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Scientific Reports Aug 2021We investigated hemodynamic, cardiac morphofunctional, and cardiovascular autonomic adaptations in spontaneously hypertensive rats (SHRs) after aerobic physical training...
Effects of chronic cholinergic stimulation associated with aerobic physical training on cardiac morphofunctional and autonomic parameters in spontaneously hypertensive rats.
We investigated hemodynamic, cardiac morphofunctional, and cardiovascular autonomic adaptations in spontaneously hypertensive rats (SHRs) after aerobic physical training associated with chronic cholinergic stimulation. Fifty-four SHRs were divided into two groups: trained and untrained. Each group was further subdivided into three smaller groups: vehicle, treated with pyridostigmine bromide at 5 mg/kg/day, and treated with pyridostigmine bromide at 15 mg/kg/day. The following protocols were assessed: echocardiography, autonomic double pharmacological blockade, heart rate variability (HRV), blood pressure variability (BPV), and baroreflex sensitivity (BRS). Physical training and pyridostigmine bromide reduced BP and HR and increased vagal participation in cardiac autonomic tonic balance. The associated responses were then potentialized. Treatment with pyridostigmine bromide increased HRV oscillation of both low frequency (LF: 0.2-0.75 Hz) and high frequency (HF: 0.75-3 Hz). However, the association with physical training attenuated HF oscillations. Additionally, treatment with pyridostigmine bromide also increased LF oscillations of BPV. Both treatment groups promoted morphofunctional adaptations, and associated increased ejection volume, ejection fraction, cardiac output, and cardiac index. In conclusion, the association of pyridostigmine bromide and physical training promoted greater benefits in hemodynamic parameters and increased vagal influence on cardiac autonomic tonic balance. Nonetheless, treatment with pyridostigmine bromide alone seems to negatively affect BPV and the association of treatment negatively influences HRV.
Topics: Animals; Blood Pressure; Cardiac Output; Cholinesterase Inhibitors; Heart; Hypertension; Physical Conditioning, Animal; Pyridostigmine Bromide; Rats; Rats, Inbred SHR; Vagus Nerve
PubMed: 34433865
DOI: 10.1038/s41598-021-96505-2 -
Case Reports in Neurology 2021It remains uncertain to what extent lower urinary tract (LUT) symptom (LUTS) is a comorbidity of myasthenia gravis (MG). We prospectively administered a LUTS...
It remains uncertain to what extent lower urinary tract (LUT) symptom (LUTS) is a comorbidity of myasthenia gravis (MG). We prospectively administered a LUTS questionnaire devised for detecting neurogenic pelvic organ dysfunction (not validated) in an MG group and a healthy control group and compared the results. The MG group comprised 21 patients: 15 women and 6 men, with age range 22-73 (mean 47) years, illness duration range 0.2-8 (mean 3.5) years, median Myasthenia Gravis Foundation of America (MGFA) grade 2, all walking independently. Therapies included thymectomy in 17, predonisolone 5-20 mg/day in 10, and pyridostigmine bromide 60-180 mg/day in 9 patients. The control group, who were undergoing an annual health survey, comprised 235 consecutive subjects: 120 women and 115 men, with age range 30-69 (mean 48) years. The questionnaire had 9 questions. Each question was scored from 0 (none) to 3 (severe) with an additional quality of life (QOL) index scored from 0 (satisfied) to 3 (extremely dissatisfied). Statistical analysis was made using Student's test. Compared with the control subjects, the frequency of LUTSs in the MG patients was significantly higher for daytime frequency (43%; < 0.01), nocturia (24%; < 0.01), and urinary incontinence (43%; < 0.05). The LUTS-related QOL index for the MG patients was significantly higher for MG patients as a whole than that for all control patients (29%) ( < 0.05). In conclusion, our study results showed that MG patients had significantly more LUTSs (overactive bladder) than healthy control subjects and had worse LUTS-related QOL; therefore, amelioration of LUTS in MG is important.
PubMed: 34413752
DOI: 10.1159/000514825 -
Life Sciences Nov 2021Approximately 30% of the nearly 700,000 Veterans who were deployed to the Gulf War from 1990 to 1991 have reported experiencing a variety of symptoms including...
AIMS
Approximately 30% of the nearly 700,000 Veterans who were deployed to the Gulf War from 1990 to 1991 have reported experiencing a variety of symptoms including difficulties with learning and memory, depression and anxiety, and increased incidence of neurodegenerative diseases. Combined toxicant exposure to acetylcholinesterase (AChE) inhibitors has been studied extensively as a likely risk factor. In this study, we modeled Gulf War exposure in male C57Bl/6J mice with simultaneous administration of three chemicals implicated as exposure hazards for Gulf War Veterans: pyridostigmine bromide, the anti-sarin prophylactic; chlorpyrifos, an organophosphate insecticide; and the repellant N,N-diethyl-m-toluamide (DEET).
MAIN METHODS
Following two weeks of daily exposure, we examined changes in gene expression by whole transcriptome sequencing (RNA-Seq) with hippocampal isolates. Hippocampal-associated spatial memory was assessed with a Y-maze task. We hypothesized that genes important for neuronal health become dysregulated by toxicant-induced damage and that these detrimental inflammatory gene expression profiles could lead to chronic neurodegeneration.
KEY FINDINGS
We found dysregulation of genes indicating a pro-inflammatory response and downregulation of genes associated with neuronal health and several important immediate early genes (IEGs), including Arc and Egr1, which were both reduced approximately 1.5-fold. Mice exposed to PB + CPF + DEET displayed a 1.6-fold reduction in preference for the novel arm, indicating impaired spatial memory.
SIGNIFICANCE
Differentially expressed genes observed at an acute timepoint may provide insight into the pathophysiology of Gulf War Illness and further explanations for chronic neurodegeneration after toxicant exposure.
Topics: Animals; Down-Regulation; Environmental Pollutants; Gene Expression Profiling; Gene Expression Regulation; Gene Ontology; Gulf War; Hippocampus; Male; Maze Learning; Mice, Inbred C57BL; Spatial Memory; Up-Regulation; Mice
PubMed: 34293396
DOI: 10.1016/j.lfs.2021.119845 -
Revista de Neurologia Aug 2021Early diagnosis based on clinical findings, neurophysiological studies and serum antibody titres allows early initiation of symptomatic treatment and oncological...
INTRODUCTION
Early diagnosis based on clinical findings, neurophysiological studies and serum antibody titres allows early initiation of symptomatic treatment and oncological screening. Reports of patients with LEMS in Latin America are scarce.
AIM
This article aims to describe the characteristics of patients with LEMS from a private centre in Buenos Aires, Argentina, and to compare them with those of other series that have been published.
PATIENTS AND METHODS
The medical records of 13 patients with LEMS with clinical findings, compatible electromyogram and/or positive antibodies were reviewed. Follow-up was performed until associated neoplasia was ruled out or confirmed according to the recommended algorithms.
RESULTS
Four patients were diagnosed with T-LEMS, two of them with small-cell lung carcinoma. Of the nine patients with NT-LEMS, five had a DELTA-P score of 3 and 4. Nine patients presented with the classic clinical triad from the onset of the disease. All patients had electromyogram findings compatible with presynaptic neuromuscular plaque defect. Of the total, 70% improved symptomatically with pyridostigmine.
CONCLUSIONS
The clinical findings, together with compatible neurophysiological studies, are sufficient for the diagnosis of LEMS. The relationship between the DELTA-P score and the risk of small-cell lung carcinoma could not be replicated. Symptomatic treatment with pyridostigmine represents an effective therapeutic alternative.
Topics: Adolescent; Adult; Aged; Argentina; Carcinoma, Small Cell; Electromyography; Female; Humans; Immunoglobulins, Intravenous; Lambert-Eaton Myasthenic Syndrome; Lung Neoplasms; Male; Middle Aged; Neuromuscular Junction; Pyridostigmine Bromide; Retrospective Studies; Symptom Assessment; Young Adult
PubMed: 34291446
DOI: 10.33588/rn.7303.2021140 -
BMJ Case Reports Jul 2021Several case reports of COVID-19 in patients with myasthenia gravis (MG) have been documented. However, new-onset autoimmune MG following COVID-19 has been reported very...
Several case reports of COVID-19 in patients with myasthenia gravis (MG) have been documented. However, new-onset autoimmune MG following COVID-19 has been reported very rarely. We report one such case here. A 65-year-old man presented to us with dysphagia 6 weeks following mild COVID-19. He was evaluated and diagnosed as antiacetylcholine receptor antibody (AchR) positive, non-thymomatous, generalised MG. He subsequently developed myasthenic crisis and improved after treatment with intravenous immunoglobulin, prednisolone and pyridostigmine. Systematic literature review showed eight more similar cases. Analysis of all cases including the one reported here showed these features: mean age 55.8 years, male gender (5), time interval between COVID-19 and MG (5-56 days), generalised (5), bulbar and/or ocular symptoms (4), anti-AchR antibodies (7) and antimuscle-specific kinase antibodies (2). All have improved with immunotherapy. Although, many hypothesis are proposed to explain causal relationship between the two, it could as well be sheer coincidence.
Topics: Aged; COVID-19; Humans; Male; Middle Aged; Myasthenia Gravis; Pyridostigmine Bromide; Receptors, Cholinergic; SARS-CoV-2
PubMed: 34290032
DOI: 10.1136/bcr-2021-244146 -
Annals of the Royal College of Surgeons... Jul 2021We present a case of a man with a background of myasthenia gravis who presented with a neck lump, which was diagnosed as thyrolipomatosis in continuity with a very large... (Review)
Review
We present a case of a man with a background of myasthenia gravis who presented with a neck lump, which was diagnosed as thyrolipomatosis in continuity with a very large thymolipoma. Following removal of these lesions, the patient's myaesthenic symptoms improved. While thymolipomas are often seen in the context of myasthenia gravis, thyrolipomatosis is a rare entity and to our knowledge the concurrent finding of both lesions with myasthenia gravis has never been reported. We highlight the important imaging features of both entities and the clinical importance of recognising them.
Topics: Adult; Humans; Lipoma; Lipomatosis; Male; Myasthenia Gravis; Prednisolone; Pyridostigmine Bromide; Thymectomy; Thymus Gland; Thymus Neoplasms; Thyroid Diseases; Thyroid Gland; Thyroidectomy; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 34192501
DOI: 10.1308/rcsann.2020.7089 -
Medicine Jun 2021To investigate clinical features and diagnosis process of ocular myasthenia gravis (OMG) in ophthalmology department.A total of 36 patients with ptosis or diplopia who... (Observational Study)
Observational Study
To investigate clinical features and diagnosis process of ocular myasthenia gravis (OMG) in ophthalmology department.A total of 36 patients with ptosis or diplopia who had follow-up for at least 3 months between March 2016 and December 2019 were included in this study. Clinical symptoms of patients and the test results were analyzed. According to the positivity of serologic test, these patients were divided into 2 groups (confirmed OMG and possible OMG with relief of symptoms after antimyasthenic treatment) for comparison.Ptosis was present in 12 (33.33%) patients, diplopia was present in 14 (38.89%) patients, and both ptosis and diplopia were present in 10 (27.78%) patients. Acetylcholine receptor auto-antibody (AchR Ab) was positive in 14 (38.89%) of 36 patients and ice test was positive in 15 (71.43%) of 21 patients with ptosis. Unequivocal response to pyridostigmine was observed in 31 (86.11%) patients. For seropositive cases, AchR Ab titer was significantly higher in the group with 2 clinical symptoms than that in the 1 clinical symptom (P = .011).This study presents the usefulness and diagnostic validity of antimyasthenic treatment for OMG, especially seronegative OMG, with detailed symptom analysis.
Topics: Adult; Aged; Autoantibodies; Blepharoptosis; Cholinesterase Inhibitors; Diagnosis, Differential; Diplopia; Feasibility Studies; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myasthenia Gravis; Oculomotor Muscles; Pyridostigmine Bromide; Receptors, Cholinergic; Treatment Outcome; Young Adult
PubMed: 34160444
DOI: 10.1097/MD.0000000000026457 -
Andes Pediatrica : Revista Chilena de... Apr 2021Juvenile myasthenia gravis (JMG) is an autoimmune disease affecting the neuromuscular junction that appears before 19 years of age with varying degrees of weakness of...
INTRODUCTION
Juvenile myasthenia gravis (JMG) is an autoimmune disease affecting the neuromuscular junction that appears before 19 years of age with varying degrees of weakness of different muscle groups. The main treatment is pharmacological, but thymectomy has also demonstrated to improve remission rates.
OBJECTIVE
To describe the clinical characteristics and postoperative course of pediatric patients with JMG who underwent video-assisted thoracoscopic (VATS) thymectomy. Clinical Serie: Six pa tients who underwent VATS thymectomy between March 2011 and June 2019. The age range at diag nosis was between 2 and 14 years and the average age at surgery was 7 years. All patients were under treatment with pyridostigmine bromide associated with immunosuppression with corticosteroids before surgery. The interval between diagnosis and thymectomy was 21.5 months on average. VATS was performed by left approach, and there was no perioperative morbidity or mortality. The average hospital stay was 2 days. Three patients remain with no symptoms and without corticotherapy. Two patients were on corticosteroids, but in smaller doses than previous to surgery. One patient presented a crisis requiring hospitalization and ventilatory support during follow-up.
CONCLUSION
VATS thy mectomy is part of the treatment for JMG. In this series, it appears as a safe approach and its results were favorable.
Topics: Adolescent; Adrenal Cortex Hormones; Child; Child, Preschool; Cholinesterase Inhibitors; Female; Humans; Length of Stay; Male; Myasthenia Gravis; Postoperative Period; Pyridostigmine Bromide; Thoracic Surgery, Video-Assisted; Thymectomy; Treatment Outcome
PubMed: 34106164
DOI: 10.32641/andespediatr.v92i2.2955 -
Neuroscience Insights 2021Gulf war illness (GWI), is a chronic multi-symptom illness that has impacted approximately one-third of the veterans who served in the 1990 to 1991 Gulf War. GWI...
Gulf war illness (GWI), is a chronic multi-symptom illness that has impacted approximately one-third of the veterans who served in the 1990 to 1991 Gulf War. GWI symptoms include cognitive impairments (eg, memory and concentration problems), headaches, migraines, fatigue, gastrointestinal and respiratory issues, as well as emotional deficits. The exposure to neurological chemicals such as the anti-nerve gas drug, pyridostigmine bromide (PB), and the insecticide permethrin (PER), may contribute to the etiologically related factors of GWI. Various studies utilizing mouse models of GWI have reported the interplay of these chemical agents in increasing neuroinflammation and cognitive dysfunction. Astrocytes are involved in the secretion of neuroinflammatory cytokines and chemokines in pathological conditions and have been implicated in GWI symptomology. We hypothesized that exposure to PB and PER causes lasting changes to hippocampal astrocytes, concurrent with chronic cognitive deficits that can be reversed by cervical vagus nerve stimulation (VNS). GWI was induced in CD1 mice by injecting the mixture of PER (200 mg/kg) and PB (2 mg/kg), i.p. for 10 consecutive days. VNS stimulators were implanted at 33 weeks after GWI induction. The results show age-related cognitive alterations at approximately 9 months after exposure to PB and PER. The results also showed an increased number of GFAP-labeled astrocytes in the hippocampus and dentate gyrus that was ameliorated by VNS.
PubMed: 34104886
DOI: 10.1177/26331055211018456 -
BMJ Case Reports May 2021An 88-year-old male patient presented with left ptosis, diplopia, muscle weakness of the lower limbs, dysphagia for solids, dysphonia and constipation. On investigation,...
An 88-year-old male patient presented with left ptosis, diplopia, muscle weakness of the lower limbs, dysphagia for solids, dysphonia and constipation. On investigation, he was found to have myasthenia gravis (MG). Further evaluation for the possible cause of MG, with CT scan, revealed that the patient had concomitant prostatic cancer. The patient was given steroids and pyridostigmine, with consequent resolution of his neurological symptoms. This is a rare case of MG associated with prostatic cancer.
Topics: Aged, 80 and over; Blepharoptosis; Diplopia; Humans; Male; Myasthenia Gravis; Prostatic Neoplasms; Pyridostigmine Bromide
PubMed: 34020991
DOI: 10.1136/bcr-2021-242416