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Anesthesia and Pain Medicine Oct 2019Neuromuscular blocking agents (NMBAs) and neuromuscular monitoring in anesthetic management are integral for endotracheal intubation, better visualization of the...
BACKGROUND
Neuromuscular blocking agents (NMBAs) and neuromuscular monitoring in anesthetic management are integral for endotracheal intubation, better visualization of the surgical field, and prevention of residual neuromuscular blockade and pulmonary complications. Sugammadex is a drug that reduces risk of residual neuromuscular blockade, with more rapid recovery compared to anticholinesterase. The purpose of this study was to investigate current usage status of NMBAs and antagonist with neuromuscular monitoring, among anesthesiologists in Korea.
METHODS
Anesthesiologists working in Korea were invited to participate in an online survey via email January 2-February 28, 2018. The questionnaire consisted of 45 items, including preferred NMBAs, antagonists, neuromuscular monitoring, and complications related to the use sugammadex. A total of 174 responses were analyzed.
RESULTS
Rocuronium was a commonly used NMBA for endotracheal intubation (98%) of hospitals, and maintenance of anesthesia (83.3%) in of hospitals. Sugammadex, pyridostigmine, and neostigmine were used in 89.1%, 87.9%, and 45.4% of hospitals. Neuromuscular monitoring was employed in 79.3% of hospitals; however only 39.7% of hospitals used neuromuscular monitoring before antagonist administration. Usual dosage range of sugammadex was 2.1-4 mg/kg in 35.1% of hospitals, within 2 mg/kg in 34.5% of hospitals, and 1 vial regardless of body weight in 22.4% of hospitals. Sugammadexrelated complications were encountered by 14.9% of respondents.
CONCLUSIONS
This survey indicates several minor problems associated with the use of antagonists and neuromuscular monitoring. However, most anesthesiologists appear to have appropriate information regarding the usage of NMBAs and sugammadex.
PubMed: 33329775
DOI: 10.17085/apm.2019.14.4.441 -
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 -
Health symptom trajectories and neurotoxicant exposures in Gulf War veterans: the Ft. Devens cohort.Environmental Health : a Global Access... Jan 2022Thirty years ago, Gulf War (GW) veterans returned home with numerous health symptoms that have been associated with neurotoxicant exposures experienced during...
BACKGROUND
Thirty years ago, Gulf War (GW) veterans returned home with numerous health symptoms that have been associated with neurotoxicant exposures experienced during deployment. The health effects from these exposures have been termed toxic wounds. Most GW exposure-outcome studies utilize group analyses and thus individual fluctuations in symptoms may have been masked. This study investigates health symptom trajectories in the same veterans over 25 years.
METHODS
Veterans were categorized into 5 a priori trajectory groups for each health symptom and Chronic Multisymptom Illness (CMI) clinical case status. Multinomial logistic regression models were used to investigate associations between these trajectories and neurotoxicant exposures.
RESULTS
Results indicate that more than 21 Pyridostigmine Bromide (PB) pill exposure was associated with consistent reporting of fatigue, pain, and cognitive/mood symptoms as well as the development of six additional symptoms over time. Chemical weapons exposure was associated with both consistent reporting and development of neurological symptoms over time. Reported exposure to tent heater exhaust was associated with later development of gastrointestinal and pulmonary symptoms. Veterans reporting exposure to more than 21 PB pills were more than 8 times as likely to consistently meet the criteria for CMI over time.
CONCLUSION
This study highlights the importance of the continued documentation of the health impacts experienced by GW veterans', their resulting chronic health symptoms, and the importance of exposure-outcome relationships in these veterans now 30 years post-deployment.
Topics: Chronic Disease; Cohort Studies; Gulf War; Humans; Persian Gulf Syndrome; Veterans
PubMed: 34998396
DOI: 10.1186/s12940-021-00812-0 -
Hypertension (Dallas, Tex. : 1979) Apr 2021[Figure: see text].
Supine Parasympathetic Withdrawal and Upright Sympathetic Activation Underly Abnormalities of the Baroreflex in Postural Tachycardia Syndrome: Effects of Pyridostigmine and Digoxin.
[Figure: see text].
Topics: Adult; Baroreflex; Blood Pressure; Cardiotonic Agents; Cholinesterase Inhibitors; Digoxin; Dizziness; Female; Heart Rate; Humans; Hypovolemia; Outcome Assessment, Health Care; Patient Positioning; Postural Orthostatic Tachycardia Syndrome; Pyridostigmine Bromide; Sympathetic Nervous System
PubMed: 33423527
DOI: 10.1161/HYPERTENSIONAHA.120.16113 -
BMC Neurology Mar 2022To investigate the clinical characteristics, treatments and outcomes of patients with myasthenia gravis with antibodies to muscle-specific tyrosine kinase (MuSK-MG).
BACKGROUND
To investigate the clinical characteristics, treatments and outcomes of patients with myasthenia gravis with antibodies to muscle-specific tyrosine kinase (MuSK-MG).
METHODS
We retrospectively reviewed the cases of 21 patients with confirmed MuSK-MG between January 2012 and January 2020 in our centre. Detailed clinical data and long-term follow-up information were summarized.
RESULTS
Females (17/21, 81%) predominated among these MuSK-MG patients, and the mean age of onset in this group was 51.86 ± 16.16 years. MuSK-MG patients were divided into three subgroups according to the symptoms of muscle weakness at onset: ocular myasthenia gravis (OMG, 47.6%), bulbar myasthenia gravis (BMG, 42.9%), and generalized myasthenia gravis (GMG, 9.5%). The mean progression time from symptom onset to other muscle group involvement in OMG patients was 4.38 ± 2.54 months. Pyridostigmine bromide was adopted in 81.0% of patients, and 90.5% of patients received corticosteroids. Compared to usage in hospitals, the median daily dose of corticosteroids decreased significantly at the last follow-up. A total of 85.7% of patients received a long-term follow-up, with an average time of 1202.17 ± 976.73 days. At the end of the follow-up period, 4.8% of patients had achieved complete stable remission, 42.9% of patients had minimal manifestations, 19.0% had improved, the condition of 4.8% of patients remained unchanged, and 9.5% of patients died.
CONCLUSION
Female patients were more prevalent in this study, and MuSK-MG patients rapidly progressed to a generalized state. Although approximately 50% of MuSK-MG patients can achieve a favourable outcome with conventional immunosuppressants, complete stable remission is rare, and approximately 15% respond poorly. More effective medications should be explored in these patients.
Topics: Adult; Aged; Autoantibodies; Fatty Acids, Monounsaturated; Female; Humans; Middle Aged; Myasthenia Gravis; Receptor Protein-Tyrosine Kinases; Receptors, Cholinergic; Retrospective Studies; Treatment Outcome
PubMed: 35246057
DOI: 10.1186/s12883-022-02593-6 -
Environmental Health : a Global Access... Oct 2023During deployment, veterans of the 1991 Gulf War (GW) were exposed to multiple war-related toxicants. Roughly a third of these veterans continue to exhibit neurotoxicant...
Cognitive decrements in 1991 Gulf War veterans: associations with Gulf War illness and neurotoxicant exposures in the Boston Biorepository, Recruitment, and Integrative Network (BBRAIN) cohorts.
BACKGROUND
During deployment, veterans of the 1991 Gulf War (GW) were exposed to multiple war-related toxicants. Roughly a third of these veterans continue to exhibit neurotoxicant induced symptoms of Gulf War Illness (GWI), a multi-faceted condition that includes fatigue, pain and cognitive decrements. When studied empirically, both deployed veterans with exposures and those who meet the criteria for GWI are more likely to show deficits in the area of neuropsychological functioning. Although studies have shown cognitive impairments in small sample sizes, it is necessary to revisit these findings with larger samples and newer cohorts to see if other areas of deficit emerge with more power to detect such differences. A group of researchers and clinicians with expertise in the area of GWI have identified common data elements (CDE) for use in research samples to compare data sets. At the same time, a subgroup of researchers created a new repository to share these cognitive data and biospecimens within the GWI research community.
METHODS
The present study aimed to compare cognitive measures of attention, executive functioning, and verbal memory in a large sample of GWI cases and healthy GW veteran controls using neuropsychological tests recommended in the CDEs. We additionally subdivided samples based on the specific neurotoxicant exposures related to cognitive deficits and compared exposed versus non-exposed veterans regardless of case criteria status. The total sample utilized cognitive testing outcomes from the newly collated Boston, Biorepository, Recruitment, and Integrative Network (BBRAIN) for GWI.
RESULTS
Participants included 411 GW veterans, 312 GWI (cases) and 99 healthy veterans (controls). Veterans with GWI showed significantly poorer attention, executive functioning, learning, and short-and-long term verbal memory than those without GWI. Further, GW veterans with exposures to acetylcholinesterase inhibiting pesticides and nerve gas agents, had worse performance on executive function tasks. Veterans with exposure to oil well fires had worse performance on verbal memory and those with pyridostigmine bromide anti-nerve gas pill exposures had better verbal memory and worse performance on an attention task compared to unexposed veterans.
CONCLUSIONS
This study replicates prior results regarding the utility of the currently recommended CDEs in determining impairments in cognitive functioning in veterans with GWI in a new widely-available repository cohort and provides further evidence of cognitive decrements in GW veterans related to war-related neurotoxicant exposures.
Topics: Humans; Veterans; Persian Gulf Syndrome; Gulf War; Boston; Acetylcholinesterase; Cognition
PubMed: 37794452
DOI: 10.1186/s12940-023-01018-2 -
BMC Infectious Diseases Oct 2020Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the causative agent of coronavirus disease 2019 (COVID-19), may lead to severe systemic...
A parallel-group, multicenter randomized, double-blinded, placebo-controlled, phase 2/3, clinical trial to test the efficacy of pyridostigmine bromide at low doses to reduce mortality or invasive mechanical ventilation in adults with severe SARS-CoV-2 infection: the Pyridostigmine In Severe...
BACKGROUND
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the causative agent of coronavirus disease 2019 (COVID-19), may lead to severe systemic inflammatory response, pulmonary damage, and even acute respiratory distress syndrome (ARDS). This in turn may result in respiratory failure and in death. Experimentally, acetylcholine (ACh) modulates the acute inflammatory response, a neuro-immune mechanism known as the inflammatory reflex. Recent clinical evidence suggest that electrical and chemical stimulation of the inflammatory reflex may reduce the burden of inflammation in chronic inflammatory diseases. Pyridostigmine (PDG), an ACh-esterase inhibitor (i-ACh-e), increases the half-life of endogenous ACh, therefore mimicking the inflammatory reflex. This clinical trial is aimed at evaluating if add-on of PDG leads to a decrease of invasive mechanical ventilation and death among patients with severe COVID-19.
METHODS
A parallel-group, multicenter, randomized, double-blinded, placebo-controlled, phase 2/3 clinical trial to test the efficacy of pyridostigmine bromide 60 mg/day P.O. to reduce the need for invasive mechanical ventilation and mortality in hospitalized patients with severe COVID-19.
DISCUSSION
This study will provide preliminary evidence of whether or not -by decreasing systemic inflammation- add-on PDG can improve clinical outcomes in patients with severe COVID-19.
TRIAL REGISTRATION
ClinicalTrials.gov NCT04343963 (registered on April 14, 2020).
Topics: Adult; Betacoronavirus; COVID-19; Cholinesterase Inhibitors; Coronavirus Infections; Humans; Inflammation; Lung; Pandemics; Pneumonia, Viral; Pyridostigmine Bromide; Respiration, Artificial; SARS-CoV-2
PubMed: 33066761
DOI: 10.1186/s12879-020-05485-7 -
Brain, Behavior, and Immunity Oct 2019Gulf War Illness (GWI), affecting 30% of veterans from the 1991 Gulf War (GW), is a multi-symptom illness with features similar to those of patients with autoimmune...
Gulf War Illness (GWI), affecting 30% of veterans from the 1991 Gulf War (GW), is a multi-symptom illness with features similar to those of patients with autoimmune diseases. The objective of the current work is to determine if exposure to GW-related pesticides, such as permethrin (PER), activates peripheral and central nervous system (CNS) adaptive immune responses. In the current study, we focused on a PER metabolite, 3-phenoxybenzoic acid (3-PBA), as this is a common metabolite previously shown to form adducts with endogenous proteins. We observed the presence of 3-PBA and 3-PBA modified lysine of protein peptides in the brain, blood and liver of pyridostigmine bromide (PB) and PER (PB+PER) exposed mice at acute and chronic post-exposure timepoints. We tested whether 3-PBA-haptenated albumin (3-PBA-albumin) can activate immune cells since it is known that chemically haptenated proteins can stimulate immune responses. We detected autoantibodies against 3-PBA-albumin in plasma from PB + PER exposed mice and veterans with GWI at chronic post-exposure timepoints. We also observed that in vitro treatment of blood with 3-PBA-albumin resulted in the activation of B- and T-helper lymphocytes and that these immune cells were also increased in blood of PB + PER exposed mice and veterans with GWI. These immune changes corresponded with elevated levels of infiltrating monocytes in the brain and blood of PB + PER exposed mice which coincided with alterations in the markers of blood-brain barrier disruption, brain macrophages and neuroinflammation. These studies suggest that pesticide exposure associated with GWI may have resulted in the activation of the peripheral and CNS adaptive immune responses, possibly contributing to an autoimmune-type phenotype in veterans with GWI.
Topics: Adaptive Immunity; Adult; Animals; Benzoates; Brain; Central Nervous System; Disease Models, Animal; Female; Gulf War; Humans; Male; Mice; Mice, Inbred C57BL; Middle Aged; Permethrin; Persian Gulf Syndrome; Pyridostigmine Bromide; Veterans
PubMed: 31325531
DOI: 10.1016/j.bbi.2019.07.015 -
Medicine Nov 2023Facial-onset sensory and motor neuronopathy (FOSMN) is a greatly rare disease, so far, autopsy evidence that is associated with neurodegenerative. Myasthenia gravis (MG)...
RATIONALE
Facial-onset sensory and motor neuronopathy (FOSMN) is a greatly rare disease, so far, autopsy evidence that is associated with neurodegenerative. Myasthenia gravis (MG) is an antibody-mediated and complement-involved acquired autoimmune disorder of the post-synaptic neuromuscular junction. There have been few reports about if there is related between the 2. In this study, we present the case of a man who was diagnosed as FOSMN with MG in continuity.
PATIENT CONCERNS
The patient chief complaints were right-side facial numbness and right-eyelid incomplete closure, followed by slurred speech and dysphagia, and the symptoms gradually progressed. The patient serum was positive for anti-AchR and anti-Titin antibodies.
DIAGNOSES
The patient was diagnosed FOSMN with MG.
INTERVENTIONS
The patient symptoms were relieved after pyridostigmine bromide and prednisolone treatment.
OUTCOMES
Symptoms have improved.
LESSONS
Facial-onset sensory and motor neuronopathy and MG have disparate clinical features. Therefore, we reported a rare case in which the 2 conditions concurrently existed. Immune dysfunction might be the pathogenesis of this association, while there is no definite evidence to support it, further studies are needed.
Topics: Male; Humans; Myasthenia Gravis; Pyridostigmine Bromide; Deglutition Disorders
PubMed: 37986404
DOI: 10.1097/MD.0000000000034215 -
Neurologia Sep 2020Myasthenia gravis (MG) is an autoimmune disease affecting nerve transmission at the level of the neuromuscular junction, and typically causes fluctuating muscle...
INTRODUCTION
Myasthenia gravis (MG) is an autoimmune disease affecting nerve transmission at the level of the neuromuscular junction, and typically causes fluctuating muscle weakness. Epidemiological studies show an increase in MG prevalence, particularly among the older population.
OBJECTIVE
We performed a retrospective epidemiological study to determine the incidence and prevalence of MG in the province of Ourense (Galicia, Spain), characterised by population ageing.
MATERIAL AND METHODS
Patients were selected from our clinical neuromuscular diseases database by searching for patients with an active prescription for pyridostigmine bromide. Incidence was estimated for the period 2009-2018. We calculated prevalence at 31/12/2018. According to census data for the province of Ourense, the population on 1/1/2019 was 307,651, of whom 96,544 (31.4%) were aged ≥ 65 years.
RESULTS
We identified 80 cases of MG, with a prevalence rate of 260 cases/1 000 000 population (95% CI, 202.7-316.4), rising to 517.9/1 000 000 population in those aged ≥ 65 (95% CI, 363.2-672.9). Cumulative incidence in the study period was 15.4 cases per 1 000 000 person-years. Early onset (≤ 50 years) was recorded in 29.1% of cases.
CONCLUSION
The prevalence of MG in our health district is one of the highest published figures, and the disease is highly prevalent in the older population.
PubMed: 32900528
DOI: 10.1016/j.nrl.2020.06.011