Generation of patient-specific induced pluripotent stem cell lines from one patient with Jervell and Lange-Nielsen syndrome, one with type 1 long QT syndrome and two healthy relatives.

Four human iPSC cell lines (one Jervell and Lange-Nielsen Syndrome, one Long QT Syndrome-type 1 and two healthy controls) were generated from peripheral blood obtained from donors belonging to the same family. CytoTune™-iPS 2.0 Sendai Reprogramming Kit (containing OCT3/4, KLF4, SOX2 and cMYC as reprogramming factors) was used to generate all cell lines. The four iPSCs have normal karyotype, express pluripotency markers as determined by RT-PCR and flow cytometry and differentiated spontaneously in vitro into cells of the three germ layers, confirming their pluripotent capacity.

The electrocardiogram in patients with multiple accessory atrioventricular pathways.

The 12 lead electrocardiographic (ECG) findings were reviewed in 17 patients having two or more accessory pathways as documented during electrophysiologic study in all 17 patients and by intraoperative mapping in 8. Twelve patients had findings suggesting the presence of more than one atrioventricular (AV) pathway. These were 1) more than one P wave configuration during orthodromic circus movement tachycardia (four patients); 2) a "mismatch" between the location of the ventricular and atrial ends of the accessory pathway as assessed when comparing exclusive AV and ventriculoatrial conduction over the accessory pathway during antidromic and orthodromic circus movement tachycardia, respectively (seven patients); 3) atrial fibrillation showing more than one pre-excitation pattern (six patients); 4) a spontaneous change from orthodromic to antidromic circus movement tachycardia and vice versa (two patients); 5) a spontaneous change from one type of antidromic tachycardia to another (two patients); and 6) a change in pre-excitation pattern after administration of a drug that prolongs the anterograde refractory period of the accessory pathway (three patients). The retrospective nature of this study does not allow conclusions as to the true value of the ECG in predicting the presence of more than one accessory pathway. This issue needs to be evaluated in a prospective study.

Reversibility of tachycardia-induced cardiomyopathy after cure of incessant supraventricular tachycardia.

Seven of 17 patients with incessant supraventricular tachycardia caused by an accessory pathway with a long retrograde conduction time were seen with symptoms or echocardiographic signs of a tachycardia-induced cardiomyopathy. Three patients were in New York Heart Association functional class II with dyspnea and four were in class III. Eight patients (six with tachycardia-induced cardiomyopathy) underwent surgery because of failure of medical treatment (including one patient in functional class I) and one underwent direct current catheter ablation of the atrioventricular (AV) node. In six patients echocardiograms recorded before and after the procedure were available. Before surgery or direct current ablation the mean left ventricular ejection fraction was 36.3 +/- 8.7%, the left ventricular end-diastolic diameter 55.7 +/- 7.6 mm and the left ventricular end-systolic diameter 44.3 +/- 7.8 mm. A mean of 21.6 +/- 6.8 months after the procedure the mean left ventricular ejection fraction increased to 58.6 +/- 8.0%, the left ventricular end-diastolic diameter decreased to 49.0 +/- 3.6 mm and the left ventricular end-systolic diameter decreased to 32.2 +/- 2.7 mm; all six patients were in functional class I. These results confirm that control of incessant tachycardia leads to a regression of symptoms and signs of cardiomyopathy and progressive normalization of the dimensions of the heart. Because of these findings, surgery should be considered early in patients with an accessory AV pathway and incessant tachycardia. The presence of a tachycardia-induced cardiomyopathy should therefore be an indication for surgery rather than a contraindication.

Longitudinal dissociation of atrioventricular accessory pathways.

Unusual properties of atrioventricular (AV) accessory pathways were found during electrophysiologic investigations in four patients (three men and one woman). Anterograde longitudinal dissociation of the accessory pathway was observed in two patients and retrograde longitudinal dissociation in two others. Two patients had an accessory pathway with a slow conduction time, one in anterograde direction and one in retrograde direction. These observations further expand our knowledge of the spectrum of electrophysiologic properties of accessory AV pathways.

Transcriptional activity of Drosophila melanogaster ecdysone receptor isoforms and ultraspiracle in Saccharomyces cerevisiae.

The Drosophila melanogaster ecdysone receptor (EcR) is produced in three isoforms, which mediate developmental processes such as metamorphosis. These isoforms were expressed in Saccharomyces cerevisiae to elucidate aspects of receptor transcription activity in a highly defined genetic model system. All three EcR isoforms showed ligand-independent transcriptional activation of an ecdysone reporter gene and the amount of activation correlated with the size of the N-terminal A/B (transactivation) domain present in the isoform: EcR-B1>EcR-A>>EcR-B2. Upon co-expression with ultraspiracle (Usp), transcriptional activation was further increased with EcR-B1 or EcR-A, but was unchanged with EcR-B2 or a truncated EcR lacking the A/B N-terminal domain (EcRDeltaA/B). Thus, the enhanced activity from Usp may depend on the presence of an N-terminal domain of EcR. Co-expression with Usp of several chimeric receptors of the EcR and the mouse androgen receptor (mAR) identified one chimera, composed of the mAR N-terminus and the remainder from EcR (mAR¿EcR-CDEF) that was transcriptionally silent and inducible by Usp. In contrast, the vertebrate homologue, human retinoic acid receptor (RXRalpha), showed ligand-independent transcription when co-expressed with EcRDeltaA/B but not mAR¿ EcR-CDEF. Therefore, RXRalpha does not require its partner to possess an N-terminal domain, yet is intolerant of a heterologous N-terminus. Similarly, the human vitamin D receptor, which has a short N-terminal region, showed greater ligand-independent transcription in the presence of RXRalpha than in the presence of Usp. These results reveal a mechanistic basis for the differential activities among the EcR isoforms, and between Usp and RXRalpha. Furthermore, they provided the foundation for a genetic screen to identify potential insecticides as well as accessory proteins for Usp and EcR.

Arrhythmogenic cardiomyopathy of the right ventricle. Predictive value of QT interval dispersion to assess arrhythmogenic risk and sudden death.

OBJECTIVE: To determine in arrhythmogenic right ventricular cardiomyopathy the value of QT interval dispersion for identifying the induction of sustained ventricular tachycardia in the electrophysiological study or the risk of sudden cardiac death. METHODS: We assessed QT interval dispersion in the 12-lead electrocardiogram of 26 patients with arrhythmogenic right ventricular cardiomyopathy. We analyzed its association with sustained ventricular tachycardia and sudden cardiac death, and in 16 controls similar in age and sex. RESULTS: (mean +/- SD). QT interval dispersion: patients = 53.8+/-14.1 ms; control group = 35.0+/-10.6 ms, p = 0.001. Patients with induction of ventricular tachycardia: 52.5+/-13.8 ms; without induction of ventricular tachycardia: 57.5+/-12.8 ms, p =0.420. In a mean follow-up period of 41+/-11 months, five sudden cardiac deaths occurred. QT interval dispersion in this group was 62.0+/-17.8, and in the others it was 51.9+/-12.8 ms, p = 0.852. Using a cutoff > or =60 ms to define an increase in the degree of the QT interval dispersion, we were able to identify patients at risk of sudden cardiac death with a sensitivity of 60%, a specificity of 57%, and positive and negative predictive values of 25% and 85%, respectively. CONCLUSION: Patients with arrhythmogenic right ventricular cardiomyopathy have a significant increase in the degree of QT interval dispersion when compared with the healthy population. However it, did not identify patients with induction of ventricular tachycardia in the electrophysiological study, showing a very low predictive value for defining the risk of sudden cardiac death in the population studied.

Radiofrequency catheter ablation of an incessant supraventricular tachycardia initiated by a Hisian parasystole.

The coexistence of a parasystolic focus, tachycardia dependent right bundle branch aberrancy, and an AV accessory pathway is reported here. This condition was present in a 40-year-old man, which led to an incessant AV reciprocating tachycardia. Further electrophysiological study revealed that the parasystolic focus was located somewhere in the His bundle; endocardial mapping disclosed a right posterior accessory pathway. Radiofrequency current was delivered at the atrial level of the right posterolateral AV groove and successfully ablated the accessory pathway, leading to a dramatic improvement in cardiac function. In conclusion, the recognition of the electrophysiological mechanism of incessant supraventricular tachycardia was of crucial importance for the therapy decision. A definitive intervention using radiofrequency catheter ablation should be considered early and not postponed in patients with tachycardia-induced cardiomyopathy.

Clinical presentation and prognosis of left main coronary artery disease in the 1980s.

Clinical presentation and course were studied in 127 consecutive patients with angiographically proven left main coronary artery disease. Mean age was 62 (37-79) years. Thirteen patients (10%) had no history of chest pain, seven (5%) had atypical chest pain, and the remaining 107 (85%) typical angina pectoris. Eighty-two patients (65%) had unstable angina, 73 had suffered a myocardial infarction (MI) in the past, and 50 (68%) had post MI angina pectoris. The electrocardiogram was analysed in 102/125 patients during an episode of chest pain and also when they were without chest pain. Outside an episode of chest pain the ST segment was normal in 42 patients (32%), the T wave was normal in 50 patients (38%) and both the ST and T were normal in 33 patients (25%). During chest pain all patients had an abnormal ECG, the most frequent pattern being ST segment depression in leads V3, V4 and V5 (with maximal depression in V4), and ST segment elevation in leads V1 and aVR. The average number of leads with ST-T abnormalities was 6.4. A symptom-limited exercise test on a treadmill with 12-lead ECG monitoring was performed in 89 patients. The exercise test was abnormal in 88 patients (99%), most of whom (74 patients) were already in the first or second stage of the Bruce protocol. The most frequently observed abnormality was ST segment depression of 2 mm or more in leads V4, V5, and V6, and ST segment elevation in leads V1 and aVR. The systolic blood pressure during exercise fell or remained at the same level in 38 patients (43%).(ABSTRACT TRUNCATED AT 250 WORDS)

Problemas sanitários do rebanho de leite: percepçäo dos criadores / Sanitary problems of dairy cattle under the perception of farmers

Utilizando-se 30 propriedades fornecedoras de leite à Cooperativa de Divinópolis - MG, estratificadas nas formas de produçäo mercantil simples, pré-empresarial e empresarial, buscou-se identificar as práticas sanitárias executadas pelos criadores, relacioná-las com os problemas sanitários por eles formulados e comparar estas informaçöes com resultados laboratoriais correspondentes. As práticas preventivas empregadas säo deficientes e desconectadas dos processos mórbidos. As principais doenças em bezerros (diarréias e tristeza parasitária) e em adultos (mastite e pododermatite) säo consistentes com os resultados laboratoriais e com as falhas de manejo identificadas. Todavia, näo apresentam tendência a se manifestarem, conjuntamente, com maior ou menor incidência em nenhum dos sentidos dos estratos pesquisados (mercantil simples - pré-empresarial - empresarial). Isto significa que a informaçäo disponível näo permite afirmar que exista correspondência entre a manifestaçäo de doenças e o grau de inserçäo das unidades produtoras no sistema capitalista de produçäo

Forma de produçäo de gado de leite: visäo dos criadores / Form of production of dairy farms: the perception of farmers

As opiniöes e preocupaçöes dos criadores de gado de leite foram estudadas segundo a forma de organizaçäo da produçäo, a partir de entrevistas a 30 fazendeiros de Divinópolis - MG, agrupados conforme a tipologia mercantil simples, pré-empresarial e empresarial. Os estratos apresentam particularidades quanto ao envolvimento com a terra e com a atividade leiteira, mas comungam opiniöes semelhantes quanto às dificuldades enfrentadas na exploraçäo de leite em relaçäo às instituiçöes de representaçäo da classe. De modo geral, os criadores declaram que se sentem explorados pelos setores industriais que minimizam ou apropriam de suas rendas, mas mesmo assim persistem na atividade em funçäo da necessidade de dinheiro para o custeio das propriedades

Avaliaçäo do desempenho técnico econômico de exploraçöes leiteiras em Divinópolis - MG, segundo a forma de produçäo / Economical and technical apraisal of a dairy cattle exploitations in Diviniopolis - MG, according to the production pattern

Com o objetivo de avaliar o desempenho técnico e econômico de exploraçöes leiteiras em Divinópolis - MG, estudaram-se 30 propriedades, sorteadas aleatoriamente entre as fornecedoras à Cooperativa local, agrupadas por forma de produçäo segundo a tipologia mercantil simples, pré-empresarial e empresarial. Os resultados revelaram prejuízos em todos os estratos, porém com dimensäo crescente no sentido de maior inserçäo no modo capitalista de produçäo, configurando um retorno financeiro inversamente proporcional à aplicaçäo de capitais no processo produtivo. A medida que se aprimoram em eficiência técnica, as exploraçöes analisadas perdem em eficiência econômica, indicando que além de enfrentar uma relaçäo de trocas desfavorável, a atividade é substancialmente penalizada por tributos de gestöes deficientes

Algumas características tecnológicas das propriedades produtoras de leite da microrregiäo homogênea de Divinópolis, MG / Some technological aspects of dairy herd production in the municipality of Divinopolis, state of Minas Gerais, Brazil

O objetivo do trabalho foi o de identificar algumas características das propriedades produtoras de leite de associados à Cooperativa Agropecuária de Divinópolis Ltda. Foram visitadas 102 propriedades, sorteadas com auxílio de uma tabela de números aleatórios, da lista de nomes fornecida pela cooperativa. Os dados foram obtidos através de entrevistas realizadas com auxílio de questionários. Os produtores foram divididos em quatro grupos, conforme a produçäo média de leite entregue à cooperativa, em julho de 1988. A idade média dos entrevistados era de 47,8 anos, dos quais 12,4 por cento näo haviam frequentado a escola e 58,1 por cento assistiram somente até a segunda série do primeiro grau. A maioria das propriedades visitadas possuía instalaçöes para ordenha. Em duas havia ordenhadeira mecânica. Em grande parte os bezerreiros eram coletivos sem divisäo por idade. O rebanho era formado por animais mestiços, holandês-zebu, sem grau de sangue definido. As pastagens ocupavam a maior parte dos estabelecimentos. Na maioria havia capineiras e se cultivavam plantas forrageiras para ensilagem. Verificou-se que eram baixas as taxas de uso de medidas sanitárias preventivas principalmente vacinaçöes, combate ao berne, carrapato e endo-parasitas. A ordenha era realizada manualmente, com o bezerro atado ao pé da vaca. Praticamente näo se utilizavam medidas higiênicas antes ou durante a ordenha. A produçäo média de leite estava em torno de 3,7 litros/vaca/dia. A carga bovina por hectare de pastagem era de 1,3 cabeças por hectare