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)

Cellular Ca(2+)-dysregulation has been proposed as an important mechanism in certain diseases such as bipolar affective disorder (BPAD) and malignant hyperthermia. Recently it has been found that in BPAD, the plasma membrane Ca(2+)-channel blockers verapamil and nimodipine are useful substitutes in Li(+)-treatable patients. We have investigated the effects of these drugs and the antipsychotic drugs (clozapine, fluspirilene, and haloperidol) on IP3-induced Ca(2+)-release from Ca(2+)-loaded rat brain microsomes. In the presence of either the Ca(2+)-channel blockers or the neuroleptic drugs, Ca(2+)-release was blocked in a dose-dependent fashion. For the neuroleptics, the EC50 ranged from 22 microM for fluspirilene to 145 microM for haloperidol. The EC50 for nimodipine was 160 microM and 450 microM for verapamil. Carbamazapine and valproic acid, anticonvulsants recently used for treating BPAD, were relatively ineffective, as were various haloperidol metabolites. The research described in this paper establishes for the first time that antipsychotic drugs, as well as certain Ca(2+)-channel blockers, directly block the IP3-induced Ca(2+)-release in a rat brain microsome assay.
Biol Psychiatry 1996 Sep 15
PMID:Antipsychotic drugs block IP3-dependent Ca(2+)-release from rat brain microsomes. 887 69

We describe a patient with osteogenesis imperfecta who developed tachycardia, metabolic and respiratory acidosis (pH 7.14, PCO2 8.4 kPa, BE -8.5 mmol.l-1) and hyperthermia up to 40 degrees C during anaesthesia with barbiturates, fentanyl, pancuronium, and nitrous oxide. Malignant hyperthermia was suspected and the patient treated accordingly. Two years later the in-vitro contracture test for malignant hyperthermia was completely normal. We conclude that hypermetabolism in patients with osteogenesis imperfecta is due to unknown mechanisms other than malignant hyperthermia.
Anaesthesia 1996 Sep
PMID:Osteogenesis imperfecta and malignant hyperthermia. Is there a relationship? 888 52

The present experiments were concerned with the examination of the hypothesis that a deficiency in calpastatin, the endogenous inhibitor of calpain, enhances learning and memory performance. In the first experiment we used rats with an altered calpain/calpastatin balance (Milan hypertensive strain, MHS, low calpastatin) to investigate the learning and memory of a spatial task in the Morris water maze in comparison with control rats with a normal calpain/calpastatin balance (Milan normotensive strain, MNS). Since the two strains also differ in blood pressure, a third strain of rats was included to assess the role of hypertension (spontaneously hypertensive rats, SHR). Although the acquisition rate of the spatial task was better in the low-calpastatin MHS rats than in their normal-calpastatin MNS controls, their performance was similar to that of the SHR rats, thus thwarting the conclusion that differences were due to the low level of calpastatin. The availability of another mutant strain, low-calpastatin level and normotensive (MH.NE), allowed a further examination of the hypothesis. In the second experiment rats of the MH.NE strain acquired the spatial task as well as their normotensive controls, but their memory retrieval was clearly less than that of their normal-calpastatin controls. This deficiency was not due to impaired visual function or a slower swimming speed. The conclusion is that an inbalanced calpain/calpastatin ratio, although favoring calpain activity, is disadvantageous for remembering a spatial task. This disadvantage is clearly overruled when this inbalance is accompanied by hypertension.
Neurobiol Learn Mem 1996 Sep
PMID:Spatial learning and memory in calpastatin-deficient rats. 894 15

Several human Mendelian diseases, including the long-QT syndrome, malignant hyperthermia, and episodic ataxia/myokymia syndrome, have recently been demonstrated to be due to mutations in ion channel genes. Systematic mapping of ion channel genes may therefore reveal candidates for other heritable disorders. In this study, the GenBank and dbEST databases were used to identify members of several ion channel families (voltage-gated calcium and sodium, cardiac chloride, and all classes of potassium channels). Genes and ESTs without prior map localization were identified based on GDB and OWL database information and 15 genes and ESTs were selected for mapping. Of these 15, only the serotonin receptor 5HT3R had been previously mapped to a chromosome. A somatic cell hybrid panel (SCH) was screened with an STS from each gene and, if necessary the results verified by a second SCH panel. For three ESTs, rodent derived PCR products of the same size as the human STS precluded SCH mapping. For these three, human P1 clones were isolated and the genomic location was determined by metaphase FISH. These genes and ESTs can now be further evaluated as candidate genes for inherited cardiac, neuromuscular and psychiatric disorders mapped to these chromosomes. Furthermore, the ESTs developed in this study can be used to isolate genomic clones, enabling the determination of each transcript's genomic structure and physical map location. This approach may also be applicable to other gene families and may aid in the identification of candidate genes for groups of related heritable disorders.
Somat Cell Mol Genet 1996 Sep
PMID:Chromosomal localization of 15 ion channel genes. 903 51

Malignant hyperthermia is clinically an uncommon disorder characterized by acute hypercatabolic reactions in muscles in response to the triggering effects of certain drugs mainly used during anesthesia or to physical or emotional stress. We present a pediatric patient with multiple caries who was suspected to contract malignant hyperthermia while underwent the operative procedure of comprehensive restoration. Sinus tachycardia, hyperthermia, hypercapnia, metabolic acidosis, hyperkalemia and hypercalcemia developed unexpectedly during the operation. Fortunately, the patient survived the episode with early recognition and prompt management.
Acta Anaesthesiol Sin 1996 Sep
PMID:A child of suspected malignant hyperthermia during general anesthesia for dental surgery. 908 42

We present tow male children who experienced cardiac arrest secondary to unrecognized rhabdomyolysis on the day following an uneventful general anesthetic and recovery room course for adenotonsillectomy. Neither child exhibited hypermetabolism typical of malignant hyperthermia or appeared to have a dystrophinophy, prompting the authors to search for other etiologies of childhood rhabdomyolysis infrequently associated with anesthesia. In this report, we review the heritable metabolic myopathies caused by enzyme deficiencies (enzymopathies) that can lead to life-threatening rhabdomyolysis following certain triggering conditions, and we offer suggestions for avoiding these triggers in the perianesthetic period. We also describe key symptoms an signs that postanesthetic caregivers should be aware of, and briefly comment on follow-up diagnostic studies.
J Clin Anesth 1997 Sep
PMID:Cardiac arrest on the day following surgery in children with unrecognized rhabdomyolysis. 927 41

Malignant hyperthermia is a pharmacogenetic disease of skeletal muscle characterized by hypermetabolism that occurs on exposure to a triggering agent or agents. The most common agents are halogenated inhalational anesthetics and succinylcholine, a depolarizing muscle relaxant. Patients who experience malignant hyperthermia are generally transferred to the ICU for ongoing treatment and monitoring for secondary complications of the disorder. Critical care practitioners must be both knowledgeable and competent to prevent and treat perioperative episodes of malignant hyperthermia. A thorough preoperative interview should be done to determine risk factors and susceptible patients. This article provides critical care nurses with sound information on the pathophysiology of malignant hyperthermia, the ability to assess the disease properly and treat the patient both before and after the crisis, and the ability to provide support and teaching to patients and patients' families to prevent the recurrence of malignant hyperthermia.
Am J Crit Care 1997 Sep
PMID:Malignant hyperthermia. 965 50

An episode of malignant hyperthermia occurring in a 42-year-old man undergoing hypothermic cardiopulmonary bypass is reported. Malignant hyperthermia is a syndrome initiated by a hypermetabolic state of skeletal muscle. A patient presented for correction of an acyanotic tetralogy of Fallot. The coincidental usage of hypothermic cardiopulmonary bypass obscured the classical presenting sings and symptoms of the malignant hyperthermia. And the disease of tetralogy of Fallot made the syndrome difficult to manage. Although the clinical diagnosis of malignant hyperthermia is difficult to be confirmed, when it is suspected, it is prudent for the case to be initially treated as malignant hyperthermia.
Kyobu Geka 1997 Sep
PMID:[A case of an adult patient of tetralogy of Fallot having malignant hyperthermia during surgery]. 930 Nov 87

Dantrolene inhibits and ryanodine stimulates calcium release from skeletal-muscle sarcoplasmic reticulum (SR), the former by an unknown mechanism, and the latter by activating the ryanodine receptor (RyR), the primary Ca2+-release channel of SR. Dantrolene is used to treat malignant hyperthermia (MH), a genetic predisposition to excessive intracellular Ca2+ release upon exposure to volatile anaesthetics. Porcine MH results from a point mutation in the SR RyR that alters the open probability of the channel, and is reflected in altered [3H]ryanodine binding parameters. Specific binding sites for [3H]dantrolene and [3H]ryanodine co-distribute on SR that has been isolated by discontinuous sucrose gradient centrifugation. If the two drug-binding sites are functionally linked, [3H]dantrolene binding might be affected both by pharmacological and by genetic modulators of the functional state of the RyR. Accordingly, we compared the characteristics of [3H]dantrolene binding to porcine malignant-hyperthermia-susceptible and normal-skeletal-muscle SR, and examined the effects of RyR modulators on [3H]dantrolene binding to these membranes. Additionally, the feasibility of separating the SR binding sites for [3H]dantrolene and [3H]ryanodine was investigated. No significant differences in [3H]dantrolene binding characteristics to SR membranes from the two muscle types were detected, and the Bmax ratio for [3H]dantrolene/[3H]ryanodine was 1.4(+/-0.1):1 in both muscle types. [3H]Dantrolene binding is unaffected by the RyR modulators caffeine, ryanodine, Ruthenium Red and calmodulin, and neither dantrolene nor azumolene have any effect on [3H]ryanodine binding. Additionally, distinct peaks of [3H]dantrolene and [3H]ryanodine binding are detected in SR membranes fractionated by linear sucrose centrifugation, although no differences in protein patterns are detected by SDS/PAGE or Western-blot analysis. We suggest that the binding sites for these two drugs are pharmacologically distinct, and may exist on separate molecules.
Biochem J 1997 Sep 15
PMID:Pharmacological distinction between dantrolene and ryanodine binding sites: evidence from normal and malignant hyperthermia-susceptible porcine skeletal muscle. 930 36

Channels involved in the influx and intracellular mobilization of calcium have been implicated as targets of diverse genetic and immune-mediated neurological diseases. These include the L-type voltage-gated calcium channel of skeletal muscle (hypokalemic periodic paralysis), the neuronal P/Q-type voltage-gated calcium channel (familial hemiplegic migraine, episodic ataxia type 2, spinocerebellar ataxia 6, and Lambert-Eaton myasthenic syndrome), and the skeletal muscle ryanodine receptor (malignant hyperthermia and central core disease). The discovery of these and other calcium channelopathies should help to clarify how different mutations affect channel function and how altered channel function produces disease, and may lead to new treatments for these conditions.
Ann Neurol 1997 Sep
PMID:Calcium channels in neurological disease. 930 47


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