tbuckley/cabot-search huggingface dataset:
Myocardial Ischemia — Silent or Symptomatic
Authors: Stephen E. Epstein, Arshed A. Quyyumi, Robert O. Bonow
Journal: New England Journal of Medicine (1988)

ALTHOUGH "silent ischemia" has recently captured the imagination of investigators and physicians, it is by no means a new concept. One of Holter's two earliest publications included ambulatory electrocardiographic recordings depicting asymptomatic episodes of spontaneously occurring ST-segment depression.1 In addition, ST-segment depression, appearing in the absence of angina pectoris, was recognized during electrocardiographic exercise stress testing as early as the 1930s,2 and ischemic electrocardiographic changes occurring during exercise stress testing have long been routinely used for diagnostic and prognostic purposes without reference to the presence or absence of accompanying angina.3 , 4 Nonetheless, silent ischemia has recently emerged as a topic of . . .
Abstract 2753: The addition of low dose 17-DMAG to BIBW-2992 effectively inhibits lung cancer cells with acquired resistance by T790M mutation
Authors: Jin Kyung Rho, Yun Jung Choi, Sun Ye Kim, Chang-Min Choi, Jae Cheol Lee
Journal: Cancer Research (2012)

Abstract The majority of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is caused by secondary T790M mutation. We established gefitinib or erlotinib-resistant cells which acquired different proportions of T790M from PC-9 cells with activating EGFR mutation. Anti-cancer effects of EGFR modulation and strategies overcoming resistance were investigated. The amount of T790M and EGFR gene copy number were proportional to increase of resistance. BIBW-2992, an irreversible EGFR-TKI, could suppress the growth and survival of cells harboring lower level of T790M while it failed in cells with higher level of T790M although p-EGFR was completely down-regulated in both, suggesting blocking of phosphorylation of EGFR is not sufficient to inhibit these cells. However, EGFR siRNA treatment could inhibit cell growth regardless of T790M level and resistance showing that EGFR dependency would be persistent. 17-DMAG, a HSP90 inhibitor, also effectively controlled both resistant cells. Considering a report showing that a HSP90 inhibitor was not clinically effective possibly because of inadequate dose, the efficacy of low dose 17-DMAG was examined. Interestingly, we found that combined treatment of BIBW-2992 with low dose 17-DMAG was very effective even in cells with higher level of T790M although either of both showed no activity in single treatment suggesting it would be one of promising strategies with immediate clinical implications overcoming T790M-mediated resistance. Further investigations on exact mechanism should be pursued even though capability of HSP90 inhibitor to modulate NF-kB signaling can be one of possible explanations. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2753. doi:1538-7445.AM2012-2753
Screening Program Raises Questions on Tumor Marker's Use, Regulation
Authors: T. Reynolds
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Screening Program Raises Questions on Tumor Marker's Use, Regulation Get access Tom Reynolds Tom Reynolds Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 6, 17 March 1993, Pages 424–427, https://doi.org/10.1093/jnci/85.6.424 Published: 17 March 1993
Abstract 712: Parf-1A (Partner of ARF isoform 1A) promotes oxaliplatin resistance and is a new prognostic marker of survival in pancreatic ductal adenocarcinoma
Authors: Viviane P. Muniz, Xuefeng Zhang, Sara M. Reed, Van S. Tompkins, Tarik Smith, Jussara KF Hagen, Matthew Fitzgerald, Anna Button, Brian Smith, Kokou D. Zamba, Frederick E. Domann, James J. Mezhir, Jamie Weydert, Ryan A. Askeland, Dawn E. Quelle
Journal: Cancer Research (2012)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is an incurable malignancy with ineffective treatments and dismal median survival. The INK4a/ARF locus, which encodes the alternative reading frame (ARF) tumor suppressor, is commonly inactivated in PDAC tumors. We recently discovered Parf-1A, a novel “Partner of ARF” whose role in ARF signaling and tumorigenesis is not known. Parf-1A is highly expressed in the normal pancreas and microarray databases suggest Parf expression is altered (both up- and down-regulated) in human PDAC tumors. We generated Parf-1A specific antibodies and examined its protein levels by immunohistochemistry in PDAC tumors from patients who underwent resective surgery. Parf-1A expression was altered in 72% of tumors (33% reduced, 39% elevated) compared to adjacent normal ductal tissue. Tumors with the highest Parf-1A levels were significantly associated with poor patient outcome (median survival 6 months) while patients with undetectable Parf-1A in tumors had a dramatically extended lifespan (median survival 59 months, p=0.0037). Notably, Parf-1A knockdown in cultured PDAC cells increased the p53-independent growth inhibitory activity of ARF. Parf-1A loss also sensitized PDAC cells to oxaliplatin, a chemotherapeutic agent used in combination with gemcitabine to treat PDAC patients. This work identifies Parf-1A as a new inhibitor of ARF p53-independent activity that promotes PDAC chemoresistance in vitro and is a novel prognostic marker of survival in PDAC patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 712. doi:1538-7445.AM2012-712
S44 Early Contrast Kinetics During Magnetic Resonance Imaging In Patients With Suspected Mesothelioma
Authors: S. Tsim, C. Humphries, D. Stobo, J. Foster, R. Woodward, C. Dick, K. Blyth
Journal: Thorax (2014)

<h3>Introduction and objectives</h3> The biology of Malignant Pleural Mesothelioma (MPM) is poorly understood, reflected in inexplicable heterogeneity in survival and therapeutic responses. Tumour angiogenesis has been identified as a therapeutic target and high tumour vascularity-to-stroma ratio is a poor prognosis marker. We report preliminary results of a pilot study conducted to establish and validate dynamic contrast-enhanced (CE) magnetic resonance imaging (MRI) methodology for the non-invasive assessment of MPM tumour vascularity. <h3>Methods</h3> 15 patients with suspected MPM were recruited prospectively. All had Pleural MRI (3T Siemens) 3–5 days prior to Medical Thoracoscopy (MT). Imaging protocols were developed utilising patients 1–6. In the remaining 9, T1-weighted VIBE images were acquired (single isotropic volume in the coronal plane) at baseline and 4.5, 9 and 13.5 min post-injection of Gadolinium contrast (0.1 mmol/kg). Signal Intensity (SI) was measured within 15 regions of interest containing representative pleural tissue at each time point and summarised as Mean (+/-SD). Pleural biopsies were obtained at MT in 8/9 patients who underwent complete CE-MRI. Paraffin-embedded tissue was available for 6/8 and stained with Factor VIII and CD34 immunostains. Blood vessel numbers and total vessel area were measured using quantitative image-analysis software (Leica Biosystems, U. K.) and correlated against contrast kinetic parameters (early SI increment (0–4.5 min) and peak SI), using Spearman’s test. Patients were followed-up in a specialist pleural clinic and survival recorded. <h3>Results</h3> Mean age was 75 years (+/- 7). 93% (n = 14) were male. Final diagnoses were: MPM (n = 6), lung adenocarcinoma (n = 1), breast adenocarcinoma (n = 1), renal cell carcinoma (n = 1), Benign Asbestos Pleural Effusion (n = 4), rheumatoid arthritis-related effusion (n = 1) and haemothorax (n = 1). Figure 1 demonstrates relationships identified between contrast kinetic parameters and tissue vascularity. Mean follow-up was 267 (+/- 149) days, over which time mortality for MPM patients exhibiting early peak CE was 100% (n = 2/2) vs. 0% (n = 0/1) for late peak CE (log rank p = 0.2). <h3>Conclusions</h3> We have established a functional MRI protocol for use in MPM. Within the limitations of this pilot study, early CE kinetics appear to reflect pleural tissue vascularity. Further work is ongoing to fully assess the diagnostic, prognostic and predictive value of this imaging biomarker.
AB0204 Tubular dysfunction in patients with rheumatoid arthritis
Authors: A. Rebrov, M. Tyapkina, E. Voloshinova
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background and Objectives</h3> Although obesity is an established risk factor in osteoarthritis (OA), there is limited information about the role of adipose tissue derived factors in bone formation. Adipocytokines such as adiponectin, resistin, and visfatin, are known to be associated with the pathogenesis of rheumatoid arthritis (RA) and OA. Adipocytokines are locally produced in RA and OA joints by osteoblasts, osteoclasts, and chondrocytes. In contrast to their joint-destructive effects in RA, the role of adipocytokines in OA bone remodelling and osteophyte formation is unclear. Therefore, the adipocytokine expression during osteophyte development and in cells of bone formation was analysed as well as their effect on these cells. <h3>Methods</h3> Osteophytes, cartilage, and osteoblasts were obtained from OA patients during joint replacement surgery. Serial sections of bone tissue were stained (Masson trichrome, TRAP) and scored from grade one (no ossification, mainly connective tissue and cartilage) to five (ossified mineralised osteophytes, &lt;10% connective tissue, ossified remodelling zones). Immunohistochemistry against alkaline phosphatase, collagen-type II, adiponectin, resistin, and visfatin was performed. OA osteoblasts were stimulated with adiponectin or resistin and immunoassays for IL-6, IL-8, and MCP-1 were performed. <h3>Results</h3> All adipocytokines were detectable in cultured osteoblasts and all osteophyte grades. In non ossified osteophytes (grade 1), especially adiponectin and to a lower extent resistin and visfatin were detectable in connective tissue fibroblasts. In ossified osteophytes (grade 2–5), resistin and visfatin and to a lower extend adiponectin were expressed by osteoblasts and resistin and visfatin by osteoclasts. In all osteophyte grades adiponectin was detectable in blood vessels and visfatin was found in about 50% of the chondrocytes. Osteoblast stimulation with adiponectin increased the release of the inflammatory mediators IL-6 (2.6-fold), IL-8 (4.9-fold), and MCP-1 (2.1-fold). In contrast, resistin led to a non-significant decrease of these factors. The osteoblast populations showed individual differences in the baseline expression of the analysed factors and in their responsiveness to adipocytokines. <h3>Conclusions</h3> The adiponectin and visfatin expression in osteophyte connective tissue and cartilage suggests their involvement in early osteophyte development. Resistin and visfatin in osteoblasts and osteoclasts in ossified osteophytes indicates a role in osteophyte formation at later stages. The stimulation of osteoblasts with adiponectin induces the release of inflammatory mediators. Therefore, the analysed adipocytokines most likely are involved in osteophyte formation at different stages and correspondingly affect cells of cartilage and bone formation to a different extent. Funded by the ANCYLOSS project of the German Ministry of Research and Education (BMBF).
Endoscopic treatment of acute ascending cholangitis in a patient with Roux-en-Y limb obstruction after a Whipple operation
Authors: T. Akaraviputh, A. Trakarnsanga, K. Tolan
Journal: Endoscopy (2010)

A 60-year-old man was diagnosed with pancreatic head adenocarcinoma. He underwent pancreaticoduodenectomy (Whipple procedure). Four months later he developed obstructive jaundice, high fever, and chills. His total bilirubin level was 2.0 mg/dL (range 0.3 – 1.2 mg/dL) and alkaline phosphatase was 270 U/L (range 39 – 117 U/L). Computed tomography (CT) of the abdomen showed marked dilatation of the afferent limb and a suspected recurrent tumor in the pancreatic area ([Fig. 1]).
The validity of Dawkins's selfish gene theory and the role of the unconscious in decision making
Authors: Tobias A Mattei
Journal: Behavioral and Brain Sciences (2014)

Although the proposed Selfish Goal Theory constitutes a major theoretical tour de force for addressing the issue of inconsistencies in human actions and the role of motivational goals in behavior, as it is based on an unproven biological paradigm (Dawkins's selfish gene theory) and overemphasizes the role of unconscious processes in decision making, it provides a questionable model of the underlying psychological structure of human agency.
TOOTH LOSS IS INDEPENDENTLY ASSOCIATED WITH ADVERSE OUTCOME BUT NOT MYOCARDIAL INFARCTION IN PATIENTS WITH CHRONIC CORONARY HEART DISEASE
Authors: Ola Vedin, Emil Hagstrom, Andrzej Budaj, Stephan Denchev, Robert Harrington, Wolfgang Koenig, Joseph Soffer, Piyamitr Sritara, Amanda Stebbins, Ralph Stewart, Henk Swart, Margus Viigimaa, Dragos Vinereanu, Lars Wallentin, Harvey White, Claes Held
Journal: Journal of the American College of Cardiology (2015)
BASELINE SYNTAX SCORE PREDICTS CLINICAL OUTCOME AFTER COMPLETE REVASCULARIZATION IN PATIENTS WITH MULTIVESSEL DISEASE
Authors: Jeehoon Kang, Kyung Woo Park, Jung-Kyu Han, Han-Mo Yang, Hyun-Jae Kang, Bon-Kwon Koo, Hyo-Soo Kim
Journal: Journal of the American College of Cardiology (2016)
PARE0014 Patients as Stepping Stone for Improved Health Care
Authors: C.R. Ziegler
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> A patientinstructor is a person with rheumatoid arthritis who teaches health care professionals. They use their own joints as examples and teach considerate joint-examination and respectful contact with patients. Results with Danish rheumatoid arthritis patients have in Denmark been stepping stone for patient-controlled teaching for five other chronic diseases – beyond the field of MSD9s. <h3>Objectives</h3> The objective was that patientconrolled teaching can add value to the usual training of health care professionals and that the results from the project with rheumatoid arthritis patients could be transferred to other chronic diseases. <h3>Methods</h3> More than 10.000 Danish students in health care educations have during more than 15 years been trained in joint-examination by people with rheumatoid arthritis. The training has been conducted by a small group of volunteers organized through the Danish Rheumatism Association. Through qualitative research conducted by Centre of Clinical Education, the Capital Region of Denmark, has it been shown what exactly the added value of patientcontrolled training is. <h3>Results</h3> The results of the research together with the volunteers longstanding and tireless commitment made it possible to transfer the project to other diseases. Now the good results have led to a grant from the Capital Region of Denmark to develop similar projects for 5 other chronic diseases, being: diabetis, heart conditions, lowbackpain, COPD and dementia. <h3>Conclusions</h3> We consider it a great success that a rheumatoid arthritis project is able to qualify the education of health care professionals on five other important areas for the benefit of even more patients in Denmark. During the presentation it will be shown how this has been possible and there will be given examples on how to maintain volunteers in a project with such great impact. <h3>Acknowledgements</h3> Centre of Clinical Education, The Capital Region of Denmark. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2314
AB0656 Clinical, serological and immunogenetic features of late-onset systemic lupus erythematosus in a colombian population:
Authors: E.A. Peñaranda-Parada, U. Panqueva, W. Rojas, R. Mantilla, F. Rondon, G. Quintana, A. Iglesias-Gamarra
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Late-onset systemic lupus erythematosus (LOSLE) is a disease-specific subgroup, which begins clinically after 50 years of age. LOSLE may have unusual clinical and laboratory characteristics, which may delay the diagnosis and timely treatment of the disease. <h3>Objectives</h3> To determine the clinical, serological and immunogenetic (HLA-DRB1) differences among patients with LOSLE versus SLE starting at younger ages. <h3>Methods</h3> Cross-sectional study in a Colombian population of individuals with SLE according to ACR criteria. Clinical and serological variables were analyzed in 98 patients with LOSLE and 72 patients with early-onset lupus. The HLA-DRB1 genotyping was analyzed in 62 samples from patients with LOSLE and 179 samples from patients without autoimmune disease. <h3>Results</h3> Table 1 show the statistically significant clinical and laboratory findings between patients LOSLE vs. early-onset SLE. In patients with LOSLE, the HLA DR17 (DR3) was found more frequently compared to individuals without autoimmune disease (OR 3.81 - 95% CI 1.47 to 10.59) (p=0.0016). <h3>Conclusions</h3> In the Colombian population with SLE, there is a probable association between various clinical and serological features, which differentiate the beginning of disease among patients with late-onset SLE vs. early-onset SLE. <h3>References</h3> Appenzeller S, Pereira DA, Costallat LT. Greater accrual damage in late-onset systemic lupus erythematosus: a long-term follow-up study. Lupus. 2008 Nov;17(11):1023-8. Boddaert J, Huong DL, Amoura Z, Wechsler B, Godeau P, Piette JC. Late-onset systemic lupus erythematosus: a personal series of 47 patients and pooled analysis of 714 cases in the literature. Medicine (Baltimore). 2004 Nov;83(6):348-59. Lalani S, Pope J, de Leon F, Peschken C; Members of CaNIOS/1000 Faces of Lupus. Clinical features and prognosis of late-onset systemic lupus erythematosus: results from the 1000 faces of lupus study. J Rheumatol. 2010 Jan;37(1):38-44. Padovan M, Govoni M, Castellino G, Rizzo N, Fotinidi M, Trotta F. Late onset systemic lupus erythematosus: no substantial differences using different cut-off ages. Rheumatol Int. 2007 Jun;27(8):735-41. <h3>Disclosure of Interest</h3> None Declared
Abstract 3332: Engineering functions in cell transduction domains: novel anticancer agents
Authors: Agamemnon A. Epenetos, christina kousparou, Spyros Stylianou, mahendra deonarain
Journal: Cancer Research (2010)

Abstract Trojantec research has focused on the design of recombinant proteins that overcome both extracellular and intracellular limitations of other delivery systems by rapidly releasing proteins into the cytoplasm and mediating efficient nuclear translocation. We have genetically engineered two fusion proteins; The first consisting of the Drosophila transcription factor Antennapedia (ANTP) and the truncated version of Mastermind-like (MAML) that behaves in a dominant negative (DN) fashion and inhibits Notch activation (ANTP/DN MAML) (TR4), and the second which is comprised of ANTP fused to the tumour suppressor protein p21, which is important in many key cell division processes including G1-arrest leading to apoptosis of damaged cells. Our results indicate that drug delivery using with the ANTP cell transduction domain induces apoptosis, abolishes colony formation in soft agar, and inhibits tumor growth in mice, without organ or systemic toxicity. These studies establish TR1 and TR4 as new cancer therapeutic agents in clinical applications. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3332.
Predictive value of endoscopic findings in the diagnosis of active intestinal amebiasis
Authors: N. Nagata, T. Shimbo, J. Akiyama, R. Nakashima, R. Niikura, S. Nishimura, T. Yada, K. Watanabe, S. Oka, N. Uemura
Journal: Endoscopy (2012)

Endoscopic diagnosis of amebic colitis can be difficult because its appearance may mimic other forms of colonic disease. The aim of this study was to identify predictive endoscopic findings for amebic colitis. Patients with suspected amebic colitis based on distinctive endoscopic findings such as aphthae or erosions, ulcers, exudates, or a bump, were included in the study. A total of 157 patients were selected, 50 of whom had amebic colitis. The sensitivity and specificity of endoscopic findings that were significantly associated with amebic colitis were: cecal lesions (80 % and 54 %), multiple number of lesions (96 % and 29 %), presence of aphthae or erosions (84 % and 37 %), and presence of exudate (88 % and 74 %). Multivariate analysis revealed that the best combination of findings to predict amebic colitis was the presence of cecal lesions, multiple lesions, and exudates, which corresponded to an area under the receiver operating characteristic curve of 0.89 (95 % confidence interval 0.82 – 0.95).