tbuckley/cabot-search huggingface dataset:
Simvastatin Versus Ezetimibe
Authors: Ulf Landmesser, Ferdinand Bahlmann, Maja Mueller, Stephan Spiekermann, Nina Kirchhoff, Svenja Schulz, Costantina Manes, Dieter Fischer, Kirsten de Groot, Danilo Fliser, Günter Fauler, Winfried März, Helmut Drexler
Journal: Circulation (2005)

Background— Statins may exert important pleiotropic effects, ie, improve endothelial function, independently of their impact on LDL cholesterol. In humans, however, pleiotropic effects of statins have never been unequivocally demonstrated because prolonged statin treatment always results in reduced LDL cholesterol levels. We therefore tested the hypothesis that similar reductions in LDL cholesterol with simvastatin and ezetimibe, a novel cholesterol absorption inhibitor, result in different effects on endothelial function. Methods and Results— Twenty patients with chronic heart failure were randomized to 4 weeks of simvastatin (10 mg/d) or ezetimibe (10 mg/d) treatment. Flow-dependent dilation (FDD) of the radial artery was determined by high-resolution ultrasound before and after intra-arterial vitamin C to determine the portion of FDD inhibited by radicals (ΔFDD-VC). Activity of extracellular superoxide dismutase, a major vascular antioxidant enzyme system, was determined after release from the endothelium by a heparin bolus injection. Endothelial progenitor cells were analyzed with an in vitro assay. Simvastatin and ezetimibe treatment reduced LDL cholesterol to a similar extent (15.6% versus 15.4%; P =NS), whereas changes in mevalonate, the product of HMG-CoA-reductase, differed between groups (Δmevalonate-simvastatin, −1.04±0.62 versus Δmevalonate-ezetimibe, 1.79±0.94 ng/mL; P &lt;0.05 between groups). Importantly, FDD was markedly improved after simvastatin (10.5±0.6% versus 5.1±0.7%; P &lt;0.01) but not after ezetimibe treatment (5.6±0.5% versus 5.8±0.6%; P =NS). ΔFDD-VC was substantially reduced after simvastatin but not after ezetimibe treatment. Extracellular superoxide dismutase activity was increased by &gt;100% ( P &lt;0.05) after simvastatin but not ezetimibe treatment. Simvastatin treatment increased the number of functionally active endothelial progenitor cells, whereas ezetimibe had no effect. Conclusions— Four weeks of simvastatin treatment improves endothelial function independently of LDL cholesterol lowering, at least in part by reducing oxidant stress. Simvastatin may thereby exert important pleiotropic effects in humans.
Insights from functional neuroimaging studies of behavioral state regulation in healthy and depressed subjects
Authors: Eric A. Nofzinger
Journal: Behavioral and Brain Sciences (2000)

New data are presented showing excellent replicability and test-retest reliability of REM sleep findings from functional brain imaging studies in healthy subjects on which newer brain-based models of human dreaming have been constructed. Preliminary region-of-interest findings related to bottom-up versus dissociable brain systems mediating REM sleep and dreaming are also presented. [Hobson et al.; Solms]&gt;
Accuracy of Currently Available Techniques for Prediction of Functional Recovery After Revascularization in Patients With Left Ventricular Dysfunction Due to Chronic Coronary Artery Disease: Comparison of Pooled Data
Authors: Jeroen J Bax, William Wijns, Jan H Cornel, Frans C Visser, Eric Boersma, Paolo M Fioretti
Journal: Journal of the American College of Cardiology (1997)
Unintended Consequences of Eliminating Medicare Payments for Consultations
Authors: Zirui Song, John Z. Ayanian, Jacob Wallace, Yulei He, Teresa B. Gibson, Michael E. Chernew
Journal: JAMA Internal Medicine (2012)

<h3>Background</h3>Prior to 2010, Medicare payments for consultations (commonly billed by specialists) were substantially higher than for office visits of similar complexity (commonly billed by primary care physicians). In January 2010, Medicare eliminated consultation payments from the Part B Physician Fee Schedule and increased fees for office visits. This change was intended to be budget neutral and to decrease payments to specialists while increasing payments to primary care physicians. We assessed the impact of this policy on spending, volume, and complexity for outpatient office encounters in 2010.<h3>Methods</h3>We examined outpatient claims from 2007 through 2010 for 2 247 810 Medicare beneficiaries with Medicare Supplemental (Medigap) coverage through large employers in the Thomson Reuters MarketScan Database. We used segmented regression analysis to study changes in spending, volume, and complexity of office encounters adjusted for age, sex, health status, secular trends, seasonality, and hospital referral region.<h3>Results</h3>"New" office visits largely replaced consultations in 2010. An average of $10.20 more was spent per beneficiary per quarter on physician encounters after the policy (6.5% increase). The total volume of physician encounters did not change significantly. The increase in spending was largely explained by higher office-visit fees from the policy and a shift toward higher-complexity visits to both specialists and primary care physicians.<h3>Conclusions</h3>The elimination of consultations led to a net increase in spending on visits to both primary care physicians and specialists. Higher prices, partially owing to the subjectivity of codes in the physician fee schedule, explained the spending increase, rather than higher volumes.
Osteoclastogenesis during Infective Exacerbations in Patients with Cystic Fibrosis
Authors: Elizabeth F. Shead, Charles S. Haworth, Elaine Gunn, Diana Bilton, Mike A. Scott, Juliet E. Compston
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Rationale: Adults with cystic fibrosis (CF) are at increased risk of developing osteoporosis. During infective exacerbations, increased production of proinflammatory cytokines and markers of bone resorption have been reported.Objective: The aim of this study is to investigate the growth and proliferation of potential osteoclast precursor cells before, during, and after intravenous antibiotic treatment of infective exacerbations in patients with CF.Methods: Hematopoietic precursor cell growth was examined using colony formation assays using Methocult culture medium. Circulating potential osteoclast precursors were identified using four-color flow cytometry by CD14, CD33, CD34, and CD45 expression.Results: At the start of an infective exacerbation increases in hematopoietic precursor colony formation (15.42 colonies/105 cells plated, p = 0.025), proliferation (28.5%, p < 0.001), and the numbers of circulating potential osteoclast precursors (6.5%, p < 0.001) were seen in comparison with baseline levels. These increases declined after treatment with intravenous antibiotics to a level close to baseline.Conclusions: The results demonstrate an increase in the production of potential osteoclast precursors in the peripheral blood during CF infective exacerbations. This may result in increased bone resorption and contribute to bone loss in patients with CF.
Bradykinin-induced increases in cytosolic calcium and ionic currents in cultured bovine aortic endothelial cells.
Authors: M Colden-Stanfield, W P Schilling, A K Ritchie, S G Eskin, L T Navarro, D L Kunze
Journal: Circulation Research (1987)

The goal of the present study was to determine if voltage-sensitive calcium channels are present in bovine aortic endothelial cell plasmalemma and if they contribute to the rise in cytosolic calcium produced by bradykinin. After bradykinin (100 nM) exposure, endothelial cell associated fura-2 fluorescence peaked within 10-20 seconds and then declined to a steady level 2- to 3-fold above resting values. Pretreatment with lanthanum (20 microM) abolished the steady level produced by bradykinin but had little effect on the initial, transient rise in cytosolic calcium. Chelation of extracellular calcium with EGTA before addition of bradykinin resulted in a substantial decrease in the fura-2 transient and elimination of the long-lasting component. Nimodipine (3 microM) and nitrendipine (1 microM) were without effect on either phase of the bradykinin-induced response. Moreover, elevation of extracellular potassium failed to produce a rise in intracellular calcium. With the use of the tight seal technique to voltage clamp the cells, inwardly rectifying and calcium-activated potassium currents were found to exist in the endothelial cells. Addition of bradykinin (100 nM) elicited a calcium-activated potassium current that was eliminated in the absence of intracellular potassium. No voltage-sensitive calcium currents were activated when the cells were exposed to 10 mM or 110 mM calcium chloride in the presence or absence of bradykinin. The binding of [3H](+)PN200-110 to endothelial cell membrane preparations was 1-3 orders of magnitude lower than that observed in PC-12, GH3, or BC3H1 cell membranes.(ABSTRACT TRUNCATED AT 250 WORDS)
6-Thioguanine nucleotide accumulation in erythrocytes during azathioprine treatment for systemic connective tissue diseases: a possible index for monitoring treatment.
Authors: K Schmiegelow, N J Kriegbaum
Journal: Annals of the Rheumatic Diseases (1993)

Owing to adverse pharmacokinetics, azathioprine treatment may fail to induce a satisfactory clinical response in systemic connective tissue diseases. The major intracellular cytotoxic metabolites of azathioprine are 6-thioguanine nucleotides (6TGNs).To assess whether the erythrocyte accumulation of 6TGN is a clinically applicable index for monitoring azathioprine treatment, erythrocyte accumulation of 6TGN was measured in patients with rheumatoid arthritis (n = 12), systemic lupus erythematosus (n = 7), polyarteritis nodosa (n = 2), myositis (n = 1), or leukocytoclastic vasculitis (n = 1). Ages ranged from 28 to 75 (median 58) years.Erythrocyte accumulation of 6TGN varied among the patients from 20 to 303 (median value 95) nmol/mmol haemoglobin. No significant correlation was found between erythrocyte accumulation of 6TGN and the dose of azathioprine/kg body weight, the age of the patients, the duration of treatment, or the presence of myelotoxicity or hepatotoxicity. The interindividual coefficient of variation (CV) in the erythrocyte accumulation of 6TGN/mg azathioprine/kg body weight was 0.65. The median intraindividual CV in erythrocyte accumulation of 6TGN at an unchanged dose of azathioprine was 0.09 (19 patients; range 0.03-0.27).The low intraindividual variation compared with the high interpatient variation in erythrocyte accumulation of 6TGN implies that erythrocyte accumulation of 6TGN may be clinically applicable for monitoring azathioprine treatment. Prospective studies are needed to clarify the relation between the erythrocyte accumulation of 6TGN and the clinical response to treatment, and to establish recommendations for dose modifications.
EFFECTS OF SPORT INVOLVEMENT IN ASSETS, ATTITUDES AND ENJOYMENT IN YOUTH SOCCER PLAYERS
Authors: AJ Santos, HM Carvalho, CE Gonçalves
Journal: British Journal of Sports Medicine (2013)

Sport involvement by youths is generally seen as positive for the youth development. Nevertheless, group norms, competition pressures and winning can lead to the adoption of anti-social and risk behaviours. A lack of enjoyment in sport is associated with burnout and dropout and consequently with lower levels of physical activity. We : a) observed the effect of sport involvement in youth soccer players during a season; b) observed the age effects in the developmental assets, attitudes and enjoyment in youth sport; c) explored the correlation between enjoyment, sport attitudes and developmental assets. This study comprised 135 male players aged 12–18 years ( M =15, SD =2). A multilevel analysis and Pearson correlation was performed. The magnitude of the changes during a season were modest. There were negative effects of a season involvement in soccer program, with increased cheating and reductions in commitment and some developmental assets. The negative attitudes are correlated with other-referenced sources and positive values. The findings suggest that a proper environment and postive role models can foster the maintenance in sport and a positive development.
Eicosapentanoic Acid Reduces Plasma Levels of Remnant Lipoproteins and Prevents in Vivo Peroxidation of LDL in Dialysis Patients
Authors: MINORU ANDO, TSUTOMU SANAKA, HIROSHI NIHEI
Journal: Journal of the American Society of Nephrology (1999)

Causative factors of uremia-associated atherosclerosis are complex. However, it is likely that atherogenic lipoproteins accumulated in plasma are involved. Remnant lipoproteins are atherogenic and are frequently observed in uremic plasma. LDL from uremic patients has been shown to be susceptible to in vitro peroxidation, suggesting that oxidized LDL (ox-LDL) could be excessively generated in those patients. No effective treatments to prevent accumulation of both atherogenic lipoproteins in dialysis patients have been published. Eicosapentanoic acid (EPA) may change synthesis and/or catabolism of remnant lipoproteins and increase stability of LDL to peroxidation by altering the fatty acid composition of lipoproteins. A prospective comparative study was conducted to assess the efficacy of EPA on metabolism of remnant lipoproteins and ox-LDL in dialysis patients using two new methods: an immunoaffinity gel separation for quantifying plasma remnant lipoproteins and an enzyme-linked immunosorbent assay for measuring plasma ox-LDL levels, a marker for in vivo LDL peroxidation. Twenty-two hemodialysis and 16 continuous ambulatory peritoneal dialysis patients with relatively high plasma levels of remnant lipoproteins and ox-LDL were randomized to either EPA or placebo. Highly purified EPA, in an ethyl-ester form (ethyl all-cis-5,8,11,14,17-icosapentanoate) with a purity greater than 91%, was administered at a dose of 1800 mg daily. Overall, 3 mo of treatment with EPA significantly reduced the levels of both remnant lipoproteins (52% reduction) and ox-LDL (38% reduction). Additionally, gel filtration chromatography of lipoproteins showed that EPA treatment concomitantly normalized other potential abnormalities in lipoproteins. Treatment compliance was good and no critical adverse effects were observed. In conclusion, EPA administration proved to be effective and safe treatment to decrease plasma remnant lipoproteins and prevent in vivo peroxidation of LDL in dialysis patients.
Anti-tumour necrosis factor agents and lipid profile: a class effect?
Authors: S P Garces, M J Parreira Santos, F M R Vinagre, R M Roque, J A C da Silva
Journal: Annals of the Rheumatic Diseases (2008)

Increased cardiovascular morbidity and mortality has been documented in several chronic inflammatory rheumatic diseases. In addition to the traditional cardiovascular risk factors, disease activity itself may contribute to this increase.

Tumour necrosis factor (TNF)-α, a pivotal cytokine in chronic inflammation, also affects lipid metabolism, insulin resistance and endothelial function. Therapeutic use of TNF-α blockers reduces inflammation and modifies the lipoprotein spectrum of patients. A significant increase in high-density lipoprotein (HDL) cholesterol levels has been documented after short-term infliximab therapy.1–5 However, this beneficial effect seems to be transient and more prolonged use of TNF-α blockers may lead to an increase in total cholesterol and low-density lipoprotein (LDL) cholesterol, inducing a more “atherogenic” phenotype.6 7

The …
Radiofrequency denervation of the inguinal ligament for the treatment of ‘Sportsman's Hernia’: a pilot study
Authors: Jules Comin, Haron Obaid, Greg Lammers, James Moore, Mark Wotherspoon, David Connell
Journal: British Journal of Sports Medicine (2012)

Background Chronic groin pain is a common and debilitating condition in highly active athletes. Symptoms are often ascribed to the so-called Sportsman's Hernia, and these patients frequently undergo prolonged and often painful remedial physiotherapy, or, if the condition is refractory, surgery to repair the posterior inguinal wall. Hypothesis We hypothesised that radiofrequency denervation (RFD) of both the ilioinguinal nerve and inguinal ligament could be used to desensitise the groin region and enable the athlete to become pain-free. Study design A prospective randomised controlled trial of three groups of patients with chronic groin pain. Methods Thirty-six patients with chronic groin pain of greater than 6 months duration, with no identifiable structural cause and which was refractory to conservative treatment, were randomised into two groups. Group 1 was treated with RFD (n=18), while group 2 was treated with local anaesthetic (Bupivicaine) and steroid (Trimacinolone) injection (n=18). A further 10 patients with previous failed surgery for the same condition were treated with RFD without randomisation. All patients then underwent a standardised physiotherapy regimen. The Visual Analogue Scale at rest (VASr) and with activity (VASa) was used to assess pain, and London Adductor and Abdominal Groin Score was used to assess function, at baseline and at 1 week, 3 months and 6 months post-treatment. Results RFD treatment resulted in a significant improvement above baseline in all measures and at each time intervals up to 6 months, in both the randomised Group 1 and in the postsurgery group (p values ranging from &lt;0.001 to 0.001). Injection of local anaesthetic and steroid resulted in a significant improvement above baseline in all measures, but only at 1 week (p values ranging from 0.001 to 0.021), and not at any of the later intervals. Improvements in all measures was significantly greater in Group 1 than in Group 2 at all follow-up intervals (p values ranging from &lt;0.001 to 0.003). No persistent adverse events were recorded. Conclusions The use of RFD in the treatment of refractory Sportsman's Hernia is safe and efficacious at least in the short term, and is superior to anaesthetic/steroid injection. The results suggest that symptoms are related to tendon inflammation and ilioinguinal nerve compression, and can be abolished with pharmacological or radiofrequency treatment, without the need for surgery. Clinical relevance This novel technique could help athletes suffering from chronic groin pain return to play more quickly, both facilitating and allowing deferral of remedial physiotherapy treatments, and potentially avoiding the need for surgery.
Systematic review and meta-analysis of randomised controlled trials of gastro-oesophageal reflux interventions for chronic cough associated with gastro-oesophageal reflux
Authors: A B Chang, T J Lasserson, T O Kiljander, F L Connor, J T Gaffney, L A Garske
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To evaluate the efficacy of treatment for gastro-oesophageal reflux disease (GORD) on chronic cough in children and adults without an underlying respiratory disease. <b>Design</b> Systematic review and meta-analysis. <b>Data sources</b> Cochrane, Medline, and Embase databases, references from review articles. <b>Included studies</b> Randomised controlled trials on GORD treatment for cough in children and adults without primary lung disease. Two reviewers independently selected studies and extracted paediatric and adult data on primary (clinical failure) and secondary outcomes. <b>Results</b> 11 studies were included. Meta-analysis was limited to five studies in adults that compared proton pump inhibitors with placebo. All outcomes favoured proton pump inhibitors: the odds ratio for clinical failure (primary outcome) was 0.24 (95% confidence interval 0.04 to 1.27); number needed to treat (NNT) was 5 (harm 50 to ∞ to benefit 2.5). For secondary outcomes, the standardised mean difference between proton pump inhibitors and placebo was −0.51 (−1.02 to 0.01) for mean cough score at the end of the trial and −0.29 (−0.62 to 0.04) for change in cough score at the end of the trial. Subgroup analysis with generic inverse variance analysis showed a significant mean change in cough (−0.41 SD units, −0.75 to −0.07). <b>Conclusion</b> Use of a proton pump inhibitor to treat cough associated with GORD has some effect in some adults. The effect, however, is less universal than suggested in consensus guidelines on chronic cough and its magnitude of effect is uncertain.
Interaction Between NFκB and NFAT Coordinates Cardiac Hypertrophy and Pathological Remodeling
Authors: Qinghang Liu, Yi Chen, Mannix Auger-Messier, Jeffery D. Molkentin
Journal: Circulation Research (2012)

Rationale: Both nuclear factors of activated T cells (NFAT) and nuclear factor-κB (NFκB) are Rel homology domain (RHD)-containing transcription factors whose independent activities are critically involved in regulating cardiac hypertrophy and failure. Objective: To determine the potential functional interaction between NFAT and NFκB signaling pathways in cardiomyocytes and its role in cardiac hypertrophy and remodeling. Methods and Results: We identified a novel transcriptional regulatory mechanism whereby NFκB and NFAT directly interact and synergistically promote transcriptional activation in cardiomyocytes. We show that the p65 subunit of NFκB coimmunoprecipitates with NFAT in cardiomyocytes, and this interaction maps to the RHD within p65. Overexpression of the p65-RHD disrupts the association between endogenous p65 and NFATc1, leading to reduced transcriptional activity. Overexpression of IκB kinase β (IKKβ) or p65-RHD causes nuclear translocation of NFATc1, and expression of a constitutively nuclear NFATc1-SA mutant similarly facilitated p65 nuclear translocation. Combined overexpression of p65 and NFATc1 promotes synergistic activation of NFAT transcriptional activity in cardiomyocytes, whereas inhibition of NFκB with IκBαM or dominant negative IKKβ reduces NFAT activity. Importantly, agonist-induced NFAT activation is reduced in p65 null mouse embryonic fibroblasts (MEFs) compared with wild-type MEFs. In vivo, cardiac-specific deletion of p65 using a Cre-loxP system causes a ≈50% reduction in NFAT activity in luciferase reporter mice. Moreover, ablation of p65 in the mouse heart decreases the hypertrophic response after pressure overload stimulation, reduces the degree of pathological remodeling, and preserves contractile function. Conclusions: Our results suggest a direct interaction between NFAT and NFκB that effectively integrates 2 disparate signaling pathways in promoting cardiac hypertrophy and ventricular remodeling.
Urbanicity, social adversity and psychosis
Authors: Andreas Heinz, Lorenz Deserno, Ulrich Reininghaus
Journal: World Psychiatry (2013)

In recent years, there has been increasing interest in research on geographical variation in the incidence of schizophrenia and other psychoses. In this paper, we review the evidence on variation in incidence of schizophrenia and other psychoses in terms of place, as well as the individual- and area-level factors that account for this variation. We further review findings on potential mechanisms that link adverse urban environment and psychosis. There is evidence from earlier and more recent studies that urbanicity is associated with an increased incidence of schizophrenia and non-affective psychosis. In addition, considerable variation in incidence across neighbourhoods has been observed for these disorders. Findings suggest it is unlikely that social drift alone can fully account for geographical variation in incidence. Evidence further suggests that the impact of adverse social contexts – indexed by area-level exposures such as population density, social fragmentation and deprivation – on risk of psychosis is explained (confounding) or modified (interaction) by environmental exposures at the individual level (i.e., cannabis use, social adversity, exclusion and discrimination). On a neurobiological level, several studies suggest a close link between social adversity, isolation and stress on the one hand, and monoamine dysfunction on the other, which resembles findings in schizophrenia patients. However, studies directly assessing correlations between urban stress or discrimination and neurobiological alterations in schizophrenia are lacking to date.