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)

A dramatic case of anaesthetic-induced malignant hyperpyrexia is described. The treatment (ice packs, treatment of acidosis, glucose-insulin, methylprednisolone, lidocaine, verapamil, muscular relaxation and oxygen breathing) was effective. In the discussion, the pharmacological effects on the cardiac muscle are considered predominantly.
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PMID:[A further case of malignant hyperpyrexia and its treatment with lidocaine, methylprednisolone and verapamil (iproveratril) (author's transl)]. 126 20

An increased glucose-induced insulin response has been observed in patients susceptible to malignant hyperpyrexia. This raises the possibility that the membrane abnormality present in the calcium-storing membranes in the muscle cell in malignant hyperpyrexia may be present also in the beta cell of the pancreas.
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PMID:Insulin secretion in malignant hyperpyrexia. 441 15

Resting metabolic rate and the energy cost of performing a specific (light work load on a bicycle ergometer were measured in nine subjects susceptible to malignant hyperpyrexia (MHS) and nine control subjects, both fasting and following a 600-kcal meal. Blood glucose, lactate, pyruvate and serum triglycerides, thyroxine, cortisol, creatine kinase, growth hormone, and calcium and potassium levels at rest and immediately following exercise, after fasting and eating, were measured. There was no evidence of increased heat production in the MHS subjects compared with controls. The MHS subjects, however, showed a complete absence of dietary-induced thermogenesis with exercise. Compared with the controls, MHS subjects had higher insulin levels for essentially the same blood glucose values. Triglycerides in the MHS group rose steadily over the course of the experiment, whereas in the controls they did not vary from the initial value. Lactate did not rise as much with exercise in the MHS group but did nor fall with rest, and pyruvate did not change from resting fasting values, whereas in the controls it rose steadily. Differences were also found in thyroxine and cortisol levels between the MHS and control groups. The shunting of blood away from thermogenic tissue is suggested as a mechanism for the absence of diet-induced thermogenesis with exercise in the MHS group and the possibility of an underlying abnormality of cardiovascular (sympathetic) control mechanisms in these subjects is discussed. The biochemical abnormalities are discussed in relation to previous biochemical data from MHS humans and pigs and in relation to the abolition of dietary-induced thermogenesis.
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PMID:Metabolic rate and blood hormone and metabolite levels of individuals susceptible to malignant hyperpyrexia at rest and in response to food and mild exercise. 724 57

Chromosome 19 is short but has higher relative density of genes than other chromosomes. Increasing number of the genes coding for proteins implicated in the pathogenesis of various human diseases have been mapped on chromosome 19. Mutations of low density lipoprotein receptor (LDL-R) result in one of the most frequent mendelian inherited disorder-familial hypercholesterolemia. Mutations of insulin receptor (INSR) are causative for rare syndromes of insulin resistance and some of non insulin dependent diabetes mellitus (NIDDM). Erythropoietin receptor (EPOR) mutations are causative for rare primary familial and congenital polycythemias (PFCP). Defects of one of the largest gene in the human genome RYR 1 (ryanodine receptor gene) (> 240 kb in size) accounts for majority of malignant hyperthermia (MH) and central core disease (CCD). All these disorders represent group of receptor diseases. The amplification of GCT trinucleotide repeats in myotonic dystrophy protein kinase (DMPK) gene is causative for myotonic dystrophy (DM) and represents a new class of human gene mutations: trinucleotide repeat mutations. Apolipoprotein E (APOE) locus plays a role in pathogenesis of the late onset familial Alzheimer's disease. Translocation of EA2 gene which encodes two helix-loop-helix (HLH) transcription proteins and its fusion with PBXI or hepatic leukemia factor (HLF) leads to the leukemogenesis in subgroup of ALL. Interestingly adeno-associated virus (AAV), currently widely used as vector for gene therapy has unique capability of specific integration into human chromosome 19q.
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PMID:Human genome--chromosome no. 19. 758 75

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

Malignant hyperthermia (MH) in humans is usually triggered by volatile anaesthetics and depolarizing muscle relaxants. However, other factors or drugs (e.g. cresol) are thought to induce MH. We report a case of fulminant MH associated with a ketoacidotic diabetic coma. After therapy for diabetic coma with insulin (containing the preservative cresol) and electrolyte solutions was started, the patient complained of increasing myalgia, developed a high fever and respiratory and metabolic acidosis and lost consciousness. MH was treated immediately with dantrolene; the patient recovered within 14 days. Five months later the patient was diagnosed as MH-susceptible by the in vitro caffeine and halothane contracture test. This case supports the assessment that MH and diabetes are associated diseases and that cresol could possibly trigger MH. Furthermore, therapy with dantrolene has been demonstrated to be beneficial in the treatment of MH associated with diabetic coma.
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PMID:Fulminant malignant hyperthermia associated with ketoacidotic diabetic coma. 888 Feb 51

Mitochondrial disorders encompass a group of syndromes produced by genetic defects that disrupt mitochondrial energy production. The impaired mitochondrial energy supply affects nearly all organs and tissues leading to a variable clinical presentation. The possible multisystem involvement complicates the management of anaesthesia and perioperative care. Exact knowledge of the path physiology of mitochondrial diseases may help to avoid perioperative anaesthesiological complications. This report describes the anaesthetic management of a patient with a mitochondrial disorder during combined pancreatic and renal transplantation, and discusses some of the anaesthetic implications of mitochondrial diseases. Due to the potential susceptibility of patients with mitochondrial diseases to malignant hyperthermia, anaesthesia was induced and maintained as total intravenous anaesthesia using propofol, alfentanil and cis-atracurium. In addition, the patient was treated intraoperatively with hydrocortisone (initial bolus of 50 mg followed by a continuous infusion of 4.8 mg/h) and insulin (continuous infusion of 2 IE/h) in order to manage the adrenocortical insufficiency as well as to treat the diabetes mellitus. Using this anaesthetic technique, satisfactory haemodynamic and metabolic conditions were achieved during surgery. The postoperative period, however, was marked by severe respiratory complications.
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PMID:[Anaesthesia for combined pancreatic and renal transplantation in a patient with mitochondrial encepahalomyopathy--a case report]. 1531 61

Hyperglycemic hyperosmolar nonketotic syndrome (HHNS) was infrequently diagnosed till recently. Now it is being diagnosed with increasing frequency in obese children with type 2 diabetes mellitus (T2 DM) and its incidence is likely to go up, given global increase in incidence of childhood obesity, increased insulin resistance, and T2 DM. The syndrome is characterized by severe hyperglycemia, a marked increase in serum osmolality and dehydration without accumulation of beta -hydroxybutyric or acetoacetic ketoacids. Significant ketogenesis is restrained by the ability of the pancreas to secrete small amount of insulin. Prolonged phase of osmotic diuresis leads to severe depletion of body water, which excees that of sodium, resulting in hypertonic dehydration. These children, usually obese adolescents with T2 DM, present with signs of severe dehydration and depressed mental status but continue to have increased rather than decreased urine output and are at increased risk of developing rhabdomyolysis and malignant hyperthermia. Emergency treatment is directed at restoration of the intravascular volume, followed by correction of deficits of fluid and electrolyte (Na+, K+, Ca++, Mg++, PO4++), hyperglycemia and serum hyperosmolarity, and a thorough search for conditions that may lead to this metabolic decompensation and their treatment. Use of iso-osomolar isotonic fluid (0.9% saline) until hemodynamic stabilization initially, followed by 0.45% saline with insulin infusion at the rate of 0.1 units/kg/hour, addition of 5% dextrose in fluids and reduction of insulin infusion once the blood glucose is 250 to 300 mg/dl is generally recommended. However, evidence-based guidelines about composition and tonicity of fluids and electrolyte solutions for early resuscitation and rehydration, the rate of infusion-rapid vs slow, and insulin dose-low vs normal, in treatment of HHNS in children are awaited. Careful monitoring of glucose levels and ensuring adequate hydration in patients 'at risk' of HHNS, including those receiving medications that interfere with the secretion or effectiveness of insulin should decrease the risk of HHNS.
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PMID:Hyperglycemic hyperosmolar nonketotic syndrome. 1644 62

Human skeletal muscles contain the largest single pool of K+ in the body (2600 mmol, 46 times the total K+ content of the extracellular space). Intense exercise may double arterial plasma K+ in one min. This is because of excitation-induced release of K+ from the working muscle cells via K+ channels. This hyperkalemia is rapidly corrected by reaccumulation of K+ into the muscle cells via Na+,K+ pumps, often leading to hypokalemia. Hyperkalemia may also arise from muscle cell damage, excessive oral or intravenous administration of K+, acidosis, renal failure, depolarization of muscle cells with succinyl choline, activation of K+ channels by fluoride poisoning, hyperkalemic periodic paralysis, malignant hyperthermia, inhibition of the Na+,K+ pumps by digitalis glycosides or treatment with nonselective beta blockers. Hyperkalemia may cause arrhythmia and can be treated with beta2 agonists, insulin or hemodialysis. Hypokalemia may be induced by the stimulation of the Na+,K+ pumps in skeletal muscles seen postexercise, or by catecholamines, beta2 agonists, pheochromocytoma, theophylline, caffeine or insulin, by sepsis, myocardial infarction, trauma, burns and heart failure. Rare causes are hypokalemic periodic paralysis, inhibition of K+ channels by barium, chloroquine or barbiturates. Hypokalemia often reflects dietary K+ deficiency, alkalosis, renal or gastrointestinal loss of K+. Hypokalemia is more likely to cause arrhythmia than hyperkalemia and can be treated by oral or intravenous administration of K+ under frequent control of electrocardiogram and plasma K+. Because of their size and high contents of K+, Na+,K+ pumps and K+ channels, the skeletal muscles play a central role in the acute, from min-to-min ongoing regulation of plasma K+. This is decisive for the maintenance of muscle contractility and heart function.
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PMID:Hormonal and pharmacological modification of plasma potassium homeostasis. 2061 71

Malignant hyperthermia (MH) and central core disease in humans have been associated with mutations in the skeletal ryanodine receptor (RyR1). Heterozygous mice expressing the human MH/central core disease RyR1 R163C mutation exhibit MH when exposed to halothane or heat stress. Considering that many MH symptoms resemble those that could ensue from a mitochondrial dysfunction (e.g. metabolic acidosis and hyperthermia) and that MH-susceptible mice or humans have a higher than normal cytoplasmic Ca(2+) concentration at rest, we evaluated the role of mitochondria in skeletal muscle from R163C compared with wild type mice under basal (untriggered) conditions. R163C skeletal muscle exhibited a significant increase in matrix Ca(2+), increased reactive oxygen species production, lower expression of mitochondrial proteins, and higher mtDNA copy number. These changes, in conjunction with lower myoglobin and glycogen contents, Myh4 and GAPDH transcript levels, GAPDH activity, and lower glucose utilization suggested a switch to a compromised bioenergetic state characterized by both low oxidative phosphorylation and glycolysis. The shift in bioenergetic state was accompanied by a dysregulation of Ca(2+)-responsive signaling pathways regulated by calcineurin and ERK1/2. Chronically elevated resting Ca(2+) in R163C skeletal muscle elicited the maintenance of a fast-twitch fiber program and the development of insulin resistance-like phenotype as part of a metabolic adaptation to the R163C RyR1 mutation.
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PMID:Basal bioenergetic abnormalities in skeletal muscle from ryanodine receptor malignant hyperthermia-susceptible R163C knock-in mice. 2097 28


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