Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024591 (malignant hyperthermia)
 2,353 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The case histories are presented including the anaesthetic and postoperative management, of two children, a two-year-old with undiagnosed Duchenne muscular dystrophy (DMD) and a three-year-old with known DMD. The child with undiagnosed DMD had no symptoms of DMD and had received halothane twice before, without succinylcholine, with no apparent difficulty. Following an uneventful induction of anaesthesia with halothane, nitrous oxide and O2, succinylcholine resulted in bilateral masseter muscle spasm and then, in rapid sequence, ventricular tachycardia and cardiac arrest. Resuscitation was difficult, prolonged and associated with hyperkalaemia (K+ = 12.57 mEq X L-1), severe metabolic and respiratory acidosis, high peripheral venous pressure and massive hepatosplenomegaly, but not hyperthermia. The patient was finally resuscitated but died two days later. Skeletal muscle biopsy results were consistent with malignant hyperthermia. The second patient was known to have DMD but did not receive prophylactic or intraoperative dantrolene nor have his anaesthetic machine flushed with oxygen for an extended period prior to induction of anaesthesia. This child was anaesthetized with fentanyl and N2O and, with the exception of a high intraoperative heart rate (155-160 beats X min-1), had an uncomplicated anaesthetic and operation (intraoperative axillary temperatures ranged between 36.8-37.9 degrees C). Postoperatively his temperature rapidly increased to 38.8 degrees C and then 40.3 degrees C and he became metabolically acidotic. Intravenous administration of dantrolene for 48 hours reduced the temperature and allowed normal recovery and discharge. A postoperative muscle biopsy was consistent with DMD.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Duchenne muscular dystrophy and malignant hyperthermia--two case reports. 374 23

We report a patient with Duchenne muscular dystrophy who developed malignant hyperpyrexia during general anaesthesia. During anaesthesia bradycardia was followed by ventricular fibrillation, on which ventricular flutter supervened and a body temperature rise of 0.6 degrees C for 15 minutes, myoglobinuria and elevation of CPK level were observed. The caffeine sensitivity test of biopsied muscle fibers revealed an increase in sensitivity, although there was no sign of muscle rigidity during or after anaesthesia. Diagnosis of Duchenne muscular dystrophy was first established after the development of malignant hyperpyrexia in the present case as well as in previously reported cases. Determination of serum CPK is very important before general anaesthesia.
 ...
PMID:Malignant hyperpyrexia and Duchenne muscular dystrophy: A case report. 621 75

In myopathic disorders, abnormal serum enzyme activities are seen primarily in diseases of skeletal muscle where the condition involves the muscle fibers themselves. In denervation myopathies, serum enzyme activities are usually normal. The most dramatic increases of serum enzymes, particularly creatine kinase, are found in the dystrophic diseases, particularly Duchenne dystrophy. A review is given here of the many causes of abnormal serum enzyme activities where the source of enzymes is believed to be skeletal muscle. These include the dystrophies, various types of trauma, exercise, drug- and poison-induced causes including alcohol, malignant hyperthermia, inflammatory diseases, and miscellaneous causes. Tissue and serum activities are summarized for the commonly performed serum enzymes, i.e., CK, LD, AST, and aldolase. An extensive tabular and current description of the various types of dystrophies is given along with serum CK and pyruvate kinase activities.
 ...
PMID:The enzymology of skeletal muscle disorders. 637 45

Using the skinned fiber preparation, the response to caffeine was studied on the skeletal muscle of malignant hyperthermia or other neuromuscular diseases. The sensitivity to caffeine was increased in the muscle of malignant hyperthermia. The sensitivity also was increased in Duchenne muscular dystrophy or asymptomatic patients with raised serum creatine kinase activity. Judging from the interaction between caffeine and the contractile system, the abnormal response originated from the sarcoplasmic reticulum in malignant hyperthermia. In Duchenne muscular dystrophy, the contractile system also might be involved in the increased sensitivity. Since the disease spectrum presenting abnormal responses is broad, it is suggested that muscle fibers become sensitive to caffeine when they are degenerating or regenerating.
 ...
PMID:Malignant hyperthermia and related neuromuscular diseases: caffeine contracture of the skinned muscle fibers. 663 64

The evaluating of palmitate oxidation in muscle tissue may be a useful screening test for detecting defects in fatty acid metabolism in human neuromuscular disease. If the test is to be useful, it is necessary to obtain data on a wide variety of muscle illnesses for comparative purposes. We report our experience with palmitate oxidation, muscle carnitine, and carnitine palmityl transferase (CPT) activity in 148 muscles biopsies from a variety of illnesses. The efficacy of using total protein, citrate synthase, and (1-14C) pyruvate oxidation as internal references was investigated. Palmitate oxidation was significantly less than normal (P less than or equal to 0.01) in Duchenne muscular dystrophy, congenital nonprogressive myopathy, congenital muscular dystrophy, malignant hyperpyrexia, and denervation, depending on the internal reference used. Muscle carnitine levels followed a similar pattern, however, CPT activity did not. The possibility of these findings being secondary to inactivity is discussed.
 ...
PMID:Palmitate oxidation in human muscle: comparison to CPT and carnitine. 708 21

Malignant hyperthermia is a pharmacogenetic disorder of skeletal muscle that may cause a life-threatening reaction during administration of general anesthesia. It is inherited in an autosomal dominant pattern and, at least in some families, is caused by a mutation in the ryanodine receptor-calcium-release channel gene on chromosome 19. Malignant hyperthermia displays heterogeneity, making the development of a simple screening test difficult. Malignant hyperthermia may be caused by other biochemical defects affecting intramyoplasmic calcium. Some myopathies, such as central core disease, are frequently associated with malignant hyperthermia susceptibility. In other myopathies, like Duchenne muscular dystrophy, unusual compensatory mechanisms may produce a hypermetabolic state identical to that of malignant hyperthermia.
 ...
PMID:Malignant hyperthermia and associated disorders. 811 33

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.
 ...
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.
 ...
PMID:[Molecular pathogenesis of muscular diseases]. 903 37

The association between malignant hyperthermia (MH) and neuromuscular disorders is controversial. An association between MH and Duchenne muscular dystrophy, a common and lethal disorder caused by deficiency of dystrophin, has been reported sporadically but is still not proved. To examine this problem, we performed halothane and caffeine in vitro contracture tests on skeletal muscles from dystrophin deficient mdx mice, an animal model for human Duchenne muscular dystrophy. As neither halothane nor caffeine triggered abnormal responses in mdx muscles, we conclude that dystrophin deficiency per se is not the primary cause of MH-like crises, as reported for patients with Duchenne muscular dystrophy.
 ...
PMID:Dystrophin deficient mdx muscle is not prone to MH susceptibility: an in vitro study. 930 1

The expression of thrombomodulin and neural cell adhesion molecule (NCAM) was studied immunocytochemically in biopsied muscle specimens from 10 patients with rhabdomyolysis with different etiologic factors, including 5 with malignant hyperthermia. We have already reported that thrombomodulin was expressed on regenerating muscle cell membranes as well as on vessel walls in patients with various neuromuscular diseases, including Duchenne muscular dystrophy, Becker muscular dystrophy and inflammatory myopathy. We found increased expression of thrombomodulin not only on the sarcolemma, but also in the sarcoplasm of a fair number of muscle fibers in the acute phase of rhabdomyolysis. The granular pattern of thrombomodulin expression in the sarcoplasm seems to be a characteristic finding in the acute phase of rhabdomyolysis. Most muscle fibers which expressed NCAM on the sarcolemma also expressed thrombomodulin. However, the muscle fibers which expressed thrombomodulin in the sarcoplasm did not express NCAM, and showed a degenerative appearance on electron microscopic examination. These results suggest that thrombomodulin is expressed in the sarcoplasm during the acute degeneration phase of rhabdomyolysis in addition to the expression on the sarcolemma during the muscle fiber regeneration as shown in our previous study, and the former process, which is characterized by the granular expression of thrombomodulin in the sarcoplasm, may be a characteristic finding in rhabdomyolysis.
 ...
PMID:Characteristic expression of thrombomodulin in the muscle sarcoplasm in patients with the acute phase of rhabdomyolysis. 1076 59


<< Previous 1 2 3 4 Next >>