tbuckley/cabot-search huggingface dataset:
Abstract IA-13: Mechanisms regulating anchorage independent survival
Authors: Zachary Schafer, Alex Grassian, Loling Song, Arnaud Mailleux, Tobias Schmelzle, Yoko Irie, Grace Gao, Michael Overholtzer, Zhenyang Jiang, Zachary Gerhart-Hines, Pere Puigsever, Joan S. Brugge
Journal: Cancer Research (2009)

Abstract One of the earliest recognized features of tumor cells in culture is their ability to proliferate and survive without attachment to extracellular matrix. This ‘anchorage independence’ of tumor cells distinguishes their behavior from normal cells and is believed to be important to allow tumor cells to proliferate outside of their natural niches during early stages of tumor formation as well as during invasion and metastasis. My presentation will focus on findings from our laboratory on the mechanisms responsible for death of cells deprived of matrix and how oncogenes and other factors promote anchorage independence. We have found that three distinct death processes — apoptosis, metabolic impairment, and a novel non-apoptotic mechanism, referred to as entosis, involving invasion of one cell within another and lysosomal degradation — contribute to death of cells deprived of their appropriate matrix. The major topic of my presentation will be new unpublished findings on metabolic pathways that are regulated by matrix attachment. We have found that detachment of mammary epithelial cells from ECM causes an ATP deficiency due to loss of glucose transport. Overexpression of ErbB2 rescues the ATP deficiency by restoring glucose uptake through PI(3)K activation. Interestingly, we found that the ATP deficiency could also be rescued by antioxidant treatment without rescue of glucose uptake. This restoration was found to be dependent on stimulation of fatty acid oxidation (FAO), which is inhibited by detachment-induced reactive oxygen species (ROS). The significance of these findings was supported by studies in 3D acinar cultures and anchorage-independent colony formation. These results reveal both the importance of matrix attachment in regulating metabolic activity and an unanticipated mechanism for cell survival in altered matrix environments through antioxidant restoration of ATP generation. Citation Information: Cancer Res 2009;69(23 Suppl):IA-13.
AB0074 Alkylating Agents Enhance Interleukin-10 Secretion from B Cells via P38 MAP Kinase Activation
Authors: L. Lu, A. Morita, K. Yoshimoto, H. Kameda, T. Takeuchi
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Alkylating agents such as melphalan and bendamustine are commonly used in the treatments of tumors, especially hematologic malignancies. However, the exact mechanisms of their actions to B cells have not been fully clarified. <h3>Objectives</h3> To investigate the effects of these alkylating agents on B cell functions, and to explore a possible clinical application of the agents to autoimmune diseases. <h3>Methods</h3> We used two alkylating agents, melphalan and bendamustine, which are inhibitors of DNA replication. We also used methotrexate (MTX), which is another inhibitor of DNA replication and commonly used in rheumatoid arthritis therapies. A human B cell line, Ramos, was cultured in the presence of various concentrations of melphalan, bendamustine or MTX for four days. The proliferation of the cells was analyzed by XTT assay and the secretions of IgM and cytokines by the cells were measured by ELISA. The cells and cellular mRNA were collected for FACS analysis and quantitative RT-PCR, respectively. Nuclear extracts were prepared from the cells and Electrophoresis Mobility Shift Assay (EMSA) was employed for detection of DNA-binding capacity. <h3>Results</h3> The proliferation of Ramos cells was significantly inhibited by melphalan (2.5-20 μM), bendamustine (25-100 μM) or MTX (0.1-20 μM) in a dose-dependent manner. Concordantly, IgM secretion from Ramos cells was significantly inhibited at these concentrations by up to 70%. Interestingly, however, the production and secretion of interleukin-10 (IL-10) from Ramos were dramatically (&gt;10-fold) increased upon treatment with these drugs. Melphalan and bendamustine induced higher levels of IL-10 than MTX. Moreover, we found that both melphalan and bendamustine enhanced the activation of p38 MAP kinase. Inhibition of p38 MAP kinase by its specific inhibitor led to the abrogation of drug-induced IL-10 production. EMSA revealed that Sp1 was the downstream transcription factor involved in p38 MAP kinase activation by all three drugs (Fig. 1). <h3>Conclusions</h3> P38 MAP kinase-Sp1 pathway plays a crucial role in IL-10 production from B cells induced by alkylating agents. Our results suggest that cessation of cell division via inhibition of DNA replication induces IL-10 production. MTX may exert its therapeutic effects partly via immunosuppressive effects of IL-10. Our results also suggest that alkylating agents provide a therapeutic tool for autoimmune diseases through anti-inflammatory effects of IL-10. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3144
Asymmetric 99mTc-MDP Uptake in Mineralized Tendons Might Mimic Bone Lesions
Authors: Yu-Ren Chen, Te-Chun Hsieh, Kuo-Yang Yen, Yeh-You Shen, Chia-Hung Kao
Journal: Clinical Nuclear Medicine (2013)

A 55-year-old man was a hepatocellular carcinoma patient, diagnosed by sonography and a biopsy. Because of his musculoskeletal tenderness, a bone scan was performed to exclude skeletal metastasis. A subsequent F-FDG PET/CT scan revealed that the unilateral abnormal uptake seen on the bone scan was actually a mineralized tendon. A mineralized tendon is easily detectable using Tc-MDP; therefore, it is imperative to differentiate between bone lesions and mineralized tendons. In addition, few studies have reported F-FDG uptake in a calcified tendon.
A Randomized Controlled Trial of Hospital Discharge Three Days after Myocardial Infarction in the Era of Reperfusion
Authors: E J Topol, K Burek, W W O'Neill, D G Kewman, N H Kander, M J Shea, M A Schork, J Kirscht, J E Juni, B Pitt
Journal: New England Journal of Medicine (1988)

To evaluate the feasibility and cost savings of hospital discharge three days after acute myocardial infarction, we screened 507 consecutive patients prospectively for clinical complications and exercise-test performance. Of 179 patients whose condition was classified as uncomplicated (no angina, heart failure, or arrhythmia 72 hours after admission), 126 underwent early exercise testing and 90 had no provocable myocardial ischemia. Eighty of these patients were randomly assigned to early (day 3) or conventional (days 7 to 10) hospital discharge. Seventy-six of them had received coronary reperfusion therapy (thrombolysis, angioplasty, or both). At six months of follow-up, there were no deaths or new ventricular aneurysms, and the early-discharge and conventional-discharge groups had similar numbers of hospital readmissions (6 and 10), reinfarctions (none and 5), and patients with angina (3 and 8). In the early-discharge group, 25 of 29 previously employed patients returned to work 40.7 +/- 21.9 days (mean +/- SD) after admission, as compared with 25 of 27 patients in the conventional-discharge group, who returned to work after a mean of 56.9 +/- 30.3 days (P = 0.054). The mean cumulative hospital and professional charges were $12,546 +/- 3,034 in the early-discharge group, as compared with $17,868 +/- 3,688 in the conventional-discharge group (P less than 0.0001). In carefully selected patients with uncomplicated myocardial infarction, hospital discharge after three days is feasible and leads to a substantial reduction in hospital charges. Before this strategy can be widely recommended, however, its safety must be confirmed in larger prospective clinical trials.
Isolation of Tumor Initiating Cells with Metastatic Potential from Human Primary Invasive Ductal Carcinoma.
Authors: C. Marsden, C. Marsden, M. Wright, M. Wright, L. Carrier, L. Carrier, R. Pochampally, R. Pochampally, R. Pochampally, B. Rowan, B. Rowan
Journal: Cancer Research (2009)

Abstract Disseminated breast cancer cells may be present at distant sites at the time of primary diagnosis of breast cancer in patients that exhibit no outward signs of clinical metastasis. It is hypothesized that early breast cancer metastasis is initiated by a small population of breast tumor initiating cells (bTICs) within the primary tumor that are inherently resistant to chemotherapy and hormonal therapy. To better understand the biological pathways that permit bTICs to metastasize and to evade current breast cancer therapies, bTICs have been isolated from breast cancer biopsies from patients diagnosed with primary invasive ductal carcinoma. Breast cancer needle biopsies from primary tumors were obtained during the routine care of patients with consent and IRB approval. Core biopsies were mechanically and enzymatically dissociated, yielding a single cell suspension which was subsequently cultured under non-adherent and serum-free conditions to obtain tumorspheres. Injection of about 500 bTICs into the mammary fat pad of female nude mice resulted in tumor formation at the site of injection within two months that was maintained as a small palpable mass for at least six months. H+E staining of sections of the primary tumors revealed complex cellular organization and both microvascular and macrovascular structures. Serial transplantation of the primary tumors from the 6/7 samples resulted in tumor formation at the site of injection. Upon primary tumor formation in the mammary fat pad, metastatic human breast cancer cells were detected within the lungs, liver, brain and bone marrow (femur) from 5/7 tumors after six months. Metastatic cells were detected by PCR for an alpha-satellite sequence in the centromeric region in human Chromosome 17, and by in situ hybridization using an human specific Alu DNA oligonucleotide probe. Metastatic bTICs were mostly detected as single cells or small clustering of cells present throughout the metastatic organ. These data demonstrate that cells with the phenotype of “tumor initiating cells” can be isolated from primary biopsies of human invasive ductal carcinoma and cultured in vitro. Unlike direct heterotransplant tissues from primary tumor biopsies, the majority of bTICs samples form tumors when injected into immunodeficient mice and further exhibit a highly metastatic phenotype. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 504.
PMO-037 Adult nutritional status assessment in a hospital: cross sectional study in a UK hospital
Authors: S Dingwal, S Shah, A Patel, J Arnold-Jellis, H Chin, S Lunt, S R Kadri
Journal: Gut (2012)

<h3>Introduction</h3> Malnutrition in hospital can result in significant health and economic consequences. It can prolong hospital stay and can increase the risk of complications. <h3>Objectives</h3> This cross sectional study was undertaken to assess nutrition status on acute in-patients using the Malnutrition Universal Screening Tool “MUST”, and compliance of completion of nutritional and hydration documentation such as nutrition care plans, food and fluid charts. <h3>Methods</h3> Ten patients were randomly selected from ten wards across the hospital. Wards included four Acute Medical, three Care of the Elderly and three surgical wards. All one hundred patients9 health records were reviewed to identify completion of the “MUST” assessment document; nutrition care plans, and food charts. Fluid chart were also reviewed to identify compliance in completion. <h3>Results</h3> “MUST”—Of all the patients who had a “MUST” assessment undertaken 47% (<i>n</i> 26/55) were found to be low risk and 52% (<i>n</i> 29/55) had a medium or high risk score. Two of the 10 wards had more than 50% completion. No wards had 100% completion of “MUST” assessments. Forty five percent did not have a “MUST” score. Nutrition Care Plan documentation—Eight out of ten of the wards had a nutrition care plan for all or some of their patients. 60% were completed daily. Food chart—In nine out of the 10 wards all or some patients received a food chart. 66% were partially or fully completed. Fluid charts—In nine out of ten wards all or some patients had a fluid chart and 78% were partially or fully completed. Twenty two percent did not receive a fluid chart. <h3>Conclusion</h3> The audit found suboptimal rates of completion of “MUST” assessment and nutrition care plan documentation. Over 50% of those assessed were found to be medium and high risk of malnutrition but it is unclear if they were the patients receiving the correct documentation. Repeat audits could identify this more clearly. We aim to put into place several improvements at ward level to increase compliance. These include; “MUST” calculators, a re-launch of “MUST” screening tools and supporting literature, ward based training. Senior management and ward sisters have been auditing own wards to ensure improvement in compliance with the introduction of ward directed monthly audits. These key clinical indicators of nutrition and hydration have also been based on key recommendations for CQC, DoH and NICE Guidelines. <h3>Competing interests</h3> None declared.
FRI0129 Similarities and Differences between Axial and Peripheral Predominant Forms in Patients with Early Spondyloathritis: Results from the Esperanza Cohort:
Authors: P. del Río-Martínez, V. Navarro-Compán, C. Castillo-Gallego, M.C. Castro, E. Collantes-Estévez, E. De Miguel
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Based on the predominant manifestation of the disease, the ASAS classification criteria for spondyloarthritis (SpA) distinguish two clinical forms: Axial SpA, including non-radiographic SpA and Ankylosing Spondylitis (AS), and peripheral SpA. Although both forms are considered as part of the same disease, published data are limited, especially in early disease. <h3>Objectives</h3> To describe and compare the characteristics of patients fulfilling the ASAS criteria for axial SpA versus peripheral SpA in patients with recent symptoms onset. <h3>Methods</h3> Baseline dataset from the early SpA ESPERANZA cohort was used. This cohort includes patients with the following referral criteria: Age &lt;45 years, symptoms duration 3-24 months and with inflammatory back pain (IBP) or asymmetrical arthritis or spinal/joint pain plus ≥1 SpA features. A total of 377 patients fulfilling the ASAS classification criteria for SpA were included. Demographic and disease characteristics were compared between patients with axial SpA versus peripheral SpA. <h3>Results</h3> Two hundred ninety one (77.2%) patients were classified as axial SpA (109 AS and 182 non-radiographic SpA) and 86 (22.8%) patients as peripheral SpA. Table shows the results (mean ± SD or relative frequency) for the comparison of demographic and disease characteristics between groups. Age, sex and disease activity scores were similar in both groups. However, axial SpA was more related to a delay in time to be referred to a specialist, uveitis and positive HLA-B27 while peripheral SpA was associated with enthesitis, psoriasis, dactylitis and inflammatory bowel disease (IBD). <h3>Conclusions</h3> Early SpA patients with predominant axial symptoms are usually referred later to rheumatologists than patients with peripheral symptoms. However, the degree of disease activity is similar in both groups. Uveitis and HLA-B27 are more frequent in patients with predominant axial symptoms, while psoriasis, enthesitis, dactylitis and IBD are more frequent in patients with peripheral involvement. <h3>Acknowledgements</h3> The EsPeranza Program has been supported by the Spanish Rheumatology Foundation and an unrestricted grant from Pfizer. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3260
SAT0383 High Dose Allopurinol in France, Germany, Italy, Spain and the UK
Authors: J. A. Singh, C. Storgard, S. Baumgartner, R. Morlock
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Allopurinol is the most commonly used urate lowering therapy in the world. Although allopurinol is EMEA authorized for up to 900 mg per day, the majority of patients receive 300 mg per day or less. <h3>Objectives</h3> To describe physician, patient and treatment characteristics in patients with gout treated with allopurinol. <h3>Methods</h3> Data from a quantitative survey of physicians were assessed and results confirmed through chart audits. Initial and current dose of allopurinol, presence of co-morbid conditions, use of prophylaxis for flare prevention, serum uric acid (sUA), physician subspecialty and patient factors were evaluated. Data on achieving target sUA were also collected. Results are presented as proportions or means and standard deviations (SD). Multivariate and descriptive statistics were used to describe patients with sUA ≤ 6 mg/dL. <h3>Results</h3> 126 rheumatologists and 126 primary care physicians were interviewed. Of 1260 patients, 816 (65%) were treated with allopurinol. Patient characteristics, treatment and percent with a sUA≤ 6 mg/dL are presented in Table 1. Across all countries, majority of patients were treated with 300mg or less of allopurinol per day. Less than 6.5% in France, Germany and Spain were given &gt; 300mg whereas 10% in Italy and 34% in the UK achieved a daily dose above 300mg (p&lt;0.01). Over 12 months, the number of patients achieving SUA≤ 6.0 mg/dL differed across the 5 countries (Spain &lt; Germany &lt; Italy &lt; France &lt; UK, Table 1), yet, there was no difference in achieving SUA≤ 6.0 mg/dL (average, min or most recent sUA) by allopurinol dose. A multivariable-adjusted model predicting use of high dose allopurinol found patients with tophi (OR 2.49; p=0.01), co-existing alcoholism (OR 2.31; p=0.02), CKD(OR 2.52; p=0.05, patients taking anti-hypertensive(OR 0.28; p=0.03) and from the UK (OR 5.26; p&lt;0.01) were more likely to be using 600mg+ of allopurinol; however, only physician sub-specialty [general practitioners vs. rheumatologists (OR 0.68; p&lt;0.05)], UK vs. other countries (OR 4.01; p&lt;0.01), time on therapy(OR 1.38; p=0.4), and chart documented co-existing CHF (OR 0.4; p&lt;0.05), hyperlipidemia (OR 0.7; p&lt;0.05), hypertension (OR 1.5; p&lt;0.05) and stones (OR 0.4; p&lt;0.05) were associated with sUA ≤ 6 mg/dL. After adjusting for confounding factors there was no impact of allopurinol dose in achieving sUA≤6 mg/dL. <h3>Image/graph</h3> <h3>Conclusions</h3> Allopurinol is the most widely used urate lowering therapy. Although it is approved for up to 900 mg the majority of patients are treated with 300mg or less per day. Less than 50% of patients achieve sUA&lt;6mg/dL at any dose of allopurinol. <h3>Disclosure of Interest</h3> J. Singh Consultant for: URL pharmaceuticals, Savient, Takeda, Ardea, Regeneron, Allergan and Novartis, C. Storgard Employee of: Ardea Biosciences, S. Baumgartner Employee of: Ardea Biosciences, R. Morlock Employee of: Ardea Biosciences
“Running late” and adenoma detection – is there an association?
Authors: Allegra Condiotte, Douglas Robertson, Cory Blodgett, Todd MacKenzie, Heiko Pohl
Journal: Endoscopy (2014)

<b>Background:</b> The efficacy of screening colonoscopy depends on adequate adenoma detection. Operating behind schedule (i. e. “running late”) might impose time pressure and affect adenoma detection. The aim of the study was to examine whether there is an association between procedural delay and adenoma detection rate (ADR). <b>Methods:</b> We retrospectively identified individuals who underwent an elective outpatient colonoscopy at an academic medical center between October 2011 and March 2012. We extracted information regarding procedure details, and patient and polyp characteristics. Procedure delay was defined as the time elapsed between the scheduled and actual procedure start times. We calculated the ADR for each 15-minute delay interval and for each quartile of procedure delay for individual endoscopists. <b>Results:</b> In total 1505 patients (mean age 61.3, 49 % men) were examined by 11 endoscopists. At least one adenomatous polyp was found in 507 patients (34 %), with a mean of 0.63 adenomas per patient. Colonoscopies started at a median 18 minutes late (IQR 3 – 36) and median delay times varied broadly between endoscopists from 4 minutes to 45 minutes. ADR was not affected by procedure delay and was similar across 15-minute delay intervals (<i>P</i> = 0.101). The ADR also remained similar across quartiles of the endoscopists’ delay times (from lowest to highest delay quartile: 34 %, 32 %, 32 %, and 37 %; <i>P</i> = 0.397). Independent factors associated with increased adenoma detection included being a man, older age, surveillance colonoscopy, and the endoscopist. <b>Conclusion:</b> In this large multiendoscopist study we did not find that procedure delay affected adenoma detection. Even when endoscopists are behind schedule, they still perform a meticulous examination with no impact on adenoma detection.
Case 23-2005
Authors: Kenneth K. Tanabe, Lawrence S. Blaszkowsky, Raymond T. Chung, Michael A. Blake, Gregory Y. Lauwers
Journal: New England Journal of Medicine (2005)

A 57-year-old man with chronic active HBV infection was found to have a mass in the liver on routine screening. The results of a fine-needle aspiration biopsy suggested hepatocellular carcinoma. A multidisciplinary group discusses pathophysiology and management.
Lumbar and Sacral Compression Radiculitis (Herniated Lumbar Disk Syndrome)
Authors: Donald Munro
Journal: New England Journal of Medicine (1956)

THIS paper is a report of a study of certain back injuries having to do with ruptured intervertebral disks, as well as the compressive radiculitis in the same area, that were admitted to the neurosurgical service of the Boston City Hospital during the seventeen years between 1937 and 1955. It is a summary of the clinical aspects of the problems and neither includes any patients with bony vertebral injuries nor any follow-up except immediate postoperative or post-hospitalization end results. Long-term end results will be reported in another communication.MaterialThe total number of patients involved was 545. Their ages ranged . . .