Death attributed to ventricular arrhythmia induced by thioridazine in combination with a single Contac C capsule.

Phenothiazines are known to produce electrocardiographic repolarization abnormalities. Thioridazine and mesoridazine appear to induce such changes more frequently than other neuroleptics and are also known to induce fatal ventricular arrhythmia. The woman described in this article died after taking her usual dose of thioridazine, 100 mg/d, in combination with a single capsule of Contac. C, a decongestant-antihistamine containing phenylpropanolamine and chlorpheniramine. Phenylpropanolamine, an ephedrine-like drug, was thought to have favoured the initiation by thioridazine of the ventricular arrhythmia that led to the woman''s death. It is therefore suggested that ephedrine-like medications not be given to patients receiving thioridazine.     

The lupus syndrome induced by hydralazine: a common complication with low dose treatment.

The true incidence of the lupus syndrome induced by hydralazine was determined in a longitudinal study of 281 patients consecutively starting hydralazine for hypertension over a 51 month period. Data on the duration of treatment and the maximum dose achieved were examined using life table analysis. After three years'' treatment with hydralazine the incidence of the lupus syndrome was 6.7% (95% confidence limits 3.2-10.2%). The incidence was dose dependent, with no cases recorded in patients taking 50 mg daily and incidences of 5.4% with 100 mg daily and of 10.4% with 200 mg daily. The incidence was higher in women (11.6%) than in men (2.8%). In women taking 200 mg daily the three year incidence was 19.4%. Hydralazine is an effective antihypertensive drug that has come to be used in restricted dosage (not more than 200 mg daily) because of its risk of inducing the lupus syndrome. This study shows that the true incidence of the syndrome is still unacceptably high even when the drug is prescribed according to current recommendations.     

36例乌头碱中毒致室性心律失常的临床研究

目的:研究乌头碱中毒致室性心律失常是为了提高对室性心律失常的诊疗水平.方法:36例乌头碱中毒患者入院,立即洗胃,心电监护.根据心电图情况及时纠正心律紊乱,选用利多卡因、硫酸镁、氯化钾静滴及电除颤抢救.结果:36例患者有效30例,显效4例,无效2例.总有效率94.44%,乌头碱中毒时间与治疗早搏消失时间的疗效比较P值<0.05,有显著性差异.结论:乌头碱中毒所致室性心律失常治疗关键:及早药物及电复律,可提高其治愈率.     

Cardiac arrhythmia mechanisms in rats with heart failure induced by pulmonary hypertension

Pulmonary hypertension provokes right heart failure and arrhythmias. Better understanding of the mechanisms underlying these arrhythmias is needed to facilitate new therapeutic approaches for the hypertensive, failing right ventricle (RV). The aim of our study was to identify the mechanisms generating arrhythmias in a model of RV failure induced by pulmonary hypertension. Rats were injected with monocrotaline to induce either RV hypertrophy or failure or with saline (control). ECGs were measured in conscious, unrestrained animals by telemetry. In isolated hearts, electrical activity was measured by optical mapping and myofiber orientation by diffusion tensor-MRI. Sarcoplasmic reticular Ca(2+) handling was studied in single myocytes. Compared with control animals, the T-wave of the ECG was prolonged and in three of seven heart failure animals, prominent T-wave alternans occurred. Discordant action potential (AP) alternans occurred in isolated failing hearts and Ca(2+) transient alternans in failing myocytes. In failing hearts, AP duration and dispersion were increased; conduction velocity and AP restitution were steeper. The latter was intrinsic to failing single myocytes. Failing hearts had greater fiber angle disarray; this correlated with AP duration. Failing myocytes had reduced sarco(endo)plasmic reticular Ca(2+)-ATPase activity, increased sarcoplasmic reticular Ca(2+)-release fraction, and increased Ca(2+) spark leak. In hypertrophied hearts and myocytes, dysfunctional adaptation had begun, but alternans did not develop. We conclude that increased electrical and structural heterogeneity and dysfunctional sarcoplasmic reticular Ca(2+) handling increased the probability of alternans, a proarrhythmic predictor of sudden cardiac death. These mechanisms are potential therapeutic targets for the correction of arrhythmias in hypertensive, failing RVs.     

Epibranchial and otic placodes are induced by a common Fgf signal, but their subsequent development is independent

The epibranchial placodes are cranial, ectodermal thickenings that give rise to sensory neurons of the peripheral nervous system. Despite their importance in the developing animal, the signals responsible for their induction remain unknown. Using the placodal marker, sox3, we have shown that the same Fgf signaling required for otic vesicle development is required for the development of the epibranchial placodes. Loss of both Fgf3 and Fgf8 is sufficient to block placode development. We further show that epibranchial sox3 expression is unaffected in mutants in which no otic placode forms, where dlx3b and dlx4b are knocked down, or deleted along with sox9a. However, the forkhead factor, Foxi1, is required for both otic and epibranchial placode development. Thus, both the otic and epibranchial placodes form in a common region of ectoderm under the influence of Fgfs, but these two structures subsequently develop independently. Although previous studies have investigated the signals that trigger neurogenesis from the epibranchial placodes, this represents the first demonstration of the signaling events that underlie the formation of the placodes themselves, and therefore, the process that determines which ectodermal cells will adopt a neural fate.     

Characteristics common to choleretic increments of bile induced by theophylline, glucagon and SQ-20009 in the dog.

Theophylline, glucagon, and SQ-20009 induce a choleresis in the dog characterized by a proportionate increase in erythritol clearance and bile flow, no increase in bile salt excretion, and by an isosmotic solution of similar electrolyte composition. The increment in bile appears to originate at the canaliculus in response to increased cyclic-AMP.