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Query: UMLS:C0024591 (malignant hyperthermia)
 2,353 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malignant hyperthermia is a rare but severe complication of modern anesthesia, induced by halothane and succinylcholine. The syndrome is characterized by a rapid sustained and extreme rise in body temperature associated with muscular rigidity, tachycardia, tachypnoea and cyanosis. The lethality is about 60%. The present paper describes the histological, histochemical and electron microscopical findings performed on muscle biopsies of 3 patients with malignant hyperthermia (1 patient died) and a so called risk patient. In all patients morphological findings consistent with a pre-existent myopathy were found. Histologically there were acute necrotic muscular fibers as well as in types I and II, variations in the fiber diameter and centralization of the nuclei. In two cases even fibers that had a normal aspect in HE slides, showed a pathologic pattern after phosphorylase reaction. In addition to acute rhabdomyolysis, electron-microscopic investigations revealed cystic expansion of the cisterns of the sarcoplasmic reticulum with a peculiar proliferation of the sarcolemma. In a degenerating mitochondrium, a crystalline inclusion was identified. These findings support the pathogenetic concept of Britt and coworkers of a functional defect in the calcium release or binding mechanism of sarcoplasmic reticulum. Since it is known that malignant hyperthermia has a familial predilection, it seems very important that clinical, biochemical, and morphological investigations be performed such as CPK estimations and muscular biopsies not only of the patients but also of the relatives in order to rule out this type of latent myopathy.
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PMID:[Histological, histochemical, and ultrastructural findings in malignant hyperthermia (author's transl)]. 80 99

In the present communication, an investigation is described into the reliability of histochemical methods for the demonstration of alpha-glucan phosphorylase activity in glycogen-depleted skeletal muscle fibres. Human skeletal muscles with glycogen-depleted fibres from patients with diseases of the neuromuscular system and from subjects who had suffered from malignant hyperthermia were used for the study. The location of phosphorylase activity and glycogen was demonstrated with histochemical techniques. Biochemical techniques were used to assay the activity of phosphorylase and the content of glycogen. Biochemical determinations of phosphorylase activity did frequently not reveal significant differences between glycogen-depleted and non-depleted skeletal muscle fibres. In contrast, all histochemical methods investigated, showed little or no phosphorylase activity in the glycogen depleted fibres, indicating that none of the existing histochemical methods revealed reliable staining results in these fibres. Owing to the invalid staining results of the histochemical methods for glycogen-depleted muscle fibres, it is necessary that for metabolic studies a biochemical assay for phosphorylase activity is also to be performed.
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PMID:Pitfalls in the histochemical demonstration of alpha-glucan phosphorylase activity in glycogen-depleted skeletal muscle fibres. 164 6

In malignant hyperthermia, myophosphorylase reaction shows characteristic changes that take place within minutes: (1) a generally strongly weakened reaction; (2) numerous negatively reacting fibres; (3) frequently, fibre sections that show spotty and/or striatal weak or negative reactions and fibre sections with strong striatal reactions with relatively narrow sarcomere spacings (a "sign of hypercontraction"). Obviously, the morphological findings that show characteristic "striated fibres" are typical of the malignant hyperthermia syndrome! It is important to note that the muscular fibres showing such changes are, as a rule, inconspicuous when using other stains and reactions. These pathological myophosphorylase reactions were observed in five deceased patients (one independently of anaesthesia after an extended walk) and in 19 pigs (18 times after halothane testing and once in an experimental animal with clinical evidence of the presence of malignant hyperthermia). These reactions were not noted in pigs with negative halothane reactivity or prior to halothane testing. They were also not seen in a large number of very different healthy and diseased control and reference cases from our biopsy and autopsy material. Myophosphorylase reaction enables convincing demonstration of malignant hyperthermia, past or present. Hence, it is possible to elucidate puzzling deaths or verify apparently clear death occurring during or subsequent to anaesthesia or simply following stress ("human stress syndrome"). Many of these deaths doubtlessly escape the attention of clinicians using the usual morphological examination methods. However, the reaction cannot be used to identify potential victims.
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PMID:[Pathological myophosphorylase reaction in malignant hyperthermia]. 405 Jan 36

Malignant hyperthermia occurs in humans with several congenital myopathies, usually in response to general anesthesia. Commonly, individuals who develop this syndrome lack symptoms of muscle disease, and their muscle lacks specific pathological changes. A biochemical marker for this myopathy has not previously been available; we found activity of adenylate cyclase and content of cyclic AMP to be abnormally high in skeletal muscle. Secondary modification of protein phosphorylation could explain observed abnormalities of phosphorylase activation and sarcoplasmic reticulum function.
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PMID:High skeletal muscle adenylate cyclase in malignant hyperthermia. 627 6

The ratio of muscle phosphorylase a to total phosphorylase, expressed as a percent, was determined in vastus lateralis muscle of 26 patients to examine the efficacy of this parameter as a method for screening for susceptibility to malignant hyperthermia (MH). As standard screening, all patients also had muscle contracture responses determined to 2% halothane and 0.25-32 mM caffeine at 37 degrees C. Each drug was given separately and not combined. Nine patients were susceptible to MH, based upon caffeine threshold of 2 mM or less (seven patients) or a rapidly developing contracture tension to halothane of more than 400 mg (seven patients, including five with positive caffeine responses). Mean phosphorylase ratio in these nine patients was 14.5 +/- 2.0% (mean, SEM). In the 17 nonsusceptible patients mean phosphorylase ratio (12.4 +/- 1.9%) was not significantly different. The range of phosphorylase ratios in susceptible patients was 6.5-26% while 13 nonsusceptible patients had ratios greater than 6% and up to 29%. The unacceptably high number of false-positive responses in nonsusceptible patients precludes the use of phosphorylase ratio as a definitive diagnostic test.
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PMID:Phosphorylase ratio and susceptibility to malignant hyperthermia. 629 36

A comparison was made of muscle from two locations in both the longissimus and the semitendinous muscles of normal and malignant hyperthermia-susceptible swine. Serial frozen sections were stained for alkali-stable adenosine triphosphatase (ATPase), phosphorylase, and the oxidative enzymes succinate dehydrogenase and reduced nicotinamide adenine dinucleotide (NADH)-diaphorase. Myofiber types were identified on the basis of these staining reactions. There was no consistent statistically significant difference between muscle from normal and muscle from susceptible swine with any system of fiber classification. This is contrary to several published reports but consistent with physiologic studies which indicate that both oxidative and glycolytic pathways are abnormally active during the onset of malignant hyperthermia.
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PMID:Histochemical observations on muscle from normal and malignant hyperthermia-susceptible swine. 644 66

Case reports are presented on 4 outpatients with hereditary disorders of metabolism. 1. In a 46-year-old male of Sicilian origin with haemolytic anaemia and leg ulcers, the blood contained numerous target cells, the sickling test was positive, and more than 80% of the haemoglobin was found to be HbS. Investigation of the family revealed double heterozygosity for HbS and beta-thalassaemia. 2. In a family with hereditary nonspherocytic haemolytic anaemic, the biochemical characterization of an abnormal pyruvate kinase is reported: the kinetic data were found to be normal, the electrophoretic migration rate of the abnormal enzyme was increased, and its thermostability was marked decreased. 3. Malignant hyperthermia was observed in an 18-year-old male. The limited value of all methods for identifying affected family members is discussed. 4. In 2 sisters who suffered life-threatening attacks of acute myoglobinuria, differential diagnosis comprised hereditary deficiency of phosphofructokinase, muscle phosphorylase and carnitine palmityl transferase. The activity of the former two enzymes was found to be normal. The circumstances of the myolytic crisis in the two patients provide strong evidence for the presence of a muscle carnitine palmityl transferase deficiency.
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PMID:[Clinical demonstrations of hereditary disorders of metabolism]. 745 56

Our knowledge of the mechanisms leading to exercise intolerance is constantly expanding. Since the discovery of the glycolysis pathway block caused by phosphorylase deficiency as the cause of McArdle's disease, several other glycolysis blocks have been identified constituting a first group of exercise intolerance syndromes. A second group involves mitochondrial anomalies. More recently diverse exercise intolerance syndromes have been associated with insufficient regulation of calcium flow through the sarcoplasmic reticulum, particularly in sporadic cases of malignant hyperthermia with or without hyperthermia. A discrete form of dystrophinopathy is expressed by exercise-induced myalgia with myoglobinuria. Proximal myotonic myopathy also produces pain at exercise. The specificity of other syndromes such as AMP deaminase deficiency or myopathy with tubular aggregates remains debatable. Our understanding of these different syndromes, and their recognized or yet to be elucidated causes, is of practical significance for developing exploration protocols for patients with exercise intolerance with or without myoglobulinuria.
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PMID:[Muscular intolerance of exercise. Current data]. 983 85

We report on 31 patients and 3 affected siblings (17 males and 17 females) from Southern France with McArdle disease (two from Spanish and three from Portuguese background). Molecular analysis revealed the presence of five previously described mutations: the common p.R50X nonsense mutation, the p.R94W and p.V456M missense mutations, the p.K609K conservative mutation which generates an aberrant splicing, and the p.K754fs frameshift mutation; and 10 new molecular defects: eight missense mutations at homozygous (p.G136D) or heterozygous state (p.T379M, p.G449R, p.T488I, p.R490Q, p.R570Q, p.R590H, and p.R715W), one nonsense mutation p.R650X and one deletion (p.delK170). Our results confirm that the p.R50X nonsense mutation is also the most common associated with myophosphorylase deficiency in the Southern French population: 21 of 25 French unrelated patients (15 homozygous and six heterozygous, i.e., 72% of the mutated alleles). Two patients, one from Algeria and one from Tunisia, were homozygous for a previously identified missense mutation p.V456M in a Moroccan subject. Our findings further demonstrate molecular heterogeneity of myophosphorylase deficiency, absence of genotype-phenotype correlation and expand the already crowded map of mutations within the myophosphorylase gene. Our study also provides evidence for increased medical interest of malignant hyperthermia susceptibility (MHS) because of 34 McArdle disease patients, three and two affected siblings were contracture-tested and found to be positive.
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PMID:Molecular characterization of myophosphorylase deficiency (McArdle disease) in 34 patients from Southern France: identification of 10 new mutations. Absence of genotype-phenotype correlation. 1732 73

A patient with McArdle disease underwent bowel surgery with general anesthesia and was successfully managed. McArdle disease is a rare skeletal muscle disorder affecting approximately 1 in 100,000 people. McArdle disease, also known as type V glycogen storage disease, is an autosomal recessive inherited condition caused by a missing or nonfunctioning enzyme called myophosphorylase C. This phosphorylase is the enzyme responsible for making glucose for energy. Individuals suffering from McArdle disease have muscles that cannot properly metabolize energy and may experience fatigue and failure during strenuous activities. When a patient with McArdle disease presents for any surgical procedure, a variety of anesthesia implications should be discussed and incorporated into the overall management of his or her care. Careful attention to adequate fluid management, appropriate neuromuscular blockade choices, normothermia maintenance, normoglycemia maintenance, blood pressure monitoring, and maintaining malignant hyperthermia precautions is critical to providing safe anesthesia to this unique patient population.
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PMID:Anesthesia considerations in a patient with mcArdle disease: a case report. 2175 93


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