-
Ugeskrift For Laeger Apr 2022
Topics: Carotid Artery, Internal; Carotid Artery, Internal, Dissection; Horner Syndrome; Humans
PubMed: 35410649
DOI: No ID Found -
Vascular Health and Risk Management 2022Bidirectional ventricular tachycardia (BiVT) is a rare form of ventricular tachycardia that manifests on surface electrocardiogram by dual QRS morphologies alternating... (Review)
Review
Bidirectional ventricular tachycardia (BiVT) is a rare form of ventricular tachycardia that manifests on surface electrocardiogram by dual QRS morphologies alternating on a beat-to-beat basis. It was first reported in the 1920s as a complication of digoxin, and since then, it has been reported in other conditions including fulminant myocarditis, sarcoidosis, catecholaminergic polymorphic ventricular tachycardia, and Andersen-Tawil syndrome. The mechanism for BiVT is not as well known as other forms of ventricular tachycardia but appears to include typical mechanisms including triggered activity from afterdepolarizations, abnormal automaticity, or reentry. This review will go beyond the definition, surface electrocardiogram, mechanisms, causes, and treatment of BiVT as per our current understanding.
Topics: Andersen Syndrome; Electrocardiography; Humans; Tachycardia; Tachycardia, Ventricular
PubMed: 35698640
DOI: 10.2147/VHRM.S274857 -
International Archives of Occupational... Oct 2022To evaluate the effects of online-supervised versus workplace corrective exercises on neck-shoulder pain (NSP), sick leave, posture, workability, and muscular activity... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To evaluate the effects of online-supervised versus workplace corrective exercises on neck-shoulder pain (NSP), sick leave, posture, workability, and muscular activity among office workers with the upper crossed syndrome (UCS).
METHODS
We performed a parallel-group randomized control trial at Shahid Beheshti University, Tehran, Iran, assigning 36 office workers to online-supervised, workplace, and control groups (mean (SD) age 38.91 ± 3.87, 38.58 ± 7.34, 37.00 ± 8.12). Inclusion criteria were alignment alteration (forward head (≥ 45°), rounding shoulder (≥ 52°), rounding back (≥ 42°), and pain intensity ≥ 3 in neck and shoulder. The two intervention groups performed 8-week exercise program, while the control group continued usual activities. Primary (NSP and sick leave) and secondary outcomes [postural angles, workability, and muscular activity were measured by VAS, outcome evaluation questionnaire (OEQ), photogrammetry, workability index, and EMG, respectively, at the baseline and an 8-week follow-up].
RESULTS
ANCOVA results revealed improvements for the online-supervised group versus control for NSP (P = 0.007), postural angles (P = 0.000, P = 0.001, P = 0.005), workability (P = 0.048, P = 0.042), and upper trapezius activation (P = 0.024, P = 0.016), respectively. Using paired t tests, both intervention groups improved from baseline to follow-up for NSP (P = 0.000, P = 0.002), forward head posture (P = 0.000, P = 0.000), round shoulders (P = 0.001, P = 0.031), and round back (P = 0.034, P = 0.008), respectively. Related parameters of workability (P = 0.041, P = 0.038), upper trapezius (P = 0.005, P = 0.005, P = 0.022), and serratus anterior (P = 0.020, P = 0.015) changed only in the online-supervised group.
CONCLUSION
Online-supervised corrective exercise seems to improve a range of parameters related to work performance. These findings are highly applicable in light of the ongoing COVID pandemic; many workers have to work from home.
Topics: COVID-19; Exercise Therapy; Humans; Iran; Musculoskeletal Pain; Superficial Back Muscles; Workplace
PubMed: 35391580
DOI: 10.1007/s00420-022-01859-3 -
Ugeskrift For Laeger Nov 2023Rusty pipe syndrome (RPS) is a benign, self-limiting condition characterized by bloody milk secretion, and is primarily seen among primiparous women. This case report...
Rusty pipe syndrome (RPS) is a benign, self-limiting condition characterized by bloody milk secretion, and is primarily seen among primiparous women. This case report highlights the clinical presentation of a 31-year-old primiparous woman with bloody milk secretion from gestational week 31. This persisted throughout pregnancy until seven days after birth. RPS should be considered in pregnant women with painless bilateral bloody milk secretion during pregnancy and/or the early days post-partum. The milk can safely be provided to the infant, and RPS is not an indication for formula feeding.
Topics: Infant; Female; Pregnancy; Humans; Adult; Animals; Breast Feeding; Lactation; Milk; Postpartum Period; Syndrome; Parity
PubMed: 38018741
DOI: No ID Found -
Indian Pacing and Electrophysiology... Jan 2006Andersen-Tawil syndrome (ATS) is a rare condition consisting of ventricular arrhythmias, periodic paralysis, and dysmorphic features. In 2001, mutations in KCNJ2, which...
Andersen-Tawil syndrome (ATS) is a rare condition consisting of ventricular arrhythmias, periodic paralysis, and dysmorphic features. In 2001, mutations in KCNJ2, which encodes the a subunit of the potassium channel Kir2.1, were identified in patients with ATS. To date, KCNJ2 is the only gene implicated in ATS, accounting for approximately 60% of cases. ATS is a unique channelopathy, and represents the first link between cardiac and skeletal muscle excitability. The arrhythmias observed in ATS are distinctive; patients may be asymptomatic, or minimally symptomatic despite a high arrhythmia burden with frequent ventricular ectopy and bidirectional ventricular tachycardia. However, patients remain at risk for life-threatening arrhythmias, including torsades de pointes and ventricular fibrillation, albeit less commonly than observed in other genetic arrhythmia syndromes. The characteristic heterogeneity at both the genotypic and phenotypic levels contribute to the continued difficulties with appropriate diagnosis, risk stratification, and effective therapy. The initial recognition of a syndromic association of clinically diverse symptoms, and the subsequent identification of the underlying molecular genetic basis of ATS has enhanced both clinical care, and our understanding of the critical function of Kir2.1 on skeletal muscle excitability and cardiac action potential.
PubMed: 16943893
DOI: No ID Found -
Circulation Research Apr 2024Andersen-Tawil syndrome type 1 is a rare heritable disease caused by mutations in the gene coding the strong inwardly rectifying K channel Kir2.1. The extracellular Cys...
BACKGROUND
Andersen-Tawil syndrome type 1 is a rare heritable disease caused by mutations in the gene coding the strong inwardly rectifying K channel Kir2.1. The extracellular Cys (cysteine)-to-Cys disulfide bond in the channel structure is crucial for proper folding but has not been associated with correct channel function at the membrane. We evaluated whether a human mutation at the Cys-to-Cys disulfide bridge leads to Kir2.1 channel dysfunction and arrhythmias by reorganizing the overall Kir2.1 channel structure and destabilizing its open state.
METHODS
We identified a Kir2.1 loss-of-function mutation (c.366 A>T; p.Cys122Tyr) in an ATS1 family. To investigate its pathophysiological implications, we generated an AAV9-mediated cardiac-specific mouse model expressing the Kir2.1 variant. We employed a multidisciplinary approach, integrating patch clamping and intracardiac stimulation, molecular biology techniques, molecular dynamics, and bioluminescence resonance energy transfer experiments.
RESULTS
Kir2.1 mice recapitulated the ECG features of ATS1 independently of sex, including corrected QT prolongation, conduction defects, and increased arrhythmia susceptibility. Isolated Kir2.1 cardiomyocytes showed significantly reduced inwardly rectifier K+ (I) and inward Na+ (I) current densities independently of normal trafficking. Molecular dynamics predicted that the C122Y mutation provoked a conformational change over the 2000-ns simulation, characterized by a greater loss of hydrogen bonds between Kir2.1 and phosphatidylinositol 4,5-bisphosphate than wild type (WT). Therefore, the phosphatidylinositol 4,5-bisphosphate-binding pocket was destabilized, resulting in a lower conductance state compared with WT. Accordingly, on inside-out patch clamping, the C122Y mutation significantly blunted Kir2.1 sensitivity to increasing phosphatidylinositol 4,5-bisphosphate concentrations. In addition, the Kir2.1 mutation resulted in channelosome degradation, demonstrating temporal instability of both Kir2.1 and Na1.5 proteins.
CONCLUSIONS
The extracellular Cys-to-Cys disulfide bond in the tridimensional Kir2.1 channel structure is essential for the channel function. We demonstrate that breaking disulfide bonds in the extracellular domain disrupts phosphatidylinositol 4,5-bisphosphate-dependent regulation, leading to channel dysfunction and defects in Kir2.1 energetic stability. The mutation also alters functional expression of the Na1.5 channel and ultimately leads to conduction disturbances and life-threatening arrhythmia characteristic of Andersen-Tawil syndrome type 1.
Topics: Humans; Mice; Animals; Andersen Syndrome; Mutation; Myocytes, Cardiac; Cardiac Conduction System Disease; Disulfides; Phosphatidylinositols
PubMed: 38497220
DOI: 10.1161/CIRCRESAHA.123.323895 -
Annals of Noninvasive Electrocardiology... May 2019We report on a 44-year-old woman with coincidence of two genetic disorders: Andersen-Tawil syndrome and Marfan syndrome. In both, life-threatening arrhythmias could... (Review)
Review
We report on a 44-year-old woman with coincidence of two genetic disorders: Andersen-Tawil syndrome and Marfan syndrome. In both, life-threatening arrhythmias could occur. A 44-year-old woman presented acute ascending aortic dissection with aortic arch involvement and chronic thoracic descending and abdominal aortic dissection. Clinical and genetic examination confirmed Marfan syndrome (MFS) diagnosis. Due to repolarization disorder in ECG and premature ventricular contractions in Holter ECG, the sequencing data were analyzed again and mutation in KCNJ2 gene was identified. The case showed that coincidence of Andersen-Tawil syndrome (ATS) and MFS did not provoke life-threatening arrhythmias. Complication was rather caused by expression of FBN1 mutation.
Topics: Adult; Andersen Syndrome; Aortic Dissection; Aortic Aneurysm, Thoracic; Electrocardiography; Emergency Service, Hospital; Female; Fibrillin-1; G Protein-Coupled Inwardly-Rectifying Potassium Channels; Genetic Predisposition to Disease; Humans; Marfan Syndrome; Monitoring, Physiologic; Multimorbidity; Mutation; Potassium Channels, Inwardly Rectifying; Rare Diseases; Risk Assessment; Severity of Illness Index; Treatment Outcome
PubMed: 30672637
DOI: 10.1111/anec.12624 -
Journal of the American College of... Apr 2020
Topics: Andersen Syndrome; Humans; Mutation; Risk Assessment
PubMed: 32299590
DOI: 10.1016/j.jacc.2020.03.005 -
Current Treatment Options in Neurology 2020This article aims to review the current and upcoming treatment options of primary muscle channelopathies including the non-dystrophic myotonias and periodic paralyses. (Review)
Review
PURPOSE OF REVIEW
This article aims to review the current and upcoming treatment options of primary muscle channelopathies including the non-dystrophic myotonias and periodic paralyses.
RECENT FINDINGS
The efficacy of mexiletine in the treatment of myotonia is now supported by two randomised placebo-controlled trials, one of which utilised a novel aggregated n-of-1 design. This has resulted in licencing of the drug via orphan drug status. There is also good evidence that mexiletine is well tolerated and safe in this patient group without the need for intensive monitoring. A range of alternative antimyotonic treatment options include lamotrigine, carbamazepine and ranolazine exist with variable evidence base. In vitro studies have shown insight into reasons for treatment failure of some medications with certain genotypes opening the era of mutation-specific therapy such as use of flecainide. In the periodic paralyses, the ability of MRI to distinguish between reversible oedema and irreversible fatty replacement makes it an increasingly useful tool to guide and assess pharmacological treatment. Unfortunately, the striking efficacy of bumetanide in hypokalaemic periodic paralysis animal models was not replicated in a recent pilot study in humans.
SUMMARY
The treatment of skeletal muscle channelopathies combines dietary and lifestyle advice together with pharmacological interventions. The rarity of these conditions remains a barrier for clinical studies but the example of the aggregated n-of-1 trial of mexiletine shows that innovative trial design can overcome these hurdles. Further research is required to test efficacy of drugs shown to have promising characteristics in preclinical experiments such as safinamide, riluzule and magnesium for myotonia or bumetanide for hypokalaemic periodic paralysis.
PubMed: 32848354
DOI: 10.1007/s11940-020-00644-2 -
Ugeskrift For Laeger Jul 2017Hyperthermia is an uncontrolled elevation of body temperature exceeding the body's ability to dissipate heat. Hyperthermia can result in dangerously high core... (Review)
Review
Hyperthermia is an uncontrolled elevation of body temperature exceeding the body's ability to dissipate heat. Hyperthermia can result in dangerously high core temperatures and can rapidly become fatal. Common causes include heat stroke, malignant hyperthermia, serotonin syndrome, neuroleptic syndrome, a few endocrine emergencies as well as numerous intoxications. Rapid diagnosis and prompt cooling are pivotal, since the condition triggers a cascade of metabolic events which may progress to irreversible injury or death. Ice-water immersion and evaporative cooling are the methods of choice.
Topics: Adrenal Insufficiency; Critical Pathways; Fever; Heat Stroke; Humans; Hypothermia, Induced; Malignant Hyperthermia; Neuroleptic Malignant Syndrome; Pheochromocytoma; Serotonin Syndrome; Thyroid Crisis
PubMed: 28789764
DOI: No ID Found