BMI and malignant hyperthermia pathogenic ryanodine receptor type 1 sequence variants in Switzerland: A retrospective cohort analysis.

Background: Ryanodine receptor type 1 (RYR1) sequence variants are pathogenic for malignant hyperthermia. Variant carriers have a subtle increase in resting myoplasmic calcium concentration compared with nonaffected individuals, but whether this has metabolic effects in daily life is unknown.

Objectives: We analysed the potential effect of malignant hyperthermia-pathogenic RYR1 sequence variants on BMI as a single factor.

Consensus guidelines on perioperative management of malignant hyperthermia suspected or susceptible patients from the European Malignant Hyperthermia Group.

Malignant hyperthermia is a potentially fatal condition, in which genetically predisposed individuals develop a hypermetabolic reaction to potent inhalation anaesthetics or succinylcholine. Because of the rarity of malignant hyperthermia and ethical limitations, there is no evidence from interventional trials to inform the optimal perioperative management of patients known or suspected with malignant hyperthermia who present for surgery. Furthermore, as the concentrations of residual volatile anaesthetics that might trigger a malignant hyperthermia crisis are unknown and manufacturers' instructions differ considerably, there are uncertainties about how individual anaesthetic machines or workstations need to be prepared to avoid inadvertent exposure of susceptible patients to trigger anaesthetic drugs.

Availability of dantrolene for the management of malignant hyperthermia crises: European Malignant Hyperthermia Group guidelines.

Faced with a malignant hyperthermia crisis, the immediate access to sufficient dantrolene is essential to achieve the best possible outcome for the patient. However, malignant hyperthermia crises are rare, and there may be administrative pressures to limit the amount of dantrolene stocked or, in some countries, not to stock dantrolene at all. There are no published guidelines to support anaesthetic departments in their effort to ensure availability of sufficient dantrolene for the management of malignant hyperthermia crises.

High dose amino acid administration achieves an anabolic response in type 2 diabetic patients that is independent of glycaemic control: A randomized clinical trial.

Background & Aims: Surgical stress provokes protein catabolism and hyperglycaemia that is enhanced in patients with type 2 diabetes (T2DM), and increases perioperative morbidity. This study hypothesized that perioperative administration of high dose intravenous (IV) amino acids (AA) will augment protein balance in T2DM patients receiving tight plasma glucose control via continuous IV insulin compared to standard plasma glucose control via subcutaneous (SC) insulin sliding scale.

Methods: Eighteen patients with well-controlled T2DM (HbA1C% < 7.

Resequencing array for gene variant detection in malignant hyperthermia and butyrylcholinestherase deficiency.

Malignant hyperthermia (MH) and butyrylcholinestherase (BCHE) deficiency are two relevant pharmacogenetic disorders in anesthetic practice linked with sequence variants, the former in the RyR1 and CACNA1S genes, the latter in the BCHE gene. Genotyping for known pathogenic variants in these genes is useful to help identify susceptible individuals, and others may exist but remain unknown, because full-length sequence of these genes is, in general, not investigated. To facilitate this task, we developed a resequencing DNA array, the perioperative patient safety (POPS) array, to be able to screen the entire coding sequences of the RyR1, CACNA1S and BCHE genes.

Contractile function and energy metabolism of skeletal muscle in rats with secondary carnitine deficiency.

The consequences of carnitine depletion upon metabolic and contractile characteristics of skeletal muscle remain largely unexplored. Therefore, we investigated the effect of N-trimethyl-hydrazine-3-propionate (THP) administration, a carnitine analog inhibiting carnitine biosynthesis and renal reabsorption of carnitine, on skeletal muscle function and energy metabolism. Male Sprague-Dawley rats were fed a standard rat chow in the absence (CON; n = 8) or presence of THP (n = 8) for 3 wk.

The analgesic effect of combined treatment with intranasal S-ketamine and intranasal midazolam compared with morphine patient-controlled analgesia in spinal surgery patients: a pilot study.

Objectives: Ketamine is a well-known analgesic and dose-dependent anesthetic used in emergency and disaster medicine. Recently, a new formulation of S-ketamine, as an intranasal spray, was developed and tested in our institution in healthy volunteers. The authors investigated the effect of intranasal S-ketamine spray combined with midazolam intranasal spray in postoperative spinal surgery patients.

Effect of L-carnitine supplementation on the body carnitine pool, skeletal muscle energy metabolism and physical performance in male vegetarians.

Purpose: More than 95% of the body carnitine is located in skeletal muscle, where it is essential for energy metabolism. Vegetarians ingest less carnitine and carnitine precursors and have lower plasma carnitine concentrations than omnivores. Principle aims of the current study were to assess the plasma and skeletal muscle carnitine content and physical performance of male vegetarians and matched omnivores under basal conditions and after L-carnitine supplementation.

JP-45/JSRP1 variants affect skeletal muscle excitation-contraction coupling by decreasing the sensitivity of the dihydropyridine receptor.

JP-45 (also JP45; encoded by JSRP1) is an integral protein constituent of the skeletal muscle sarcoplasmic reticulum junctional face membrane interacting with Ca(v) 1.1 (the α.1 subunit of the voltage-sensing dihydropyridine receptor, DHPR) and the luminal calcium-binding protein calsequestrin.

Rare, potentially fatal, poorly understood propofol infusion syndrome.

We present the case of a 7-year old boy with traumatic brain injury who received propofol during 38 h. Thirty-six hours after cessation of propofol infusion asystole occurred. After immediate mechanical and medical resuscitation, unreactive dilated pupils were observed.

Tropisetron blocks analgesic action of acetaminophen: a human pain model study.

Because the mechanism underlying the analgesic action of acetaminophen remains unclear, we investigated the possible interaction of acetaminophen with central serotonergic pathways. The effects of acetaminophen, tropisetron, the combination of both drugs, and saline on pain perception and central sensitization in healthy volunteers were compared. Sixteen healthy volunteers were included in this randomized, double-blind, placebo-controlled crossover study.

Enhanced excitation-coupled Ca(2+) entry induces nuclear translocation of NFAT and contributes to IL-6 release from myotubes from patients with central core disease.

Prolonged depolarization of skeletal muscle cells induces entry of extracellular calcium into muscle cells, an event referred to as excitation-coupled calcium entry. Skeletal muscle excitation-coupled calcium entry relies on the interaction between the 1,4-dihydropyridine receptor on the sarcolemma and the ryanodine receptor on the sarcoplasmic reticulum membrane. In this study, we directly measured excitation-coupled calcium entry by total internal reflection fluorescence microscopy in human skeletal muscle myotubes harbouring mutations in the RYR1 gene linked to malignant hyperthermia (MH) and central core disease (CCD).

Analgesic and antihyperalgesic properties of propofol in a human pain model.

Background: Propofol (Disoprivan, AstraZeneca AG, Zug, Switzerland) has long been considered to be nonanalgesic. However, accumulating evidence shows that propofol possesses modulatory action on pain processing and perception. In this study, the authors investigated the modulatory effects of propofol and a formulation similar to the solvent of propofol (10% Intralipid; Fresenius Kabi, Stans, Switzerland) on pain perception and central sensitization in healthy volunteers.

Language difficulties in outpatients and their impact on a chronic pain unit in Northwest Switzerland.

Introduction: Many foreign patients attending our pain clinic are unable to understand one of the four Swiss national languages and are also unable to speak English. Therefore, communication with these patients can be very difficult or even impossible. Consequently, diagnosis and treatment may also prove difficult.

Serious complications associated with external intrathecal catheters used in cancer pain patients: a systematic review and meta-analysis.

Background: Potential risks of intrathecal catheters in cancer patients include infection, bleeding, and neurologic injury.

Methods: A systematic review and a pooled analysis of observational studies were performed. Articles reporting on adverse events (infections, bleeding, granuloma, and death) associated with intrathecal catheters and external pumps in cancer patients were identified.

A mathematical model to improve on phenotyping for molecular genetic research in malignant hyperthermia.

Background: The in-vitro contracture test is the standard test to diagnose malignant hyperthermia (MH) susceptibility. Maximum sensitivity is important for patient safety. For scientific purposes, the reduced specificity of contracture testing is a major drawback, and precise phenotyping is of utmost importance.

In vitro effects of propofol and volatile agents on pharmacologically induced chloride channel myotonia.

Background: Anesthetic choice for patients with chloride channel myotonia remains under debate. The authors have, therefore, investigated the in vitro effects of various anesthetic agents on pharmacologically induced chloride channel myotonia.

Methods: Functionally viable (> 10 mN force generation) rectus abdominis muscle preparations obtained from normal swine were investigated using in vitro muscle contracture test baths.

Increasing the number of diagnostic mutations in malignant hyperthermia.

Malignant hyperthermia (MH) is an autosomal dominant disorder characterized by abnormal calcium homeostasis in skeletal muscle in response to triggering agents. Today, genetic investigations on ryanodine receptor type 1 (RYR1) gene and alpha1 subunit of the dihydropyridine receptor (DHPR) (CACNA1S) gene have improved the procedures associated with MH diagnosis. In approximately 50% of MH cases a causative RYR1 mutation was found.

Rapid and accurate detection of atypical and Kalow variants in the butyrylcholinesterase gene using denaturing high performance liquid chromatography.

Background: Variations in the butyrylcholinesterase (BCHE) gene can prolong neuromuscular block after the administration of the neuromuscular blocking drugs succinylcholine and mivacurium. The most frequent variations in the BCHE gene are the atypical (A) and Kalow (K) variants. We, therefore, developed a detection approach for these most common variants based on the method of denaturing high-performance liquid chromatography (dHPLC).

Evaluation of a standardized internet-based and telephone-based patient monitoring system for pain therapy with transdermal fentanyl.

The aim of the present observational 4-week study was to document the feasibility and utility of telephone-based or Internet-based pain monitoring in patients with chronic cancer or noncancer pain, such as nociceptive or neuropathic pain, using transdermal fentanyl. Pain intensity, treatment tolerability, activities of daily living, quality of life, and patient and physician satisfaction were evaluated in 60 (60% women, 42% opioid-naive) chronic pain patients who were switched from oral pain therapy to transdermal fentanyl therapy because of persisting severe pain. When the total dataset of all patient entries was analyzed, treatment with transdermal fentanyl led to decreases in maximal and mean pain scores as reported by the patients (-14% and -19%, respectively, last observation carried forward vs.