Abstract：
:The study of rare families with inherited pain insensitivity can identify new human-validated analgesic drug targets. Here, a 66-yr-old female presented with nil requirement for postoperative analgesia after a normally painful orthopaedic hand surgery (trapeziectomy). Further investigations revealed a lifelong history of painless injuries, such as frequent cuts and burns, which were observed to heal quickly. We report the causative mutations for this new pain insensitivity disorder: the co-inheritance of (i) a microdeletion in dorsal root ganglia and brain-expressed pseudogene, FAAH-OUT, which we cloned from the fatty-acid amide hydrolase (FAAH) chromosomal region; and (ii) a common functional single-nucleotide polymorphism in FAAH conferring reduced expression and activity. Circulating concentrations of anandamide and related fatty-acid amides (palmitoylethanolamide and oleoylethanolamine) that are all normally degraded by FAAH were significantly elevated in peripheral blood compared with normal control carriers of the hypomorphic single-nucleotide polymorphism. The genetic findings and elevated circulating fatty-acid amides are consistent with a phenotype resulting from enhanced endocannabinoid signalling and a loss of function of FAAH. Our results highlight previously unknown complexity at the FAAH genomic locus involving the expression of FAAH-OUT, a novel pseudogene and long non-coding RNA. These data suggest new routes to develop FAAH-based analgesia by targeting of FAAH-OUT, which could significantly improve the treatment of postoperative pain and potentially chronic pain and anxiety disorders.
journal_name
Br J Anaesthjournal_title
British journal of anaesthesiaauthors
Habib AM,Okorokov AL,Hill MN,Bras JT,Lee MC,Li S,Gossage SJ,van Drimmelen M,Morena M,Houlden H,Ramirez JD,Bennett DLH,Srivastava D,Cox JJdoi
10.1016/j.bja.2019.02.019subject
Has Abstractpub_date
2019-08-01 00:00:00pages
e249-e253issue
2eissn
0007-0912issn
1471-6771pii
S0007-0912(19)30138-2journal_volume
123pub_type
杂志文章abstract：:Recent research has shown that high-frequency, gamma-band electroencephalographic (EEG) oscillations (40-60 Hz) may be an important marker of the conscious state. We compared the ability of the bispectral index (BIS) to distinguish the awake and anaesthetized states during the induction of general anaesthesia with: (i...
journal_title：British journal of anaesthesia
pub_type： 杂志文章
doi：10.1093/bja/86.1.50
更新日期：2001-01-01 00:00:00
abstract：:Zomepirac 100 mg and dihydrocodeine 30 mg were compared with placebo in a controlled randomized, double-blind, single-dose postoperative study. Patients continued to receive either zomepirac or dihydrocodeine for pain relief for 5 days at home in a double-blind study, being allowed to titrate the consumption of tablet...
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/57.4.412
更新日期：1985-04-01 00:00:00
abstract：BACKGROUND:ROTEM(®)/TEG(®) (rotational thromboelastometry) assays appear to be useful for the treatment of bleeding trauma patients. However, data on the prevalence and impact of abnormal ROTEM(®) assays are scarce. METHODS:This is a prospective cohort study of blunt trauma patients (Injury Severity Score ≥15 or Glasg...
journal_title：British journal of anaesthesia
pub_type： 杂志文章
doi：10.1093/bja/aer158
更新日期：2011-09-01 00:00:00
abstract：BACKGROUND:Recent investigations showed that isoflurane can induce pharmacological preconditioning. The present study aimed to compare the potency of four different halogenated anaesthetics to induce preconditioning. METHODS:Anaesthetized open-chest rabbits underwent 30 min of coronary artery occlusion followed by 3 h...
journal_title：British journal of anaesthesia
pub_type： 杂志文章
doi：
更新日期：2002-09-01 00:00:00
abstract：:Quality of recovery after anaesthesia is an important measure of the early postoperative health status of patients. We attempted to develop a valid, reliable and responsive measure of quality of recovery after anaesthesia and surgery. We studied 160 patients and asked them to rate postoperative recovery using three me...
journal_title：British journal of anaesthesia
pub_type： 杂志文章
doi：10.1093/oxfordjournals.bja.a013366
更新日期：2000-01-01 00:00:00
abstract：BACKGROUND:Increasing fresh gas flow (FGF) to a circle breathing system reduces carbon dioxide (CO2) absorbent consumption. We assessed the environmental and economic impacts of this trade-off between gas flow and absorbent consumption when no inhalational anaesthetic agent is used. METHODS:A test lung with fixed CO2 ...
journal_title：British journal of anaesthesia
pub_type： 杂志文章
doi：10.1016/j.bja.2020.07.043
更新日期：2020-11-01 00:00:00
abstract：BACKGROUND:Perioperative warming is recommended for surgery under anaesthesia, however its role during Caesarean delivery remains unclear. This meta-analysis aimed to determine the efficacy of active warming on outcomes after elective Caesarean delivery. METHODS:We searched databases for randomized controlled trials u...
journal_title：British journal of anaesthesia
pub_type： 杂志文章,meta分析,评审
doi：10.1093/bja/aev325
更新日期：2015-10-01 00:00:00
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
更新日期：1993-06-01 00:00:00
abstract：:We have compared, in a randomized study in 26 patients, immediate and late postoperative recovery after elective laparoscopic cholecystectomy using the gasless, mechanical abdominal wall lift method with conventional carbon dioxide pneumoperitoneum. After the gasless method, tracheal extubation was performed significa...
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/77.5.576
更新日期：1996-11-01 00:00:00
abstract：Background:Kidney transplantation is associated with harmful processes affecting the viability of the graft. One of these processes is associated with the phenomenon of ischaemia-reperfusion injury. Anaesthetic conditioning is a widely described strategy to attenuate ischaemia-reperfusion injury. We therefore conducted...
journal_title：British journal of anaesthesia
pub_type： 杂志文章,随机对照试验
doi：10.1093/bja/aex057
更新日期：2017-05-01 00:00:00
abstract：:The serum concentrations of fazadinium and its metabolites were measured in 14 surgical patients with end-stage renal failure and in 11 patients free from kidney disease undergoing abdominal surgery. A two-compartment open model was used in the pharmacokinetic analysis of the data. The elimination half-life (T 1/2 bet...
journal_title：British journal of anaesthesia
pub_type： 杂志文章
doi：10.1093/bja/51.10.943
更新日期：1979-10-01 00:00:00
abstract：:To understand the cellular and molecular basis of the anaesthetic state, it is important to remember that, in the intact CNS, synapses operate within elaborate nerve networks. From the data presented above, it is evident that block of impulse conduction in presynaptic fibres does not explain the effects of most anesth...
journal_title：British journal of anaesthesia
pub_type： 杂志文章,评审
doi：10.1093/bja/71.1.134
更新日期：1993-07-01 00:00:00
abstract：:Thirty-two patients received lumbar extradural anaesthesia for elective Caesarean section. The results obtained from this series were compared with those from a similar (control) group of parturients who received general anaesthesia. The extradural group (mothers and infants) were metabolically acidaemic relative to c...
journal_title：British journal of anaesthesia
pub_type： 杂志文章
doi：10.1093/bja/51.4.367
更新日期：1979-04-01 00:00:00
abstract：:Thirty patients took part in a double-blind trial to compare morphine 10 mg i.m. with morphine 5 mg into the extradural space for pain relief following Caesarean section. With the extradural route the mean time to first analgesia was 7.95 h compared with 4.75 h for the i.m. route. The mean number of further doses of d...
journal_title：British journal of anaesthesia
pub_type： 临床试验,杂志文章
doi：10.1093/bja/55.12.1201
更新日期：1983-12-01 00:00:00
abstract：:The effect of diluting propofol in 5% dextrose on the incidence of i.v. injection pain was studied in 100 adult patients. Severe injection pain occurred in 32% (16 patients) who received undiluted propofol, compared with 10% (five patients) who received dilute propofol. We concluded that the dilution of propofol signi...
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/62.2.202
更新日期：1989-02-01 00:00:00
abstract：:The calculation of pharmacokinetic parameters after a bolus injection of fentanyl allowed an i.v. infusion scheme which guarantees analgesia for the entire duration of surgery, with the advantage of steady plasma concentration and body content. In the initial phase after bolus injection, the serum concentration decrea...
journal_title：British journal of anaesthesia
pub_type： 杂志文章
doi：10.1093/bja/52.10.1021
更新日期：1980-10-01 00:00:00
abstract：:We have investigated the effect of a bolus injection of atracurium 0.6 mg kg-1 on the cardiovascular system in 16 patients undergoing aortocoronary bypass surgery. H1- and H2-receptor antagonists were administered to eight patients before the neuromuscular blocker. A standard anaesthetic was used comprising fentanyl, ...
journal_title：British journal of anaesthesia
pub_type： 临床试验,杂志文章
doi：10.1093/bja/68.2.155
更新日期：1992-02-01 00:00:00
abstract：:Patients receiving opioids report feeling sleepy, but opioids actually inhibit the rapid eye movement phase of sleep (REM). Inhibition of REM sleep is followed by a rebound increase in REM sleep associated with cardiopulmonary complications. The medial pontine reticular formation (mPRF) is a brain region from which mo...
journal_title：British journal of anaesthesia
pub_type： 杂志文章
doi：10.1093/bja/74.2.188
更新日期：1995-02-01 00:00:00
abstract：:Before the induction of labour in 34 pregnant women 1.5% lignocaine 10 ml was injected into the lumbar extradural space at constant rates between 0.143 and 0.333 ml s-1. Injection pressures and residual pressures were recorded and the extent of analgesia to pinprick was assessed. No significant correlation was found b...
journal_title：British journal of anaesthesia
pub_type： 杂志文章
doi：10.1093/bja/52.1.55
更新日期：1980-01-01 00:00:00
abstract：:We studied the interactive effect of dexmedetomidine and morphine on gastric emptying and gastrointestinal transit in the rat. In one group of rats, to examine the interactive effect on gastrointestinal transit, the two drugs were injected i.p. in a fixed ratio (30: 1)--that of their ED50 values--in six doses (0.062-1...
journal_title：British journal of anaesthesia
pub_type： 杂志文章
doi：10.1093/bja/80.1.63
更新日期：1998-01-01 00:00:00
abstract：:We have estimated the effect of omitting antagonism of neuromuscular block on postoperative nausea and vomiting. A systematic search (MEDLINE, EMBASE, Biological Abstracts, Cochrane library, reference lists and hand searching; no language restriction, up to March 1998) was performed for relevant randomized controlled ...
journal_title：British journal of anaesthesia
pub_type： 杂志文章,meta分析
doi：10.1093/bja/82.3.379
更新日期：1999-03-01 00:00:00
abstract：:This paper describes the use of solenoid valves for the production of binary gas mixtures. The system is controlled by a microprocessor and is capable of delivering accurate flows and concentrations of gases over the ranges commonly used in anaesthesia. Since the flow produced by the valves is pulsatile, a system for ...
journal_title：British journal of anaesthesia
pub_type： 杂志文章
doi：10.1093/bja/58.9.1041
更新日期：1986-09-01 00:00:00
abstract：:The Gapmeter Lab Kit series of flowmeters has been calibrated using air. Two of the flowmeters were also calibrated using argon and oxygen as the priming gases. Linear calibration graphs have been obtained for all the Gapmeters. The two low flow Gapmeters are extremely susceptible to back-pressure. ...
journal_title：British journal of anaesthesia
pub_type： 杂志文章
doi：10.1093/bja/49.3.277
更新日期：1977-03-01 00:00:00
abstract：:We have examined the effects of two types of insulin therapy (continuous i.v. infusion (group A: 1.25 u. h-1) and direct i.v. bolus administration of 10 u. every 2 h (group B: 10 u./2 h)) on the metabolic and endocrine responses to surgery in 60 adult diabetic patients undergoing general anaesthesia for elective proce...
journal_title：British journal of anaesthesia
pub_type： 临床试验,杂志文章
doi：10.1093/bja/72.1.5
更新日期：1994-01-01 00:00:00
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
更新日期：2007-12-01 00:00:00
abstract：:Using respiratory inductive plethysmography, we have measured rib cage and abdominal motion during isoflurane anaesthesia in 16 healthy day-surgery patients. Anaesthesia was induced with propofol and maintained with 1 MAC isoflurane in air-oxygen via a laryngeal mask. Measurements were taken during both resting ventil...
journal_title：British journal of anaesthesia
pub_type： 杂志文章
doi：10.1093/bja/67.6.712
更新日期：1991-12-01 00:00:00
abstract：:We have investigated the effects of clonidine on gastric emptying of liquids in 30 patients. In a double-blind, randomized design, clonidine 150 micrograms, morphine 10 mg or saline in 1 ml was given i.m. One hour later, the patient drank a paracetamol solution (1.5 g in 50 ml water). Venous blood samples were obtaine...
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/78.1.28
更新日期：1997-01-01 00:00:00
abstract：:The value of the continuous monitoring of end-tidal carbon dioxide concentration as an indicator of the acute intraoperative interruption of pulmonary blood flow, in patients with pre-existing restrictions of pulmonary blood flow undergoing closed heart surgery, is illustrated by two case reports. Decreases in end-tid...
journal_title：British journal of anaesthesia
pub_type： 杂志文章
doi：10.1093/bja/57.12.1257
更新日期：1985-12-01 00:00:00
abstract：BACKGROUND:Dynamic arterial elastance (Eadyn) has been proposed as an indicator of vascular tone that predicts the decrease in arterial pressure in response to changes in norepinephrine (NE). The purpose of this study was to determine whether Eadyn measured by uncalibrated pulse contour analysis (UPCA) can predict a de...
journal_title：British journal of anaesthesia
pub_type： 杂志文章
doi：10.1016/j.bja.2018.01.032
更新日期：2018-09-01 00:00:00
abstract：:The identification of a serum marker to assist in the diagnosis of cerebral injury after cardiac surgery is potentially useful. S100 protein is an early marker of cerebral damage. It is released after cardiac surgery performed under cardiopulmonary bypass (CPB). Its level is correlated with the duration of CPB, deep c...
journal_title：British journal of anaesthesia
pub_type： 杂志文章,评审
doi：10.1093/bja/85.2.287
更新日期：2000-08-01 00:00:00
