tbuckley/cabot-search huggingface dataset:
Clinical and pathologic predictors of locoregional recurrence (LR), distant metastasis (DM) and overall survival (OS) in patients treated with chemoradiation and mesorectal excision for locally advanced rectal cancer
Authors: P. Das, J. M. Skibber, M. A. Rodriguez-Bigas, B. Feig, P. M. Hoff, C. Eng, N. A. Janjan, S. Krishnan, L. M. Ellis, C. H. Crane
Journal: Journal of Clinical Oncology (2005)

3597 Background: Our goal was to identify predictive factors for LR, DM and OS in patients treated with chemoradiation and surgery for rectal cancer. Methods: Between 1989 and 2001, 470 patients with rectal cancer and no evidence of distant metastasis were treated with pre-operative (89%) or post-operative (11%) chemoradiation. Clinical T stage was ≤ T2 in 7%, T3 in 78%, T4 in 8% and unknown in 6%. Clinical nodal stage was N0 in 30%, N1–2 in 53% and unknown in 16%. Median radiation dose was 45 Gy (range 19.8–58.6 Gy), 97% received concurrent infusional 5-FU, and 65% received adjuvant chemotherapy. Median follow-up was 5.7 years (range 0.3–14.3 years). Results: The 5-year LR-free survival, DM-free survival and OS were 90%, 79% and 80% respectively. On univariate analysis, significant predictors of LR were gender, clinical T and N stage, and pathologic T and N stage. Significant univariate predictors of DM were circumferential extent of tumor, tumor mobility, lymphovascular invasion, perineural involvement, and pathologic T and N stage. Significant univariate predictors of OS were age, circumferential extent of tumor, distance from anal verge, tumor size, tumor mobility, anal canal involvement, lymphovascular invasion, perineural involvement, and pathologic T and N stage. On Cox multivariate analysis, pathologic T stage (HR 1.7, p=0.004) and pathologic N stage (HR 1.9, p=0.002) independently predicted for LR, and pathologic T stage independently predicted for DM (HR 2.1, p=0.001) and OS (HR 2.0, p=0.001). Conclusions: Pathologic T and N stage were the only independent predictors of LR, and pathologic T stage was the only independent predictor of DM and OS. Investigations of more aggressive adjuvant chemotherapy appear warranted in patients with pathologic stage T3/ T4 or N1/2. No significant financial relationships to disclose.
Keeping mum over child abuse
Authors: Raj Persaud
Journal: BMJ (2005)

Is media coverage of Munchausen syndrome by proxy putting children at risk? 

J ust before Christmas the media moved rapidly to cover the sensational story of the “controversial diagnosis” of Munchausen syndrome by proxy, coverage in which the main villains of the piece seemed to be paediatricians hell bent on destroying families. This followed a statement by the attorney general that there was “cause for concern” and that appeals could be made in 28 out of 297 cases after a review of cases of children taken into care in the wake of the quashing of the Angela Cannings' conviction for murder ( BMJ 2004;329: 1256).

On 20 December the Daily Telegraph devoted a full page to a first person account by Angela Cannings, who was released from prison a year ago after the Court of Appeal overturned her convictions for murdering two baby sons. Yet what this article, and the subsequent raft of media coverage, failed to report was that the vociferous campaigners against Munchausen syndrome by proxy, and their supporters in the press, had expected that hundreds of parents who had been jailed for convictions linked to this diagnosis would be released. The attorney general's statement to parliament made it clear that this …
Abstract 17761: PPARα is Essential for Cardiac Metabolic Adaptation to Chronic Hypoxia
Authors: Mark A Cole, Amira Abd Jamil, Elizabeth Sutton, Lisa Heather, Daniel Stuckey, Andrew Murray, Rhys Evans, Kieran Clarke
Journal: Circulation (2010)

We postulated that PPARα plays a role in the metabolic changes caused by hypoxia in the heart, and used high fat feeding and gene deletion to alter PPARα activity. Control mice (129EvSv, n = 82) were exposed to 3 weeks of normobaric hypoxia at 11% oxygen, or to normoxia. Half the mice were fed a high (55%) fat diet, and half were chow fed (7.5% fat).  In vivo  cardiac function was measured using cine MRI. Hearts were isolated and perfused to measure fatty acid oxidation and glycolytic flux using  3 H labeling. Hypoxia plus a high fat diet decreased cardiac output of control animals by 21% (p  −/−  mouse hearts (n = 70), cardiac metabolism and UCP3 expression were unaltered by hypoxia and/or high fat feeding. In conclusion, PPARα activation, using high fat feeding, increased cardiac fatty acid oxidation and UCP3 expression, and decreased glycolytic flux, which decreased ejection fraction during hypoxia. Deletion of PPARα prevented metabolic adaptation to hypoxia, and consequently impaired cardiac function. Therefore PPARα plays pivotal metabolic, and thereby functional, roles in the hypoxic heart.
Abstract 1450: Scar-Derived Nestin(+) Neural-Like Stem Cells Contribute to de novo Blood Vessel Formation in the Infarct Region
Authors: Viviane El-Helou, Cindy Proulx, Robert Clement, Hugues Gosselin, Louis Villeneuve, Angelino Calderone
Journal: Circulation (2006)

It has been shown that CNS- and follicle-derived neural stem cells can differentiate to an endothelial cell phenotype. The following study examined whether nestin(+) neural-like stem cells residing...
Abstract 6241: Proton Pump Inhibitors May Attenuate the Benefits of Clopidogrel among ACS Patients: Empirical Evidence from 3,311 ACS Patients
Authors: P. Michael Ho, Thomas M Maddox, Li Wang, Stephan D Fihn, Robert L Jesse, Eric D Peterson, John S Rumsfeld
Journal: Circulation (2008)

Background: A prior report showed omeprazole decreases platelet inhibitory effects of clopidogrel (clopid). However, the clinical impact of these findings is unknown. We studied outcomes of patients taking clopid alone versus clopid and proton-pump inhibitor (PPI) after acute coronary syndrome (ACS) in a national VA registry. Methods: This was a retrospective cohort study of 3,311 ACS patients discharged from 127 VA hospitals on either clopid alone or clopid+PPI based on pharmacy dispensing data. The main outcome was AMI/death. Cox proportional hazards regression models assessed the association between drug use as a time varying covariate and outcomes. Mean follow-up was &gt;1 year. During follow-up, patients could have gaps in their treatment and thus could be categorized as “no drugs” or “PPI-only” for short durations. Results: At discharge, 34% were prescribed clopid alone and 66% clopid+PPI. Baseline characteristics were quite similar (e.g. mean age 68.1 yrs for clopid vs 68.3 yrs for clopid+PPI) except clopid+PPI patients had less diabetes and more renal insufficiency. In multivariable analyses, clopid+PPI was associated with a higher risk of AMI/death risk compared to clopid alone (HR 1.28; 95% CI 1.07–1.53) (Figure ). Findings were consistent excluding patients with bleeding event during follow-up and using a nested case-control study design. Conclusion: Concomitant use of clopidogrel and PPI after ACS is associated with higher risk of adverse outcomes than clopidogrel use without PPI. These findings, coupled with the prior mechanistic study, suggest that concomitant PPI use attenuates the benefits of clopidogrel after ACS.
Stress CMR Imaging Observation Unit in the Emergency Department Reduces 1-Year Medical Care Costs in Patients With Acute Chest Pain
Authors: Chadwick D. Miller, Wenke Hwang, Doug Case, James W. Hoekstra, Cedric Lefebvre, Howard Blumstein, Craig A. Hamilton, Erin N. Harper, W. Gregory Hundley
Journal: JACC. Cardiovascular imaging (2011)
Abstract 19226: Inhibition of PKC-Delta Increases Cardiac Contractile Performance and Coronary Perfusion Following Cold Cardioplegic Arrest in Isolated Hearts.
Authors: Richard T Clements, Jun Feng, Cesario Bianchi, Frank W Sellke
Journal: Circulation (2010)

Introduction: Cardioplegia and cardiopulmonary bypass(CP/CPB) subjects myocardium to hypothermic reversible ischemic injury that impairs cardiac function (a.k.a — “myocardial stunning”). Protein ki...
Adjunctive surgery after chemotherapy for nonseminomatous germ cell tumors: recommendations for patient selection.
Authors: G C Toner, D M Panicek, R T Heelan, N L Geller, S Y Lin, D Bajorin, R J Motzer, H I Scher, H W Herr, M J Morse
Journal: Journal of Clinical Oncology (1990)

One hundred eighty-five patients who underwent surgery within 6 months of completing chemotherapy were identified from 360 patients with nonseminomatous germ cell tumors (NSGCT) treated with Memorial Hospital front-line cisplatin- or carboplatin-based combination chemotherapy protocols between 1979 and 1988. Clinical, pathologic, and radiologic features were correlated with the pathologic findings at surgery. The size of a residual retroperitoneal mass, the degree of shrinkage that occurred with chemotherapy, and the presence of teratomatous elements in pretreatment pathology specimens were each correlated with the pathologic findings of retroperitoneal resections after chemotherapy. Multivariable logistic regression analysis of those undergoing retroperitoneal resections identified the size and shrinkage of the residual mass and the prechemotherapy lactate dehydrogenase (LDH) and alphafetoprotein (AFP) levels as the best predictors of finding only necrotic debris. No factors could be found, however, that could selectively exclude patients who had residual viable malignancy or teratoma in the retroperitoneum. Of 39 patients with residual retroperitoneal masses measuring less than or equal to 1.5 cm in maximal diameter, three had residual malignancy and five had teratoma resected. No factors were identified for residual lung or mediastinal masses that could be used to select a group of patients who could safely avoid surgery. If serum markers have normalized after chemotherapy for NSGCT, resection of all residual abnormalities on imaging studies of the retroperitoneum, lungs, and mediastinum is recommended. In addition, retroperitoneal lymph node dissection (RPLND) is recommended for all patients with initial bulky metastases (greater than or equal to 3 cm in diameter) in the retroperitoneum, irrespective of the findings of postchemotherapy computed tomography (CT).
Abstract 15126: Adventitial Plaque Microvessels in Apoe-/- Mice Show Angiogenic Activity, Active Perfusion, Increased Leukocyte Adhesion and Permeability, and Reduced Blood Flow Velocity
Authors: Timo Rademakers, Kim Douma, Tilman M Hackeng, Mark J Post, Judith S Sluimer, Mat J Daemen, Erik A Biessen, Sylvia Heeneman, Marc A van Zandvoort
Journal: Circulation (2011)

Background Neovascularization of human atherosclerotic plaques is implicated in plaque progression and destabilization. We hypothesized that plaque microvessels exhibit specific functional characteristics, contributing to plaque development. Here, we studied functional properties of adventitial plaque microvessels in mice in vivo .

Methods Carotid arteries from aged ApoE-/- mice (>40 wks; n=45), age-matched C57Bl/6 mice (n=20) and young ApoE-/- mice (16 wks; n=8) were imaged using in vivo multiphoton laser scanning microscopy. Mice were injected with fluorescently labeled probes to label the vascular endothelium (anti-CD31) and assess angiogenic properties (cNGR). Fluorescently labeled dextrans, leukocytes and platelets allowed assessment of microvessel perfusion, permeability and blood flow velocity. Also, leukocyte adhesion to and extravasation from adventitial microvessels were determined.

Results Adventitial microvessels were found in close proximity of the atherosclerotic plaque in 87% of aged ApoE-/- mice, while absent in younger ApoE-/- and aged C57Bl/6 mice. Median diameter was 18.5 ± 0.4 and 5.9 ± 0.05 μm for 1st and 2nd order microvessels. In vivo imaging of adventitial microvessels showed angiogenic activity (cNGR). Co-injection of FITC-dextran and anti-CD31 confirmed active perfusion, and revealed increased permeability for 70 kDa, but not 150 kDa dextran. Blood flow velocity in adventitial microvessels was 0.14 ± 0.01 mm/s (mean ± SEM), representing a 50% lower flow velocity compared to control microvessels of equal diameter (0.30 ± 0.01 mm/s; p<0.005). Both adhesion (1.25 ± 0.26 vs. 0.22 ± 0.14 x10-2 cells/mm2/min, p<0.05) and extravasation (1.75 ± 0.37 vs. 0.29 ± 0.24 x10-2cells/mm2/min, p<0.05) of leukocytes were increased in adventitial microvessels compared to control microvessels.

Conclusion Plaques of aged ApoE-/- mice showed adventitial microvessels, which were angiogenically active and, albeit lowly, perfused. These microvessels showed increased permeability, decreased blood flow and flow velocity, yet increased leukocyte adhesion and extravasation. The increased leakiness and extravasation of leukocytes suggest an important role for adventitial microvessels in contributing to plaque progression.
Immunostaining for c-kit (CD117) in well differentiated and poorly differentiated neuroendocrine tumors
Authors: S. Della Torre, E. Bajetta, L. Ferrari, G. Procopio, P. Collini, L. Catena, R. Ricotta, P. Bidoli, A. Denaro, A. Martinetti
Journal: Journal of Clinical Oncology (2004)

9733 Background: The expression of c-kit, a receptor-associated tyrosine kinase, and its biological significance in solid tumor has been carefully studied in the last years. The c-kit overexpression seems to be associated with aggressive tumour types and poor outcome, and it may also be an important target for new anti-tumour drugs. We investigated the immunohistochemical (IHC) expression of c-kit (CD117) in neuroendocrine tumours (NETs) to evaluate its correlation with the grade and the proliferative index. Methods: Thirty-three formaline-fixed and paraffin-embedded tumour tissues from patients with diagnosis of NETs (22 well-differentiated tumours/carcinomas and 11 poorly differentiated carcinomas) were examined by IHC with a polyclonal antibody against c-kit (DAKO). The CD117 immunostaining was considered positive when strong and diffuse stain was present. The proliferative index was considered high if more than 70% of neoplastic nuclei were decorated. Results: Only 7/33 (21%) specimens were positive for c-kit expression (3 gastroenteropancreatic, 2 lung and 2 other localizations). Three tumours were strongly positive. 4/7 (57%) c-kit positive tumours were poorly differentiated carcinomas. C-kit was expressed in 36% and 13% of poorly and well-differentiated NETs, respectively. Most of the c-kit positive tumours showed a high proliferating index. Conclusion: The IHC positivity for c-kit is mainly related to poorly differentiated NET hystotipes. In our study, the percentage of c-kit positive tumours, both in well and poorly differentiated NETs, is significantly lower than that of previously published data. This difference could be accounted for the different IHC procedure and the different antibodies used. Before starting a targeted therapy with STI571, the c-kit positive tumours should be investigated to detect activating mutations. No significant financial relationships to disclose.
Abstract 11158: The Role of Repeat Procedures for Catheter Ablation of Ventricular Tachycardia with Non-Ischemic Cardiomyopathy
Authors: Michifumi Tokuda, Ioanna Kosmidou, Usha Tedrow, William Stevenson
Journal: Circulation (2011)

Background In patients with non-ischemic cardiomyopathy (NICM), ventricular tachycardia (VT) is associated with increased mortality and morbidity. Catheter ablation is useful for reducing VT therap...
Abstract 5284: In Vivo MRI Tracking of Cardiosphere-Derived Stem Cells in the Infarcted Rat Heart
Authors: Carolyn A Carr, Daniel J Stuckey, Jun Jie Tan, Dominic Sweeney, Damian J Tyler, Suat Cheng Tan, Emma E Carter, Enca Martin-Rendon, Suzanne M Watt, Kieran Clarke
Journal: Circulation (2008)

Cardiosphere-derived stem cells (CDCs) offer a potential therapy for the infarcted heart, but in vivo methods to confirm their successful administration and retention are required. Here we investig...
Placebo-controlled trial of fluoxetine as an adjunct to relapse prevention in alcoholics
Authors: H R Kranzler, J A Burleson, P Korner, F K Del Boca, M J Bohn, J Brown, N Liebowitz
Journal: American Journal of Psychiatry (1995)

The authors tested the hypothesis that fluoxetine, when used in combination with relapse prevention psychotherapy, directly reduces relapse frequency and severity for alcoholics.The authors conducted a randomized, placebo-controlled trial of fluoxetine (up to a maximum of 60 mg/day) for 12 weeks in combination with weekly psychotherapy for 101 alcohol-dependent subjects who were not selected on the basis of comorbid major depression. Outcomes were measured at the end of treatment and 6 months after treatment.Placebo-treated subjects were more complaint with the medication regimen and remained in the study longer than fluoxetine-treated subjects. There was significantly less alcohol consumption in both groups during treatment than before treatment. These effects persisted during the posttreatment period. Although fluoxetine treatment had no significant effects on alcohol consumption, it reduced Hamilton Depression Rating Scale scores more than placebo treatment among subjects with current major depression.Fluoxetine at a dose of 60 mg/day is probably not of use for relapse prevention in alcoholics with mild to moderate alcohol dependence and no comorbid depression. In alcoholics with major depression, the drug may reduce depressive symptoms. Subsequent studies with fluoxetine should probably focus on more severely alcohol-dependent subjects or those with comorbid depression.
Multiplex PCR for Virus Infections after Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Natsuko Inazawa, Tsukasa Hori, Masaki Yamamoto, Keita Igarashi, Hiroyuki Tsutsumi, Masanori Nojima, Nobuhiro Suzuki, Norio Shimizu, Naoki Hatakeyama
Journal: Blood (2014)
Abstract 4389: Right Ventricular Diastolic Function in Pulmonary Hypertension
Authors: Angel Lopez-Candales, Ananth Eleswarapu, Kathy Edelman
Journal: Circulation (2008)

Background : Left ventricular diastolic dysfunction is associated with worse outcomes in patients with severe chronic elevation in pulmonary artery systolic pressures (PASP); however, little is known if right ventricular diastolic dysfunction (RVDD) is also present in these patients. Methods : Color M-mode to measure RV propagation velocity (Vp) and tissue Doppler imaging (TDI) of the tricuspid valve annulus (TVa) were done in 21 patients (Group I: mean age 54 ± 15, mean PASP 80 ± 31 mmHg) and in 19 healthy individuals (Group II: mean age 51 ± 14 years, PASP 30 ± 7 mmHg). All subjects were in normal sinus rhythm and normal left ventricular systolic function. Results : Despite elevation in PASP, Group I RV systolic function measured by both TVa excursion (2.01 ± 0.7 cm) and TVa systolic velocity (0.10 ± 0.04 cm/s) were no different than Group II (2.5 ± 0.5 cm and 0.12 ± 0.03 cm/s, respectively). Even though there was no difference in either early (0.11 ± 0.04 versus 0.13 ± 0.04 cm/s) versus late (0.15 ± 0.05 versus 0.13 ± 0.04 cm/s) diastolic velocities by TDI; a lower Vp was seen in Group I (28 ± 12 cm/s) than Group II (41 ± 15 cm/s, p &lt; 0.01) with a significantly shorter diastolic interval (259 ± 90 versus 390 ± 80 ms, p &lt; 0.0001). Representative color M-mode images are shown in the Figure . Conclusions : Routine use of TVA TDI appears to be less useful than color M-mode to appreciate RV diastole as it shows a slower Vp with flows shifted later in diastole. In addition, these patients also demonstrate a shorter diastolic interval. Further studies are now required to prospectively assess the effects of pulmonary hypertension in clinical outcomes in patients manifesting RVDD. Figure. (A) Color M-mode image of a patient artery systolic pressures demonstrating predominantly early diastolic flow. (B) Color M-mode image from a patient with pulmonary hypertension showing predominantly late diastolic flow.
Abstract 13031: Novel Predictors of Left Ventricular Reverse Remodeling in Individuals with Recent Onset Dilated Cardiomyopathy
Authors: Milos Kubanek, Marek ramko, Dana Kautznerova, Petr Lupinek, Jana Vrbska, Ivan Malek, Josef Kautzner
Journal: Circulation (2012)

Purpose: We aimed to compare performance of contrast-enhanced cardiac magnetic resonance imaging (CMRI), biomarkers and endomyocardial biopsy (EMB) results with conventional methods of follow-up to...
Phase I/IIa trial of the novel microtubule inhibitor BAL101553 in advanced solid tumors: Phase I completed.
Authors: L Rhoda Molife, Georgios Imseeh, Marta Capelan, Fatima El-Khouly, Nicola Cresti, Alan David Smith, Dexter Averion, Noor Md. Haris, Sarah Jane Stimpson, Todd Gumbleton, Heidi A Lane, Felix Bachmann, Anne Schmitt-Hoffmann, Alexandar Tzankov, Alison L. Hannah, Stephanie Anderson, Ullrich Bette, Alan Hilary Calvert, Ruth Plummer, Rebecca Sophie Kristeleit
Journal: Journal of Clinical Oncology (2014)

2562 Background: BAL101553 is a prodrug of the small molecule BAL27862, a novel microtubule-targeting agent (MTA) with potent activity in tumor models refractory to conventional MTAs. Its anti-cancer activity is related to cytotoxic effects on tumor cells as well as vascular disruption at higher doses. A NSCLC xenograft mouse model demonstrated similar BAL27862 tumor exposure (AUC) at the MTD and a sub-MTD dose, with the lower dose resulting in higher peak intratumoral levels. Phase I objectives of this trial included determination of maximum tolerated dose (MTD) and dose-limiting toxicity (DLT), evaluation of pharmacokinetics, pharmacodynamics (PD) and anti-tumor activity. Methods: Eligible patients (pts) with advanced solid tumors, having failed standard therapy, received BAL101553 as a 2-h IV infusion on days 1, 8 and 15 of a 28-day cycle (accelerated dose-escalation). Adverse events (AEs) were assessed by CTCAEv4 grade (G); tumor response was assessed every 2 cycles by RECIST 1.1. Results: 24 pts (12 males; median age 54.5 years; range 29-80) were treated at 15, 30, 45, 60 or 80 mg/m2 of BAL101553. At 80 mg/m2, 2 out of 6 evaluable pts experienced a DLT of G2-3 gait disturbance (fully or partially reversible with follow-up ongoing) related to G1-2 peripheral neuropathy. 60 mg/m2 was defined as MTD with 1 DLT observed out of 6 pts (G3 reduced mobility with dizziness). Frequent drug-related AEs up to the MTD included injection site reactions, nausea, vomiting, diarrhea, fatigue, peripheral neuropathy (all G1-2) and asymptomatic hypertension (G2-3, transient during the infusion; responding to nifedipine). 1 confirmed partial response (ampullary cancer, for >2 years) and 5 stable diseases were observed, predominantly at sub-MTD doses. Reproducible exposure to BAL27862 was seen across all dose levels. Comparison of post- to pre-treatment tumor biopsies indicated PD effects on tumor cell proliferation and vascularization. Conclusions: BAL101553 is well tolerated up to the MTD of 60 mg/m2. As a lower dose may be preferred (providing cytotoxic and intermediate anti-vascular effects), treatment at MTD and a lower dose is being considered for the randomized Phase IIa part. Clinical trial information: NCT01397929.
Abstract 16871: Microscopic Systolic Pressure Alternans in Human Cardiomyopathy: Noninvasive Evaluation of a Novel Risk Marker and Correlation with Microvolt T wave Alternans
Authors: Raja J Selvaraj, Adrian M Suszko, Anandaraja Subramanian, Susanna Mak, Vijay S Chauhan
Journal: Circulation (2010)

Introduction: In patients with severe LV dysfunction, visible pulsus alternans accompanies visible T wave alternans, possibly due to abnormal intracellular calcium cycling. However, it is not known...
Abstract 16497: Characterization of ATP Binding Cassette Protein B8 (ABCB8) as a Mitochondrial Iron and Glutathione Exporter
Authors: Marina Bayeva, Yoshihiko Ichikawa, Mohsen Ghanefar, Vishnu Potini, Lin Sun, Kannan Mutharasan, Rongxue Wu, Jerry Kaplan, Hossein Ardehali
Journal: Circulation (2011)

Background: Mitochondrial iron is required for the synthesis of heme and Fe/S clusters, but can also be cytotoxic via production of reactive oxygen species (ROS). The process of mitochondrial iron ...