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)

In a study of human malignant hyperpyrexia-susceptible muscle a comparison between pancuronium and methylprednisolone showed that both drugs produced qualitatively similar depression of the halothane-induced muscle contracture. From this and other evidence, it is suggested that pancuronium is a suitable drug for use in malignant hyperpyrexia-susceptible patients.
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PMID:Anaesthesia for patients susceptible to malignant hyperpyrexia. A study of pancuronium and methylprednisolone. 91 94

Data are presented on ten cases of anaesthesia-induced malignant hyperthermia in Norway. Seven of the patients died, three recovered. The fatal cases were all boys in the age group 11-20 years. This age and sex distribution suggests that puberty with the increase in androgens is a precipitating factor in malignant hyperthermia. One of the victims who survived was a 4 1/2-year-old pseudohermaphrodite girl with the adrenogenital syndrome. The coincidence of malignant hyperthermia in a patient with such a rare syndrome points to the excessive formation of androgens in patients with this syndrome as a predisposing factor. The indications for surgery were traumatic injuries in five cases, congenital abnormalities in three and appendicitis in two cases. These conditions in themselves may cause an increased sensitivity to suxamethonium. One patient received only hexobarbitone, halothane and suxamethonium. After the last drug jaw rigidity and temperature rise to 41.3 degrees C prompted the anaesthetist to end the anaesthetic. The fact that the patient survived proves that suxamethonium induced jaw rigidity is valuable as a warning. The absence of cardiovascular depression after procaine 3.5 g in one patient is ascribed to the correction of acidosis at the time of infusion of this drug. It is suggested that procaine should be withheld until other measures such as cooling, correction of acidosis and steroid therapy have been tried.
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PMID:Ten cases of malignant hyperthermia in Norway. 97 60

This review deals with the adverse reactions associated with general anaesthetic agents in current use. These reactions fall into 2 categories; those which are more common, predictable and often closely related, and those which are rare, unpredictable and carry a high mortality. Both inhalational and intravenous anaesthetic agents affect the central nervous and cardio-respiratory systems in a dose-related manner. Neuronal inhibition results in decreasing levels of consciousness and depression of the medullary vital centres which can lead to cardiorespiratory failure. Both groups of agents have some depressant effect on the myocardium and vascular smooth muscle leading to a fall in cardiac output and hypotension. Centrally-mediated respiratory depression is common to both groups and the inhalational agents have a direct effect on lung physiology. The most important idiosyncratic reactions to the volatile agents are malignant hyperpyrexia and 'halothane hepatitis'. Malignant hyperpyrexia has an incidence of 1:12,000 with a mortality of about 24%. It is triggered most often by halothane together with suxamethonium. Post halothane hepatic necrosis is rare. Evidence points to 2 distinct syndromes; direct toxicity from the products of reductive metabolism, and a more serious illness, immunologically mediated via haptens formed by liver proteins and the products of oxidative metabolism. Prolonged nitrous oxide exposure can cause bone marrow depression and life-threatening pressure effects by expansion of air-filled spaces within the body. The idiosyncratic reactions to the intravenous agents include anaphylactoid reactions (which are rare) and triggering of acute porphyria. Etomidate is immunologically 'clean', but it inhibits cortisol synthesis.
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PMID:Adverse effects of general anaesthetics. 141 99

Malignant hyperthermia syndrome (MHS) is rare, inherited, and triggered by volatile anesthetics and depolarizing muscle relaxants. While potentially fatal, if recognized and treated early recovery is usual. However, the condition is often not recognized until an extreme increase in temperature develops with profound circulatory depression. In this stage the syndrome is irreversible, despite specific treatment with dantrolene. At present, the only reliable diagnostic test for susceptibility to malignant hyperthermia requires sampling of viable muscle for in vitro contracture tests with caffeine and halothane. Until our malignant hyperthermia diagnostic center was opened, such tests could not be performed in Israel. Since then we encountered a 22-year-old man who developed the partial picture of malignant hyperthermia syndrome during anesthesia for inguinal herniorrhaphy. He received dantrolene and recovered. 4 months later in vitro contracture tests with caffeine and halothane performed on biopsied muscle confirmed the diagnosis.
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PMID:[In vitro diagnosis of malignant hyperpyrexia syndrome]. 179 53

Piglets less than 8 wk of age that are known by genotype to be malignant hyperthermia-susceptible (MHS) do not usually develop characteristic hyperthermia and limb muscle rigidity in response to a brief halothane exposure (5 min of 3%). To determine whether a malignant hyperthermia (MH) episode could nevertheless be provoked by a more rigorous challenge, both genetically MHS (Pietrain) and normal (Yorkshire) 5-wk-old piglets were exposed to a combined halothane-succinylcholine challenge. Only two of eight MHS piglets developed limb rigidity; however, all MHS piglets (and no normal piglets) developed clinical signs of MH episode initiation during the 30-min challenge. Temperatures rose from 37.4 to 38.6 degrees C in MHS piglets while falling slightly in normal piglets. In MHS piglets, venous pH fell from 7.46 +/- 0.02 to 6.88 +/- 0.07, PVCO2 rose from 36 +/- 2 to 126 +/- 17 mmHg, and plasma concentration of K+ rose from 4.0 +/- 0.1 to 7.1 +/- 0.6 mM, whereas all values remained stable in normal piglets. Muscles removed from the same piglets before the halothane-succinylcholine challenge were exposed to halothane in vitro. The muscles from genetically MHS piglets responded to halothane with characteristic depression of tetanic tension and prolonged tetanus relaxation time but did not develop halothane-induced contractures. We conclude that, in the absence of either halothane-induced limb rigidity or in vitro contractures, these young animals were still susceptible to potentially fatal MH episodes on exposure to appropriate triggering agents. The MH defect is apparently partially masked in piglets and expressed fully only in older pigs.
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PMID:Halothane sensitivity of young pigs in vivo and in vitro. 237 22

Neuromuscular blockade was obtained with vecuronium 108 micrograms kg-1 in 44 patients undergoing diagnostic muscle biopsy as part of an investigation of malignant hyperthermia (MH) susceptibility. At the termination of anaesthesia doxapram 1.43 mg kg-1 was given in an attempt to antagonize postoperative respiratory depression. Rectal, muscle and skin temperatures, blood lactate concentration and venous PCO2 were measured before, during and after anaesthesia. Susceptibility to MH was established by in vitro contracture tests according to the protocol of the European MH Group. Twenty patients were susceptible to MH (MHS), 19 were MH non-susceptible (MHN) and five MH equivocal (MHE). No adverse effects of the drugs were observed. There were no differences between the three groups in rectal or muscle temperature, blood lactate concentration or venous PCO2 at any time. Doxapram did not prevent an increase in postoperative PCO2. It is concluded that vecuronium and doxapram may be safely administered to patients susceptible to MH.
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PMID:Use of vecuronium and doxapram in patients susceptible to malignant hyperthermia. 289 65

Fatal malignant hyperthermia occurred in a patient who was taking tranylcypromine (Parnate) and ingested wine and cheese. The case findings are presented along with a review of the literature concerning adverse interactions between monoamine oxidase (MAO) inhibitors and certain foods and beverages. Hyperthermia and its possible causative mechanisms and treatments are discussed. The facts suggest that the complicated dietary restrictions attending the use of MAO inhibitors and the possibility of severe and even catastrophic reactions resulting from violations of these restrictions make the use of these drugs fraught with danger and therefore not a first choice for the treatment of depression.
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PMID:Fatal malignant hyperthermia as a result of ingestion of tranylcypromine (Parnate) combined with white wine and cheese. 398 Nov 12

We have investigated the hypothesis that the calcium antagonist verapamil might be useful for prevention or treatment of malignant hyperthermia (MH) in MH-susceptible (MHS) swine. MH episodes were triggered in four groups of four swine with halothane alone or combined with succinylcholine (SCh) and, with and without verapamil. MH episodes were reversed by therapy with dantrolene and NaHCO3 in all groups. Verapamil did not alter MH episodes triggered by halothane alone or combined with SCh. The dantrolene-NaHCO3 requirements for reversal of MH were greater for the groups receiving halothane-SCh, but did not differ in groups pretreated with and without verapamil. In vitro verapamil (25 microM) did not reduce responses of intact muscle fibers to halothane and, in fact, exaggerated some halothane-induced responses. High concentrations of verapamil (0.5 mM) caused contractures in MHS but not in normal muscles. Neither our in vivo nor in vitro results support the use of verapamil in the treatment of MH. Further, doses of dantrolene used to reverse these MH episodes, although admittedly small (1-2 mg/kg), did not produce myocardial depression when used in combination with verapamil.
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PMID:Verapamil is not a therapeutic adjunct to dantrolene in porcine malignant hyperthermia. 400 78

During 15 years of inbreeding of pigs (Canadian Landrace) a semi-inbred line has been developed. The inbreeding coefficient (FX) is 0.84, which theoretically corresponds to between 8-9 generations of brother/sister matings. At the highest inbreeding level (0.84) the mean number of newborn piglets in the litter was 7.2 (5 litters, n = 36) including 5 stillborn (13.8%). The mean birth weight of the litter was 8.56 kg (5 litters, n = 31) the mean piglet birth weight was 1.23 kg and at the age of 21 days the mean weight of a litter was 33.24 kg with a mean piglet weight of 5.44 kg. During inbreeding, immunogenetic alloantigenic systems were investigated. Of 15 known erythrocyte systems, alleles of loci J, K, and of the most polymorphic system E, segregated. As to other immunogenetic systems (histocompatibility, leucocyte and allotypes) 2 SLA haplotypes (major histocompatibility complex) and 2 alleles of the SLC leucocyte system segregated. Allotransplants of the skin in SLA compatible siblings survived for a mean of 50.7 days (n = 77) compared with 10.8 days (n = 29) in non-inbred siblings. Tests of blastic transformation activated by T and B lymphocyte mitogens revealed a normal cell-mediated immune response. After immunization with some cell membrane alloantigens a normal humoral response was also recorded. All tested animals were halothane-resistant and tolerated a 10-min exposure to 5% without developing malignant hyperthermia. Depression due to inbreeding was manifested by a reduced reproductive ability (smaller number of piglets, frequent incidence of gonadal hypoplasia, diminution or loss of libido).
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PMID:Development of a semi-inbred line of Landrace pigs. I. Breeding performance and immunogenetic characteristics. 406 54

Out of five injectable long-acting neuroleptics (LANs) in general use in France, two are french derivatives. LANs in France have been introduced at high dosages, because of the administration of high doses of oral activating neuroleptics at that time. Despite the apparent lack of relationship between dosage and adverse effects, the clinical use of LANs has nowadays moved to lower doses, probably because of the treatment of a greater proportion of less severely-ill outpatients and of patients at an early stage. The "sectorial" organization of community psychiatry in France has contributed to the low-dose LAN strategy. French authors pointed to an original indication of LANs, namely very low dosages in chronic alcoholism characterized by a high frequency of early personality disorders, such as paranoid or psychopathic traits. Adverse reactions are more pronounced in such patients at high dosages, esp. depression and sedation. The authors have been the first ones to report the incidence of depressive reactions in prolonged treatments with LANs (1967). Malignant hyperthermia, though rare, has been related to a direct onset of treatment with a LAN and not to its dosage.
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PMID:Some aspects of the French contribution during the past ten years to the study and use of injectable long-acting neuroleptics. 611 80


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