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)

Malignant hyperthermia developed in a 4-year-old Thoroughbred horse following 3 hours and 15 minutes of halothane anesthesia, with supplementary succinylcholine. Clinical signs included fever, sweating, hyperventilation, tachycardia, and decreased blood pressure followed by a rapid increase in blood pressure. Biochemical aberrations included hypocalcemia, hyperkalemia, hyperphosphatemia, myoglobinuria, and high creatine phosphokinase and ornithine carbamyl transferase activities. Treatment consisted initially of surface cooling with cold water, alcohol and ice, IV administration of cooled balanced electrolyte solutions and sodium bicarbonate, and removal from the anesthetic and rebreathing circuit. Oxygen was given by endotracheal insufflation. The rectum was then packed with ice, the horse was moved to a recovery raft and pool, and his body was packed in ice. Xylazine and dantrolene were given during recovery from anesthesia. Following recovery, treatment consisted of administration of balanced electrolyte solutions, calcium borogluconate, potassium penicillin, meperidine, and additional dantrolene. Muscle biopsy demonstrated exaggerated contracture responses to halothane and caffeine, confirming a diagnosis of malignant hyperthermia. The horse was returned to training following a routine postsurgical convalescent period.
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PMID:Malignant hyperthermia in a halothane-anesthetized horse. 734 3

The abnormal increase in intracellular Ca++ in malignant hyperthermia (MH) is well documented, but the link between the increased Ca++ concentration and high temperature remains speculative. We investigated the possibility that the Ca(++)-induced change in the state of cell membranes may contribute to the temperature elevation. Calcium ion transforms phospholipid membranes from the fluid to solid state. This is analogous to the freezing of water, and liberates latent heat. Differential titration calorimetry (DTC) measures heat production or absorption during ligand binding to macromolecules. When CaCl2 solution was added to anionic dimyristoylphosphatidic acid (DMPA) and dimyristoylphosphatidylglycerol (DMPG) vesicle membranes in incremental doses, DTC showed that the heat production suddenly increased when the Ca++ concentration exceeded about 120 microM. At this Ca++ concentration range, these lipid membranes underwent phase transition. The latent heat of transition was measured by differential scanning calorimetry (DSC). The values were 7.1 +/- 0.7 (SD, n = 4) kcal.mol-1 of DMPA and 6.8 +/- 0.7 (SD, n = 4) kcal.mol-1 of DMPG. The study shows that Ca++ produces heat when bound to lipid membranes. We are not proposing, however, that this is the sole source of heat. We contend that the lipid phase transition is one of the heat sources and it may trigger a hypermetabolic state by elevating the temperature of cell membranes. Because Ca++ is implicated as the second messenger in signal transduction, multiple systems may be involved. More studies are needed to clarify how Ca++ increases body temperature.
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PMID:Malignant hyperthermia and calcium-induced heat production. 805 15

Using portacaval anastomosis (PCA) rats as a model with or without injection of ammonium acetate, we investigated the effects of MHS-G on the abnormalities of electroencephalogram (EEG) and brain amines metabolism in comparison with those of SF-1008C, a commercial nutritional preparation for hepatic failure. MHS-G (0.68 g/kg, p.o.) clearly improved both the abnormalities of EEG (such as reduction of amplitude, increasing delta wave distribution and decreasing beta wave distribution) and brain amines metabolism (such as increasing of Trp and DOPAC content) after injection of ammonium acetate. Moreover, MHS-G significantly increased branched chain amino acid concentrations and decreased aromatic amino acid concentrations in plasma and brain in comparison with water, and it significantly decreased the ammonia level in plasma in comparison with water and SF-1008C. These results suggest that MHS-G has a positive effect on abnormalities of EEG and amino acids metabolism in the plasma and brain of PCA rats.
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PMID:[Effect of MHS-G, an amino acids granule, on hepatic encephalopathy in portacaval anastomosis rats]. 828 69

A total of 913 boned pork loins were selected in a commercial cutting operation on the basis of color measured by a Colormet surface colorimeter. Color (L, a, b values) at three locations, free water, and ultimate pH were measured on each loin. In addition, the genotype with respect to malignant hyperthermia was determined by a restriction endonuclease assay. Six hundred ninety-three loins were determined to be of normal (NN) genotype, 198 heterozygote (Nn), and 22 homozygote (nn). This distribution reflected the selection strategy and not the incidence in the general population. Meat was darker (P < .01) and free water was reduced (P < .01) in NN loins compared to Nn or nn loins. Ultimate pH was lower (P < .01) in Nn loins than in NN loins. An increase in the incidence of Nn or nn meat samples was observed as the paleness of the loins or their free water content increased, or as the ultimate pH of the meat decreased. Based on this study, approximately 30% of meat classified as PSE on a color basis would come from heterozygote pigs.
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PMID:Effect of the genotype for malignant hyperthermia as determined by a restriction endonuclease assay on the quality characteristics of commercial pork loins. 844 Jun 62

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.
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PMID:Spatial learning and memory in calpastatin-deficient rats. 894 15

A 34 year-old-man was scheduled for clipping and bypass surgery of dissecting aneurysm of the right vertebral artery. He previously had an episode suggesting malignant hyperthermia susceptibility during anesthesia managed with suxamethonium and isoflurane. Before the present operation, oral dantrolene 200 mg was administered. Anesthesia was induced with 120 mg of propofol and maintained with 10-6 mg.kg-1.hr-1 of propofol and 60 micrograms.hr-1 of fentanyl for 24 hours. Total dose of propofol amounted to 9,900 mg. Because propofol is formulated as a 10% oil in water emulsion, its high dose administration could alter serum lipid concentrations. However postoperative triglyceride and cholesterol concentrations remained within normal ranges in our case.
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PMID:[A case of high dose administration of propofol]. 1107 66

Malignant hyperthermia (MH) is a genetic, potentially life-threatening disorder of the skeletal muscle presenting during or following general anaesthesia. Trigger agents are volatile anaesthetics and depolarising muscle relaxants. Dantrolene is the only available drug for effective and specific MH therapy, which reduces significantly the mortality rate. Dantrolene is a skeletal muscle relaxant that depresses the excitation-contraction coupling,however, the specificity of action remains unknown. Recent studies identified the ryanodine receptor, the calcium release channel of the sarcoplasmic reticulum, as the direct molecular target of dantrolene. In addition to its use for MH, dantrolene is used in other disorders such as neuroleptic malignant syndrome and spasticity. Since dantrolene is weakly water soluble, the clinical preparation is time and manpower consuming. New agents have been synthesized, but because of economic considerations no registration for clinical usage has been realised.
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PMID:[Dantrolene. Pharmacological and therapeutic aspects]. 1266 6

Human malignant hyperthermia is a life-threatening genetic sensitivity of skeletal muscles to volatile anaesthetics and depolarizing neuromuscular blocking drugs occurring during or after anaesthesia. The skeletal muscle relaxant dantrolene is the only currently available drug for specific and effective therapy of this syndrome in man. After its introduction, the mortality of malignant hyperthermia decreased from 80% in the 1960s to < 10% today. It was soon discovered that dantrolene depresses the intrinsic mechanisms of excitation-contraction coupling in skeletal muscle. However, its precise mechanism of action and its molecular targets are still incompletely known. Recent studies have identified the ryanodine receptor as a dantrolene-binding site. A direct or indirect inhibition of the ryanodine receptor, the major calcium release channel of the skeletal muscle sarcoplasmic reticulum, is thought to be fundamental in the molecular action of dantrolene in decreasing intracellular calcium concentration. Dantrolene is not only used for the treatment of malignant hyperthermia, but also in the management of neuroleptic malignant syndrome, spasticity and Ecstasy intoxication. The main disadvantage of dantrolene is its poor water solubility, and hence difficulties are experienced in rapidly preparing intravenous solutions in emergency situations. Due to economic considerations, no other similar drugs have been introduced into routine clinical practice.
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PMID:Dantrolene--a review of its pharmacology, therapeutic use and new developments. 1547 27

The interactions between a polar analyte, 2-cyclopentyl-cyclopentanone, and a solid polar matrix, polyamide 6.6, during multiple headspace solid-phase microextraction (MHS-SPME) were studied. Strong hydrogen bonding between the analyte and the matrix was observed and shown to cause slow migration and adsorption of the analyte. These matrix effects led to erroneous quantitation despite the use of multiple headspace extraction. Addition of water disrupted the hydrogen bonding between the analyte and the matrix and a valid quantitation was achieved. The addition of water also increased the sensitivity and allowed the identification of 2,5-bis(cyclopentyl)-1-cyclopentanone. The amount of 2-cyclopentyl-cyclopentanone in five different polyamide 6.6 samples was measured using the developed multiple headspace solid-phase microextraction method with water-displacer. The measured concentrations were in the range of 1.44-15.61 microg/g. These concentrations were up to 30% higher than the concentrations measured after microwave-assisted extraction (MAE), which indicates incomplete recovery by MAE. The use of water as a displacer eliminated the matrix effects and complete recovery of the analyte was achieved by MHS-SPME.
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PMID:Multiple headspace solid-phase microextraction of 2-cyclopentyl-cyclopentanone in polyamide 6.6: possibilities and limitations in the headspace analysis of solid hydrogen-bonding matrices. 1552 21

Multiple headspace solid-phase microextraction (MHS-SPME) coupled with gas chromatography-mass spectrometry has been applied in order to determine 2,4,6-trichloroanisole (2,4,6-TCA), guaiacol, 1-octen-3-ol and 1-octen-3-one in three samples of cork stoppers. These compounds are responsible for cork taint in wine and can modify the organoleptic properties of bottled wine. Variables such as temperature, addition of water, extraction time, and amount of cork were studied. The extractions were performed with a 50/30 microm divinylbenzene-carboxen-polydimethylsiloxane (DVB-CAR-PDMS) fibre for 45 min at 100 degrees C using 20 mg of cork. For calibration, 50 microL of VOC aqueous solutions were used and the extraction were carried out for 45 min at 75 degrees C. The limits of detection of the method expressed as ng of VOC per g of cork were 0.3 for 2,4,6-TCA, 7.5 for guaiacol, 1.7 for 1-octen-3-one and 1.9 for 1-octen-3-ol. Relative standard deviation of replicate samples was less than 10%. Significant losses of analytes were observed when the samples were ground at room temperature. Finally, a recovery study was performed and the MHS-SPME results were validated using Soxhlet extraction results.
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PMID:Determination of odour-causing volatile organic compounds in cork stoppers by multiple headspace solid-phase microextraction. 1583 Sep 25


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