Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026837 (muscle rigidity)
 1,077 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Trace amounts of [14C]2-deoxyglucose (2-DG) were used to detect regions of the brainstem involved in forelimb stepping in thalamic and low spinal cats. Under ether anesthesia, cats were transected at the stereotaxic A12 level and T10 segment. Two hours later, 50 microCi/kg of 2-DG was infused i.v. and one of 4 procedures was followed: 3 cats stepped on a motor-drive treadmill (Stepping), 3 were kept in a stationary standing position (Rigidity), 2 were anesthetized with sodium pentobarbital (Anesthetized), and 2 were stimulated in the mesencephalic locomotor region (MLR-induced). Absolute optical densities of the autoradiograms corresponding to identified anatomical structures of the brainstem were generally in the following order: Stepping greater than Anesthetized greater than MLR-induced greater than Rigidity. The 2-DG uptake relative to the pyramidal tract (2-DG ratio) also was compared for each of the 4 experimental procedures. In the Stepping cats, the 2-DG ratio was highest in the vestibular nuclei, periaqueductal gray, red nucleus and thalamic nuclei. In the Rigid cats, the 2-DG ratio was highest in the medial vestibular nucleus and subthalamic and thalamic nucleus. These findings suggest that the 2-DG tracer method can be useful in associating neural structures with specific kinds of motor functions within a cat. This is particularly true when using the relative activities of different neural structures and in comparing specific neural structures across cats under different experimental conditions when the amount of 2-DG infused is standardized and the optical densities of the autoradiograms are calibrated to a specific level of 2-DG.
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PMID:Application of autoradiographic analysis of 2-deoxyglucose in the study of locomotion. 368 80

Rigor complexes between actin and myosin have been shown to cause increased binding of Ca2+ to troponin C. A similar effect of force-generating crossbridges has been suggested as an explanation for the coupling between load and activation which has been observed in skeletal and cardiac muscle. The goal of this study was to test the hypothesis that Ca2+-troponin affinity during crossbridge cycling is load-dependent. Ca2+-binding to detergent-extracted rabbit psoas fibres was measured during ATP-induced force generation and in the relaxed state. To compare Ca2+ binding in the latter two states it was necessary to establish conditions in which ATP-induced force could be regulated independently of free Ca2+ concentration. Such conditions were obtained by the use of either the ATPase inhibitor sodium vanadate or the substitution of MgITP for MgATP as an energy source. This study showed that in the presence of MgATP (or MgITP) the amount of Ca2+ bound to the myofilaments at a given free Ca2+ concentration was independent of the force generated. Thus force per se is not a determinant of Ca2+-troponin affinity.
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PMID:The binding of calcium to detergent-extracted rabbit psoas muscle fibres during relaxation and force generation. 385 10

Sex differences in physical dependence on sodium pentobarbital in the rat were studied by the drug-admixed food (DAF) method. With male rats, the concentration of pentobarbital in the food was gradually increased from 2 to 30 mg/g over a period of 50 days. The final level of drug intake was approximately 1.7 g/kg/day. At pentobarbital concentrations of 20 and 22 mg/g of food, sedation and mild muscle relaxation were observed. At the highest drug concentration, 30 mg/g of food, marked muscle relaxation was noted. With female rats, the concentration of pentobarbital in the food was gradually increased from 1 to 16 mg/g over a period of 47 days. The final level of intake was approximately 1.0 mg/kg/day. At drug concentrations of 12 and 14 mg/g, sedation and mild muscle relaxation appeared. At 16 mg/g, female rats showed marked muscle relaxation similar to that of the male rats. To produce severe loss of muscle tone, the male rats required twice as much pentobarbital as the female rats. After substitution of normal food for the pentobarbital-admixed food, various signs of pentobarbital withdrawal occurred in both sexes. These signs included vocalization, irritability, muscle rigidity, tremors and convulsions. Onset of withdrawal was more rapid in the females, and the maximum weight loss was greater, 8.0% compared to 3.8% in the males. Physical dependence on pentobarbital was easily developed in both sexes by the DAF method. There was a marked sex difference in withdrawal which we attribute to sex differences in drug metabolizing enzyme activity.
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PMID:Sex differences in the induction of physical dependence on pentobarbital in the rat. 409 88

A non-lethal procedure for identifying pigs apt to develop malignant hyperthermia is described. Susceptible animals were exposed to a variety of anaesthetic and other agents and it was shown that thiopentone sodium and CT 1341 (Glaxo) afforded a measure of protection against the development of the syndrome. Pretreatment with procaine did not prevent the onset of the condition and the administration of procaine when muscle rigidity was present failed to prevent a fatal outcome. The syndrome was induced in susceptible animals by halothane, chloroform, and a combination of halothane with suxamethonium. The effects of cyclopropane in susceptible pigs could not be predicted, and other tests showed that suxamethonium alone would not induce muscle contracture. Pretreatment with lignocaine failed to prevent induction of the syndrome by halothane.We believe that the porcine syndrome may result from more than one defect and that in one particular type the most effective treatment is immediate cooling coupled with the administration of sodium bicarbonate.
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PMID:Further studies of porcine malignant hyperthermia. 501 6

1 Full-wave rectification and integration of the EMG signal recorded from the hamstring muscles of the spastic mouse was used to evaluate the actions of a variety of drugs on the muscle rigidity of these mutants, animals in which no histological lesion has yet been found. 2 Profound and long-lasting muscle relaxant responses were consistently observed upon the injection of diazepam (2 mg/kg, i.p.) and flunitrazepam (2 mg/kg, i.p.). Such responses were always greater than those obtained upon injection of 40% (v/v) propylene glycol (10 ml/kg) alone, the vehicle for the benzodiazepines. 3 The muscle relaxant action of a low dose (0.25 mg/kg i.p.) of the benzodiazepine Roll-6896 was not shared by the same dose of its enantiomer Roll-6893. 4 Profound and long-lasting muscle relaxation was caused by sodium valproate (696 mg/kg, i.p.). Consistent muscle relaxant responses were also observed upon the injection of pentobarbitone (30 mg/kg, i.p.), but not phenobarbitone (30 mg/kg, i.p.). 5 Other drugs that had little or no detectable effect on the muscle rigidity of the spastic mouse included diphenylhydantoin (30 mg/kg, i.p.) and bromocriptine (10 mg/kg, s.c.) while, in some animals, benztropine (2 mg/kg, i.p.) and baclofen (10 mg/kg, i.p.) increased muscle rigidity. 6 The development of full muscle relaxant responses to flunitrazepam (2 mg/kg, i.p.) and to sodium valproate (696 mg/kg, i.p.) was shown to depend upon mild warming of the animals with radiant heat, a procedure which can increase muscle spindle afferent input to the spinal cord. 7 The results suggest a hyperactivity of stretch reflexes in the spastic mouse, ameliorated selectively by those drugs that enhance the GABA-mediated presynaptic inhibition of such pathways.
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PMID:Some pharmacological studies on the spastic mouse. 707 84

Malignant hyperthermia is an autosomal dominant disorder with variable expressivity that is caused by a membrane defect in the sarcolemma of myofibrils. A patient with strabismus (esotropia) had tachycardia and masseter muscle rigidity on exposure to succinylcholine chloride and halothane, but because of rapid recognition of the condition and discontinuation of the procedure, the potentially lethal complications of malignant hyperthermia did not develop. A serum creatine phosphokinase level showed a substantial increase above normal. Two weeks later, the patient underwent successful correction of the strabismus under general anesthesia, using morphine sulfate and thiopental sodium without complication. This condition is of interest to ophthalmologists because it occurs with increasing frequency in patients with strabismus and ptosis, and it may be triggered by certain local anesthetic agents often used by ophthalmologists.
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PMID:Suspected malignant hyperthermia in a strabismus patient. A case report. 725 98

The incidence, etiology, clinical manifestations, and management of malignant hyperthermia (MH) are reviewed. The syndrome of MH is recognized as one of the causes of anesthesia-related deaths. It is considered pharmacogenetic because both an abnormal gene and precipitating environmental factors are necessary to produce an acute reaction. Metabolic defects, involving a derangement of calcium dynamics, appear to be the common characteristic of susceptible individuals. Calcium release and uptake from the sarcoplasmic reticulum is altered when an individual with MH is exposed to certain anesthetic agents or triggering physical and emotional stresses. Muscle rigidity, tachycardia, tachypnea, and high fever can lead to other complications and death. Management of an acute reaction of MH includes cooling methods to lower body temperature, hyperventilation, sodium bicarbonate control of acidosis, maintenance of fluid and electrolyte balance, and the administration of dantrolene sodium. A thorough family history, baseline CPKs, caffeine-halothane contracture tests, and ultramicroscopic examination of muscle biopsy specimens are recommended as screening techniques. The early administration of dantrolene sodium in acute reaction of MH has been shown to rapidly alleviate the symptoms and ensuing severe complications. Individuals with a strong family history of MH or previous episodes may be treated with oral dantrolene sodium before surgery to effectively prevent a crisis, and after surgery to prevent recurrence.
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PMID:Malignant hyperthermia: current perspectives. 728 92

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle. In humans, MH is inherited in an autosomal dominant fashion; in swine, the principal model for MH, it is in a recessive fashion. Those with MH susceptibility usually are asymptomatic except in the presence of certain "triggering" anaesthetic agents such as isoflurane, enflurane and the muscle relaxant succinylcholine. Upon such exposure hypermetabolism, increased CO2 production, acidosis, muscle rigidity, rhabdomyolysis and hyperthermia occur. Untreated, death may result in 70% of patients. With prompt diagnosis and treatment with dantrolene sodium, the mortality is less than 10%. The overall incidence of MH is low (perhaps 1:50,000 anaesthetics), but it is more common in children. Children also display a paradoxical increase in jaw muscle tone to succinylcholine which often presages MH, but confusing clinically, may also be a normal response to succinylcholine. The pathophysiology of MH centres around a defect in calcium flux in skeletal muscle. A specific base pair change in the gene that codes for the ryanodine receptor calcium channel in muscle has been demonstrated in susceptible swine, but occurs rarely in humans. It is hoped that the understanding of the molecular genetics of MH will lead to a simpler diagnostic test than is currently available, and enhance our understanding of MH and its relation to other myopathies.
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PMID:An update on the malignant hyperthermia syndrome. 771 Feb 42

Neuroleptic malignant syndrome (NMS) is a potentially fatal complication which may develop in psychiatric patients taking neuroleptic drugs. We report herein the successful treatment of a 33-year-old schizophrenic man, prescribed neuroleptic drugs, who underwent an emergency operation for traumatic duodenal perforation with a retroperitoneal infection. Five days after the operation, he began to demonstrate clinical features consistent with NMS such as high fever, abnormalities in vital signs, leukocytosis, and an elevated serum level of creatine phosphokinase; however, these findings were first presumed to be secondary to either the preexisting tissue injuries or to postoperative complications. A definite diagnosis of NMS was thus delayed until muscle rigidity and autonomic instability became evident. After a tentative diagnosis of NMS had been made, sodium dantrolene, a drug used specifically for the treatment of NMS, was administered and the patient's condition remarkably improved. Since NMS can be induced by either interrupting the course of neuroleptic drugs or by the additional administration of sedative drugs, and since its mortality rate is high if prompt and appropriate treatment is not carried out, surgeons should bear in mind the possibility of NMS developing postoperatively in psychiatric patients.
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PMID:Neuroleptic malignant syndrome occurring after an emergency operation for traumatic duodenal perforation: report of a case. 791 92

We describe a case of generalized muscle rigidity in a 2-year-old patient with Freeman-Sheldon syndrome undergoing surgery for eventration of the diaphragm after anesthetic induction with halothane and succinylcholine. Anesthetic induction was by mask with oxygen, nitrous oxide and halothane, with succinylcholine as a muscle relaxant. Approximately 10 minutes after start of induction, muscular rigidity appeared and developed rapidly, becoming severe and compromising ventilation. Tracheal intubation was attempted without success, owing to stiffness of the masseter muscles. Sodium dantrolene 2.5 mg/kg was administered and relaxation was achieved immediately for both masseter and peripheral muscles, such that the patient recovered spontaneous breathing. We conclude that there is risk of association between Freeman-Sheldon syndrome and malignant hyperthermia.
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PMID:[Freeman-Sheldon syndrome: generalized muscular rigidity after anesthetic induction]. 805 48


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