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)

Dantrolene is an effective antagonist of anesthesia-induced malignant hyperthermia due to a poorly understood action on skeletal muscle. The present study examines whether the red blood cell can be used as a model to investigate the mechanism of dantrolene action. Halothane (4.7 mM) caused 9% hemolysis of red blood cells. Phospholipase A2 (1 microM) alone caused less than 2% hemolysis, despite high levels (54%) of phosphatidylcholine hydrolysis. Incubation of red blood cells with halothane and phospholipase A2 caused 72% hemolysis. Halothane addition caused 100% hydrolysis of all diacylphosphoglycerides by phospholipase A2, suggesting a mutual potentiation. The major products of phospholipase A2 activity, arachidonic acid and lysophosphatidylcholine, when exogenously added, also greatly increased hemolysis induced by halothane, with arachidonic acid most closely resembling the synergism observed with phospholipase A2. Dantrolene (10 microM) and mepacrine (10 microM) significantly antagonized hemolysis induced by halothane and phospholipase A2 or halothane and exogenously added arachidonic acid and lysophosphatidylcholine. Dantrolene and mepacrine did not antagonize phospholipid hydrolysis or free fatty acid levels. Dantrolene and mepacrine antagonized the synergism between halothane and phospholipase A2 most likely by reducing the lytic action of halothane in the presence of arachidonic acid. The red blood cell is a useful model for studying the antagonism of halothane and phospholipase A2 toxicity by dantrolene and mepacrine.
Toxicol Appl Pharmacol 1987 Sep 30
PMID:Dantrolene and mepacrine antagonize the hemolysis of human red blood cells by halothane and bee venom phospholipase A2. 366 Apr 10

Malignant hyperpyrexia developed, and was successfully treated, in a 50-year old man undergoing pyelolithotomy. Early diagnosis with the assistance of end-tidal carbon dioxide monitoring facilitated prompt treatment with i.v. dantrolene. A positive muscle biopsy subsequently confirmed the diagnosis. The only likely triggering agent used was isoflurane.
Br J Anaesth 1987 Sep
PMID:Malignant hyperpyrexia and isoflurane. A case report. 366 43

Binding of monoclonal antibody MHS-5 to western blots of human seminal plasma was employed to follow the fate of a seminal vesicle-specific antigen (SVSA) during semen liquefaction. Ejaculates from four vasectomized donors were collected in a manner to inhibit liquefaction or to allow liquefaction to proceed at room temperature. Aliquots of the liquefying seminal fluid were removed at specific time points and further liquefaction inhibited with sodium dodecyl sulfate (SDS). Western blot analysis using monoclonal antibody MHS-5 demonstrated that the SVSA epitope in all donors was located on multiple bands ranging in mass from 15-92 kDa in unliquefied ejaculates; immunoreactive peptides below 15 kDa were not detected. As early as 5 min post ejaculation, immunoreactive bands below 15 kDa were identified in liquefying samples. During the same time period (5 min), immunoreactive bands of 69-71 and 58 kDa could not be immunologically detected in liquefying samples. A decrease in immunoreactive staining of components higher molecular mass was accompanied by a concomitant increase in immunoreactive staining of intermediate and small molecular mass molecules during the first 2 h of liquefaction. After 8-24 h of liquefaction, two immunoreactive bands of 10.9 and 12.5 kDa predominated. Between 24 and 48 h, each donor's ejaculate demonstrated a common single immunoreactive band of 10.9 kDa. These results indicate that there is a rapid transformation in mass of the SVSA with major 69-71 and 58 kDa bands being converted to forms of lower mass within 5 min of ejaculation.
Biol Reprod 1987 Sep
PMID:Human seminal vesicle-specific antigen during semen liquefaction. 367 97

Trismus, or masseter hypertonia, that results from the use of succinylcholine during induction of anesthesia is a rare and dangerous phenomenon. It presents to the anesthesiologist the immediate problem of airway management but it also must be recognized by the physician as a harbinger of malignant hyperthermia. We report a case of induction trismus and discuss its association with malignant hyperthermia. The pathophysiology, diagnosis and treatment of malignant hyperthermia are reviewed.
J Urol 1986 Sep
PMID:Anesthetic induction trismus, more than a closed-mouth problem. 373 51

Dantrolene sodium, a skeletal-muscle relaxant known to be effective for treatment of malignant hyperthermia, was evaluated for efficacy in treatment of heatstroke. Non-exertional heatstroke was induced in 11 dogs by external heating following barbiturate anesthesia. When core temperature reached 43 degrees C (109.4 degrees F) heating was discontinued and control animals (n = 6) were allowed to cool passively in room air. Treatment animals (n = 5) received 5 mg/kg dantrolene sodium intravenously at the start of room-air cooling. Serial temperatures (pulmonary arterial, rectal, cerebral, and subcutaneous), blood chemistry tests (including electrolytes, liver enzymes, and complete blood count), and hemodynamic parameters (including cardiac output, arterial pressure, and urinary output) were followed for 12 hours after induction of heatstroke. Autopsies, including gross and microscopic examination, were performed on all animals. Dantrolene administration did not significantly affect cooling rates, hemodynamic parameters, pathological changes, or clinical outcome. Statistically significant changes in urinary output and serum creatinine observed in the first hours after dantrolene administration can be attributed to the mannitol vehicle in which the drug was delivered. There were no statistically significant differences in these values at 12 hours. Dantrolene sodium does not appear to enhance passive cooling in treatment of non-exertional canine heatstroke.
Am J Emerg Med 1986 Sep
PMID:Dantrolene sodium for treatment of heatstroke victims: lack of efficacy in a canine model. 374 58

Myoadenylate deaminase deficiency, the most common of the known enzyme deficits of muscle, appears to occur in two forms. The primary type seems to be inherited as a complete gene block in an autosomal recessive pattern. Although occasionally diagnosed in infancy, when muscle biopsy is performed on a hypotonic but normoreflexic child, the deficiency is usually not symptomatic until adult or middle age, when muscle cramping and exercise intolerance develop. The skeletal muscle isozyme is immunologically, and presumably genetically, unique, and these patients have normal levels of adenylate deaminase in their other cells and tissues. A presumptive diagnosis can usually be made by an ischemic forearm exercise test, which shows a negligible increase in blood ammonia, despite a normal rise in lactate. Despite the absence of more than 99% of normal adenylate deaminase activity, the muscle biopsy shows no anatomic pathology, and other enzymes are at normal levels. These patients do not suffer progressive disease, and should be reassured and encouraged to maintain physical activity. The heterozygous state is probably asymptomatic, except, perhaps, on extreme exercise, but may be associated with an increased incidence of malignant hyperthermia susceptibility. Since the gene defect is not rare, it is not surprising that some cases of the deficiency will be coincidentally associated with other neuromuscular disease. However, there is also a secondary form of myoadenylate deaminase deficiency, consequent to muscle damage from other disease. In this form, the residual activity is higher (1-10% of normal), may present rare foci of positive stain in the section, and reacts normally with antibody to the muscle isozyme. Other muscle enzymes are also depleted, although not as severely, and the prognosis in such cases is dictated by the primary disease. Since the heterozygous state is common, these patients might have been carriers whose adenylate deaminase levels have been lowered to the deficient category by the advent of other neuromuscular disease.
Toxicol Ind Health 1986 Sep
PMID:Myoadenylate deaminase deficiency: primary and secondary types. 378 46

Malignant hyperthermia is an often lethal hypermetabolic crisis state precipitated by a variety of pharmacological and environmental triggers in genetically susceptible persons. The present report documents, by medical history and necropsy, a fatal malignant hyperthermic crisis in a 20-year-old man after an evening of recreational cocaine and ethanol abuse.
Am J Forensic Med Pathol 1986 Sep
PMID:Fatal malignant hyperthermia associated with recreational cocaine and ethanol abuse. 378 15

A bioassay, using high-performance liquid chromatography (HPLC) analysis of platelet adenosine nucleotides and hypoxanthine, was studied for its potential use as a test for MH susceptibility. A protocol for the assay was developed, based on the method outlined by Solomons and Masson. The HPLC procedure was a rapid, efficient, sensitive, and highly reproducible technique for measuring ATP, ADP, AMP, and hypoxanthine in platelets. Conditions of extraction and storage were critical for preventing degradation of the nucleotides. Extraction of nucleotides at icebath temperature was found necessary. Storage of platelet extract in PCA, even at -20 degrees C, showed loss of ATP and ADP; hence, neutralization with KOH was essential before storage. Contrary to the findings of Solomons et al., the present study demonstrated that neither ATP depletion nor per cent reduction in nucleotide ratios in platelets treated with halothane can be used as a definitive test for the diagnosis of MH susceptibility. The reason for this disagreement is unclear; however, differences in methods and altitude are implicated. It is possible that the platelet is not affected by malignant hyperthermia and thus cannot serve as a test system for the detection of the syndrome.
Anesthesiology 1985 Sep
PMID:The use of a platelet nucleotide assay as a possible diagnostic test for malignant hyperthermia. 402 92

Muscle biopsy is often incorrectly performed despite the fact that it is a relatively simple procedure. A consistently reproducible surgical technique in 93 open vastus lateralis muscle biopsies implemented in conjunction with neuromuscular and malignant hyperthermia research demonstrated 14 cases of malignant hyperthermia and a variety of forms of neuromuscular pathology. No wound complications or disabilities have resulted from this procedure. The procedure includes careful selection of biopsy site, regional anesthesia, atraumatic dissection, and immediate processing of the biopsy sample. A new muscle biopsy clamp is described. The authors recommend the vastus lateralis for the biopsy site unless another area of involvement is specifically indicated. Careful attention to technical details is required for optimal results.
Clin Orthop Relat Res 1985 Sep
PMID:Muscle biopsy: proper surgical technique. 402 56

A syndrome similar to malignant hyperthermia developed in a 545-kg Quarter Horse while anesthetized with halothane for cataract removal. Succinylcholine administration caused prolonged, severe muscle fasciculations followed by tachycardia, and an elevated blood pressure. Later, while the horse was still under anesthesia, its body temperature rose 2 degrees C, and respiratory acidosis developed. Myositis developed after surgery, but the horse recovered.
J Am Vet Med Assoc 1985 Sep 01
PMID:Unusual response following use of succinylcholine in a horse anesthetized with halothane. 405 81


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