tbuckley/cabot-search huggingface dataset:
OP0203-HPR Does Enat-Focused Education Improve Health Outcomes in Ra? A Randomised Controlled Trial: Table 1
Authors: B. Hardware, T. Young, D.B. Johnson, M. Ndosi, C. Hale, J.R. Maxwell, E. Roussou, A. Adebajo
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> The aim of this study was to evaluate the effectiveness of ENAT-focused patient education on self-efficacy, health status and patient knowledge. We hypothesised that, the use of the ENAT to help focus patient education on patients9 priority educational needs, would improve their self-efficacy and health status. <h3>Methods</h3> This study was a pragmatic 7-centre RCT. The inclusion criteria were: a diagnosis of RA, age 18+ years and ability to complete questionnaires. Patients were randomised to either the ENAT group where patients completed the ENAT which was then used as a template by the Clinical Nurse Specialist (CNS) to meet their educational needs; or usual care by CNS without the ENAT. Patients were seen at baseline then at weeks 16 and 32. The outcomes were self-efficacy (ASES), health status (AIMS2-SF) and patient knowledge (PKQ). We investigated between-group differences (t-test) and trends over time (repeated measures ANOVA). Intention-to-treat results are reported (multiple imputation for missing data) except AIMS2-SF-Work data, where complete case analysis was used for patients who were working. <h3>Results</h3> A total of 132 patients were recruited, 70 EG (53%) and 62 UC (47%). Their mean (SD) age was 54 (12.3), 56 (13.3) and disease duration 5.2 (4.9), 6.7 (8.9) for EG and UC respectively. Questionnaire completion rates (EG, UC) were; 97%, 97% (baseline) 90%, 85% (week 16) and 79%, 76% (week 32). Significant between-group differences were found, in favour of the EG at week 32 in ASES-Pain, MD (SE)=-4.36 (1.6), t=-2.72, P=0.008; ASES-Other symptoms, MD (SE)=-5.84 (3.06), t=-3.07, p=0.003; AIMS2-SF Symptoms, MD (SE)=1.04 (0.41), t=5.54, p=0.013 and AIMS2-SF Affect, MD (SE)=0.86 (0.30), t=2.84, p=0.006. Between-group differences were not significant in other time-points or in the total PKQ score. Table 1 presents within-group changes over time. Scores are mean (SD) after multiple imputations. The ENAT group showed significant improvements in most outcomes while usual care showed significant improvements only on AIMS2-SF work. <h3>Conclusions</h3> This is the first study to report the effects of ENAT-focused education in people with RA, suggesting improvements in self-efficacy and aspects of health status. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3541
Positive and Negative Selection of T Cells
Authors: Timothy K. Starr, Stephen C. Jameson, Kristin A. Hogquist
Journal: Annual Review of Immunology (2003)

A functional immune system requires the selection of T lymphocytes expressing receptors that are major histocompatibility complex restricted but tolerant to self-antigens. This selection occurs predominantly in the thymus, where lymphocyte precursors first assemble a surface receptor. In this review we summarize the current state of the field regarding the natural ligands and molecular factors required for positive and negative selection and discuss a model for how these disparate outcomes can be signaled via the same receptor. We also discuss emerging data on the selection of regulatory T cells. Such cells require a high-affinity interaction with self-antigens, yet differentiate into regulatory cells instead of being eliminated.
James McGregor (“Greg”) Imray
Authors: George Robertson
Journal: BMJ (2004)

Former consultant anaesthetist and intensive care specialist Aberdeen Royal Infirmary (b Inverness 1933; q Aberdeen 1957; DA, FFA RCS), d 19 August 2004.​2004.




Figure 1




After several years in surgical posts in Tasmania, Greg returned to Aberdeen in 1962. He was appointed consultant anaesthetist in 1971 and was instrumental in establishing Aberdeen as the fourth centre in Scotland for open cardiac surgery. In 1988 he was flown offshore to the scene of the disaster caused by a major explosion on the Piper Alpha drilling platform. In 1994 a modern intensive therapy unit was opened in which a plaque was unveiled to recognise and commemorate Greg's central initiatives in establishing intensive therapy in Aberdeen. He leaves a wife, Lucy, and a daughter.
Light Delivery over Extended Time Periods Enhances the Effectiveness of Photodynamic Therapy
Authors: Mukund Seshadri, David A. Bellnier, Lurine A. Vaughan, Joseph A. Spernyak, Richard Mazurchuk, Thomas H. Foster, Barbara W. Henderson
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The rate of energy delivery is a principal factor determining the biological consequences of photodynamic therapy (PDT). In contrast to conventional high-irradiance treatments, recent preclinical and clinical studies have focused on low-irradiance schemes. The objective of this study was to investigate the relationship between irradiance, photosensitizer dose, and PDT dose with regard to treatment outcome and tumor oxygenation in a rat tumor model. Experimental Design: Using the photosensitizer HPPH (2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide), a wide range of PDT doses that included clinically relevant photosensitizer concentrations was evaluated. Magnetic resonance imaging and oxygen tension measurements were done along with the Evans blue exclusion assay to assess vascular response, oxygenation status, and tumor necrosis. Results: In contrast to high-incident laser power (150 mW), low-power regimens (7 mW) yielded effective tumor destruction. This was largely independent of PDT dose (drug-light product), with up to 30-fold differences in photosensitizer dose and 15-fold differences in drug-light product. For all drug-light products, the duration of light treatment positively influenced tumor response. Regimens using treatment times of 120 to 240 min showed marked reduction in signal intensity in T2-weighted magnetic resonance images at both low (0.1 mg/kg) and high (3 mg/kg) drug doses compared with short-duration (6-11 min) regimens. Significantly greater reductions in pO2 were observed with extended exposures, which persisted after completion of treatment. Conclusions: These results confirm the benefit of prolonged light exposure, identify vascular response as a major contributor, and suggest that duration of light treatment (time) may be an important new treatment variable.
The <i>N</i>-Glycans Determine the Differential Blood Clearance and Hepatic Uptake of Human Immunoglobulin (Ig)a1 and Iga2 Isotypes
Authors: Abdalla Rifai, Kim Fadden, Sherie L. Morrison, Koteswara R. Chintalacharuvu
Journal: The Journal of Experimental Medicine (2000)

Human immunoglobulin (Ig)A exists in blood as two isotypes, IgA1 and IgA2, with IgA2 present as three allotypes: IgA2m(1), IgA2m(2), and IgA2m(n). We now demonstrate that recombinant, chimeric IgA1 and IgA2 differ in their pharmacokinetic properties. The major pathway for the clearance of all IgA2 allotypes is the liver. Liver-mediated uptake is through the asialoglycoprotein receptor (ASGR), since clearance can be blocked by injection of excess galactose-Ficoll ligand and suppressed in ASGR-deficient mice. In contrast, only a small percentage of IgA1 is cleared through this pathway. The clearance of IgA1 lacking the hinge region with its associated O-linked carbohydrate was more rapid than that of wild-type IgA1. IgA1 and IgA2 that are not rapidly eliminated by the ASGR are both removed through an undefined ASGR-independent pathway with half-lives of 14 and 10 h, respectively. The rapid clearance of IgA2 but not IgA1 through the liver may in part explain why the serum levels of IgA1 are greater than those of IgA2. In addition, dysfunction of the ASGR or altered N-linked glycosylation, but not O-glycans, that affects recognition by this receptor may account for the elevated serum IgA seen in liver disease and IgA nephropathy.
Phase I Study of PARP Inhibitor ABT-888 in Combination with Topotecan in Adults with Refractory Solid Tumors and Lymphomas
Authors: Shivaani Kummar, Alice Chen, Jiuping Ji, Yiping Zhang, Joel M. Reid, Matthew Ames, Lee Jia, Marcie Weil, Giovanna Speranza, Anthony J. Murgo, Robert Kinders, Lihua Wang, Ralph E. Parchment, John Carter, Howard Stotler, Larry Rubinstein, Melinda Hollingshead, Giovanni Melillo, Yves Pommier, William Bonner, Joseph E. Tomaszewski, James H. Doroshow
Journal: Cancer Research (2011)

Abstract A phase I trial of ABT-888 (veliparib), a PARP inhibitor, in combination with topotecan, a topoisomerase I–targeted agent, was carried out to determine maximum tolerated dose (MTD), safety, pharmacokinetics, and pharmacodynamics of the combination in patients with refractory solid tumors and lymphomas. Varying schedules and doses of intravenous topotecan in combination with ABT-888 (10 mg) administered orally twice a day (BID) were evaluated. Plasma and urine pharmacokinetics were assessed and levels of poly(ADP-ribose) (PAR) and the DNA damage marker γH2AX were measured in tumor and peripheral blood mononuclear cells (PBMC). Twenty-four patients were enrolled. Significant myelosuppression limited the ability to coadminister ABT-888 with standard doses of topotecan, necessitating dose reductions. Preclinical studies using athymic mice carrying human tumor xenografts also informed schedule changes. The MTD was established as topotecan 0.6 mg/m2/d and ABT-888 10 mg BID on days one to five of 21-day cycles. Topotecan did not alter the pharmacokinetics of ABT-888. A more than 75% reduction in PAR levels was observed in 3 paired tumor biopsy samples; a greater than 50% reduction was observed in PBMCs from 19 of 23 patients with measurable levels. Increases in γH2AX response in circulating tumor cells (CTC) and PBMCs were observed in patients receiving ABT-888 with topotecan. We show a mechanistic interaction of a PARP inhibitor, ABT-888, with a topoisomerase I inhibitor, topotecan, in PBMCs, tumor, and CTCs. Results of this trial reveal that PARP inhibition can modulate the capacity to repair topoisomerase I–mediated DNA damage in the clinic. Cancer Res; 71(17); 5626–34. ©2011 AACR.
Downregulation of N-cadherin in the neointima stimulates migration of smooth muscle cells by RhoA deactivation
Authors: R Blindt
Journal: Cardiovascular Research (2004)

Objective: The aim of the study was to analyze whether cadherin- and Rho-family GTPases-mediated dynamic rearrangement of cell–cell adhesion play an important role during human arterial smooth muscle cell (haSMC) migration. Methods: Expression patterns of N-cadherin and β-catenin were analyzed in a domestic pig restenosis model after 14, 28, and 90 days as well as in quiescent and migratory haSMCs in vitro. N-cadherin expression was upregulated by transient sense; downregulation was induced by antisense transfection. For functional inhibition, antibody GC-4 was used. Cell migration was quantified using Boyden chamber assays. Regulation of RhoA GTPase was tested by assessment of RhoA activity. Results: In vivo analysis of N-cadherin expression in a porcine restenosis model revealed downregulation in the neointima after 14 days. After 28 days, N-cadherin expression was slightly restored, while after 90 days, no difference between medial and neointimal expression was detectable. β-Catenin levels remained unchanged during the whole period. According to the in vivo situation, N-cadherin was significantly downregulated in migratory haSMCs compared to quiescent cells in vitro. After N-cadherin overexpression, haSMC migration was reduced by 87% (P<0.001). By contrast, inhibition of N-cadherin in quiescent haSMCs by GC-4 increased the migratory potential by 87% (P<0.01). In haSMCs overexpressing N-cadherin, a significant upregulation of RhoA activity was demonstrated, while RhoA activity was blocked by GC-4. Conclusions: These results indicate that the regulation of haSMC attachment by N-cadherins is essential for haSMC migration. Modification of N-cadherin expression and activity induces RhoA signaling with relevance for the reorganization of the actin cytoskeleton.
Assessment of Low-Gradient Aortic Stenosis With Dobutamine
Authors: Paul A. Grayburn
Journal: Circulation (2006)

ow-gradient aortic stenosis (AS) has been a vexing problem for cardiologists since its original description in 1980 by Carabello et al. 1 In that study, 3 of 4 patients with low-gradient AS died at surgery, and the other patient had persistent severe heart failure postoperatively.Subsequent studies showed that although operative mortality is high, most patients survive aortic valve replacement (AVR), and some have dramatic improvement in symptoms and left ventricular (LV) function. 2,3The challenge facing clinicians is how to accurately distinguish those patients who will benefit from AVR from those who will not.The American College of Cardiology/American Heart Association guidelines for valvular heart disease recommend hemodynamic evaluation of low-gradient AS with dobutamine echocardiography to distinguish patients with fixed anatomic AS from those with flow-dependent ("relative") AS in patients with LV dysfunction. 46][7] To understand how dobutamine infusion helps sort out the dilemma of low-gradient AS, it is useful to revisit the hemodynamic principles that govern the relationship between AVA, flow, and gradient. Article p 711 The Gorlin FormulaIn 1951, Gorlin and Gorlin proposed the "hydraulic orifice equation" for calculation of valve area in valvular stenosis. 8he Gorlin formula was based on the fundamental equation:in which valve area (A) is equal to transvalvular flow (F), divided by transvalvular velocity (V).In AS, the Gorlin formula is used to calculate AVA as:
Combined-Modality Therapy for Clinical Stage I or II Hodgkin's Lymphoma: Long-Term Results of the European Organisation for Research and Treatment of Cancer H7 Randomized Controlled Trials
Authors: Evert M. Noordijk, Patrice Carde, Noëlle Dupouy, Anton Hagenbeek, Augustinus D.G. Krol, Johanna C. Kluin-Nelemans, Umberto Tirelli, Mathieu Monconduit, José Thomas, Houchingue Eghbali, Berthe M.P. Aleman, Jacques Bosq, Marjeta Vovk, Tom A.M. Verschueren, Anne-Marie Pény, Théodore Girinsky, John M.M. Raemaekers, Michel Henry-Amar
Journal: Journal of Clinical Oncology (2006)

Purpose In early-stage Hodgkin's lymphoma (HL), subtotal nodal irradiation (STNI) and combined chemotherapy/radiotherapy produce high disease control rates but also considerable late toxicity. The aim of this study was to reduce this toxicity using a combination of low-intensity chemotherapy and involved-field radiotherapy (IF-RT) without jeopardizing disease control. Patients and Methods Patients with stage I or II HL were stratified into two groups, favorable and unfavorable, based on the following four prognostic factors: age, symptoms, number of involved areas, and mediastinal-thoracic ratio. The experimental therapy consisted of six cycles of epirubicin, bleomycin, vinblastine, and prednisone (EBVP) followed by IF-RT. It was randomly compared, in favorable patients, to STNI and, in unfavorable patients, to six cycles of mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine (MOPP/ABV hybrid) and IF-RT. Results Median follow-up time of the 722 patients included was 9 years. In 333 favorable patients, the 10-year event-free survival rates (EFS) were 88% in the EBVP arm and 78% in the STNI arm (P = .0113), with similar 10-year overall survival (OS) rates (92% v 92%, respectively; P = .79). In 389 unfavorable patients, the 10-year EFS rate was 88% in the MOPP/ABV arm compared with 68% in the EBVP arm (P &lt; .001), leading to 10-year OS rates of 87% and 79%, respectively (P = .0175). Conclusion A treatment strategy for early-stage HL based on prognostic factors leads to high OS rates in both favorable and unfavorable patients. In favorable patients, the combination of EBVP and IF-RT can replace STNI as standard treatment. In unfavorable patients, EBVP is significantly less efficient than MOPP/ABV.
Erlotinib and the Risk of Oral Cancer
Authors: William N. William, Vassiliki Papadimitrakopoulou, J. Jack Lee, Li Mao, Ezra E. W. Cohen, Heather Y. Lin, Ann M. Gillenwater, Jack W. Martin, Mark W. Lingen, Jay O. Boyle, Dong M. Shin, Nadarajah Vigneswaran, Nancy Shinn, John V. Heymach, Ignacio I. Wistuba, Ximing Tang, Edward S. Kim, Pierre Saintigny, Elizabeth A. Blair, Timothy Meiller, J. Silvio Gutkind, Jeffrey Myers, Adel El-Naggar, Scott M. Lippman
Journal: JAMA Oncology (2015)

<h3>Importance</h3> Standard molecularly based strategies to predict and/or prevent oral cancer development in patients with oral premalignant lesions (OPLs) are lacking. <h3>Objective</h3> To test if the epidermal growth factor receptor inhibitor erlotinib would reduce oral cancer development in patients with high-risk OPLs defined by specific loss of heterozygosity (LOH) profiles. Secondary objectives included prospective determination of LOH as a prognostic marker in OPLs. <h3>Design</h3> The Erlotinib Prevention of Oral Cancer (EPOC) study was a randomized, placebo-controlled, double-bind trial. Accrual occurred from November 2006 through July 2012, with a median follow-up time of 35 months in an ambulatory care setting in 5 US academic referral institutions. Patients with OPLs were enrolled in the protocol, and each underwent LOH profiling (N = 379); they were classified as high-risk (LOH-positive) or low-risk (LOH-negative) patients based on their LOH profiles and oral cancer history. The randomized sample consisted of 150 LOH-positive patients. <h3>Interventions</h3> Oral erlotinib treatment (150 mg/d) or placebo for 12 months. <h3>Main Outcomes and Measures</h3> Oral cancer–free survival (CFS). <h3>Results</h3> A total of 395 participants were classified with LOH profiles, and 254 were classified LOH positive. Of these, 150 (59%) were randomized, 75 each to the placebo and erlotinib groups. The 3-year CFS rates in placebo- and erlotinib-treated patients were 74% and 70%, respectively (hazard ratio [HR], 1.27; 95% CI, 0.68-2.38;<i>P</i> = .45). The 3-year CFS was significantly lower for LOH-positive compared with LOH-negative groups (74% vs 87%, HR, 2.19; 95% CI, 1.25-3.83;<i>P</i> = .01). Increased<i>EGFR</i>gene copy number correlated with LOH-positive status (<i>P</i> &lt; .001) and lower CFS (<i>P</i> = .01). The<i>EGFR</i>gene copy number was not predictive of erlotinib efficacy. Erlotinib-induced skin rash was associated with improved CFS (<i>P</i> = .01). <h3>Conclusions and Relevance</h3> In this trial, LOH was validated as a marker of oral cancer risk and found to be associated with increased<i>EGFR</i>copy number (the target of the intervention). Erlotinib did not, however, improve CFS in high-risk patients with LOH-positive or high-<i>EGFR</i>-gene-copy-number OPLs. These results support incorporation of LOH testing as a prognostic tool in routine clinical practice but do not support erlotinib use in this setting. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT00402779
Human interleukin 1 induces interleukin 1 gene expression in human vascular smooth muscle cells.
Authors: S J Warner, K R Auger, P Libby
Journal: The Journal of Experimental Medicine (1987)

The recognition that cells of the vascular wall can secrete cytokines such as IL-1 suggests new mechanisms for initiating or sustaining inflammatory responses in blood vessels. We report that purified human monocyte-derived IL-1 or recombinant human IL-1 (rIL-1 beta and rIL-1 alpha) induce cultured human smooth muscle cells derived from veins or arteries to synthesize IL-1 beta mRNA and produce and release biologically active IL-1. rIL-1 beta also stimulated the production of PGE2 by smooth muscle cells. Exposure to rIL-1 beta (1-100 ng/ml), or rIL-1 alpha (0.01-10 ng/ml) increased IL-1 beta mRNA levels within 30 min. Actinomycin D (1 microgram/ml) prevented the induction of IL-1 beta mRNA by rIL-1. IL-1 alpha mRNA was detected in SMC treated with cycloheximide (1 microgram/ml) and rIL-1 beta, or cycloheximide alone. rIL-1 alpha and rIL-1 beta produced maximal levels of IL-1 beta mRNA after 4 h, and intracellular IL-1 biological activity after 6 h of exposure. Release of IL-1 activity in the extracellular medium began after 1 h of incubation with rIL-1 beta or rIL-1 alpha, and continued for up to 24 h. Anti-TNF antiserum that neutralized the biological activity of rTNF did not affect rIL-1-induced production of IL-1 beta mRNA or IL-1 release, suggesting that the release of TNF does not mediate these processes. Several experimental approaches indicated that the release of IL-1 by smooth muscle cells was not due to endotoxin contamination of the IL-1 preparations. Anti-IL-1 antiserum blocked the induction of smooth muscle cell IL-1 gene expression by rIL-1 beta. Polymyxin B did not prevent IL-1-induced IL-1 expression by these cells, but blocked the effect of endotoxin. Heat treatment destroyed the stimulatory capacity of rIL-1 beta, but did not affect the ability of bacterial endotoxin to induce IL-1 expression. The production of IL-1 by human vascular smooth muscle cells was not due to contamination of the cell cultures with blood monocytes, inasmuch as treatment with an antimonocyte antibody (anti-Mo2) and complement did not alter IL-1 beta mRNA content or the amount of IL-1 released from the cells in response to endotoxin, rIL-1 alpha, or rIL-1 beta.(ABSTRACT TRUNCATED AT 400 WORDS)
Successful rechallenge to etoposide after an acute vasomotor response.
Authors: W J Tester, J B Cohn, P D Fleekop, M S Rabinowitz, J S Lieberman
Journal: Journal of Clinical Oncology (1990)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1990.8.9.1600 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2391561 Successful rechallenge to etoposide after an acute vasomotor response. W J TesterxW J TesterSearch for articles by this author , J B CohnxJ B CohnSearch for articles by this author , P D FleekopxP D FleekopSearch for articles by this author , M S RabinowitzxM S RabinowitzSearch for articles by this author , J S LiebermanxJ S LiebermanSearch for articles by this author https://doi.org/10.1200/JCO.1990.8.9.1600 PDF "Successful rechallenge to etoposide after an acute vasomotor response.." Journal of Clinical Oncology, 8(9), pp. 1600–1601© 1990 by American Society of Clinical Oncology
Pediatrician-Psychiatrist Partnerships Expand Access to Mental Health Care
Authors: Bridget M. Kuehn
Journal: JAMA (2011)

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