tbuckley/cabot-search huggingface dataset:
Abstract 9958: The Cardiovascular Risk Factor 8-iso-Prostaglandin F2alpha Independently Predicts Mortality in Pulmonary Artery Hypertension
Authors: Edzard Schwedhelm, Jean-Luc Cracowski, Ghainsom D Kom, Bruno Degano, Francois Chabot, José Labarère, Rainer H Böger, Marc Humbert
Journal: Circulation (2011)

Background. F2-isoprostanes, among them 8-iso-Prostaglandin F2alpha (8-iso-PGF2α), have emerged as cardiovascular risk factors, activating the thromboxane A2 receptor (TP) and mediating vasoconstriction, impaired angiogenesis, altered platelet activity, and smooth muscle cell proliferation. Pulmonary artery hypertension (PAH) is a rare progressive disease with a 3-year mortality rate of 30-50 %. To date, new therapeutic options in PAH are sparse. Methods. We therefore investigated the prognostic value of 8-iso-PGF2α in a cohort of 110 newly diagnosed, treatment naïve, PAH patients. Eligible patients from 6 centers of the French Network on Pulmonary Hypertension were screened and patients were followed for 3 years. Urinary 8-iso-PGF2α determined by gas chromatography-mass spectrometry (GC-MS), along with other clinical and biochemical characteristics was evaluated at the time of diagnosis, i.e. right heart catheterisation. Results. Among 110 enrolled patients, 11 underwent heart and/or lung transplantation and 27 died during follow-up. Plasma big endothelin-1 (hazard ration [HR] per 1 standard deviation [SD] increase, 1.48, 95 % confidence interval [CI] 1.14 - 1.92), serum troponin T &gt;0.01 mg/L (HR: 2.35, CI: 1.05 - 5.3], and urinary 8-iso-PGF2α (HR: 1.76, CI: 1.31 - 2.36) were associated with unadjusted risk. In multivariate Cox proportional hazard models, adjusting for variables with p&lt;0.1, only 8-iso-PGF2α was independently associated with mortality (HR:1.82, CI:1.28 - 2.60). Conclusions. The endogenous TP agonist 8-iso-PGF2α independently predicts mortality in newly diagnosed PAH patients. Pharmacological inhibition of the TP in these selected patients may be a new valuable option additive to standard treatment.
Complexity science: The challenge of complexity in health care
Authors: P. E Plsek, T. Greenhalgh
Journal: BMJ (2001)

This is the first in a series of four articles 

Across all disciplines, at all levels, and throughout the world, health care is becoming more complex. Just 30 years ago the typical general practitioner in the United Kingdom practised from privately owned premises with a minimum of support staff, subscribed to a single journal, phoned up a specialist whenever he or she needed advice, and did around an hour's paperwork per week. The specialist worked in a hospital, focused explicitly on a particular system of the body, was undisputed leader of his or her “firm,” and generally left administration to the administrators. These individuals often worked long hours, but most of their problems could be described in biomedical terms and tackled using the knowledge and skills they had acquired at medical school.

You used to go to the doctor when you felt ill, to find out what was wrong with you and get some medicine that would make you better. These days you are as likely to be there because the doctor (or the nurse, the care coordinator, or even the computer) has sent for you. Your treatment will now be dictated by the evidence—but this may well be imprecise, equivocal, or conflicting. Your declared values and preferences may be used, formally or informally, in a shared management decision about your illness. The solution to your problem is unlikely to come in a bottle and may well involve a multidisciplinary team.

Not so long ago public health was the science of controlling infectious diseases by identifying the “cause” (an alien organism) and taking steps to remove or contain it. Today's epidemics have fuzzier boundaries (one is even known as “syndrome X”1): they are the result of the interplay of genetic predisposition, environmental context, and lifestyle choices.

The experience of …
Abstract 5078: Physical Training Reduces the Ability of Serum from Patients with Heart Failure to Induce Endothelial Cell Death
Authors: Caterina Mammi, Massimiliano Caprio, Stefania Gorini, Andrea la Sala, Antonella Antelmi, Lucia Gatta, Giuseppe Marazzi, Giuseppe Caminiti, Maurizio Volterrani, Giuseppe Rosano
Journal: Circulation (2008)

Physical training improves endothelial function and exercise capacity in patients with heart failure (HF). Serum from patients with cardiovascular diseases shows increased ability to induce apoptosis in human endothelial cells potentially contributing to the progression of atherosclerotic and endothelial dysfunction. Aim of this study was to evaluate the effect of cardiac rehabilitation on the pro-apoptotic properties of serum in patients with heart failure. Human Umbilical Vein Endothelial Cells (HUVECs) were incubated with 20% serum from 24 patients with HF (HYHA II) before and after cardiovascular rehabilitation. For apoptosis quantification, fragmented DNA was determined using Cell Death detection ELISA kit and propidium iodide (PI) staining analyzed by flow cytometry. The expression on endothelial cells of proteins involved in apoptotic pathway (bax, caspasi-3, bcl-2) was studied by Western blot analysis. Necrosis was evaluated measuring the lactate dehydrogenase released from damaged cells into the supernatant using a cytotoxicity detection kit. Serum from patients with heart failure showed a significantly greater ability to induce apoptosis (67 ± 4,6% vs 23 ± 5,2%, p&lt;0,001) and necrosis (44 ± 3% vs 32 ± 2,1%, p&lt;0,05) of HUVEC cells compared with controls. Cardiac rehabilitation significantly reduced the ability of patient serum to induce apoptosis (PI: 40.44% ± 3,9 vs 25.22% ± 2,6, p&lt;0,01; ELISA: 67 ± 4,6% vs 42 ± 4,4%, p&lt;0,001) and necrosis (44 ± 3% vs 33 ± 2%, p&lt;0,01) of HUVEC cells compared to baseline. Moreover endothelial cells treated with serum after rehabilitation showed a significant decrease of bax expression (1,12 ± 0,06 vs 0,89 ± 0,08, p&lt;0,05) and a significant decrease of cleaved Caspase-3 expression (0,91 ± 0,16 vs 0,72 ± 0,08, p&lt;0.05). Serum of patients with heart failure has increased pro-apoptotic properties. Physical training reduces the ability of serum-contained factors to induce cell death of endothelial cells in patient with heart failure.
Abstract 4296: Allogeneic Bone Marrow Mesenchymal Cells Improved Heart Function but Were Rejected after Myogenic Differentiation
Authors: Xi-Ping Huang, Zhuo Sun, Yasuo Miyagi, Shafie Fazel, Richard D Weisel, Ren-Ke Li
Journal: Circulation (2008)

Rationale: Allogeneic bone marrow mesenchymal stem cells (MSC) are currently undergoing clinical trials to test their potential to repair the heart after a myocardial infarction (MI). MSCs can improve function, but neither the host immune responses nor the fate of these cells has been extensively investigated. This study compared the outcomes of allogeneic and syngeneic MSC transplantation after an MI. Methods: Female Lewis rat underwent coronary ligation. Three weeks later, allogeneic or syngeneic MSCs (3×10 6 /rat) from male rats (Wister or Lewis, respectively) were implanted into the infracted region. We evaluated implanted cell survival (real-time PCR to quantify Y-chromosomes), cytokines (RT-PCR) and infiltrating cells (immunostaining) in the heart, and allogeneic antibodies in the blood. Cardiac function was assessed by echocardiography and pressure-volume catheters. Immune antigen expression (RT-PCR, immunostaining and flow cytometry) was characterized in the MSCs before and after myogenic differentiation. Results: At 1 week post implantation, cell survival was similar in the allogeneic and syngeneic groups. Gene expression of 11 cytokines and T-cell infiltration into the cell-implanted region were also similar, but more B-cells were observed in the allogeneic group (p&lt;0.05 vs. syngeneic group). Allo-antibodies (IgG1) against Wistar MSCs were detected in the peripheral blood of animals that received allogeneic cells. At 5 weeks after delivery, implanted MSCs were detected only in the syngeneic group. Cardiac function was equally restored in both cell groups (ejection fraction: allogeneic=30.4±1.8%; syngeneic=29.5±2.8%; p&lt;0.05 vs. media controls; control=24.8±3.2%); these data were supported by the pressure-volume analysis. Myogenic differentiation (expression of Nkx2.5, MyoD, MHCβ), CD86 expression and MHC class II molecules were observed in the MSCs after prolonged culture, which could explain why the cells were rejected. Conclusions: Allogeneic BMSC transplantation produced a robust cardiac functional improvement, but following myogenic differentiation the cells were no longer immunoprivileged. Rejection of the allogeneic cells could limit their long term benefit on cardiac remodeling after an MI.
Abstract 422: Lox-1 Receptor Contributes to Oxldl-dependent Arginase Activation Through Rho-Dependent Mechanism
Authors: Sungwoo Ryoo, Andre Camara, Gautam Sikka, Fumin Chang, Artin Shoukas, Lewis H Romer, Dan E Berkowitz
Journal: Circulation (2008)

Oxidized LDL increases arginase activity and reciprocally decreases endothelial NO production.Inhibition of arginase II attenuates cholesterol-mediated atherogenesis through by recoupling NOS3, imp...
Preparedness activities ahead of the Beijing 2008 Olympic Games - enhancing EU epidemic intelligence
Authors: L Payne, P Arias, P Kreidl, M Ciotti, D Coulombier
Journal: Eurosurveillance (2008)

This Friday, 8 August 2008 will see the official opening of the Beijing 2008 Olympic Games. In the following weeks (8-24 August) an estimated 10,500 athletes from 205 participating countries will compete in the Olympics, followed by the Paralympics (6-17 September). Sporting events will be held in Olympic venues hosted mainly in Beijing city, Tianjin, Hong Kong, Shanghai, Shenyang, Qinhuangdao and Qingdao (See Figure). An estimated 2.4 million spectators are anticipated to join in the celebration of the Olympics alone, with over 20,000 accredited media present [1] and 450,000 foreigners expected [2].
Synovium as a source of increased amino-terminal parathyroid hormone-related protein expression in rheumatoid arthritis. A possible role for locally produced parathyroid hormone-related protein in the pathogenesis of rheumatoid arthritis.
Authors: J L Funk, L A Cordaro, H Wei, J B Benjamin, D E Yocum
Journal: Journal of Clinical Investigation (1998)

One of the hallmarks of SLE is the loss of tolerance to chromatin. The genes and mechanisms that trigger this loss of tolerance remain unknown. Our genetic studies in the NZM2410 lupus strain have implicated genomic intervals on chromosomes 1 (Sle1), 4 (Sle2), and 7 (Sle3) as conferring strong lupus susceptibility. Interestingly, B6 mice that are congenic for Sle1 (B6.NZMc1) have elevated IgG antichromatin Abs. This study explores the antinuclear antibody fine specificities and underlying cellular defects in these mice. On the B6 background, Sle1 by itself is sufficient to generate a robust, spontaneous antichromatin Ab response, staining Hep-2 nuclei homogeneously, and reacting primarily with H2A/H2B/DNA subnucleosomes. This targeted immune response peaks at 7-9 mo of age, affects both sexes with equally high penetrance (> 75%), and interestingly, does not "spread" to other subnucleosomal chromatin components. Sle1 also leads to an expanded pool of histone-reactive T cells, which may have a role in driving the anti-H2A/H2B/DNA B cells. However, these mice do not exhibit any generalized immunological defects or quantitative aberrations in lymphocyte apoptosis. We hypothesize that Sle1 may lead to the presentation of chromatin in an immunogenic fashion, or directly impact tolerance of chromatin-specific B cells.
The corticotropin-releasing hormone stimulation test in patients with panic disorder
Authors: Peter P. Roy-Byrne, Thomas W. Uhde, Robert M. Post, William Gallucci, George P. Chrousos, Philip W. Gold
Journal: American Journal of Psychiatry (1986)

Eight patients with panic disorder had significantly lower ACTH and cortisol responses to corticotropin-releasing hormone and a significantly lower ratio of ACTH to cortisol response than 30 normal control subjects. These responses resemble those previously reported for depressed patients except that they occurred in the face of significantly elevated basal cortisol and ACTH levels. These results suggest that patients with panic disorder have an element of chronic hypercortisolemia, like depressed patients, but also a more acute perturbation in ACTH secretion, not previously seen in depressed patients.
Exaggerated platelet reactivity in major depression
Authors: Dominique L. Musselman, Aaron Tomer, Amita K. Manatunga, Bettina T. Knight, Maryfrances R. Porter, Suha Kasey, Ulla Marzec, Laurence A. Harker, Charles B. Nemeroff
Journal: American Journal of Psychiatry (1996)

This study investigated whether depressed patients exhibit exaggerated platelet reactivity.In vivo platelet activation, secretion, and dose-response aggregation were measured in 12 depressed patients and eight normal comparison subjects after overnight bed rest and following orthostatic challenge.The depressed patients exhibited increased platelet activation at baseline, demonstrated by increased binding of monoclonal antibody (moAb) annexin V protein reacting with prothrombinase complex binding sites. Following orthostatic challenge, the depressed patients exhibited increases in binding of moAbs PAC1 and anti-LIBS1 against activated glycoprotein IIb/IIIa and GE12 against P-selectin expressed upon secretion. The normal comparison subjects exhibited increases in platelet activation only with GE12.Depressed patients exhibit enhanced baseline platelet activation and responsiveness in comparison with normal subjects. Heightened susceptibility to platelet activation may be a mechanism by which depression is a significant risk factor for ischemic heart and cerebrovascular disease and/or mortality after myocardial infarction.
Abstract 19183: Overexpression of Apom in Liver Stimulates Formation of Larger, Apom/S1P-Enriched Plasma HDL
Authors: Mingxia Liu, Jeongmin Seo, Jeremy Allegood, Xin Bi, Xuewei Zhu, Elena Boudyguina, Abraham K Gebre, Mary Sorci-Thomas, Mike S Thomas, Gregory S Shelness, Sarah Spiegel, John S Parks
Journal: Circulation (2013)

Apolipoprotein M (ApoM), a lipocalin family member, preferentially associates with plasma HDL and binds plasma sphingosine 1-phosphate (S1P), a critical signaling molecule in immune homeostasis and endothelial barrier function. ApoM overexpression in ABCA1-expressing HEK293 cells stimulates larger nascent HDL particle formation compared to non apoM-expressing cells, but the in vivo role of apoM in HDL metabolism is poorly understood. To test whether hepatic apoM overexpression increases plasma HDL size, we generated liver-specific apoM transgenic (apoM Tg) mice displaying ~5-fold increase in plasma apoM levels compare to wild type (WT) mice. Although plasma HDL cholesterol concentrations were similar to WT mice, apoM Tg mice had larger plasma HDL particles, enriched in apoM, cholesteryl ester, lecithin:cholesterol acyltransferase and S1P. Despite the presence of larger plasma HDL particles in apoM Tg mice, in vivo macrophage reverse cholesterol transport capacity was similar to WT mice. ApoM Tg mice had ~5-fold increase in plasma S1P that was predominantly associated with larger plasma HDL particles. Primary hepatocytes from apoM Tg vs. WT mice generated larger nascent HDL particles, stimulated sphingolipid synthesis, and increased secretion of S1P. Chemical inhibition of ceramide synthase in hepatocytes stimulated S1P synthesis, but not secretion, suggesting that apoM is rate limiting in export of hepatocyte S1P. Our data suggest that liver-specific apoM overexpression: 1) generates large nascent HDLs and large plasma HDL particles that preferentially bind apoM and S1P, and 2) stimulates S1P synthesis for secretion into plasma. The unique apoM/S1P-enriched plasma HDL may serve to deliver S1P to extrahepatic tissues for atheroprotection or other as yet unidentified functions.
Seasonal Changes in Iodine Metabolism
Authors: G. D. Broadhead, I. B. Pearson, G. M. Wilson
Journal: BMJ (1965)

Regional differences in the prevalence of goitre in Britain were recognized during the early part of the last century (Inglis, 1838) and there is evidence that these still persist (Kilpatrick, Milne, Rushbrooke, Wilson, and Wilson, 1963).The importance of iodine deficiency in the pathogenesis of goitre has been established beyond reasonable doubt, though it is now clear that other factors may also be important in the development of thyroid enlargement.In the past considerable attention has been paid to the concentration of iodine in water-supplies (Murray, Ryle, Simpson, and Wilson, 1948) but in Britain this usually lies between 1 and 4 ptg./litre.Consequently the human requirement of iodine for health, often placed at about 100 /Ag. a day, must be met largely from the diet.The food richest in iodine is undoubtedly marine fish (Chilean Iodine Educational Bureau, 1952), but this is only an occasional item in the diet.Another foodstuff relatively rich in iodine is cows' milk, and this is important, particularly in childhood, as it is consumed daily in large amounts.During the course of investigations into the pathogenesis of non-toxic goitre a large seasonal fluctuation was observed in the iodine content of milk which entirely overshadowed any regional differences.The extent and cause of this fluctuation in iodine concentration were accordingly investigated further. Methods Determination of Iodine in MilkThis method was developed from that described by Acland (1957) for the measurement of serum-protein-bound iodine.AnalaR reagent grade chemicals and deionized water were used in all the determinations.Reagents.-Sodiumcarbonate solution :-Anhydrous sodium carbonate (102 g.) was dissolved in 1,000 ml. of water; carrier-free "'I was added (50 pc.).Ceric ammonium sulphate solution:-Ceric ammonium sulphate, low in rare earths (8.15 g.), was dissolved in water; concentrated sulphuric acid (80 ml.) was added, and the volume made up to 1,000 ml. with water.Arsenious acid solution: -Arsenious oxide (3.15 g.) was dissolved in water containing sodium hydroxide (1.65 g.); concentrated sulphuric acid (70 ml.) was added, and the volume made up to 1,000 ml. with water.Hydrochloric acid solution :-Concentrated hydrochloric acid (63 ml.) was added to water and then diluted to 1,000 ml.Standard iodine solution :-Potassium iodide (0.13 g.) was dissolved in 1,000 ml. of water; 1 ml. of this solution was diluted to 100 ml. and the standard solution containing iodine 0.02 .lg./ml.was made by diluting 5 ml. of the final solution to 250 ml.Measurement of Iodine in Liquid Milk.-Twelve hard-glass tubes (10 by 1.5 cm.) were taken and 2 ml. of sodium carbonate solution containing "'I was put into each.One was left blank, and into the next was placed a standard urine sample (1 ml.), which was used as a reference standard in all iodine determinations made in the department.These provided evidence of the reproducibility of the results.Five milk samples were taken and 3 ml.was placed in each of two test-tubes.In one of each pair of test-tubes con-
Relation of leukocyte counts during clozapine treatment to serum concentrations of clozapine and metabolites
Authors: F Centorrino, R J Baldessarini, J G Flood, J C Kando, F R Frankenburg
Journal: American Journal of Psychiatry (1995)

This study was done to test the hypothesis that serum concentration of norclozapine is a risk factor for leukopenia during treatment with clozapine.Maximum decreases in leukocyte counts in 44 unselected patients treated with clozapine were determined and then correlated with drug doses and serum concentrations of clozapine, norclozapine, and clozapine-N-oxide.White cell and granulocyte counts decreased by up to 60%-73%, but there were no positive correlations between these decrements and drug dose, drug level, ratio of drug level to drug dose, or ratio of norclozapine level to clozapine level, nor were the decreases related to age or gender.While these results do not suggest in vivo hemotoxicity of norclozapine, further study of patients with clinically significant leukopenia is required.
Abstract 016: Sugar-Sweetened Beverage Consumption is Inversely Associated with Coronary Flow Reserve among Male Middle-Aged Twins
Authors: Silvia C Eufinger, Viola Vaccarino
Journal: Circulation (2012)

Introduction: Several previous studies have reported a link between sugar-sweetened beverage (SSB) consumption and numerous cardiovascular disease (CVD) risk factors including hypertension, dyslipidemia, and obesity. However, our understanding of how SSB consumption affects cardiovascular function remains limited. We sought to investigate the association between SSB consumption and coronary flow reserve (CFR), a measure of overall coronary vasodilator capacity and microvascular function. Hypothesis: Increased SSB consumption is associated with lower CFR. Methods: A sample of 320 male middle-aged twins, including 128 monozygotic and dizygotic twin pairs and 64 unpaired twins, with no previous history of coronary heart disease (CHD) and diabetes, was recruited from the Vietnam Era Twin Registry. All twins underwent comprehensive cardiovascular assessments and completed the Willett food-frequency questionnaire. Reported intakes of fruit drinks, regular carbonated beverages with sugar, low-calorie carbonated beverages with sugar, and other SSBs were used to derive habitual daily SSB consumption for the previous 12 months. Positron emission tomography [N 13 ] ammonia with quantitation of myocardial blood flow at rest and after adenosine stress was used to measure CFR. Mixed-effect regression analysis was used to examine the association between SSB consumption and CFR both at the individual level and between and within twin pairs. Potential confounders included demographic characteristics, lifestyle factors (including physical activity), traditional CVD risk factors, total energy intake, and other nutritional factors such as intake of cholesterol, fiber, sodium, alcohol, and saturated, monounsaturated, and polyunsaturated fatty acids. Results: The mean age of the twins was 55 years (SD = 3.2) and 94.4% (302 out of 320) were white. Across quintiles of twins consuming less than 2 SSBs per day, 2 to less than 4, 4 to less than 6, 6 to less than 8, and 8 or more, adjusted geometric mean CFR measurements were, respectively, 2.49, 2.45, 2.43, 2.37, and 2.18 ( P = 0.032 for linear trend) with the top quintile having a 12.4% lower CFR than the bottom quintile. The inverse association observed at the individual level persisted between-pairs ( P = 0.042), but was substantially reduced and no longer significant within twin pairs. These associations did not differ by zygosity. Conclusions: SSB consumption is inversely associated with CFR, a measure of coronary microvascular function, independent of traditional CVD risk factors. However, shared familial factors, such as growing up in the same home environment and adopting parental behaviors throughout youth and adolescence, may mediate the association between SSB consumption and CFR. Our study supports the importance of early-life, family-level interventions to promote healthy eating and improve cardiovascular health.
Abstract 87: Effects of Variable Depth of Chest Compression on Outcomes of CPR
Authors: Giuseppe Ristagno, Wanchun Tang, Dawn Jorgenson, James K Russell, Tong Wang, Shijie Sun, Max H Weil
Journal: Circulation (2006)

Introduction. Both in- and out-of-hospital chest compressions are typically delivered ineffectively. We therefore evaluated the quality of chest compressions (CC) as recommended in the AHA CPR Guid...