Influenza vaccination in secondary prevention from coronary ischaemic events in coronary artery disease: FLUCAD study.

AIMS: To evaluate the effect of influenza vaccination on the coronary events in patients with confirmed coronary artery disease (CAD). METHODS AND RESULTS: Randomized, double-blind, placebo controlled study. We included 658 optimally treated CAD patients; 477 men, mean age 59.9+/-10.3 years. Three hundred and twenty-five patients received the influenza vaccine, and 333 patients placebo. Median follow-up was 298 (interquartile range 263-317) days. Primary endpoint was the cardiovascular death. Its estimated 12-month cumulative event rate was 0.63% in the vaccine vs. 0.76% in controls (HR 1.06 95% CI: 0.15-7.56, P = 0.95). There were two secondary composite endpoints: (i) the MACE (cardiovascular death, myocardial infarction, coronary revascularization) tended to occur less frequently in the vaccine group vs. placebo with the event rate 3.00 and 5.87%, respectively (HR 0.54;95% CI: 0.24-1.21, P = 0.13). (ii) Coronary ischaemic event (MACE or hospitalization for myocardial ischaemia) estimated 12-month event rate was significantly lower in the vaccine group 6.02 vs. 9.97% in controls (HR 0.54; 95% CI: 0.29-0.99, P = 0.047). CONCLUSION: In optimally treated CAD patients influenza vaccination improves the clinical course of CAD and reduces the frequency of coronary ischaemic events. Large-scale studies are warranted to evaluate the effect of influenza vaccination on cardiovascular mortality. (ClinicalTrials.gov: NCT 00371098).     

MR‐PET head motion correction based on co‐registration of multicontrast MR images

Head motion is a major source of image artefacts in neuroimaging studies and can lead to degradation of the quantitative accuracy of reconstructed PET images. Simultaneous magnetic resonance‐positron emission tomography (MR‐PET) makes it possible to estimate head motion information from high‐resolution MR images and then correct motion artefacts in PET images. In this article, we introduce a fully automated PET motion correction method, MR‐guided MAF, based on the co‐registration of multicontrast MR images. The performance of the MR‐guided MAF method was evaluated using MR‐PET data acquired from a cohort of ten healthy participants who received a slow infusion of fluorodeoxyglucose ([18‐F]FDG). Compared with conventional methods, MR‐guided PET image reconstruction can reduce head motion introduced artefacts and improve the image sharpness and quantitative accuracy of PET images acquired using simultaneous MR‐PET scanners. The fully automated motion estimation method has been implemented as a publicly available web‐service.     

The Number of Lymph Nodes Involved with Metastatic Disease Does Not Affect Outcome in Melanoma Patients as Long as All Disease Is Confined to the Sentinel Lymph Node

Background  In melanoma, a direct relationship exists between the number of nodes involved with metastatic disease and prognosis. This study was undertaken to determine whether an individual with metastatic disease confined to the sentinel lymph nodes (SLNs) would have a better prognosis than individuals with metastatic disease that has spread to the non-SLNs, regardless of the number of nodes involved. Methods  The study group consists of 229 melanoma patients with a positive SLN who underwent regional nodal dissection. Cox proportional hazard regression models were used to assess association of the number of SLNs and non-SLNs involved with disease with overall survival (OS) and disease-free survival (DFS). Results  DFS and OS were unchanged regardless of how many SLNs were positive, as long as all disease was confined to SLNs. Among 183 patients without involvement of non-SLNs, OS remained the same despite an increasing number of SLNs involved (P = .59). This was true after controlling for ulceration, Breslow depth, age, sex, and adjuvant treatment. Once disease was present beyond the SLN, DFS and OS were negatively affected. Among patients with involvement of non-SLNs, there was no statistically significant association between the number of positive SLNs and survival. The risk of mortality increased with the number of non-SLNs involved with metastatic disease (P < .001). Conclusions  The number of regional nodes involved with metastatic disease does not affect DFS and OS if disease is confined to the SLNs. Consideration should be given to specifying SLN versus non-SLN involvement in the American Joint Committee on Cancer staging manual.     

Effects of preoccupation on interpersonal recall: a pilot study

Background: The aim of this pilot study was to examine whether priming preoccupation (rumination) in healthy participants adversely affects the processing of interpersonal information. Methods: Sixty female undergraduates with moderate or marked preoccupation proneness (selected on the basis of their high preoccupation on eating, shape, and weight issues) were randomized to receive either a general preoccupation prime, a standardized preoccupation prime, or a control prime. Following the prime, participants watched an 8‐min videotape of a family interaction and then were asked free recall questions about the tape. Results: Participants who received the general preoccupation prime scored lower than the other two groups in response to free recall questions regarding emotion‐related topics. Conclusions: These findings suggest that when primed by everyday worries and concerns, individuals prone to preoccupation may have their capacity to recall emotion‐related interpersonal information compromised. Depression and Anxiety, 2009. © 2008 Wiley‐Liss, Inc.     

Predictors of nonresponse to cognitive behavioural therapy or venlafaxine using glucose metabolism in major depressive disorder

Background

Longitudinal neuroimaging investigations of antidepressant treatment offer the opportunity to identify potential baseline biomarkers associated with poor outcome.

Methods

To explore the neural correlates of nonresponse to cognitive behavioural therapy (CBT) or venlafaxine (VEN), we compared pretreatment (18)F-fluoro-2-deoxy-d-glucose positron emission tomography scans of participants with major depressive disorder responding to either 16 weeks of CBT (n = 7) or VEN treatment (n = 9) with treatment nonresponders (n = 8).

Results

Nonresponders to CBT or VEN, in contrast to responders, exhibited pretreatment hypermetabolism at the interface of the pregenual and subgenual cingulate cortices.

Limitations

Limitations of our study include the small sample sizes and the absence of both arterial sampling to determine absolute glucose metabolism and high-resolution structural magnetic resonance imaging coregistration for region-of-interest analyses.

Conclusion

Our current findings are consistent with those reported in previous studies of relative hyperactivity in the ventral anterior cingulate cortex in treatment-resistant populations.     

Insights into the mechanism of FTY720 and compatibility with regulatory T cells for the inhibition of graft-versus-host disease (GVHD)

The immunomodulator FTY720 (FTY) has been shown to be beneficial in experimental models of organ transplantation and autoimmunity. We show that FTY significantly inhibited but did not prevent graft-versus-host disease (GVHD) in lethally irradiated or nonirradiated allogeneic recipients. Although most studies implicate prevention of lymphocyte egress from lymphoid organs as the primary mechanism of action, our data indicate that FTY effects on the host are more likely to be responsible for GVHD inhibition. FTY reduced splenic CD11c+ cells by 50%, and similarly reduced CD4+ and CD8+ T-cell responder frequencies in the spleen early after transplantation. Imaging of GFP+ effectors indicated that FTY modified donor effector T-cell migration to secondary lymphoid organs, but did not uniformly trap T cells in lymph nodes or prevent early effector migration to GVHD parenchymal target organs. Administration of FTY only prior to transplantation inhibited GVHD, indicating that the primary function of FTY may be targeted to host cells. FTY was additive with regulatory T cells for GVHD inhibition. FTY slightly impaired but did not abrogate a graft-versus-leukemia (GVL) effect against C1498, a myeloid leukemia. Our data further define the mechanisms of action and provide insight as to the potential clinical uses of FTY in allogeneic bone marrow transplant recipients.     

Melatonin is more effective than taurine and 5-hydroxytryptophan against hyperglycemia-induced kidney-cortex tubules injury

The antioxidative effects of melatonin (Mel), 5-hydroxytryptophan (5-HTP) and taurine (TAU) on hyperglycemia-induced oxidative stress was investigated in primary cultures of kidney-cortex tubule cells grown in metabolically and hormonally defined medium. In the presence of 30 mm glucose (hyperglycemic conditions), cell viability was decreased by about 35% in comparison with that estimated in the glucose-depleted medium probably as a result of induction of apoptosis, as concluded from: (i) chromatin condensation and DNA fragmentation assays, (ii) a significant enhancement of reactive oxygen species (ROS) production, (iii) 8-hydroxydeoxyguanosine (8-OHdG) generation, (iv) an increased protein peroxidation and (v) a decline of reduced glutathione (GSH) levels leading to a disturbed glutathione redox state. The addition of 100 microm Mel to the hyperglycemic medium resulted in a twofold decrease in both 8-OHdG accumulation and protein peroxidation as well as restoration of the control intracellular ROS levels accompanied by a substantial increase in GSH/oxidized glutathione (GSSG) ratio due to a decline in GSSG content. ROS elimination was also achieved in the presence of 1 mm TAU which diminished protein and DNA injuries by about 25% and 30%, respectively. On the contrary, the action of 100 microm 5-HTP on ROS level, 8-OHdG generation, protein peroxidation and GSH/GSSG ratio was negligible. Thus, in contrast to 5-HTP and TAU, Mel might be considered as beneficial for diabetes therapy, particularly in terms of reduction of hyperglycemia-induced kidney injury.     

Kinetic studies of novel inhibitors of endomorphin degrading enzymes

Endomorphins (EMs), two endogenous μ-opioid receptor selective ligands, are attractive lead compounds for opioid-based pain management studies. However, these peptides are quickly degraded by peptidases, in particular by dipeptidylpeptidase IV (DPP IV) and aminopeptidase M (APM). Targeting enzymatic degradation is one approach to prolong endomorphin activity. In this study we characterized the action of two new inhibitors of similar to endomorphins structure, Tyr-Pro-Ala-NH(2) (EMDB-2) and Tyr-Pro-Ala-OH (EMDB-3), which were designed earlier in our laboratory. The presented data give evidence that EMDB-2 and EMDB-3 are potent inhibitors of enzymes responsible for endomorphin cleavage. These compounds are stable and easily synthesized. EMDB-2 and EMDB-3 are competitive inhibitors of both, DPP IV and APM, with K(i) values in micromolar range. They are less potent than diprotin A in protecting EMs against DPP IV but more potent than actinonin in protecting these peptides against APM.