[Does research in anesthesia-intensive care improve our practice?].
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Biomedical subjects
Publications and source records attributed to J Mantz.
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We hypothesized that anesthetic dose of riluzole, an inhibitor of glutamate neurotransmission, may affect the activity and/or expression of neuronal NOS (nNOS). Riluzole, N(G)-nitro-L-arginine-methyl ester (L-NAME) and 7-nitro indazole (7-NI) produced a concentration-related inhibition of nNOS activity in vitro. Riluzole competed with 7-NI for inhibition of nNOS activity, but had no effect on nNOS or endothelial NOS (eNOS) protein expression. Also, nNOS activity was significantly decreased in riluzole-anesthetized rats (40 mg kg(-1) i.p., -32+/-6% from controls, P<0.05). Therefore, blockade of nNOS activity may be involved in the anesthetic effects of riluzole in vivo.
UNLABELLED: Adolescents' fatigue is a worrying subject. PATIENTS AND METHOD: A survey was carried out over a period of ten days (a school week between two weekends). Through a daily questionnaire, 386 adolescents aged 15-20 years were asked about sleep onset and offset, time delay of sleep onset, quality of sleep, daytime sleepiness and naps. RESULTS: The results confirmed that the length of sleep was lessened during weekdays. This duration was one hour shorter than on Saturday nights or during holidays. However, a significant delay occurs in sleep onset on Saturday nights and sleep offset on Sunday mornings, which represents the main irregularity in the sleep schedule. Poor quality of sleep is due to difficulties in sleep onset (16%) and night awakenings (39%). Daytime sleepiness is reported by 38% of the adolescents, and many of them have a nap on Sundays, or other days of the week. Daytime activities (out-of-school sports, particularly) and evening activities were studied as well as the use of hypnotics and stimulants. CONCLUSION: This work stresses sleep insufficiency during the week at school, changes in sleeping patterns during weekends, and sometimes poor quality of sleep. Similar facts have already been found in children, and this may explain the consequences on the life and behaviour of adolescents. The population has to be informed about the effects of sleep on health.
OBJECTIVE: Recent studies confirmed the deleterious role of glutamate in the pathophysiology of spinal cord ischemia induced by aortic cross-clamping. We investigated the effect of riluzole, an anti-glutamate drug, in a rat model of spinal cord ischemia. MATERIALS AND METHODS: Spinal cord ischemia was induced in normothermia for 14 min in Sprague-Dawley rats using direct aortic arch plus left subclavian artery cross-clamping through a limited thoracotomy. Experimental groups were as follows: sham-operation (n=15), control (n=15) receiving only vehicle, riluzole (n=15) receiving riluzole (4 mg/kg) before clamping and at the onset of reperfusion. Separate animals were used for monitoring physiologic parameters in the sham-operation (n=3), control (n=5), and riluzole (n=5) groups. Neurologic status was assessed at 6, 24 h, and then daily up to 96 h. Rats were randomly killed at 24, 48, or 96 h (n=5 for each time). Spinal cords were harvested for histopathology, immunohistochemistry for microtubule-associated protein 2 (MAP-2), TUNEL staining, and analysis of DNA fragmentation by agarose gel electrophoresis. RESULTS: All sham-operated rats had a normal neurologic outcome, whereas all control rats suffered severe and definitive paraplegia. Riluzole-treated rats had significantly better neurologic function compared to the control. Histopathology disclosed severe neuronal necrosis in the lumbar gray matter of control rats, whereas riluzole-treated rats suffered usually mild to moderate injury. Riluzole particularly prevented motor neurons injury. MAP-2 immunoreactivity was completely lost in control rats, whereas it was preserved either completely or partly in riluzole-treated rats. TUNEL staining revealed numerous apoptotic neurons scattered within the whole gray matter of control rats. Riluzole prevented or dramatically attenuated apoptotic neuronal death in treated rats. DNA extracted from lumbar spinal cords of sham-operated and riluzole-treated rats exhibited no laddering, whereas spinal cords from control rats showed DNA laddering with fragmentation into approximately 180 multiples of base pairs. CONCLUSIONS: Riluzole may protect the spinal cord in a setting of severe ischemia by preventing neuronal necrosis and apoptosis. This drug may therefore be considered for clinical use during 'high risk' surgical procedures on the thoracoabdominal aorta.
OBJECTIVES: To determine bronchoalveolar lavage (BAL) fluid concentrations of keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF), two potent growth factors for alveolar type II epithelial cells, in patients with acute respiratory distress syndrome (ARDS). DESIGN: Prospective study. SETTING: An adult trauma/surgical intensive care unit in an urban teaching hospital. PATIENTS: A total of 32 ventilated patients with pulmonary infiltrates prospectively identified with ARDS (n = 17) or without ARDS (n = 15), including eight patients with hydrostatic edema (HE), and ten nonventilated patients serving as controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: BAL was performed 2.88 days +/- 2.4, 3.5 days +/- 2.4, and 2.3 days +/- 2.2 after the lung insult in ARDS, HE, and other non-ARDS patients respectively (p = .32). KGF was detected in BAL fluid in 13 of the 17 ARDS patients (median, 31.6 pg/mL), in one patient with HE, and in none of other non-ARDS patients. In ARDS patients, detection of KGF in BAL was associated in BAL fluid with the detection of type III procollagen peptide (PIIIP), a biological marker of fibroproliferation. In ARDS patients, detection of KGF in BAL was associated with death (p = .02). HGF was detected in 15 ARDS patients (median, 855 pg/mL), in seven patients with HE (median, 294 pg/mL; p = .05 for the comparison with ARDS group), in six of other non-ARDS patients (median, 849 pg/mL; p = .32 with ARDS group). HGF concentrations were higher in nonsurvivors than in survivors (p = .01). None of the ten BAL of controls contained either KGF or HGF. CONCLUSION: KGF was detected almost exclusively in BAL fluid from ARDS patients and correlated with a poor prognosis in this group. In contrast, HGF was detected in the BAL fluid from a majority of patients with or without ARDS. Elevated HGF concentrations were associated with a poor prognosis in the overall group.
OBJECTIVES: To display theorical and methodological basis of the molecular biology. To point out its main medical applications. DATA SOURCES: For this review, we analysed the English and French literature concerning the research and clinical aspects of the molecular biology, especially in anaesthesiology and intensive care, using the Medline database. The current textbooks were also used. STUDY SELECTION: We selected: 1) the original articles corresponding to the main advances that resulted in the present state of this discipline; 2) the reviews; 3) some chapters of textbooks. DATA EXTRACTION: In this review, we report: 1) the current knowledge concerning the conservation and the expression of the genome; 2) the principles of the most widely used experimental techniques; 3) the medical applications of this knowledge in anaesthesiology and intensive care; 4) the more recent developments of this research field. DATA SYNTHESIS: Within medical biology, molecular biology essentially corresponds to the study of nucleic acids. In this review, the general principles governing the organization and expression of the genome are discussed. The expansion of molecular biology has been a consequence of the widespread use of enzymatic tools, of which bacterial restriction enzymes were the first. Numerous enzymes are now available, permitting DNA strands to be cut, linked, synthesized and sequenced. Several of the most representative molecular biology techniques are described. Some of them, such as PCR, are commonly used in clinical situations. Animal experimental models have also been generated by genome altering methods, in order to analyse the phenotypic consequences of these modifications. Recently, a viable mammal, deriving from a differentiated cell, has been cloned. Human embryonic totipotent stem cells are now available in cultures. These advances have important ethical implications whilst, at the same time, offering new opportunities for medical applications. The state of gene therapy and human genome sequencing programmes is discussed.
During cerebral ischaemia, energetic failure of injured cells together with excessive release of glutamate the most common excitatory amino acid in the brain, lead to excitotoxicity and immediate or delayed neuronal death. There is strong experimental evidence to support the neuroprotective role played by anaesthetic agents. Hence, barbiturates, volatile anesthetics or ketamine exhibit significant protective effects against ischaemic injury in numerous experimental models of ischaemia in vitro or in vivo. The neurobiological substrate of this action is probably a reduction of the activity of glutamate receptors (N-methyl-D-aspartate and kainate), and/or downstream biochemical events. Reduction of cerebral metabolism by these agents seems not to be their primary neuroprotective mechanism. However, no data are available at the present time to support any clinical benefit of these actions in neurosurgical patients, head trauma in contrast to mild hypothermia or cerebrovascular disease. Future research should develop models as close as possible to the clinical situation to examine further pathophysiological hypotheses and clinical implications.
The post-operative period is particularly dangerous for obese patients. The aim of this study was to compare the immediate post-operative course after either laparoscopic or open gastroplasty. We studied retrospectively 20 and 14 consecutive patients who underwent laparoscopic or open adjustable silicone gastric banding, respectively. After the laparoscopic procedure, patients had a significantly shorter stay in the post-anaesthesia care unit (0.3 +/- 0.4 and 1.1 +/- 1 days), reduced analgesic requirements, a shorter period of intravenous catheter use (2.3 +/- 1.9 and 4.8 +/- 1.4 days), were able to walk sooner (1 +/- 0.4 and 2.1 +/- 1.6 days) and had a significantly shorter duration of in-hospital stay (5.4 +/- 2.3 and 15.8 +/- 4.5 days) than after an open procedure. This report suggests that the use of laparoscopy for gastroplasty in morbidity obese patients may significantly improve the immediate post-operative course.
In the surgical intensive care unit of a university hospital, we investigated the frequency of and the risk factors for acquisition of methicillin-resistant Staphylococcus aureus (MRSA) during postoperative intra-abdominal infection (pIAI). We conducted a prospective MRSA nasal screening and case evaluation for 17 months among 73 consecutive patients with having pIAI. MRSA pIAI was diagnosed when MRSA was obtained from culture of intraperitoneal fluids. The identity of nasal and peritoneal MRSA strains was assessed by genomic analysis. Twelve patients had MRSA pIAI, representing 21% of all MRSA infections acquired by the 73 patients. An organ system failure score of >/=1 and MRSA nasal carriage prior to pIAI were the independent risk factors for acquisition of MRSA pIAI. Patients with MRSA pIAI had a longer intensive care unit stay and more reoperations than did those free of MRSA pIAI. We conclude that MRSA may be a causative pathogen in pIAI and may be related to nasal colonization.
UNLABELLED: Changes in intracellular pH (pHi) of alveolar type II (ATII) cells have been involved in the pathophysiology of pulmonary edema. ATII cells have evolved several ions transporters to regulate their pHi, including a Na+H+ antiporter. Because halothane alters the activity of ion transporters in various cells types, it may also affect the activity of this Na+H+ antiporter. This study was performed 1) to characterize a Na+H+ antiporter in a model of ATII cells and 2) to investigate the effect of halothane on the activity of this antiporter. ATII cells were obtained from primary rat ATII cells transfected with a mutant of simian virus SV40 large T antigen (SV40-T2), and their pHi was monitored using the pH-sensitive fluorescent probe 2'-7' (bis carboxyethyl)-5(6')-carboxyfluorescein. We demonstrated in vitro that 1) a Na+H+ antiporter (apparent Km 6.8 +/- 3.4 mM, Vmax 0.0105 +/- 0.0013 delta UpHi/s) regulates the pHi of SV40-T2 cells and 2) at clinically relevant concentrations (10(-3) to 10(-5) M) and for a short exposure duration (60 min), halothane enhances the activity of this antiporter. Because ATII cell acidification has been associated with alterations in the alveolar epithelial barrier, halothane-induced intracellular alkalinization might exhibit some protective effect in clinical situations, such as aspiration pneumonia. IMPLICATIONS: In vitro, halothane induces an intracellular alkalinization of pneumocytes II via the activation of a Na+H+ antiporter. Because acidification of these cells has been associated with alterations in the alveolar epithelial barrier, halothane might exhibit some protective effect in clinical situations, such as aspiration pneumonia.
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BACKGROUND: Experimental data suggest that volatile anesthetics induce significant changes in extracellular dopamine concentrations in the striatum, a restricted but functionally important brain area. In the present study, the authors used a superfused slice preparation to examine the effects of halothane and isoflurane on both spontaneous and N-methyl-D-aspartate (NMDA)-evoked dopamine release in the striatum, and whether these effects involved actions of these anesthetics mediated by gamma-aminobutyric acid receptors in this structure. METHODS: Radioactivity collected from 5-min fractions was compared in the absence (basal release) or presence (evoked release) of NMDA alone and combined with various pharmacologic or anesthetic agents in slices of the dorsolateral striatum and synaptosomes of the whole striatum preloaded with 3H-dopamine and superfused with artificial cerebrospinal fluid. RESULTS: In tetrodotoxin-treated striatal slices, halothane and isoflurane significantly increased dopamine basal release (EC50 = 0.33 mM and 0.41 mM for halothane and isoflurane, respectively). Both agents decreased the NMDA-evoked dopamine release in both the absence (IC50 = 0.15 mM and 0.14 mM for halothane and isoflurane, respectively) and presence (IC50 = 0.15 mM for both halothane and isoflurane) of tetrodotoxin in slices, and in synaptosomes (IC50 = 0.19 mM for both halothane and isoflurane). NMDA-induced dopamine release was significantly enhanced by bicuculline, a gamma-aminobutyric acid receptor antagonist. Halothane and isoflurane inhibitory effects on NMDA-evoked dopamine release were significantly reduced in the presence of bicuculline. CONCLUSION: These results indicate that halothane and isoflurane decrease the NMDA-evoked dopamine release by acting directly at dopamine terminals in striatal slices. They support the involvement of both depression of presynaptic NMDA receptor-mediated responses and enhancement of gamma-aminobutyric acid receptor-mediated responses in these effects.
Pharmacological manipulation of the sympathetic tone has led to the synthesis of novel compounds to control stress-induced hemodynamic disorders. The use of alpha(2)-adrenoceptor agonists is particularly interesting in this regard, since these agents decrease sympathetic activity by reducing norepinephrine release from nerve terminals. Dexmedetomidine is a potent, highly selective alpha(2)-adrenoceptor agonist. Its use is associated with a decrease in heart rate and blood pressure both in animals and humans. Several lines of evidence suggest that this compound increases perioperative cardiovascular stability and reduces the incidence of ischemic episodes in patients with coronary artery disease. In addition to its cardiovascular properties, dexmedetomidine possesses anxiolytic, hypnotic/sedative, anesthetic-sparing and analgesic actions and is devoid of significant respiratory depressant effects. Targeted mutations of the alpha(2) receptor site indicate that the alpha(2A) subtype is primarily involved in its sedative and anesthetic-sparing effects. Because of these properties, dexmedetomidine may be particularly useful during the perioperative period, as well as for sedation of patients in critical care settings.
PURPOSE: To compare recovery of psychomotor function in elderly and young surgical patients at emergence from propofol-alfentanil anaesthesia. METHODS: Ten elderly (> 70 yr) and 10 younger (< 40 yr) patients scheduled for orthopaedic surgery of less than three hours, were anesthetized with nitrous oxide, propofol and alfentanil. Propofol and alfentanil cumulative doses, time from cessation of propofol infusion to eye opening (EO) on verbal command and to extubation were recorded. Psychomotor performance was assessed by the Mini-Mental State (MMS) performed the day prior to surgery and postoperatively at 30, 60, and 120 min, following extubation. Propofol blood concentrations were measured at EO and at each MMS task. RESULTS: Elderly patients were comparable with young patients for preoperative MMS scores, surgery and anaesthesia duration, propofol and alfentanil cumulative doses. Postoperative MMS scores were lower at 30, 60 and 120 min, in elderly patients. Propofol blood concentrations were not different between elderly and young patients at EO, 30, 60 and 120 min. CONCLUSION: Psychomotor performance is impaired in elderly compared with young patients at emergence from propofol-alfentanil anaesthesia. These differences are not likely to be related to propofol accumulation in elderly subjects.
The influence of a single dose of clonidine (5 micrograms kg-1) or hydroxyzine (1 mg kg-1) on intraoperative propofol requirements was determined in 28 male patients (ASA I) undergoing elective orthopaedic surgery. Patients were randomly allocated to receive either clonidine or hydroxyzine orally 2 h before induction of anaesthesia. After a loading dose of propofol (2.5 mg kg-1), mivacurium (0.2 mg kg-1) and alfentanil (15 micrograms kg-1), anaesthesia was maintained with a standardized propofol infusion supplemented with nitrous oxide (66%) in oxygen. During surgery, additional propofol boluses (1 mg kg-1) were administered when heart rate or mean arterial pressure increased by more than 10% compared with preinduction values. The clonidine group demonstrated a 14.5% decrease in total propofol requirements (P < 0.05) and a 52.2% reduction in additional propofol boluses (P < 0.02) in comparison with the hydroxyzine group. intraoperative heart rate and mean arterial pressure were significantly lower in the clonidine group but no patients needed treatment with ephedrine for hypotension or bradycardia. Recovery of psychomotor function and discharge from the recovery room were not delayed in the clonidine group. This study indicates that 5 micrograms kg-1 clonidine given as premedication in ASA I patients reduces intraoperative propofol requirements in comparison with 1 mg kg-1 hydroxyzine without inducing adverse effects on recovery or haemodynamic stability.
The influence of aging on the pharmacodynamics of anaesthetic agents in the central nervous system remains poorly understood. As alpha-aminobutyric acid (GABA)-mediated neurotransmission appears to be an important target for anaesthetics in the brain, we hypothesized that aging could alter the sensitivity of the GABA carrier to anaesthetics. We have examined the effects of etomidate and propofol on the uptake of [3H]-GABA (5 min, 37 degrees C) into striatal synaptosomes of rats aged 2, 18 and 24 months. In 2-month-old rats, [3H]-GABA uptake was inhibited by nipecotic acid, a competitive inhibitor of the GABA carrier (IC50 = 3.6 SD 0.3 microM). Etomidate and propofol markedly reduced the activity of the GABA carrier, with IC50 values 58 (SD 3) and 46 (SD 3) mumol litre-1, respectively. Aging increased IC50 values for these anaesthetics. Nipecotic acid was unaffected. These data suggest that aging selectively alters the action of etomidate and propofol in the mammalian CNS.
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BACKGROUND: General anesthetics are thought to produce their hypnotic effects mainly by acting at ligand-gated ionic channels in the central nervous system (CNS). Although it is well established that volatile anesthetics significantly modify the activity of the acetylcholine nicotinic receptors of the neuromuscular junction, little is known about their actions on the acetylcholine receptors in the CNS. In this study, the effects of halothane and isoflurane on the regulation of dopamine (DA) (gamma-aminobutyric acid [GABA]) depolarization-evoked release mediated by nicotinic (muscarinic) presynaptic receptors were studied in the rat striatum. METHODS: Assay for GABA (dopamine) release consisted of 3H-GABA (3H-DA)-preloaded synaptosomes with artificial cerebrospinal fluid (0.5 ml/min, 37 degrees C) and measuring the radioactivity obtained from 1-min fractions for 18 min, first in the absence of any treatment (spontaneous release, 8 min), then in the presence of depolarizing agents combined with vaporized halothane and isoflurane (0.5-5%, 5 min), and finally with no pharmacologic stimulation (5 min). The depolarizing agents were potassium chloride (KCl; 9 mM) alone or with acetylcholine (10(-6)-10(-4) M) and/or atropine (10(-5) M) for experiments with 3H-GABA, and KC1 (15 mM) and nicotine (10(-7) - 5 x 10(-4) M) alone or with mecamylamine (10(-5) M) for experiments with 3H-DA. RESULTS: Potassium chloride induced a significant, Ca(2+)-dependent release of both 3H-GABA and 3H-DA. Nicotine produced a concentration-related, mecamylamine-sensitive 3H-DA release that was significantly attenuated by nicotine (10(-7) M) preincubation. Acetylcholine elicited a dose-dependent, atropine-sensitive reduction of the KC1-evoked 3H-GABA release. Halothane and isoflurane significantly decreased the nicotine-evoked 3H-DA release but had only limited depressant effects on the KC1-stimulated 3H-DA and no action on the KC1-induced 3H-GABA release. The effects of acetylcholine on 3H-GABA release were reversed by halothane but not by isoflurane. CONCLUSIONS: Clinically relevant concentrations of halothane and isoflurane significantly, but differentially, alter the presynaptic cholinergic regulation of the release of inhibitory neurotransmitters in the striatum. These results suggest that the cholinergic transmission may represent an important and specific presynaptic target for volatile anesthetics in the CNS.