We report the case of a 41-year-old man admitted for lower limb and liver trauma following a car accident. Surgical repair of a tibial fracture was performed under general anesthesia 5 days after ...admission while the liver injury was managed conservatively. At the time of tourniquet inflation, the patient presented a pulmonary embolism. Low-molecular-weight heparin administration had been delayed for 72 hours after admission due to the liver injury. Risk factors for bleeding and thromboembolism in trauma patients with liver injury are discussed.
Using fluo‐3 calcium imaging, we demonstrate that glycine induces an increase in intracellular calcium concentration (Ca2+i) in cortical oligodendrocyte progenitor (OP) cells. This effect results ...from a calcium entry through voltage‐gated calcium channels (VGCC), as it is observed only in OP cells expressing such channels, and it is abolished either by removal of calcium from the extracellular medium or by application of an l‐type VGCC blocker. Glycine‐triggered Ca2+ influx in OP cells actually results from an initial depolarization that is the consequence of the activation of both the ionotropic glycine receptor (GlyR) and Na+‐dependent transporters, most probably the glycine transporters 1 (GLYT1) and/or 2 (GLYT2) which are colocalized in these cells. Through this GlyR‐ and transporter‐mediated effect on OP intrcellular calcium concentration Ca2+i, glycine released by neurons may, as well as other neurotransmitters, serve as a signal between neurons and OP during development.
In this study in vitro and in vivo approaches were combined in order to investigate if the anti‐epileptic mechanism(s) of action of levetiracetam (LEV; Keppra®) may involve modulation of inhibitory ...neurotransmission.
GABA‐ and glycine‐gated currents were studied in vitro using whole‐cell patch‐clamp techniques applied on cultured cerebellar granule, hippocampal and spinal neurons. Protection against clonic convulsions was assessed in vivo in sound‐susceptible mice. The effect of LEV was compared with reference anti‐epileptic drugs (AEDs): carbamazepine, phenytoin, valproate, clonazepam, phenobarbital and ethosuximide.
LEV contrasted the reference AEDs by an absence of any direct effect on glycine‐gated currents. At high concentrations, beyond therapeutic relevance, it induced a small reduction in the peak amplitude and a prolongation of the decay phase of GABA‐gated currents. A similar action on GABA‐elicited currents was observed with the reference AEDs, except ethosuximide.
These minor direct effects contrasted with a potent ability of LEV (EC50=1 – 10 μM) to reverse the inhibitory effects of the negative allosteric modulators zinc and β‐carbolines on both GABAA and glycine receptor‐mediated responses.
Clonazepam, phenobarbital and valproate showed a similar ability to reverse the inhibition of β‐carbolines on GABA‐gated currents. Blockade of zinc inhibition of GABA responses was observed with clonazepam and ethosuximide. Phenytoin was the only AED together with LEV that inhibited the antagonism of zinc on glycine‐gated currents and only clonazepam and phenobarbital inhibited the action of DMCM.
LEV (17 mg kg−1) produced a potent suppression of sound‐induced clonic convulsions in mice. This protective effect was significantly abolished by co‐administration of the β‐carboline FG 7142, from a dose of 5 mg kg−1. In contrast, the benzodiazepine receptor antagonist flumazenil (up to 10 mg kg−1) was without any effect on the protection afforded by LEV.
The results of the present study suggest that a novel ability to oppose the action of negative modulators on the two main inhibitory ionotropic receptors may be of relevance for the anti‐epileptic mechanism(s) of action of LEV.
British Journal of Pharmacology (2002) 136, 659–672; doi:10.1038/sj.bjp.0704766
TAVR for Stenotic Bicuspid Aortic Valve Radermecker, Marc A.; Sprynger, Muriel; Hans, Gregory
Journal of the American College of Cardiology,
12/2020, Letnik:
76, Številka:
22
Journal Article
Summary Anaesthesia produces muscle relaxation and consequently reduces lung volumes, especially the functional residual capacity. This leads to repeated closure of small airways and constitution of ...atelectases. Repeated closure of small airways and atelectases not only alter gas exchanges but also contribute to ventilator-induced lung injury. Over the last decade, accumulating experimental and clinical data encourage to revise ventilation of anaesthetized patients. Alveolar collapse can be prevented as soon as the induction of anaesthesia by positioning the patient in head-up position, applying a continuous positive airway pressure, and lowering the inspired oxygen fraction. During mechanical ventilation, positive end-expiratory pressure becomes the cornerstone of the prevention of alveolar de-recruitment. Despite these measures, atelectases do develop in some circumstances and need to be reversed by recruitment manoeuvres. In addition, the extent of the tidal volume should be decreased to limit pulmonary overdistension and subsequently ventilator-induced lung injury. The extubation phase is also critical since hypoventilation and re-occurrence of atelectases secondary to the administration of pure oxygen can occur during the transition between controlled and spontaneous ventilation. The efficient measures recommended during the induction of anaesthesia should be also applied during extubation. An assisted mode of ventilation could be beneficial to smoothen this transition phase.
Preoperative anaemia Hans, GA; Jones, N
Continuing education in anaesthesia, critical care & pain,
06/2013, Letnik:
13, Številka:
3
Journal Article, Web Resource
Some synthetic ligands of the peripheral-type benzodiazepine receptor (PBR), an 18
kDa protein of the outer mitochondrial membrane, are cytotoxic for several tumor cell lines and arise as promising ...chemotherapeutic candidates. However, conflicting results were reported regarding the actual effect of these drugs on cellular survival ranging from protection to toxicity. Moreover, the concentrations needed to observe such a toxicity were usually high, far above the affinity range for their receptor, hence questioning its specificity. In the present study, we have shown that micromolar concentrations of FGIN-1-27 and Ro 5-4864, two chemically unrelated PBR ligands are toxic for both PBR-expressing SK-N-BE neuroblastoma cells and PBR-deficient Jurkat lymphoma cells. We have thereby demonstrated that the cytotoxicity of these drugs is unrelated to their PBR-binding activity. Moreover, Ro 5-4864-induced cell death differed strikingly between both cell types, being apoptotic in Jurkat cells while necrotic in SK-N-BE cells. Again, this did not seem to be related to PBR expression since Ro 5-4864-induced death of PBR-transfected Jurkat cells remained apoptotic. Taken together, our results show that PBR is unlikely to mediate all the effects of these PBR ligands. They however confirm that some of these ligands are very effective cytotoxic drugs towards various cancer cells, even for reputed chemoresistant tumors such as neuroblastoma, and, surprisingly, also for PBR-lacking tumor cells.
Background: Intravenous lidocaine can be used intraoperatively for its analgesic and antihyperalgesic properties but local anaesthetics may also prolong the duration of action of neuromuscular ...blocking agents. We hypothesized that intravenous lidocaine would prolong the time to recovery of neuromuscular function after cisatracurium.
Methods: Forty‐two patients were enrolled in this randomized, double‐blind, placebo‐controlled study. Before induction, patients were administered either a 1.5 mg/kg bolus of intravenous lidocaine followed by a 2 mg/kg/h infusion or an equal volume of saline. Anaesthesia was induced and maintained using propofol and remifentanil infusions. After loss of consciousness, a 0.15 mg/kg bolus of cisatracurium was administered. No additional cisatracurium injection was allowed. Neuromuscular function was assessed every 20 s using kinemyography. The primary endpoint was the time to spontaneous recovery of a train‐of‐four (TOF) ratio ≥0.9.
Results: The time to spontaneous recovery of a TOF ratio ≥0.9 was 94 ± 15 min in the control group and 98 ± 16 min in the lidocaine group (P=0.27).
Conclusions: No significant prolongation of spontaneous recovery of a TOF ratio ≥0.9 after cisatracurium was found in patients receiving intravenous lidocaine.
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