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)

In vitro contracture tests for susceptibility to malignant hyperthermia (MH) were performed with halothane and caffeine in 34 patients, according to the protocol of the European MH Group. Additional halothane and caffeine tests were performed in the presence of salbutamol 50 micrograms/l. Contractures after exposure to halothane were seen only in MH-susceptible (MHS) patients (n = 16), and were not changed by salbutamol. Salbutamol did not influence the caffeine dose-response curves in any of the groups (n = 14 in the MH-non-susceptible (MHN) group). The caffeine threshold concentration was significantly increased by salbutamol in the MHS group.
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PMID:Influence of salbutamol on the in vitro muscle response to caffeine and halothane in malignant hyperthermia. 227 27

Caffeine and halothane contracture testing is widely used to detect malignant hyperthermia (MH) susceptibility. The accuracy and reliability of the 3% halothane test and the incremental caffeine test, as recommended by the North American MH Group, were assessed in 11 swine (five MHS, six control). Nine swine were tested twice, 4-6 weeks apart. Accuracy of the in vitro diagnosis was also assessed by in vivo anesthetic challenge. Of all muscle bundles from MH-susceptible swine, 65% reacted positively to 3% halothane and 70% to 2 mM caffeine. Only 35% had a positive caffeine-specific concentration, and 25% developed an increase in baseline tension greater than or equal to 7% at 2 mM caffeine. However, when only the most positive response to 3% halothane or to 2 mM caffeine was used (a minimum of three fresh muscle strips is recommended), these two tests were highly sensitive and specific. In control swine one of 30 muscle bundles reacted positively to 3% halothane. A positive caffeine-specific concentration developed in one of 25 control muscle bundles exposed to caffeine. The variability in the results of these tests mandated that at least three muscle bundles be used for each test. Nonviable muscle bundles could not be relied upon to provide accurate results. In this porcine model, MH susceptibility could be detected by performing the Caffeine Halothane Contracture Test (CHCT) according to the guidelines of the North American MH Group. However, only the 3% halothane test and the response to 2 mM caffeine produced adequate diagnostic results in this breed of swine.
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PMID:Caffeine and halothane contracture testing in swine using the recommendations of the North American Malignant Hyperthermia Group. 222 56

This study provides the first comprehensive characterisation of the calcium (Ca) homeostasis defects found in muscle and lymphocytes of a malignant hyperthermia (MH)-susceptible dog. Novel findings regarding this dog are reported, compared to controls. First, a canine stress syndrome occurs, analogous to the porcine stress syndrome; susceptibility can be identified by exercise challenge testing. Secondly, caffeine causes Ca release from muscle sarcoplasmic reticulum in a greater amount and at a greater rate. Thirdly, there is a compensatory increase in Ca sequestration by sarcoplasmic reticulum. Fourthly, lymphocytes have lower cytosolic-free Ca and a greater ability to prevent Ca increase. Halothane increases Ca by a greater amount and rate. Fifthly, muscle is more resistant to the contracture-producing effects of caffeine, as occurs in the non-rigid variant of MH susceptibility in man. This resistance, despite increased caffeine-induced release through the Ca channel, may be attributable to increased Ca sequestration by sarcoplasmic reticulum. Finally, erythrocyte osmotic fragility and creatine kinase tests fail to distinguish between the MH-susceptible dog and controls.
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PMID:Canine stress syndrome/malignant hyperthermia susceptibility: calcium-homeostasis defect in muscle and lymphocytes. 230 Jul 6

We examined the effects of verapamil on the in vitro caffeine and halothane tests for malignant hyperpyrexia (MH) susceptibility. Ten consecutive MH-susceptible patients were investigated according to the protocol of the European MH group. Additional tests were carried out in the presence of verapamil 10(-6) mol litre-1. In four of the 10 patients, the halothane contracture response following pretreatment with verapamil was classified as positive to halothane. In contrast, in nine of the 10 patients, contracture tests of muscle in the presence of verapamil were classified as negative to caffeine. It is advised that verapamil should be discontinued before performing a contracture test.
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PMID:Clinical concentrations of verapamil affect the in vitro diagnosis of susceptibility to malignant hyperpyrexia. 230 78

Anesthetic management and outcome were examined in patients with negative in vitro contracture tests for malignant hyperthermia (MH). Contracture testing was performed in a standardized fashion using 3% halothane alone and incremental doses of caffeine alone. Medical records were examined for 54 anesthetic exposures in 42 MH(-) patients who had received anesthesia since their MH testing. Sixteen patients received anesthesia with known MH triggering agents on 23 occasions, all without incident. In six MH(-) patients with previous masseter muscle rigidity, no adverse reactions occurred in response to volatile anesthetic agents. Succinylcholine was avoided in these patients. Eleven MH(-) patients were managed as if MH-susceptible, although it was known that these patients had tested MH(-). Two of these patients also receive prophylactic iv dantrolene. These results suggest that "triggering" anesthetic agents may be safely administered to patients who test MH(-) by in vitro contracture testing. However, until the anesthetic experience of larger numbers of MH(-) patients is known, these results should be interpreted cautiously.
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PMID:Safety of general anesthesia in patients previously tested negative for malignant hyperthermia susceptibility. 239 53

When compared to normal pig sarcoplasmic reticulum (SR), SR from malignant hyperthermia susceptible (MHS) porcine skeletal muscle has been shown to exhibit an increased rate of calcium release, as well as alterations in [3H]ryanodine-binding activity in the presence of microM Ca2+ (Mickelson et al., 1988, J. Biol. Chem. 263, 9310). In the present study, various stimulators (adenine nucleotides and caffeine) and inhibitors (ruthenium red and Mg2+) of the SR calcium release channel were examined for effects on MHS and normal SR [3H]ryanodine binding. The apparent affinity of the MHS SR receptor for ryanodine in the presence of 10 mM ATP (Kd = 6.0 nM) or 10 mM caffeine (Kd = 28 nM) was significantly greater than that of the normal SR (Kd = 8.5 and 65 nM in 10 mM ATP or caffeine, respectively), the Bmax (12-16 pmol/mg) was similar in all cases. The Ca2+(0.5) for inhibition of [3H]ryanodine binding in the presence of 5 mM AMPPNP (238 vs 74 microM for MHS and normal SR, respectively) and the Ca2+(0.5) for stimulation of [3H]ryanodine binding in the presence of 5 mM caffeine (0.049 vs 0.070 microM for MHS and normal SR, respectively) were also significantly different. Furthermore, in the presence of optimal Ca2+, MHS SR [3H]ryanodine binding was more sensitive to caffeine stimulation (C0.5 of 1.7 vs 3.4 mM) and was less sensitive to ruthenium red (C0.5 of 1.9 vs 1.2 microM) or Mg2+ inhibition (C0.5 of 0.34 vs 0.21 mM) than was normal SR. These results further support the hypothesis that differences in the ryanodine/receptor calcium release channel regulatory properties are responsible for the abnormal calcium releasing activity of MHS SR.
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PMID:Stimulation and inhibition of [3H]ryanodine binding to sarcoplasmic reticulum from malignant hyperthermia susceptible pigs. 232 64

Malignant hyperthermia (MH) is a rare genetic myopathy whose hallmark is rise in body temperature. This hypermetabolic state is triggered by inhalational anesthetics and/or depolarizing muscle relaxants such as succinylcholine. Even the use of dantrolene may not be protective against the hypermetabolic crisis. Eight patients at risk for MH undergoing tonsillectomy, adenoidectomy, and/or myringotomy with ventilation tube insertion were anesthetized with nitrous oxide, barbiturates, opiates, tranquilizers, and nondepolarizing muscle relaxants without dantrolene and without complication. Cardiac monitoring and rectal temperatures were followed. In order to provide additional evidence, all eight patients had vastus lateralis muscle biopsies with subsequent caffeine-halothane contracture studies performed. The contracture study showed positive results in seven of eight patients studied, indicating MH-susceptible muscle. No anesthetic or operative complications were encountered. This study demonstrates that patients at risk of developing MH crisis can have otolaryngologic procedures performed relatively safely while undergoing appropriately selected anesthesia.
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PMID:Malignant hyperthermia in the otolaryngologic patient: prospective anesthetic and surgical management of eight children. 232 99

Halothane in concentrations exceeding 1.2 mmol litre-1 increased (P less than 0.05) the apparent intracellular concentration of calcium in lymphocytes from 12 patients being tested for susceptibility to malignant hyperthermia (MH) using the fluorescent Ca2+ indicator, fura2. There was no difference in [Ca2+]i between lymphocytes from patients found to be MH susceptible (n = 5) on in vitro contracture testing with halothane and caffeine and those from MH negative patients (n = 6). Thus determination of [Ca2+]i in lymphocytes after exposure to halothane could not be used as a diagnostic test for MH susceptibility.
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PMID:Cytosolic free calcium concentrations in lymphocytes from malignant hyperthermia susceptible patients. 232 83

Biopsy specimens of the cutaneous omobrachialis muscle were obtained from 10 horses with a problem of myositis from mild exercise. One horse had been evaluated previously and malignant hyperthermia-like contractures developed in its muscle biopsy specimen during the contracture test. In this study, the halothane-caffeine contracture test and histologic and histochemical evaluations were performed on muscle biopsy specimens. In the contracture test, no muscle biopsy specimen developed contracture in the presence of 2 or 4% halothane alone. The mean (+/- SEM) caffeine-specific concentration in the presence of halothane was 5.23 +/- 0.5 mM for 2% halothane, and 4.46 +/- 0.6 mM for 4% halothane. The caffeine-specific concentration values were not significantly different. Contracture response for any muscle specimen did not resemble contracture associated with malignant hyperthermia. The cutaneous omobrachialis muscle was composed of type-II fibers, with type-I fibers seldom seen. For 9 of the 10 horses, overall fiber morphology was normal; 1 horse had necrotic fibers. Of the 10 muscle specimens, 9 had fibers that had positive reaction for alkaline phosphatase activity; 3 muscle specimens contained ringed myofibers. Three horses of this study were administered general anesthesia; 2 were research horses, anesthetized with halothane and succinylcholine, and 1 was a clinical case given halothane anesthesia plus a non-depolarizing muscle relaxant. One research horse developed a malignant hyperthermia-like reaction to anesthesia, with severe rhabdomyolysis evident after anesthesia, and an episode of muscle cramping in its stall 2 days after anesthesia. The other 2 horses had unremarkable postanesthetic periods.
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PMID:Contracture test and histologic and histochemical analyses of muscle biopsy specimens from horses with exertional rhabdomyolysis. 232 77

Although an association between malignant hyperthermia (MH) and congenital abnormalities has been recorded, no prospective study has been attempted to investigate this relationship. Standardised in vitro muscle tests were performed, because of impending anaesthesia for corrective surgery, on 25 children with birth defects similar to those induced by hyperthermia in laboratory animals, and in whom excessive pyrexial reactivity to anaesthesia, drugs or stress were recorded. Fifteen of the 25 children were MH positive by responding abnormally to the administration of halothane/caffeine. Five of these patients reacted positively to both caffeine and halothane, while the remainder manifested a contractile response to halothane only. This study underlines the existence of an anaesthetic risk factor associated with certain congenital abnormalities and neurodevelopmental delay and emphasises the need for further research to elucidate the possible importance of heat stress during fetal development in genetically susceptible individuals.
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PMID:An association between certain congenital abnormalities and the malignant hyperthermia trait. 234 83


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