Vagus Nerve Stimulation in Refractory Epilepsy: Effects on Pro- and Anti-Inflammatory Cytokines in Peripheral Blood

Objective: The vagus nerve has important immunological functions that may be relevant for its anticonvulsive action. We postulate that this anticonvulsive action is activated by a shift in the immune system resulting in a reduction of neurotoxic and an increase of neuroprotective tryptophan metabolites. Methods: Eleven patients with refractory epilepsy and 11 controls matched for age and gender were included in this study. The primary outcome measure was a 50% seizure reduction. Other variables were pro-inflammatory cytokines IL-6 and TNF-alpha, anti-inflammatory cytokine IL-10, cortisol, and the tryptophan metabolites 3-hydroxykynurenine (3-OH-KYN), kynurenic acid (KYNA), kynurenine, serotonin (5-HT) and 5-hydroxyindol acetic acid (5-HIAA). Blood samples were scheduled during baseline, and in week 28 of add-on treatment. Results: IL-6 levels were higher in the responders than in the control group, and decreased after vagus nerve stimulation (VNS), whereas IL-10 was low and increased after VNS. In nonresponders, VNS resulted in an increase of IL-6 plasma levels and in a decrease of IL-10. Cortisol concentrations are higher in the epilepsy group than in the control group. After VNS, these concentrations decreased. The concentrations of the tryptophan metabolites were lower in the epilepsy group than in the control group. The KYNA ratios are defined as the ratio of neuroprotective KYNA versus neurotoxic 3-OH-KYN and KYNA versus neurotoxic kynurenine: these ratios were lower in epilepsy patients than in controls, and they both moderately increased after VNS. Conclusion: The outcome of this preliminary study indicates that VNS causes a rebalancing of the immune system. This results in: (1) a reduction of neurotoxic and an increase of neuroprotective kynurenine metabolites and (2) in the normalization of cortisol levels. Copyright (C) 2010 S. Karger AG, Base

Effect of age on the prognostic value of left ventricular function in patients with acute coronary syndrome:a prospective registry study

Objective: This study aims to study the prognostic impact of LV function on mortality and examine the effect of age on the prognostic value of left ventricular function.  Methods: We examined the Myocardial Ischaemia National Audit Project (MINAP) registry (2006-2010) data with a mean follow up of 2.1 years. LV function was categorized into good (ejection fraction (EF) ≥50%), moderate (EF 30-49%) and poor (EF <30%) categories. Cox-proportional hazards models were constructed to examine the prognostic significance of LV function in different age groups (<65, 65-74, 75-84 and ≥85 years) on all-cause mortality adjusting for baseline variables.  Results: Of 424,848 patients, LV function data available for 123,609. Multiple imputations were used to impute missing values of LV function and the final sample for analyses were drawn from 414,305. After controlling for confounders, 339,887 participants were included in the regression models. For any age group, mortality was higher with worsening degree of LV impairment. Increased age reduced the adverse prognosis associated with reduced LV function (hazard ratios (HRs) of death comparing poor LV function to good LV function were 2.11 95%CI 1.88-2.37 for age <65 years and 1.28 95%CI 1.20-1.36 for age ≥85 years. Older patients had a high mortality risk even in those with good LV function. HRs of mortality for ≥85 compared to <65 years (HR=1.00) within good, moderate and poor ejection fractions groups were 5.89, 4.86 and 3.43, respectively.  Conclusions: In patients with ACS, clinicians should interpret the prognostic value of LV function taking into account patient’s age

ΛΛ\Lambda\Lambda-ΞN\Xi N-ΣΣ\Sigma\Sigma coupling in ΛΛ 6^{~6}_{\Lambda\Lambda}He with the Nijmegen soft-core potentials

The $\Lambda\Lambda$-$\Xi N$-$\Sigma\Sigma$ coupling in $^{~6}_{\Lambda\Lambda}$He is studied with the [$\alpha$ + $\Lambda$ + $\Lambda$] + [$\alpha$ + $\Xi$ + $N$] + [$\alpha$ + $\Sigma$ + $\Sigma$] model, where the $\alpha$ particle is assumed as a frozen core. We use the Nijmegen soft-core potentials, NSC97e and NSC97f, for the valence baryon-baryon part, and the phenomenological potentials for the $\alpha-B$ parts ($B$=$N$, $\Lambda$, $\Xi$ and $\Sigma$). We find that the calculated $\Delta B_{\Lambda\Lambda}$ of $^{~6}_{\Lambda\Lambda}$He for NSC97e and NSC97f are, respectively, 0.6 and 0.4 MeV in the full coupled-channel calculation, the results of which are about half in comparison with the experimental data, $\Delta B^{exp}_{\Lambda\Lambda}=1.01\pm0.20^{+0.18}_{-0.11}$ MeV. Characteristics of the $S=-2$ sector in the NSC97 potentials are discussed in detail.Comment: 18 pages, 4 figure

Hyperonic mixing in five-baryon double-strangeness hypernuclei in a two-channel treatment

Properties of hypernuclei $_{\Lambda \Lambda}^5$H and $_{\Lambda \Lambda }^5$He are studied in a two-channel approach with explicit treatment of coupling of channels ^3\text{Z}+\Lambda+\Lambda and \alpha+\Xi. Diagonal \Lambda\Lambda and coupling \Lambda\Lambda-\Xi N interactions are derived within G-matrix procedure from Nijmegen meson-exchange models. Bond energy \Delta B_{\Lambda\Lambda} in $_{\Lambda \Lambda}^5$He exceeds significantly that in $_{\Lambda \Lambda}^5$H due to the channel coupling. Diagonal \Xi\alpha attraction amplifies the effect, which is sensitive also to \Lambda-core interaction. The difference of the \Delta B_{\Lambda\Lambda} values can be an unambiguous signature of the \Lambda\Lambda-\Xi N coupling in \Lambda\Lambda hypernuclei. However, improved knowledge of the hyperon-nucleus potentials is needed for quantitative extraction of the coupling strength from future data on the \Lambda\Lambda hypernuclear binding energies.Comment: 11 pages with 3 figures; Phys. Rev. C, accepte

Circulating endothelial microparticles reduce in concentration following an exercise programme in women with polycystic ovary syndrome

Purpose: Endothelial dysfunction is a known comorbidity in women with polycystic ovary syndrome (PCOS). The aim was to assess if supervised, moderate intensity exercise could potentially impact markers of endothelial disruption; endothelial cell derived microparticles (EMP). Methods: The current study investigated the effects of a supervised 8-week moderate intensity exercise programme on EMP in women with PCOS (n=11) and control women free from any known disease (n=10). EMP were enumerated via specific antibody (CD105, CD106) labelling and flow cytometry.Results: CD105+MP significantly reduced in women with PCOS from pre to post exercise programme, with CD105+ MP reducing from 2114 CD105+ MP per µl platelet free plasma (PFP) to 424 CD105+ MP per µl PFP (p = 0.025). Control women showed no significant change in CD105+ MP (p = 0.25) after completing the same exercise programme. CD106+ MP showed no change in either PCOS (p = 0.95) or control groups (p = 0.99). No significant correlations existed with the changes in endothelial microparticles (EMP) compared to body composition changes as a result of exercise. Conclusion: Supervised, moderate intensity exercise independent of substantial weight loss reduced circulating CD105+MP, likely reflecting an improvement in endothelial function in women with PCOS compared to healthy control women. Additionally, EMP may be a useful marker for physical improvement in exercise programmes for clinical populations

Determinants and outcomes of stroke following percutaneous coronary intervention by indication

Background and Purpose—Stroke after percutaneous coronary intervention (PCI) is a serious complication, but its determinants and outcomes after PCI in different clinical settings are poorly documented. Methods—The British Cardiovascular Intervention Society (BCIS) database was used to study 560 439 patients who underwent PCI in England and Wales between 2006 and 2013. We examined procedural-type specific determinants of ischemic and hemorrhagic stroke and the likelihood of subsequent 30-day mortality and in-hospital major adverse cardiovascular events (a composite of in-hospital mortality, myocardial infarction or reinfarction, and repeat revascularization). Results—A total of 705 stroke cases were recorded (80% ischemic). Stroke after an elective PCI or PCI for acute coronary syndrome indications was associated with a higher risk of adverse outcomes compared with those without stroke; 30-day mortality and major adverse cardiovascular events outcomes in fully adjusted model were odds ratios 37.90 (21.43–67.05) and 21.05 (13.25–33.44) for elective and 5.00 (3.96–6.31) and 6.25 (5.03–7.77) for acute coronary syndrome, respectively. Comparison of odds of these outcomes between these 2 settings showed no differences; corresponding odds ratios were 1.24 (0.64–2.43) and 0.63 (0.35–1.15), respectively. Conclusions—Hemorrhagic and ischemic stroke complications are uncommon, but serious complications can occur after PCI and are independently associated with worse mortality and major adverse cardiovascular events outcomes in both the elective and acute coronary syndrome setting irrespective of stroke type. Our study provides a better understanding of the risk factors and prognosis of stroke after PCI by procedure type, allowing physicians to provide more informed advice around stroke risk after PCI and counsel patients and their families around outcomes if such neurological complications occur

Relationship between anemia and mortality outcomes in a national acute coronary syndrome cohort: Insights from the UK Myocardial Ischemia National Audit Project registry

Background: We aim to determine the prevalence of anemia in ACS patients and compared their clinical characteristics, management and clinical outcomes to those without anemia in an unselected national ACS cohort. Methods and Results: The Myocardial Ischemia National Audit Project (MINAP) registry collects data on all adults admitted to hospital trusts in England and Wales with diagnosis of an ACS. We conducted a retrospective cohort study by analyzing patients in this registry between January 2006 and December 2010 and followed them up until August 2011. Multiple logistic regressions were used to determine factors associated with anemia and the adjusted odds of 30-day mortality with 1 g/dl incremental hemoglobin increase and the 30-days and 1-year mortality for anemic compared to non-anemic groups. Analyses were adjusted for covariates. Our analysis of 422,855 patients with ACS showed that 27.7% of patients presenting with ACS are anemic, and that these patients are older, have a greater prevalence renal disease, peripheral vascular disease, diabetes mellitus and previous acute myocardial infarction and are less likely to receive evidence based therapies shown to improve clinical outcomes. Finally our analysis suggests that anemia is independently associated with 30-day (OR 1.28, 95%CI 1.22-1.35) and 1-year mortality (OR 1.31, 95%CI 1.27-1.35) and we observed a reverse J-shaped relationship between hemoglobin levels and mortality outcomes. Conclusion: The prevalence of anemia in a contemporary national ACS cohort is clinically significant. Patients with anemia are older and multi-morbid, and less likely to receive evidence-based therapies shown to improve clinical outcomes with the presence of anemia independently associated mortality outcomes

QCD chiral Lagrangian on the lattice, strong coupling expansion and Ward identities with Wilson fermions

We discuss a general strategy to compute the coefficients of the QCD chiral Lagrangian using lattice QCD with Wilson fermions. This procedure requires the introduction of a lattice chiral Lagrangian as an intermediate step in the calculation. The QCD chiral Lagrangian is then obtained by expanding the lattice effective theory in increasing powers of the lattice spacing and the external momenta. In order to investigate the consequences of the chiral symmetry breaking induced by the Wilson term, we study the lattice chiral Lagrangian at the leading order of the strong coupling and large $N$ expansion. We show that the effects of the Wilson term can be conveniently taken into account, in the lattice effective theory, by a suitable renormalization procedure. In particular, we show that, at the leading order of the strong coupling and large N expansion, the chiral symmetry is exactly recovered on the lattice provided that the bare quark mass and the lattice operators are properly renormalized.Comment: 45 pages, no figures. Latex fil

Does anticholinergics drug burden relate to global neuro-disability outcome measures and length of hospital stay?

Primary objective: To assess the relationship between disability, length of stay (LOS) and anticholinergic burden (ACB) with people following acquired brain or spinal cord injury. Research design: A retrospective case note review assessed total rehabilitation unit admission. Methods and procedures: Assessment of 52 consecutive patients with acquired brain/spinal injury and neuropathy in an in-patient neuro-rehabilitation unit of a UK university hospital. Data analysed included: Northwick Park Dependency Score (NPDS), Rehabilitation complexity Scale (RCS), Functional Independence Measure and Functional Assessment Measure FIM-FAM (UK version 2.2), LOS and ACB. Outcome was different in RCS, NPDS and FIM-FAM between admission and discharge. Main outcomes and results: A positive change was reported in ACB results in a positive change in NPDS, with no significant effect on FIM-FAM, either Motor or Cognitive, or on the RCS. Change in ACB correlated to the length of hospital stay (regression correlation = −6.64; SE = 3.89). There was a significant harmful impact of increase in ACB score during hospital stay, from low to high ACB on NPDS (OR = 9.65; 95% CI = 1.36–68.64) and FIM-FAM Total scores (OR = 0.03; 95% CI = 0.002–0.35). Conclusions: There was a statistically significant correlation of ACB and neuro-disability measures and LOS amongst this patient cohort