Malignant Hyperthermia: An Anesthesiology Simulation Case for Early Anesthesia Providers.

INTRODUCTION: The patient is a 40-kg, 12-year-old Caucasian male with history of asthma who is undergoing an elective inguinal hernia repair. There is no family history of anesthesia-related complications. The surgery proceeds under general anesthesia with an IV induction with propofol, fentanyl, and succinylcholine; intubation under direct laryngoscopy; and maintenance with isoflurane. During the surgery, he develops malignant hyperthermia (MH). METHODS: Learners are to identify the signs of MH, including tachycardia, hypercapnia, muscle rigidity, and renal failure, and provide the appropriate treatment, resuscitation, and follow-up care. Anesthesiology faculty in the room assist and offer guided instruction to aid the learners in achieving these goals. RESULTS: The simulation was completed by 24 medical students with 2 weeks of anesthesia training and daily lectures on various anesthesia topics. Verbal feedback from the learners was positive, and many appreciated the preparation in how to prioritize the management of such a rare but life-threatening anesthesia emergency. Based on reviewers' recommendations, a learner evaluation of the session and pre- and posttest exams have been developed but have not yet been used with learners. DISCUSSION: The simulation not only was received well by the students but was also crucial to understanding the benefits of simulation training in the field of anesthesiology, especially when rare diseases are difficult to encounter in real life. Future simulations will incorporate other rare but important disease processes in the simulation training environment to allow anesthesia providers to learn in a safe setting without detriment to any patient.

Post-transcriptional regulation of GABAB receptor and GIRK1 channels by Nogo receptor 1.

BACKGROUND: Type B GABA receptors (GABA Rs) play a critical role in synaptic transmission. We carried out studies to determine whether neuronal cell surface expression of GABAB-Rs might be regulated by the Nogo receptor 1 (NgR1). RESULTS: siRNA knock-down of NgR1 resulted in a selective increase of GABAB R1 and GABAB R2 protein without altering the expression of GABAA receptor or GAD65. The increase in GABAB receptor subunits was unaccompanied by a change in mRNA, but inhibition of mTOR by rapamycin blocked the increase in GABAB protein. NgR1 siRNA also caused an increase in G protein coupled inwardly rectifying potassium channel (GIRK1). The increase in GABAB receptor and GIRK1 channel proteins was in the plasma membrane, determined by cell surface biotinylation. In NgR1 knockout mice, the amount of GABAB R2 and GIRK1 in hippocampus-derived synaptosomes was increased. CONCLUSIONS: Together these findings suggest that NgR1 mediated modulation of synaptic transmission may be accomplished, at least in part, through modulation of G protein coupled receptors and channels.

Pseudomonas aeruginosa alginate promotes Burkholderia cenocepacia persistence in cystic fibrosis transmembrane conductance regulator knockout mice.

Pseudomonas aeruginosa, a major respiratory pathogen in cystic fibrosis (CF) patients, facilitates infection by other opportunistic pathogens. Burkholderia cenocepacia, which normally infects adolescent patients, encounters alginate elaborated by mucoid P. aeruginosa. To determine whether P. aeruginosa alginate facilitates B. cenocepacia infection in mice, cystic fibrosis transmembrane conductance regulator knockout mice were infected with B. cenocepacia strain BC7 suspended in either phosphate-buffered saline (BC7/PBS) or P. aeruginosa alginate (BC7/alginate), and the pulmonary bacterial load and inflammation were monitored. Mice infected with BC7/PBS cleared all of the bacteria within 3 days, and inflammation was resolved by day 5. In contrast, mice infected with BC7/alginate showed persistence of bacteria and increased cytokine levels for up to 7 days. Histological examination of the lungs indicated that there was moderate to severe inflammation and pneumonic consolidation in isolated areas at 5 and 7 days postinfection in the BC7/alginate group. Further, alginate decreased phagocytosis of B. cenocepacia by professional phagocytes both in vivo and in vitro. P. aeruginosa alginate also reduced the proinflammatory responses of CF airway epithelial cells and alveolar macrophages to B. cenocepacia infection. The observed effects are specific to P. aeruginosa alginate, because enzymatically degraded alginate or other polyuronic acids did not facilitate bacterial persistence. These observations suggest that P. aeruginosa alginate may facilitate B. cenocepacia infection by interfering with host innate defense mechanisms.