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1.
PLoS One ; 17(9): e0274161, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36129914

RESUMO

OBJECTIVE: To study the updated prevalence and clinical features of myasthenia gravis (MG) in Japan during 2017. METHODS: We sent survey sheets to the randomly selected medical departments (number = 7,545). First, we asked the number of MG patients who visited medical departments from January 1, 2017, to December 31, 2017. Then, we sent the second survey sheet to the medical departments that answered the first survey to obtain the clinical information of patients who received MG diagnosis between January 1, 2015, and December 31, 2017. RESULTS: The received answer to the first survey were 2,708 (recovery rate: 35.9%). After all, the prevalence of the 100,000 population was estimated as 23.1 (95%CI: 20.5-25.6). As a result of the second survey, we obtained 1,464 case records. After checking the duplications and lacking data, we utilized 1,195 data for further analysis. The median [interquartile range (IQR)] from the onset age of total patients was 59 (43-70) years old. The male-female ratio was 1: 1.15. The onset age [median (IQR)] for female patients was 58 (40-72) years old, and that for male patients was 60 (49-69) years old (Wilcoxon-Mann-Whitney test, p = 0.0299). We divided patients into four categories: 1) anti-acetylcholine receptor antibody (AChRAb) (+) thymoma (Tm) (-), 2) AChRAb(+)Tm(+), 3) anti-muscle-specific kinase antibody (MuSKAb) (+), and AChRAb(-)MuSKAb(-) (double negative; DN). The onset age [median (IQR)] of AChRAb(+)Tm(-) was 64 (48-73) years old, and AChRb(+)Tm(+) was 55 (45-66), MuSKAb(+) was 49 (36-64), DN was 47 (35-60) year old. The multivariate logistic regression analysis using sex, initial symptoms, repetitive nerve stimulation test (RNST), and edrophonium test revealed that sex, ocular symptoms, bulbar symptoms, and RNST were factors to distinguish each category. The myasthenia gravis activities of daily living profile at the severest state were significantly higher in MuSKAb(+). MuSKAb(+) frequently received prednisolone, tacrolimus plasmapheresis, and intravenous immunoglobulin; however, they received less acetylcholine esterase inhibitor. 99.2% of AChRAb(+)Tm(+) and 15.4% of AChRAb(+)Tm(-) received thymectomy. MuSKAb(+) did not receive thymectomy, and only 5.7% of DN received thymectomy. The prognosis was favorable in all categories. CONCLUSION: Our result revealed that the prevalence of Japanese MG doubled from the previous study using the same survey method in 2006. We also found that the onset age shifted to the elderly, and the male-female ratio reached almost even. Classification in four categories; AChRAb(+)Tm(-), AChRAb(+)Tm(+), MuSKAb(+), and DN, well describe the specific clinical features of each category and differences in therapeutic approaches.


Assuntos
Miastenia Gravis , Timoma , Neoplasias do Timo , Atividades Cotidianas , Adulto , Idoso , Autoanticorpos , Edrofônio/uso terapêutico , Esterases , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/epidemiologia , Prednisolona/uso terapêutico , Inquéritos e Questionários , Tacrolimo/uso terapêutico , Timectomia/métodos
2.
Rinsho Shinkeigaku ; 61(9): 630-634, 2021 Sep 28.
Artigo em Japonês | MEDLINE | ID: mdl-34433744

RESUMO

A 78-year-old man was treated with ipilimumab and nivolumab for advanced renal cell carcinoma with liver and lymph node metastasis. He developed diplopia, ptosis, dysphagia, and weakness of the limbs and neck, 1 month after treatment. Serum creatine kinase (CK) levels were elevated, and neck MRI revealed inflammation of the deep trunk muscles. Although anti-acetylcholine receptor antibody was negative, the edrophonium test was positive. Anti-striational antibodies such as the anti-titin and the anti-muscular voltage-gated potassium channel (Kv 1.4) antibodies (which serve as biomarkers of immune checkpoint inhibitors associated with myasthenia gravis and myositis) were positive (anti-titin antibody titer 11.51, normal <1 index; anti-Kv 1.4 antibody titer 15.13, normal <1 index). Intravenous methylprednisolone pulse therapy (1,000 mg/day for 3 days), plasmapheresis, and oral prednisolone (PSL) (20 mg/day) administration improved the patient's neurological function and normalized the serum CK levels. The PSL dosage was tapered without any worsening of clinical signs. The antibody titers decreased but remained positive (anti-titin antibody 5.00, anti-Kv 1.4 antibody 3.83) one year after the initial evaluation. Therefore, low-dose PSL (5 mg/day) administration was continued, and the patient was in remission.


Assuntos
Miastenia Gravis , Miosite , Idoso , Autoanticorpos , Edrofônio , Humanos , Inibidores de Checkpoint Imunológico , Masculino , Miastenia Gravis/tratamento farmacológico , Miosite/tratamento farmacológico
3.
Neuropharmacology ; 182: 108303, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32918950

RESUMO

The beneficial effects of acetylcholinesterase inhibitors for the treatment of myasthenia gravis (MG) was a major discovery that came about through one young physician putting together a string of previous observations. To understand how this discovery came to light, we must first go back to earlier times when men hunted by bow-and-arrow to capture their prey. The substance used to poison the prey was eventually was identified as curare. Centuries later, a connection was made between the physiological effects of curare and a disease entity with no known pathological mechanism or treatment, myasthenia gravis. In 1935, house officer Dr. Mary Walker was the first physician to try physostigmine in the treatment of MG, which had previously been used to treat curare poisoning. What she saw was a dramatic improvement in the symptoms experienced in patients with MG, and thus became the first documented case of use of physostigmine, an acetylcholinesterase inhibitor, in the treatment of MG. This article is a summary of the history of the use of acetylcholinesterase inhibitors in the treatment of myasthenia gravis. This article is part of the special issue entitled 'Acetylcholinesterase Inhibitors: From Bench to Bedside to Battlefield'.


Assuntos
Acetilcolinesterase/metabolismo , Inibidores da Colinesterase/história , Miastenia Gravis/história , Médicos/história , Fisostigmina/história , Inibidores da Colinesterase/uso terapêutico , Curare/história , Curare/uso terapêutico , Edrofônio/história , Edrofônio/uso terapêutico , História do Século XIX , História do Século XX , História do Século XXI , Humanos , Miastenia Gravis/tratamento farmacológico , Fisostigmina/uso terapêutico
4.
Intern Med ; 59(14): 1763-1767, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32669516

RESUMO

The patient was a 70-year-old man with idiopathic orbital inflammation (IOI) that appeared on the severely affected side of preceding myasthenia gravis (MG). The patient was diagnosed with MG 5 years prior to the onset of IOI. When IOI was diagnosed, an edrophonium test was negative. IOI was considered because he complained of left orbital pain, eyelid swelling, and cerebral MRI exhibited the enhanced lesions along the left orbital periosteum. A biopsy specimen revealed pathological findings compatible with IOI. The administration of corticosteroids was effective for improving the ocular symptoms. IOI should be considered when ocular symptoms deteriorated with soft tissue swelling/pain in MG patients.


Assuntos
Imunoglobulina G/análise , Miastenia Gravis/complicações , Órbita/imunologia , Pseudotumor Orbitário/etiologia , Idoso , Biópsia , Encéfalo/diagnóstico por imagem , Edrofônio , Humanos , Imageamento por Ressonância Magnética , Masculino , Órbita/diagnóstico por imagem , Órbita/patologia , Pseudotumor Orbitário/diagnóstico , Pseudotumor Orbitário/patologia , Periósteo/diagnóstico por imagem , Periósteo/patologia
5.
Chem Biol Interact ; 308: 350-356, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31173753

RESUMO

Activation of human butyrylcholinesterase by small quaternary ammonium ions is known. Here, additional ligands in this series are presented: edrophonium and choline, and the reactivator pyridine-2-aldoxime methochloride. Kinetic analysis of the progress curves with these compounds indicates the mechanism of enhanced deacylation by the ligand bound to the catalytic anionic site (Trp82) at the base of the active site. The larger, bis-quaternary ligands examined, as propidium, hexamethonium, decamethonium, and bis-thiocholine, show only competitive inhibition of butyrylcholinesterase, by preventing substrate approach. This hypothesis of enhanced deacylation was tested for reactivation of methanesulfonylfluoride-inactivated butyrylcholinesterase, a complex analogous to organophosphate-aged cholinesterases. The combination of substrate/products and pyridine-2-aldoxime methochloride improved butyrylcholinesterase activity over 2 h of continuous measurements, before which time substrate depletion prevailed. Similar reactivation of Torpedo californica acetylcholinesterase was unsuccessful, but both of these cholinesterases regain some activity if they have been inhibited and aged for days by diisopropylfluorophosphate.


Assuntos
Butirilcolinesterase/metabolismo , Inibidores da Colinesterase/metabolismo , Oximas/metabolismo , Butirilcolinesterase/química , Domínio Catalítico , Colina/química , Colina/metabolismo , Inibidores da Colinesterase/química , Edrofônio/química , Edrofônio/metabolismo , Humanos , Cinética , Ligantes , Oximas/química , Especificidade por Substrato
6.
Rinsho Shinkeigaku ; 59(6): 345-348, 2019 Jun 22.
Artigo em Japonês | MEDLINE | ID: mdl-31142707

RESUMO

A 69-year-old woman presented with acute bilateral ptosis, ophthalmoplegia, ataxia, and hyporeflexia in the extremities following an antecedent upper respiratory infection. We suspected that she had Miller Fisher syndrome (MFS) and performed an edrophonium test (ET) to rule out myasthenia gravis (MG). Edrophonium chloride improved the patient's bilateral ptosis, but not her ophthalmoplegia. Given the absence of the waning phenomenon on electrophysiological examination, the anti-acetylcholine receptor antibody, and a diurnal variation of symptoms, we concluded that the ET result was a false-positive. A diagnosis of MFS was confirmed by the presence of a positive anti-GQ1b antibody. To our knowledge, this is the first case report of MFS with a false-positive ET.


Assuntos
Edrofônio , Gangliosídeos/imunologia , Síndrome de Miller Fisher/diagnóstico , Síndrome de Miller Fisher/tratamento farmacológico , Idoso , Autoanticorpos/sangue , Biomarcadores/sangue , Diagnóstico Diferencial , Reações Falso-Positivas , Feminino , Humanos , Miastenia Gravis
8.
Acta Anaesthesiol Scand ; 63(5): 564-575, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30548256

RESUMO

BACKGROUND: Mivacurium is a short-acting non-depolarizing muscle relaxant, which is hydrolyzed by butyrylcholinesterase. The neuromuscular block (NMB) can be antagonized with cholinesterase inhibitors (CHEI), but the short duration of action of mivacurium questions the need. This systematic review evaluated if the use of CHEIs (neostigmine, pyridostigmine or edrophonium) facilitates reversal of mivacurium-induced NMB. METHOD: Randomized controlled trials and crossover-studies comparing spontaneous recovery with CHEI reversal in patients with mivacurium-induced NMB, assessed with quantitative neuromuscular monitoring, were included. Mean time from injection of the CHEI or allowing of spontaneous recovery to an endpoint representing full recovery was used as outcome. First response to train-of-four nerve stimulation (T1 ) described the level of NMB for administration of the CHEI. Moderate NMB refers to T1  ≥ 5% and deeper NMB refers to T1  < 5%. Systematic critical appraisal was performed using the Scottish Intercollegiate Guidelines Network guidelines. Overall quality assessment was done using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Sixteen studies with data from 546 patients were included. Low quality of evidence was found that neostigmine and edrophonium administered at moderate NMB accelerated recovery with up to approximately 5.5-6.5 and 6.5-9.0 minutes, respectively. At deeper NMB only edrophonium accelerated recovery. The effect of neostigmine was not clarified at deeper mivacurium-induced NMB. No studies with reversal by pyridostigmine were identified. CONCLUSION: Low quality of evidence supports that neostigmine and edrophonium accelerate the recovery of mivacurium-induced NMB with 5-6.5 and 6-9.0 minutes respectively, when administered at moderate NMB. At deeper NMB only edrophonium accelerated the recovery.


Assuntos
Inibidores da Colinesterase/farmacologia , Mivacúrio/farmacologia , Bloqueio Neuromuscular , Edrofônio/farmacologia , Humanos , Neostigmina/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo
9.
Circ Arrhythm Electrophysiol ; 11(9): e006330, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30354290

RESUMO

Background We explored the hypothesis that increased cholinergic tone exerts its proarrhythmic effects in Brugada syndrome (BrS) through increasing dispersion of transmural repolarization in patients with spontaneous and drug-induced BrS. Methods BrS and supraventricular tachycardia patients were studied after deploying an Ensite Array in the right ventricular outflow tract and a Cardima catheter in the great cardiac vein to record endo and epicardial signals, respectively. S1-S2 restitution curves from the right ventricular apex were conducted at baseline and after edrophonium challenge to promote increased cholinergic tone. The local unipolar electrograms were then analyzed to study transmural conduction and repolarization dynamics. Results The study included 8 BrS patients (5 men:3 women; mean age, 56 years) and 8 controls patients with supraventricular tachycardia (5 men:3 women; mean age, 48 years). Electrophysiological studies in controls demonstrated shorter endocardial than epicardial right ventricular activation times (mean difference: 26 ms; P<0.001). In contrast, patients with BrS showed longer endocardial than epicardial activation time (mean difference: -15 ms; P=0.001). BrS hearts, compared with controls, showed significantly larger transmural gradients in their activation recovery intervals (mean intervals, 20.5 versus 3.5 ms; P<0.01), with longer endocardial than epicardial activation recovery intervals. Edrophonium challenge increased such gradients in both controls (to a mean of 16 ms [ P<0.001]) and BrS (to 29.7 ms; P<0.001). However, these were attributable to epicardial and endocardial activation recovery interval prolongations in control and BrS hearts, respectively. Dynamic changes in repolarization gradients were also observed across the BrS right ventricular wall in BrS. Conclusions Differential contributions of conduction and repolarization were identified in BrS which critically modulated transmural dispersion of repolarization with significant cholinergic effects only identified in the patients with BrS. This has important implications for explaining the proarrhythmic effects of increased vagal tone in BrS, as well as evaluating autonomic modulation and epicardial ablation as therapeutic strategies.


Assuntos
Síndrome de Brugada/fisiopatologia , Inibidores da Colinesterase/farmacologia , Edrofônio/farmacologia , Endocárdio/efeitos dos fármacos , Ventrículos do Coração/efeitos dos fármacos , Pericárdio/efeitos dos fármacos , Função Ventricular Direita/efeitos dos fármacos , Potenciais de Ação/efeitos dos fármacos , Adulto , Idoso , Síndrome de Brugada/diagnóstico , Cateterismo Cardíaco , Estudos de Casos e Controles , Eletrocardiografia , Técnicas Eletrofisiológicas Cardíacas , Endocárdio/fisiopatologia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Pericárdio/fisiopatologia , Taquicardia Supraventricular/diagnóstico , Taquicardia Supraventricular/fisiopatologia , Fatores de Tempo
10.
Am J Vet Res ; 79(9): 915-920, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30153055

RESUMO

OBJECTIVE To evaluate effects of 2 levels of partial neuromuscular block on the ventilatory response to a hypercapnic challenge in anesthetized dogs and to evaluate effects of edrophonium for reversing partial neuromuscular block. ANIMALS 6 healthy adult Beagles. PROCEDURES Each dog was anesthetized twice with propofol and dexmedetomidine. End-tidal partial pressure of CO2 (Petco2), tidal volume (Vt), and peak inspiratory flow (PIF) were measured during breathing at rest. Maximal Vt and PIF (VtMAX and PIFMAX, respectively) in response to a hypercapnic challenge consisting of 10% CO2 inhaled for 1 minute were measured. Variables were measured before administration of atracurium (baseline), during moderate (train-of-four [TOF] ratio, 0.3 to 0.5) and mild (TOF ratio, 0.6 to 0.8) atracurium-induced neuromuscular block, and after neuromuscular block recovery (TOF ratio, ≥ 0.9) following administration of edrophonium or saline (0.9% NaCl) solution. Dogs for which any variable returned to < 80% of the baseline value were identified. RESULTS Partial neuromuscular block increased Petco2; it impaired Vt at rest and VtMAX but not PIF at rest and PIFMAX. All variables except Petco2 returned to baseline values when the TOF returned to ≥ 0.9. After recovery from neuromuscular block, significantly more dogs had a VtMAX < 80% of the baseline value when edrophonium was not administered. CONCLUSIONS AND CLINICAL RELEVANCE Partial neuromuscular block in anesthetized Beagles decreased spontaneous ventilation at rest and impaired the response to a hypercapnic challenge. Response to hypercapnic challenge might remain partially impaired after recovery of the TOF ratio to ≥ 0.9.


Assuntos
Atracúrio/administração & dosagem , Edrofônio/administração & dosagem , Hipercapnia/veterinária , Bloqueio Neuromuscular/veterinária , Animais , Capnografia , Dexmedetomidina/farmacologia , Cães , Masculino , Propofol/farmacologia , Respiração/efeitos dos fármacos , Espirometria , Volume de Ventilação Pulmonar
11.
Eur J Neurol ; 25(10): 1235-1242, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29802670

RESUMO

BACKGROUND AND PURPOSE: Diagnosis of pharyngeal dysphagia caused by myasthenia gravis (MG) based on clinical examination alone is often challenging. Flexible endoscopic evaluation of swallowing (FEES) combined with Tensilon (edrophonium) application, referred to as the FEES-Tensilon test, was developed to improve diagnostic accuracy and to detect the main symptoms of pharyngeal dysphagia in MG. Here we investigated inter- and intra-rater reliability of the FEES-Tensilon test and analyzed the main endoscopic findings. METHODS: Four experienced raters reviewed a total of 20 FEES-Tensilon test videos in randomized order. Residue severity was graded at four different pharyngeal spaces before and after Tensilon administration. All interpretations were performed twice per rater, 4 weeks apart (a total of 160 scorings). Intra-rater test-retest reliability and inter-rater reliability levels were calculated. RESULTS: The most frequent FEES findings in patients with MG before Tensilon application were prominent residues of semi-solids spread all over the hypopharynx in varying locations. The reliability level of the interpretation of the FEES-Tensilon test was excellent regardless of the rater's profession or years of experience with FEES. All four raters showed high inter- and intra-reliability levels in interpreting the FEES-Tensilon test based on residue clearance (kappa = 0.922, 0.981). The degree of residue normalization in the vallecular space after Tensilon application showed the highest inter- and intra-rater reliability level (kappa = 0.863, 0.957) followed by the epiglottis (kappa = 0.813, 0.946) and pyriform sinuses (kappa = 0.836, 0.929). CONCLUSION: Interpretation of the FEES-Tensilon test based on residue severity and degree of Tensilon clearance, especially in the vallecular space, is consistent and reliable.


Assuntos
Transtornos de Deglutição/diagnóstico , Deglutição/fisiologia , Miastenia Gravis/complicações , Idoso , Idoso de 80 Anos ou mais , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/fisiopatologia , Edrofônio , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/fisiopatologia , Reprodutibilidade dos Testes
12.
J Pharm Biomed Anal ; 155: 177-184, 2018 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-29635172

RESUMO

In the continuous research for potential drug lead candidates, the availability of highly informative screening methodologies may constitute a decisive element in the selection of best-in-class compounds. In the present study, a surface plasmon resonance (SPR)-based assay was developed and employed to investigate interactions between human recombinant AChE (hAChE) and four known ligands: galantamine, tacrine, donepezil and edrophonium. To this aim, a sensor chip was functionalized with hAChE using mild immobilization conditions to best preserve enzyme integrity. Binding affinities and, for the first time, kinetic rate constants for all drug-hAChE complexes formation/disruption were determined. Inhibitors were classified in two groups: slow-reversible and fast-reversible binders according to respective target residence time. Combining data obtained on drug-target residence time with data obtained on serum albumin binding levels, a good correlation with potency, plasma protein binding in vivo, and administration regimen was found. The outcomes of this work demonstrated that the developed SPR-based assay is suitable for the screening, the binding affinity ranking and the kinetic evaluation of hAChE inhibitors. The method proposed ensures a simpler and cost-effective assay to quantify kinetic rate constants for inhibitor-hAChE interaction as compared with other proposed and published methods. Eventually, the determination of residence time in combination with preliminary ADME studies might constitute a better tool to predict in vivo behaviour, a key information for the research of new potential drug candidates.


Assuntos
Acetilcolinesterase/química , Inibidores da Colinesterase/química , Albumina Sérica/química , Donepezila , Edrofônio/química , Enzimas Imobilizadas/química , Galantamina/química , Humanos , Indanos/química , Cinética , Ligantes , Piperidinas/química , Proteínas Recombinantes de Fusão/química , Ressonância de Plasmônio de Superfície/métodos , Tacrina/química
13.
Vet Anaesth Analg ; 44(6): 1313-1320, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29066245

RESUMO

OBJECTIVE: Anticholinesterase drugs may produce paradoxical neuromuscular block when administered at shallow levels of neuromuscular block. The objective of this study was to evaluate the effects of neostigmine and edrophonium when administered at near-complete reversal from nondepolarizing block in anesthetized dogs. STUDY DESIGN: Incomplete crossover, randomized, blinded experimental study. ANIMALS: A total of 12 Beagle dogs. METHODS: Each dog was anesthetized twice with propofol and maintained with isoflurane and dexmedetomidine. Intravenous (IV) vecuronium (0.1 mg kg-1) was administered. When the mechanographic train-of-four (TOF) ratio had spontaneously recovered to ≥0.9, either neostigmine (0.04 mg kg-1) or edrophonium (0.5 mg kg-1) was administered IV, preceeded by atropine. Changes in twitch height or TOF ratio were measured for the next 10 minutes. Recurarization was considered to be present if values decreased by ≥10%. RESULTS: Data from four dogs in each treatment were excluded from analysis, resulting in data from five dogs administered both treatments, three dogs administered neostigmine and three dogs administered edrophonium. There was no difference between groups for age, weight, T1 and T4 twitch heights or TOF ratio values, before or after anticholinesterase administration. The TOF ratio decreased by 17% and 18% in two of the eight dogs administered neostigmine, resulting from a larger increase in T1 relative to T4. No reductions in individual twitch amplitudes were recorded in those dogs. When edrophonium was used, no cases of recurarization were observed. CONCLUSIONS AND CLINICAL RELEVANCE: The results support use of edrophonium for reversal of shallow neuromuscular block. The decreases in TOF ratio recorded after neostigmine does not necessarily indicate muscular weakness. Although the clinical implications are uncertain, the results suggest that, at these doses, edrophonium may be preferable to neostigmine for reversal of shallow neuromuscular block in dogs.


Assuntos
Edrofônio/farmacologia , Neostigmina/farmacologia , Bloqueio Neuromuscular/veterinária , Bloqueadores Neuromusculares/antagonistas & inibidores , Anestesia Geral/efeitos adversos , Anestesia Geral/métodos , Anestesia Geral/veterinária , Animais , Estudos Cross-Over , Cães , Contração Muscular/efeitos dos fármacos , Bloqueio Neuromuscular/efeitos adversos , Bloqueio Neuromuscular/métodos , Monitoração Neuromuscular/métodos , Monitoração Neuromuscular/veterinária
14.
Intern Med ; 56(18): 2415-2421, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28824069

RESUMO

Objective To examine whether or not an edrophonium challenge test is useful for diagnosing cervical dystonia. Patients We evaluated 10 patients with cervical dystonia and 10 with hemifacial spasms (disease controls). We administered edrophonium and saline in this double-blinded study. Before and after the injection, we recorded the participants' clinical signs using a video camera to assess the objective symptoms every two minutes. Ten minutes after the saline and edrophonium injections, participants evaluated their subjective clinical signs using a visual analog scale. The objective signs on the video recordings were scored by specialists who were blinded to the treatment. The mean visual analog scale scores were compared using the Wilcoxon rank-sum test for paired continuous variables. Results The clinical signs of participants with cervical dystonia were amplified by edrophonium. In contrast, the clinical signs in participants with hemifacial spasms were not affected by the edrophonium challenge test. Conclusion The edrophonium challenge test may be useful for diagnosing cervical dystonia.


Assuntos
Edrofônio/farmacologia , Torcicolo/diagnóstico , Adulto , Idoso , Método Duplo-Cego , Feminino , Espasmo Hemifacial/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade
15.
J Int Med Res ; 45(5): 1466-1469, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28379106

RESUMO

A case of laryngeal myasthenia gravis in a 65-year-old woman presenting with hoarseness as the sole symptom is reported. Voice spectrography was performed before and after injection of intravenous edrophonium. There was a marked improvement in the patient's voice after the administration of edrophonium, which was confirmed by the changes seen on the sound spectrogram. This was the only objective indication of a diagnosis of myasthenia gravis. No thymoma was seen on chest X-ray and the patient was negative for anti-acetylcholine receptor antibodies. Treatment for laryngeal myasthenia gravis was initiated and the patient's vocal problems resolved. This case emphasizes the need to consider systemic diseases in the differential diagnosis of hoarseness and demonstrates the need for careful follow-up in such patients.


Assuntos
Edrofônio/uso terapêutico , Laringe/patologia , Laringe/fisiopatologia , Miastenia Gravis/tratamento farmacológico , Miastenia Gravis/fisiopatologia , Voz , Idoso , Edrofônio/administração & dosagem , Feminino , Humanos , Injeções Intravenosas , Laringe/efeitos dos fármacos , Espectrografia do Som , Voz/efeitos dos fármacos
16.
Am J Trop Med Hyg ; 96(4): 876-884, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28138054

RESUMO

AbstractWe describe 70 cases of monocled cobra (Naja kaouthia) bite admitted to Chittagong Medical College Hospital, Bangladesh. The biting snakes were identified by examining the dead snake and/or detecting N. kaouthia venom antigens in patients' serum. Bites were most common in the early morning and evening during the monsoon (May-July). Ligatures were routinely applied to the bitten limb before admission. Thirty-seven patients consulted traditional healers, most of whom made incisions around the bite site. Fifty-eight patients experienced severe neurotoxicity and most suffered swelling and pain of the bitten limb. The use of an Indian polyvalent antivenom in patients exhibiting severe neurotoxicity resulted in clinical improvement but most patients experienced moderate-to-severe adverse reactions. Antivenom did not influence local blistering and necrosis appearing in 19 patients; 12 required debridement. Edrophonium significantly improved the ability of patients to open the eyes, endurance of upward gaze, and peak expiratory flow rate suggesting that a longer-acting anticholinesterase drug (neostigmine) could be recommended for first aid. The study suggested that regionally appropriate antivenom should be raised against the venoms of the major envenoming species of Bangladesh and highlighted the need to improve the training of staff of local medical centers and to invest in the basic health infrastructure in rural communities.


Assuntos
Antivenenos/uso terapêutico , Elapidae/fisiologia , Mordeduras de Serpentes/epidemiologia , Mordeduras de Serpentes/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antivenenos/administração & dosagem , Bangladesh/epidemiologia , Criança , Pré-Escolar , Edrofônio , Venenos Elapídicos/toxicidade , Feminino , Primeiros Socorros , Humanos , Masculino , Pessoa de Meia-Idade , Mordeduras de Serpentes/patologia , Adulto Jovem
17.
Chem Biol Interact ; 259(Pt B): 78-84, 2016 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-27297626

RESUMO

Natural product inhibitors of AChE are of interest both because they offer promise as inexpensive drugs for symptomatic relief in Alzheimer's disease and because they may provide insights into the structural features of the AChE catalytic site. Hopeahainol A is an uncharged polyphenol AChE inhibitor from the stem bark of Hopea hainanensis with a constrained, partially dearomatized bicyclic core. Molecular modeling indicates that hopeahainol A binds at the entrance of the long but narrow AChE active site gorge because it is too bulky to be accommodated within the gorge without severe distortion of the gorge as depicted in AChE crystal structures. We conducted inhibitor competition experiments in which AChE inhibition was measured with hopeahainol A together with either edrophonium (which binds at the base of the gorge) or thioflavin T (which binds to the peripheral or P-site near the gorge mouth). The results agreed with the molecular modeling and indicated that hopeahainol A at lower concentrations (<200 µM) bound only to the P-site, as hopeahainol A and thioflavin T were unable to form a ternary complex with AChE while hopeahainol A and edrophonium did form a ternary complex with essentially no competition between them. Inhibition increased to a striking extent at higher concentrations of hopeahainol A, with plots analogous to classic Dixon plots showing a dependence on hopeahainol A concentrations to the third- or fourth order. The inhibition at higher hopeahainol A concentrations was completely reversed on dilution and blocked by bound edrophonium. We hypothesize that bound hopeahainol A induces conformational changes in the AChE active site that allow binding of additional hopeahainol A molecules, a phenomenon that would be unprecedented for a reversible inhibitor that apparently forms no covalent bonds with AChE.


Assuntos
Acetilcolinesterase/metabolismo , Inibidores da Colinesterase/metabolismo , Compostos Heterocíclicos de 4 ou mais Anéis/metabolismo , Acetilcolinesterase/química , Benzotiazóis , Sítios de Ligação , Domínio Catalítico , Inibidores da Colinesterase/química , Dipterocarpaceae/química , Dipterocarpaceae/metabolismo , Edrofônio/química , Edrofônio/metabolismo , Compostos Heterocíclicos de 4 ou mais Anéis/química , Cinética , Simulação de Acoplamento Molecular , Casca de Planta/química , Casca de Planta/metabolismo , Especificidade por Substrato , Termodinâmica , Tiazóis/química , Tiazóis/metabolismo
18.
Bogotá; IETS; mayo 2016. tab, graf.
Monografia em Espanhol | LILACS, BRISA/RedTESA | ID: biblio-846926

RESUMO

Tecnologías evaluadas: -Tecnologías actuales: electromiografía con electrodo de fibra única e ICE test;\r\n-Tecnología nueva: anticuerpos bloqueadores de acetilcolina receptores, prueba de Tensilon, prueba de estímulo repetitivo. Población: Esta prueba se puede aplicar a todas las edades y a todos los sexos, ya que la aparición de la enfermedad puede presentarse en toda la población. Perspectiva: Tercer pagador - Sistema General de Seguridad en Salud (SGSSS) colombiano. Horizonte temporal: El horizonte temporal de este AIP en el caso base corresponde a un año. Adicionalmente se reportan las estimaciones del impacto presupuestal para los años 2 y 3, bajo el supuesto de la inclusión en el POS en el año 1. Costos incluidos: Solo se tuvieron en cuenta los costos de las pruebas: -Electromiografía con electrodo de fibra única: $71.262,1; -Ice test: $26.223,3; Prueba completa de Tensilon: $24.000; -Prueba de estímulo repetitivo: $46.219,1; -Test de anticuerpos contra receptor de acetilcolina por RIA (ACRA): $45.416. Fuente de costos: Para todas las pruebas diagnósticas se utilizó el promedio ponderado estimado desde los registros de uso de servicios de 2014 SISPRO (módulo de prestación de servicios, mediante conexión OBDS), teniendo como corte de búsqueda la fecha del desarrollo de este impacto (20/10/2015). Todos los costos de las pruebas son ponderados por el número de unidades utilizadas que reporta la misma base de datos. Además, todas\r\nlas tecnologías son costeadas desde bases de aseguradores, para confirmación de precios. Resultados: Actualmente, el mercado se encuentra dominado por la electromiografía con electrodo de fibra única, la cual se encuentra dentro del plan de beneficios, pero por opinión de los realizadores, una vez que la prueba de acetilcolina receptores y de Lambert entre al plan de beneficios, se aumentará su participación, lo cual repercutirá en un ahorro al sistema, dado que dichas pruebas son menos costosas.(AU)


Assuntos
Humanos , Acetilcolina/análise , Anticorpos Bloqueadores/uso terapêutico , Edrofônio/análise , Eletromiografia/métodos , Miastenia Gravis/terapia , Tecnologia Biomédica , Colômbia , Custos e Análise de Custo/métodos , Eletrodos , Reprodutibilidade dos Testes
20.
Expert Opin Pharmacother ; 17(6): 819-33, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26799963

RESUMO

INTRODUCTION: Acetylcholinesterase inhibitors (neostigmine, edrophonium) and encapsulating agents (sugammadex and calabadion) can be used to reverse residual neuromuscular blockade (NMB). AREAS COVERED: This review provides information about efficacy, effectiveness, and side effects of drugs (acetylcholinesterase inhibitors and encapsulating agents) used to reverse neuromuscular blocking agents (NMBAs). EXPERT OPINION: The therapeutic range of acetylcholinesterase-inhibitors is narrow and effectiveness studies demonstrate clinicians don't use these unspecific reversal agents effectively to increase postoperative respiratory safety. The encapsulating drugs sugammadex and calabadion reverse all levels of NMB, and complete recovery of muscle strength can be achieved almost immediately after administration. For this reason encapsulating agents can be used as a solution for "cannot intubate cannot ventilate"- situations. Poor binding selectivity of encapsulating agents carries the risk of displacement of the NMBA by a competitively binding drug, which may lead to recurarization. In order to avoid side-effects, related to unspecific binding of endogenous proteins and drugs administered perioperatively it is prudent to titrate the dose of reversal agents to the minimal effective dose, depending on the depth of neuromuscular transmission block identified by neuromuscular transmission monitoring. Calabadions provide a diversified (increased binding selectivity) and expanded (reversal of benzylisoquinolines) spectrum of possible indications.


Assuntos
Inibidores da Colinesterase/uso terapêutico , Recuperação Demorada da Anestesia/tratamento farmacológico , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Bloqueio Neuromuscular , Ácidos Sulfônicos/uso terapêutico , gama-Ciclodextrinas/uso terapêutico , Período de Recuperação da Anestesia , Anestesia Geral , Edrofônio/uso terapêutico , Humanos , Neostigmina/uso terapêutico , Fármacos Neuromusculares não Despolarizantes , Sugammadex
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