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 pre-anaesthetic administration of dantrolene sodium to individuals at risk from malignant hyperthermia has not yet found an accepted place in human anaesthetic practice, although the effectiveness of dantrolene sodium as a prophylactic drug has been clearly shown in animal studies. In the patient described in this report, no conclusion is drawn about the effectiveness of dantrolene sodium, but attention is drawn to a brief episode of vomiting and diarrhoea some two hours after ingestion of the drug. Modification of the dosage scheme may be advisable.
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PMID:Pre-anaesthetic administration of dantrolene sodium to a patient at risk from malignant hyperthermia: case report. 28 30

Dantrolene sodium or dantrolene1 is 1([5-(nitrophenyl)furfurylidend] amino) hydantoin sodium hydrate. It is indicated for use in chronic disorders characterised by skeletal muscle spasticity, such as spinal cord injury, stroke, cerebral palsy and multiple sclerosis. Dantrolene is believed to act directly on the contractile mechanism of skeletal muscle to decrease the force of contraction in the absence of any demonstrated effects on neural pathways, on the neuromuscular junction, or on the excitable properties of the muscle fibre membranes. Controlled trials have demonstrated that dantrolene is superior to placebo in adults or children with spasticity from various causes, as evidenced by clinical assessments of disability and daily activities, and by muscle and reflex responses to mechanical and electrical stimulation. It is somewhat less effective in patients with multiple sclerosis than in those with spasticity from other causes. There has been a general clinical impression in controlled trials that dantrolene caused less sedation than would have been expected from therapeutically comparable doses of diazepam. In 2 controlled trials, there was no significant difference between dantrolene and diazepam in terms of reductions in spasticity, clonus, and hyperreflexia, but side-effects such as drowsiness and inco-ordination occurred significantly more frequently on diazepam. Long-term studies have indicated continuing benefit for patients taking dantrolene, though the incidence of side-effects has often been high and there has been a suggestion of exacerbation of seizures in children with cerebral palsy. Dantrolene may be of value in the medical treatment of spasm of the external urethral sphincter due to neurological and non-neurological disease, and animal studies suggest a potential use in the management of malignant hyperpyrexia. Chemical evidence of liver dysfunction may occur in 0.7 to 1% of patients on long-term treatment with dantrolene, with symptomatic hepatitis in 0.35 to 0.5% and fatal hepatitis in 0.1 to 0.2%. The drug commonly causes transient drowsiness, dizziness, weakness, general malaise, fatigue and diarrhoea at the start of therapy. Muscle weakness may be the principal limiting side-effect in ambulant patients, particularly in those with multiple sclerosis, and therapy could be hazardous in patients with pre-existing bulbar or respiratory weakness. The dosage of dantrolene has been fixed in most controlled trials, though long-term studies have indicated the need for individualisation of dosage. The initial dose is usually 25mg once daily, increasing to 25mg two, three or four times daily, and then by increments of 25mg up to as high as 100mg two, three or four times daily. The lowest dose compatible with optimal response is recommended.
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PMID:Dantrolene sodium: a review of its pharmacological properties and therapeutic efficacy in spasticity. 31 89

Malignant hyperpyrexia is a genetically related syndrome that cannot be predicted reliably in advance of administration of anesthesia except by a strong family history. The definitive etiology is unknown, although triggering agents that release calcium from the calcium-storing sarcoplasmic membrane of the muscle cell are highly suspect. As soon as the syndrome is diagnosed, therapy must be prompt, vigorous, and carried out with the same urgency as a cardiac arrest. Specific therapy with dantrolene sodium may prove to be an answer to this serious problem in anesthetic practice.
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PMID:Malignant hyperpyrexia. 32 54

Malignant hyperthermia is an inherited muscular disorder and a cause of sudden death in afflicted patients. Stress arising from tramuma, surgery, and other causes can initiate the syndrome. We studied the types of orthopaedic problems commonly seen in patients with this condition as well as the clinical manifestations and pathophysiology of the syndrome. Recognition, management, and understanding of the pathophysiology of malignant hyperthermia can be aided by a study of its similarities to porcine stress syndrome. We performed experimental studies of muscle and prophylaxis in swine. We also demonstrated the extension of the prophylactic use of dantrolene sodium in a management protocol in eighty surgical procedures in humans.
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PMID:Malignant hyperthermia. A potentially fatal syndrome in orthopaedic patients. 48 49

We present a case of malignant hyperthermia in which successful management included the intravenous use of dantrolene sodium. A subsequent operation under spinal anaesthesia with oral dantrolene prophylaxis did not lead to development of malignant hyperthermia. Since this syndrome is rare during regional anaesthesia, the role of prophylactic oral dantrolene in preventing the redevelopment of malignant hyperthermia in our patient is open to question.
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PMID:Successful use of dantrolene sodium in human malignant hyperthermia syndrome: a case report. 50 49

Halothane, at clinical concentrations, depolarizes the plasma membrane of skeletal muscle from Poland China pigs susceptible to malignant hyperthermia but does not affect the resting membrane potential of muscle from normal poland China pigs, mice, or frogs. The depolarization is reduced or partially reversed in the presence of dantrolene sodium. We suggest the possibility that malignant hyperthermia may be initiated by this abnormal depolarization of skeletal muscle by halothane.
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PMID:Role of plasma membrane defect of skeletal muscle in malignant hyperthermia. 51 15

A case of possible malignant hyperthermia in a 6-month-old child is presented. Malignant hyperthermia was manifested in this patient by persistent metabolic acidosis in the intraoperative and postoperative periods, by a rapid rise in temperature with concomitant unresponsiveness in the postoperative period, and by a positive caffeine-halothane stimulation test. The malignant hyperthermia occurring in the postoperative period resolved promptly following administration of dantrolene sodium. An unusual aspect of this case is that both of the child's parents had normal CPK values and negative caffeine-halothane stimulation tests.
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PMID:Management of suspected malignant hyperpyrexia in an infant. 57 Dec 20

A case of malignant hyperthermia in a Black boy is presented. He developed this condition during repair of a cleft palate, with halothane as the triggering agent. The importance of the high incidence of malignant hyperthermia in patients with certain musculoskeletal abnormalities is stressed. Despite a cool and well air-conditioned theatre, the patient's temperature was 41 degree C when the condition was suspected. At that stage general muscle rigidity was present. The patient was successfully treated with procainamide, sodium bicarbonate and hydrocortisone; surface cooling (with ice packs) was instituted and the stomach was washed out with ice-cold Ringer's solution. Over a period of 14 days serum creatine phosphokinase values decreased from 630 IU (on the day of the incident) to 12 IU. A muscle biopsy showed variation in muscle fibre size. Electron microscopical studies showed myofibrillar disruption and folding of the basement membrane. A modified version of Denborough's technique was used for the in vitro exposure of muscle strips to halothane and suxamethonium. Isometric contraction was measured and recorded. A severe contraction followed the exposure of muscle strips to halothane, which confirmed the diagnosis.
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PMID:[Malignant hyperthermia in a black child. A case report]. 69 25

Malignant hyperthermia is now recognized as a distinct entity in anesthetic practice and can be considered as a pharmacogenetic disease of obscure etiology occuring in man and pigs with a dominant inheritance. A close association with myopathy has been noted. Commonly used muscle relaxants or anesthetic drugs can act as triggering agents in genetically susceptible patients, who develop a real hypermetabolic state, characterized by a rapid rise in body temperature, muscular rigidity, tachycardia and tachypnoea, cyanosis and severe respiratory and metabolic acidosis, the lethality being about 60%. Other clinical, biochemical and histopathological features of this condition are described. The prevention and early diagnosis of this syndrome is very important. Therefore, it is necessary in the preanesthetic evaluation, to obtain information from the patient, with regard to previous anesthetic experiences, and to have a more exact anamnesis in patients with muscular diseases or with other members of the family under suspicion. Some screening methods are described. The prognosis of malignant hyperthermia depends on an early diagnosis. Although the incidence is, fortunately, small, this condition is sufficiently significant and acute in nature to require that anesthesiologist be aware of its clinical pathophysiology and prepared to recognize and treat it promptly. Therefore body temperature should be controlled continuously in all anesthetized patients, particularly in the younger age group and especially in those in which symptoms of muscle rigor have been observed particularly after application of succinylcholine and halothane. A regime of treatment is suggested, based on current concepts of the pathogenesis. It consists in establishing effective and rapid cooling, reversal of tissue hypoxia and correction of respiratory and metabolic acidosis and hyperkalemia. Specific therapy with dantrolene sodium may prove to be an answer to this serious problem.
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PMID:Malignant hyperthermia. 70 24


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