tbuckley/cabot-search huggingface dataset:
SP0135 Mononuclear cells and the reoslution of acute inflammation
Authors: D. Gilroy
Journal: Annals of the Rheumatic Diseases (2013)

Inflammation is a primordial response to infection and injury that seeks to neutralise and eliminate foreign organisms and/or material. Thus, inflammation is no trivial event. Life depends upon it. In general, the innate inflammatory response initiates within minutes and resolves within hours. Chronic inflammation, on the other hand, persists for weeks, months or even years and, unlike the acute response, is the side of host immunity we need to avoid. Notwithstanding, dispersed among this black and white view of inflammation are shades of grey. We are constantly reminded that defining inflammation is not so easy and that while acute inflammation can resolve, it can also be recurrent and that, over time, chronic inflammation can also resolve or persist with devastating consequences to the host. In this presentation, one of these many aspects of the inflammatory response – how acute inflammation resolves, will be discussed. In doing so it will be argued that resolution is as active process, whose failure may predispose the host to chronic inflammatory diseases and autoimmunity. At the very least it is hoped we can highlight resolution as a critical facet of the inflammatory response and serve to underline the importance of not altering its normal course of action when developing novel anti-inflammatory drugs. Ultimately, it will be proposed here that resolution is controlled by endogenous pro-resolution factors, which, for the future, may represent a treasure trove for drug discovery in terms of designing drugs that mimic their mode of action or enhance their synthesis. Specifically, I will recount the earlier work done on cyclooxygenase and lipoxygenase-derived lipid mediators (cyclopentenone prostaglandins, prostaglandin D<sub>2</sub>, lipoxins and aspirin-triggered epi-lipoxins) in limiting the continuity of the inflammatory response; bring the audience up to date with a more recent understanding of some of the cellular players in this setting and introduce some new soluble mediators (resolvins) and their receptors as potentially novel pro-resolving agents. In this setting, macrophage phenotype as a critical determinant of inflammation longevity will also be discussed. <h3>Disclosure of Interest</h3> None Declared
THU0159 Beneficial Effect of Methotrexate in Combination with a Biotherapy for the Long Maintenance of Biotherapy in RA Patients
Authors: C. Hilaire, B. Pallot-Prades, P. Collet, A. Amouzougan, H. Locrelle, T. Thomas, H. Marotte
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> At this time, no predictive factor for response to biotherapy in RA patients is available in the daily practice. <h3>Objectives</h3> The objective is to determine predictive factors for the first biological maintenance in rheumatoid arthritis (RA) treatment. <h3>Methods</h3> From our database including 663 RA patients, 289 RA patients were received their first biotherapy between 2000 and 2009. Among these 289 RA patients, we selected 2 subsets of patients. In the first group, RA patients received the same biological therapy for at least 3 years (n=56). In the second group, RA patients required at least 3 different biological therapies over the 3 years following the first biological (n=36). Demographic parameters (age, sex, smoking, body mass index), RA activity (DAS28), biological parameters, DMARDs and glucocorticoid therapy were recorded. Chi-squared statistical analysis and odds ratios (OR) were performed. <h3>Results</h3> Due to the follow-up of three years, TNFa blockers were mainly used as first biotherapy (Etanercept, adalimumab, or infliximab) in 93%. Biotherapies were equally distributed in both groups. Demographic parameters and disease ac tivity were similar in the two groups. In the same way, biological parameters of RA severity were not different in both groups. However, combination of DMARDs before starting the first biotherapy was associated with requirement to switch frequently biotherapy compared to the first goup (OR = 4.2; 95%CI: 1.193 to 14.79; p&lt;0.05). However, in patients receiving DMARDs, using MTX compared to other DMARDs was associated with the maintenance of the first biological therapy (OR = 3.9; 95%CI: 1.216 to 11.55; p&lt;0.01). <h3>Conclusions</h3> Our study shows that the presence of méthotrexate at the starting time of a biotherapy is a factor for maintenance of the first biological therapy for at least three years. However, our result is mainly relevant for TNFa blockers which was the mainly biotherapy used at the first line. <h3>Disclosure of Interest</h3> None Declared
SAT0246 Physical Activity in Patients with Ankylosing Spondylitis Compared to Healthy Controls.
Authors: S. van Genderen, A. Boonen, P. Jacobs, L. Heuft, J. Luime, A. Spoorenberg, S. Arends, D. van der Heijde, R. Landewe, G. Plasqui
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Ankylosing spondylitis (AS) is a rheumatic inflammatory disease that mainly affects the axial skeleton. Important symptoms comprise pain, (morning) stiffness, fatigue, reduced mobility and limitations in the physical function. Likely this will lead to a decrease of physical activity (PA) compared to a healthy population. <h3>Objectives</h3> The aim of this study was to compare patients with AS and healthy controls regarding their PA, using a tri-axial accelerometer. <h3>Methods</h3> In this cross-sectional study, PA was measured using a tri-axial accelerometer (Actigraph GT3X+) attached to the lower back by means of an elastic belt. Subjects wore the accelerometer for 7 consecutive days, during waking hours. From accelerometer output, total activity counts per day was calculated, as well as the average minutes per day subjects spent in light i.e. &lt;3.00 Metabolic Equivalent of Task (MET), moderate (3.00-5.99 MET) vigorous (6.00-8.99 MET) or very vigorous activity (&gt;8.99 MET). Subjects also completed an online questionnaire including the BASDAI (disease activity, 0 no symptoms to 10 worst symptoms), BASFI (limitations in physical function, 0 no limitations to 10 most limitations), disease duration in years (patients only), height and weight. <h3>Results</h3> A total of 135 AS patients (mean age 51 ± 13 y; 60% males; disease duration of 17 ± 12 y) and 100 healthy controls (mean age 44 ± 12 years; 66% males) were included. Patients with AS were significantly older, <i>P</i> &lt;0.001 and had a mean ± SD body mass index (BMI) in kg/m<sup>2</sup> of 26.0 ± 4.3, compared to 24.8 ± 5.0 in controls (NS). Patients showed the same total amount of PA as well as time spent in low and moderate activity as controls (Table 1). Controls spent slightly more time in vigorous and very vigorous PA. Patients reported significantly higher on the BASDAI 4.3 ± 2.2 and BASFI 4.1 ± 2.6 opposed to controls 1.3 ± 1.2 and 0.38 ± 0.7 respectively, (both <i>P</i> &lt;0.001). <h3>Conclusions</h3> Despite experiencing more limitations and disease activity, patients with AS scored a similar amount of total PA as controls and spent equal time in light and moderate PA, except for vigorous and very vigorous PA even though the patients were older. This study indicates the importance of including objective measures of physical functioning in patients with AS. <h3>Disclosure of Interest</h3> S. van Genderen: None Declared, A. Boonen Grant/research support from: MSD, Pfizer, Amgen, Abbott, Consultant for: Pfizer, Speakers bureau: Pfizer, UCB, P. Jacobs: None Declared, L. Heuft: None Declared, J. Luime: None Declared, A. Spoorenberg: None Declared, S. Arends: None Declared, D. van der Heijde: None Declared, R. Landewe: None Declared, G. Plasqui: None Declared
Peter Henry Dickinson
Authors: Michael Griffin
Journal: BMJ (2015)

In his time as a consultant at the Royal Victoria Infirmary, Newcastle upon Tyne, from 1958 to 1986, Peter Henry Dickinson was one of the major figures in vascular surgery in the United Kingdom. Together with his colleague, Ian McNeill, he developed vascular surgery as a specialty and the Newcastle unit as one of the premier services in the UK. This was based on excellent clinical care and technical expertise. 

Peter Dickinson was born in Newcastle as a twin. His …
P5-14-17: Stage IV at Presentation – Are HER2 Positive Tumors Overrepresented?
Authors: R Woods, R Yerushalmi, C Speers, S Tydesley, K Gelmon
Journal: Cancer Research (2011)

Abstract Background: A minority of patients are diagnosed with Stage IV breast cancer at presentation. Recent studies (Dawood 2010) have suggested a better outcome for de novo vs. recurrent Stage IV but they did not account for the variation of molecular subtype. We questioned whether HER2 overexpressing tumors were over-represented in de novo Stage IV disease, and whether this impacted on survival compared to other subtypes. Further, if different subtypes are more likely to present with metastatic disease, then this factor may need to be considered when developing guidelines for staging. With such considerations in mind, the purpose of this study was to determine the breast cancer subtypes according to stage. The main hypothesis was that HER2 positive tumors would be more prevalent in stage IV presentations. Methods: Using the Breast Cancer Outcomes Unit database from the BC Cancer Agency (BCCA), patients referred to the BCCA with a new diagnosis of breast cancer between 2005 and 2010 were selected. Patients with a previous or synchronous contralateral breast cancer, male cases, and patients with referrals for reasons other than new disease were excluded. Four subtypes according to available markers were defined: ER+/HER2−, ER+/HER2+, ER-/HER2+, and ER-/HER2−. Results: Using these criteria, 485 cases of de novo stage IV disease and 10,723 stages I — III cases were extracted. After excluding cases with missing data, our final cohort consisted of 10,186 stage I-III cases and 425 stage IV cases. Distribution by subtype is presented in the Table below. Assessment of other patient characteristics for the group of Stage IV de novo patients revealed that age (younger for HER+ subgroups), site of metastases (more visceral vs. non- visceral for ER-/HER2+ and ER-/HER2−) and type of systemic therapy (chemotherapy (CT), hormone therapy (HT), trastuzumab (T) or not) were significant. Surgery rates for both mastectomy and breast-conserving surgery were similar for all subtypes. The ER-/HER2− subtype had the worst overall survival (p &amp;lt; 0.001). Conclusion: Young age and HER2 overexpression is more common in stage IV de novo presentations (26.6% of stage IV tumors were HER2+ vs. only 16% of stage I-III tumors). This data may be important in considering routine staging guidelines at diagnosis to ensure correct diagnosis and treatment recommendations. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-14-17.
Abstract B21: Defining the DNA damage response-mediated barrier to ErbB2-induced transformation of somatic mammary cells <i>in vivo</i>
Authors: Jay P. Reddy, Sirisha Peddibhotla, Wen Bu, Jing Zhao, Svasti Haricharan, Yi-Chieh Nancy Du, Katrina Podyspanina, Jeffrey M. Rosen, Larry A. Donehower, Yi Li
Journal: Cancer Research (2009)

Abstract The DNA damage response (DDR) represents a signaling cascade, which is comprised of DNA damage sensors (such as γH2AX and 53BP1), ATM, Chk2, p53, among others, that becomes activated when confronted with DNA double strand breaks and other forms of DNA damage. The activation of the DDR, in addition to the ARF pathway, has recently been found to elicit apoptosis and senescence in response to oncogene activation. However, the significance of a DDR in blocking cancer progression has not been tested in breast carcinogenesis. Preneoplastic lesions in four germline transgenic models of breast cancer that express polyoma middle T antigen (PyMT), ErbB2, c-Myc, or H-Ras do not exhibit a DDR. We have previously reported a novel mouse model of mammary cancer, where oncogenes can be introduced into somatic mammary epithelial cells via retroviral infection of RCAS vectors into MMTV-tva mice (termed RCAS-TVA). Hyperplastic lesions in the mammary gland induced by somatic introduction of PyMT using the RCAS-TVA system display a robust DDR accompanied by increased p53 and apoptosis. This observation represents the first study, to our knowledge, to fully recapitulate DDR signaling in response to acute oncogenic stress in the in vivo mammary gland. 20–30% of all breast cancers display amplification of ErbB2, a cellular oncogene which, when activated in somatic murine mammary cells, forms sporadic tumors with a long latency. Like RCAS-PyMT, we found that p53 stabilization and apoptosis, as well as senescence, are induced by somatic activation of RCAS-ErbB2. In advanced RCAS-ErbB2-induced tumors, DDR signaling and ARF induction persist, yet p53 stabilization and apoptosis are lost. Surprisingly, attributes of senescence remain in some of the ErbB2 tumor cells. To demonstrate that the DDR is critical for oncogene-induced apoptosis and senescence, we generated RCAS-ErbB2 lesions in ATM-deficient mice. Strikingly, p53 stabilization, apoptosis, and senescence were no longer activated following ErbB2 activation in the absence of ATM signaling. These data suggest that a DDR plays a critical role in inhibiting breast carcinogenesis by inducing senescence and apoptosis, the latter, but not the former, of which is lost in progression to tumors. Furthermore, these findings indicate that therapies designed to bolster the activity of DDR signaling kinases and effectors may have a broad role in breast cancer prevention. Citation Information: Cancer Res 2009;69(23 Suppl):B21.
Abstract 3820: Inhibition of M1 macrophages may aid the conversion process to M2, which may aid tumor survival and growth
Authors: Ryley A. Enz, Charles Knechtel, Amanda Dee Enz, Bryan Swanson, Richard Robison, Kim O'Neill
Journal: Cancer Research (2010)

Abstract Macrophages perform a variety of functions, from phagocytosis to the repair and remodeling of damaged tissues. Two phenotypes have been proposed: M1 and M2. The M1 macrophage performs phagocytosis of tumor cells and releases pro-inflammatory cytokines. The M2 macrophage acts as a support cell by promoting the healing of damaged cells by angiogenesis and tissue remodeling. The transition from M1 to M2 may be facilitated by tumor environments. To further study the relationship between cancer and macrophages we developed a live-cell migration assay, which measures cancer's ability to recruit macrophages. We hypothesize that cancer cell lines have varied abilities to recruit macrophages and convert them into M2, and that this ability corresponds to the aggressiveness of the cell line. Macrophages were derived from the human mononuclear phagocyte cell line U937, after addition of phorbol 12-myristate 13-acetate (PMA). These U937 cells were incubated with three adenocarcinomas of varying aggressivity. The adenocarcinomas were MDA-MB-435, MDA-MB-231, and MCF7. The U937 cells were separated from the three cell lines by 3.0 µm trans-permeable polycarbonate membranes (Corning Inc.) which allowed the U937 cells to migrate to the cell lines. After 1 hour non-migratory U937 cells were isolated and counted by means of a hemocytometer. The control without cancer caused 73.86% of U937 cells to remain, MDA-MB-435 69.28% (N=24, P=0.29), MCF7 61.09% (N=24, P&amp;lt;0.01), and MDA-MB-231 55.83% (N=24, P&amp;lt;0.01). This data was then compared with expression levels of macrophage Migration Inhibition Factor (MIF) analyzed from Real Time PCR data. These samples consisted of monocytes, from human blood, which were co-incubated with the cell lines for 48 hours. The cells were separated by 0.4 µm trans-permeable polycarbonate membranes (Corning Inc.) to prevent cells from coming into contact and allowing signal exchange. The RT-PCR data correlated with the migration data. The amount of MIF increased 7.56 fold, (N=9) in MDA-MB-435 when compared to controls, 3.13 fold for MCF7 (N=9), and 1.33 fold for MDA- MB-231 (N=9). This data suggests that the more aggressive the cancer the more MIF emitted and the greater the potential to inhibit macrophages. Previous studies have shown Interleukin-10, (IL-10), IL-6, IL-4, and prostaglandin F2 (PGF2) to be released from tumors and inhibit the cytotoxic activity of macrophages. This exposure to IL-10 has been suggested to convert M1 macrophages to a M2 phenotype. The migration inhibition observed from this study might be the initial step in the conversion process from M1 to M2. 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 3820.
Productivity of Nuclear Medicine Physicians and Radiologists
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2010)

Work relative value units are only one consideration of the total work output of a nuclear medicine physician or radiologist. It is also important to consider methodological issues with the relative value units. Other important issues are how much work the individual does in areas such as administration, volunteering in societies, research, developing new protocols, introducing new studies, and various teaching activities. The quality of the work done by the physician is also important.
Maternal-Fetal Transfer of Thyroxine in Congenital Hypothyroidism Due to a Total Organification Defect or Thyroid Agenesis
Authors: Thomas Vulsma, Margareth H. Gons, Jan J.M. de Vijlder
Journal: New England Journal of Medicine (1989)

The fact that neonates who subsequently have severe hypothyroidism have no evidence of the condition at birth suggests the possibility of the placental transfer of thyroid hormones. Recent studies have demonstrated the existence of such transfer in hypothyroid rats. To determine whether there is a transfer of thyroxine (T4) from mother to fetus, we studied 25 neonates born with a complete inability to iodinate thyroid proteins and therefore to synthesize T4. This total organification defect is an autosomal recessive disorder with an incidence of approximately 1 in 60,000 neonates in the Netherlands. In the cord serum of affected neonates, T4 levels ranged from 35 to 70 nmol per liter. Since these patients were unable to produce any T4, the T4 must have originated in their mothers. The estimated biologic half-life of serum T4 was 3.6 days (95 percent confidence interval, 2.7 to 5.3). In 15 neonates with thyroid agenesis, the serum levels and the disappearance kinetics of T4 were the same as those in the neonates with a total organification defect, suggesting that in these infants, the T4 also had a maternal origin. We conclude that in infants with severe congenital hypothyroidism, substantial amounts of T4 are transferred from mother to fetus during late gestation. (N Engl J Med 1989;321:13–6.)
Hemolytic Anemia in Wilson's Disease
Authors: N. McIntyre, H. M. Clink, A. J. Levi, J. N. Cumings, Sheila Sherlock
Journal: New England Journal of Medicine (1967)

JAUNDICE is a common presentation of Wilson's disease and may precede the neurologic features by many years.1 , 2 Infective hepatitis is often invoked as an explanation of the initial episode, and Wilson's disease is rarely considered at that time. Subsequently, neurologic symptoms may lead to a correct diagnosis when such features as jaundice and ascites are attributed, in retrospect, to the cirrhosis of Wilson's disease. After this initial episode no further features suggesting hepatic involvement may appear despite neurologic abnormalities of many years' duration. Furthermore, ascites, of grave prognostic significance in most forms of cirrhosis, is often an early feature in . . .
Crohn’s Disease of the Esophagus Visualized by Tc-99m Antigranulocyte Antibodies
Authors: Drazen Huić, Damir Dodig, Marina Premuzić, Zeljko Krznarić, Boris Vucelić
Journal: Clinical Nuclear Medicine (2002)

HUIĆ, DRAZEN M.D., Ph.D.*; DODIG, DAMIR M.D., Ph.D.*; PREMUZIĆ, MARINA M.D.†; KRZNARIĆ, ZELJKO M.D., Ph.D.†; VUCELIĆ, BORIS M.D.† Author Information
A Phase 2 Study of Trastuzumab Emtansine in Japanese Patients with HER2 Positive Metastatic Breast Cancer
Authors: S. Takahashi, M. Kashiwaba, S. Takao, Y. Ito, H. Doihara, Y. Rai, M. Matsubara, K. Kanatani, N. Masuda
Journal: Annals of Oncology (2013)
Tobacco and the Developing World: An Old Threat Poses Even Bigger Problems
Authors: S. Wagner, R. M. Romano
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Tobacco and the Developing World: An Old Threat Poses Even Bigger Problems Get access Sally Wagner, Sally Wagner Search for other works by this author on: Oxford Academic PubMed Google Scholar Rose Mary Romano Rose Mary Romano Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 23, 7 December 1994, Page 1752, https://doi.org/10.1093/jnci/86.23.1752 Published: 07 December 1994
P3-07-46: Accuracy of SPIO-Enhanced MR Imaging Alone for the Diagnosis of Sentinel Node Metastases in Patients with Breast Cancer.
Authors: K Motomura, S Nakahara, M Ishitobi, Y Komoike, H Koyama, H Inaji, T Horinouchi, K Nakanishi
Journal: Cancer Research (2011)

Abstract Background Superparamagnetic iron oxide (SPIO)-enhanced MR imaging has been reported to be promising for the detection of metastases in sentinel nodes localized by CT lymphography in patients with breast cancer (Motomura, Ann Surg Oncol 2011). The current SPIO technique involves imaging before and after contrast administration. This study evaluated the accuracy of SPIO-enhanced MR imaging alone without unenhanced imaging. Methods: This study included 120 patients with breast cancer demonstrating clinically negative nodes. Sentinel nodes were identified by CT lymphography, and MR imaging of the axilla before and 18–24 hr after interstitial administration of SPIO was performed. A node was considered non-metastatic if it showed a homogenous low signal intensity and metastatic if there was an absence of low signal intensity either in the entire node or in a focal area on SPIO-enhanced MR imaging. The diagnostic accuracy of the SPIO-enhanced imaging alone was compared with that of combined unenhanced and SPIO-enhanced imaging. Results: The mean number of sentinel nodes identified by CT lymphography was 1.2 (range 1–3). Pathologic evaluation demonstrated that 28 (23.3%) of 120 patients showed metastasis to at least one node. One false negative result was added when the evaluation was based solely on SPIO-enhanced MR imaging. Consequently, the sensitivity decreased from 84.0% to 80.0% and the accuracy decreased from 89.2% to 88.3%, respectively, in the SPIO-enhanced MR imaging alone. However, the differences in sensitivity and accuracy between SPIO-enhanced MR imaging alone and the combined unenhanced and SPIO-enhanced imaging were not significant (McNemar's test; p=1.0). The specificity of enhanced imaging alone and that of combined unenhanced and SPIO-enhanced imaging were both 90.5%. Conclusions: A single MR imaging examination performed after SPIO administration can be used for accurate diagnosis of sentinel node metastases, and thus reduce the time and cost of imaging. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-46.
EFFECT OF SPINAL CORD STIMULATION ON CARDIAC SYMPATHETIC NERVE ACTIVITY IN PATIENTS WITH HEART FAILURE
Authors: Jan Naar, Deborah A. Jaye, Cecilia Linde, Petr Neuzil, Petr Doskar, Filip Malek, Frieder Braunschweig, Lars Lund, Lars Mortensen, Bengt Linderoth, Göran Lind, Dianna Bone, Arthur Scholte, Aimee Pol, Fred Kueffer, Jodi Koehler, Kamibiz Shahgaldi, Otto Lang, Marcus Stahlberg
Journal: Journal of the American College of Cardiology (2016)
A phase 1 study of imatinib for corticosteroid-dependent/refractory chronic graft-versus-host disease: response does not correlate with anti-PDGFRA antibodies
Authors: George L. Chen, Sally Arai, Mary E. D. Flowers, Joanne M. Otani, Jingxin Qiu, Ethan C. Cheng, Alex McMillan, Laura J. Johnston, Judith A. Shizuru, David B. Miklos
Journal: Blood (2011)