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International Journal of Environmental... Mar 2019Prevalence of nine chronic medical conditions in the population-based Ft. Devens Cohort (FDC) of GW veterans were compared with the population-based 2013⁻2014 National...
Prevalence of nine chronic medical conditions in the population-based Ft. Devens Cohort (FDC) of GW veterans were compared with the population-based 2013⁻2014 National Health and Nutrition Examination Survey (NHANES) cohort. Excess prevalence was calculated as the difference in prevalence estimates from the Ft. Devens and NHANES cohorts; and confidence intervals and -values are based on the standard errors for the two prevalence estimates. FDC males were at increased risk for reporting seven chronic medical conditions compared with NHANES males. FDC females were at decreased risk for high blood pressure and increased risk for diabetes when compared with NHANES females. FDC veterans reporting war-related chemical weapons exposure showed higher risk of high blood pressure; diabetes; arthritis and chronic bronchitis while those reporting taking anti-nerve gas pills had increased risk of heart attack and diabetes. GW veterans are at higher risk of chronic conditions than the general population and these risks are associated with self-reported toxicant exposures.
Topics: Adult; Chronic Disease; Female; Gulf War; Humans; Male; Middle Aged; Nutrition Surveys; Persian Gulf Syndrome; Prevalence; Risk Factors; Self Report; Veterans
PubMed: 30884809
DOI: 10.3390/ijerph16060949 -
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 -
British Journal of Haematology Feb 2019
Topics: Adult; Blepharoptosis; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Myasthenia Gravis; Neostigmine; Prednisolone; Pyridostigmine Bromide
PubMed: 30203413
DOI: 10.1111/bjh.15557 -
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 -
Scientific Reports Jan 2018Non-selective inhibitors of cholinesterases (ChEs) are clinically used for treatment of myasthenia gravis (MG). While being generally safe, they cause numerous adverse...
Non-selective inhibitors of cholinesterases (ChEs) are clinically used for treatment of myasthenia gravis (MG). While being generally safe, they cause numerous adverse effects including induction of hyperactivity of urinary bladder and intestines affecting quality of patients life. In this study we have compared two ChEs inhibitors, a newly synthesized compound C547 and clinically used pyridostigmine bromide, by their efficiency to reduce muscle weakness symptoms and ability to activate contractions of urinary bladder in a rat model of autoimmune MG. We found that at dose effectively reducing MG symptoms, C547 did not affect activity of rat urinary bladder. In contrast, at equipotent dose, pyridostigmine caused a significant increase in tonus and force of spontaneous contractions of bladder wall. We also found that this profile of ChEs inhibitors translates into the preparation of human urinary bladder. The difference in action observed for C547 and pyridostigmine we attribute to a high level of pharmacological selectivity of C547 in inhibiting acetylcholinesterase as compared to butyrylcholinesterase. These results raise reasonable hope that selective acetylcholinesterase inhibitors should show efficacy in treating MG in human patients with a significant reduction in adverse effects related to hyperactivation of smooth muscles.
Topics: Animals; Cholinesterase Inhibitors; Humans; Intestines; Muscle Contraction; Muscle, Smooth; Myasthenia Gravis, Autoimmune, Experimental; Pyridostigmine Bromide; Quaternary Ammonium Compounds; Rats; Uracil; Urinary Bladder
PubMed: 29321572
DOI: 10.1038/s41598-017-18307-9 -
Clinical Autonomic Research : Official... Jun 2015Acetylcholine (Ach) is the pre-synaptic neurotransmitter of the sympathetic nervous system. Increased pre-synaptic Ach may augment post-synaptic release of... (Clinical Trial)
Clinical Trial
INTRODUCTION
Acetylcholine (Ach) is the pre-synaptic neurotransmitter of the sympathetic nervous system. Increased pre-synaptic Ach may augment post-synaptic release of norepinephrine, thereby increasing systemic blood pressure (BP).
OBJECTIVES
The primary objective of this investigation was to determine the hemodynamic effect of pyridostigmine bromide (PYRIDO: 60 mg), an Ach inhibitor (AchI), compared to no-drug (NO-D) during head-up tilt (HUT) in individuals with spinal cord injury (SCI). Secondarily, we aimed to determine the effects of PYRIDO compared to NO-D on symptoms of orthostatic intolerance (OI) and adverse event reporting (AE).
METHODS
Ten individuals with SCI (C4-C7) were studied on two occasions: visit (1) NO-D and visit (2) PYRIDO. On each visit subjects underwent a progressive HUT maneuver to 15°, 25°, 35° for 5 min at each angle and 45 min at 45°. Supine and orthostatic heart rate (HR), systolic and diastolic BP (SBP and DBP), as well as monitored and symptoms of OI and AE were monitored and recorded.
RESULTS
Supine hemodynamics did not differ between the trials. The significant fall in SBP during the NO-D trial was diminished with PYRIDO, and five subjects had an increased DBP during HUT with PYRIDO compared to the NO-D trial. Individuals that responded to PYRIDO with an increase in orthostatic BP had significantly lower resting HR than non-responders (p < 0.01), which suggests increased levels of pre-synaptic Ach. Subjective symptoms of OI and AE reporting did not differ between the two trials.
CONCLUSIONS
These preliminary data suggest that PYRIDO is safe and may be effective at ameliorating the orthostatic fall in BP in select individuals with SCI.
Topics: Adult; Blood Pressure; Cholinesterase Inhibitors; Female; Heart Rate; Hemodynamics; Humans; Male; Middle Aged; Orthostatic Intolerance; Pyridostigmine Bromide; Quadriplegia; Spinal Cord Injuries; Supine Position; Tilt-Table Test; Young Adult
PubMed: 25916633
DOI: 10.1007/s10286-015-0272-3 -
Neurology Dec 2015To describe the clinical and electrophysiologic features of synaptotagmin II (SYT2) mutations, a novel neuromuscular syndrome characterized by foot deformities and...
OBJECTIVES
To describe the clinical and electrophysiologic features of synaptotagmin II (SYT2) mutations, a novel neuromuscular syndrome characterized by foot deformities and fatigable ocular and lower limb weakness, and the response to modulators of acetylcholine release.
METHODS
We performed detailed clinical and neurophysiologic assessment in 2 multigenerational families with dominant SYT2 mutations (c.920T>G [p.Asp307Ala] and c.923G>A [p.Pro308Leu]). Serial clinical and electrophysiologic assessments were performed in members of one family treated first with pyridostigmine and then with 3,4-diaminopyridine.
RESULTS
Electrophysiologic testing revealed features indicative of a presynaptic deficit in neurotransmitter release with posttetanic potentiation lasting up to 60 minutes. Treatment with 3,4-diaminopyridine produced both a clinical benefit and an improvement in neuromuscular transmission.
CONCLUSION
SYT2 mutations cause a novel and potentially treatable complex presynaptic congenital myasthenic syndrome characterized by motor neuropathy causing lower limb wasting and foot deformities, with reflex potentiation following exercise and a uniquely prolonged period of posttetanic potentiation.
Topics: 4-Aminopyridine; Adolescent; Adult; Aged; Amifampridine; Child; Electrophysiological Phenomena; Female; Humans; Male; Middle Aged; Mutation; Myasthenic Syndromes, Congenital; Potassium Channel Blockers; Pyridostigmine Bromide; Reflex; Synaptic Transmission; Synaptotagmin II; Young Adult
PubMed: 26519543
DOI: 10.1212/WNL.0000000000002185 -
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