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Les personnes atteintes de paralysie cérébrale suivent des prises en charge tout au long de leur vie. Parmi ces prises en charge, les stages de rééducation motrice sont démontrés dans la littérature comme ayant un intérêt. Pour autant, il n’existe à ce jour aucune donnée décrivant le recours aux stages de rééducation motrice réalisés par les enfants et adolescents atteints de paralysie cérébrale en France.

Xenon treatment attenuates delayed kidney graft function and prolongs graft survival in rats.

Prolonged hypothermic storage causes ischemia-reperfusion injury (IRI) in the renal graft, which is considered to contribute to the occurrence of the delayed graft function (DGF) and chronic graft failure. Strategies are required to protect the graft and to prolong renal graft survival. We demonstrated that xenon exposure to human proximal tubular cells (HK-2) led to activation of range of protective proteins. Xenon treatment prior to or after hypothermia–hypoxia challenge stabilized the HK-2 cellular structure, diminished cytoplasmic translocation of high-mobility group box (HMGB) 1 and suppressed NF-κB activation. In the syngeneic Lewis-to-Lewis rat model of kidney transplantation, xenon exposure to donors before graft retrieval or to recipients after engraftment decreased caspase-3 expression, localized HMGB-1 within nuclei and prevented TLR-4/NF-κB activation in tubular cells; serum pro-inflammatory cytokines IL-1β, IL-6 and TNF-α were reduced and renal function was preserved. Xenon treatment of graft donors or of recipients prolonged renal graft survival following IRI in both Lewis-to-Lewis isografts and Fischer-to-Lewis allografts. Xenon induced cell survival or graft functional recovery was abolished by HIF-1α siRNA. Our data suggest that xenon treatment attenuates DGF and enhances graft survival. This approach could be translated into clinical practice leading to a considerable improvement in long-term graft survival.

While most patients recover uneventfully from the effects of anesthesia and surgery, for a small percentage of patients the immediate postoperative period can be a period of significant physiological stress. Hence the goal for a Post Anesthesia Care Unit (PACU) is to provide a safe environment for a patient to recover, while avoiding the undesirable side effects of pain, nausea, vomiting and shivering, and to monitor for potentially life threatening hemodynamic and respiratory complications that may require admission into the intensive care unit (ICU). Anesthetic techniques in the operating room are extremely important as these may have significant bearing on the post-operative course. The type of surgery, the patients' co morbid conditions, anticipated extubation and recovery of the patient, as well as the sophistication of the PACU and the expertise of its staff, all influence the choice of anesthetic technique. These agents, however, may themselves contribute to some of the complications and unpleasant events encountered in the PACU. Therefore, evaluation of newer and safer agents, which promote a smoother PACU transition, are warranted. Alpha 2 agonists are increasingly being used as adjuvant therapeutic agents in the perioperative period because of their ability to block the sympathetic stress response, complete with their anesthetic and analgesic sparing properties, lack of respiratory depression and low and predictable side effect profile.

Anaesthetic agents display remarkable neuroprotective potential; here, we describe the evidence supporting its use and highlight areas for future development of the field. In particular the application of isoflurane and/or xenon as inhalational neuroprotectants is advocated and evidence for the neuroprotection provided by barbiturates and suppression of cerebral metabolic rate is discussed.

There is increasing emphasis on performance-based assessment of clinical competence. The High Fidelity Patient Simulator (HPS) may be useful for assessment of clinical practice in anaesthesia, but needs formal evaluation of validity, reliability, feasibility and effect on learning. We set out to assess the reliability of a global rating scale for scoring simulator performance in crisis management.

Antagonists of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors have been shown not only to have neuroprotective effects but also to exhibit neurotoxic properties. In this study, we used c-Fos, a protein product of an immediate early gene, as a marker of neuronal injury to compare the neuroprotective effects of xenon and the neurotoxic properties of xenon, nitrous oxide, and ketamine, three anaesthetics with NMDA receptor antagonist properties.

Changes in medical practice that limit instruction time and patient availability, the expanding options for diagnosis and management, and advances in technology are contributing to greater use of simulation technology in anaesthesiology training. The impact of simulation training includes competency training, crisis-management training, retraining and certification, team training and behavioural change. Benefits of simulation technology include improvements in physical diagnosis and technical skills, and in acquisition and retention of knowledge in a fun and supportive environment compared with traditional methods of learning. In addition, simulation offers exposure to rare and dangerous adverse events, and allows the recreation of real near-miss and adverse events, as a novel way of improving awareness of events and performance. Learning through simulation offers a unique learning opportunity and has become a vital part of today's anaesthesiology curriculum.

The 75Se-selenomethionine pancreas scan cannot differentiate between chronic pancreatitis and carcinoma of the pancreas and may—although chiefly in certain defined clinical conditions—give a false-positive result. It is also rather more time-consuming than other radioisotopic scanning procedures. Its value in clinical practice stems from the fact that all the other methods currently available for studying the pancreas have their own disadvantages. Because a normal scan is only rarely seen in patients with carcinoma of the pancreas, pancreatic scanning can be particularly useful in helping to decide which patients should, and which should not, be subjected to other procedures involving greater discomfort or risk.

Recently, we determined that the transduction mechanism for the hypnotic response to dexmedetomidine, a highly selective alpha 2 agonist, resides in the locus coeruleus (LC) of the rat. Candidates for the effector mechanism of this alpha 2 adrenoceptor-mediated hypnotic response include inhibition of adenylate cyclase, which has been shown to be pivotal to the cellular response of alpha 2 agonists in some, but not in all, cases. The LC of rats were stereotaxically cannulated with an indwelling catheter, and after the 2nd day, the hypnotic response to 7 micrograms of dexmedetomidine into the LC (an effective hypnotic dose for 95% of animals) was tested. Other groups of rats were pretreated with the permeable nonhydrolyzable cyclic AMP (cAMP) analog, dibutyryl cAMP (dB cAMP), at a dose of 0.2 to 1.2 ng into the LC, or 2.75 to 275 micrograms.kg-1 i.p. rolipram, a cAMP-specific phosphodiesterase inhibitor, and the hypnotic response to 7 micrograms of dexmedetomidine into the LC was tested. Both dB cAMP and rolipram reversed the hypnotic response to dexmedetomidine. To test for the specificity of these hypnotic-reversing perturbations, rats were pretreated with Rp-adenosine-3',5'-cyclic phosphorothioate, a cAMP-dependent protein kinase inhibitor, and the experiments were repeated. The hypnotic-reversing property of either dB cAMP or rolipram could be prevented by blocking cAMP-dependent protein kinase ("A" kinase) activity with Rp-adenosine-3',5'-cyclic phosphorothioate.(ABSTRACT TRUNCATED AT 250 WORDS)

Four 75Se-labelled amino acids have been tested in 22 patients. In 11 of the patients pancreatic function was estimated by the Lundh test.Scans at varying time intervals up to 30 hours from isotope administration were assessed by blind marking. Pancreatic visualization with all four agents was markedly poorer than would have been expected with 75Se-selenomethionine. Whole-body retention was estimated for all four agents; two showed faster 75Se clearance than selenomethionine. Radioactivity in duodenal aspirate was measured for two of the agents.

The effect of halothane on isoproterenol-stimulated lipolysis was determined in isolated rat epididymal fat cells. The maximal lipolytic response (Emax) activated by isoproterenol was 350 +/- 61 nmol of glycerol/10(5) cells/hr with an EC50 of 5.1 X 10(-9) M. When the adipocytes were simultaneously bubbled with 2.5% halothane, the Emax decreased to 158 +/- 43 nmol of glycerol/10(5) cells/hr and the dose response curve for isoproterenol was shifted to the right (EC50 3.5 X 10(-8) M, p less than 0.05). When lipolysis was maximally stimulated with (-)-isoproterenol (10(-6)M), the inhibitory effect of halothane was found to be both dose dependent (IC50 approximately 2.5%, v/v) and reversible following washout. Neither the nonhydrolyzable cAMP analog, 8-(4-chlorophenylthio) adenosine 3',5'-cyclic monophosphate (2 X 10(-3)M), nor forskolin (10(-6) M) was able to normalize lipolysis in the presence of halothane. The activation of cAMP-dependent protein kinase (EC 2.7.1.37) activity by isoproterenol was not different in halothane-exposed cells when compared to unexposed cells. When control adipocytes were exposed to isoproterenol (10(-6) M), there was a 2.5-fold increase in the activity of hormone-sensitive lipase (EC 3.1.1.3) from 0.64 +/- 0.13 to 1.53 +/- 0.32 pkat (pmol/sec) per mg (p less than 0.005, n = 10). However, in the presence of halothane (2.5%, v/v) isoproterenol stimulation of hormone-sensitive lipase was attenuated by 50% to values of 1.06 +/- 0.23 pkat/mg (p less than 0.01, n = 10). Halothane had no direct inhibitory effect on hormone-sensitive lipase since this enzyme's activity was unaffected when homogenates of isoproterenol-stimulated control cells were incubated with halothane. These studies suggest that halothane impairs the activation of hormone-sensitive lipase by cAMP-dependent protein kinase and in this manner inhibits beta-adrenergic-stimulated lipolysis.

Alpha adrenergic agonists such as clonidine are widely used for their antihypertensor effects, but they also cause sedation. The mechanisms underlying soporific effects of such compounds are poorly understood, but appear to involve the alpha-2 adrenergic receptor sub-type. To further investigate the role of this receptor in sleep-wake regulation, rats received injections i.p. either during their peak of activity (circadian time CT-18: 6 hr after lights out) or near the mid-point of their sleep-dominated phase (CT-5: 5 hr after lights on) with either the highly selective alpha-2 agonist dexmedetomidine (dMED) 0.02 to 0.04 mg/kg or the less selective alpha-2 agonist, clonidine 0.04 to 0.08 mg/kg, or vehicle. Clonidine and dMED showed remarkable overall similarities in their soporific profiles. Except for the lower dose of clonidine, both CT-5 and CT-18 treatments increased the percent of time spent in non-REM (NREM) sleep. The increase in NREM was followed by a reduction of NREM sleep that was accompanied by locomotor activity and body temperature above control levels. After CT-5 treatments, this period of reduced NREM sleep was followed by a secondary increase in NREM 7 to 10 hr posttreatment. REM sleep was markedly reduced for 9 to 10 hr after all treatments at both times of day, with elevated REM levels 18 to 30 hr posttreatment. Pre-treatment with the selective alpha-2 antagonist atipamezole (0.5 mg/kg) reversed the effects of CT-18 dMED 0.04 mg/kg except REM sleep suppression, which was only partially reversed. The NREM-inducing potency of dMED 0.02 mg/kg was greater when administered at CT-18 than at CT-5. Taken together with other evidence, these findings suggest that the profound NREM-inducing effects of dMED may be mediated by postsynaptic alpha-2 adrenoceptors. Furthermore, the pharmacodynamic action of alpha-2 adrenergic agonists, like many other sedative hypnotics (e.g., benzodiazepines), produce a hysteresis in sleep-wake regulation characterized by "rebound" waking after drug-induced sleep.

Hypertension due to pheochromocytoma is generally considered to be a straightforward, direct consequence of the elevated concentrations of circulating catecholamines. However, clonidine, a centrally acting antihypertensive drug, has been reported to lower blood pressure in patients with pheochromocytoma, suggesting the possibility that the sympathetic nervous system is involved in the maintenance of hypertension in this disease. We have investigated this possibility in New England Deaconess Hospital rats harboring a transplantable pheochromocytoma that secretes norepinephrine and dopamine. Both clonidine and chlorisondamine, a ganglionic blocker, markedly decreased blood pressure in tumor-bearing rats. However, in other rats made acutely hypertensive with a norepinephrine infusion, neither clonidine nor chlorisondamine decreased blood pressure. This result indicates that in an acute model of hypertension, where baroreflex mechanisms have likely withdrawn sympathetic tone, neither clonidine nor chlorisondamine had nonspecific antihypertensive effects. A central nervous system site of action for the antihypertensive effect of clonidine in the rats harboring pheochromocytoma was suggested by the observation that the opiate antagonist naloxone both reversed and prevented clonidine's effect on blood pressure. Prazosin and yohimbine were utilized to determine the respective contributions of alpha-1 and alpha-2 adrenergic receptors in the maintenance of hypertension in rats harboring pheochromocytoma. Both drugs markedly lowered blood pressure in these rats. Our data suggest that both the sympathetic nervous system and circulating catecholamines are involved in the maintenance of hypertension due to pheochromocytoma.

Dexmedetomidine, an alpha-2 adrenoceptor (AR) agonist, produces a biphasic hypnotic response in rats. Since central alpha-1 AR stimulation may reverse the hypnotic response produced by central alpha-2 AR stimulation, we have investigated, in both in vivo and in vitro models, the functional effects of dexmedetomidine on alpha-1 AR. For in vivo studies, stainless steel cannulas were inserted stereotaxically into the lateral ventricle of halothane-anesthetized rats to facilitate i.c.v. drug administration. Four to 7 days later, the alpha-1 AR antagonist prazosin (1 mg/kg-1) or saline was administered i.p. 15 min before i.c.v. injections of dexmedetomidine (10-333 micrograms) and the sleep-time (duration of loss of righting reflex) was assessed. The sleep-time increased, in a linear fashion, up to 33 micrograms; above this dose, there was a decrease in sleep-time. Pretreatment with prazosin prevented the decrease in sleep-time which was seen at higher doses. For in vitro studies, binding parameters of dexmedetomidine and its anesthetically inert L-isomer were determined from competition binding curves using [125I]2-[beta-(4-hydroxy-3-[125I]iodo- phenyl)ethylaminomethyl]-tetralone as the radiolabeled ligand and membranes prepared from HeLa cell lines stably expressing either alpha-1B or alpha-1C AR subtypes. Dexmedetomidine bound with equal affinity to both the alpha-1B (1178 +/- 63 nM) and the alpha-1C (1344 +/- 230 nM) isoreceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

G protein-coupled receptors (GPCRs) have seven hydrophobic domains, which are thought to span the lipid bilayer as alpha helical transmembrane domains (TMDs). The tertiary structure of GPCRs has not been determined; however, molecular models of GPCRs have generally been based on bacteriorhodopsin, which is functionally unrelated to GPCRs but has a similar secondary structure. We sought to examine the validity of using bacteriorhodopsin as a scaffold for GPCR model building by experimentally determining the orientation of the TMDs of adrenergic receptors in the plasma membrane. In separate experiments, three sequential amino acid residues (Leu-310, Leu-311, Asn-312) in TMD VII of the beta 2 adrenoreceptors were mutated to the amino acids found in the homologous domain of the alpha 2 adrenoceptor (Phe, Phe, Phe). Exchange of Asn-312 and Leu-311 in the beta 2 adrenoceptor resulted in nonfunctional proteins, most likely due to incompatibility of the introduced bulky phenylalanine side chain with adjacent structural domains in the beta 2 adrenoreceptor. This structural incompatibility was "repaired" by replacing the specific beta 2 TMD sequence with an alpha 2 receptor sequence. TMD I and TMD II complemented the Asn-312-->Phe mutation, and TMD III and TMD VI complemented the Leu-311-->Phe mutation. These results indicate that TMDs I, II, III, and VI surround TMD VII in a counter-clockwise orientation analogous to the orientation of TMDs in bacteriorhodopsin.

ABSTRACTWe report results of Neisseria gonorrhoeaenucleic acid amplification testing (NAAT) with the Abbott m2000 PCR at a tertiary laboratory 6 months after its introduction. Of 5,475 specimens tested, 45 samples (0.82%) tested positive for N. gonorrhoeae. Eight were not cultured, but seven tested positive with a porApseudogene NAAT.

For the first 150 yr after the introduction into clinical practice, anaesthesia was considered to be produced through non-specific perturbations of lipids. In the past decade, a series of seminal discoveries by Professor Franks and Dr Lieb indicated that anaesthesia is transduced at specific sites on a relatively small number of proteins. Our programme focuses on the mechanisms whereby α2 adrenoceptors and their transmembrane signalling, in defined neuronal pathways, produce anaesthesia and analgesia, both in response to direct activation by exogenously administered α2 agonists (such as dexmedetomidine) and by indirect activation via release of the endogenous α2 ligand norepinephrine (as is the case with nitrous oxide analgesia). We now report on the mechanism of the analgesic action of nitrous oxide.Using the tail-flick latency response, we have shown that systemically administered antagonists of opioid (naloxone) and α2 adrenergic (yohimbine, atipamezole) receptors block its antinociceptive action. This is a result of opioid receptors in the periaqueductal gray and α2 adrenoceptors in the spinal cord. As spinal cord transection blocks the analgesic properties of nitrous oxide, a descending pathway is involved. At the level of the dorsal horn of the spinal cord, nitrous oxide provokes the release of norepinephrine. The released norepinephrine is responsible for analgesia as depletion of spinal stores of this neurotransmitter blocks the analgesic action of nitrous oxide. Using genetically modified reagents, we have now identified the species of endogenous opioid ligand and the α2 adrenoceptor involved. PENK 2 mice which lack preproenkephalin (the precursor of enkephalin) have no analgesic effect to nitrous oxide. Also, mice which lack the α2B adrenoceptor subtype also have no analgesic action to nitrous oxide (Fig. 7). The analgesic action of nitrous oxide could also be blocked by prazosin, an antagonist of the α2B adrenoceptor subtype. Both PENK 2 and α2 adrenoceptor subtype knockout mice have normal anaesthetic (hypnotic) responses to nitrous oxide.In summary, nitrous oxide produces its analgesic mechanism via different neuronal pathways (descending spinal noradrenergic) and molecular mechanisms (α2B adrenoceptor in the spinal cord and release of enkephalin in the periaqueductal grey) than that for transduction of its anaesthetic response (NMDA receptor).

Background. Some anaesthetic agents exhibit an age-dependent analgesic effect, for example nitrous oxide, which is ineffective in newborn rats. We investigated whether a similar time dependency existed for the responses to the volatile anaesthetic isoflurane. Methods. The analgesic and hypnotic properties of isoflurane at various ages was assessed using four cohorts of Fischer rats aged approximately 7, 16, and 28 days and adults (11–12 weeks old). Intraplantar administration of formalin mimicked inflammatory pain, and its effects were assessed using immunohistochemical (c-Fos staining) and behavioural paradigms. The hypnotic properties of isoflurane were assessed using loss of righting reflex. Results. Formalin administration produced a typical nociceptive response observed both behaviourally and immunohistochemically in all age groups; these nociceptive responses were significantly attenuated by isoflurane 0.5% at each age (P<0.05). Interestingly 7-day-old animals showed a significantly more potent hypnotic response than older animals (P<0.01): with adult rats being most resistant to isoflurane induced hypnosis (P<0.05). Conclusion. In contrast to nitrous oxide, isoflurane is an effective antinociceptive agent in neonatal rats. If the data can be extrapolated to clinical scenarios these results suggest that isoflurane may be analgesic in newborns as well as adult humans. In addition, isoflurane is a potent hypnotic, especially in the very young, which is in contrast to the neonate's relative resistance to anaesthesia as assessed by minimum alveolar concentration.