Kinin B2-Receptor in human iPSC differentiation into cardiomyocytes / Receptor B2 de cininas na diferenciação de iPSC humanas em cardiomiócitos

Cardiovascular diseases are responsible for almost one third of all global deaths yearly, and therefore are largely studied. Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CM) have emerged as an exciting technology for cardiac disease modelling and personalised therapy. Nevertheless, issues concerning functional and molecular maturation are still faced. In addition to this, differentiation protocols generally yield a heterogeneous mixed population comprised of nodal, atrial and ventricular-like subtypes, being unsuitable for therapeutic purposes. Bradykinin (BK) is a vasoactive peptide which exerts important physiological roles in the cardiovascular system, having been previously described as important for cellular, keratinocyte and skeletal muscle differentiation. This project performed in cooperation with PluriCell Biotech, a startup specialized in the production and differentiation of hiPSC-CM, has sought (1) characterizing gene and protein expression of molecular markers of maturation and of subtype specification throughout of differentiation; (2) Assessing the electrical functionality of hiPSC-CM through the characterization of subtype-specific action potentials (APs) and (3) Investigating whether the progress of hiPSCCM maturation is regulated by BK through kinin-B2 receptors (B2R). Our results have validated the model that proposes a developmental-dependent switch between skeletal (ssTnI) and cardiac (cTnI) isoforms of troponin I as differentiation progresses, at least to some extent. Furthermore, prolonged time in culture has resulted in higher levels of expression of the ventricular marker MLC2v and in increased rates of ventricular-like action APs. Electrophysiological analysis of hiPSC-CM reveals a mixed population with AP morphologies correspondent to nodal, atrial and ventricular subtypes, all showing pronounced automaticity as well as other features of immature cardiomyocytes, such as low amplitude and depolarization velocity. Such findings are coherent with those from other groups who have attempted to differentiate mature native-like cardiac cells from pluripotent stem cells sources, without fully succeeding. After showing that differentiating hiPSC-CM express a functional and responsive B2R, the receptor was subjected to chronic activation with 10µM BK and 1µM BK or inhibition with 5µM Firazyr+BK. Even though B2R modulation has not interfered negatively with differentiation yields nor cell morphology, analysis of gene andprotein expression of ssTnI or cTnI and of the ventricular marker MLC2v, have revealed no significant results in comparison to untreated controls. This suggests that BK does not interfere on hiPSC-CM maturation nor subtype specification, although we cannot rule out that it could be leading to other unexplored effects. We recommend a closer look into which intracellular signalling pathways become active upon B2R stimulation in hiPSC-CM, in order to narrow down cellular processes for further investigation

Doenças cardiovasculares são responsáveis por quase um terço de todas as mortes globais anualmente, e por isto o sistema cardiovascular é amplamente estudado. Cardiomiócitos derivados a partir de células-tronco pluripotentes induzidas humanas (hiPSCCM) emergiram como uma promissora tecnologia para modelagem de doenças cardíacas e terapia personalizada. No entanto, desafios acerca de sua maturação funcional e molecular ainda são enfrentados. Além disso, protocolos de diferenciação geralmente levam à obtenção de populações heterogêneas contendo células com fenótipos similares aos de cardiomiócitos nodais, atriais e ventriculares sendo, portanto, inapropriadas para fins terapêuticos. A bradicinina (BK) é um peptídio vasoativo que exerce importantes papeis fisiológicos no sistema cardiovascular, além de ter sido previamente descrita como importante para a diferenciação neuronal, de queratinócitos e de músculo esquelético. Este projeto foi realizado em colaboração com a empresa PluriCell Biotech, uma startup especializada na produção e diferenciação de hiPSC-CM, e buscou (1) caracterizar a expressão gênica e proteíca de marcadores moleculares de maturação e de especificação de subtipos cardíacos durante a diferenciação; (2) avaliar a funcionalidade elétrica de hiPSC-CM por meio da caracterização de seus potenciais de ação (PAs) e (3) Investigar se o progresso da diferenciação de hiPSCCM é regulado por bradicinina por meio do receptor B2 (B2R). Nossos resultados validaram o modelo que propõe um switch na expressão das isoformas funcionais de troponina I esquelética (ssTnI) e cardíaca (cTnI), durante o desenvolvimento e diferenciação celular, pelo menos parcialmente. Além disso, tempo prolongado em cultura resultou em maiores níveis de expressão do marcador ventricular MLC2v, assim como maiores frequências de PAs com morfologias similares a de cardiomiócitos ventriculares. Análise eletrofisiológica de hiPSCCM revelam a existência de uma população mista contendo PAs correspondentes aos subtipos nodais, atriais e ventriculares, assim como pronunciada automaticidade e outros atributos típicos de cardiomiócitos imaturos, como baixa amplitude e devagar velocidade de despolarização. Estes resultados são coerentes com os de outros grupos que ainda não foram totalmente bem-sucedidos em diferenciar células cardíacas maduras similares acardiomiócitos nativos a partir de células-troncos pluripotentes. Após mostrar que as hiPSCCM expressam receptores B2 funcionais e responsivos, submetemos o receptor a uma ativação crônica com BK 10µM e BK 1µM ou inibição crônica com Firazyr 5µM + BK. Apesar da modulação do B2R não ter interferido de forma negativa no rendimento da diferenciação ou na morfologia celular, análise de expressão gênica e proteica de ssTnI e cTnI e do marcador ventricular MLC2v não revelou resultados significativos em comparação aos controles não-tratados. Isto sugere que a BK não interfere na maturação e especificação de subtipos cardíacos em hiPSC-CM, apesar de não podermos ignorar o fato de que ela poderia estar desencadeando outros efeitos inexplorados. Nós recomendamos um estudo mais aprofundado acerca de quais vias de sinalização se tornam ativas após estimulação do receptor B2 em hiPSC-CM, com o objetivo de afunilar quais processos celulares poderiam ser investigados em uma próxima etapa deste estudo

Achados da avaliação comportamental e eletrofisiológica do processamento auditivo / Findings in behavioral and electrophysiological assessment of auditory processing

Objetivo Realizar uma análise descritiva do desempenho de pacientes encaminhados a um hospital de uma instituição de ensino público, para avaliação do processamento auditivo, e correlacionar os achados desta avaliação à idade, queixas, resultados e às avaliações auditivas comportamental e eletrofisiológica.Métodos O estudo incluiu 159 indivíduos encaminhados pelo sistema público de saúde para avaliação do processamento auditivo. Todos os participantes realizaram audiometria tonal liminar, medidas de imitância acústica, testes comportamentais do processamento auditivo e avaliação eletrofisiológica da audição.Resultados A principal queixa referida foi a de dificuldade de aprendizagem e os testes que avaliam processamento temporal e escuta dicótica foram os que apresentaram maior prevalência de alteração. Em todos os testes eletrofisiológicos, o número de resultados normais foi superior aos alterados. A proporção de indivíduos normais e alterados, nos testes comportamentais e eletrofisiológicos, não diferiu em relação ao gênero. Houve correlação fraca entre fechamento auditivo e potencial evocado auditivo de média latência da orelha direita; potencial evocado auditivo de média latência da orelha esquerda e potencial evocado auditivo de média latência total; ordenação temporal e efeito eletrodo direito e P300; processamento temporal e potencial evocado auditivo de média latência da orelha direita; escuta dicótica e P300 e entre interação binaural e reflexo acústico das orelhas direita e esquerda.Conclusão A dificuldade de aprendizagem prevaleceu sobre as queixas dos participantes e as habilidades de processamento temporal e escuta dicótica apresentaram maior prevalência de alteração. A maioria dos participantes foi encaminhada para a avaliação do processamento auditivo pelo fonoaudiólogo. Os testes eletrofisiológicos apresentaram correlação fraca com os testes comportamentais.

Purpose To perform a descriptive analysis of the performance of patients referred to a public educational institution to take part in the assessment of auditory processing and to correlate the assessment findings to the variables of age and hearing complaints, also to correlate results to behavioral and electrophysiological assessments.Methods The study included 159 individuals that were referred to the public health system to take part in an assessment of auditory processing. All participants underwent pure-tone audiometry, acoustic immittance measures, behavioral tests of auditory processing, and electrophysiological hearing assessment.Results The main complaint was learning disability and the tests that presented higher prevalence of abnormal results were temporal processing and dichotic listening tests. In all electrophysiological tests the number of normal results was higher than the altered ones. The proportion of normal and abnormal individuals in behavioral and electrophysiological tests did not differ in relation to gender. There was weak correlation between auditory closure and right ear middle latency responses; between left ear middle latency responses and total middle latency responses; among temporal ordering and electrode effect and P300; between temporal processing and right ear middle latency responses; between dichotic listening and P300 and also between binaural interaction and right and left ears acoustic reflexes.Conclusion The most frequent complaint among participants of this study was learning disability. Temporal processing and dichotic listening skills showed higher prevalence of alteration in the assessment. Most participants were referred to assessment of auditory processing by the speech-language pathologist. Correlation between behavioral and electrophysiological assessments was weak.

Pure neural leprosy: steroids prevent neuropathy progression

Multidrug therapy (MDT), with rifampicin, dapsone, and clofazimine, treats leprosy infection but is insufficient in arresting or preventing the nerve damage that causes impairments and disabilities. This case-series study evaluates the benefits of the combined use of steroids and MDT in preventing nerve damage in patients with pure neural leprosy (PNL). In addition to MDT, 24 patients (88 percent male aged 20-79 years, median=41) received a daily morning dose of 60 mg prednisone (PDN) that was gradually reduced by 10 mg during each of the following 5 months. PNL was clinically diagnosed and confirmed by nerve histopathology or PCR. A low prevalence (8.3 percent) of reaction was observed after release from treatment. However, most of the clinical parameters showed significant improvement; and a reduction of nerve conduction block was observed in 42 percent of the patients. The administration of full-dose PDN improved the clinical and electrophysiological condition of the PNL patients, contributing to the prevention of further neurological damage.

A poliquimioterapia (PQT), com rifampicina, dapsona, e clofazimina, trata a infecção na hanseníase, mas é insuficiente para interromper ou prevenir o comprometimento neurológico que causa as incapacidades e desabilidades, nesta enfermidade. Este estudo de série de casos avalia o benefício do uso combinado de prednisona e PQT na prevenção do dano neurológico em pacientes com a forma neural pura da hanseníase (FNP). Além do PQT, 24 pacientes (88 por cento homens, com idade variando entre 20-79, mediana=41) receberam uma dose diária de 60 mg prednisona que foi reduzida gradualmente na dose de 10 mg durante cada um dos 5 meses subseqüentes. FNP foi diagnosticada clinicamente e confirmada através do estudo histopatológico ou PCR. Baixa prevalência de reação (8,3 por cento) foi observada apenas após o final do tratamento. A maioria dos parâmetros clínicos mostrou melhora significativa e redução do bloqueio de condução foi observada em 42 por cento dos pacientes. A administração de doses altas de prednisona melhora a evolução clínica e eletrofisiológica de pacientes com a FNP de hanseníase, contribuindo na prevenção de novos comprometimentos neurológicos.

Changes in cortical relative power in patients submitted to a tendon transfer: a pre and post surgery study

The aim of this study is analyze possible modifications in the cerebral cortex, through quantitative electroencephalography (qEEG) in patients submitted to a tendon transfer procedure (posterior tibialis) by the Srinivasan's technique. Four subjects (2 men and 2 women), 49.25 age average (SD±21.4) were studied. All subjects have been through surgical procedure due to leprosy and had, at least, two years of drop foot condition. The qEEG measured the electrocortical activity (relative power) between 8 and 25 Hz frequencies pre and post surgery. A paired t test analyzed all data (p<0,05). The results show significant alterations in the alpha relative power, electrodes F7 (p=0.01) and F8 (p=0.021). Altogether, based on findings of the current literature, we can conclude that the tendon transfer procedure suggests electrocortical alterations sensitive to specific qEEG bands.

O objetivo deste estudo é analisar possíveis modificações no córtex cerebral, através da electrencefalografia quantitativa (EEGq), em pacientes submetidos a um procedimento de transferência de tendão (tibial posterior) pela técnica de Srinivasan. Quatro sujeitos (2 homens e 2 mulheres), com média de idade de 49,25 anos (±21,4 DP) foram estudados. Todos os sujeitos realizaram o procedimento cirúrgico devido a hanseníase e tinham, pelo menos, dois anos de pé caído. O EEGq mediu a atividade electrocortical (potencia relativa) entre freqüências de 8 e 25 Hz, no pré e pós-operatório. Um teste t pareado analisou todos os dados (p<0,05). Os resultados mostram alterações significativas na potência relativa em alfa, nos elétrodos F7 (p=0,01) e F8 (p=0,021). Baseados em recentes achados na literatura, podemos concluir que o procedimento de transferência de tendão sugere alterações eletrocorticais sensíveis às freqüên-cias específicas do EEGq.

Programa de ablación con catéter de lafibrilación auricular en el Instituto Nacional de Cardiología Ignacio Chávez / Ablation catheter program implemented for atrial fibrillation at the National Institute of Cardiology of Mexico

The present report describes the program of radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) in patients referred to the AF Clinic of the National Heart Institute. If the patient had specific inclusion criteria for RFCA of AF, and electrophysiological study is performed. A trans-septal approach and special mapping catheters are used to detect abnormal electrical activity (AEA). Pulmonary vein isolation is performed at the ostium/antrum of those veins with AEA if the patient had paroxysmal AF. Global pulmonary vein isolation with some additional lines guided by electroanatomical mapping is performed in the case of chronic AF. Postoperative follow-up includes consultation, ECG and Holter monitoring at 1, 3, 6 and 12-month. RFCA is a useful and relatively safe procedure for the treatment of AF and the only one with curative potential.

Integración neuronal de memoria de trabajo a través de la actividad oscilatoria sincrónica en sujetos sanos y en pacientes esquizofrénicos / Neuronal integration of working memory through oscillatory brain sunchronization in healthy subjects and in schizophrenic patients

Se presenta un resumen de la tesis realizada para optar al grado de Doctor en Ciencias Médicas del programa de Postgrado de la Pontificia Universidad Católica de Chile. Desde el año 1995este programa ha permitido la formación de Médicos que sean capaces de originar investigación independiente en el área biomédica, de constituir un puente entre la investigación básica y la práctica clínica, y que contribuyan al mejoramiento de la docencia académica. El resumen de la tesis que se presenta a continuación fue realizado en el laboratorio de Neurociencias cognitivas del Dr. Francisco Aboitiz, perteneciente al departamento de Psiquiatría de la Pontificia Universidad Católica de Chile en estrecha colaboración con dos centros de investigación internacionales: El F.C. Donders Center para el estudio de neuroimágenes cognitivas, de la universidad de Radboud en Holanda, y el Laboratorio de imagen cerebral y neurociencia cognitiva (LENA ) en Francia.

This work corresponds to a summary of doctoral thesis performed to apply to the doctoral degree in medical science the Pontifical Catholic University of Chile. Since 1995, this program has allowed the training of medical doctors able to produce independent research in the biomedical sciences, bridging the gap between basic research and clinical practice and improving academic teaching. The following summary was made in the Cognitive Neuroscience Laboratory of the psychiatry department of the Pontifical Catholic University of Chile led by Dr. Francisco Aboitiz. This work was performed in close collaboration with two international research centers: The F.C. Donders Center for cognitive neuroimaging (Radboud University, Netherlands) and the cognitive neuroscience and brain-imaging laboratory (LENA, France).

Polineuropatías desmielinizantes crónicas: dificultades en el diagnóstico electrofisiológico / Chronic demyelating polyneuropathies: difficulties in the electrophysiologic diagnosis

Chronic demyelinating polyneuropathies are a group of disease with a difficult differential diagnosis especially if they are axonal, demyielinating, hereditary or adquired. The clinical electrophisiology and laboratories study can help to classificated and to determinate if are susceptible to treat. We described the types of demyelinating polyneuropathies and the clinical and electrophisyology criteria used to diagnosis, remarking the limitation of these criteria.

Coerência espectral do eletrencefalograma em pacientes submetidos a transposição tendinosa: estudo pré e pós-operatório / EEG spectral coherence at patients submitted to tendon transfer surgery: study pre and post surgery

A transferência tendinosa do músculo tibial posterior é intervenção cirúrgica bastante utilizada na ortopedia para correção do pé caído por seqüela de hanseníase. Poucos modelos propuseram investigações mais significativas sobre os fenômenos plásticos cerebrais nas transferências tendinosas. O presente estudo teve como objetivo analisar a coerência espectral (CE) na Eletroencefalografia (EEG) em pacientes submetidos a transferência do tendão do tibial posterior pela técnica de Srinivasan através da EEG quantitativa (EEGq). A amostra foi composta de quatro sujeitos com pé caído devido a seqüela de hanseníase. Os parâmetros de CE do EEG foram quantificados no momento pré e pós-operatório. Os resultados mostraram que houve efeito principal para o fator momento, significativo, no par de eletrodos C3-CZ, com aumento da coerência. Entretanto, os achados da ANOVA não revelaram interação significativa entre bandas versus momento. A recuperação funcional promovida por tal cirurgia parece gerar alterações corticais.

Effect of sildenafil citrate on the cardiovascular system

Sildenafil citrate is a drug commonly used to manage erectile dysfunction. It is designated chemically as 1-[[3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H -pyrazolo[4,3-d]pyrimidin-5-yl)-4 ethoxyphenyl] sulfonyl]-4-methylpiperazine citrate (C22H30N6O4 S). It is a highly selective inhibitor of cyclic guanine monophosphate-specific phosphodiesterase type 5. In late March through mid-November 1998, the US Food and Drug Administration (FDA) published a report on 130 confirmed deaths among men (mean age, 64 years) who received prescriptions for sildenafil citrate, a period during which >6 million outpatient prescriptions (representing about 50 million tablets) were dispensed. The US FDA recently reported that significant cardiovascular events, including sudden cardiac death, have occurred in men with erectile dysfunction who were taking sildenafil citrate. These reports have raised concerns that sildenafil citrate may increase the risk of cardiovascular events, particularly fatal arrhythmias, in patients with cardiovascular disease. In the past few years, the cardiac electrophysiological effects of sildenafil citrate have been investigated extensively in both animal and clinical studies. According to extensive data available to date, sildenafil citrate has been shown to pose minimal cardiovascular risks to healthy people taking this drug. Some precautions are needed for patients with cardiovascular diseases. However, the only absolute contraindication for sildenafil citrate is the concurrent use of nitrates. This article is intended to review sildenafil citrate's cardiovascular effects, as well as current debates about its arrhythmogenic effects.

Acute effect of amiodarone on cardiovascular reflexes of normotensive and renal hypertensive rats

The aim of the present study was to evaluate the effect of amiodarone on mean arterial pressure (MAP), heart rate (HR), baroreflex, Bezold-Jarisch, and peripheral chemoreflex in normotensive and chronic one-kidney, one-clip (1K1C) hypertensive rats (N = 9 to 11 rats in each group). Amiodarone (50 mg/kg, iv) elicited hypotension and bradycardia in normotensive (-10 ± 1 mmHg, -57 ± 6 bpm) and hypertensive rats (-37 ± 7 mmHg, -39 ± 19 bpm). The baroreflex index (deltaHR/deltaMAP) was significantly attenuated by amiodarone in both normotensive (-0.61 ± 0.12 vs -1.47 ± 0.14 bpm/mmHg for reflex bradycardia and -1.15 ± 0.19 vs -2.63 ± 0.26 bpm/mmHg for reflex tachycardia) and hypertensive rats (-0.26 ± 0.05 vs -0.72 ± 0.16 bpm/mmHg for reflex bradycardia and -0.92 ± 0.19 vs -1.51 ± 0.19 bpm/mmHg for reflex tachycardia). The slope of linear regression from deltapulse interval/deltaMAP was attenuated for both reflex bradycardia and tachycardia in normotensive rats (-0.47 ± 0.13 vs -0.94 ± 0.19 ms/mmHg and -0.80 ± 0.13 vs -1.11 ± 0.13 ms/mmHg), but only for reflex bradycardia in hypertensive rats (-0.15 ± 0.02 vs -0.23 ± 0.3 ms/mmHg). In addition, the MAP and HR responses to the Bezold-Jarisch reflex were 20-30 percent smaller in amiodarone-treated normotensive or hypertensive rats. The bradycardic response to peripheral chemoreflex activation with intravenous potassium cyanide was also attenuated by amiodarone in both normotensive (-30 ± 6 vs -49 ± 8 bpm) and hypertensive rats (-34 ± 13 vs -42 ± 10 bpm). On the basis of the well-known electrophysiological effects of amiodarone, the sinus node might be the responsible for the attenuation of the cardiovascular reflexes found in the present study.

Síndrome do túnel do carpo: controvérsias a respeito de diagnóstico clínico e eletrofisiológico e a relaçäo com o trabalho / Carpal tunnel syndrome: controversies regarding clinical and electrodiagnosis and its work-relatedness

O diagnóstico de síndrome do túnel do carpo (STC) apresenta dificuldades porque dormência e formigamento nos membros superiores e alteraçöes de conduçäo nervosa no nervo mediano säo comuns na populaçäo, havendo baixa concordância entre sintomas e alteraçöes eletrofisiológicas. O diagnóstico de STC deve ser feito somente na presença de sintomas característicos acompanhados de alteraçöes eletrofisiológicas significativas. Os casos duvidosos devem ser observados. A associaçäo da STC com certas atividades é controversa

Valor preditivo de variáveis clínicas e eletrofisiológicas em pacientes com cardiopatia chagásica crônica e taquicardia ventricular näo-sustentada / Predictive value of clinical and electrophysiological variables in patients with chronic chagasic cardiomyopathy and nonsustained ventricular tachycardia

OBJECTIVE: Risk stratification of patients with nonsustained ventricular tachycardia (NSVT) and chronic chagasic cardiomyopathy (CCC). METHODS: Seventy eight patients with CCC and NSVT were consecutively and prospectively studied. All patients underwent to 24-hour Holter monitoring, radioisotopic ventriculography, left ventricular angiography, and electrophysiologic study. With programmed ventricular stimulation. RESULTS: Sustained monomorphic ventricular tachycardia (SMVT) was induced in 25 patients (32 percent), NSVT in 20 (25.6 percent) and ventricular fibrillation in 4 (5.1 percent). In 29 patients (37.2 percent) no arrhythmia was inducible. During a 55.7-month-follow-up, 22 (28.2 percent) patients died, 16 due to sudden death, 2 due to nonsudden cardiac death and 4 due to noncardiac death. Logistic regression analysis showed that induction was the independent and main variable that predicted the occurrence of subsequent events and cardiac death (probability of 2.56 and 2.17, respectively). The Mantel-Haenszel chi-square test showed that survival probability was significantly lower in the inducible group than in the noninductible group. The percentage of patients free of events was significantly higher in the noninducible group. CONCLUSION: Induction of SMVT during programmed ventricular stimulation was a predictor of arrhythmia occurrence cardiac death and general mortality in patients with CCC and NSVT

Evidencias de compromiso cerebral en el estadio crónico de la enfermedad de Chagas obtenidas por medio del potencial P300 y de electroencefalografía cuantificada / P300 event related potentials and qEEG evidenced a cerebral dysfunction in human chronic Chagas disease

Es reconocido el compromiso del sistema nervioso periférico en la etapa crónica de la enfermedad de Chagas, incorporándose últimamente evidencias tomográficas y neuropsicológicas de compromiso cerebral. Con el objetivo de evaluar dicho compromiso por medio del potencial P 300 y la electroencefalografía cuantificada (EEGc) se estudiaron 35 pacientes (26 a 55 años), comparados con un grupo control de similar número y edad (29 a 55 años). Se observó: latencia de la onda P 3 mayor en el grupo en estudio (331,24 +/- 24,02 contra 318,86 +/- 23,18) (p=0,01716). El EEGc mostró diferencias en la potencia relativa de la banda Beta 1, menor en los pacientes (p=1,62834E5) y en la frecuencia dominante, 1 Hz menor en los chagasicos (p=0,01077). El análisis multivariado discrimina tres subpoblaciones: una normal, una de enfermos con incremento alfa y otra de enfermos con decremento alfa e incremento delta y theta (p=0,00004). La proporción de resultados patológicos fue del 20 por ciento en los EEGc y el 11,43 por ciento en los potenciales cognitivos. No se correlacionó el compromiso neurológico y el cardíaco. Se concluye que existen francos indicadores electrofisiológicos de compromiso cerebral en el estadio crónico de la enfermedad de Chagas, hallazgo que refuerza a los obtenidos por otros métodos.

Sera from chronic chagasic patients depress cardiac electrogenesis and conduction

We report results obtained with sera from 58 chronic chagasic patients that were evaluated for effects on heart rate and atrioventricular (AV) conduction in isolated rabbit hearts and screened for the presence of muscarinic and beta-adrenergic activity. We show that sera from 26 patients decreased heart rate, while 10 increased it and 22 had no effect. Additionally, sera from 20 of the 58 patients blocked AV conduction. Muscarinic activation seems to be involved in both effects, but is not the only mechanism, since atropine did not antagonize the decrease in heart rate in 23 percent of sera or AV block in 40 percent. Sera from patients with complex arrhythmias were significantly more effective in depressing both heart rate and AV conduction. Sera that induce increases in heart rate seem to operate exclusively through beta-adrenergic activation. Two of these sera, evaluated with respect to intercellular communication in primary cultures of embryonic cardiomyocytes were able to block gap junction conductance evaluated by a dye injection technique after 24-h exposure. The mechanisms underlying this uncoupling effect are currently being investigated

Polineuropatía inflamatoria desmielinizante crónica: presentación de 6 casos / Chronic inflammatory demyelinating polyneuropathy: report of 6 cases

Chronic inflammatory demyelinating polyneuropathy is a heterogeneous disease characterized by symmetrical motor and sensitive alterations, absence of tendom reflexes and increased cerebrospinal fluid protein levels. We report 6 patients with the disease (3 males) aged 41 to 70 years old. Four had tha classical presentation and two had an asymmetrical paresis, that predominated in superior limbs. These patients had proximal block with scarce prolongation of distal nerve conduction velocity. In all patients, underlying illnesses were discarded with a full diagnostic work up. Subjects were followed from 2 to 14 months after the diagnosis. In all, treatment with steroids improved muscle strength and sensivity

Clinical manifestations of peripheral nervous system involvement in human chronic Chagas disease

We conducted a clinical and electromyographical study in patients with Chagas' disease indeterminiate or chronic stages of the illness. Altogether 841 patients were examined. Only 511 Were admitted within the protocol; the remainder patients were rejected because they showed other causes able to danage the nervous system. Fifty two (1O. 17 per cent) out of the 511 patients showed signs and symptoms of peripheral nervous system involvement in the form of sensory impairiment and diminished tendon jerks suggesting the presence neuropathy. Forty five of them were submitted to a conventional electromygraphical examination. Fifthem of the showed normal results, while the remainder 30 disclosed a rcduced interference pattern, being most of the remainig motor unit potentials fragmented or poliphasic, reduced sensory and motor conduction velocities and diminished amplitude of the sensory action potential. 'The findings suggest that some chagasic paties in the determinate or chronic stages of the disease may develop a clinical mild sensory-motor peripheral neuropathy.

Electrophysiologic study in chronic Chagas' heart disease

Cardiac arrhythmias are common in chagasic patients. Electrophysiologic study is an invasive procedure for the investigation of sinus node function, atrioventricular node conduction and intraventricular (His-Purkinje) conduction and the mechanism of tachycardias. It is useful in elucidating syncope, dizziness and tachycardiac palpitations that remain unexplained by non-invasive diagnostic methods. It is fundamental in directing non-pharmacological therapy, especially in "sudden death" survivors. Chagasic patients may benefit from electrophysiologic study after a critical clinical evaluation.

Fundamentos de electrocardiografia clinica / Foundations of clinical electrocardiography

Contenido: Electrofisiologia,bases tecnicas,rutina de interpretecion,electrocardiograma normal,crecimientos auriculares,crecimientos ventriculares,bloqueos de rama,arritmias cardiacas,trastornos de la conducicion,sindrome de preexitacion,isquemia lesion y necrosis,el E.CG. en las valvulopatias,el E.C.G. en la pericarditis,el E.C.G. en la miocardia chagasica cronica,el E.C.G. en el embolismo pulmonar cronica,el E.C.G. en las cardiopatias congenitas,el E.C.G. en las alteraciones electroliticas y por accion de medicamentos,el E.C.G. en los marcapasos