Celebrating the 70 years of pyridostigmine on therapy of Myasthenia Gravis: historical aspects of the preliminary trials / Celebrando os 70 anos da piridostigmina no tratamento da Miastenia Gravis: aspectos históricos dos ensaios clínicos preliminares

Abstract Currently, pyridostigmine bromide is an indispensable anticholinesterase agent used worldwide to treat patients with Myasthenia Gravis (MG). However, pyridostigmine bromide was unsuccessful in its "pioneering trials" to treat a series of MG patients. There are important historical landmarks before pyridostigmine bromide becomes useful, safe and indispensable for MG therapy. After 70 years of these "pioneering trials", this article reviews some historical aspects related to them, as well as other preliminary trials using pyridostigmine bromide as therapy for MG patients.

Resumo Atualmente, o brometo de piridostigmina é um indispensável agente anticolinesterásico usado em todo o mundo no tratamento de pacientes com Miastenia Gravis (MG). Contudo, o brometo de piridostigmina não foi bem-sucedido, em seus "ensaios clínicos pioneiros", no tratamento de uma série de pacientes com MG. Existem importantes marcos históricos antes do brometo de piridostigmina se tornar útil, seguro e indispensável no tratamento da MG. Após 70 anos desses "ensaios clínicos pioneiros", este artigo revisa alguns aspectos históricos a eles relacionados, bem como a outros estudos preliminares que usaram o brometo de piridostigmina como um tratamento para pacientes com MG.

Miastenia Gravis: reporte de dos casos y revisión de la literatura / Myasthenia Gravis: two case reports and review

Myasthenia gravis is an acquired autoimmune disorder of the neuromuscular junction characterized by fluctuating weakness and fatigability of skeletal muscles. The diagnosis can be established by clinical and serologic testing, with predominance of autoantibodies against the acetylcholine receptor, and Muscle-specific kinase antibodies. We report two cases of Myasthenia gravis, the first one is a 31 year old patient with a debut of the disease, mainly with bulbar symptoms, and the second one is a 29 year old patient diagnosed with generalized Miasthenia Gravis also mainly with bulbar symptoms with worsening of symptomatology. In this report treatments alternatives and management approaches are discused

Síndrome miasténico congénito por deficiencia de rapsina: reporte de caso con nueva mutación y heterocigosidad compuesta / Congenital myasthenic syndrome due to rapsyn deficiency: A case report with a new mutation and compound heterozygosity

INTRODUCCIÓN Los síndromes miasténicos congénitos son un grupo heterogéneo de desórdenes genéticos, caracterizados por una transmisión sináptica anormal en la placa neuromuscular. REPORTE Presentamos el caso de un paciente de dos años, varón, con hipotonía, ptosis palpebral y debilidad simétrica y de predominio proximal, características que aparecieron desde el nacimiento y que motivaron varias hospitalizaciones por neumonía e insuficiencia ventilatoria. Desde el inicio de la deambulación a los dos años, los padres notaron que la debilidad empeoraba por las tardes y con la actividad física repetida o prolongada. El examen físico a los dos años mostró ptosis palpebral, debilidad de predominio proximal y fatigabilidad con el esfuerzo sostenido. La electro-miografía evidenció decremento del 27% en el potencial de acción muscular compuesto. El análisis de tríos mostró heterocigosis compuesta por transmisión de dos mutaciones diferentes en el gen de rapsina, una ya conocida procedente del padre y la otra no reportada previa-mente, procedente de la madre. El paciente recibió piridostigmina obteniendo mejoría inmediata y logrando un desempeño óptimo en actividades escolares, deportivas y de la vida cotidiana. A la fecha, no ha presentado nuevos episodios de insuficiencia ventilatoria. CONCLUSIONES La debilidad de inicio neonatal y la fatigabilidad o agotamiento con el esfuerzo sostenido, con afección principalmente de los músculos con inervación troncal y con un decremento mayor al 10% en el potencial de acción muscular compuesto en la electromiografía, deben hacer sospechar en un síndrome miasténico congénito. Se revisan los puntos clínicos clave que permiten establecer el diagnóstico oportuno y las opciones de tratamiento efectivo para algunos de estos síndromes.

INTRODUCTION The congenital myasthenic syndromes are a heterogeneous group of genetic disorders characterized by an abnormal synaptic transmission in the neuromuscular plate. REPORT We present a two-year-old patient, male, with hypotonia, palpebral ptosis, and proximal symmetric weakness with a neonatal onset that motivated several and prolonged hospitalizations for pneumonia and respiratory failure. From two years of age, the parents noticed that the facial and general weakness worsened in the afternoons and with repeated or prolonged physical activity. The physical examination showed palpebral ptosis, predominantly proximal weakness, and fatigability with sustained muscular effort. The electromyography showed a 27% decrement in the Compound Muscular Action Potential and the case-parents genetic study showed compound heterozygosity with the transmission of two different mutations in the rapsyn gene from both parents. The patient received pyridostigmine with great improvement, achieving optimal performance in school, sports, and daily life activities. CONCLUSIONS Weakness and fatigability with neonatal onset, mainly affecting the muscles with brain stem innervation and the decrement greater than 10 percent in the Compound Muscular Action Potential in the electromyographic studies, should make us suspect in a congenital myasthenic syndrome. We review the literature and key clinical points to establish a timely diagnosis and effective treatment in some of these syndromes.

Gluten and Neuroimmunology. Rare association with Myasthenia Gravis and Literature Review

SUMMARY As the celiac disease (CD), the non-celiac gluten sensitivity (NCGS) has also been associated with several autoimmune manifestations. It is rarely associated with myasthenia gravis (MG). This paper shall introduce the case of a young female patient, initially presenting a peripheral neuropathy framework. During clinical and neurological follow-up, she began to present symptoms of various immune-mediated morbidities. Diseases related to gluten represent a clinical spectrum of manifestations with a trigger in common, the ingestion of gluten. CD is the most well-known and serious disease of the spectrum, also called gluten-sensitive enteropathy. The NCGS is diagnosed from clinical evidence of improvement in symptoms followed by a Gluten Free Diet (GFD) in patients without signs of enteropathy in duodenal biopsy. There are indications that, although rare, with a prevalence of 1 in 5000, myasthenia gravis (MG) may occur more often when CD is also present. Between 13 to 22% of the patients with MG have a second autoimmune disorder. However, it is often associated with dermatomyositis or polymyositis, lupus erythematosussystemic lupus erythematosus, Addison's disease, Guillain-Barré syndrome and juvenile rheumatoid arthritis. Thus, the symptoms of neuromuscular junction involvement may give a diagnostic evidence of this rare association.

Miastenia gravis y su asociación con trastornos linfoproliferativos: casos clínicos / Myasthenia gravis and its association with lymphoproliferative disorders: a case series

Myasthenia gravis (MG) is a rare autoimmune disease of the neuromuscular junction. It is characterized by variable weakness and excessive fatigability of skeletal muscles. In the last few years, numerous reports have been published showing the association between autoimmune diseases, such as systemic erythematous lupus or rheumatoid arthritis, with lymphoid neoplasias. The association between MG and lymphoid neoplasia seems to be less frequent. To analyze this association we reviewed the MG patients in the Department of Neurology, Hospital Salvador of Santiago, Chile. During a three-year period we identified four patients who developed different lymphoproliferative disorders: two with B-cell lymphoma, one with chronic lymphocytic leukaemia and one plasmacytoma with an associated amyloidosis. The MG was generalized but mild, all cases classified as type IIa according to the definition proposed by the MG Foundation of America. The neoplasia appeared two to 36 years after the onset of MG. These cases provide additional evidence of the association between MG and lymphoproliferative disorders.

Interação da atividade autonômica e resposta imunomoduladora na fase aguda do infarto do miocárdio experimental / Interaction of autonomic activity and immunomodulatory response in acute experimental myocardial infarction

INTRODUÇÃO: A atuação do sistema nervoso parassimpático em células imunes é conhecida como "Via Anti-inflamatória Colinérgica". Trabalhos prévios demonstraram que a estimulação vagal reduz a inflamação e melhora a sobrevida em modelos experimentais com sepse. Neste estudo avaliamos se o uso do anticolinesterásico piridostigmina: altera o número de linfócitos T (CD4+ e CD8+) convencionais (CD25+Foxp3-) e reguladores (CD25+Foxp3+) no sangue periférico, no baço e no miocárdio; modifica a concentração de citocinas (interleucina 1, interleucina 6, TNFalfa) no miocárdio; e influencia a função ventricular após infarto agudo do miocárdio experimental (IAM) em ratos. MÉTODOS: Utilizamos ratos machos adultos da linhagem Wistar, com peso variando entre 200 e 250 g, divididos em 3 grupos de 20 animais cada: grupo controle (GC), grupo infartado sem tratamento (IC) e grupo infartado tratado com piridostigmina (IP). O infarto agudo do miocárdio (IAM) foi obtido com a técnica da ligadura da artéria coronária esquerda, e o grupo IP recebeu piridostigmina na dose de 40mg/kg/dia na água de beber, iniciada 4 dias antes do IAM. Todos os animais foram submetidos à canulação da artéria femoral no dia seguinte ao IAM para registro das curvas de pressão arterial, e posterior análise dos componentes da variabilidade da freqüência cardíaca (VFC), domínio do tempo (SDNN e RMSSD) e da freqüência (componentes LF e HF); o estudo ecocardiográfico foi realizado no segundo dia pós IAM. No terceiro dia pós IAM, os ratos foram divididos em subgrupos de 10 animais, e sacrificados de forma específica para coleta de materiais: 500 ul de sangue periférico e baço fresco para realização da técnica de citometria de fluxo; ventrículo esquerdo para dosagem de citocinas pela técnica de ELISA; e ventrículo esquerdo para realização de imunohistoquímica. Foram usadas as técnicas padronizadas e de uso corrente nos laboratórios...

INTRODUTION: The role of the parasympathetic nervous system in immune cells is known as "Cholinergic anti-inflammatory pathway". In previous work has demonstrated that vagal stimulation reduces inflammation and improves survival in experimental sepsis models. The aim of the present study evalued the use of anticholinesterase pyridostigmine: change the number of T lymphocytes (CD4+ and CD8+) conventional (CD25+Foxp3-) and regulatory (CD25+Foxp3+) in peripheral blood, spleen, and myocardium: modifies the concentration of cytokines (interleukin-1, interleukin-6, TNFalfa) in the myocardium, and influences ventricular function after experimental myocardial infarction (MI) in rats. METHODS: Adult male rats of Wistar strain, weighing between 200 and 250 g were divided into 3 groups of 20 animals each: control group (GC); untreated group without treatment (IC) and infarcted group treated with pyridostigmine (IP). Acute myocardial infarction (AMI) was obtained with the technique of ligation of the left coronary artery, and the IP group received pyridostigmine dose of 40 mg/Kg/day in drinking water starting 4 days before the AMI. All animals underwent cannulation of the femoral artery on the day following AMI to record the blood pressure curves, and subsequent analysis of the components of heart rate variability (HRV), the time domain (SDNN and RMSSD) and frequency (components LF and HF), the echocardiografic study was performed on the second day after AMI. On the third day post-MI, mice were divided into subgroups of 10 animals, and were sacrificed in order to collet specific materials: 500 ul of fresh peripheral blood and spleen technique for performing flow cytometry left ventricle for measurement of cytokine ELISA, and the left ventricle to perform immunohistochemistry. Techniques used were standardized and commonly used in laboraties. The results were evaluated by analysis of variance (ANOVA) multifactorial, using the GraphPad Prism with Tukey post hoc test...

Diagnóstico de miastenia gravis en perros / Miastenia gravis diagnostic in dogs

La miastenia gravis (MG) es una enfermedad neuromuscular de causa autoinmune, en la que es importante realizar un diagnóstico clínico y bioquímico oportuno para instaurar la terapéutica adecuada que cambiará la calidad y expectativa de vida de los caninos. En el presente trabajo se describen los métodos diagnósticos habitualmente utilizados y el tratamiento de treinta y dos caninos con sospecha de MG, y se propone la administración de bromuro de piridostigmina como una herramienta más, útil en el diagnóstico de la MG canina.

Miastenia Gravis is a neuromuscular disease caused by autoantibodies. Early Clinical and biochemical diagnosis and treatment is demanded in the assurement of quality and time of life in all dogs. In this study we describe the conventional diagnosis methods and therapy in 32 dogs with suspected myasthenia gravis and propose the administration of bromide of piridostigmin as another usefull diagnosis method in dogs.

Acute electrophysiologic consequences of pyridostigmine inhibition of cholinesterase in humans

The cardiovascular electrophysiologic basis for the action of pyridostigmine, an acetylcholinesterase inhibitor, has not been investigated. The objective of the present study was to determine the cardiac electrophysiologic effects of a single dose of pyridostigmine bromide in an open-label, quasi-experimental protocol. Fifteen patients who had been indicated for diagnostic cardiac electrophysiologic study underwent two studies just before and 90-120 min after the oral administration of pyridostigmine (45 mg). Pyridostigmine was well tolerated by all patients. Wenckebach nodal anterograde atrioventricular point and basic cycle were not altered by pyridostigmine. Sinus recovery time (ms) was shorter during a 500-ms cycle stimulation (pre: 326 ± 45 vs post: 235 ± 47; P = 0.003) but not during 400-ms (pre: 275 ± 28 vs post: 248 ± 32; P = 0.490) or 600-ms (pre: 252 ± 42 vs post: 179 ± 26; P = 0.080) cycle stimulation. Pyridostigmine increased the ventricular refractory period (ms) during the 400-ms cycle stimulation (pre: 238 ± 7 vs post: 245 ± 9; P = 0.028) but not during the 500-ms (pre: 248 ± 7 vs post: 253 ± 9; P = 0.150) or 600-ms (pre: 254 ± 8 vs post: 259 ± 8; P = 0.255) cycle stimulation. We conclude that pyridostigmine did not produce conduction disturbances and, indeed, increased the ventricular refractory period at higher heart rates. While the effect explains previous results showing the anti-arrhythmic action of pyridostigmine, the clinical impact on long-term outcomes requires further investigation.

Impacto da preservação parassimpática sobre os aspectos morfofuncionais cardíacos em ratos infartados / Parassympathic preservation impact in cardiac morphofunctional aspects in myocardial infarcted rats

Neste estudo, testamos a hipótese de que a estimulação colnérgica pela administração de piridostigmina, um agente anticolinesterásico reversível, protege o miocárdio submetido à isquemia miocárdica crônica durante 3 tempos de observação: 7, 21 e 42 dias. Para essa avaliação foram medidos a área de acinesia (índicador de área de infarto), os índíces das funções sistólica e diastólica pela ecocardiografia e por medida direta bem como marcadores da função autonômica como a sensibilidade do barorreflexo e a variabilidade da frequência cardíaca (FC) e da pressão arterial (PA). O bloqueio farmacológico do sistema nervoso autônomo e o estudo da via eferente parassimpática foram também realizados. Utilizou-se ratos Wistar machos divididos em 4 grupos: controle, controle piridostigmina, infartado e infartado piridostigmina. Os resultados mostraram os efeitos protetores da piridostigmina nos diferentes tempo de infarto com redução da área de acinesia ( maior que 80%) tanto pelo ecocardiograma quanto pela histologia. Além disso observou-se recuperação das funções sistólica e diastólica, com normalização da pressão diastólica final e das derivadas de contração e relaxamento. Essas melhoras foram mais consistentes em 21 e 42 dias, sem diferenças entre esses tempos de tratamento. Em 7 dias ainda persistiram alguns índices de disfunção ventricular, embora a função autonômica estivesse bem preservada. Parte dessa melhora se deve, provavelmente, ao aumento do tônus vagal e redução do simpático. A potenciação da bradicardia pela estimulação elétrica do vago induzida pela piridostigmina confirma seu papel com estimulador colinérgico. A sensibilidade do barorreflexo reduzida de forma semelhante pelo infarto do miocárdio aos 7, 21 e 42 dias, voltou aos valores controle após o tratamento com piridostigmina, sem diferenças devidas ao tempo de tratamento. Da mesma forma, a variabilidade da FC foi aumentada após o tratamento com o brometo de piridostigmina no grupo infartado...

In this study we tested the hypothesis that cholinergic stimulation by pyridostigmine administration, a reversible cholinergic inhibitor, protects the ischemic myocardial in three periods of follow-up: 7, 21 and 42 days. For this evaluation we measured the akinetic area (infacrtion area indicator), systolic and diastolic indexes by echocardiography and left ventricle direct measurements as well as autonomic function markers, as baroreflex sensitivity and heart rate (HR) and blood pressure (BP) variabilities. Pharmacological blockade of the autonomic nervous system and the study of the efferent parasympathetic pathway were also performed. Male Wistar rats were divided in 4 groups: control, control treated with pyridostigmine, infarcted and infarcted treated with pyridostigmine. The results showed the protective effects of pyridostigmine in the different periods of infarction, with the reduction of the akinetic area (more than 80%), either by the echocardiography and by histology. Moreover, we observed systolic and diastolic functions recovery, with normalization of the end diastolic pressure and the maximum rates of left ventricle BP rise and fall. These improvements were more consistent in 21 and 42 days, with no differences between these two periods of treatment. In 7-day treatment, some indexes of ventricular dysfunction remained, although the autonomic function seemed to be preserved. Part of these improvements is probably due to the increase in the vagal tonus and the decrease in the sympathetic tonus. The pyridostigmine effects in the potencialization of the bradycardia induced by vagus nerve electrical stimulation confirms its role as a cholinergic stimulator. The reduced baroreflex sensitivity by myocardial infarction, which was similar in 7, 21 and 42 days, returned to control values after pyridostigmine treatment, without differences related to treatment extent. Similarly, HR variability was increased after pyridostigmine treatment in the infarcted...

Cholinergic stimulation with pyridostigmine reduces the QTc interval in coronary artery disease

Parasympathetic dysfunction is an independent risk factor in patients with coronary artery disease; thus, cholinergic stimulation is a potential therapeutic measure that may be protective by acting on ventricular repolarization. The purpose of the present study was to determine the effects of pyridostigmine bromide (PYR), a reversible anticholinesterase agent, on the electrocardiographic variables, particularly QTc interval, in patients with stable coronary artery disease. In a randomized double-blind crossover placebo-controlled study, simultaneous 12-lead electrocardiographic tracings were obtained at rest from 10 patients with exercise-induced myocardial ischemia before and 2 h after the oral administration of 45 mg PYR or placebo. PYR increased the RR intervals (pre: 921 ± 27 ms vs post: 1127 ± 37 ms; P<0.01) and, in contrast with placebo, decreased the QTc interval (pre: 401 ± 3 ms vs post: 382 ± 3 ms; P<0.01). No other electrocardiographic variables were modified (PR segment, QT interval, QT and QTc dispersions). Cholinergic stimulation with PYR caused bradycardia and reduced the QTc interval without important side effects in patients with coronary disease. These effects, if confirmed in studies over longer periods of administration, may suggest a cardioprotection by cholinergic stimulation with PYR

Miastenia gravis congênita e oftalmoplegia externa / Congenital myastenia gravis and external ophthalmoplegia

A miastenia gravis é uma doença crônica, caracterizada por fatigabilidade anormal de músculos estriados, podendo acometer grupos musculares isolados ou tornar-se generalizada. Os autores descrevem um caso de miastenia gravis congênita generalizada e oftalmoplegia parcial em um paciente de 10 anos de idade, portador de sintomas sistêmicos motores e de ausência na aduçäo, abduçäo e elevaçäo em ambos os olhos e com ptose palpebral bilateral, sendo reduzida à funçäo de infraversäo. O paciente foi diagnosticado aos dois anos e seis meses, sendo iniciado tratamento com piridostigmina em doses subterapêuticas, sem alteraçäo importante no quadro clínico. Aos quatro anos de idade, procurou esta instituiçäo, sendo ajustada à dose da medicaçäo, seguindo-se melhora significativa dos sintomas motores sistêmicos, melhora parcial da ptose palpebral e sem alteraräo na oftalmoplegia externa.

Myasthenia gravis in children: analysis of 18 patients

Myasthenia gravis (MG) in childhood is rare comprising 10 to 20 percent of all myasthenic patients. We studied 18 patients with MG whose first symptoms started from 1 to 12 years of age, followed at the Department of Neurology of the UNIFESP-EPM, from January 1983 to August 1997. There were 10 girls and 8 boys (1.2:1). Eleven patients (61 percent) presented moderate or severe generalized disease and 4 (22 percent) had at least one myasthenic crisis. EMG with supramaximal repetitive nerve stimulation was diagnostic in 8 (47 percent) out of 17 patients, and chest CT was normal in 14 patients. Seropositivity to acetylcholine receptor antibodies was found in 81.6 percent (9 out of 11 tested) and the levels had no relation to clinical severity. Nine out of 16 patients (56 percent) worsened with pyridostigmine alone and were treated with prednisone. Four out of those nine continued worsening despite steroids and were subjected to thymectomy (all showed thymic lymphoid follicular hyperplasia). Three patients (75 percent) improved markedly after thymectomy and one (25 percent) worsened, eventually getting better with intravenous immunoglobulin and oral azathioprine. MG treatment, using all resources available, has to be individualized for each child

Teste de esforço cardiopulmonar durante estimulaçäo colinérgica com dose única de piridostigmina em indivíduos saudáveis / Exercise stress testing in healthy subjects during cholinergic stimulation after a single dose of pyridostigmine

OBJETIVE: The evaluation, by exercise stress testing, of the cardiorespiratory effects of pyridostigmine (PYR), a reversible acetylcholinesterase inhibitor. METHODS: A double-blind, randomized, cross-over, placebo-controlled comparison of hemodynamic and ventilation variables of 10 healthy subjects who underwent three exercise stress tests (the first for adaptation and determination of tolerance to exercise, the other two after administration of placebo or 45mg of PYR). RESULTS: Heart rate at rest was: 68 + or - 3 vs 68 + or - 3bpm before and after placebo, respectively (P=0.38); 70 + or - 2 vs 59 + or - 2bpm, before and after pyridostigmine, respectively (P<0.01). During exercise, relative to placebo: a significantly lower heart rate after PYR at, respectively, 20 per cent (P=0.02), 40 per cent (P=0.03), 80 per cent (P=0.05) and 100 per cent (P=0.02) of peak effort was observed. No significant differences were observed in arterial blood pressure, oxygen consumption at submaximal and maximal effort, exercise duration, respiratory ratio, CO2 production, ventilation threshold, minute ventilation, and oxygen pulse. CONCLUSION: Pyridostigmine, at a dose of 45mg, decreases heart rate at rest and during exercise, with minimal side effects and without interfering with exercise tolerance and ventilation variables.

Reduçäo da dispersäo do intervalo QTc: potencial mecanismo de proteçäo cardíaca do brometo de piridostigmina / Reduction of QTc interval dispersion: potential mechanism of cardiac protection of pyridostigmine bromide

OBJECTIVE: Parasympathetic dysfunction is an independent risk factor in individuals with coronary artery disease, and cholinergic stimulation is a potential therapeutical option. We determined the effects of pyridostigmine bromide, a reversible anticholinesterase agent, on electrocardiographic variables of healthy individuals. METHODS: We carried out a cross-sectional, double blind, randomized, placebo-controlled study. We obtained electrocardiographic tracings in 12 simultaneous leads of 10 healthy young individuals at rest before and after oral administration of 45 mg of pyridostigmine or placebo. RESULTS: Pyridostigmine increased RR intervals (before: 886 + or - 27 ms vs after: 1054 + or - 37 ms) and decreased QTc dispersion (before: 72 + or - 9ms vs after: 45 + or - 3ms), without changing other electrocardiographic variables (PR segment, QT interval, QTc, and QT dispersion). CONCLUSION: Bradycardia and the reduction in QTc dispersion induced by pyridostigmine may effectively represent a protective mechanism if these results can be reproduced in individuals with cardiovascular diseases.

Estimulação colinérgica com peridostigmina em coronariopatas durante o exercício diâmico / Cholinergic stimulation with peridostigmina during exercise in patients with coronary diâmico

A disfunção parassimpática correlaciopna-se com pior prognóstico após infarto agudo do miocárdio e na insuficiência cardíaca, independente da presença de outros fatores de risco. A atualização de uma droga que atue aumentando a ação colinérgica, tem potencial efeito benéfico em portadores de cardiopatias. O objetivo foi estudar o efeito do brometo de piridostigmina(PIR). um inibidor reversível da atividade colinesterásica, portanto um parassimpaticomimético indireto, sobre as respostas cardiorespiratórias no teste cardioplumunar de exercício (TCPE) em portadores de doença coronariana estável. PIR inibiu FC no exercício submáxino, aumentou a intensidade na qual a isquemia miocárdica ocorreu e melhorou a tolerância ao exercício. Estas alterações sugerem que PYR pode apresentar potencial efeito cardioprotetor em pacientes com doença arterial coronária que apresentem isquemia miocárdica induzida pelo esforço.

Ventilação pulmonar mecânica em Pediatria / Mechanic pulmonary ventilation in Pediatrics

Os autores analisam exaustivamente todos os aspectos da ventilaçäo pulmonar mecânica em Pediatria, destacando a importância dos diferentes procedimentos e técnicas utilizados, suas indicaçöes, cuidados a observar no seu emprego, objetivos, parâmetros iniciais, uso da sedaçäo, analgesia e bloqueio neuromuscular do paciente, finalizando com a descriçäo da ventilaçäo pulmonar mecânica nas situaçöes clínicas mais encontradiças nos Centros de Terapia Intensiva pediátrica, limitaçöes ao seu emprego e possíveis avanços em futuro próximo

Estimulaçäo colinérgica com piridostigmina. Análise Hemodinâmica e ecocardiográfica em indivíduos normais / Cholinergic stimulation with pyrodostigmine, hemodynamic and echocardiographic analysis in healthy subjects

Objetivo - Crescentes evidências indicam que a morte súbita em pacientes pós-infarto agudo do miocárdio (IAM) correlaciona-se com desequilíbrio do sistema nervoso autônomo. Drogas parassimpaticométricas têm sido testadas com a finalidade de reverter essas alterações. Porém, seus efeitos sobre a função ventricular necessitam de uma avaliação específica. Nosso objetivo foi analisar o efeito da pridostigmina (PIR) sobre variáveis hemodinâmicas e ecocardiográficas da função ventricular. Métodos - Vinte voluntários sadios foram submetidos a avaliações ecodopplercardiográficas e aferições de pressão arterial (PA) e freqüência cardíaca (FC) em repouso, antes e 120min após a ingestão de 30mg de PIR ou placebo, seguindo-se um protocolo duplo-cego, placebo-controlado, cruzado e randomizado, em dias diferentes. Resultados - PIR foi bem tolerada e não provocou alterações de PA ou função sistólica ventricular. A FC apresentou redução de 10,9+1,3 por cento (p<0,00001). Houve redução da onda A ao fluxo mitral (p<0,01) e aumento da relação E/A (p<0,001) sem alterar os demais índices de função diastólica (p>0,05). Conclusão - A PIR reduz a FC e aumenta a relação E/A, sem prejuízo hemodinâmico ou alteração da função ventricular.

Miastenia Gravis en el Hospital Santo Tomás 1990-1997 / Myasthenia gravis in Santo Tomás Hospital 1990-1997

Myasthenia Gravis is an infrequent disease. Diagnosis and treatment must be done early to avoid high morbidity that can compromise patients lives. Nine cases were identified during the eight year 1990-1997 at the Santo Tomas Hospital of Panama city but one had to be excluded because he refused treatment. Most of the patients (7/8) had symptoms for more than 3 months. The diagnosis of Myasthenia Gravis requires a high index of suspicion and the clinical impressión must be confirmed by various diagnostic studies that include the edrophonium test, the repetitive stimulation test, the therapeutic test with pyridostigmine, the determination of acetylcholine anti-receptor antibodies and a CT Scan of the thorax. Medical treatment consists mainly of anticholinesterase agents and surgical treatment consists of thymectomy by means of an extended transternal ablation. Operative results were excellent, seven out of eight improved

Diagnóstico en Miastenia Gravis / Myasthemia gravis diagnosis

La miastenia gravis (MG) es uno de los desórdenes neuromusculares con involucro oftalmológico inicial más frecuente, por lo que el oftalmólogo debe conocer esta patología. Se debe sospechar de esta entidad en los casos en que se presenta ptosis y estrabismo con limitación en las ducciones; se deben realizar pruebas clínicas y de laboratorio para el diagnóstico de certeza. Se mencionan las pruebas clínicas, serológicas y electromiográficas diagnósticas más importantes, las ateraciones genéticas asociadas a este padecimiento y, brevemente, el tratamiento