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)

Three months before this study, susceptibility for malignant hyperthermia (MH) had been tested in 15 pigs. In all pigs, MH was triggered by administration of 1% halothane. Brain electrical activity was examined during therapy of MH with and without administration of dantrolene. From the EEG, power densities in selected frequencies and the median frequency of the power spectrum were calculated. Therapy was started when severe respiratory changes were observed (PaCO2 > 10 kPa, mixed venous oxygen tension (PvO2) < 4 kPa). At this time, heart rate exceeded 150 beat min-1, mean arterial pressure (MAP) was less than 60 mm Hg and median frequency was less than 2 Hz. EEG was isoelectric (n = 6) or showed slow polymorphic delta-activity. For therapy, administration of all anaesthetics was terminated, 100% oxygen was delivered and ventilation was increased four-fold. Acidosis was treated by administration of sodium bicarbonate 2-4 mmol litre-1 kg-1. Animals were allocated randomly to one of two groups: group I (control, n = 7) received no dantrolene; group II (n = 8) received dantrolene 2.5 mg kg-1 i.v. All variables were measured over a period of 60 min after therapy: EEG, HR and MAP were recorded continuously and blood-gas tensions, arterial potassium and glucose concentrations and pH were measured every 150 s. In group I (no dantrolene) minor, transient improvements in EEG activity were noted, but all animals died within 15-25 min after the start of therapy. In dantrolene-treated animals, EEG total power and median frequency increased within 5 min.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Improvement of brain electrical activity during treatment of porcine malignant hyperthermia with dantrolene. 828 May 59

A 53-year-old woman was scheduled for elective surgery of a L4-L5 lumbar disc prolapse. Preoperatively, she reported of a hereditary muscle disease in her family which could be identified as familial hyperkalaemic periodic paralysis. In patients with familial periodic paralysis, only limited information is available in the current anaesthesiological literature. This is especially true of the hyperkalaemic form which was separated from the hypokalaemic form in 1957. Most patients suffering from periodic paralysis will develop myotonic symptoms in time, but evidence is lacking that the incidence of malignant hyperthermia (MH) is higher than in normals. However, abnormalities of the electrocardiogram (ECG) due to changes in the potassium serum levels are not unusual, and the anaesthesiologist must be aware of cardiac arrhythmias. In the present case, the patient was anaesthetized using fentanyl, midazolam, and vecuronium, and ventilated with 66% nitrous oxide in oxygen. Radial artery blood pressure, end-tidal CO2, and nasopharyngeal temperature were monitored continuously. Surgery was completed after 2 hours with no abnormalities in the intraoperative course. Recovery from anaesthesia was uneventful. During the postoperative follow-up for 1 week, further attacks of paralysis, intermittent sodium-potassium imbalance of the muscle cell membrane appears to be the primary pathogenetic factor. In this special disease, prevention of carbohydrate depletion and the avoidance of muscle relaxants are recommended in the anaesthesiological literature. However, a specified regimen of general anaesthesia has not yet been outlined. In our special case, the use of anaesthetics deemed to be safe in MH susceptible patients produced an uneventful perioperative course.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Anesthesia in familial hyperkalemic periodic paralysis]. 832 4

We report on the occurrence of cardiac arrests within a few minutes following succinylcholine in 9 children, all of whom were later shown to have occult neuromuscular disease. Five of the children did not survive the catastrophic event. The anaesthetist in most cases, when discussing premedication, got the impression that the patients were in good health; just in 2 children were there indications of myopathy. Myopathic children coming to surgery and anaesthesia are rare. In these cases the administration of succinylcholine is contraindicated. But the anaesthetist must be aware of the fact that a small number of paediatric patients with unknown/subclinical myopathies might be referred to him. In these cases, without warning muscle rigor, bradycardia and hyperkalemia cardiac arrest may develop within minutes following administration of succinylcholine. The anaesthetist must be prepared for such a challenging event--particularly mentally. Misinterpretation of the symptoms as signs of malignant hyperthermia should be excluded. Resuscitation must start without delay and must continue for more than 30 minutes. Therapeutic attempts to lower extracellular potassium with glucose and insulin must fail for pharmacokinetic reasons. Therapy with intravenous calcium under control of the e.c.g. seems to be the only rational approach to the problem. It is suggested that in every healthy child coming to anaesthesia the physician should consider whether relaxation could not be achieved by other agents. Succinylcholine may well be defined as a "membrane poison"--especially considering the efflux of potassium, myoglobin and creatine kinase from the intracellular space into the bloodstream. The answer to the question asked in the title must therefore be: definitely--yes.
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PMID:[Should the use of succinylcholine in pediatric anesthesia be re-evaluated?]. 836 12

We report two boys aged 4 and 10 months who suffered cardiac arrests after induction of anaesthesia. Both infants had no personal or family history of myopathy. In both cases anaesthesia was induced by inhalation with halothane and N2O/O2 (70/30). To facilitate tracheal intubation both were given succinylcholine after the administration of atropine. The 4-month-old developed muscle rigidity and cardiac arrest occurred immediately after tracheal intubation. Resuscitation was unsuccessful. Laboratory findings during resuscitation showed elevated serum potassium levels of more than 10 mmol/l and serum creatine phosphokinase 17.700 IU/l. Histopathologic examination of the skeletal muscle revealed congenital muscular dystrophy. In the older boy no muscle contractures were noted after administration of succinylcholine. He developed bradycardia that progressed to asystole 15 min after induction of anaesthesia. After 1 h of resuscitation a sinus rhythm could be established. The boy developed myoglobinuria and his serum creatine phosphokinase reached a maximum level of 45,000 IU/l on the 2nd day. The child survived and made a complete recovery. Two months later a muscle biopsy taken from the quadriceps showed marked muscular dystrophy. Duchenne's muscular dystrophy could be excluded. The most likely underlying reasons for these complications are discussed: anaesthesia-induced acute rhabdomyolysis or malignant hyperthermia.
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PMID:[Anesthetic-induced heart arrest. A case report of 2 infants with previously unrecognized muscular dystrophy]. 844 72

The purpose of this study was to show the behaviour of the plasma level of catecholamines in stress-susceptible pigs during an acute stress and to gain new insights in the role of catecholamines in the initiation of malignant hyperthermia. Therefore, a halothane challenge test was performed in stress-susceptible growing pigs, and the changes of haematocrit, hormones and metabolites were monitored during the handling before the test, during halothane exposure and thereafter. Already in connection with the handling before the test, haematocrit values and plasma levels of epinephrine, norepinephrine, glucose, lactate and potassium increased significantly. However, the plasma concentration of cortisol and free glycerol increased gradually and the level of nonesterified fatty acids did not show any changes. While the levels of catecholamines and potassium decreased already during halothane exposure, haematocrit values and concentrations of glucose and lactate continued to increase. The present results indicate that the catecholamines are not involved in the initiation of malignant hyperthermia.
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PMID:[Effect of acute stress on plasma levels of catecholamines and cortisol in addition to metabolites in stress-susceptible growing swine]. 899 69

In 1992, the Malignant Hyperthermia Association of the United States and The North American Malignant Hyperthermia Registry received reports of cardiac arrest in apparently healthy children given succinylcholine. Using data from 1990 to 1993, this study analyzes: (1) etiology of all reported pediatric arrests and (2) whether survival was associated with certain patient or treatment variables. We reviewed retrospectively all reports of pediatric (age < 18 years) arrests occurring within 24 hours of anesthesia. Etiology of arrests and presence of myopathy were determined. Twenty-five patients (92% male, median 45 months old) arrested; 23/25 (92%) were scheduled for minor surgery. Before receiving a potent inhalational anesthetic (92%) and/or succinylcholine (72%), these patients were evaluated by the anesthesiologist as being healthy with no personal or family history of myopathy. Serum potassium during arrest was measured in 18/25 (72%) patients; hyperkalemia (mean [K+] = 7.4 +/- 2.8, median 7.5 mmol/L) was detected in 13/18 (72%) patients. Postarrest resuscitations lasted a median of 42 minutes (range 10-296). Ten (40%) patients died, 1 (4%) is vegetative, and 14 (56%) returned to baseline neurologic function. A previously unrecognized Duchenne dystrophy (n = 8) or unspecified myopathy (n = 4) was diagnosed in 12 (48%) patients. Eight of these 12 patients' arrests were associated with hyperkalemia. Ten (40%) patients had no postarrest evaluation to exclude occult myopathy. No patient or treatment variables were statistically associated with survival. We conclude that, whenever possible, pediatricians should evaluate their patients (especially male infants and children) preoperatively for the presence of occult myopathy. During perianesthetic resuscitations, the pediatric advanced life support protocol should be modified to detect and treat hyperkalemia, a potentially reversible state even after prolonged resuscitation efforts. Following anesthetic deaths, pathologists should examine body fluid electrolytes and skeletal muscle for myopathy and dystrophin. If a preanesthetic creatine kinase screen for myopathy in male patients and restrictions on succinylcholine had been used, 64% of arrests and 60% of deaths might have been prevented. A formal prospective risk/benefit analysis for preventive measures is needed.
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PMID:Hyperkalemic cardiac arrest during anesthesia in infants and children with occult myopathies. 900 42

Recent advances in the field of molecular myology have provided significant insight into the pathological mechanisms underlying a variety of neuromuscular disorders. Genetic abnormalities can now be linked to primary and secondary pathophysiological changes in muscle fibres which compromise structural, metabolic, regulatory or contractile mechanisms. Ion channel myopathies such as paramyotonia congenita, hyper- and hypokalaemic periodic paralysis, myotonia congenita, episodic ataxia and malignant hyperthermia were established as linked to mutations in genes encoding the sodium channel, dihydropyridine receptor, chloride channel, potassium channel and the ryanodine receptor calcium release channel, respectively. Metabolic disorders affecting skeletal muscle were found to be due to deficiencies in a variety of enzymes. Identification of defects in components belonging to the gigantic dystrophin-glycoprotein complex led to the discovery of the molecular pathogenesis of Duchenne muscular dystrophy and related disorders. Based on these molecular findings, it is now feasible to design and evaluate new techniques such as gene and myoblast transfer therapy in order to replace defective components in diseased muscle fibres.
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PMID:[Molecular pathogenesis of muscular diseases]. 903 37

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.
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PMID:Chromosomal localization of 15 ion channel genes. 903 51

Among all the drugs used for general anaesthesia, neuromuscular blockers appear to play a prominent role in the incidence of severe adverse reactions. It now seems likely that most serious adverse drug reactions occurring during anaesthesia are immunological in type. The frequency of life-threatening anaphylactic or anaphylactoid reactions occurring during anaesthesia has been estimated to be between 1 in 1000 and 1 in 25,000 anaesthetic procedures, with the neuromuscular blockers being involved in 80% of cases. The mortality from such serious reactions is reported to be in the range of 3.4 to 6%. The highly immunogenic drug, suxamethonium chloride (succinylcholine), was found to be the most hazardous agent. Drug-specific immunoglobulin E antibodies to suxamethonium chloride and other neuromuscular blockers have been demonstrated. This sensitivity to neuromuscular blockers seems to be a long-lasting phenomenon. During anaesthesia, the clinical features of an allergic reaction are often masked. Tachycardia and circulatory collapse may be the only signs of an allergic reaction, and they are easily misdiagnosed. Bronchospasm is reported to be present in about 40% of cases. Successful management of these patients includes stabilisation during the acute reaction and avoidance of future reactions. The latter is based on the identification of the causative drug and potentially cross-reacting compounds. The use of suxamethonium chloride is associated with many other adverse effects, such as fasciculations, myalgia, potassium release, changes in the heart rate, increases in intragastric and intraocular pressures, and malignant hyperthermia. Because of the dangers of hyperkalaemic cardiac arrest after suxamethonium chloride administration in children with unrecognised muscular dystrophy, there have now been moves to limit the use of this drug in children. Although neuromuscular blockers are designed to specifically block nicotinic cholinergic receptors at the neuromuscular junction, many bind to muscarinic cholinergic receptors on ganglia and smooth muscle, and alter parasympathetically mediated heart rate and airway calibre. Most benzylisoquinolinium muscle relaxants can induce histamine release, especially when they are administered rapidly, which can lead to disturbances of cardiovascular function. In addition, nondepolarising neuromuscular blockers have been implicated in causing generalised weakness following their long term administration to patients on an intensive care unit. The problem with these adverse drug reactions is their unpredictable nature. Therefore, prompt recognition with appropriate therapy can help to improve the outcome.
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PMID:Adverse effects of neuromuscular blockers and their antagonists. 951 17

The relationship between blood pressure and sodium (Na) excretion is less steep in hypertension caused by increased renal tubular reabsorption. We recently demonstrated that one mutation in rat alpha-adducin gene: (1) is responsible for approximately 50% of the hypertension of MHS rats, and (2) stimulates tubular Na-K pump activity when transfected in renal epithelial cell, suggesting that its pressor effect may occur because an increased tubular reabsorption. Linkage and association studies demonstrated that the alpha-adducin locus is relevant for human hypertension. A point mutation (G460W) was found in human alpha-adducin gene, the 460W variant (G/W) is more frequent in hypertensives than in normotensives. The aim of this study was to test whether acute changes in body Na may differently affect blood pressure in humans as a function of alpha-adducin genotype. The pressure-natriuresis relationship was analyzed in 108 hypertensive using two different acute maneuvers: Na removal (furosemide 25 mg p.o.) and, two days later, Na load (310 mmoles i.v. in 2 hr). We found that 80 patients were wild-type homozygous (G/G), 26 were G/W heterozygous, and 2 were W/W homozygous with similar blood pressure, age body mass index, gender, plasma and urinary sodium and potassium. In basal condition G/W-W/W patients showed a lower plasma renin activity and fractional excretion of Na. In either case the pressure-natriuresis relationship was less sleep in G/W-W/W than in G/G patients, obviously negative for Na depletion with furosemide (-0.011 +/- 0.004 vs. -0.002 +/- 0.002 mm Hg/mumol/min, P < 0.03), and positive for Na load (0.086 +/- 0.02 vs. 0.027 +/- 0.007 mm Hg/mumol/min, P < 0.001). The finding of reduced slope after Na depletion or Na load supports the hypothesis that, as MHS rats, humans bearing one W alpha-adducin variant display an increased of renal tubular sodium reabsorption.
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PMID:Alpha-adducin polymorphisms and renal sodium handling in essential hypertensive patients. 960 77


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