Interaction of C/EBPalpha and the glucocorticoid receptor in vivo and in nontransformed human cells.

Belonging to the family of steroid hormones, glucocorticoids are essential for development and survival of vertebrates. The cellular response to glucocorticoids is attributed to the glucocorticoid receptor, which functions as a transcription factor. However, the majority of glucocorticoid-modulated genes lack a DNA binding site for the glucocorticoid receptor, raising the question of which mechanism mediates the responses to glucocorticoids. It has been suggested that besides direct DNA binding of the glucocorticoid receptor, interaction with members of other transcription factor families modulates the effect of the glucocorticoid receptor. However, the significance of such transcription factor interaction is not clear. In cultured human mesenchymal cells and peripheral blood leukocytes of human volunteers treated with glucocorticoids, we detected the formation of a complex between the GR and the CCAAT/enhancer binding protein alpha. In in vitro experiments, this interaction turned out to be responsible for the inhibitory action of glucocorticoids on lymphocytic and mesenchymal cell proliferation. Our results suggest that complex formation of the GR with C/EBPalpha accounts for a novel pathway of glucocorticoid action.

Impact of left ventricular lead position on the incidence of ventricular arrhythmia and clinical outcome in patients with cardiac resynchronization therapy.

PURPOSE: The aim of the study was to evaluate the incidence of ventricular arrhythmia and clinical outcome in patients receiving a cardiac resynchronization therapy (CRT) depending on the left ventricular (LV) lead position. METHODS: A total of 187 consecutive patients with advanced heart failure who received a CRT-implantable cardioverter defibrillator were analyzed. Forty patients (21%) had a LV lead in the anterior/apical (anterior) and 147 patients (79%) in the posterior/posterolateral (posterior) region. The total median follow-up time was 644 days. RESULTS: The incidence of ventricular arrhythmia was 35% in patients with an anterior LV lead versus 30% in patients with a posterior LV lead (p = 0.53). The 1- and 2-year mortality in the anterior LV lead group was 19% and 22%, as compared with 0.7% and 3.2%, respectively, in the posterior LV lead group (p < 0.001). In a multivariable analysis, an anterior LV lead was independently associated with an increased mortality (hazard ratio 5.88, 95% confidence interval 2.22-16.67). The major cause of death was end-stage heart failure whereas the incidence of sudden cardiac death was not different between both groups. CONCLUSIONS: Thus, biventricular pacing with an anterior LV lead seems to have no impact on the incidence of ventricular arrhythmia but may be associated with an increased mortality rate due to worsening heart failure.

Tako-tsubo cardiomyopathy after administration of ergometrine following elective caesarean delivery: a case report.

INTRODUCTION: Tako-tsubo cardiomyopathy (stress-induced cardiomyopathy or transient left ventricular ballooning) is characterized by clinical suspicion of an acute myocardial infarction with transient apical or midventricular dyskinesia of the left ventricle without significant coronary stenosis on angiography. The etiology of this disease remains obscure. One of the possible causes is myocardial ischemia induced by coronary vasospasm due to sympathetic activation. It has been hypothesized that the application of ergometrine could induce tako-tsubo cardiomyopathy. CASE PRESENTATION: We report the case of a 28-year-old Turkish woman who developed tako-tsubo cardiomyopathy after administration of ergometrine for release of placenta and prevention of bleeding during the post-partum phase in the course of an elective caesarean delivery. Tako-tsubo cardiomyopathy was diagnosed by echocardiography and urgent cardiac magnetic resonance imaging. A coronary angiography was not performed because of the absence of myocardial necrosis or ischemia and signs of myocarditis on cardiac magnetic resonance imaging. CONCLUSION: This life-threatening disease should be excluded in the differential diagnosis by comparing the symptoms with those of typical heart failure, particularly after use of ergometrine.

Clinical, angiographic and cardiovascular magnetic resonance findings in consecutive patients with Takotsubo cardiomyopathy.

BACKGROUND: The aim was to assess clinical, angiographic and cardiovascular magnetic resonance (CMR) findings in patients with Takotsubo cardiomyopathy. METHODS: Between 2003 and 2007, 20 consecutive patients admitted to our hospital with suspected acute myocardial infarction and presenting with apical ballooning in the left ventricular (LV) angiogram in the absence of a significant coronary artery disease, were included in the study. Echocardiography and CMR was performed in all patients. RESULTS: The mean age of patients with Takotsubo cardiomyopathy was 62 +/- 8 years (range 43-78 years). Eighteen (90%) were female. Clinical presentations included chest pain (95%) and cardiogenic shock (5%). The mean angiographic LV ejection fraction on admission was 45% +/- 9% (range 26%-60%) and resolved rapidly in all cases. Mean time delay between presentation CMR was 2 +/- 1 days (range 1-6 days). Mean ejection fraction was 51% +/- 15% (range 25%-81%). While 19 (95%) patients showed no evidence of late enhancement or signs of myocarditis in the CMR, 1 (5%) patient who was resuscitated showed hyperenhancement confined to the apex. CONCLUSION: In patients showing the clinical picture of an acute myocardial syndrome and angiographic picture of a TakoTsubo cardiomyopathy, CMR might be helpful in confirming the diagnosis through the exclusion of other causes for the acute LV dysfunction.