Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026837 (muscle rigidity)
 1,077 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malignant hyperthermia (MH) is a rare clinical syndrome characterized by hypermetabolism and triggered by specific anesthetic agents. The mechanism of this abnormal reaction is due to uncontrolled calcium flux in the skeletal muscles resulting in a variable clinical syndrome of muscle rigidity, respiratory and metabolic acidosis, and elevation of temperature. The specific genetic defect underlying this condition has not been identified in humans, though in susceptible swine a mutation of the gene for the ryanodine receptor, a large protein which comprises the calcium channel in the sarcoplasmic reticulum, has been identified recently. Inheritance in humans appears to be autosomal dominant with variable penetrance. Patients with MH rarely have physical or laboratory signs of muscle disease. However, scattered case reports and investigations of individuals with known myopathies and other muscle related problems, such as acute rhabdomyolysis or idiopathic persistently elevated creatine kinase, suggest a possible association of MH with a variety of neuromuscular diseases and stress syndromes. This association is very strong in the case of central core disease (CCD) where it is supported by clinical and laboratory evidence, including the proximity of the CCD gene to the ryanodine receptor gene on chromosome 19. A variety of other diseases have been implicated and can be classified as possibly associated (King-Denborough syndrome, Duchenne muscular dystrophy) or unlikely to be associated (myotonia congenita, sudden infant death syndrome, limb girdle dystrophy, neuroleptic malignant syndrome, etc.).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Malignant hyperthermia and neuromuscular disease. 148 40

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle. In humans, MH is inherited in an autosomal dominant fashion; in swine, the principal model for MH, it is in a recessive fashion. Those with MH susceptibility usually are asymptomatic except in the presence of certain "triggering" anaesthetic agents such as isoflurane, enflurane and the muscle relaxant succinylcholine. Upon such exposure hypermetabolism, increased CO2 production, acidosis, muscle rigidity, rhabdomyolysis and hyperthermia occur. Untreated, death may result in 70% of patients. With prompt diagnosis and treatment with dantrolene sodium, the mortality is less than 10%. The overall incidence of MH is low (perhaps 1:50,000 anaesthetics), but it is more common in children. Children also display a paradoxical increase in jaw muscle tone to succinylcholine which often presages MH, but confusing clinically, may also be a normal response to succinylcholine. The pathophysiology of MH centres around a defect in calcium flux in skeletal muscle. A specific base pair change in the gene that codes for the ryanodine receptor calcium channel in muscle has been demonstrated in susceptible swine, but occurs rarely in humans. It is hoped that the understanding of the molecular genetics of MH will lead to a simpler diagnostic test than is currently available, and enhance our understanding of MH and its relation to other myopathies.
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PMID:An update on the malignant hyperthermia syndrome. 771 Feb 42

The most venomous scorpion species are Buthotus tamulus of India, the Leiurus quinquestriatus and Androctonus crassicauda of North Africa and the Middle East, the Tityus serrulatus of Brazil, and the Centruroides suffussus of Mexico. The severity of scorpion envenomation varies with the scorpion's species, age, and size, and is much greater in children. Systemic intoxication reflects the overstimulation of the CNS, the sympathetic and parasympathetic nervous system. Severity ranges from local pain and paresthesia to fatal cardiotoxicity and encephalopathy. Symptoms include: agitation, tachycardia, vomiting, abdominal pain, salivation, diaphoresis, dehydration, muscle rigidity and twitching, tremor, seizures, coma, pupillary changes, hyperthermia, tachyarrythmias and occasionally bradyarrhythmias, hypertension, and less often hypotension, cardiac failure, and priapism in males. Laboratory abnormalities include: hyperglycemia, leucocytosis, transient elevation of cardiac and pancreatic enzymes, ischemic changes in the ECG, and evidence of cardiac dysfunction on echocardiography. The principles of management are: observation, cardiac monitoring, supportive treatment with intravenous fluids and electrolytes, and a meticulous use of cardiovascular agents: vasodilators, adrenergic antagonists, or calcium channel blockers in the hypertensive phase; and inotropic agents in the event of hypotension. Antiarrhythmics such as lidocaine, may be required. There is increasing evidence for the efficacy of specific antivenom. The advance in supportive care and antivenom efficacy has markedly improved the outcome of patients with scorpion envenomation.
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PMID:Clinical manifestations and management of scorpion envenomation. 1044 63

Besides antipsychotics, several drugs can induce parkinsonism. We review spontaneous notifications of drug-induced or -worsened parkinsonism to a French regional pharmacovigilance center between 1993 and 2009. During these 17 years, 20,855 adverse drug reactions have been reported, including 155 (0.7%) cases of drug-induced or -worsened parkinsonism. Most of the notifications have involved aged patients (48% between 60 and 79 years) and females (60%). "Seriousness" was found in 43.9% of cases. Worsening of parkinsonism occurred in 28 patients suffering from idiopathic Parkinson's disease. Sixty-nine percent of drug-induced or -worsened parkinsonism cases were observed during the first 3 months after introduction of the "suspect" drug (involving mainly central dopaminergic antagonists). A second peak (20%) was found 12 months after drug introduction (mainly caused by calcium channel blockers). The most frequently reported parkinsonian symptom was rigidity (78.7%). The three cardinal symptoms were found in 37.4% of notifications. Evolution was favorable (after partial or complete withdrawal of suspect drug[s]) in 88.7% of cases. Among the 261 suspect drugs, most involved central dopaminergic antagonists (49%), followed by antidepressants (8%), calcium channel blockers (5%), peripheral dopaminergic antagonists (5%), and H1 antihistamines (5%). Cases with lithium, valproic acid, amiodarone, anticholinesterases, or trimetazidine were also found. Three notifications were the result of pharmacokinetic interactions. We found that drug-induced or -worsened parkinsonism is an often "serious," but reversible, adverse drug reaction. It occurred more frequently between 60 and 79 years. Rigidity was the most frequently reported symptom. Approximately 50% of drug-induced or -worsened parkinsonism cases spontaneously reported were related to drugs other than antipsychotics. Drug-induced or -worsened parkinsonism can also be explained by pharmacokinetic drug interactions.
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PMID:Drug-induced parkinsonism: a review of 17 years' experience in a regional pharmacovigilance center in France. 2167 26