Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024591 (malignant hyperthermia)
 2,353 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent advances of research on malignant hyperthermia(MH) were reviewed. The rate of Ca-induced Ca release(CICR) from the sarcoplasmic reticulum(SR) was measured on the skinned muscle fiber preparation of porcine and human MH. The rate of CICR was significantly increased both in porcine and human MH. These observations supported conclusion obtained by genetical studies that the ryanodine receptor (RYR1) was site of abnormality in most of porcine and part of human MH. The RYR1 is Ca release channel of skeletal muscle SR and CICR is one of main function of the channel. Subsequently, point mutation of RYR1 gene was found in the foot domain of the molecule. Heretofore, 9 kind of mutations were described in association of MH-susceptible(MHS) trait. 4 of them were accompanied by a form of congenital myopathy, central core disease(CCD). CCD is considered as an allelic disease of MH. But pathogenesis of peculiar morphological abnormality of CCD is mostly unknown. Mutations are identified only in half of familial MH cases, suggesting MH is heterogeneous. Recently, it was reported that mutation of the dihydropyridine receptor gene was associated with MHS in a french family. The dihydropyridine receptor is distributed on the transverse tubule membrane and constitutes the triad structure with RYR1.
Nihon Rinsho 1997 Dec
PMID:[Molecular pathology of malignant hyperthermia and central core disease]. 943 56

Malignant hyperthermia, although an uncommon condition, has dramatic consequences when it occurs. The exact cause of MH is unknown but it is triggered by agents such as suxamethonium and volatile anaesthetic agents, especially Halothane. The condition can occur at anytime during the perioperative period and practitioners need to be vigilant towards its signs and symptoms as well as fully aware of the need for prompt action should it occur. The management of MH also includes identifying those at risk and taking measures to minimise these risks during anaesthesia.
Br J Theatre Nurs 1997 Dec
PMID:Malignant hyperthermia. 943 8

For incidents of malignant hyperthermia (MH) outside the hospital, a high number of unrecorded cases must be reckoned with because of an insufficient knowledge of emergency services and poor identification and documentation that make it impossible to classify acute situations under the diagnosis of malignant hyperthermia crisis. As a result, there are no statistical data in this field, and only case reports with a broad spectrum of suspected trigger mechanisms have been published. The case described in this report is a proved example of a non-anesthesia-related triggering of MH in a 21-year-old man who had had an anesthetic-induced MH manifestation in childhood, which was confirmed with an in vitro contracture test. After visiting a restaurant, he became unconscious and convulsive after consuming a high level of alcohol (2.9/1000). The first cardiocirculatory arrest occurred directly before hospitalization. After admission, the patient showed a full-blown MH episode whose subsequent fatality was unavoidable in spite of adapted and optimal therapy. Suspected trigger mechanisms seem to be multifactoral (excessive alcohol consumption, over-heating, mental stress) as a forensic investigation did not point to any particular signs of typical trigger substances. The case demonstrates again that an MH attack might be triggered under certain non-anaesthesia-related situations. For patients with an MH disposition, additional information on their behavior outside the hospital is required.
Anaesthesist 1997 Dec
PMID:[Anesthesia unrelated triggering of a fatal malignant hyperthermia crisis]. 945 92

This report describes a 13-month-old-girl with Duchenne's muscular dystrophy (DMD) who had radical repair for tetralogy of Fallot safely. Patients with DMD are considered to be at risk of malignant hyperthermia (MH). Drugs for induction and maintenance were chosen from a list of agents rarely associated with MH. To wash out the inhalation anesthetics from the equipment, oxygen was circulated continuously for 24 hours. Dantrolene sodium was kept readily available in case of MH occurrence. Differential diagnosis during surgery is difficult in term of the episodes of MH and complications of cardiac surgery, as cardiac surgery is also associated with tachycardia, tachyarrhythmias, metabolic asidosis and red colored urine, which are frequently accompanied by MH. Although increased levels of CK, GOT, LDH and myoglobin strongly support the diagnosis of MH, such evidence can only be confirmed after operation. Fortunately, these factors recovered to the normal range without treatment by dantrolene sodium. During the cardiac surgery, treatment of MH may be delayed due to its late confirmation.
Masui 1997 Dec
PMID:[Anesthetic management of a patient with Duchenne's muscular dystrophy undergoing radical repair for tetralogy of Fallot]. 945 83

The ryanodine receptor 1 (RYR1) mutation C1840T has been reported to segregate with malignant hyperthermia (MH) susceptibility in several families. We have investigated several Scandinavian MH families with respect to five different RYR1 mutations reported to cause predisposition to MH, and we here report on two of the families in which the C1840T mutation was detected. In these two families there was recombination between MH susceptibility and this mutation in one and three individuals, respectively. These findings may suggest that it is necessary to reconsider the specificity of the IVCT and the role of C1840T as a cause of MH susceptibility in some families exhibiting this mutation.
Clin Genet 1997 Dec
PMID:Discordance between malignant hyperthermia susceptibility and RYR1 mutation C1840T in two Scandinavian MH families exhibiting this mutation. 952 Feb 51

In two Siberian swine populations, the halothane test and PCR were used to determine the halothane susceptibility of the animals and to reveal a point mutation in their RYR1 gene, respectively. No correlations were found between the halothane susceptibility of an animal and the presence or absence of a point mutation at its RYR1 locus. However, the population changes in halothane susceptibility and the frequency of the mutation proved to be unidirectional. In the studied swine populations, the halothane-susceptible animals had no hyperthermia and the frequencies of their Hal and RYR1 genes changed similarly. These phenomena along with the phylogenesis of malignant hyperthermia and the porcine stress syndromes (PSS) in different breeds are discussed. In the populations studied, PSS is suggested to be under the polygenic control.
Genetika 1998 Dec
PMID:[Discordance and cosegregation of swine halothane susceptibility and 1843 C-T mutation of their RYR1 locus responsible for the ryanodine receptor]. 1020 43

Time-dependent effects of cysteine modification were compared in skeletal ryanodine receptors (RyRs) from normal pigs and RyR(MH) (Arg(615) to Cys(615)) from pigs susceptible to malignant hyperthermia, using the oxidizing reagents 4,4'-dithiodipyridine (4, 4'-DTDP) and 5,5'-dithio-bis(2-nitrobenzoic acid) (DTNB) or the reducing agent dithiothreitol (DTT). Normal and RyR(MH) channels responded similarly to all reagents. DTNB (1 mM), either cytoplasmic (cis) or luminal (trans), or 1 mM 4,4'-DTDP (cis) activated RyRs, introducing an additional long open time constant. 4,4'-DTDP (cis), but not DTNB, inhibited channels after >5 min. Activation and inhibition were relieved by DTT (1-10 mM). DTT (10 mM, cytoplasmic or luminal), without oxidants, activated RyRs, and activation reversed with 1 mM DTNB. Control RyR activity was maintained with 1 mM DTNB and 10 mM DTT present on the same or opposite sides of the bilayer. We suggest that 1) 4,4'-DTDP and DTNB covalently modify RyRs by oxidizing activating or inhibiting thiol groups; 2) a modified thiol depresses mammalian skeletal RyR activity under control conditions; 3) both the activating thiols and the modified thiols, accessible from either cytoplasm or lumen, reside in the transmembrane region; 4) some cardiac sulfhydryls are unavailable in skeletal RyRs; and 5) Cys(615) in RyR(MH) is functionally unimportant in redox cycling.
Biophys J 1999 Dec
PMID:Oxidation and reduction of pig skeletal muscle ryanodine receptors. 1058 23

General anaesthetics exhibit a relatively close relationship between their pharmacological potency and their lipid solubility and may thus act by non-specific perturbation of biomembranes. However, more recent data on anaesthetic action suggests that inhalational drugs such as halothane bind directly to hydrophobic protein domains, thereby modulating important receptor functions. In support of this protein theory of anaesthetic action our native gel analysis presented here shows that halothane induces oligomerization of the skeletal muscle ryanodine receptor (RyR) 1 Ca(2+)-release channel, but not its cardiac RyR-2 isoform. Thus, inhalational anaesthetics are not only able to influence protein-protein interactions directly but also appear to differentiate between protein isoforms and/or configurations. This suggests that distinct peptide binding sites exist for these pharmacological agents. In addition, similar mutations in the RyR-2 isoform, which would trigger an episode of malignant hyperthermia in skeletal muscle fibres via abnormal RyR-1 isoforms, would probably not induce an increase in cardiac Ca(2+)-release upon administration of halothane.
Naturwissenschaften 1999 Dec
PMID:Isoform-specific interactions between halothane and the ryanodine receptor Ca(2+)-release channel: implications for malignant hyperthermia and the protein theory of anaesthetic action. 1064 91

Rapid progress in the complementary fields of molecular genetics and cellular electrophysiology has led to a better understanding of many disorders which are caused by ion channel dysfunction. These channelopathies may manifest in a multitude of ways depending on the tissue specificity of the channel that is affected. Several important general medical conditions are now known to be channelopathies but the neurological members of this family are amongst the best characterized. Over recent years, ion channel dysfunction in skeletal muscle in particular has emerged as a paradigm for understanding neurological ion channel disorders. This review concentrates mainly on the diseases caused by dysfunction of the voltage-gated ion channels. We initially focus on the skeletal muscle channelopathies (the periodic paralyses, malignant hyperthermia, paramyotonia congenita and myotonia congenita). The central nervous system channelopathies are then explored, with particular reference to the advances which have implications for understanding the mechanisms of common neurological disorders such as epilepsy and migraine. Looking towards the new millennium, DNA-based diagnosis will become a realistic proposition for most neurological channelopathies. Furthermore, it seems likely that new therapies will be designed based on genotype and mode of ion channel dysfunction.
Ann Med 1999 Dec
PMID:Neurological channelopathies: diagnosis and therapy in the new millennium. 1068 Aug 55

We have investigated if cultivated muscle cells from malignant hyperthermia (MH) patients can be distinguished pharmacologically from controls. Muscle specimens from four individuals carrying the Gly2435Arg mutation of the skeletal muscle ryanodine receptor protein (RYR1) and from four controls were used to culture myotubes. Resting intracellular calcium concentration ([Ca2+]i) of MH myotubes was similar to controls. However, when ryanodine 0.5 mumol litre-1 was added, the kinetics of the increase in the calcium signals in MH and control cells were significantly different; the time for half maximum increase was mean 197 (SD 131) s for MH cells and 474 (61) s for controls (n = 80 cells each). On average, the area under the MH response curves was twice the control value. These results give rise to hopes that the phenotype of MH can be characterized using cultured human muscle and that a culture-based test for MH susceptibility may eventually be developed.
Br J Anaesth 1999 Dec
PMID:Malignant hyperthermia causing Gly2435Arg mutation of the ryanodine receptor facilitates ryanodine-induced calcium release in myotubes. 1070 Jul 82


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