tbuckley/cabot-search huggingface dataset:
Left Ventricular Mass Measured by Myocardial Perfusion Gated SPECT
Authors: Ola Akinboboye, Guido Germano, Olajide Idris, Kenneth Nichols, Aasha Gopal, Daniel Berman, Steven R Bergmann
Journal: Clinical Nuclear Medicine (2003)

Purpose The purpose of this investigation was to determine whether left ventricular mass (LVM) assessed from myocardial perfusion gated SPECT (GSPECT) data corresponds with echocardiographic estimates, and whether mass accuracy decreases as relative myocardial wall thickness increases. Materials and Methods Myocardial perfusion tomograms were selected retrospectively for 37 patients, of whom 18 had Tl-201 and 19 had Tc-99m sestamibi GSPECT poststress data collections, which were subsequently processed using quantitative gated SPECT software (Cedars Sinai Medical Center, Los Angeles, CA). These patients also had clinically indicated echocardiograms for assessment of wall thickness and possible valvular involvement. In addition, LV internal diameter and posterior wall thickness were measured at end-diastole by two-dimensional guided M-mode echocardiography to assess relative myocardial wall thickness, and LVM was measured by three-dimensional echocardiography using an acoustic spatial locator device. Results LVM values were not significantly different between GSPECT and three-dimensional echocardiography (153 ± 39 g versus 146 ± 35 g, respectively;P = NS). GSPECT correlated significantly (r = 0.63, P < 0.0001) with three-dimensional echocardiography, with a mean difference of 7 ± 32 g but a substantial root mean squared error of 31 g. Results were similar for similar mass ranges when subgrouped by isotope and by the presence of significant myocardial perfusion defects. Results were independent of relative myocardial wall thickness determined by two-dimensional echocardiography. The two methods yielded similar results in the highest mass range of 400 to 500 g. Conclusions GSPECT and three-dimensional echo LVM correlated significantly, but given the large spread of statistical errors, these two techniques should not be considered interchangeable. Because gamma camera resolution is limited, GSPECT LVM should be viewed as an approximation.
O101 INTERFERON γ AND TUMOR NECROSIS FACTOR a TREATMENT INDUCE COVALENTLY CLOSED CIRCULAR DNA DEGRADATION IN HEPATITIS B VIRUS INFECTED HEPATOCYTES
Authors: Y. Xia, D. Stadler, J. Lucifora, F. Reisinger, D. Webb, M. Feuerherd, M. Hösel, F. Bohne, M. Heikenwaelder, U. Protzer
Journal: Journal of Hepatology (2014)
AB0580 The effect of anti-tnf treatment in psoriatic arthritis patients treated in an ordinary clinical practice
Authors: G. Haugeberg, A. M. Gulati, A. P. Diamantopoulos, K. H. Gabrielsen, M. Hoff, A. Kavanaugh
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Treatment with anti-TNF drugs in psoriasis arthritis (PsA) have in several randomized studies shown to have a favorable effect by reducing signs and symptoms and reducing the rate of radiographic progression (ref.1,2). However real life data obtained from clinical practice is more scarce. <h3>Objectives</h3> To explore in an ordinary rheumatology clinic the effect of anti-TNF treatment in PsA. <h3>Methods</h3> The PsA patients were recruited from an ordinary rheumatology clinic located in the most southern part of Norway. The PsA patients are monitored using outcome measures and data is primarily registered for benchmarking in a clinical hospital computer database. Data collected for structured follow up and monitoring includes demographics, measures for disease activity, health status and treatment registration. Anonymised data was analyzed using SPSS. <h3>Results</h3> Mean (SD) age for the 148 (men 84, women 64) anti-TNF treated PsA patients was 52.7 (11.0) yrs. Among them 72 had tried only one, 54 had tried 1 and 2 and 22 patients had tried 1, 2, 3 or more anti-TNF drugs. First anti-TNF treatment, sequence 1 (seq.1) was in median (IQR) used for 24 (43), seq.2 was used for 7 (24) and seq.3 or more for 9 (16) months. In the table mean baseline and last visit data for anti-TNF treatment is shown for seq.1, 2, and 3. <h3>Conclusions</h3> Our real life data shows that when anti-TNF treatment is used for the first time in PsA the effect is better than when an anti-TNF drug is used for the second or third time. The clinical implication is that treatment effect diminishes with increasing number of TNF inhibitors used. <h3>References</h3> Mease P et al. Arthritis Rheum 2004;50:2264-72. Kavanaugh A et al. ARD 2007;66:498-505 <h3>Disclosure of Interest</h3> G. Haugeberg Shareholder of: in and founder of DiaGraphIT selling the computer tool GoTreatIT, Grant/research support from: Unrestricted research grant from Pfizer, A. Gulati: None Declared, A. Diamantopoulos: None Declared, K. Gabrielsen: None Declared, M. Hoff: None Declared, A. Kavanaugh: None Declared
Cholangioscopie (Spyglass®) et endomicroscopie confocale (Cellvizio®): résultats préliminaires d'une approche combinée dans les sténoses biliaires indéterminées
Authors: S Leblanc, A Vienne, U Chaput, JC Duchmann, J Boyer, L Mangialavori, M Gaudric, S Chaussade, F Prat
Journal: Endoscopy (2011)

Introduction: Le diagnostic étiologique des sténoses biliaires reste difficile avec une rentabilité diagnostique de l'ordre de 50% des techniques usuelles (aspiration, biopsies, brossage biliaire). De nouvelles techniques, la cholangioscopie et l'endomicroscopie confocale, ont montré, de manière isolée, un apport diagnostique dans la caractérisation des sténoses biliaires. Le but de cette étude était d'évaluer la combinaison de la cholangioscopie selon le système Spyglass® et de l'endomicroscopie confocale par sonde Cellvizio® dans le diagnostic des Sténoses Biliaires d'origine Indéterminée (SBI).
ROS1 — Targeting the One Percent in Lung Cancer
Authors: Kathryn A. Gold
Journal: New England Journal of Medicine (2014)

Lung cancer is the leading cause of cancer-related death worldwide. For certain patients with non–small-cell lung cancer (NSCLC), molecularly targeted therapies have transformed treatment and improved outcomes. In patients with NSCLC with EGFR mutations or ALK rearrangements, targeted therapies represent the standard of care, with superior efficacy and improved tolerability, as compared with cytotoxic chemotherapy.1,2 These two genetic alterations are relatively common and are found in about 15% and 5% of patients with NSCLC, respectively. Extensive profiling efforts have identified molecular drivers that are found in smaller subsets of NSCLC, often in just 1 or 2% of patients. Although . . .
Neuroendocrine cancer of the kidney: Clinical implications of expression microarray analysis
Authors: W. B. Harris, V. Assikis, Q. Yin-Goen, M. M. Lewis, D. Lawson, M. B. Amin, A. N. Young, J. A. Petros
Journal: Journal of Clinical Oncology (2006)

20093 Background: Conventional clinical trial strategies cannot be used to develop new therapies for rare malignancies. Neuroendocrine neoplasms of the kidney are extremely rare. Here we compare the gene expression profiles of a neuroendocrine tumor from a 32 year old male with a horseshoe kidney, a large renal primary and metastatic thyroid lesions to the profiles of other cancers. Response to systemic therapy is also reported. The ultimate objective of this project is to identify new therapeutic targets for patient-specific cancer therapy. Methods: After informed consent, tissue from the patient was analyzed by cytology and immunohistochemistry. Total RNA was isolated from formalin-fixed paraffin-embedded archival reference tissues with Arcturus Paradise Reagents. Gene expression was analyzed with Affymetrix X3P arrays of the entire expressed genome. A supervised significance analysis of microarrays (SAM) procedure, using 400 data permutations, was performed to identify gene products that were differentially expressed. Clinical outcomes were documented in the patient’s medical record on the basis of standard medical imaging. Results: Cytology, immunohistochemistry and microarray studies revealed similar patterns for the primary and metastatic lesions. Gene expression profiles of the patient’s kidney and thyroid lesions, as well as other kidney and neuroendocrine tumors, identified 11 genes overexpressed significantly in the neuroendocrine tumors. Each was associated with neuroendocrine biology. The patient had a mixed response to chemotherapy with gemcitabine and cisplatin and progressive disease after 3 monthly treatments with sandostatin. He awaits assessment of response to metaiodobenzylguanidine (MIBG). Conclusions: Gene expression profiling was effective in characterizing an unusual case of renal cancer with metastasis to thyroid, though no new therapeutic target has yet been identified. Comparing response or resistance to therapy with microarray analysis may prove to be an effective strategy for developing patient-specific cancer therapy. This work was supported, in part, by a VA Merit Review Award. No significant financial relationships to disclose.
AB0733 Comparison of MRNA expression of transglutaminase 2 on peripheral blood mononuclear cells in patients with systemic lupus erythematosus and rheumatoid arthritis
Authors: W.-N. Huang, T.K. Tso, H.-C. Wu, Y.-F. Hsieh, J.-H. Yen, G.J. Tsay
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Transglutaminase 2 (TG 2) is a crosslinking enzyme that is known for tissue stabilization and immediate defense against injury or infection in many biological systems. Abnormal TG 2 activity in tissues contributes to a variety of diseases including autoimmune diseases. <h3>Objectives</h3> The aim of this study was to investigate the mRNA expression of TG 2 on peripheral blood mononuclear cells (PBMCs) in patients with systemic lupus erythematosus (SLE) and in patients with rheumatoid arthritis (RA) and further to determine its association with clinical features. <h3>Methods</h3> Forty patients with SLE (3 males, 37 females) and thirty two patients with RA (8 males, 24 females) attending outpatient clinics at Taichung Veterans General Hospital were enrolled in this study. Thirty three age-matched healthy subjects from the local community served as controls. About 30 mL blood was collected into sterile tubes containing EDTA. PBMCs were isolated with lymphocyte-separation medium by the density gradient separation. Total RNA was isolated from PBMCs of patients with SLE, patients with RA, and healthy subjects. RNA was extracted by using Trizol reagent and RNA samples were resuspended in diethyl pyrocarbonate-treated water followed by quantification of RNA concentration and purity by a spectrophotometer with calculating the ration of optical density at wavelengths of 260 and 280 nm. The first-strand cDNA for RT-PCR was synthesized from total RNA using the RT-PCR system. The cDNAs encoding human TG 2 and GAPDH were amplified by RT-PCR using the appropriate primer pairs, respectively. <h3>Results</h3> The mRNA expression of TG 2 in SLE patients was significantly higher than that in RA patients and healthy controls. However, there was no significant difference for mRNA expression of TG 2 between RA patients and healthy controls. In SLE patients with aged 20-50 years, the mRNA expression of TG 2 tended to increase with age but was decreased in elderly SLE patients. In contrast, the mRNA expression of TG 2 tended to decrease with age in RA patients and elderly RA patients had lower mRNA expression of TG 2. In addition, there were correlations of TG 2 mRNA expression with clinical features in both SLE and RA patients. <h3>Conclusions</h3> The mRNA expression of TG 2 was increased in patients with SLE. Age-related change in mRNA expression of TG 2 was observed in both SLE patients and RA patients. However, the differential mechanism for TG 2 involvement in the pathogeneses of autoimmune diseases including SLE and RA needs further investigation. <h3>Disclosure of Interest</h3> None Declared
Circulating Tumor Cells and FDG-PET/CT for the Therapeutic Monitoring of Bone Metastases from Breast Cancer.
Authors: U. De Giorgi, U. De Giorgi, M. Mego, E. Rohren, V. Valero, B. Handy, S. Jackson, J. Reuben, H. Macapinlac, M. Cristofanilli, N. Ueno
Journal: Cancer Research (2009)

Abstract Background: Circulating tumor cells (CTCs) and [18F]fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) are two promising new tools for monitoring therapy in patients with metastatic breast cancer. The two modalities showed high sensitivity in detection of bone relapse/progression from breast cancer (De Giorgi U et al. Ann Oncol 2009). In this study, we sought to evaluate the prognostic significance of two different modalities represented by the detection of CTC and FDG-PET/CT in patients with bone metastases from breast cancer treated with standard therapies. Our objective was to compare the two modalities to identify which technology could be more sensitive in prospectively monitoring such patients.Patients and Methods: This is a retrospective study of 54 patients with bone metastases from breast cancer without visceral metastases treated at The University of Texas M. D. Anderson Cancer Center from September 2004 to May 2008. CTC were detected and enumerated using the CellSearch system (Veridex LLC, Rariten NJ, USA). Patients were categorized according to first follow-up CTC counts as having a favorable (&amp;lt; 5 CTC/7.5 mL of blood) or unfavorable (≥ 5 CTC) outcome. Reassessment of disease status by CTC count and FDG-PET/CT was performed approximately 2-3 months after initiation of the new treatment, depending on treatment type and schedule. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier product limit method, and compared between groups with the log-rank test.Results: In 54 evaluable patients, the median overall survival time was 17 months (range, 3 to &amp;gt;36). Follow-up CTC levels and FDG-PET/CT response predicted both PFS (p = 0.02 and p = 0.0001, respectively) and OS (p = 0.01 and p = 0.02, respectively), while baseline CTC predicted neither PFS (p = 0.8) nor OS (p = 0.76). In patients with either CTC or FDG-PET/CT response PFS has been 13 months, while in patients with discordant CTC and FDG-PET/CT response PFS has been 6 months and in patients with neither CTC nor FDG-PET/CT response PFS has been 5 months (p = &amp;lt;0.00002). In patients with either CTC or FDG-PET/CT response, OS has not been reached (&amp;gt;31 months); in patients with discordant CTC and FDG-PET/CT response, OS has been 24 months; and in patients with neither CTC nor FDG-PET/CT response, OS has been 18 months (p = 0.02).Conclusions: CTC and FDG-PET/CT are useful tools for therapeutic monitoring of bone metastases from breast cancer. Prospective studies in this specific clinical context are needed to assess the critical roles that CTC and FDG-PET/CT individually as well as collectively play in the prognostic and therapeutic monitoring of bone metastases from breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1109.
Distinction entre polypes hyperplasiques et adénomateux grâce au Narrow Band Imaging
Authors: V Phoutthasang, C Bories, JF Bourgaux, E Assenat, JL Faillie, P Pouderoux
Journal: Endoscopy (2011)

Introduction: La résection d'adénomes en coloscopie permet de diminuer l'incidence de cancer colique. Tous les polypes doivent être réséqués actuellement, car le diagnostic est histologique mais ce geste reste risqué. La distinction entre polypes hyperplasiques et adénomateux grâce au Narrow Band Imaging (NBI) permettrait de l'éviter et de diminuer les coûts de l'examen. Notre étude prospective évaluait les performances de gastroentérologues à distinguer ces polypes, et d'évaluer l'effet d'une formation dédiée. Le deuxième objectif était d'identifier les caractéristiques macroscopiques en NBI et d'en évaluer la validité.
Antitumor activity of sorafenib in osteosarcoma (OS) preclinical models
Authors: Y. Pignochino, G. Grignani, G. Cavalloni, M. Motta, S. Bruno, G. Camussi, S. Ferrari, P. Picci, M. Berger, M. Aglietta
Journal: Journal of Clinical Oncology (2008)

10540 Background: Osteosarcoma is the most common primary bone tumor in young adults. Despite improved prognosis, resistance to chemotherapy remains responsible for failure of OS treatment. The search for alternative agents focused on specific molecular mechanisms in OS is mandatory. Sorafenib (BAY 43–9006) is a multitarget antitumoral drug (RAF, VEGFR-2/3, FLT-3, KIT, FGFR-1, RET, MCL- 1; PDGFR-β). We explored the expression of main sorafenib targets in OS and its activity in preclinical models. Methods: In 30 samples from OS patients and in 7 OS cell lines we performed immunohistochemistry for MAPK-P and Mcl-1 expression as well as mutational analysis of B-RAF and K-RAS. We assessed the cell proliferation inhibition both in vitro (Cell Titer-Glo) and in vivo (xenografts in SCID mice) caused by Sorafenib treatment. The sorafenib molecular mechanism was investigated by Western blot (MAPK-P, MCL-1) and ELISA tests (VEGF, MMP2/9). Results: Expression of MAPK-P and MCL-1 was shown in 20/30 and 24/30 specimens, respectively (normal bone counterpart constantly negative). B-RAF exon 15 displayed mutations in 4/30 samples (G615R, S602Y, H608L, G596delA). Sorafenib caused a dose and time dependent OS cell line growth inhibition (72h IC50: 4.6–8.3 μM). OS xenografts confirmed sorafenib antitumoral activity (average tumor volume 335.3±97.9 in untreated vs. 44.4±18.5 mm3 in treated mice). MAPK-P and MCL-1 at 24h in OS cells were down-regulated in a dose dependent manner. Sorafenib at 5μM induced reduction of VEGF and MMP2/9 production. Conclusions: These data support to test sorafenib in phase II clinical trials in osteosarcoma patients relapsing after standard treatment. No significant financial relationships to disclose.
Elevated Glucose Threshold in Kimmelstiel–Wilson Syndrome
Authors: Joseph L. Grant
Journal: New England Journal of Medicine (1954)

PATIENTS with intercapillary glomerulosclerosis often have an elevated renal threshold for sugar. This was noticed in 2 elderly diabetic patients with Kimmelstiel–Wilson syndrome who persistently showed markedly elevated blood sugar levels in the absence of glycosuria. The records of all cases of intercapillary glomerulosclerosis proved at autopsy at the Mary Hitchcock Memorial Hospital, Hanover, New Hampshire, and the Veterans Administration Hospital, White River Junction, Vermont, have therefore been investigated from this point of view, and the results indicate that there is a statistically significant elevation in the threshold in these patients as compared with other diabetic patients without the glomerular . . .
OP0057 Anti-TNFΑ Therapy Targets PKB/C-AKT Induced Resistance of Effector Cells to Suppression in Juvenile Idiopathic Arthritis
Authors: E. J. Wehrens, S. J. Vastert, G. Mijnheer, J. M. Meerding, M. Klein, N. M. Wulffraat, B. J. Prakken, F. van Wijk
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Resistance of effector T cells (Teff) to suppression contributes to disturbed immune regulation in autoimmune disease. Targeting this unresponsiveness to suppression might therefore have beneficial effects in autoimmune inflammation<sup>1</sup>. In juvenile idiopathic arthritis (JIA) we have recently shown that Teff from inflamed joints are refractory to suppression, which was associated with enhanced PKB/c-akt activation in these cells<sup>2</sup>. <h3>Objectives</h3> To investigate whether anti-IL-6 and anti-TNFa influence unresponsiveness of Teff to suppression in patients with JIA. <h3>Methods</h3> Resistant Teff from the inflamed joints of JIA patients were cultured in the presence of etanercept or anti-IL-6 in vitro and PKB/c-akt activation and responsiveness to suppression was measured. In addition, in vivo effects of TNFa blockade were investigated using peripheral blood samples of patient before and after start of etanercept therapy. <h3>Results</h3> <i>In vitro</i> treatment of synovial fluid Teff with anti-IL-6 led to improved Treg mediated suppression of cell proliferation in some, but not all patients. Blocking TNFa with etanercept however clearly enhanced suppression in all samples analyzed. In the presence of etanercept PKB/c-akt activation of Teff was reduced and Teff became more susceptible to TGFb mediated suppression, indicating that anti-TNFa directly targets resistant Teff. This was confirmed by <i>ex vivo</i> data from patients treated with etanercept demonstrating enhanced responsiveness of effector cells to suppression after therapy. <h3>Conclusions</h3> This study is the first to show resistance of Teff to suppression as a target of anti-TNFatherapy in arthritis, resulting in improved regulation of inflammatory effector cells. <h3>References</h3> Wehrens EJ, Prakken BJ, van WF. T cells out of control-impaired immune regulation in the inflamed joint. Nat.Rev.Rheumatol. Nat Rev Rheumatol. 2012 Sep 18;9(1):34-42. Wehrens EJ, Mijnheer G, Duurland CL et al. Functional human regulatory T cells fail to control autoimmune inflammation due to PKB/c-akt hyperactivation in effector cells. Blood 2011;118:3538-3548. <h3>Disclosure of Interest</h3> None Declared
Cis-regulatory architecture of a brain signaling center predates the origin of chordates
Authors: Yao Yao, Paul J Minor, Ying-Tao Zhao, Yongsu Jeong, Ariel M Pani, Anna N King, Orsolya Symmons, Lin Gan, Wellington V Cardoso, François Spitz, Christopher J Lowe, Douglas J Epstein
Journal: Nature Genetics (2016)
Intensive Chrysotherapy (with Lauron) in Rheumatoid Arthritis
Authors: H. Harold Friedman, Otto Steinbrocker
Journal: New England Journal of Medicine (1949)

THIS report presents the results obtained with intensive chrysotherapy in the treatment of 18 patients with rheumatoid arthritis. The purpose of the study was to investigate the usefulness of large quantities of gold salts administered over a relatively short period. In spite of the limited number of cases treated, our observations are reported for whatever significance they may have, since we do not plan to continue the investigation.Although there has been a trend in this country toward relatively small doses of gold salts, intensive treatment with gold compounds was employed for several reasons. The manufacturer of the preparation used . . .
Pharmacokinetics (PK) of the Pan-Her Inhibitor Dacomitinib (D) in Subjects with Mild or Moderate Hepatic Impairment
Authors: J. O'Connell, A. Plotka, Y. Liang, T. Boutros, G. Ni, J. Masters, M. DeMicco, P. Pardo, C. Bello, N. Giri
Journal: Annals of Oncology (2013)