Adenosine-induced ST segment depression with normal perfusion

Background: Intravenous adenosine in conjunction with myocardial perfusion imaging is commonly used for the detection of coronary artery disease and risk assessment. We have previously shown that patients with ischemic changes on the 12-lead electrocardiogram (ECG) in response to adenosine but with normal perfusion pattern have a benign outcome on shortintermediate follow-up. The long-term outcome of these patients is unknown. Methods: Patients with ischemic ECG response (≥ 1 mm ST depression) to adenosine infusion but with normal perfusion on single-photon emission computed tomography (SPECT) imaging in the absence of a history of myocardial infarction or coronary revascularization were followed up for mortality, myocardial infarctions, and coronary revascularization. Results: The cohort consisted of 73 patients (81% women) who were followed up for mortality for a mean of 61 ± 15 months. There were 10 deaths, and the cause of death was determined to be non-cardiac in half of those. Follow-up for the other endpoints was complete for 21 ± 10 months during which no patient had myocardial infarction and seven underwent coronary revascularization. Conclusions: Patients with ischemic ECG response to intravenous adenosine administration and normal perfusion on SPECT are at low risk of cardiovascular events. The ST segment response to adenosine in this setting is likely related to non-ischemic mechanisms

Microscopic description of Coulomb and nuclear excitation of multiphonon states in 40^{40}Ca + 40^{40}Ca collisions

We calculate the inelastic scattering cross sections to populate one- and two-phonon states in heavy ion collisions with both Coulomb and nuclear excitations. Starting from a microscopic approach based on RPA, we go beyond it in order to treat anharmonicities and non-linear terms in the exciting field. These anharmonicities and non-linearities are shown to have important effects on the cross sections both in the low energy part of the spectrum and in the energy region of the Double Giant Quadrupole Resonance. By properly introducing an optical potential the inelastic cross section is calculated semiclassically by integrating the excitation probability over all impact parameters. A satisfactory agreement with the experimental results is obtained.Comment: 20 pages, 2 figures, revtex, to be published in Phys. Rev.

Hypertrophic obstructive cardiomyopathy in liver transplant patients

The optimal treatment strategy for patients with symptomatic hypertrophic obstructive cardiomyopathy (HOCM) and end-stage liver disease (ESLD) is not well defined. Although medical management is the accepted first line treatment, patients who are unresponsive to medication require further interventions. Since ESLD patients have a high operative risk for surgical myomectomy, alcohol septal ablation (ASA) emerges as a good alternative in these cases. The timing of ASA in relation to liver transplantation is still unclear. We report here on the first case of an orthotopic liver transplant-recipient undergoing ASA and the second of a cirrhotic patient requiring ASA as a bridge to liver transplantation. Both patients had a good clinical outcome and we argue that ASA in HOCM patients should be driven by symptom onset, and that in the asymptomatic patient it can be safely deferred until after liver transplantation. (Cardiol J 2008; 15: 74-79

Synthesis and characterisation of ruthenium complexes containing a pendent catechol ring

A series of [Ru(bipy)₂L]⁺ and [Ru(phen)₂L]⁺ complexes where L is 2-[5-(3,4-dimethoxyphenyl)-4H-1,2,4-triazol-3-yl]pyridine (HL1) and 4-(5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)benzene-1,2-diol (HL2) are reported. The compounds obtained have been characterised using X-ray crystallography, NMR, UV/Vis and emission spectroscopies. Partial deuteriation is used to determine the nature of the emitting state and to simplify the NMR spectra. The acid-base properties of the compounds are also investigated. The electronic structures of [Ru(bipy)₂L1]⁺ and Ru(bipy)₂HL1]²⁺ are examined using ZINDO. Electro and spectroelectrochemical studies on [Ru(bipy)₂(L2)]⁺ suggest that proton transfer between the catechol and triazole moieties on L2 takes place upon oxidation of the L2 ligand

The impact of loco-regional recurrences on metastatic progression in early-stage breast cancer: a multistate model

To study whether the effects of prognostic factors associated with the occurrence of distant metastases (DM) at primary diagnosis change after the incidence of loco-regional recurrences (LRR) among women treated for invasive stage I or II breast cancer. The study population consisted of 3,601 women, enrolled in EORTC trials 10801, 10854, or 10902 treated for early-stage breast cancer. Data were analysed in a multivariate, multistate model by using multivariate Cox regression models, including a state-dependent covariate. The presence of a LRR in itself is a significant prognostic risk factor (HR: 3.64; 95%-CI: 2.02-6.5) for the occurrence of DM. Main prognostic risk factors for a DM are young age at diagnosis (</=40: HR: 1.79; 95%-CI: 1.28-2.51), larger tumour size (HR: 1.58; 95%-CI: 1.35-1.84) and node positivity (HR: 2.00; 95%-CI: 1.74-2.30). Adjuvant chemotherapy is protective for a DM (HR: 0.66; 95%-CI: 0.55-0.80). After the occurrence of a LRR the latter protective effect has disappeared (P = 0.009). The presence of LRR in itself is a significant risk factor for DM. For patients who are at risk of developing LRR, effective local control should be the main target of therapy

Assessment of charged AuNPs: from synthesis to innate immune recognition

Gold nanoparticle (AuNP) physicochemical characteristics, mainly size and charge, modulate their biodistribution, cytotoxicity, and immunorecognition as reported from in vitro and in vivo studies. While data from in vitro studies could be biased by several factors including activation of cells upon isolation and lack of sera proteins in the microenvironment of primary generated cell lines, in vivo studies are costly and time-consuming and require ethics consideration. In this study, we developed a simple and novel in vivo-like method to test for NP immunorecognition from freshly withdrawn human blood samples. AuNPs with a size range of 30 ± 5 nm coated with cationic poly(L-lysine) (PLL) dendrigraft and slightly negative poly(vinyl alcohol) (PVA) were synthesized in water. PLL-capped AuNPs were further coated with poly(ethylene glycol) (PEG) to obtain nearly neutrally charged PEG-AuNPs. Physicochemical properties were determined using zeta potential measurements, UV-Vis spectroscopy, dynamic light scattering (DLS), and scanning electron microscopy (SEM). Gel electrophoretic separation, zeta potential, and DLS were also used to characterize our NPs after human blood plasma treatment. PLL-AuNPs showed similar variation in charge and binding affinity to plasma proteins in comparison with PVA-AuNPs. However, PLL-AuNPs.protein complexes revealed a drastic change in size compared to the other tested particles. Results obtained from the neutrophil function test and pyridine formazan extraction revealed the highest activation level of neutrophils (~70%) by 50 μg/mL of PLL-AuNPs compared to a null induction by PEG- and PVA-AuNPs. This observation was further verified by flow cytometry analysis of polymorphonuclear cell size variation in the presence of coated AuNPs. Overall, our in vivo-like method, to test for NP immunorecognition, proved to be reliable and effective. Finally, our data supports the use of PEG-AuNPs as promising vehicles for drug delivery, as they exhibit minimal protein adsorption affinity and insignificant charge and size variation once introduced in whole blood

Enhanced insulin sensitivity associated with provision of mono and polyunsaturated fatty acids in skeletal muscle cells involves counter modulation of PP2A

International audienceAims/Hypothesis: Reduced skeletal muscle insulin sensitivity is a feature associated with sustained exposure to excess saturated fatty acids (SFA), whereas mono and polyunsaturated fatty acids (MUFA and PUFA) not only improve insulin sensitivity but blunt SFA-induced insulin resistance. The mechanisms by which MUFAs and PUFAs institute these favourable changes remain unclear, but may involve stimulating insulin signalling by counter-modulation/repression of protein phosphatase 2A (PP2A). This study investigated the effects of oleic acid (OA; a MUFA), linoleic acid (LOA; a PUFA) and palmitate (PA; a SFA) in cultured myotubes and determined whether changes in insulin signalling can be attributed to PP2A regulation. Principal Findings: We treated cultured skeletal myotubes with unsaturated and saturated fatty acids and evaluated insulin signalling, phosphorylation and methylation status of the catalytic subunit of PP2A. Unlike PA, sustained incubation of rat or human myotubes with OA or LOA significantly enhanced Akt-and ERK1/2-directed insulin signalling. This was not due to heightened upstream IRS1 or PI3K signalling nor to changes in expression of proteins involved in proximal insulin signalling, but was associated with reduced dephosphorylation/inactivation of Akt and ERK1/2. Consistent with this, PA reduced PP2Ac demethylation and tyrosine 307 phosphorylation-events associated with PP2A activation. In contrast, OA and LOA strongly opposed these PA-induced changes in PP2Ac thus exerting a repressive effect on PP2A.Conclusions/Interpretation: Beneficial gains in insulin sensitivity and the ability of unsaturated fatty acids to oppose palmitate-induced insulin resistance in muscle cells may partly be accounted for by counter-modulation of PP2A

Evolution of Th2 responses : Characterization of IL-4/13 in sea bass (Dicentrarchus labrax L.) and studies of expression and biological activity

Acknowledgements This research was funded by the European Commission under the 7th Framework Programme for Research and Technological Development (FP7) of the European Union (Grant Agreement 311993 TARGETFISH). T.W. received funding from the MASTS pooling initiative (The Marine Alliance for Science and Technology for Scotland). MASTS is funded by the Scottish Funding Council (grant reference number HR09011) and contributing institutions.Peer reviewedPublisher PD

Efficacy of adjuvant chemotherapy according to hormone receptor status in young patients with breast cancer: a pooled analysis

Introduction Breast cancer at a young age is associated with an unfavorable prognosis. Very young patients with breast cancer therefore are advised to undergo adjuvant chemotherapy irrespective of tumor stage or grade. However, chemotherapy alone may not be adequate in young patients with hormone receptor-positive breast cancer. Therefore, we studied the effect of adjuvant chemotherapy in young patients with breast cancer in relation to hormone receptor status. Methods Paraffin-embedded tumor material was collected from 480 early-stage breast cancer patients younger than 41 years who participated in one of four European Organization for Research and Treatment of Cancer trials. Using immunohistochemistry on the whole series of tumors, we assessed estrogen receptor (ER) status and progesterone receptor (PgR) status in a standardized way. Endpoints in this study were overall survival (OS) and distant metastasis-free survival (DMFS). The median follow-up period was 7.3 years. Results Overall, patients with ER-positive tumors had better OS rates (hazard ratio [HR] 0.63; P = 0.02) compared with those with ER-negative tumors. However, in the subgroup of patients who received chemotherapy, no significant difference in OS (HR 0.87; P = 0.63) and DMFS (HR 1.36; P = 0.23) was found between patients with ER-positive tumors or those with ER-negative tumors. These differences were similar for PgR status. Conclusion Young patients with hormone receptor-positive tumors benefit less from adjuvant systemic chemotherapy than patients with hormone receptor-negative tumors. These results confirm that chemotherapy alone cannot be considered optimal adjuvant systemic treatment in breast cancer patients 40 years old or younger with hormone receptor-positive tumors