tbuckley/cabot-search huggingface dataset:
Abstract 18082: Left Atrial Strain in Normal Individuals is Influenced by Age and Left Atrial Volume: Implications for Evaluation of Atrial Function in Hypertensive Patients with Diastolic Dysfunction.
Authors: Marcello Chinali, Gerard P Aurigemma, Umar Khan, Jeffrey C Hill, Giovanni de Simone, Dennis A Tighe, David McManus
Journal: Circulation (2010)

Background:  LA size is a potent predictor of cardiovascular risk. Less is known about the prognostic value of LA function, however. We have shown that left atrial (LA) strain (e LA ), a descriptor of LA reservoir function, is reduced in hypertensives (HTN). However, e LA  , might deteriorate with age and decrease at higher LA volumes. Our goal was to derive a model for e LA  which took age and LA size into account, so as to more precisely diagnose LA dysfunction.   Methods:  100 healthy volunteers (NLS; 50±15yrs; 58 women) underwent standard echocardiography with evaluation of diastolic function, LA volume (area-length) and e LA  by speckle tracking (STI) (GE). Multivariate models were derived from NLS to generate regression equations that were tested in 50 HTN with grade 1–2 diastolic dysfunction (76±14yrs; 72%females) without significant valvular disease.   Results:  Reduced LA function was defined as e LA   th  percentile in normals). In stepwise multiple regression, as hypothesized, e LA  was significantly and inversely associated with age (β=−0.29: p LA  (e LA 	-c): e LA_ c=e LA +0.198x(age-50)+0.155×(LAvol)-4, where LAvol is unadjusted LA volume in mL. We then repeated the analysis using this ‘corrected’ e LA -c, with a partition value of  th  percentile). Prevalence of reduced LA function was significantly higher in HTN as compared to NLS by both classifications (p LA , prevalence of LA dysfunction was significantly lower by e LA -c (16% vs 47%; p   Conclusions:  Atrial function by e LA  decreases physiologically with ageing and increasing LA size. These associations should be taken into account when evaluating LA reservoir function. We speculate that e LA -c might conceivably refine cardiovascular risk prediction of LA size.   Graph:  Prevalence of reduced atrial function by unadjusted and adjusted LA strain.
Abstract 9411: Urine Aquaporin-2 Level is a Novel Marker for the Better Prognosis After Long-Term Tolvaptan Treatment in Patients With Advanced Heart Failure
Authors: Teruhiko Imamura, Koichiro Kinugawa, Takeo Fujino, Toshiro Inaba, Hisataka Maki, Maasaru Hatano, Atsushi Yao, Issei Komuro
Journal: Circulation (2014)

Introduction: Preserved function of collecting duct is essential for the response to tolvaptan (TLV), and urinary level of aquaporin 2 (U-AQP2) can be a marker for vasopressin-dependent activity of collecting duct. Hypothesis: Higher levels of U-AQP2 in proportion to plasma levels of vasopressin (P-AVP) may be associated with better initial responses to TLV and eventually result in the improved prognosis after long-term treatment of TLV. Methods: Consecutive 60 in-hospital patients with stage D heart failure (HF) who received TLV on a de novo basis were enrolled during 2011-2013. We also selected 60 HF patients by propensity score matching who were hospitalized during the same period but never treated with TLV. Events were defined as death and/or HF re-hospitalization. Results: TLV (3.75-15 mg/day) was continuously administered except death or ventricular assist device implantation occurred. There were 41 patients (group 1) who had increases in UV over the first 24 h after TLV initiation, and all of them had U-AQP2/P-AVP ≥0.5 х103 with higher U-AQP2 levels (5.42 ± 3.54 ng/mL) before TLV treatment. On the other hand, UV rather decreased even after TLV initiation in 19 patients over the first 24 h (group 2). Those in the group 2 universally had U-AQP2/P-AVP &lt;0.5 х103, extremely low U-AQP2 levels (0.76 ± 0.59 ng/mL, p&lt;0.001 vs. group 1), and similar P-AVP with the group 1 at baseline. The 41 and 19 patients without TLV treatment (group 3 and 4) were respectively matched to the group 1 and 2 by propensity scores. Interestingly, every patient in the group 3 had U-AQP2/P-AVP ≥0.5 х103, and vice versa in the group 4. Among the four groups, congestion-related symptoms were only improved in the group 1 after 1 month of enrollment. The patients in the group 1 had significantly better event-free survival over 2-year by TLV treatment compared with the group 3 (76% vs. 43%, p&lt;0.014). In contrast, the patients in the group 2 and 4 had very poor prognoses regardless of TLV treatment (7% vs. 11%, p=0.823). Conclusions: U-AQP2/P-AVP is a novel predictor for the initial response to TLV in HF patients. Patients with higher U-AQP2/P-AVP may enjoy a better prognosis by long-term TLV treatment probably due to efficient resolution of congestion.
Aspirin for primary prevention
Authors: L. E Ramsay, P. S Sanmuganathan, E. J Wallis, P. R Jackson, A. Alkhenizan
Journal: BMJ (2000)

<h3>BACKGROUND</h3> Patients with cystic fibrosis (CF) have many risk factors for reduced bone mineral density (BMD). The aim of this study was to determine the prevalence of osteoporosis and osteopenia in a large cross section of patients and to identify risk factors. <h3>METHODS</h3> All patients attending the regional centre were invited to participate in the study. Bone mineral density was measured at the lumbar spine, femoral neck, and for total body with a Lunar DPX-L densitometer. Multiple indices of disease severity were investigated, and liver and thyroid function, blood calcium, phosphate, 25-OH vitamin D, follicle stimulating and luteinising hormone, oestradiol, and testosterone levels were measured. Patients completed a four day prospective dietary diary. Exercise was assessed by a seven day activity recall questionnaire. Sexual development and treatment histories were obtained. The relationship between all these variables and BMD measurements was analysed. <h3>RESULTS</h3> Sixty six percent of 114 patients assessed had osteopenia or osteoporosis. The Shwachman-Kulczycki (SK) clinical score (higher score = less severe disease) correlated significantly with BMD at the lumbar spine and femoral neck, and with total body BMD (p&lt;0.001). There was a predicted increase of 0.0032 g/cm<sup>2</sup> in lumbar spine BMD for every unit increase in the SK score. Oral steroid use was significantly associated with reduced BMD at the lumbar spine (p = 0.017) and femoral neck (p = 0.027). <h3>CONCLUSIONS</h3> Osteopenia and osteoporosis are common findings in a heterogeneous population of adults with CF. Patients at most risk are those with severe disease and those who have used corticosteroids.
Abstract 3502: First in Man Transendocardial Injection of Autologous Aldehyde Dehydrogenase-Bright Cells in Heart Failure Patients (FOCUS-Bright)
Authors: Emerson C Perin, Guilherme V Silva, Yi Zheng, Marlos R Fernandes, Warren Moore, Stephanie Coulter, Sandi Shaw, Deirdre Smith, Lynette Westbrook, John Canales, Xin Quan, Cristiano Cardoso, Maria G Cabreira, Fred Baimbridge, Amir Gahremanpour, Dia Tisdel, Casey Kappenman, Dipsu Patel, Laurence H Keller, James T Willerson
Journal: Circulation (2009)

Background: Stem cell therapy has been investigated in ischemic heart failure (IHF) patients. Although several clinical studies have utilized autologous bone marrow (BM) mononuclear cells, it is un...
Patients' trust must be respected
Authors: G. Ness
Journal: BMJ (1995)

EDITOR,—When I empathised with the patient in the medicolegal case discussed by John Mitchell and others (that is, I considered what I might feel if I were her) I felt that I too would have been perturbed.1 Putting aside complex issues of consent, I hope that a simple emphatic account of her experience and a comment may elucidate the core problem of her complaint.

“As a married woman of 22, I went in for a straightforward tooth extraction, …
Abstract 43: Comparative Study of Survival After In-Hospital Cardiac Arrest in Patients with Chagas Cardiomyopathy and Idiopathic Dilated Cardiomyopathy
Authors: Maria Margarita Gonzalez, Caio B Vianna, Renan Gianotto-Oliveira, Sergio Timerman, Roberto Kalil Filho
Journal: Circulation (2012)

INTRODUCTION: Chagas Cardiomipathy, among all causes of cardiac insufficiency, appears to be what brings the worst prognosis. The evolution of these patients after in-hospital cardiac arrest is not adequately evaluated in the medical literature. METHODS: To this propose, from April 2004 to June 2008, Utstein-style data, were prospectively collected from 1027 consecutive in-patient adult index cardiac arrests in an observational, single-center study at a tertiary cardiac care hospital. Of them, 715 (77%) patients performed echocardiograms during admission or until three months pre arrest. We compare the evolution of hospital patients with moderate or severe systolic dysfunction (LVEF &lt;45%) and diagnosis of Chagas Cardiomyopathy (74 patients) and Idiopathic Dilated Cardiomyopathy (74 patients), by univariate and multivariate (logistic regression). The primary end-point was survival to discharge. Secondary outcomes were return of spontaneous circulation for more than 20 minutes, 24-hour survival after cardiac arrest, and discharged with satisfactory neurological evaluation, defined as cerebral performance category 1 or 2. RESULTS: Survival to discharge was 15% in patients with Idiopathic Dilated Cardiomyopathy compared with 4% in patients with Chagas Cardiomyopathy (after logistic regression; “odds ratio” adjusted = 0.89, 95% CI, 0.09 to 0.907, P &lt;0.001). Another factor associated with lower hospital survival was use of atropine during resuscitation. The rhythm of VF /VT pulseless as the initial rhythm of arrest was associated with higher hospital survival. Both groups did not differ regarding return of spontaneous circulation (54% vs. 58%, P = 0.468), 24-hour survival (39% vs. 41 %, P =0.550), or survival with CPC 1 or 2 (100% vs. 91%, P =0.660). CONCLUSION: As hypnotized, Chagas Cardiomiopathy was associated with lower rates of survival to hospital discharge, despite similar rates of sustained return of spontaneous circulation and 24-hour survival post-arrest. Peculiarities of Chagas Cardiomyopathy associated with myocardial dysfunction, hyperadrenergic state, postresuscitation inflammatory response seem to contribute strongly to this development more unfavorable.
A Phase III Study Of Enzastaurin In Patients With High-Risk Diffuse Large B Cell Lymphoma Following Response To Primary Treatment: The Prelude Trial
Authors: Michael Crump, Sirpa Leppä, Luis E Fayad, Je-Jung Lee, Alice Di Rocco, Michinori Ogura, Hans Hagberg, Frederick Schnell, Robert M Rifkin, Andreas Mackensen, Fritz Offner, Lauren Pinter-Brown, Sonali M. Smith, Kensei Tobinai, Su-Peng Yeh, Jun Zhu, Marjo Hahka-Kemppinen, Donald Thornton, Peipei Shi, Boris Lin, Brad S. Kahl, Norbert Schmitz, Kerry J. Savage, Thomas M Habermann
Journal: Blood (2013)
2-Year Results of CoreValve Implantation Through the Subclavian Access
Authors: Anna Sonia Petronio, Marco De Carlo, Francesco Bedogni, Francesco Maisano, Federica Ettori, Silvio Klugmann, Arnaldo Poli, Antonio Marzocchi, Gennaro Santoro, Massimo Napodano, Gian Paolo Ussia, Cristina Giannini, Nedy Brambilla, Antonio Colombo
Journal: Journal of the American College of Cardiology (2012)
Abstract 3777: High Rates of Recidivism in Patients Presenting to a Chest Pain Unit: Incidence, Patient Profiles and Outcomes in a Total Cohort of Over 3,000 Patients
Authors: Adam Kupersmith, Deborah B Diercks, Erin Madriago, Larry Baker, J D Kirk, Ezra A Amsterdam
Journal: Circulation (2007)

Background: There are minimal data on the magnitude of recidivism and clinical course in patients (pts) with multiple negative evaluations (NE) for acute coronary syndrome (ACS) in a chest pain unit (CPU). Methods: We identified pts with multiple NE in our CPU to determine the incidence, clinical characteristics and ultimate outcomes of this group. Results: During a 7.5 year interval, 3,432 pts were admitted to our CPU of whom 2,249 (66%) had NE. Multiple (≥ 2) NE occurred in 13% (289/2,249) of these pts but they accounted for 26% (696/2656) of total NE. Of the multiple NE pts, 261 (90%) had 2–3 NE and 28 (10%) had ≥ 4 NE (mean 2.7). Characteristics of pts (n=289) with multiple NE: age 52 yr, 54% (156/289) women, 14% (40/289) known coronary artery disease (CAD), 59% (169/289) ≥ 2 risk factors, 65% (188/289) uninsured, 58% (169/289) non-White. During 11.5 yr follow-up, 25% (72/289) of multiple NE pts had a major clinical event (MCE) (2.2%/yr): all-cause mortality 11% (31/289), ACS 8% (24/289), revascularization 10% (28/289), cardiac failure 10% (29/289). Mean time to MCE was 5 yr. MCE was associated with age ≥ 65yrs (47% of 43 pts had MCE), positive insurance (52% of 101), and known CAD (53% of 40 pts) (all p &lt;0.01). Conclusions: Our findings indicate that pts with multiple NE in a CPU accounted for a disproportionate number of all NE one-fourth developed a MCE during longterm follow-up, the majority of which were temporally remote from initial NE, and included 1% annual mortality MCE were associated with older age, known CAD and positive insurance status. NE pts with the latter characteristics may warrant earlier and more aggressive management.
Abstract #877: Tamoxifen rescues the ovarian follicular reserve following exposure to multiple classes of ovotoxic drugs including cancer chemotherapy.
Authors: Alison Ting, Brian Petroff
Journal: Cancer Research (2009)

Over 400,000 premenopausal women are diagnosed with cancer each year in the US. 50-80% of patients that receive cytotoxic chemotherapy suffer premature ovarian failure and infertility due to a rapid and permanent loss of ovarian follicles. Chemotherapy-induced ovarian damage was previously viewed by physicians and cancer patients as an acceptable cost of curative chemotherapy and radiation regimens. However, as more women survive their cancers and strive to resume normal family life, sterilization and premature menopause from cancer therapy has become a major survivorship issue. Currently embryo freezing and GnRH suppression are the only options to preserve fertility and each has significant limitations. Recently, we serendipitously discovered a protective effect of the selective estrogen receptor modulator tamoxifen against the destruction of oocytes by toxic chemicals. To explore this novel ovoprotective property of tamoxifen further ,  5-week-old rats received placebo or tamoxifen pellets (5mg) followed by weekly injections of vehicle, 7,12-dimethylbenzanthracene (DMBA, a well characterized ovotoxicant; 10mg) or cyclophosphamide (Cy, the most ovotoxic cancer drug; 50mg/kg). Following 2 or 4 weeks of DMBA or Cy treatment, respectively, ovaries were collected and processed for histological evaluation.  In vitro , ovulated oocytes were incubated with doxorubicin (another ovotoxic cancer drug), with or without the active metabolite of tamoxifen, 4-hydroxytamoxifen for 24 hours. In an organ culture experiment, postnatal day 4 ovaries were treated with DMBA or vehicle with or without 4-hydroxytamoxifen for 7 days and processed for histological examination. Follicle populations were classified and counted in every 10 th  sections of the ovaries obtained from  in vivo  and organ culture studies. For cultured oocytes, morphological changes indicative of apoptosis were examined. Both  in vivo  and  in vitro  studies confirmed that primordial and total follicles are depleted by DMBA and Cy (p in vivo  and  in vitro  studies. Tamoxifen may provide a novel and safe molecular shield to the ovary against chemotherapy-induced infertility in young cancer patients. Clinically, tamoxifen has already been tested for safe first-line use for several cancers allowing these observations to be readily translated from bench to bedside.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 877.
Human Cytokine-Induced Memory-Like (CIML) NK Cells Exhibit Potent Anti-Leukemia Cytotoxicity and Maintain Memory-Like Functionality After Adoptive Transfer Into Immunodeficient NOD-SCID-Gc-/- (NSG) Mice
Authors: Rizwan Romee, Jeffrey W Leong, Stephanie E Schneider, Ryan P Sullivan, Megan Cooper, Todd A. Fehniger
Journal: Blood (2013)
Abstract 2316: Myocardial PAI-1 Over-expression Mediates Graft Sclerosis in Cardiac Transplant Recipients with Idiopathic Dilated Cardiomyopathy
Authors: Seyedhossein Aharinejad, Katharina Krenn, Romana Schäfer, Andreas Zuckermann, Patrick Paulus, Michael Grimm
Journal: Circulation (2007)

Idiopathic dilated cardiomyopathy (DCM) is associated with reduced myocardial vascular density and increased collagen deposition with subsequent myocardial fibrosis and heart failure. The urokinase plasminogen activator (uPA)/plasminogen activator inhibitor (PAI) system plays an important role in extracellular matrix homeostasis as well as in preserving the integrity of the vascular endothelial cell (EC) intimal layer and EC regeneration, proliferation and motility. However, the involvement of the uPA/PAI system in DCM and graft remodeling following cardiac transplantation remains unclear. Gene expression of uPA, the uPA receptor uPAR and PAI-1 was examined in left ventricular (LV) biopsies of explanted hearts in 24 ischemic cardiomyopathy (ICM) and 60 DCM patients and 12 controls by real time RT-PCR and Western blotting. Vascular endothelial growth factor (VEGF) and uPA/PAI interplay was examined in stimulated DCM and ICM myocardium in vitro. Expression of uPA and PAI-1 mRNA was evaluated in endomyocardial biopsies (EMB) at 1, 2, 3, 4, 7, 12, 24 and 52 weeks post-transplant. The mRNA levels of uPA and uPAR were unchanged in both ICM and DCM patients compared to controls. PAI-1 mRNA and protein were up-regulated in DCM compared to ICM and controls (p&lt;0.01). Active and inactive uPA protein was down-regulated in DCM and ICM compared to controls (p&lt;0.05). VEGF stimulation in vitro did not affect uPA, uPAR or PAI-1 expression. Following transplantation, PAI-1 expression returned to baseline control levels in EMB from both patient groups, although PAI-1 expression increased at 24 and 52 weeks post-transplant in DCM patients (p&lt;0.01 compared to post-transplant weeks 6 and 12). These data indicate a significant PAI-1 up-regulation associated with uPA down-regulation in DCM, independent of VEGF, which was temporarily corrected by cardiac transplantation. However, recurring up-regulation of myocardial PAI-1 levels at 6 and 12 months post-transplant suggest a persistent PAI-1-related molecular pathology in DCM. We have previously shown increased endothelin-1 expression and collagen deposition in grafts of DCM patients at 1 year post-transplant. The present data point to a previously unknown role of PAI-1 in mediating graft sclerosis.
Regulating the surface poly(ethylene glycol) density of polymeric nanoparticles and evaluating its role in drug delivery in vivo
Authors: Xiao-Jiao Du, Ji-Long Wang, Wei-Wei Liu, Jin-Xian Yang, Chun-Yang Sun, Rong Sun, Hong-Jun Li, Song Shen, Ying-Li Luo, Xiao-Dong Ye, Yan-Hua Zhu, Xian-Zhu Yang, Jun Wang
Journal: Biomaterials (2015)
Abstract 14155: Xbp1 Splicing is Crucial in Endothelial Cell Proliferation
Authors: lingfang zeng, Qingzhong Xiao, Hongling Li, Andriana Margariti, yanhua hu, Qingbo Xu
Journal: Circulation (2010)

The X-box binding protein 1 (XBP1) is an endoplasmic reticulum stress response transcription factor. Our previous study revealed that sustained activation of XBP1 splicing led to atherosclerosis de...
Abstract 3673: Metabolism Of Advanced Glycation End Products (AGEs) By The Polyol Pathway Enzyme - Aldose Reductase Decreases AGE Accumulation In Diabetes
Authors: Shahid P Baba, Oleg Barski, Yonis Ahmed, Timothy O’Toole, Daniel J Conklin, Aruni Bhatnagar, Sanjay Srivastava
Journal: Circulation (2008)

Diabetes is a major risk factor for cardiovascular disease. Diabetes induces endothelial dysfunction and nephropathy, and accelerates atherogenesis. Metabolic changes in diabetes include activation of the polyol pathway and protein kinase C and the accumulation of advanced glycation end products (AGEs). The relationships between these pathways are; however, unclear. Increased formation and accumulation of AGEs, in particular, has been linked to the stimulation of inflammatory pathways and the development of secondary diabetic complications. Herein, we report that aldose reductase (AR) metabolizes AGE precursors in the heart and in endothelial cells. Human umbilical vein endothelial cells (HUVEC) cultured in high (25 mM) glucose were found to accumulate intracellular AGEs resulting in increased glycation of the heat shock protein (HSP27).  In vitro  several aldo-keto reductases catalyzed the reduction of AGE precursors although highest catalytic efficiency was observed with AR. Methylglyoxal (MG)-treated HUVEC or hearts perfused with MG generated a reduced product which was identified as acetol by GC/MS analysis. Acetol formation and the generation of AGEs in HUVEC were prevented by treatment with AR inhibitors sorbinil (48±3%; P
Abstract 211: A novel FRET assay for the intracellular activation of ADC linkers
Authors: Byoung-Chul Lee, Cecile Chalouni, Sam Nalle, Sophia Doll, Martine Darwish, Ira Mellman, Richard Vandlen
Journal: Cancer Research (2015)

Abstract Evaluating the intracellular activation of ADC by a novel FRET assay. Despite the recent success of ADCs as cancer therapeutics, their mechanisms of action are not fully understood. In this study, we developed ADCs using a novel fluorescence resonance energy transfer (FRET) linker in order to facilitate monitoring the details of intracellular uptake, vesicular trafficking and payload release. In the FRET linker, the cathepsin-cleavable dipeptide of val-cit was inserted between a fluorescence donor Alexa Fluor 488 (or later, fluorescein) and an acceptor tetramethylrhodamine (TAMRA). Upon cleavage of the val-cit linker, a fluorescence signal from Alexa Fluor 488 or fluorescein is expected to appear as a probe for monitoring intracellular activation of ADC. We used two in-vitro human cancer cell lines, SKBR3 and PC3. SKBR3 is a Her2-positive breast cancer cell line and PC3 is a prostate cancer cell line that has been engineered to express a prostate cancer-specific growth factor receptor, tomoregulin-2 (TenB2). We assessed the intracellular processing of the FRET conjugates using flow cytometry. We found that 74% and 41% of the linker was cleaved in PC3 and SKBR3 cells after 20 hours of treatment, respectively. In the live-celling imaging of the FRET probe in SKBR3 and PC3 cells, Anti-Her2 and TenB2 FRET ADCs showed a remarkable difference of internalization pathways and cleavage following receptor-mediated endocytosis. In PC3 cells, FRET ADCs were internalized and congregated into a certain localized area during the early stage of uptake in 2 to 3 hours. The ADC-containing vesicles were spread over the cytosol and near the plasma membrane in a subset of cells. A similar directed localization at the early stage of uptake was not observed for the SKBR3 cells. The endosomal vesicles in SKBR3s were spread over the cytosol during the course of ADC internalization. The amount of the release payload in the cytosol of SKBR3s was 3-fold greater than that of PC3 cells, suggesting that the endosomal/lysosomal membrane of SKBR3 may be more permeable than that of PC3. In summary, our ADC FRET probes allowed for the facile, robust and non-invasive evaluation of intracellular processing for ADC linkers. Quantitative measurements for the rate of antigen-mediated intracellular cleavage of the FRET linker as well as cytosolic release could be evaluated by our FRET probes. Citation Format: Byoung-Chul Lee, Cecile Chalouni, Sam Nalle, Sophia Doll, Martine Darwish, Ira Mellman, Richard Vandlen. A novel FRET assay for the intracellular activation of ADC linkers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 211. doi:10.1158/1538-7445.AM2015-211