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Malignant Hyperthermia (malignant + hyperthermia)

Distribution by Scientific Domains

Medical Sciences	80%
Life Sciences	20%

Selected Abstracts

Analysis of RYR1 Haplotype Profile in Patients with Malignant Hyperthermia

ANNALS OF HUMAN GENETICS, Issue 1 2009
D. Carpenter
Summary This study represents a new approach to characterising patients at risk of malignant hyperthermia (MH) through the use of a recently published method for identifying high-risk haplotypes in candidate genes. We present analysis based upon the largest standardised and genotyped database of MH patients worldwide. We used unphased RYR1 SNP data directly to (1) assess RYR1 haplotype frequency differences between susceptible cases and control groups and (2) analyse population-based association via clustering of RYR1 haplotypes based on disease risk. Our results show a significant difference in RYR1 haplotype frequency between susceptible cases and UK Caucasian population controls. Furthermore we identify a high-risk cluster of haplotypes that is associated with the commonest UK MH mutation p.G2434R/c.7300G>A. These results demonstrate the applicability of this new and practical method for population based association analysis. [source]

Malignant hyperthermia , who should be tested?

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 8 2008
J. Punj
No abstract is available for this article. [source]

Diagnosis of malignant hyperthermia susceptibility during CABG surgery

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2003
T. Girard
A 55-year-old man presented for coronary artery bypass graft (CABG) surgery. Malignant hyperthermia (MH) was suspected in his family. This case report describes a diagnostic approach to obtain a definite MH diagnosis by performing an in vitro contracture test at the time of CABG surgery in combination with molecular genetic investigations. [source]

Caffeine impairs intramuscular energy balance in patients susceptible to malignant hyperthermia

MUSCLE AND NERVE, Issue 3 2003
Zoran Textor MD
Abstract Malignant hyperthermia (MH) is a metabolic myopathy with an abnormal release of calcium by the sarcoplasmic reticulum (SR), triggered by volatile anesthetics and succinylcholine. Similarly, caffeine enhances Ca2+release by the SR in vitro. In a prospective, randomized study, high-energy phosphates were studied by intramuscular 31-phosphorus magnetic resonance spectroscopy (31P-MRS) in 10 MH-susceptible (MHS) and 7 MH-nonsusceptible (MHN) subjects before and after injection of 0.5 ml caffeine (20 mM). Intramuscular energy balance, measured by the ratios of Pi/PCr and Pi/,-ATP, did not differ between MHS and MHN patients before and after intramuscular caffeine injection. However, within each group, Pi/PCr and Pi/,-ATP increased significantly only in the MHS group. Intramuscular caffeine injection seemed to impair the metabolic balance in MHS individuals. This may reflect a local calcium overload leading to consumption of high-energy phosphates and increase of inorganic phosphate. Intramuscular stimulation by caffeine and 31P-MRS may provide a valuable tool to investigate MH-related metabolic disturbances. Muscle Nerve 28: 353,358, 2003 [source]

Malignant hyperthermia presenting during laparoscopic adrenalectomy

ANAESTHESIA, Issue 5 2008
S. S. O'Neill
Summary A 44-year-old man presented for elective laparoscopic adrenalectomy. During the procedure his end-tidal carbon dioxide readings rose steadily. We assumed that this was due to a prolonged carbon dioxide pneumoperitoneum until he developed ST segment depression on his electrocardiogram and a rapid rise in temperature. A diagnosis of malignant hyperthermia was made in view of the rising temperature and carbon dioxide. He responded to cooling and intravenous dantrolene. He was later confirmed to be malignant hyperthermia-susceptible on in vitro contracture testing of a muscle biopsy. The diagnosis was delayed as the early signs of malignant hyperthermia are the same as the expected physiological changes in laparoscopic surgery. As laparoscopic surgery continues to expand we advocate vigilance to ensure early identification of this rare but potentially devastating condition. [source]

Mutations in RYR1 in malignant hyperthermia and central core disease,

HUMAN MUTATION, Issue 10 2006
Rachel Robinson
Abstract The RYR1 gene encodes the skeletal muscle isoform ryanodine receptor and is fundamental to the process of excitation,contraction coupling and skeletal muscle calcium homeostasis. Mapping to chromosome 19q13.2, the gene comprises 106 exons and encodes a protein of 5,038 amino acids. Mutations in the gene have been found in association with several diseases: the pharmacogenetic disorder, malignant hyperthermia (MH); and three congenital myopathies, including central core disease (CCD), multiminicore disease (MmD), and in an isolated case of a congenital myopathy characterized on histology by cores and rods. The majority of gene mutations reported are missense changes identified in cases of MH and CCD. In vitro analysis has confirmed that alteration of normal calcium homeostasis is a functional consequence of some of these changes. Genotype,phenotype correlation studies performed using data from MH and CCD patients have also suggested that mutations may be associated with a range of disease severity phenotypes. This review aims to summarize the current understanding of RYR1 mutations reported in association with MH and CCD and the present viewpoint on the use of mutation data to aid clinical diagnosis of these conditions. Hum Mutat 27(10), 977,989, 2006. © 2006 Wiley-Liss, Inc. [source]

Uneventful anaesthesia does not exclude malignant hyperthermia

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 7 2008
T. Girard
No abstract is available for this article. [source]

A RYR1 mutation associated with recessive congenital myopathy and dominant malignant hyperthermia in Asian families

MUSCLE AND NERVE, Issue 4 2009
Danielle Carpenter PhD
Abstract In this study we present 3 families with malignant hyperthermia (MH), all of Indian subcontinent descent. One individual from each of these families was fully sequenced for RYR1 and presented with the non-synonymous change c.11315G>A/p.R3772Q. When present in the homozygous state c.11315*A is associated with myopathic symptoms. Muscle Nerve, 2009 [source]

Central core disease due to recessive mutations in RYR1 gene: Is it more common than described?

MUSCLE AND NERVE, Issue 5 2007
Patrícia M. Kossugue MS
Abstract Central core disease (CCD) is an autosomal-dominant congenital myopathy, with muscle weakness and malignant hyperthermia (MH) susceptibility. We identified two of nine Brazilian CCD families carrying two mutations in the RYR1 gene. The heterozygous parents were clinically asymptomatic, and patients were mildly affected, differing from the few autosomal-recessive cases described previously. Recessive inheritance in CCD may therefore be more common than previously appreciated, which has important implications for genetic counseling and MH prevention in affected families. Muscle Nerve, 2007 [source]

Sarcoplasmic reticulum: The dynamic calcium governor of muscle

MUSCLE AND NERVE, Issue 6 2006
Ann E. Rossi MS
Abstract The sarcoplasmic reticulum (SR) provides feedback control required to balance the processes of calcium storage, release, and reuptake in skeletal muscle. This balance is achieved through the concerted action of three major classes of SR calcium-regulatory proteins: (1) luminal calcium-binding proteins (calsequestrin, histidine-rich calcium-binding protein, junctate, and sarcalumenin) for calcium storage; (2) SR calcium release channels (type 1 ryanodine receptor or RyR1 and IP3 receptors) for calcium release; and (3) sarco(endo)plasmic reticulum Ca2+ -ATPase (SERCA) pumps for calcium reuptake. Proper calcium storage, release, and reuptake are essential for normal skeletal muscle function. We review SR structure and function during normal skeletal muscle activity, the proteins that orchestrate calcium storage, release, and reuptake, and how phenotypically distinct muscle diseases (e.g., malignant hyperthermia, central core disease, and Brody disease) can result from subtle alterations in the activity of several key components of the SR calcium-regulatory machinery. Muscle Nerve, 2006 [source]

Caffeine impairs intramuscular energy balance in patients susceptible to malignant hyperthermia

Mutation screening in the ryanodine receptor 1 gene (RYR1) in patients susceptible to malignant hyperthermia who show definite IVCT results: identification of three novel mutations

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 6 2002
H. Rueffert
Background: The ryanodine receptor of the skeletal muscle (RYR1) seems to be of outstanding importance in the pathogenesis of malignant hyperthermia (MH). It has been shown that point mutations in the RYR1 gene are strongly associated with the MH phenotype. A correctly determined phenotype is the basic prerequisite for adequate genetic MH screening. In this study we examined only those MH susceptible patients for the presence of potential RYR1 mutations who showed strong pathological muscle responses in the in vitro contracture test (IVCT). Methods: A total of 56 MHS index patients who complied with the following IVCT criteria were included in the molecular genetic investigation: Contracture forces ,4 mN at a caffeine concentration of 2.0 mmol/l and ,8 mN at a halothane concentration of 0.44 mmol/l. DNA sequences of exons 2, 6, 9, 11, 12, 14, 15, 17, 39, 40, 45, 46, 102 of the RYR1 gene were analysed by the direct sequencing technique. Furthermore, if an MH mutation was identified in an index patient, all relatives were screened for their family specific RYR1 defect. Results: In 39 index patients an RYR1 mutation was detected: Arg163Cys (n = 2), Asp166Asn (n = 1), Gly341Arg (n = 2), Arg401His (n = 2), Arg614Cys (n = 12), Asp2129Glu (n = 1),Vol2168Met (n = 1), Thr2206Met (n = 9), Ala2428Thr (n = 1), Gly2434Arg (n = 2), Arg2435His (n = 1), Arg2452Trp (n = 1), Arg2454His (n = 4). Three new RYR1 mutations were identified. We found a potential MH mutation in a further 130 relatives of the 39 index patients. Thirty-seven individuals were classified as MHS exclusively by molecular genetic techniques and did not have to undergo the IVCT. Conclusions: The ascertained high rate of successful MH mutation screening (69.64%) is obviously associated with the more clearly defined MHS diagnosis in the IVCT. According to the EMHG guidelines for the molecular genetic detection of MH susceptibility, a positive MH disposition could be determined in numerous persons by a less invasive technique. [source]

How do anaesthesiologists treat malignant hyperthermia in a full-scale anaesthesia simulator?

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 8 2001
T. i Gardi
Background: Clinical malignant hyperthermia (MH) is rare and usually occurs unexpectedly. Prompt diagnosis and correct treatment is crucial for survival of the patient developing fulminant MH. The aims of the present study were to investigate whether anaesthesiologists could make a correct diagnosis of MH and to evaluate their treatment of fulminant MH in a simulator. Methods: Thirty-two teams (one anaesthesiologist/one nurse anaesthetist) were exposed to an event of clinical MH in a full-scale simulator. Their performance was videotaped for retrospective analysis of the treatment on the basis of the recommendations of the Danish Malignant Hyperthermia Register. Results: All 32 teams asked the surgeon to terminate the surgery as fast as possible, switched off the vaporiser and administered 100% oxygen. Although all intended to hyperventilate the patient, only 14 teams actually managed to perform the hyperventilation. Most problems were found in teams that switched to manual ventilation. All teams treated the patient with dantrolene, and symptomatic treatment was initiated by all even though some elements of the full treatment were lacking, possibly due to the limited time available. Conclusion: All teams diagnosed MH in the simulator satisfactorily. The surprising negative finding was that more than half of the participants failed to hyperventilate the "patient" although they intended to do so. This investigation shows that the problem in these teams' treatment of MH was more a question of practical management of the resources than lack of theoretical knowledge. [source]

A cognitive aid for neonatal resuscitation: a randomized controlled trial

PEDIATRIC ANESTHESIA, Issue 7 2009
M.D. Bould
Introduction:, Anaesthetists are among several health care practitioners responsible for neonatal resuscitation in Canada. The Neonatal resuscitation program (NRP) courses are the North American educational standard. NRP has been shown to be an effective way of learning skills and knowledge but retention has been found to be problematic [1]. The use of cognitive aids is mandatory in industries such as aviation, to avoid dependence on memory when decision making in critical situations. Visual cognitive aids have been studied retrospectively in resuscitation and performance was found to correlate to the frequency of use of the aid [2]. Cognitive aids have been found to be of benefit in an unblinded prospective study [3]. We aimed to conduct the first blinded study on the effect of a cognitive aid on the performance of simulated resuscitation. Methods:, We conducted a single-blind randomized controlled trial to investigate whether the presence of a cognitive aid improved performance in a simulated neonatal resuscitation. After ethics board approval we recruited 32 anaesthesia residents who had previously passed the NRP. Subjects were randomized to an intervention group that had a poster detailing the NRP algorithm and a control group without the poster. The cognitive aid was positioned so that it could not be seen on the video recordings of the simulation that was used to assess performance. The scenario was piloted to confirm adequate blinding. Both groups had their performance in a simulated neonatal resuscitation recorded and subsequently analyzed by a peer, an expert anaesthetist and an expert neonatologist, using a previously validated checklist. A further rater observed the scenario in real time to examine frequency of use of the cognitive aid. Results:, The inter-rater reliability of the checklist was excellent with an intraclass correlation coefficient of 0.88. Consequently the mean of the scores assigned by all three raters was used for analysis. The median checklist score in the control group 18.2 [15.0,20.5 (10.7,25.3)] was not significantly different from that in the intervention group 20.3 [18.3,21.3 (15.0,24.3)] (P = 0.08). Retention of NRP skills and knowledge of was poor: when evaluated by the neonatologist none of the subjects correctly performed all life-saving interventions necessary to pass the checklist. Although only one subject in the intervention group did not use the aid at all, only 26.7% used the aid frequently and none used it extensively. Discussion:, Retention of skills after NRP training was poor. Our study confirms previous findings of poor retention of skills after NRP training: Kaczorowski et al. investigated family medicine trainees and found that none of 44 residents that were retested 6,8 months after an NRP course would have passed the course due to errors in life-saving interventions [1]. Previous research has shown that the presence of a cognitive aid can improve performance in the simulated management of a rare, high stakes scenario: malignant hyperthermia [3]. Our negative findings contrast with this and another previous study [2]. A potential reason for this discrepancy is that the raters in the previous studies were not blinded to group allocation, nor were the rating scales used validated. The infrequent use of the cognitive aid may be the reason that it did not improve performance in. Further research is required to investigate whether cognitive aids can be useful if their use is incorporated into NRP training. Conclusion:, A randomized single-blinded trial found that a cognitive aid did not improve performance at simulated resuscitation, in contrast to previous retrospective and unblended studies. Retention of skills and knowledge after resuscitation training remains an ongoing challenge for medical educators. [source]

Anaesthetic management of a child with a positive family history of malignant hyperthermia for posterior fossa surgery in the sitting position

PEDIATRIC ANESTHESIA, Issue 4 2001
M.A. Wootton FRCA
A 6-year-old boy with a positive family history of malignant hyperthermia presented for posterior fossa craniectomy and excision of medulloblastoma. A nontriggering anaesthetic was therefore planned using infusions of propofol and remifentanil and a vapour free anaesthetic system delivering an oxygen/air mixture. The surgery was carried out with the child in the sitting position. [source]

Malignant hyperthermia presenting during laparoscopic adrenalectomy

Caesarean section in a complicated case of central core disease

ANAESTHESIA, Issue 5 2008
R. N. Foster
Summary We describe the anaesthetic management of a 21-year-old lady with central core disease for elective Caesarean section. Central core disease is characterised by muscle weakness, skeletal deformities and susceptibility to malignant hyperthermia. Total intravenous anaesthesia was used because of the combination of potential malignant hyperthermia, severe kyphoscoliosis and extensive spinal scarring. The authors believe there is no previous report of propofol and remifentanil being used in these circumstances. A short review of central core disease and its anaesthetic implications is provided. [source]

Analysis of RYR1 Haplotype Profile in Patients with Malignant Hyperthermia

The ryanodine receptor type 1 gene variants in African American men with exertional rhabdomyolysis and malignant hyperthermia susceptibility

CLINICAL GENETICS, Issue 6 2009
N Sambuughin
It has been suggested that exertional rhabdomyolysis (ER) and malignant hyperthermia (MH) are related syndromes. We hypothesize that patients with unexplained ER harbor mutations in the ryanodine receptor gene type 1 (RYR1), a primary gene implicated in MH, and therefore ER patients are at increased risk for MH. Although there are reported cases of MH in individuals of African descent, there are no data available on molecular characterization of these patients. We analyzed RYR1 in six, unrelated African American men with unexplained ER, who were subsequently diagnosed as MH susceptible (MHS) by the Caffeine Halothane Contracture Test. Three novel and two variants, previously reported in Caucasian MHS subjects, were found in five studied patients. The novel variants were highly conserved amino acids and were absent among 230 control subjects of various ethnic backgrounds. These results emphasize the importance of performing muscle contracture testing and RYR1 mutation screening in patients with unexplained ER. The MHS-associated variant Ala1352Gly was identified as a polymorphism predominant in individuals of African descent. Our data underscore the need for investigating RYR1 across different ethnic groups and will contribute to interpretation of genetic screening results of individuals at risk for MH. [source]