tbuckley/cabot-search huggingface dataset:
Abstract 9071: P-Selectin Glycoprotein Ligand-1 Deficiency is Protective Against Perivascular Macrophage Infiltration and Obesity-Induced Endothelial Dysfunction
Authors: Hui Wang, Wei Luo, Chiao Guo, Peter F Bodary, Daniel T Eitzman
Journal: Circulation (2011)

Introduction: P-selectin glycoprotein ligand-1 (Psgl-1) is a leukocyte ligand which binds to selectins and mediates leukocyte trafficking in several disease states. The goal of the current study was to assess the effects of Psgl-1 deficiency on perivascular adipose tissue (PVAT) macrophage accumulation and endothelial dysfunction in the setting of obesity. Methods: Psgl-1 deficient ( Psgl-1 -/- ) and control ( Psgl-1 +/+ ) mice were fed either normal or DIO chow for 10 weeks (n=5-7 mice per group). Mesenteric arterioles were then mounted on a pressure myograph to evaluate vascular function. Norepinephrine (NE)-induced vasoconstriction, acetylcholine (Ach)-induced (with and without N-nitro-L-arginine methyl ester (L-NAME)) and sodium nitroprusside (SNP)-induced vasorelaxation were evaluated. Mesenteric PVAT macrophage content was assessed with Mac-3 immunohistochemistry. Results: The body weight of DIO mice was greater than standard chow-fed mice (46.5±1.4 vs 21.2±1.6g, p&lt;0.01). NE-induced vasoconstrictions were similar between Psgl-1 +/+ and Psgl-1 -/- mice on DIO or standard chow, however, relaxation responses to Ach were significantly impaired in DIO Psgl-1 +/+ mice compared with standard chow-fed Psgl-1 +/+ mice (maximal relaxation, 36.0±7.8% vs 73.4±5.3%, p&lt;0.01). In contrast Psgl-1 -/- DIO mice were protected from endothelial dysfunction and were similar to Psgl-1 -/- mice on standard chow (maximal relaxation, 75.1±4.8% and 83.8±3.7%). Ach-induced vasorelaxation was completely inhibited in all groups in the presence of L-NAME. Endothelium-independent relaxation responses to SNP were similar in all groups. Mac-3 staining showed reduced macrophage content in mesenteric PVAT of DIO Psgl-1 -/- mice compared to DIO Psgl-1 +/+ mice (18.2±1.5% vs 30.0±2.6% , p&lt;0.01). Treatment of DIO Psgl-1 +/+ mice with a Psgl-1 antibody for 4 weeks resulted in Ach-induced relaxation of 71.6±10.9%, which was similar to Psgl-1 -/- DIO mice. Conclusions: Endothelial function and vascular NO bioavailability are impaired in a DIO mouse model. Psgl-1 deficiency is protective against PVAT inflammation and endothelial dysfunction induced by obesity. Psgl-1 inhibition may be useful for treatment of obesity-related vascular diseases.
Nocturnal Enuresis and Daytime Wetting: A Multicentric Trial with Oxybutynin and Desmopressin
Authors: P. Caione, F. Arena, M. Biraghi, R.M. Cigna, D. Chendi, M.L. Chiozza, A. De Lisa, E. De Grazia, M. Fano, P. Formica, S. Garofalo, R. Gramenzi, M. von Heland, P. Lanza, T. Lanza, S. Maffei, C. Manieri, E. Merlini, L. Miano, S. Nappo, A. Pagliarulo, F. Paolini Paoletti, A.C. Pau, D. Porru, G. Riccipetitoni, R.M. Scarpa, P. Seimandi, W. Artibani
Journal: European Urology (1997)
Efficacy Of a Pharmacokinetics-Directed IV Busulfan (Bu), Plus Cyclophosphamide (Cy) and Etoposide (E) Preparative Regimen With Autologous Hematopoietic Stem Cell Transplantation For Lymphoma: Final Report Of a Multi-Center Phase 2 Study In North America
Authors: Christopher R. Flowers, Michael Lill, Luciano J Costa, Tsiporah B. Shore, William Vaughan, Michael Craig, Cesar O. Freytes, Thomas C. Shea, Mitchell E. Horwitz, Joseph W. Fay, Shin Mineishi, Damiano Rondelli, James Mason, Vijay Reddy, Ira Braunschweig, Weiyun Ai, Elizabeth Armstrong, Angela Smith, Cathy Zhao, Agnes Elekes, Kazunobu Kato, Edmund K. Waller
Journal: Blood (2013)
Abstract 9230: Arrhythmias After the Fontan Operation; Which is Superior: Intracardiac Lateral Tunnel or Extracardiac Conduit? An International Multicenter Study of 1271 Patients
Authors: Seshadri Balaji, David J Bradley, Susan P Etheridge, Ian H Law, Anoop K Singh, Kelly K Gajewski, Harinder R Singh, Anjan S Batra, Sabrina Tsao, Svjetlana Tisma-Dupanovic, Shigeru Tateno, Motoki Takamuro, Hiromichi Nakajima, Shubayan Sanatani, Jolien W Roos-Hesselink, Maully Shah
Journal: Circulation (2012)

Background: Arrhythmias, both brady and tachyarrhythmias, are common after the Fontan operation for single ventricle. By avoiding surgery near the sinus node, reducing pressure overload of the right atrium (RA), and decreasing RA scarring, the extracardiac conduit (ECC) is thought to be less arrhythmogenic than the intracardiac lateral tunnel (ILT). Evidence of such superiority is, however, lacking or inconclusive. Methods: An international multi-center retrospective study of 1271 patients was performed comparing early and late bradyarrhythmia (defined as need for pacing) and tachyarrhythmia (defined as needing any acute or chronic anti-arrhythmic therapy) between 669 ECC and 602 ILT patients. Age at Fontan was ILT 2.8 +/- 2.2 vs ECC 3.5 +/- 2.2 (p&lt;0.0001). Results: In the early post-operative period, bradyarrhythmias requiring pacing were noted in 83 (11%) ECC patients vs 24 (4%) ILT patients (p &lt; 0.0001) and tachyarrhythmias were noted in 53 (8%) ECC patients vs 32 (5%) ILT (p=ns). At follow-up (FU) (ECC 4.8+/- 4 years Vs ILT 8.9 +/- 5.4, mean +/- SD p&lt;0.0001)), bradyarrhythmias were seen in 39 (6%) ECC vs 62 (10%) ILT (P &lt;0.003) and tachyarrhythmias in 23 (3%) ECC vs 58 (10%) ILT (p&lt; 0.0001). However, when length of FU was factored in, the incidence of brady and tachyarrhythmias did not differ between the 2 groups (p=ns). Conclusions: ECC has a higher incidence of early bradyarrhythmias. When length of FU is accounted for, late arrhythmia burden is similar between the two groups. Overall, the ECC does not appear to be less arrhythmogenic than the ILT. Therefore, the decision of which type of Fontan to perform may best be based upon individual patient anatomy, hemodynamic factors and surgeon preference rather than on a desired decrease in arrhythmia burden from the ECC.
Abstract 17209: Impact of Female Sex on Discontinuation Rates and Creatine Kinase Elevations in Atorvastatin Trials
Authors: Priscilla Hsue, Rana Fayyad, Rachel Laskey, John Betteridge, Vera A Bittner, Helen Colhoun, Nanette Wenger, David D Waters
Journal: Circulation (2013)

Objectives: We evaluated the impact of female sex on discontinuation rates and creatine kinase (CK) elevations in large clinical trials of atorvastatin (A). Methods: In IDEAL (A 80 mg vs. simvastat...
Abstract 18505: High-sensitive Troponin T Levels Independently Predict Survival in TAVI Patients
Authors: Derk Frank, Sophia Stark, Matthias Lutz, Anne Weissbrodt, Sandra Freitag-Wolf, Rainer Petzina, Mark Rosenberg, Georg Lutter, Norbert Frey
Journal: Circulation (2012)

TAVI (transcatheter aortic valve implantation) has become a valuable therapeutic tool in the treatment of inoperable or high risk patients with severe aortic stenosis. Several risk scores have been proposed to estimate the perioperative and long-term risk of patients undergoing TAVI. However, exact estimation of perioperative and long term risk remains difficult. We thus sought to investigate whether biomarkers may improve risk stratification in this setting. We included 111 consecutive patients undergoing TAVI (using Edwards Sapien and Sapien XT prostheses) at our institution from February 2011 until May 2012. 109 patients were available for complete follow up. 61% were females, mean age was 80.6 years (+/- 11.0 years), 55% were treated via transfemoral access. Since elevated troponin T levels have been associated with adverse outcome in various forms of cardiac disease, high sensitive troponin T (hsTNT) values and other parameters were measured a day before TAVI (baseline) and 1, 3, and 7 days post-procedure. Mean EF was 48.3% (+/- 10.3%) and mean logistic Euroscore 20.8% (+/- 13.1%). Mean follow-up was 163 days (+/-144 days), The primary endpoint was all-cause mortality and a total of 18 deaths (16.51%) occurred. 30 day mortality was 6.4% (7/109). Median baseline hsTNT values were 22.7 ng/ml with an interquartile range (IQR) of 12-47 ng/ml. Cox regression analyses including age, sex, procedural access site, NYHA class, renal function [creatinine], NTproBNP, STS score, and logistic Euroscore revealed only baseline hsTNT (HR for upper quartile 6.32 vs. quartiles 1-3, CI 2.15-18.55, p=0.001) and the baseline creatinine level (HR=1.89 per quartile, CI 1.02-3.48, p=0.043) as independent prognostic parameters for cumulative mortality. At 72 hours post-TAVI, hsTNT increased to a median of 178 ng/ml, IQR 88.7-361.52 ng/ml. hsTNT levels at day 3 were associated with adverse outcome, but did not offer additional prognostic information when compared to preprocedural hsTNT levels. However, the individual raise in hsTNT at day 3 is associated with the incidence of cumulative death (p=0.034). In conclusion, elevated hsTNT the day before TAVI is an independent risk predictor of all-cause death in TAVI patients.
Abstract 2484: The Prognostic Value of Doppler Echocardiographic Derived Coronary Flow Reserve is Not Affected by Concomitant Anti-Ischemic Therapy at the Time of Testing.
Authors: Rosa Sicari, Fausto Rigo, Sonia Gherardi, Lauro Cortigiani, Maria Luisa Gianfaldoni, Maurizio Galderisi, Ana Djordjevic-Dikic, Giovanni Ossena, Eugenio Picano
Journal: Circulation (2007)

Background: When wall motion abnormality is the diagnostic end-point, concomitant anti-ischemic therapy heavily modulates the prognostic value of dipyridamole echo test (DET). Coronary flow reserve...
Surgical Treatment of Invasive Penile Cancer - The Heidelberg Experience from 1968 to 1994
Authors: Drasko Brkovic, Tilman Kälble, Joachim Dörsam, Sigmund Pomer, Cornelia Lötzerich, Ramin Banafsche, Gerd Riedasch, Gerd Staehler
Journal: European Urology (1997)
Abstract 16914: Expression of Lamin Mutation p.R644C, The Most Common Known Cause of Cardiolaminopathies, Causes Cardiac Fibroblasts Senescence
Authors: Hwang-Hwan Song, Un-Ho Jin, Ju-Yun Tsai, Ali J Marian
Journal: Circulation (2011)

Background: Mutations in LMNA, encoding lamin A/C (LMNA), cause a diverse array of distinct phenotypes, including progeroid syndromes. The phenotype in the heart, referred to as cardiolaminopathies, typically manifests as early onset and progressive dilated cardiomyopathy (DCM), atrial bradyarrhythmias and conduction defects. The most commonly reported mutation in cardiolaminopathies is the p.R644C, which is located in the C-terminus. The domain is involved in progeroid syndromes. We posit that cardiolaminopathies caused by the p.R644C mutation represent non-syndromic premature cardiac aging. Methods and Results: We expressed wild type and mutant LMNA (LMNA-WT and LMNA-R644C, respectively) in cardiac fibroblasts isolated from adult mouse hearts using recombinant adenoviruses. Expression of LMNA-R644C was associated with blebbing of the nuclear membrane, a characteristic of progeroid syndromes. Co-immunopreciptation studies showed reduced binding of LMNA-R644C to its interactome proteins, namely retinoblastoma (Rb), lamin-associated protein 2α and protein phosphatase 2A, leading to reduced inactivation of Rb by hyperphosphorylation. Consequently, levels of Cdkn1a (P19) and Cdkn2d (P21), well-established inhibitors of cell cycle progression were increased and levels of Cyclin A2 and Cyclin B1, markers of cell cycle progression to mitosis, were reduced. In accord with cell cycle inhibition, proliferation rate of cardiac fibroblasts was decreased, as indicated by increased cell doubling time and reduced BrdU incorporation, while expression level of senescence-associated β-galactosidase, a marker for cell senescence was increased. Conclusions: Expression of LMNA-R644C mutation, the most common mutation found in cardiolaminopathies, impairs interactions among constituents of the LMNA/Rb/LAP2α/PP2A complex leading to hypophosphorylation of Rb, suppression of cell cycle progression and senescence of cardiac fibroblasts. We conclude that cardiolaminopathies represent non-syndromic premature cardiac senescence.
Abstract 14440: Alcohol Intake and Outcomes Following Coronary Artery Bypass Grafting
Authors: Umberto Benedetto, Giovanni Melina, Davide Sansone, Roberta Di Bartolomeo, Emiliano Angeloni, Simone Refice, Ivan Stigliano, Antonino Roscitano, Tommaso Hinna Danesi, Riccardo Sinatra
Journal: Circulation (2010)

Background: Light to moderate alcohol consumption has been consistently associated with a lower cardiovascular risk in apparently healthy people, but its effects among patients with established coronary heart disease are less clear. We aimed to investigate the impact of alcohol intake on risk of cardiovascular events after coronary artery bypass grafting (CABG). Methods and Results: Alcohol consumption was assessed in 1221 patients (median age 68 years[60-74]) undergoing CABG using a validated food-frequency questionnaire. Participants were followed after surgery for occurrence of major cardiac and cerebrovascular events (MACCE) including death, myocardial infarction, repeat revascularization and stroke. A Cox proportional hazards regression adjusted for all relevant risk factors including blood pressure and medications was used to assess the impact of alcohol intake on outcomes. After a median follow-up of 3.5 years, we documented 205 (17%) MACCEs . An inverse association (P trend=0.009) between alcohol ...
Medical omniscience
Authors: W G Pickering
Journal: BMJ (1998)

The incalculable number of medical problems and questions to which the medical profession has no certain answer is balanced by the incalculable number of times that its members none the less provide one. Many patients, not unnaturally, want definitive answers on diagnosis, prognosis, and side effects. When doctors are uncertain or do not know, they think that the patient should believe otherwise. An answer, any answer, it is felt, assuages the patient's fear and anxiety, as well as confirming a doctor's omniscience. Abating a patient's anxiety indubitably promotes their health, but what if the answers given are wrong?

Doctors can be comparatively certain about some matters—for example, uncomplicated appendicectomy or antibiotics for impetigo. They can give an educated guess about some others—for example, Bell's palsy, treated asthma—and have little idea about others—for example, the outcome of some major operations, the value of antidepressants, the side effects of many drugs. That they sometimes dissemble with their confident answers is an involuntary habit that can be medically dangerous, …
Abstract 15500: Dabigatran is Associated with Higher Risk of Myocardial Infarction or Acute Coronary Syndromes: a Meta-analysis of Non-Inferiority Randomized Controlled Trials
Authors: Ken Uchino, Adrian V Hernandez
Journal: Circulation (2011)

Introduction: The original RE-LY trial suggested a small increased risk of myocardial infarction (MI) with the use of dabigatran vs. warfarin in atrial fibrillation (Afib) patients. We systematical...
Safety of influenza A (H1N1) 2009 monovalent vaccines - United States, October 1-November 24, 2009.
Authors: K. Broder, C. Vellozzi, C. Weinbaum, Y. Zheteyeva, P. Tosh, A. Rao, S. Hocevar, D. Esposito
Journal: MMWR Morbidity and Mortality Weekly Report (2009)
Efficacy of Psychosocial Interventions in Inducing and Maintaining Alcohol Abstinence in Patients With Chronic Liver Disease: A Systematic Review
Authors: Anam Khan, Aylin Tansel, Donna L. White, Waleed Tallat Kayani, Shah Bano, Jan Lindsay, Hashem B. El-Serag, Fasiha Kanwal
Journal: Clinical Gastroenterology and Hepatology (2015)
Abstract 5998: Final Results of the HEALING 2B Trial to Evaluate a Bioengineered CD34 Antibody Coated Stent (Genous <sup>™</sup> Stent) Designed to Promote Vascular Healing by Capture of Circulating Endothelial Progenitor Cells in CAD Patients
Authors: H Duckers, Yoshinobu Onuma, Edouard Benit, Robert J de Winter, William Wijns, Manfred Grisold, Stephan Verheye, Sigmund Silber, Emmanuel Teiger, Jonathan Hill, Patrick W Serruys
Journal: Circulation (2008)

Background: In contrast to a cytotoxic or cytostatic pharmacotherapy, promoting the vascular healing response by capturing and sequestering circulating endothelial progenitor cells (EPC) to the stent surface by a CD34 antibody coating (Genous ™ stent) may accelerate stent reendo-thelialization and prevent restenosis formation, as well as stent thrombosis (ST) Methods: The HEALING IIB study was a multi-center, prospective trial designed to assess the safety and efficacy of the Genous ™ bio-engineered stent in conjunction with HmG CoA reductase inhibitors (statins) to stimulate EPC recruitment, in the treatment of patients with de novo coronary artery lesions (n=100 pts). The primary safety endpoint was major adverse cardiac events (MACE) at 30 days, whereas the primary efficacy endpoint was late luminal loss by QCA at 6 months follow-up. Results: At interim analysis of the first 45 patients that completed the 6-month angiographic follow-up, the composite MACE rate was 11.1%, whereas 6.6% clinically justified target lesion revascularizations were observed. 2 Patients died within the first 30 days after stent implantation due to angiographically verified stent thrombosis. Low circulating EPC titers were previously associated with a poor response to the EPC capture stent with TLR events and high late loss. Therefore, patients were pre-treated with Atorvastatin 80 mg qd prior to the PCI in order to augment EPC levels. Statin therapy stimulated the levels of committed EPCs by +294%, but failed to increase the titer of CD34+cells (+25%). Although statin pretreatment stimulated EPC levels, the angiographic outcome of the EPC capture stent was not improved in these patients: in-stent late luminal loss was 0.77±0.46 mm. We anticipate to complete analysis of the 6 month angiographic follow-up of all 100 patients by the time of the AHA2008. Conclusions: The HEALING-IIB study suggests that the EPC capture coronary stent in combination with statin therapy does not sufficiently impede stent restenosis formation for the treatment of de novo coronary artery disease. Although concomitant statin therapy was able to stimulate EPC recruitment, it failed to stimulate CD34+ stem cell levels and did not improve the angiographic outcome of the bioengineered EPC capture stent.
Abstract 14027: Xanthelasmata Predict Risk of Ischemic Heart Disease, Myocardial Infarction, and Overall Death in the General Population Independent of Cholesterol Levels
Authors: Mette Christoffersen, Ruth Frikke-Schmidt, Peter Schnohr, Gorm B Jensen, Børge G Nordestgaard, Anne Tybjærg-Hansen
Journal: Circulation (2010)

Objectives:  Xanthelasmata are cholesterol deposits of the eyelids which like atheromas are composed of macrophages that have taken up cholesterol and become foam cells. Because 50% of individuals with xanthelasmata are normolipidemic, this suggests that xanthelasmata may be an important cutaneous marker of underlying atherosclerotic disease independent of plasma cholesterol levels. We examined this hypothesis.   Methods:  Presence or absence of xanthelasmata was registered at baseline in 12,939 individuals from the Danish general population. Of these, 1,903 developed myocardial infarction (MI), 3,761 developed ischemic heart disease (IHD), and 8,663 died during up to 33 years of follow-up.   Results:  The cumulative incidence of IHD and MI as a function of age was increased in individuals with xanthelasmata compared to those without, and the proportion surviving was decreased (Figure 1). Xanthelasmata predicted multivariately adjusted hazard ratios for MI and IHD of 1.51 (95% CI, 1.26-1.81) and 1.40 (95% CI, 1.22-1.60), respectively. Multivariately adjusted hazard ratio for mortality in individuals with xanthelasmata was 1.17 (95% CI, 1.06-1.28). Adjustment was for all well-known cardiovascular risk factors including plasma cholesterol levels.   Conclusion:  In this prospective study of 12,939 individuals followed for up to 33 years we show that presence of xanthelasmata is an independent predictor of risk of MI, IHD, and early death. This suggests that other factors besides cholesterol levels, such as capillary leakage, characteristics of macrophages, or characteristics of intercellular matrix components, may predispose certain individuals to both xanthelasmata and to atherosclerotic disease and early death. In societies where other cardiovascular risk factors cannot be readily measured, presence of xanthelasmata may therefore be a useful predictor of underlying atherosclerotic disease.
Hyponatraemia after orthopaedic surgery
Authors: A. M Severn, C. Dodds, P Harrington, A. Marino, S. Krikler, M. Blakemore, O. A Mojiminiyi, B. Hoffbrand, N. Lane, K. Allen
Journal: BMJ (1999)

Editor—There are errors and omissions in Lane and Allen’s editorial about hyponatraemia1 and the subsequent responses in the eBMJ.2 The assumption that orthopaedic patients are badly managed has been robustly criticised by those who are insulted about allegations of poor care in this specialty.

What is it about the patients that may put them at risk? Firstly, orthopaedic patients probably represent the largest group of elderly patients undergoing major and emergency surgery. Secondly, many take non-steroidal anti-inflammatory drugs. Thirdly, the use of spinal anaesthesia may result in too much intravenous fluid being given to counteract the effects of sympathetic block. The discussion about the role of the angiotensin-renin system, though interesting, is not relevant to the pathogenesis of hyponatraemia in these circumstances. An old patient who takes non-steroidal anti-inflammatory drugs and receives too much free water while the adrenal axis is affected by a spinal block will probably have problems with sodium balance. The tragedy is that it takes a clinical disaster and an editorial to spell this out.

The adverse outcome that prompted the editorial was an example of a failed system. There are always several steps in a critical incident that lead to adverse outcomes. The solution is to have a failsafe system. We believe that protocols in fluid management have a role, and unless the junior medical staff understand fluid management (and recent changes in training can only make this harder to obtain) the job could be done by specialist nurses acting under the authority of senior medical staff. The issue then is which specialty these senior medical staff should be in: surgical, anaesthetic, or geriatric medicine?

Frail old women are nursed on busy surgical wards. They have their broken hips mended late in the evening and return to the wards when many of the nurses have gone home and the ones who remain are busy with high dependency nursing interventions on fitter patients having more radical surgery. Signs of hyponatraemia in such patients may be mistaken for postoperative confusion.

Notwithstanding its limitations and the expected criticism, we are pleased that the editorial has alerted the profession to the problem, even though we believe that the proposed solution is inappropriate. A system that fails to prevent progressive symptomatic hyponatraemia should not be further challenged by the use of hypertonic infusions but should be replaced.
Characterization of acinar airspace involvement in asthmatic patients by using inert gas washout and hyperpolarized 3helium magnetic resonance
Authors: Sherif Gonem, Steven Hardy, Niels Buhl, Ruth Hartley, Marcia Soares, Richard Kay, Rino Costanza, Per Gustafsson, Christopher E. Brightling, John Owers-Bradley, Salman Siddiqui
Journal: Journal of Allergy and Clinical Immunology (2015)