Assessing the pathogenicity of RYR1 variants in malignant hyperthermia.

Abstract:

Background:. Missense variants in the ryanodine receptor 1 gene ( RYR1 ) are associated with malignant hyperthermia but only a minority of these have met the criteria for use in predictive DNA diagnosis. We examined the utility of a simplified method of segregation analysis and a functional assay for determining the pathogenicity of recurrent RYR1 variants associated with malignant hyperthermia. Methods:. We identified previously uncharacterised RYR1 variants found in four or more malignant hyperthermia families and conducted simplified segregation analyses. An efficient cloning and mutagenesis strategy was used to express ryanodine receptor protein containing one of six RYR1 variants in HEK293 cells. Caffeine-induced calcium release, measured using a fluorescent calcium indicator, was compared in cells expressing each variant to that in cells expressing wild type ryanodine receptor protein. Results.:We identified 43 malignant hyperthermia families carrying one of the six RYR1 variants. There was segregation of genotype with the malignant hyperthermia susceptibility phenotype in families carrying the p.E3104K and p.D3986E variants, but the number of informative meioses limited the statistical significance of the associations. HEK293 functional assays demonstrated an increased sensitivity of RyR1 channels containing the p.R2336H, p.R2355W, p.E3104K, p.G3990V and p.V4849I compared with wild type, but cells expressing p.D3986E had a similar caffeine sensitivity to cells expressing wild type RyR1. Conclusions:. Segregation analysis is of limited value in assessing pathogenicity of RYR1 variants in malignant hyperthermia. Functional analyses in HEK293 cells provided evidence to support the use of p.R2336H, p.R2355W, p.E3104K, p.G3990V and p.V4849I for diagnostic purposes but not p.D3986E.

journal_name

Br J Anaesth

authors

Merritt A,Booms P,Shaw MA,Miller DM,Daly C,Bilmen JG,Stowell KM,Allen PD,Steele DS,Hopkins PM

doi

10.1093/bja/aex042

subject

Has Abstract

pub_date

2017-04-01 00:00:00

pages

533-543

issue

4

eissn

0007-0912

issn

1471-6771

pii

S0007-0912(17)31362-4

journal_volume

118

pub_type

杂志文章
  • Pre-operative oral erythromycin reduces residual gastric volume and acidity.

    abstract::We investigated whether low-dose erythromycin (200 mg) given as an oral premedicant altered the residual gastric volume and its acidity in fasted patients at induction of anaesthesia in a single-blinded study. Sixty patients were allocated randomly to receive either an erythromycin tablet (200 mg) or nothing with 10 m...

    journal_title:British journal of anaesthesia

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1093/bja/85.6.861

    authors: Asai T,Murao K,Shingu K

    更新日期:2000-12-01 00:00:00

  • Components of the inspiratory-arterial isoflurane partial pressure difference.

    abstract::We have measured the partial pressure of isoflurane simultaneously in inspired gas (PIiso), end-expired gas (PE'iso), mixed-expired gas (PEiso), arterial (Paiso) and mixed venous blood (Pviso) in six patients (aged 57-79 yr) anaesthetized with nitrous oxide, oxygen and isoflurane before surgery and after PE'iso had be...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章

    doi:10.1093/bja/70.6.605

    authors: Landon MJ,Matson AM,Royston BD,Hewlett AM,White DC,Nunn JF

    更新日期:1993-06-01 00:00:00

  • Development of atelectasis and arterial to end-tidal PCO2-difference in a porcine model of pneumoperitoneum.

    abstract:BACKGROUND:Intraperitoneal insufflation of carbon dioxide (CO2) may promote collapse of dependent lung regions. The present study was undertaken to study the effects of CO2-pneumoperitoneum (CO2-PP) on atelectasis formation, arterial oxygenation, and arterial to end-tidal PCO2-gradient (Pa-E'(CO2)). METHODS:Fifteen an...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章

    doi:10.1093/bja/aep102

    authors: Strang CM,Hachenberg T,Fredén F,Hedenstierna G

    更新日期:2009-08-01 00:00:00

  • A dose-response study with nalbuphine hydrochloride for pain in patients after upper abdominal surgery.

    abstract::Six male patients were studied on the morning following upper abdominal surgery for highly selective vagotomy. Nalbuphine hydrochloride was infused i.v. at different rates that increased progressively in each hour over a 4-h period. In the last 15 min of each hour, the plasma nalbuphine concentrations were almost stea...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章

    doi:10.1093/bja/59.11.1356

    authors: Pugh GC,Drummond GB

    更新日期:1987-11-01 00:00:00

  • Fatal myocardial infarction after lung resection in a patient with prophylactic preoperative coronary stenting.

    abstract::In this report we present the case of a 77-yr-old man who underwent resection of the upper lobe of the left lung for a carcinoma, six weeks after percutaneous transluminal coronary angioplasty (PTCA) with stenting of the left anterior descending (LAD) and circumflex coronary arteries. Antiplatelet therapy with clopido...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章

    doi:10.1093/bja/aeh110

    authors: Marcucci C,Chassot PG,Gardaz JP,Magnusson L,Ris HB,Delabays A,Spahn DR

    更新日期:2004-05-01 00:00:00

  • 4-Aminopyridine reversal of fentanyl-induced respiratory depression in normocapnic and hypercapnic patients.

    abstract::Profound postoperative respiratory depression after larger doses of fentanyl was partially reversed by 4-aminopyridine. This reversal was independent of FIO2' suggesting that the response was not dependent upon peripheral chemoreceptor-mediated drive. Similar reversal of fentanyl-induced depression by 4-aminopyridine ...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章

    doi:10.1093/bja/53.4.373

    authors: Sia RL,Zandstra DF

    更新日期:1981-04-01 00:00:00

  • Dexmedetomidine as an adjuvant to ropivacaine prolongs peripheral nerve block: a volunteer study.

    abstract:BACKGROUND:Dexmedetomidine is an α-2-receptor agonist which might be used as an additive to local anaesthetics for various regional anaesthetic techniques. We therefore designed this prospective, double-blinded, controlled volunteer study to investigate the effects of dexmedetomidine as an adjuvant to ropivacaine on pe...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章,随机对照试验

    doi:10.1093/bja/aes400

    authors: Marhofer D,Kettner SC,Marhofer P,Pils S,Weber M,Zeitlinger M

    更新日期:2013-03-01 00:00:00

  • Effect of communication on pain during intravenous cannulation: a randomized controlled trial.

    abstract:BACKGROUND:Clinicians frequently warn patients of discomfort before potentially painful procedures, despite the lack of evidence that such communications are helpful. We aimed to compare two communications (one with, and the other without, a warning of a 'sting') immediately before i.v. cannulation in order to measure ...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章,随机对照试验

    doi:10.1093/bja/aem308

    authors: Dutt-Gupta J,Bown T,Cyna AM

    更新日期:2007-12-01 00:00:00

  • Cytokines and the immunomodulatory function of the vagus nerve.

    abstract::Cytokine synthesis and release is an essential component of the innate immune system, but inappropriate, excessive production results in a generalized systemic inflammatory response which damages distant organs. Recent research has identified an immunomodulatory function of the vagus nerve whereby activation of the ef...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章,评审

    doi:10.1093/bja/aep037

    authors: Johnston GR,Webster NR

    更新日期:2009-04-01 00:00:00

  • Epidural analgesia compared with peripheral nerve blockade after major knee surgery: a systematic review and meta-analysis of randomized trials.

    abstract::The relative analgesic efficacy and side-effect profile of peripheral nerve blockade (PNB) techniques compared with lumbar epidural analgesia for major knee surgery is unclear. We undertook a systematic review and meta-analysis of all randomized trials comparing epidural analgesia with PNB for major knee surgery. Eigh...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章,meta分析,评审

    doi:10.1093/bja/aem373

    authors: Fowler SJ,Symons J,Sabato S,Myles PS

    更新日期:2008-02-01 00:00:00

  • Difficult arterial cannulation in children: is a near-infrared vascular imaging system the answer?

    abstract:BACKGROUND:Arterial cannulation is a common anaesthetic procedure that can be challenging and time-consuming in small children. By visualizing the position of the radial artery, near-infrared vascular imaging systems (NIRVISs) might be of assistance in arterial cannulation. The present study evaluates the effectiveness...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章

    doi:10.1093/bja/aes193

    authors: Cuper NJ,de Graaff JC,Hartman BJ,Verdaasdonk RM,Kalkman CJ

    更新日期:2012-09-01 00:00:00

  • Efficacy of palonosetron for the prevention of postoperative nausea and vomiting: a randomized, double-blinded, placebo-controlled trial.

    abstract:BACKGROUND:The aim of this study was to evaluate the efficacy of palonosetron, the latest 5-HT3 receptor antagonist, for the prevention of postoperative nausea and vomiting (PONV) during the first 72 h after operation. METHODS:In this randomized, double-blinded, placebo-controlled study, 204 healthy inpatients who wer...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章,随机对照试验

    doi:10.1093/bja/aet340

    authors: Chun HR,Jeon IS,Park SY,Lee SJ,Kang SH,Kim SI

    更新日期:2014-03-01 00:00:00

  • Efficacy of low-dose bupivacaine in spinal anaesthesia for Caesarean delivery: systematic review and meta-analysis.

    abstract::Spinal anaesthesia is the preferred anaesthetic technique for elective Caesarean deliveries. Hypotension is the most common side-effect and has both maternal and neonatal consequences. Different strategies have been attempted to prevent spinal-induced hypotension, including the use of low-dose bupivacaine. We conducte...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章,meta分析,评审

    doi:10.1093/bja/aer200

    authors: Arzola C,Wieczorek PM

    更新日期:2011-09-01 00:00:00

  • The lumbar extradural structure changes with increasing age.

    abstract::We have examined the extradural space using a flexible extraduroscope in 74 patients undergoing extradural anaesthesia at the L2-3 interspace. Extraduroscopy showed that the extradural space becomes widely patent and the fatty tissue in the extradural space diminishes with increasing age. We postulate that these age-r...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章

    doi:10.1093/bja/78.2.149

    authors: Igarashi T,Hirabayashi Y,Shimizu R,Saitoh K,Fukuda H,Mitsuhata H

    更新日期:1997-02-01 00:00:00

  • Low-dose clonidine infusion during labour.

    abstract::In this study, we have compared two different doses of clonidine (bolus of 25 micrograms and infusion of 19 micrograms h-1; bolus of 50 micrograms and infusion of 37 micrograms h-1, both added to 0.03% bupivacaine) with a control group of 0.03% bupivacaine alone. The study was performed in a randomized, double-blind m...

    journal_title:British journal of anaesthesia

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1093/bja/83.2.257

    authors: Tremlett MR,Kelly PJ,Parkins J,Hughes D,Redfern N

    更新日期:1999-08-01 00:00:00

  • Does a first-case on-time-start initiative achieve its goal by starting the entire process earlier or by tightening the distribution of start times?

    abstract:BACKGROUND:We explored whether a previously successful initiative to improve first-case on-time starts succeeded because (i) preoperative steps started earlier (but the process did not necessarily improve) or (ii) the process was brought into better control. METHODS:We analysed 35 months of data comprising 28 882 firs...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章

    doi:10.1016/j.bja.2018.05.043

    authors: Tiwari V,Ehrenfeld JM,Sandberg WS

    更新日期:2018-11-01 00:00:00

  • Infusion of vecuronium assessed by tactile evaluation of evoked thumb twitch.

    abstract::In 15 patients (ASA I-II) undergoing intraabdominal gynaecological surgery, muscle paralysis for tracheal intubation and surgery was achieved by a combined bolus and demand infusion of vecuronium. The initial loading dose of 67 micrograms kg-1 and the rate of subsequent infusion were determined by evaluation of the ta...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章

    doi:10.1093/bja/61.4.479

    authors: Haraldsted VY,Nielsen JW,Joensen F,Dilling-Hansen B,Hasselstrøm L

    更新日期:1988-10-01 00:00:00

  • Calcium homeostasis during i.v. infusion of 1.5% glycine in anaesthetized pigs.

    abstract::We have examined changes in plasma concentrations of calcium in seven anaesthetized pigs during i.v. infusion of irrigating fluid containing 1.5% glycine. Volumes infused were 875 ml at 20 min (22 ml kg-1), 1475 ml at 40 min and 2075 ml at 60 min (75 ml kg-1). Plasma concentrations of sodium decreased from 134.5 (SD 3...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章

    doi:10.1093/bja/77.2.271

    authors: Chassard D,Berrada K,Tournadre JP,Boulétreau P

    更新日期:1996-08-01 00:00:00

  • Anaesthesia of the upper airway using topical anaesthetic and superior laryngeal nerve block.

    abstract::Bilateral superior laryngeal nerve block was combined with topical application of local anaesthetic 140 times in 135 patients to anaesthetize the upper airway and facilitate tracheal intubation, laryngeal instrumentation, or to diminish the response to the endotracheal tube, in a patient already intubated. The techniq...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章

    doi:10.1093/bja/53.10.1055

    authors: Gotta AW,Sullivan CA

    更新日期:1981-10-01 00:00:00

  • Isoflurane exposure for three hours triggers apoptotic cell death in neonatal macaque brain.

    abstract:Background:Retrospective clinical studies suggest there is a risk for neurodevelopmental impairment following early childhood exposure to anaesthesia. In the developing animal brain, including those of non-human primates (NHPs), anaesthetics induce apoptotic cell death. We previously reported that a 5 h isoflurane (ISO...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章

    doi:10.1093/bja/aex123

    authors: Noguchi KK,Johnson SA,Dissen GA,Martin LD,Manzella FM,Schenning KJ,Olney JW,Brambrink AM

    更新日期:2017-09-01 00:00:00

  • Remifentanil does not impair left ventricular systolic and diastolic function in young healthy patients.

    abstract:BACKGROUND:Experimental studies and investigations in patients with cardiac diseases suggest that opioids at clinical concentrations have no important direct effect on myocardial relaxation and contractility. In vivo data on the effect of remifentanil on myocardial function in humans are scarce. This study aimed to inv...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章

    doi:10.1093/bja/aeq414

    authors: Bolliger D,Seeberger MD,Kasper J,Skarvan K,Seeberger E,Lurati Buse G,Buser P,Filipovic M

    更新日期:2011-04-01 00:00:00

  • Intelligent dynamic clinical checklists improved checklist compliance in the intensive care unit.

    abstract:Background:Checklists can reduce medical errors. However, the effectiveness of checklists is hampered by lack of acceptance and compliance. Recently, a new type of checklist with dynamic properties has been created to provide more specific checklist items for each individual patient. Our purpose in this simulation-base...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章,随机对照试验

    doi:10.1093/bja/aex129

    authors: De Bie AJR,Nan S,Vermeulen LRE,Van Gorp PME,Bouwman RA,Bindels AJGH,Korsten HHM

    更新日期:2017-08-01 00:00:00

  • Xenon decreases cell migration and secretion of a pro-angiogenesis factor in breast adenocarcinoma cells: comparison with sevoflurane.

    abstract:BACKGROUND:While volatile agents have been implicated in metastasis-enhancing effects on cancer cells, the effects of xenon are unknown. We investigated xenon- and sevoflurane-mediated effects on migration and expression of angiogenesis biomarkers in human breast adenocarcinoma cells. METHODS:MDA-MB-231 and MCF-7 cell...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章

    doi:10.1093/bja/aeu191

    authors: Ash SA,Valchev GI,Looney M,Ni Mhathuna A,Crowley PD,Gallagher HC,Buggy DJ

    更新日期:2014-07-01 00:00:00

  • Comparison of hyperbaric and plain articaine in spinal anaesthesia for open inguinal hernia repair.

    abstract:BACKGROUND:Fast onset and short duration are prominent properties of the amide-type local anaesthetic articaine. Similar to bupivacaine, a hyperbaric solution of articaine may produce faster onset and shorter duration of spinal anaesthesia than a plain solution. METHODS:Patients undergoing open inguinal hernia repair ...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章,随机对照试验

    doi:10.1093/bja/aen294

    authors: Bachmann M,Pere P,Kairaluoma P,Rosenberg PH,Kallio H

    更新日期:2008-12-01 00:00:00

  • Respiratory complications and hypoxic episodes during inhalation induction with isoflurane in children.

    abstract::We have studied the incidence of respiratory complications and hypoxic episodes during inhalation induction with isoflurane in 75 healthy unpremedicated children. Problems occurred less frequently when 4% isoflurane in oxygen was used from the outset than with traditional techniques using nitrous oxide and a gradually...

    journal_title:British journal of anaesthesia

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1093/bja/66.3.327

    authors: Warde D,Nagi H,Raftery S

    更新日期:1991-03-01 00:00:00

  • Using educational video to enhance protocol adherence for medical procedures.

    abstract:BACKGROUND:Better education of clinicians is expected to enhance patient safety. An important component of education is adherence to standard protocols, which are mainly available in written form. Believing in the potential power of videos, we hypothesized that the introduction of an educational video, based on an inst...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章

    doi:10.1093/bja/aew030

    authors: Kandler L,Tscholl DW,Kolbe M,Seifert B,Spahn DR,Noethiger CB

    更新日期:2016-05-01 00:00:00

  • One-lung ventilation induces hyperperfusion and alveolar damage in the ventilated lung: an experimental study.

    abstract:BACKGROUND:One-lung ventilation (OLV) increases mechanical stress in the lung and affects ventilation and perfusion (V, Q). There are no data on the effects of OLV on postoperative V/Q matching. Thus, this controlled study evaluates the influence of OLV on V/Q distribution in a pig model using a gamma camera technique ...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章

    doi:10.1093/bja/aen021

    authors: Kozian A,Schilling T,Fredén F,Maripuu E,Röcken C,Strang C,Hachenberg T,Hedenstierna G

    更新日期:2008-04-01 00:00:00

  • Isolated lung transplantation: a review of problems and guide to anaesthesia.

    abstract::Some recipients of isolated, orthotopic lung transplants have now survived to leave hospital with greatly improved quality of life. Inevitably, the successful demonstration of the feasibility of these operations means that transplant centres throughout the world may wish to participate in a lung transplant programme. ...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章,评审

    doi:10.1093/bja/61.4.468

    authors: Conacher ID

    更新日期:1988-10-01 00:00:00

  • Covert stroke after non-cardiac surgery: a prospective cohort study.

    abstract:BACKGROUND:Overt stroke after non-cardiac surgery has a substantial impact on the duration and quality of life. Covert stroke in the non-surgical setting is much more common than overt stroke and is associated with an increased risk of cognitive decline and dementia. Little is known about covert stroke after non-cardia...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章,多中心研究

    doi:10.1093/bja/aew179

    authors: Mrkobrada M,Hill MD,Chan MT,Sigamani A,Cowan D,Kurz A,Sessler DI,Jacka M,Graham M,Dasgupta M,Dunlop V,Emery DJ,Gulka I,Guyatt G,Heels-Ansdell D,Murkin J,Pettit S,Sahlas DJ,Sharma M,Sharma M,Srinathan S,St John P

    更新日期:2016-08-01 00:00:00

  • Pharmacokinetics of Org NC45 (norcuron) in patients with and without renal failure.

    abstract::To determine the influence of renal failure on the pharmacokinetics and neuromuscular blockade of Org NC 45 (Norcuron), a new monoquaternary homologue of pancuronium, 13 patients under halothane and nitrous oxide anesthesia were studied. Org NC 45 was administered by 2-min infusion in doses of 0.28 mg kg-1 (normal ren...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章

    doi:10.1093/bja/53.10.1049

    authors: Fahey MR,Morris RB,Miller RD,Nguyen TL,Upton RA

    更新日期:1981-10-01 00:00:00