, in part, explain some toxic effects of local anesthetics, such as bupivacaine-induced myocardial depression. The purpose of this study was to compare the optically pure isomers of bupivacaine on heart mitochondrial bioenergetics. METHODS: Both bupivacaine enantiomers were tested on rat heart isolated mitochondria. Oxygen consumption, adenosine triphosphate synthesis, and enzymatic activities of the four complexes of the respiratory chain were measured. RESULTS: No significant differences were found between R(+)- and S(-)-bupivacaine on mitochondrial oxidative phosphorylation with a similar dose-dependent decrease in adenosine triphosphate synthesis. Complex I (nicotinamide adenine dinucleotide ubiquinone reductase) was the enzymatic complex of the respiratory chain most sensitive to the bupivacaine isomers. Half-inhibitory concentrations for R(+)- and S(-)-bupivacaine were not statistically different (3.3 +/- 0.4 mm and 2.8 +/- 0.6 mm, respectively). CONCLUSIONS: No stereospecific effects of bupivacaine enantiomers were shown in the inhibition of complex I activity and uncoupling of oxidative phosphorylation. This can be correlated with the lack of stereospecific effects of bupivacaine on myocardial depression. The lipid solubility of local anesthetics appears to be the principal physicochemical factor affecting the potency of these tertiary amines on mitochondrial bioenergetics.

Adenosine Triphosphate↗
PubMed2000

Mitochondrial energy metabolism in brain-dead organ donors.

OBJECTIVES: Change from aerobic to anaerobic metabolism has been described in brain-dead organ donors (BDOD) managed for organ procurement. Such modifications could lead to a depletion in intracellular adenine nucleotides and in part explain primary graft dysfunction. The purpose of this study was to investigate the mitochondrial energy metabolism in BDOD using permeabilized muscle fibers. METHODS: With institutional approval, the study was performed prospectively in 15 consecutive BDOD. In each patient, muscle biopsy and blood samples for the determination of plasma lactate and pyruvate were obtained just before organ removal. Mitochondrial respiratory parameters of skeletal muscle were determined in saponin-skinned muscle fibers. Mitochondrial oxygen consumption rates were measured polarographically using different substrates and inhibitors of the respiratory chain complexes. Results were compared to those obtained from muscle biopsies performed in 10 healthy patients during orthopedic surgery. RESULTS: Fifteen donors, 13 men and 2 women, aged 35 +/- 11 yrs, were studied. All patients had a high lactate-to-pyruvate ratio (10). Mitochondrial respiration rates were significantly decreased during adenosine triphosphate (ATP) synthesis. CONCLUSIONS: Major changes in energy metabolism occurred during brain death with a decrease in ATP synthesis capacity. High-risk donors should be recognized for a better graft evaluation.

Adenosine Triphosphate↗
PubMed1999

[Medico-legal dimension of informed consent in medicine].

The practice of the medical arts is more and more becoming framed by laws and regulations. Concurrently, the civil liability in the medical field has also been deeply changed, in particular by reversing the charge of proof of the information given to the patient. After having been reminded of the place in the juridical arsenal of informed consent to a medical procedure, its value is discussed regarding the explanations given by the physicians. Guidelines for a forensic appraisal, with the aim of evaluating and appreciating the information received by the patient, are proposed. Recent judiciary decisions about refusal of care, especially blood transfusions, are discussed.

France↗
PubMed1998

[Medical treatment of spinal cord injury in the acute stage].

OBJECTIVES: To evaluate the effect on neurologic outcome and the safety of nimodipine (N), methylprednisolone (M), or both (MN) versus no medical treatment (P) in spinal cord injury at the acute phase. STUDY DESIGN: Prospective, randomized clinical trial. PATIENTS: One hundred and six patients with a spinal trauma, including 48 with paraplegia and 58 with tetraplegia. METHOD: After eligibility, patients were randomly allocated in one of the following groups: M = methylprednisolone 30 mg.kg-1 over 1 hour, followed by 5.4 mg.kg-1.h-1 for 23 hours, N = nimodipine 0.015 mg.kg-1.h-1 over 2 hours followed by 0.03 mg.kg-1.h-1 for 7 days, MN or P. Neurologic assessment (ASIA score) was performed by a senior neurologist before treatment and at the 1-year follow-up. Early spinal decompression and stabilization was performed as soon as possible after injury. RESULTS: One hundred patients were reassessed at the 1-year follow-up. Neurologic improvement was seen in each group (P < 0.0001), however no neurologic benefit from treatment was observed. Infectious complications occurred more often in patients treated with M. Early surgery (49 patients), within the first 8 hours did not influence the neurologic outcome. The only predictor of the latter was the extent of the spinal injury (complete or incomplete lesion). CONCLUSION: Currently, no evidence of the benefit of medical treatment in this indication is existing. Because of the lack of clinical studies proving efficacy of pharmacological treatment in this specific pathology, a systematic use of medications cannot be recommended.

Acute Disease↗
PubMed1998

Comparison of the effects of bupivacaine and ropivacaine on heart cell mitochondrial bioenergetics.

BACKGROUND: High lipophilic local anesthetics interfere with mitochondrial energy metabolism. These metabolic effects could in part explain some of the toxic effects of local anesthetics, such as bupivacaine-induced myocardial depression. The aim of this study was to compare the bioenergetic effects of the local anesthetics bupivacaine and ropivacaine. METHODS: The effects of both local anesthetics on mitochondrial energy metabolism were studied in rat heart isolated mitochondria and in saponin-skinned left ventricle fibers. Oxygen consumption, adenosine triphosphate synthesis, and enzymatic activities of the complexes of the respiratory chain were measured. RESULTS: Bupivacaine and ropivacaine acted, in isolated mitochondria, as uncouplers between oxygen consumption and phosphorylation of adenosine diphosphate. Further, an inhibitory effect of mitochondrial respiration was evidenced with both anesthetics during maximal respiration and was assigned to a direct inhibition of complex I of the respiratory chain. Mitochondrial adenosine triphosphate synthesis was decreased by both mechanisms. However, both in isolated mitochondria and in permeabilized heart fibers, ropivacaine was less potent than bupivacaine. Adenosine triphosphate synthesis was completely suppressed at 3 mM (approximately 0.1%) bupivacaine, whereas 3 mM ropivacaine induced only about a 40% inhibition. CONCLUSIONS: Ropivacaine disturbs mitochondrial energy metabolism less than bupivacaine does. The lower lipid solubility of ropivacaine may be responsible for the lesser dose-dependent effects of this drug on mitochondrial bioenergetics.

Amides↗
PubMed1997

[Hemodynamic effects of hypertonic saline solutions].

Haemodynamic effects of hypertonic saline solutions (HSS) have been extensively studied in animals and humans. Hypertonic sodium chloride (7.5%, 2,500 mOsm.L-1) either alone or combined with colloids, remains the standard solution. The haemodynamic response of HSS observed during treatment of hypovolaemic shock is explained by 1) an increase in preload due to the expansion of the plasma volume and a musculocutaneous vasoconstriction and 2) a decrease in systemic vascular resistance and afterload. A myocardial stimulation has been shown in various experimental conditions and in humans. However, the clinical relevance of this inotropic effect is questionable. Haemorrhagic shock is the main indication for small volume resuscitation with HSS. Other potential situations for the use of HSS are volume replacement in perioperative period, septic shock or burn injury and cardiopulmonary resuscitation. Before recommending the clinical use of HSS, additional clinical studies are required to substantiate the benefits of HSS over colloids.

Burns↗
PubMed1997

Objective measurement of sleepiness in summer vacation long-distance drivers.

The study investigated whether sleepiness at the wheel is a problem in non-commercial drivers going on summer vacation. All drivers, who stopped at a rest area on a large European freeway while one of the interviewers was available, were systematically approached and asked to respond to a questionnaire. All subjects who had driven at least 400 km (240 miles), whose age was between 20 and 46 years of age, and who agreed to participate were asked to undergo a longer investigation that included a short sleep/wake diary describing overall sleep habits during the year, a sleep/wake log covering the days just prior to departure, an analog visual scale indicating sleepiness at time of interview, and a polygraphically monitored two nap sleep test (TNST). A control group was recruited that consisted of subjects of the same age range, normal sleep habits, and normal nocturnal sleep time before administration of the TNST. One hundred and four drivers (2 women) participated between 08:00 and 20:00 h. The total group was subdivided into 6 subgroups based upon the time of day of their investigation (08:00-10:00 h, 10:01-12:00 h, etc.). The control group included 50 men with 50-55% of control subjects, relative to the total number of index-cases, in each subgroup. Eighty-eight percent (n = 92) of studied drivers had experienced acute sleep deprivation within one day prior to departure due to the planned long driving. The TNST demonstrated that, overall, drivers had a significantly shorter sleep latency in nap 1 and nap 2 than controls, had a significantly longer sleep duration in nap 1 and nap 2, and there was a significant correlation between the sleep debt prior to departure and the sleep stage reached during the TNST. It is concluded that the TNST is a test which allows the objective study of sleepiness in drivers without the burden of the multiple sleep latency test. Many drivers are excessively sleepy when making long summer vacation journeys.

Adult↗
PubMed1997

Effects of the local anesthetic bupivacaine on mitochondrial energy metabolism: change from uncoupling to decoupling depending on the respiration state.

The local anesthetic bupivacaine has been found to uncouple oxidative phosphorylation. However, the precise mechanisms of bupivacaine uncoupling have not been elucidated. In the present paper, we demonstrate that the uncoupling effect of the local anesthetic depends on the respiration state. In state 4-respiration (no ADP phosphorylation), bupivacaine acts as a true protonophoretic uncoupler. On the other hand, in state 3-respiration (ADP phosphorylation), bupivacaine induces a change in proton pump stoichiometry and appears to be a decoupler (slip inducer). Moreover, at high concentration, the local anesthetic inhibits the respiratory chain itself. Thus, the divergent reports in the literature on the action of bupivacaine show in fact the various mechanisms by which the local anesthetic may alter mitochondrial energy metabolism.

Adenosine Diphosphate↗
PubMed1997

The use of 0.25% lidocaine with fentanyl and pancuronium for intravenous regional anesthesia.

The present study was designed to assess the efficacy of fentanyl and pancuronium combined with dilute lidocaine solution for intravenous regional anesthesia of the arm. Forty adult patients undergoing upper limb surgery were randomly allocated to receive either 0.6 mL/kg of 0.5% lidocaine (3 mg/kg) or 0.6 mL/kg of 0.25% lidocaine (1.5 mg/kg) with 1 microg/kg of fentanyl and 0.5 mg of pancuronium. The onset of sensory and motor blocks was significantly shorter in the 0.5% lidocaine group (P < 0.05). However, no differences in analgesia or motor blockade were found between the two groups at 20 min tourniquet time. Regional anesthesia was considered successful in more than 85% of patients. One patient in the 0.25% lidocaine group experienced a transient diplopia after tourniquet release. Postoperative analgesia time was similar in the two groups. We conclude that the addition of fentanyl plus pancuronium to the lidocaine solution reduces the dose of the local anesthetic and possibly systemic toxicity.

Adult↗
PubMed1996

Determinants of sleepiness in automobile drivers.

Governmental agencies do not systematically investigate the presence of daytime sleepiness as a determinant of driving accidents. We surveyed automobile drivers traveling on summer vacations and driving long distances on a European highway. We evaluated their subjective daytime sleepiness while driving and any sleep deprivation just prior to departure. Five-hundred sixty-seven automobile drivers (mean age 37.7 +/- 11 years) were interviewed at a roadside rest-stop. Questions covered the sleep/wake schedule during the year, sleep habits, and the presence of symptoms frequently associated with sleep-disordered breathing. Sleep behavior just prior to departure was compared to the usual sleep schedule during the year. Fifty percent of the responders had a sleep restriction just prior to departure (mean -203 minutes) compared to usual total sleep time during the year; 10% had no nocturnal sleep prior to departure. Drivers younger than 30 years were significantly more acutely sleep deprived than other drivers. Economic migrants (subjects with low economic status) also experienced significant acute sleep restriction.

Accidents, Traffic↗