The role of attentional deployment during distancing in adolescents with major depression.

Individuals with major depression (MD) show deficits in cognitive reappraisal. It is yet unexplored how the act of directing visual attention away from/towards emotional aspects impacts on cognitive reappraisal in MD. Thus, we examined the role of attentional deployment during cognitive reappraisal (specifially during distancing) in adolescent MD. 36 MD adolescents and 37 healthy controls (12-18 years) performed a cognitive reappraisal task during which they a) down-regulated self-reported negative affective responses to negative pictures via distancing, or b) simply attended to the pictures. During the task, attentional focus was systematically varied by directing participants' gaze to emotional vs. non-emotional picture aspects. The validity of this experimental manipulation was checked by continuous eye-tracking during the task. Across groups and gaze focus conditions, distancing diminished negative affective responses to the pictures. Regulation success significantly differed between groups dependent on gaze focus: MD adolescents showed relatively less regulation success than controls in the emotional gaze focus condition, while the reverse was true for the non-emotional gaze focus condition. The results suggest that in MD adolescents, an emotional context might interfere with emotion regulatory aims. The findings can provide an important starting point for the development of innovative training regimes that target deficient reappraisal processes in adolescents suffering from MD.

Neonatal murine macrophages show enhanced chemotactic capacity upon toll-like receptor stimulation.

BACKGROUND: The neonatal surgical patient is threatened by exuberant inflammatory reactions. Neonatal macrophages are key players in this process. We investigated the ability of neonatal macrophages to initiate a local inflammatory reaction upon exposure to different bacterial or viral ligands to toll-like receptors (TLRs). METHODS: Peritoneal wash outs from neonatal (<24 h) and adult (42 days) C57BL/6J mice were gained by peritoneal lavages. In a first set of experiments, macrophages were purified and stimulated for 6 h by four different TLR ligands. mRNA was extracted for transcriptome analysis. In a second set of experiments, lipopolysaccharide was applied into peritoneal cavities. After 6 h of incubation, the cellular composition of the inflamed cavities was evaluated by cytological staining as well as chipcytometry. RESULTS: Neonatal murine peritoneal macrophages differed significantly in the expression of pro- and anti-chemotactic genes. Functional assignment of these genes revealed enhanced chemotactic potential of neonatal macrophages and was confirmed by a higher influx of pro-inflammatory cells into neonatal peritoneal cavities. CONCLUSION: Neonatal peritoneal macrophages demonstrated an enhanced chemotactic potential upon stimulation with four TLR ligands. This was associated with an increased influx of inflammatory cells to the peritoneal cavity. This might contribute to the strong inflammatory responses of neonates and preterms.

Efficacy and safety of an oral fixed low-dose perindopril 2 MG/indapamide 0.625 MG combination: a randomized, double-blind, placebo-controlled study in elderly patients with mild to moderate hypertension.

The efficacy and safety of 12 weeks treatment with an oral fixed low-dose perindopril 2 mg + indapamide 0.625 mg (Per/Ind) combination in elderly and very elderly patients (65-85 years) with mild to moderate systolic and diastolic hypertension (SDH) or isolated systolic hypertension (ISH) were investigated vs placebo. This trial was a multinational randomized double-blind study with doubling of active drug dosage in nonresponders. Intention to treat analysis was performed in 383 patients (age 72.4 years; ISH 32%). 58.5% remained on their initial dosage. Per/Ind decreased supine diastolic and systolic blood pressure (sDBP/sSBP) by 13.2+/-8.0 mm Hg and 22.5+/-13.9 mm Hg (P <.0001) versus placebo -7.3+/-9.0 mm Hg and -12.3+/-15.2 mm Hg, respectively. In ISH (n = 123), Per/Ind decreased sSBP by 23.0+/-11.8 mm Hg (P <.0001). Overall response and normotension rates was 81.3% with Per/Ind (P <.0001). Adverse event rates (including hypokalemia) were similarly low in both groups. Analysis in the over-75 year subgroup showed similar safety and efficacy results. Fixed low-dose Per/Ind is a safe and effective treatment of hypertension including isolated systolic hypertension in the elderly.

Prognostic value of thrombolysis, coronary artery patency, signal-averaged electrocardiography, left ventricular ejection fraction, and Holter electrocardiographic monitoring for life-threatening ventricular arrhythmias after a first acute myocardial infarction.

Prognostic studies after acute myocardial infarction (AMI) have mainly been performed in the prethrombolytic era. Despite the fact that modern management of AMI has reduced mortality rates, the occurrence of malignant ventricular arrhythmias in the late phase of AMI remains an important issue. We prospectively studied 244 consecutive patients (97 treated with thrombolytics) who survived a first AMI. All patients underwent time domain signal-averaged electrocardiography (vector magnitude: measurements of total QRS duration, terminal low [<40 microV] amplitude signal duration, and root-mean-square voltage of the last 40 ms of the QRS complex), Holter electrocardiographic monitoring, and cardiac catheterization. Late life-threatening ventricular arrhythmias were recorded. Eighteen arrhythmic events occurred during a mean follow-up period of 57 +/- 18 months. Three independent factors were associated with a higher risk of arrhythmic events: (1) left ventricular ejection fraction (odds ratio 1.9/0.10 decrease), (2) terminal low-amplitude signal duration (odds ratio 1.5/5 ms increase), and (3) absence of thrombolytic therapy (odds ratio 3.9). Low-amplitude signal duration sensitivity for sudden cardiac death was low (30%). Left ventricular ejection fraction had the highest positive predictive value for sudden cardiac death (10%). Thus, thrombolysis decreases both the incidence of ventricular tachycardia and sudden cardiac death with a higher reopening rate of the infarct-related vessel. Signal averaging predicts the occurrence of ventricular tachycardia and an impaired left ventricular ejection fraction predicts the occurrence of sudden cardiac death.

Additional predictive value of both left and right ventricular ejection fractions on long-term survival in idiopathic dilated cardiomyopathy.

BACKGROUND: In idiopathic dilated cardiomyopathy, long-term outcome is poor and left ventricular ejection fraction is a major powerful predictor of survival. However, right ventricular function might also play an important role in the long-term prognosis of this disease. AIM: The aim of this study was to determine the role of right ventricular parameters, mainly right ventricular ejection fraction, on survival in idiopathic cardiomyopathy. METHODS: We prospectively assessed long-term follow-up and predictors of survival in 62 consecutive patients referred from 1990 to 1992 for evaluation of idiopathic dilated cardiomyopathy, including haemodynamic evaluation, thermodilution right ventricular ejection fraction and volume measurements. RESULTS: At the time of catheterization, dyspnoea class III or IV was present in 60% of the patients, atrial fibrillation in 19% and complete left bundle branch block in 35%. Left ventricular ejection fraction was 30 +/- 10% and right ventricular ejection fraction was 30 +/- 16%. During follow-up (2.2 +/- 1.3 years), 15 patients (24%) had heart transplantation and nine (14%) died before cardiac transplantation. Cumulative survival rate without heart transplantation was 74% and 56% at 1 and 4 years, respectively. In univariate analysis, survival was related to: dyspnoea class I or II (P < 0.04), absence of complete left bundle branch block (P < 0.05), administration of lower doses of furosemide (P < 0.01), high left ventricular ejection fraction (P < 0.001), low pulmonary artery pressure (P < 0.002), high cardiac index (P < 0.006), and low right ventricular volumes (P < 0.001). Multivariate analysis showed only two independent predictors of survival: left ventricular ejection fraction (P < 0.001) and right ventricular ejection fraction (P < 0.004). CONCLUSION: In addition to left ventricular ejection fraction, right ventricular ejection fraction appears to be a complementary predictor of survival in idiopathic dilated cardiomyopathy, suggesting the importance of assessing right ventricular function in this disease.

Frequencies of five genetic polymorphisms in coronarographed patients and effects on lipid levels in a supposedly healthy population.

Allele frequencies of genetic polymorphisms were compared between supposedly healthy subjects and angiographically proven coronary artery disease patients. The polymorphic candidate loci investigated were the apolipoprotein (apo) B signal peptide and XbaI polymorphism, the apo E polymorphism and two polymorphism of lipoprotein lipase (LPL) gene: Hind/III and PvuII. Apo B signal peptide and HindIII/LPL polymorphisms showed significant differences in allele partition between cases and controls; the rare alleles of both polymorphisms were less frequent (p < 0.05) in cases. We looked for associations between the polymorphisms and lipid concentration variability in a supposedly healthy population (145 men and 144 women). Apo B signal peptide, apo E and PvuII/LPL polymorphisms seem to influence some lipid metabolism parameters significantly. Apo AI and LpCIII levels were significantly different among apo B signal peptide genotypes: Del homozygotes had the highest concentrations of both variables. The epsilon 4 allele of apo E polymorphism was associated with increased concentrations of total cholesterol, LDL cholesterol and apo B. Increased LpAI:AII levels observed in E3 homozygotes (p < 0.01) have not previously been reported. LpAI:AII concentration was also influenced by PvuII/LPL polymorphisms.

Influence of cigarette smoking on rate of reopening of the infarct-related coronary artery after myocardial infarction: a multivariate analysis.

OBJECTIVES: This study sought to determine whether the reopening of the infarct-related vessel is related to clinical characteristics or cardiovascular risk factors, or both. BACKGROUND: In acute myocardial infarction, thrombolytic therapy reduces mortality by restoring the patency of the infarct-related vessel. However, despite the use of thrombolytic agents, the infarct-related vessel remains occluded in up to 40% of patients. METHODS: We studied 295 consecutive patients with an acute myocardial infarction who underwent coronary angiography within 15 days (mean [+/- SD] 6.7 +/- 3.2 days) of the onset of symptoms. Infarct-related artery patency was defined by Thrombolysis in Myocardial Infarction trial flow grade > or = 2. Four cardiovascular risk factors--smoking, hypertension, hypercholesterolemia and diabetes mellitus--and eight different variables-age, gender, in-hospital death, history of previous myocardial infarction, location of current myocardial infarction, use of thrombolytic agents, time interval between onset of symptoms, thrombolytic therapy and coronary angiography--were recorded in all patients. RESULTS: Thrombolysis in current smokers and anterior infard location on admission were the three independent factors highly correlated with the patency of the infarct-related vessel (odds ratios 3.2, 3.0 and 1.9, respectively). In smokers, thrombolytic therapy was associated with a higher reopening rate of the infard vessel, from 35% to 77% (p < 0.001). Nonsmokers did not benefit from thrombolytic therapy, regardless of infarct location. CONCLUSIONS: These observational data, if replicated, suggest that in patients with acute myocardial infarction, thrombolytic therapy may be most effective in current smokers, whereas nonsmokers and ex-smokers may require other management strategies, such as emergency percutaneous transluminal coronary angioplasty.

[Predictive value of intracellular accumulation of daunorubicin and P-glycoprotein expression simultaneously determined by flow cytometry in adult acute myeloid leukemias]. / Intérêt prédictif de l'accumulation intracellulaire de daunorubicine et de l'expression de la glycoprotéine P déterminées simultanément par cytométrie en flux dans les leucémies aiguës myéloïdes de l'adulte.

Multidrug resistance (MDR) phenotype expression was evaluated retrospectively in 87 patients with acute myeloid leukemia (AML), 69 with de novo AML, ten with relapsed AML and eight with AML secondary to myelodysplastic syndrome (MDS). MDR phenotype, characterized by P-glycoprotein expression (MRK16 monoclonal antibody) and decrease in intracellular daunorubicin (DNR) accumulation was determined using flow cytometry. All patients received chemotherapy including cytosine-arabinoside and anthracycline (daunorubicin, zorubicin, idarubicin) or mitoxantrone, and quinine in ten cases. The predictive value of the MDR phenotype for clinical responsiveness was studied using uni- and multivariate analyses. Univariate analysis showed that DNR accumulation (p < 10(-4)), P-glycoprotein expression (p = 10(-4)) and disease status (de novo versus recurrent AML and acute MDS) (p = 10(-4)) were predictive of clinical responsiveness. The significance of these three parameters was maintained in multivariate analysis. When de novo AML was considered, only DNR accumulation was of predictive value (p < 10(-4)) for complete response to chemotherapy.

Beneficial cumulative role of both nitroglycerin and dobutamine on right ventricular systolic function in congestive heart failure patients awaiting heart transplantation.

End-stage idiopathic dilated cardiomyopathy or ischemic heart disease usually present with very low cardiac output and severe ventricular dysfunction which may require pharmacological support before heart transplantation. Right ventricular ejection fraction might be an important factor of functional capacity and survival in congestive heart failure. In order to test the immediate response of right ventricular hemodynamic parameters to nitroglycerin and dobutamine usually used to treat severe left ventricular dysfunction, we studied 17 congestive heart failure patients (15 men, two women; mean age 55 +/- 13 years) with end-stage idiopathic dilated cardiomyopathy (n = 10) or end-stage ischemic heart disease (n = 7), left ventricular ejection fraction < 35% (mean 22 +/- 8%), and sinus rhythm. A well validated thermodilution technique using a dedicated catheter with a fast catheter-computer response, permitting instantaneous measurements of right ventricular ejection fraction, was used. Right ventricular hemodynamic parameters were recorded at baseline, after an intravenous bolus injection of 3 mg nitroglycerin and after an intravenous infusion of dobutamine administered after nitroglycerin until normalization of cardiac index or a maximal dose of 15 micrograms/kg/min. Pulmonary artery mean pressure significantly decreased after nitroglycerin (43 +/- 9 mmHg at baseline vs. 31 +/- 10 mmHg after nitroglycerin, P < 0.0001) and did not subsequently change after dobutamine (32 +/- 10 mmHg after dobutamine, ns). Cardiac index was not affected by nitroglycerin (1.7 +/- 0. l/min/m2 at baseline vs. 2.0 +/- 0.3 l/min/m2 after nitroglycerin, ns), but dramatically increased after dobutamine (3.0 +/- 1.0 l/min/m2 after dobutamine, P < 0.0001). Concomitantly to the changes of these two parameters, right ventricular ejection fraction progressively increased (14 +/- 8% at baseline vs. 20 +/- 10% after nitroglycerin (P < 0.0006) vs. 28 +/- 13% after dobutamine (P < 0.0001)). Progressive increase of right ventricular ejection fraction after administration of nitroglycerin followed by administration of dobutamine suggests the beneficial cumulative role of both medications on right ventricular systolic function in severe congestive heart failure.

Long-term prediction of major ischemic events by exercise thallium-201 single-photon emission computed tomography. Incremental prognostic value compared with clinical, exercise testing, catheterization and radionuclide angiographic data.

OBJECTIVES: This study sought to evaluate the prognostic role of exercise thallium-201 (Tl-201) single-photon emission computed tomography (SPECT) in patients with known or suspected coronary artery disease. BACKGROUND: Compared with planar Tl-201 scintigraphy, Tl-201 SPECT allows enhanced assessment of myocardial perfusion abnormalities. However, the long-term prognostic value of exercise Tl-201 SPECT has not been ascertained and compared with that of other techniques of investigation. METHODS: Predictors of ischemic events were sought in 217 patients with known or suspected coronary artery disease who underwent exercise Tl-201 SPECT, coronary angiography and rest radionuclide angiography and who initially received medical therapy. Predictive values were determined using Cox proportional hazards regression models. RESULTS: During a mean (+/- SD) follow-up period of 70 +/- 19 months, 29 patients had a major ischemic event (cardiac death or myocardial infarction). Total extent of exercise defects was the best independent predictor by Tl-201 SPECT of major events (p < 0.001) and provided additional prognostic information compared with clinical, exercise testing and catheterization variables (p < 0.02). Extent of reversible Tl-201 SPECT perfusion defects provided additional prognostic information compared with extent of irreversible defects (p < 0.001) and was the sole Tl-201 SPECT variable providing additional prognostic information compared with radionuclide left ventricular ejection fraction (p < 0.02). CONCLUSIONS: Total extent of exercise Tl-201 SPECT defects is a powerful long-term predictor of major ischemic events that enhances the prediction provided by clinical, exercise testing and coronary angiographic data. In view of its prognostic significance, extent of reversible Tl-201 SPECT defects might provide original information about improving prognosis by coronary revascularization.