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)

Malignant hyperthermia is a disease resulting from defective cellular membranes, usually presenting as drug-induced pyrexic crises. We describe four patients with life threatening ventricular arrhythmias or chest pain in the absence of pyrexic crises. Three presented with life threatening arrhythmias and the fourth with severe atypical chest pain. Two patients had a family history of multiple sudden deaths. Resting CKs were elevated in three patients while CK-MB was elevated in one. Resting ECGs were abnormal in three. Three patients had recurrent ventricular tachycardia, two had recurrent ventricular fibrillation and multiple cardiac arrests. Cardiac catheterization showed abnormal left ventricular wall motion in two and minimal mitral valve prolapse in one while all had normal coronary arteries. Thallium-201 myocardial imaging demonstrated large perfusion defects in the patient with electrocardiographic Q waves and normal coronary arteries. Myocardial involvement has been demonstrated by clinical, electrocardiographic, hemodynamic, angiographic and myocardial imaging abnormalities. Malignant arrhythmias occurred in these patients in the absence of pyrexic crises or drug admininstration. Abnormal calcium release in the myocardium, as documented in skeletal muscle membranes, may be a unifying concept for the various manifestations described.
 ...
PMID:Cardiac manifestations of malignant hyperthermia susceptibility. 69 60

Malignant hyperpyrexia is a dangerous complication of general anesthesia occurring in individuals with an underlying disease of muscle. The essential clinical features of the syndrome are a drastic and sustained rise in body temperature, metabolic acidosis, and widespread muscular rigidity. The results of experiments on susceptible pigs and in vitro studies of human muscle have shown that all the clinical features of the syndrome can be explained by a raised level of calcium ions in the myoplasm. This is caused by a massive and sudden release of calcium into the myoplasm from the calcium-storing membranes in the muscle cell when exposed to general anesthetic agents. Two myopathies predisposing to malignant hyperpyrexia have been identified. One is usually subclinical, dominantly inherited, and manifested only by raised serum CPK levels. The other occurs in young boys with a number of physical abnormalities, whose relatives are unaffected. The serum CPK is a useful screening test in families in which malignant hyperpyrexia has occurred. Unfortunately, though, the serum CPK is not a specific test, and in doubtful cases the only unequivocal method of establishing susceptibility to malignant hyperpyrexia is to carry out an in vitro muscle test in which the muscle is exposed to caffeine, halothane, succinylcholine, and potassium chloride. Susceptible individuals should be given local, regional, or spinal anesthesia if an operation is needed. If this form of anesthesia is unsuitable, barbiturates such as thiopentone, tranquilizers such as diazepam, narcotics such as Pantopon, and neuroanaleptics such as fentanyl, nitrous oxide, d-tubocurarine, and althesin appear to be safe. By far the most important aspect of treatment is prophylaxis. Early diagnosis and immediate cessation of the offending anesthetic agents are the most important factors in trying to reduce the very high mortality of the syndrome.
 ...
PMID:Malignant hyperpyrexia. 77 64

The muscular rigidity associated with anesthetically induced malignant hyperthermia has been attributed to an increase in myoplasmic free calcium concentration. However, previous in-vitro studies have shown that increased temperature can eliminate the calcium requirement for actin-myosin interaction. Therefore, the calcium dependency of human skeletal muscle actomyosin in response to temperature increases of the magnitude encountered in human muscle during hyperthermic episodes was investigated. Calcium dependency is expressed in terms of the ability of a calcium-chelating agent, EGTA, to inhibit the ATP-induced turbidity increase of actomyosin suspensions (superprecipitation). In the presence of millimolar concentrations of ATP and magnesium, EGTA completely inhibits superprecipitation at temperatures as high as 35 C. With further increase in temperature this inhibition is progressively reduced until, at 45 C, the extent of superprecipitation is independent of the calcium concentration. Loss of calcium control is potentiated by reduction in the ATP concentration. Since the muscular rigidity of malignant hyperthermia is associated with both an elevation of muscle temperature and a decline in muscle ATP content, it is evident that in this disorder conditions might exist for an increase in muscle tension that is independent of changes in intracellular free calcium concentration.
 ...
PMID:Thermal inactivation of the calcium regulatory mechanism of human skeletal muscle actomyosin: a possible contributing factor in the rigidity of malignant hyperthermia. 80 55

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.
 ...
PMID:[Histological, histochemical, and ultrastructural findings in malignant hyperthermia (author's transl)]. 80 99

Of the various drugs currently suggested for the treatment of malignant hyperpyrexia, dantrolene sodium was the most effective in reversing and inhibiting drug induced contractures in vitro, both in normal muscle and in muscle from patients who are susceptible to malignant hyperpyrexia. It is suggested that dantrolene sodium is the drug of choice for lowering the raised myoplasmic calcium concentrations in malignant hyperpyrexia.
 ...
PMID:Drug treatment of malignant hyperpyrexia. 90 Apr 61

The calcium and magnesium contents of muscle obtained by muscle biopsy of patients referred for malignant hyperpyrexia screening were determined. The susceptibility to malignant hyperpyrexia was made on the basis of the halothane contracture test. No difference in cation concentrations was found between the normal and malignant hyperpyrexia-susceptible groups.
 ...
PMID:Calcium and magnesium contents of malignant hyperpyrexia-susceptible human muscle. 92 75

Metabolic, haemodynamic and neuroendocrine responses to suxamethonium (SCh) were measured in five normal swine and five swine susceptible to malignant hyperthermia (MH), to compare the responses with those previously reported for halothane. Following SCh, the onset of MH was sooner and more abrupt than following halothane. The maximal changes in aerobic metabolism and body temperature sere similar, while the changes in lactate, potassium, hydrogen ion and catecholamine concentrations were smaller than those observed following halothane. These results are discussed in terms of the action of chemical depolarizing drugs such as suxamethonium and acetylcholine. The propagated muscle action potentials produce an increase in the free intracellular calcium concentration which may be self-regenerative, but which may become uncontrollable because of the peculiarities of MH that effect the calcium pump or storage areas.
 ...
PMID:Suxamethonium-induced porcine malignant hyperthermia. 95 85

Thirteen of 31 Belgian Landrace pigs developed malignant hyperthermia (MH) after breathing halothane. A short period of exercise 1 h before the administration of the triggering agent increased the incidence of the syndrome to 100% in eight similar pigs. Clinical symptoms were more marked and developed more rapidly in the exercised pigs. All the reacting pigs became typically acidotic, developed rigor and died. Serum Na+, K+, Ca2+, c.p.k., l.d.h. and protein concentrations were increased to a variable extent during the reaction and there was an increase in p.c.v. also. No hyperglycaemia was detected in pigs which were rested before receiving halothane. Four of the eight exercised pigs became markedly hyperglycaemic and plasma noradrenaline increased to higher values. Phosphocreatine and ATP decreased to low values and lactate increased in the muscles of all pigs which reacted. At the time of death, muscle glycogen had decreased significantly in the rested, but not in the exercised, MH pigs.
 ...
PMID:Malignant hyperthermia in Belgian Landrace pigs rested or exercised before exposure to halothane. 97 90

The use of intravenous procaine in the treatment of hyperpyrexia in a patient with hyperparathyroidism has not been previously reported. A case of metastatic malignant melanoma precipitating the syndrome of hypertonicity of muscle, hyperpyrexia, acidemia, hypercalcemia and elevated serum parathormone levels is presented. Mithramycin was used in an attempt to reduce elevated serum calcium concentrations. The use of intravenous procaine in "caffeine rigor" and malignant hyperthermia due to succinylcholine and halothane formed the basis for its trial in this case. The relationship between cyclic AMP and calcium ions is discussed in postulating mechanism of procaine action.
 ...
PMID:The use of procaine in acquired malignant hyperthermia in a patient with malignant melanoma metastatic to the parathyroid gland: a case report. 99 Sep 78

Malignant hyperthermia is a life-threatening complication of general anesthesia. Its cause is not precisely known but it appears to be related to a genetic defect that allows increased release or decreased reaccumulation of calcium by the sarcoplasmic reticulum whech then results in a hypermetabolic state. As with any unexpected complication when a patient is under general anesthesia, early diagnosis and treatment are essential. The early clinical signs that the surgeon and anesthesiologist shoulc be alert to are unexplained tachycardia, unexplained tachypnea, muscular rigidity, and increased temperature. Therapy should be accurate and immediate. The essentials of therapy are discontinuance of the anesthetic agent; immediate, active, and aggressive cooling; administration of procaine or procaine amide, 1 mg/kg/min until the pulse slows; correction of electrolyte and acid-base imbalances; maintenance of urinary output with furosemide and large volumes of fluids, intravenously; and supportive care. A thorough knowledge of the management of malignant hyperthermia ahd the pathophysiology of the complications that may occur with general anesthesia will allow the oral surgeon to fully meet his obligations to his patients.
 ...
PMID:Survival of an oral surgery patient with malignant hyperthermia. 105 44


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>