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Missouri Medicine 2019Malignant Hyperthermia (MH) is a life-threatening pharmacogenetic disorder which results from exposure to volatile anesthetic agents and depolarizing muscle relaxants.... (Review)
Review
Malignant Hyperthermia (MH) is a life-threatening pharmacogenetic disorder which results from exposure to volatile anesthetic agents and depolarizing muscle relaxants. It manifests as a hypermetabolic response resulting in tachycardia, tachypnea, hyperthermia, hypercapnia, acidosis, muscle rigidity and rhabdomyolysis. An increase in the end-tidal carbon dioxide is one of the earliest diagnostic signs. Dantrolene sodium is effective in the management of MH, and should be available whenever general anesthesia is administered. This review also aims to highlight the genetics and pathology of MH, along with its association with various inherited myopathy syndromes like central core disease, multi-mini core disease, Native-American myopathy, and King-Denborough syndrome.
Topics: Anesthetics; Dantrolene; Humans; Malignant Hyperthermia; Muscle Relaxants, Central; Neuromuscular Depolarizing Agents
PubMed: 31040503
DOI: No ID Found -
Toxins Apr 2021The simple definition of tone as the resistance to passive stretch is physiologically a complex interlaced network encompassing neural circuits in the brain, spinal... (Review)
Review
The simple definition of tone as the resistance to passive stretch is physiologically a complex interlaced network encompassing neural circuits in the brain, spinal cord, and muscle spindle. Disorders of muscle tone can arise from dysfunction in these pathways and manifest as hypertonia or hypotonia. The loss of supraspinal control mechanisms gives rise to hypertonia, resulting in spasticity or rigidity. On the other hand, dystonia and paratonia also manifest as abnormalities of muscle tone, but arise more due to the network dysfunction between the basal ganglia and the thalamo-cerebello-cortical connections. In this review, we have discussed the normal homeostatic mechanisms maintaining tone and the pathophysiology of spasticity and rigidity with its anatomical correlates. Thereafter, we have also highlighted the phenomenon of network dysfunction, cortical disinhibition, and neuroplastic alterations giving rise to dystonia and paratonia.
Topics: Animals; Brain; Dystonia; Humans; Muscle Contraction; Muscle Hypertonia; Muscle Rigidity; Muscle Spasticity; Muscle Tonus; Muscle, Skeletal; Neural Pathways; Spinal Cord
PubMed: 33923397
DOI: 10.3390/toxins13040282 -
Orphanet Journal of Rare Diseases Aug 2015Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as... (Review)
Review
Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane, isoflurane and the depolarizing muscle relaxant succinylcholine, and rarely, in humans, to stressors such as vigorous exercise and heat. The incidence of MH reactions ranges from 1:10,000 to 1: 250,000 anesthetics. However, the prevalence of the genetic abnormalities may be as great as one in 400 individuals. MH affects humans, certain pig breeds, dogs and horses. The classic signs of MH include hyperthermia, tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, hyperkalaemia, muscle rigidity, and rhabdomyolysis, all related to a hypermetabolic response. The syndrome is likely to be fatal if untreated. An increase in end-tidal carbon dioxide despite increased minute ventilation provides an early diagnostic clue. In humans the syndrome is inherited in an autosomal dominant pattern, while in pigs it is autosomal recessive. Uncontrolled rise of myoplasmic calcium, which activates biochemical processes related to muscle activation leads to the pathophysiologic changes. In most cases, the syndrome is caused by a defect in the ryanodine receptor. Over 400 variants have been identified in the RYR1 gene located on chromosome 19q13.1, and at least 34 are causal for MH. Less than 1 % of variants have been found in CACNA1S but not all of these are causal. Diagnostic testing involves the in vitro contracture response of biopsied muscle to halothane, caffeine, and in some centres ryanodine and 4-chloro-m-cresol. Elucidation of the genetic changes has led to the introduction of DNA testing for susceptibility to MH. Dantrolene sodium is a specific antagonist and should be available wherever general anesthesia is administered. Increased understanding of the clinical manifestation and pathophysiology of the syndrome, has lead to the mortality decreasing from 80 % thirty years ago to <5 % in 2006.
Topics: Genetic Counseling; Humans; Malignant Hyperthermia
PubMed: 26238698
DOI: 10.1186/s13023-015-0310-1 -
British Journal of Pharmacology Apr 2023Fentanyl is a key therapeutic, used in anaesthesia and pain management. It is also increasingly used illicitly and is responsible for a large and growing number of... (Review)
Review
Fentanyl is a key therapeutic, used in anaesthesia and pain management. It is also increasingly used illicitly and is responsible for a large and growing number of opioid overdose deaths, especially in North America. A number of factors have been suggested to contribute to fentanyl's lethality, including rapid onset of action, in vivo potency, ligand bias, induction of muscle rigidity and reduced sensitivity to reversal by naloxone. Some of these factors can be considered to represent 'anomalous' pharmacological properties of fentanyl when compared with prototypical opioid agonists such as morphine. In this review, we examine the nature of fentanyl's 'anomalous' properties, to determine whether there is really a pharmacological basis to support the existence of such properties, and also discuss whether such properties are likely to contribute to overdose deaths involving fentanyls. LINKED ARTICLES: This article is part of a themed issue on Advances in Opioid Pharmacology at the Time of the Opioid Epidemic. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.7/issuetoc.
Topics: Humans; Fentanyl; Analgesics, Opioid; Narcotic Antagonists; Naloxone; Drug Overdose
PubMed: 34030211
DOI: 10.1111/bph.15573 -
Internal Medicine (Tokyo, Japan) Jan 2020Various methods of rehabilitation for dysphagia have been suggested through the experience of treating stroke patients. Although most of these patients recover their... (Review)
Review
Various methods of rehabilitation for dysphagia have been suggested through the experience of treating stroke patients. Although most of these patients recover their swallowing function in a short period, dysphagia in Parkinson's disease (PD) and Parkinson-related disorder (PRD) degenerates with disease progression. Muscle rigidity and bradykinesia are recognized as causes of swallowing dysfunction, and it is difficult to easily apply the strategies for stroke to the rehabilitation of dysphagia in PD patients. Disease severity, weight loss, drooling, and dementia are important clinical predictors. Silent aspiration is a pathognomonic sign that may lead to aspiration pneumonia. Severe PD patients need routine video fluoroscopy or video endoscopy to adjust their food and liquid consistency. Patients with PRD experience rapid progression of swallowing dysfunction. Nutrition combined with nasogastric tube feeding or percutaneous endoscopic gastrostomy feeding should be considered owing to the increased risk of aspiration and difficulty administrating oral nutrition.
Topics: Deglutition; Deglutition Disorders; Disease Progression; Enteral Nutrition; Humans; Hypokinesia; Muscle Rigidity; Parkinson Disease; Pneumonia, Aspiration; Respiratory Aspiration; Stroke Rehabilitation
PubMed: 30996170
DOI: 10.2169/internalmedicine.2373-18 -
Frontiers in Sports and Active Living 2019The foot is a complex system with multiple degrees of freedom that play an essential role in running or sprinting. The intrinsic foot muscles (IFM) are the main local... (Review)
Review
The foot is a complex system with multiple degrees of freedom that play an essential role in running or sprinting. The intrinsic foot muscles (IFM) are the main local stabilizers of the foot and are part of the active and neural subsystems that constitute the foot core. These muscles lengthen eccentrically during the stance phase of running before shortening at the propulsion phase, as the arch recoils in parallel to the plantar fascia. They play a key role in supporting the medial longitudinal arch, providing flexibility, stability and shock absorption to the foot, whilst partially controlling pronation. Much of the foot rigidity in late stance has been attributed to the windlass mechanism - the dorsiflexion of the toes building tension up in the plantar aponeurosis and stiffening the foot. In addition, recent studies have shown that the IFM provide a necessary active contribution in late stance, in order to develop sufficient impedance in the metatarsal-phalangeal joints. This in turn facilitates the propulsive forces at push-off. These factors support the critical role of the foot in providing rigidity and an efficient lever at push-off. During running or sprinting, athletes need to generate and maintain the highest (linear) running velocity during a single effort in a sprinting lane. Acceleration and sprinting performance requires forces to be transmitted efficiently to the ground. It may be of particular interest to strengthen foot muscles to maintain and improve an optimal capacity to generate and absorb these forces. The current evidence supports multiple exercises to achieve higher strength in the foot, such as the "short foot exercise," doming, toes curl, towing exercises or the more dynamic hopping exercises, or even barefoot running. Their real impact on foot muscle strength remains unclear and data related to its assessment remains scarce, despite a recognized need for this, especially before and after a strengthening intervention. It would be optimal to be able to assess it. In this article, we aim to provide the track and field community with an updated review on the current modalities available for foot strength assessment and training. We present recommendations for the incorporation of foot muscles training for performance and injury prevention in track and field.
PubMed: 33344969
DOI: 10.3389/fspor.2019.00046 -
Nature Reviews. Molecular Cell Biology Dec 2017A growing body of evidence suggests that mechanical signals emanating from the cell's microenvironment are fundamental regulators of cell behaviour. Moreover, at the... (Review)
Review
A growing body of evidence suggests that mechanical signals emanating from the cell's microenvironment are fundamental regulators of cell behaviour. Moreover, at the macroscopic scale, the influence of forces, such as the forces generated by blood flow, muscle contraction, gravity and overall tissue rigidity (for example, inside of a tumour lump), is central to our understanding of physiology and disease pathogenesis. Still, how mechanical cues are sensed and transduced at the molecular level to regulate gene expression has long remained enigmatic. The identification of the transcription factors YAP and TAZ as mechanotransducers started to fill this gap. YAP and TAZ read a broad range of mechanical cues, from shear stress to cell shape and extracellular matrix rigidity, and translate them into cell-specific transcriptional programmes. YAP and TAZ mechanotransduction is critical for driving stem cell behaviour and regeneration, and it sheds new light on the mechanisms by which aberrant cell mechanics is instrumental for the onset of multiple diseases, such as atherosclerosis, fibrosis, pulmonary hypertension, inflammation, muscular dystrophy and cancer.
Topics: Acyltransferases; Adaptor Proteins, Signal Transducing; Animals; Atherosclerosis; Cell Shape; Extracellular Matrix; Fibrosis; Humans; Hypertension, Pulmonary; Mechanotransduction, Cellular; Muscular Dystrophies; Neoplasms; Phosphoproteins; Shear Strength; Transcription Factors; Transcription, Genetic; YAP-Signaling Proteins
PubMed: 28951564
DOI: 10.1038/nrm.2017.87 -
Physiological Research Mar 2019Parkinson's disease (PD), which is the second most common neurodegenerative disorder after Alzheimer's disease, is firstly defined after James Parkinson's report. It... (Review)
Review
Parkinson's disease (PD), which is the second most common neurodegenerative disorder after Alzheimer's disease, is firstly defined after James Parkinson's report. It carries motor symptoms such as resting tremor, bradykinesia and rigidity of skeletal muscle and freezing of gait. Furthermore, non-motor symptoms such as cognitive and behavioral problems, besides sensory impairments are seen in the patients. However, they may also suffer from sleep disorders or autonomic dysfunction. Although there are some medications in order to symptomatic management, but unfortunately, scientist could not have found exact approaches to cure this disease. Hence, producing a model which can express the most pathophysiologic and behavioral aspects of the disease is a desire. In this paper, we aimed to describe the different models of Parkinson's disease in brief.
Topics: Animals; Disease Models, Animal; Humans; MPTP Poisoning; Oxidopamine; Parkinson Disease
PubMed: 30433804
DOI: 10.33549/physiolres.933895