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)

Enzymatic properties of erythrocyte membranes in Duchenne muscular dystrophy (DMD) and malignant hyperthermia (MH), two genetically determined abnormalities of skeletal muscle, were examined. Acetylcholinesterase (AChE) and ATPase activities were chosen for investigation since alterations in these enzymes have been demonstrated in animal models of dystrophy. A significant decrease in Na+,K+-ATPase activity was noted in DMD patients and a number of possible DMD carriers, suggesting that this enzyme may provide a useful marker of the carrier state in carriers not exhibiting an elevation in plasma creatine phosphokinase activity. No abnormalities in AChE were demonstrable in any of our DMD patients, indicating that human dystrophy is biochemically distinct from certain animal models of dystrophy (e.g., dystrophic mice) where erythrocyte AChE is decreased. In contrast, evidence was found in two known MH carriers, who had normal erythrocyte ATPase activities, for the presence of an altered membrane AChE characterized by an increase in substrate affinity and a large decrease in maximal hydrolytic rate. While the exact relevance of this membrane defect, if any, to the pathogenesis of MH remains to be seen, the presence of this modified enzyme may serve to identify those individuals in a family where a positive history of MH exists who are at risk of developing a hyperthermic crisis during anesthesia.
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PMID:Erythrocyte membrane enzyme abnormalities in two hereditary disorders of muscle. 23 Oct 77

The muscle biopsy from a 12-year-old boy with chronic creatine kinase elevation was studied by electron microscopy. At the age of 7 years the patient had a possible abortive attack of malignant hyperthermia. The biopsy specimen contained many fibres with segmental contracture and necrosis; thin sections showed defects of the plasma membrane with loss of glycogen granules into the interstitium. Freeze-fracturing of the plasma membrane showed clustering of intramembranous particles and some membrane areas were devoid of particles and of pinocytotic caveolae. The E-face showed irregular elevations and the P-face corresponding defects. These deviations of the fracture-plane were due to manifest membrane openings, to abnormalities of the structure of the lipid bilayer, to clustering of membrane particles or to the fact that intracellular membranes often were abnormally close to the plasma membrane. The findings suggest that a disintegration of the lipid-protein system of the membrane precedes the formation of manifest defects. The manifest defects resembled those in Duchenne muscular dystrophy. It is unknown whether the changes seen by freeze-fracturing were specific for a myogenic disorder and whether they were due to a basic membrane abnormality or to defects in other systems of the muscle cell.
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PMID:A freeze-fracture study of the plasma membrane of muscle fibres of a patient with chronic creatine kinase elevation suspected for malignant hyperthermia. 44

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

We studied 27 Duchenne muscular dystrophy patients having spinal fusion for scoliosis. One patient died intraoperatively of cardiac arrest; all others have done well with no instances of malignant hyperthermia, postoperative ventilatory system dependence, pneumothorax, persisting infection, neurologic damage, nonunion, or pain. The anesthetic management included primarily intravenous general anesthetics with minimal myocardial depressant effects, avoiding succinylcholine and inhalation agents. Preoperative cardiac studies aided anesthetic management intra-operatively. There was an almost universal sinus tachycardia. Holter monitoring defined 4 of 16 with ventricular premature beats, 4 of 16 with atrial premature beats, and no ventricular tachycardia or atrial flutter or fibrillation. Echocardiogram demonstrated mitral prolapse in 2 of 22, frequent abnormal systolic performance with abnormal shortening fraction less than 28% in 7 of 16, and reduced rate-corrected velocity of fiber shortening in 9 of 15. Afterload was elevated in 7 of 15. The mean forced vital capacity (FVC) preoperatively was 45.3 +/- 15.9% with continuing diminution to 28.7 +/- 14.9% at 3.3 +/- 2.2 years after surgery. The main benefit of surgical stabilization is the relative ease and comfort of wheelchair seating compared with those nonoperated patients who develop progressive deformity. We have not seen lasting improvement or stabilization in FVC following surgery as decreasing function is related primarily to muscle weakness.
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PMID:Spinal fusion in Duchenne muscular dystrophy: a multidisciplinary approach. 158 53

Two 2-year-old males underwent muscle biopsy that established the histopathologic diagnosis of Becker dystrophy in one, and Duchenne dystrophy in the other. Concomitant contracture testing with caffeine or halothane was normal for malignant hyperthermia (MH). The results suggest that acute hypermetabolism or acute rhabdomyolysis during anesthesia, in patients with these disorders, is related to the X-linked myopathy and its associated muscle deterioration, rather than to the autosomal dominant MH.
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PMID:Absence of malignant hyperthermia contractures in Becker-Duchenne dystrophy at age 2. 173 62

The genetics of malignant hyperthermia (MH) are ill-understood; however, the association of Duchenne muscular dystrophy (DMD) with MH is well known. A deficiency of dystrophin is common to both the DMD and mdx mouse, an animal model for DMD. Using muscle contracture tests for MH, we have shown that in the mdx mouse there is no MH susceptibility, suggesting the lack of a direct role of the dystrophin in the development of MH syndrome.
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PMID:Negative halothane-caffeine contracture test in mdx (dystrophin-deficient) mice. 189 52

So far there is no causal treatment for Duchenne muscular dystrophy up to now, it has been proven, however, that its course can be considerably improved by an early contracture-prophylactic operation of both lower limbs--mostly between age 4 and 6 years--as well as by a surgical stabilization of the spine before any progressive scoliosis appears, that is at the very beginning of the wheel-chair stage: Walking and standing ability can be prolonged for several years and a significant scoliosis can be avoided. A decisive prolongation of life can be achieved by treating the fatal respiratory insufficiency with timely started mechanical ventilation. Our first experiences have shown, that there is no proven justification for a reserved attitude against early lower limb surgery in view of modern anaesthesia. Malignant hyperthermia-reaction and hyperkalaemia are the known anaesthetic rise factors of operations in Duchenne muscular dystrophy. However, we could exclude virtually these rises by choosing the right anaesthesia and by a comprehensive monitoring routine. If need be, malignant hyperthermia can be treated effectively by using the obligatory antidote (Dantrolene). In view of an expected causal treatment in future, early detection of Duchenne muscular dystrophy by newborn screening ("CK-Test") as well as a comprehensive stage-depending treatment programme (early surgery/mechanical ventilation) are nowadays of outstanding importance.
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PMID:[Duchenne muscular dystrophy--contracture preventive operations of the lower extremities with special reference to anesthesiologic aspects]. 202 63

The concept of the cytosolic homeostasis of calcium is presented, and the mechanisms by which a very low cytosolic concentration of Ca is maintained are considered. The transient increase of intracellular Ca2+ when muscles fibres are stimulated illustrates the role of Ca as an intracellular messenger. The author presents his own kinetic analysis of the interaction of Ca with several intracellular targets and describes the Ca translocations which take place. Two examples of deficiency in the control of the intracellular Ca2+ are examined: malignant hyperthermia and Duchenne muscular dystrophy.
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PMID:[Control and kinetics of intracellular calcium movement in striated muscle]. 248 52

The association of malignant hyperthermia (MH) with neuromuscular disorders has been recognized since 1970. These disorders include central core disease, Duchenne muscular dystrophy, myotonia congenita, myotonic dystrophy, nonspecific myopathies, and King-Denborough syndrome. In order to assess the anesthetic risk of MH in the neuromuscular population, we performed halothane and caffeine contracture testing for MH susceptibility on biopsied muscle removed from 25 consecutive neuromuscular patients during diagnostic evaluation. Positive contracture tests were found in 7 of 18 patients with myopathic disorders and 3 of 7 patients with neurogenic disorders. Two of our patients had anesthetic events suggesting MH. These findings suggest that myopathic and neuropathic disorders share pathogenic mechanisms with MH, resulting in positive contracture tests and possibly leading to clinical events during anesthesia. Although there is controversy regarding the interpretation of a positive contracture test, contracture testing remains the most widely accepted test for MH susceptibility. Thus, a variety of neuromuscular disorders may be associated with MH susceptibility, and caution should be exercised during anesthesia in this group of patients.
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PMID:Halothane-caffeine contracture testing in neuromuscular diseases. 337 16

To evaluate malignant hyperthermia (MH) susceptibility in X-linked muscular dystrophies, halothane and caffeine contracture tests were performed on muscle fiber bundles from five patients with Duchenne muscular dystrophy (DMD) and two patients with Becker muscular dystrophy (BMD). Two DMD patients and one BMD patient had positive contracture tests. Since a positive contracture test is currently the best indicator of anesthetic susceptibility in the MH population, and episodes of MH in dystrophic patients have been reported, patients with DMD and BMD may be at risk for developing similar anesthetic complications. Awareness of this potential anesthetic risk is of importance because orthopedic interventions are increasingly more common in these patients.
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PMID:Malignant hyperthermia susceptibility in X-linked muscle dystrophies. 350 9


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