tbuckley/cabot-search huggingface dataset:
SAT0118 Impact of disease activity on lipid profiles and adipocytokines in patients with rheumatoid arthritis –the tomorrow study-:
Authors: Y. Sugioka, T. Koike, K. Mamoto, T. Okano, M. Tada, S. Wakitani, H. Nakamura
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Arteriosclerosis is a risk factor for mortality among patients with rheumatoid arthritis (RA) and it is associated with changes in lipid profiles. Therefore, the present prospective cohort study evaluates risk factors and lipid profiles associated with disease activity in patients with RA (TOMORROW study; TOtal Management Of Risk factors in Rheumatoid arthritis patients to lOWer morbidity and mortality, clinical trial registration number: UMIN000003876). <h3>Methods</h3> Lipid profiles and serum levels of adipocytokines such as adiponectin or leptin were prospectively evaluated relative to disease activity in 202 consecutive patients with RA (109 of whom were treated with biological agents) and 202 age- and sex-matched healthy volunteers (HV). The mean age of the 341 females and 61 males was 57.9 (20.9 - 79.3) years. <h3>Results</h3> The following were lower in patients with RA than in HV at baseline: serum total cholesterol, 210 vs. 222 mg/dL (p&lt;0.01); high-density lipoprotein (HDL) cholesterol, 65.4 vs. 69.1 mg/dL (p&lt;0.05) and low-density lipoprotein (LDL) cholesterol, 120 vs. 126 mg/dL (p&lt;0.05). However, serum levels of both leptin and adiponectin and ratio of body fat were higher in patients with RA than in HV (7.5 vs. 5.6 μg/mL, p&lt;0.001, 12.2 vs. 11.2 μg/mL, p&lt;0.05 and 29.4 vs. 27.2%, p&lt;0.001 respectively). Changes in all three cholesterol values after one year inversely correlated with those in disease activity score (DAS) 28 (Table 1).Serum adiponectin was associated with DAS28 at baseline (r =0.248; p=0.003), but changes in these values did not correlate with DAS28 scores after one year (Table 1). <h3>Conclusions</h3> Improvements in disease activity increased lipid levels but did not change plasma levels of adiponectin after one year in patients with RA. <h3>Disclosure of Interest</h3> Y. Sugioka: None Declared, T. Koike Grant/Research support from: Takeda Pharmaceutical, Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical, Eisai, Abbott Japan, Teijin Pharma, Banyu Pharmaceutical and Ono Pharmaceutical, K. Mamoto: None Declared, T. Okano: None Declared, M. Tada: None Declared, S. Wakitani: None Declared, H. Nakamura Grant/Research support from: Chugai Pharmaceutical, Astellas, Speakers Bureau: Ono
The Effect of Cigarette Smoking on Neutrophil Kinetics in Human Lungs
Authors: William MacNee, Barry Wiggs, Alan S. Belzberg, James C. Hogg
Journal: New England Journal of Medicine (1989)

Neutrophils may play a part in the pathogenesis of the centrilobular emphysema associated with cigarette smoking. The capillary bed of the lungs concentrates neutrophils approximately 100-fold with respect to erythrocytes, producing a large pool of marginated cells. We examined the effect of cigarette smoking on the kinetics of this pool of cells, using 99mTc-labeled erythrocytes to measure regional blood velocity and 111In-labeled neutrophils to measure the removal of neutrophils during the first passage through the pulmonary circulation, their subsequent washout from the lungs, and the effect of local blood velocity on the number of neutrophils retained in each lung region. We observed no difference in these measurements between subjects who had never smoked (n = 6) and smokers who did not smoke during the study (n = 12). However, subjects who did smoke during the study (n = 12) had a significantly slower rate of washout of Radio-labeled neutrophils from the lung (0.08±0.04 of the total per minute, as compared with 0.13±0.06 in smokers who did not smoke during the experiment and 0.14±0.08 in nonsmokers) (P = 0.02). We also observed an increase in the regional retention of labeled neutrophils with respect to blood velocity in 5 of the 12 subjects who smoked during the study, but in none of the other subjects. We conclude that the presence of cigarette smoke in the lungs of some subjects increases the local concentration of neutrophils, and suggest that the lesions that characterize emphysema may be a result of the destruction of lung tissue by neutrophils that remain within pulmonary microvessels. (N Engl J Med 1989; 321: 924–8.)
THU0411 Secukinumab Efficacy in Anti-TNF-Naive and Anti-TNF-IR Patients with Psoriatic Arthritis: Results of a Phase 3 Multicenter, Double-Blind, Placebo-Controlled Study (Future 2)
Authors: A. Kavanaugh, I.B. McInnes, S. Hall, H. Chinoy, A. Kivitz, S. Kandala, M. Patekar, S. Mpofu
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Secukinumab, a human anti–IL-17A monoclonal antibody, demonstrated significant efficacy in the randomized, double-blind, placebo (PBO)-controlled phase 3 FUTURE 2 study (NCT01752634).<sup>1</sup> <h3>Objectives</h3> To evaluate secukinumab efficacy by prior tumor necrosis factor inhibitor (anti-TNF) therapy status. <h3>Methods</h3> 397 adults with active PsA were randomized to subcutaneous (s.c.) secukinumab (300, 150 or 75 mg) or PBO at baseline, Week (Wk) 1, 2, 3, 4 and every 4 wks thereafter. Pts were stratified according to inadequate response or intolerance to prior anti-TNF therapy (anti-TNF-IR), or no prior exposure (anti-TNF-naive). The primary endpoint was American College of Rheumatology 20 (ACR20) response at Wk 24. Secondary endpoints were Psoriasis Area-and-Severity Index (PASI) 75/90 response, Disease Activity Score 28 using C-reactive protein (DAS28-CRP), Short Form-36 Physical Component Summary (SF-36 PCS), Health Assessment Questionnaire-Disability Index (HAQ-DI), ACR50, dactylitis and enthesitis. <h3>Results</h3> 35% of pts enrolled were anti-TNF-IR and 65% were anti-TNF-naive. At Wk 24, ACR20 responses were greater with secukinumab vs PBO regardless of anti-TNF status. The highest responses were generally observed among anti-TNF-naive pts (Table). Improvements were observed with secukinumab vs PBO for secondary endpoints of ACR50, PASI 75/90, DAS28-CRP, dactylitis, enthesitis, SF-36 PCS and HAQ-DI in both anti-TNF-IR and anti-TNF-naive pts. Greatest improvements in the anti-TNF-IR group were generally observed with secukinumab 300 mg (Table). <h3>Conclusions</h3> Efficacy was demonstrated with secukinumab 300 mg and 150 mg in both anti-TNF-naive and anti-TNF-IR pts, with secukinumab 300 mg being associated with the highest responses in anti-TNF-IR pts. <h3>References</h3> McInnes IB, et al. Presented at ACR 2014; L1 <h3>Acknowledgements</h3> Medical writing support was provided by Rachel Mason at Seren Communications (Tytherington, UK), and was funded by Novartis. <h3>Disclosure of Interest</h3> A. Kavanaugh Consultant for: Novartis, I. McInnes Consultant for: Novartis, Amgen, Janssen, BMS, Pfizer, UCB, Abbvie, Celgene, and Lilly, S. Hall: None declared, H. Chinoy Grant/research support from: Novartis, Janssen, Pfizer, UCB, Abbvie, Celgene, Servier, Roche, MSD, and aTyr, Consultant for: Novartis, Janssen, Pfizer, UCB, Abbvie, Celgene, Servier, Roche, MSD, and aTyr, A. Kivitz Grant/research support from: Novartis, S. Kandala Employee of: Novartis, M. Patekar Employee of: Novartis, S. Mpofu Shareholder of: Novartis, Employee of: Novartis
COMPLICACIONES DIFERIDAS DE LA SEDACION CON PROPOFOL EN EL SERVICIO DE ENDOSCOPIAS. HOSPITAL RIO CARRION DE PALENCIA ENERO A MARZO 2012
Authors: S Castillo Rocío, K De Jesus Geneaux, A Germade, B Moreira, F Igea, J Barcenilla, A Santamaria, E Madrigal Rosa, E Saracibar, A Perez
Journal: Endoscopy (2013)

Introducción: El propofol es un agente hipnótico de acción rápida utilizado de forma frecuente en endoscopia digestiva. Existen controversias sobre su utilización y múltiples referencias que presenta efectos adversos serios inmediatos durante su utilización pero no se conoce los efectos a medio plazo sobretodo relacionadas con eventos de broncoaspiración o efectos diferidos secundarios a la sedación profunda. Objetivo: Determinar las complicaciones por infecciones respiratorias diferidas de la sedación con propofol. Material y Método: En este estudio retrospectivo, hemos analizado las atenciones en el servicio de urgencia en un periodo de 2 meses posterior a la realización de todas las gastroscopias y colonoscopias bajo sedación con propofol durante el periodo de enero -marzo 2012, se incluyeron un total de 745 colonoscopias; siendo 270 (36.24%) endoscopias en mayores de 65 años y 475 (63.76%) en pacientes menores de 65 años. Un total de 449 gastroscopias. Resultados: Dosis media fue de 108 mg y 215 mg en gastroscopias y colonoscopías respectivamente. En los que se realizo colonoscopia; 4 (0,53%) acudieron al servicio de urgencias presentando infección respiratoria; dos de ellos a los 8 días, uno a los 12 y otro al día 20. Dos precisaron ingreso hospitalario. Estos pacientes presentaron una clasificación de ASA previa III y eran mayores de 65 años. En las gastroscopias; 5 (1,11%) acudieron a urgencias presentando infección respiratoria; todos precisaron ingreso hospitalario. Presentaban una clasificación de ASA III- IV; solo uno menor de 65 años. Ninguno presento durante las pruebas endoscopicas eventos graves. Ninguno de estos casos requirió ingreso en UCI.
"Good Clinical Practice" Taking Hold in EC
Authors: C. Vanchieri
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article “Good Clinical Practice” Taking Hold in EC Get access Cori Vanchieri Cori Vanchieri Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 16, August 1993, Pages 1275–1276, https://doi.org/10.1093/jnci/85.16.1275 Published: 01 August 1993
Killer cell immunoglobulin-like receptor 3DL1 polymorphism defines distinct hierarchies of HLA class I recognition
Authors: Philippa M. Saunders, Phillip Pymm, Gabriella Pietra, Victoria A. Hughes, Corinne Hitchen, Geraldine M. O’Connor, Fabrizio Loiacono, Jacqueline Widjaja, David A. Price, Michela Falco, Maria Cristina Mingari, Lorenzo Moretta, Daniel W. McVicar, Jamie Rossjohn, Andrew G. Brooks, Julian P. Vivian
Journal: The Journal of Experimental Medicine (2016)

Natural killer (NK) cells play a key role in immunity, but how HLA class I (HLA-I) and killer cell immunoglobulin-like receptor 3DL1 (KIR3DL1) polymorphism impacts disease outcome remains unclear. KIR3DL1 (*001/*005/*015) tetramers were screened for reactivity against a panel of HLA-I molecules. This revealed different and distinct hierarchies of specificity for each KIR3DL1 allotype, with KIR3DL1*005 recognizing the widest array of HLA-I ligands. These differences were further reflected in functional studies using NK clones expressing these specific KIR3DL1 allotypes. Unexpectedly, the Ile/Thr80 dimorphism in the Bw4-motif did not categorically define strong/weak KIR3DL1 recognition. Although the KIR3DL1*001, *005, and *015 polymorphisms are remote from the KIR3DL1–HLA-I interface, the structures of these three KIR3DL1–HLA-I complexes showed that the broader HLA-I specificity of KIR3DL1*005 correlated with an altered KIR3DL1*005 interdomain positioning and increased mobility within its ligand-binding site. Collectively, we provide a generic framework for understanding the impact of KIR3DL1 polymorphism on the recognition of HLA-I allomorphs.
Intraosseous Lipoma of Rib With Intense Radiotracer Uptake on Bone Scintigraphy
Authors: Le Song, Yanyan Zhang, Zhonghui Jin, Xinxin Li, Fang Mei
Journal: Clinical Nuclear Medicine (2011)

A 55-year-old woman complaining of discomfort and tenderness on the right inferior thorax for 2 weeks underwent thoracic CT scan on which a well-defined expansile lesion with fat and calcification density was demonstrated in the right ninth rib. The lesion showed marked radiotracer uptake on bone scintigraphy. Histology confirmed intraosseous lipoma with inflammatory infiltration.
Abstract P5-10-06: TACT2 Randomised Adjuvant Trial in Early Breast Cancer (EBC): Tolerability and Toxicity of Standard 3 Weekly Epirubicin (E) Versus Accelerated Epirubicin (aE) in 129 UK Hospitals (4391 Patients) (CRUK/05/019)
Authors: D Cameron, P Barrett-Lee, G Velikova, P Canney, H Moyses, M McDermaid, J Banerji, C Gaunt, C Reynolds, A Wardley, A Bowman, G Bertelli, N Murray, JM Bliss
Journal: Cancer Research (2010)

Abstract Introduction: TACT2, a multicentre phase III trial with E-CMF as control (NEAT Poole NEJM 2006), tests 2 hypotheses in a 2x2 factorial design: A) accelerating chemotherapy (CT) offers superior benefits (CALGB9741 Citron JCO 2003); B) the oral 5FU prodrug capecitabine (X) gives similar efficacy but preferential side-effect profile to CMF. Here, focus is on hypothesis A with results for compliance, QL and acute toxicities (physician &amp; patient (pt) reported) during E vs aE. Materials &amp; Methods: Dec 2005-08 4391 pts (4371 women, 20 men) with node +ve or high risk node -ve invasive EBC were recruited. Pts were randomised to receive either E (100mg/m2 x 4) q3wk or q2wk aE (100mg/m2 x 4 plus pegfilgrastim, 6mg d2) followed by classical CMF q4wk x 4 or X (2500mg/m2/day x 14) q3wk x 4. Detailed CTCAE toxicity was to be assessed in subset (38 centres, 2137 pts). Of these, 2127 pts received ≥1 cycle CT. 1279 of these pts completed pt-reported outcomes (EORTC QLQ-C30 and pre-defined pt-reported TACT2 toxicities) with 910 completing baseline on time and having end cycle 4 data. P&amp;lt;0.01 classed as significant. Toxicities/which differ between groups are shown where p-values are trend tests across all grades &amp; % grade 3+ are reported. QL assessed via linear regression models. Results: 33/4391 pts did not start CT. 4259 (97%) completed the initial 4 cycles (E 2143 (96%), aE 2116 (98%) with RDI &amp;gt;85% for E 2058 (93%) and aE 1983 (91%). During cycles 1-4 higher rates of hand-foot syndrome &amp; anaemia were seen with aE vs E (P&amp;lt;0.001). Few were grade 3+ (E 0%, aE 0.9% &amp; E 0%, aE 0.1%) respectively. Lower grade 3+ rates (all P&amp;lt;0.001) were seen with aE vs E for: ANY toxicity (E 27%, aE 18%), leucopenia (E 4%, aE 1%), neutropenia (E 17%, aE 2%) &amp; febrile neutropenia (E 4%, aE 2%). Change from baseline in global QL, role functioning &amp; fatigue was worse with aE vs E (P&amp;lt;0.001); no differences were reported for aE vs E for impact of individual pre-defined TACT2 toxicities on daily activities (Nausea, vomiting, tingling hands and/or feet, diarrhoea, constipation, sore mouth, mouth ulcers). Conclusion: In TACT2, the largest adjuvant trial reporting acute toxicities for standard vs accelerated E in EBC, serious CTCAE toxicity was less common with aE compared with E, however pts report poorer global QL, fatigue &amp; role function which does not appear to be explained by impact on daily activities due to individual side-effects. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-10-06.
Abstract 3708: Carbon nanotubes: Feasibility as nano-bio agents to target cancer
Authors: Vera Neves, Elena Heister, Johnjoe McFadden, Ravi P. Silva, Helen M. Coley
Journal: Cancer Research (2010)

Abstract The targeting of genes in cancer cells to stop tumour growth and kill the cancer cells has emerged as a promising approach for cancer therapy. The key challenges for the application of this kind of approach are largely dependent on the development of suitable delivery systems. None of the current transfection methods are ideal, mainly because they often provoke immune responses. Recently, carbon nanotubes (CNTs) have been shown to transverse cellular membranes and shuttle biological molecules, including DNA, siRNA, and proteins into cancer cells. The main advantages of carbon nanotubes compared with other delivery agents are their biocompatibility and the large surface area. To consider carbon nanotubes as nano-bio agents for gene therapy it is important first, understand how they behave at a cellular level. In our lab, we have carried out studies to determine the fate and trafficking of carbon nanotubes in cancer cells. Evidence of carbon nanotube uptake and release has been shown with no significant changes in cell components, such as DNA/RNA, proteins and lipids. Moreover, no significant stress was induced when cells were exposed to carbon nanotubes. Intracellular localisation and trafficking of carbon nanotubes was carried out by antibody staining of specific compartments within the cell and reveal that an endocytic pathway is involved on the internalisation of carbon nanotubes. Finally, our work is currently focusing on the development of an in vitro model to examine the feasibility of using functionalized, CNTs as a means of delivering gene therapy using siRNA. We will then use this as a basis for further in vivo work using human tumour xenograft models with characterised genotypes (e.g. mutated p53 etc) to validate this approach. 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 3708.
Abstract 455: Adipocyte sTNFR2 secretion and macrophage migration in the breast tumors
Authors: Stephen Rego, Muthulekha Swamydas, Krista Ricci, Didier Dréau
Journal: Cancer Research (2011)

Abstract The breast tumor microenvironment greatly influences tumor progression and modulates the migratory abilities of both cancer cells and macrophages, especially M2 macrophages, at the tumor site. The pleiotropic inflammatory cytokine TNFα through interactions with TNFR promotes macrophage migration and tumor cell apoptosis. The shedding of TNFR increases the concentration of sTNFR within the tumor microenvironment. We determined whether sTNFR modulates the trafficking of specific macrophage subtypes in the tumor microenvironment. Concentrations of TNFα, sTNFR1 and sTNFR2 secreted by 4T1 and NMuMG mammary epithelial cells, stroma mesenchymal stem cells, and adipocyte-derived cells were measured by cytokine arrays and ELISA. The migration of murine monocytes cultured in media promoting preferential expression of M0, M1, or M2 phenotypes toward tumor or stroma cell conditioned media (CM) was determined by transwell assays. The effects of conditioned media obtained following treatment with the sheddase inhibitor TAPI-0 on cell migration were also assessed. The concentrations of sTNFR2 secreted were drastically higher in the CMs from 4T1 cells compared to NMuMG cells (p&amp;lt;0.05). In addition, adipocytes secreted markedly more sTNF2 compared to D1 mesenchymal stem cells (p&amp;lt;0.05). sTNFR2 concentrations were significantly decreased in the presence of a sheddase inhibitor (p&amp;lt;0.05). The transwell migration of M2 phenotype macrophages toward 4T1-CM was significantly greater than the migration of M0 or M1 phenotype macrophages (p&amp;lt;0.05). Furthermore, only the migration of the M2 macrophage subtype following TAPI-0 treatment toward 4T1 CM was markedly higher (p&amp;lt;0.05). These results strongly suggest a role for sTNFR secreted by tumor cells and adipocytes in the infiltration of M2 phenotype macrophages within the tumor microenvironment. Whether selective prevention of sTNFR shedding may have therapeutic benefit for breast cancer patients remains to be determined. This work was supported by grants from the Department of Defense Era of Hope program (BC044778) and the National Science Foundation EFRI program (CBE0736007). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 455. doi:10.1158/1538-7445.AM2011-455
Clinical Consequences of Acquired Transfusional Iron Overload in Adults
Authors: Andrew I. Schafer, Robert G. Cheron, Robert Dluhy, Barry Cooper, Ray E. Gleason, J. S. Soeldner, H. Franklin Bunn
Journal: New England Journal of Medicine (1981)

We assessed the clinical sequelae of transfusional iron overload in 15 nonthalassemic adults (40 to 71 years of age) with anemias requiring transfusions. Iron loading had been present for less than four years in 14 patients. The number of units of blood transfused ranged from 60 to 210 (mean, 120). Liver-biopsy specimens in 10 patients contained seven to 26 times the normal amount of iron and typically showed focal portal fibrosis. Left ventricular cardiac function was impaired in only the most heavily transfused patients or in those with coexisting coronary-artery disease, All patients had glucose intolerance associated with significantly reduced insulin output, compared with controls (P < 0.01). Pituitary reserve of ACTH was limited in 10 of 12 patients, and that of gonadotropin in five of 13. We conclude that widespread subclinical organ dysfunction can result from transfusional iron overload developing in adulthood. The pattern of organ involvement resembles that encountered in idiopathic hemochromatosis.
Ga-67 Citrate Uptake in Bilateral Endogenous Endophthalmitis
Authors: PETER DAVIES, GEOFFREY STOREY, PAUL ROACH
Journal: Clinical Nuclear Medicine (1999)

A 58-year-old woman was hospitalized with sepsis and visual loss. An abdominal CT revealed a hepatic abscess, which was surgically drained, and Klebsiella pneumoniae was cultured from the aspirate. Ga-67 citrate imaging, which was performed to screen for metastatic sites of infection, showed avid uptake by both eyeballs. This is consistent with the clinical diagnosis of bilateral endogenous endophthalmitis obtained by ocular examination. Ga-67 citrate is commonly used to assess ocular sarcoidosis. Its diagnostic utility has been investigated in malignant ocular conditions such as melanoma and orbital lymphoma. Increased Ga-67 uptake by the lacrimal glands occurs physiologically and may be confused with pathologic ocular uptake.