tbuckley/cabot-search huggingface dataset:
Interobserver reliability of rheumatologists performing musculoskeletal ultrasonography: results from a EULAR "Train the trainers" course
Authors: A K Scheel
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objective:</b> To evaluate the interobserver reliability among 14 experts in musculoskeletal ultrasonography (US) and to determine the overall agreement about the US results compared with magnetic resonance imaging (MRI), which served as the imaging "gold standard". <b>Methods:</b> The clinically dominant joint regions (shoulder, knee, ankle/toe, wrist/finger) of four patients with inflammatory rheumatic diseases were ultrasonographically examined by 14 experts. US results were compared with MRI. Overall agreements, sensitivities, specificities, and interobserver reliabilities were assessed. <b>Results:</b> Taking an agreement in US examination of 10 out of 14 experts into account, the overall κ for all examined joints was 0.76. Calculations for each joint region showed high κ values for the knee (1), moderate values for the shoulder (0.76) and hand/finger (0.59), and low agreement for ankle/toe joints (0.28). κ Values for bone lesions, bursitis, and tendon tears were high (κ = 1). Relatively good agreement for most US findings, compared with MRI, was found for the shoulder (overall agreement 81%, sensitivity 76%, specificity 89%) and knee joint (overall agreement 88%, sensitivity 91%, specificity 88%). Sensitivities were lower for wrist/finger (overall agreement 73%, sensitivity 66%, specificity 88%) and ankle/toe joints (overall agreement 82%, sensitivity 61%, specificity 92%). <b>Conclusion:</b> Interobserver reliabilities, sensitivities, and specificities in comparison with MRI were moderate to good. Further standardisation of US scanning techniques and definitions of different pathological US lesions are necessary to increase the interobserver agreement in musculoskeletal US.
Clinical, biochemical and morphological features of hepatocerebral syndrome with mitochondrial DNA depletion due to deoxyguanosine kinase deficiency
Authors: François Labarthe, Dries Dobbelaere, Louise Devisme, Anne De Muret, Claude Jardel, Jan-Willem Taanman, Frédéric Gottrand, Anne Lombès
Journal: Journal of Hepatology (2005)
Directional Kinetics of Geographic Atrophy Progression in Age-Related Macular Degeneration with Foveal Sparing
Authors: Moritz Lindner, Alexander Böker, Matthias M Mauschitz, Arno P Göbel, Rolf Fimmers, Christian K Brinkmann, Steffen Schmitz-Valckenberg, Matthias Schmid, Frank G Holz, Monika Fleckenstein
Journal: Ophthalmology (2015)
What Is the Evidence That Tumors Are Angiogenesis Dependent?
Authors: Judah Folkman
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article What Is the Evidence That Tumors Are Angiogenesis Dependent? Get access Judah Folkman Judah Folkman Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 1, 3 January 1990, Pages 4–7, https://doi.org/10.1093/jnci/82.1.4 Published: 03 January 1990 Article history Received: 24 November 1989 Accepted: 27 November 1989 Published: 03 January 1990
LADA and CARDS: A Prospective Study of Clinical Outcome in Established Adult-Onset Autoimmune Diabetes
Authors: Mohammed Iqbal Hawa, Ana Paula Buchan, Thomas Ola, Chuan Chuan Wun, David A. DeMicco, Weihang Bao, D. John Betteridge, Paul N. Durrington, John H. Fuller, H. Andrew W. Neil, Helen Colhoun, Richard David Leslie, Graham A. Hitman
Journal: Diabetes Care (2014)

OBJECTIVE Diabetes-associated autoantibodies can be detected in adult-onset diabetes, even when initially non–insulin requiring, i.e., with latent autoimmune diabetes. We aimed to identify adult-onset autoimmune diabetes in patients with established “type 2 diabetes” participating in the Collaborative Atorvastatin Diabetes Study (CARDS) to characterize their phenotype and clinical outcome. RESEARCH DESIGN AND METHODS We prospectively studied 2,425 European patients with presumed type 2 diabetes (mean age 62 years, diabetes duration 7.9 years) for outcomes at 3.9 years after randomization to either atorvastatin or placebo. Subjects were screened for autoantibodies to GAD (GADA), insulinoma-associated antigen-2 (IA-2A), and zinc-transporter 8 (ZnT8A). RESULTS A total of 173 patients (7.1%) had GADA, of whom 11 (0.5%) and 5 (0.2%) were also positive for IA-2A and ZnT8A, respectively. At baseline, 44% of GADA-positive patients were not on insulin. Fewer autoantibody-positive than autoantibody-negative patients had metabolic syndrome (64 vs. 80%), and more were on insulin (56 vs. 17%) (P &amp;lt; 0.0001 for each) without lower HbA1c (69 mmol/mol [8.5%] vs. 62 mmol/mol [7.8%]). The frequency of microvascular and macrovascular events was similar in both cohorts, independent of atorvastatin. CONCLUSIONS Adult-onset autoimmune diabetes was prevalent, even in patients with established diabetes presumed to have type 2 diabetes. After 11.8 years’ diabetes duration, nearly half the patients with autoimmune diabetes were not on insulin treatment and almost two-thirds had metabolic syndrome. The type of diabetes, whether autoimmune diabetes or type 2 diabetes, did not impact the risk of microvascular disease.
Results from a nationwide postmarketing cohort study of patients in Sweden treated with etanercept
Authors: N Feltelius
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objectives:</b> To describe a nationwide system for postmarketing follow up of new antirheumatic drugs in Sweden, and to analyse safety and effectiveness in an etanercept treated patient cohort. <b>Methods:</b> Etanercept became available in Sweden for prescribing on a named patient basis in 1999. All patients treated were included in a follow up of intensified adverse event reporting and recording of clinical outcome during 24 months, according to the EULAR core set. <b>Results:</b> The mean (SD) disease activity score (DAS 28) value at inclusion among 820 patients recruited on a named patient basis during year 1 was 5.99 (1.19). After two years, 21% (n = 172) of these patients had discontinued the treatment. Of the remaining 648 patients, 68% (n = 442) responded to the treatment. However, in 55% of the responders, the disease activity was intermediate or high (mean DAS 28, 3.37 (1.20)). In all, 540 adverse events were reported in 421 adverse drug reaction (ADR) reports, in 294 patients. The events in 80 reports (19%) were serious. Twenty two per cent of the events were infections, of which 24% (n = 29) were serious. The incidence of serious adverse events remained constant over time. <b>Conclusions:</b> At start of etanercept treatment, patients had high disease activity. Activity remained high in a large proportion of the responding patients. Although serious ADRs occurred during late phases of treatment, no unexpected safety problems arose. No specific indicators of ADR risk were found. The monitoring system that was established may be useful in future postmarketing surveillance.
<i>In vivo</i> Radioiodide Imaging and Treatment of Breast Cancer Xenografts after MUC1-Driven Expression of the Sodium Iodide Symporter
Authors: Roisin M. Dwyer, Elizabeth R. Bergert, Michael K. O'Connor, Sandra J. Gendler, John C. Morris
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Expression of the sodium iodide symporter (NIS) in the thyroid gland provides for effective imaging and treatment of thyroid cancer using radiolabeled iodide. Transfer of NIS into other tumors would expand the utility of this treatment to tumors of nonthyroid origin. MUC1 is a transmembrane glycoprotein that is overexpressed in many tumor types, including breast, pancreatic, and ovarian. The aim of this study was to create a construct containing NIS under the control of the MUC1 promoter to target expression specifically to MUC1-positive breast cancer cells. Experimental Design: A replication-deficient adenoviral construct was created containing the MUC1 promoter followed by the human NIS gene. Iodide uptake assays, Western blot, and immunohistochemistry were used to confirm NIS expression and function. Breast cancer xenografts in mice were infected with Ad5/MUC1/NIS and then imaged and treated using radioiodide. Results: A 58-fold increase in iodide uptake was observed in infected MUC1-positive T47D cells with no significant increase observed in MUC1-negative MDA-MB-231 cells or in cells infected with the control virus. The in vivo study yielded clear images of Ad/MUC1/NIS-infected tumor xenografts using 123I. Administration of a therapeutic dose of 131I resulted in an 83% reduction in tumor volume, whereas control tumors continued to increase in size (P &amp;lt; 0.01). Conclusions: These results show that the MUC1 promoter is capable of directing efficient and selective expression of the NIS gene in MUC1-positive breast tumor cells. This could potentially have applications for both imaging and therapy in a range of MUC1-positive tumor types.
Metabolic Syndrome and 10-Year Cardiovascular Disease Risk in the Hoorn Study
Authors: Jacqueline M. Dekker, Cynthia Girman, Thomas Rhodes, Giel Nijpels, Coen D.A. Stehouwer, Lex M. Bouter, Robert J. Heine
Journal: Circulation (2005)

Different definitions of the metabolic syndrome have been proposed. Their value in a clinical setting to assess cardiovascular disease (CVD) risk is still unclear. We compared the definitions proposed by the National Cholesterol Education Program Adult Treatment Panel III (NCEP), World Health Organization (WHO), European Group for the Study of Insulin Resistance (EGIR), and American College of Endocrinology (ACE) with respect to the prevalence of the metabolic syndrome and the association with 10-year risk of fatal and nonfatal CVD.The Hoorn Study is a population-based cohort study. The present study population comprised 615 men and 749 women aged 50 to 75 years and without diabetes or a history of CVD at baseline in 1989 to 1990. The prevalence of the metabolic syndrome at baseline ranged from 17% to 32%. The NCEP definition was associated with about a 2-fold increase in age-adjusted risk of fatal CVD in men and nonfatal CVD in women. For the WHO, EGIR, and ACE definitions, these hazard ratios were slightly lower. Risk increased with the number of risk factors. Elevated insulin levels were more prevalent in subjects with multiple risk factors, but metabolic syndrome definitions including elevated insulin level were not more strongly associated with risk.The metabolic syndrome, however defined, is associated with an approximate 2-fold increased risk of incident cardiovascular morbidity and mortality in a European population. In clinical practice, a more informative assessment can be obtained by taking into account the number of individual risk factors.
The Microinflammatory State in Uremia
Authors: GEORGE A. KAYSEN
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Mortality is markedly elevated in patients with end-stage renal disease. The leading cause of death is cardiovascular disease. Lipoprotein levels are only slightly elevated in dialysis patients, and cardiovascular risk is inversely correlated with serum cholesterol, suggesting that a process other than hyperlipidemia plays a role in the incidence of cardiovascular disease. Hypoalbuminemia, ascribed to malnutrition, has been one of the most powerful risk factors that predict all-cause and cardiovascular mortality in dialysis patients. The presence of inflammation, as evidenced by increased levels of specific cytokines (interleukin-6 and tumor necrosis factor α) or acute-phase proteins (C-reactive protein and serum amyloid A), however, has been found to be associated with vascular disease in the general population as well as in dialysis patients. The process of inflammation, also called the acute-phase response, additionally causes loss of muscle mass and changes in plasma composition—decreases in serum albumin, prealbumin, and transferrin levels, also associated with malnutrition. Inflammation alters lipoprotein structure and function as well as endothelial structure and function to favor atherogenesis and increases the concentration of atherogenic proteins in serum, such as fibrinogen and lipoprotein (a). Inflammation in dialysis patients is episodic. The causes are likely to be multifactorial and include vascular access infection, less-than-sterile dialysate, dialysate back leak, and nonbiocompatible membranes in addition to clinically apparent infection. In addition, proinflammatory compounds, such as advanced glycation end products, accumulate in renal failure, and defense mechanisms against oxidative injury are reduced, contributing to inflammation and to its effect on the vascular endothelium.
The immunoadhesin glycoprotein VI-Fc regulates arterial remodelling after mechanical injury in ApoE−/− mice
Authors: Tanja Schönberger, Dorothea Siegel-Axel, Renate Bußl, Sabine Richter, Martin S. Judenhofer, Roland Haubner, Gerald Reischl, Karin Klingel, Götz Münch, Peter Seizer, Bernd J. Pichler, Meinrad Gawaz
Journal: Cardiovascular Research (2008)

Rupture of advanced atherosclerotic plaques initiates platelet activation and aggregation as subendothelial collagen is exposed. Platelet collagen receptor glycoprotein VI (GPVI) was found to bind preferentially to the core region of human plaques. Consequently, platelets contribute to inflammatory processes and trigger atherosclerotic lesion progression. In this study, we examined binding of soluble platelet collagen receptor GPVI-Fc to atherosclerotic lesions and its effect on platelet-triggered atheroprogression and neointima formation after wire-induced carotid injury. For binding studies after ligation-induced arterial injury, the left common carotid artery of C57BL/6J mice was ligated. For binding studies at spontaneously formed atherosclerotic lesion sites, Apolipoprotein E-deficient (ApoE−/−) mice were fed a 0.25% cholesterol diet over 16 weeks. Binding of [124I]GPVI-Fc was monitored by autoradiography 48 h after intravenous injection and by immunostaining. To study the effect of GPVI-Fc on neointima formation vs. control-Fc, a wire-induced injury of the left A. carotis communis of ApoE−/−-mice was performed. Mice were treated intraperitoneally with GPVI-Fc for 8 days and neointima formation was assessed 4 weeks after intervention. [124I]GPVI-Fc preferentially bound to injury sites after carotid ligation in C57BL/6J mice and to lipid-rich atherosclerotic lesions of the carotid artery and aortic arch in uninjured ApoE−/−-mice. Histological examinations of wire-injured carotid arteries showed that neointima formation was significantly reduced in GPVI-Fc-treated ApoE−/− mice compared to ApoE−/− mice receiving control-Fc (P < 0.05). GPVI-Fc preferentially bound to sites of vascular injury and was able to inhibit neointima formation after wire-induced vascular injury in ApoE−/− mice. Thus, soluble GPVI-Fc might be also a promising compound to attenuate lesion progression after plaque rupture.
Importance of low affinity Elf-1 sites in the regulation of lymphoid-specific inducible gene expression.
Authors: S John, R Marais, R Child, Y Light, W J Leonard
Journal: The Journal of Experimental Medicine (1996)

Elf-1 is an Ets family transcription factor that regulates a number of inducible lymphoid-specific genes, including those encoding interleukin 3 (IL-3), granulocyte/macrophage colony-stimulating factor (GM-CSF), and the IL-2 receptor (IL-2R) alpha chain. A minimal oligonucleotide spanning the IL-2R alpha Elf-1 site (-97/-84) bound Elf-1 poorly, but binding activity markedly increased when this oligonucleotide was multimerized or flanking sequences were added. This result is consistent with the requirement of accessory proteins for efficient Elf-1 binding, as has been demonstrated for the GM-CSF and IL-3 promoters. A binding site selection analysis revealed the optimal Elf-1 consensus motif to be A(A/t)(C/a)CCGGAAGT(A/S), which is similar to the consensus motif for the related Drosophila E74 protein. This minimal high affinity site could bind Elf-1 and functioned as a stronger transcription element than the -97/-84 IL-2R alpha oligonucleotide when cloned upstream of a heterologous promoter. In contrast, in the context of the IL-2R alpha promoter, conversion of the naturally occurring low affinity Elf-1 site to an optimal site decreased inducible activation of a reporter construct in Jurkat cells. This finding may be explained by the observation that another Ets family protein, ER GB/Fli-1, can efficiently bind only to the optimal site, and in this context, interferes with Elf-1 binding. Therefore, high affinity Elf-1 sites may lack sufficient binding specificity, whereas naturally occurring low affinity sites presumably favor the association of Elf-1 in the context of accessory proteins. These findings offer an explanation for the lack of optimal sites in any of the known Elf-1-regulated genes.
Successful use of rituximab in a patient with recalcitrant Churg-Strauss syndrome
Authors: V V Kaushik
Journal: Annals of the Rheumatic Diseases (2006)

Churg-Strauss syndrome (CSS) is a disorder characterised by hypereosinophilia and systemic vasculitis occurring in people with asthma and allergic rhinitis. Corticosteroids in combination with a cytotoxic agent are the most effective treatment for CSS. Rituximab, a genetically engineered chimeric anti-CD20 monoclonal antibody has recently been tried with favourable responses in chronic immunological diseases.1 Several published reports have shown its effectiveness in ANCA mediated vasculitides.2,3 We present a patient with CSS who responded well to rituximab after conventional treatments had failed.

A 49 year old, white male patient with a long history of asthma presented in 2000 with inflammatory polyarthritis, bilateral scleritis, and negative autoantibodies. He was managed as a patient with seronegative …
Addition of infliximab compared with addition of sulfasalazine and hydroxychloroquine to methotrexate in early rheumatoid arthritis: 2-year quality-of-life results of the randomised, controlled, SWEFOT trial
Authors: Johan A Karlsson, Martin Neovius, Jan-Åke Nilsson, Ingemar F Petersson, Johan Bratt, Ronald F van Vollenhoven, Sofia Ernestam, Pierre Geborek
Journal: Annals of the Rheumatic Diseases (2012)

Objective To compare EuroQol 5-Dimensions (EQ-5D) utility and quality-adjusted life-years (QALYs) in patients with early, methotrexate (MTX) refractory rheumatoid arthritis (RA), randomised to addition of infliximab (IFX) or sulfasalazine and hydroxychloroquine (SSZ+HCQ). Methods RA-patients with symptoms &lt;1 year were enrolled between 2002 and 2005 at 15 Swedish centres. After 3–4 months of MTX monotherapy, patients with a remaining DAS28&gt;3.2 were randomised to addition of IFX or SSZ+HCQ and followed for 21 months. EQ-5D profiles were collected every 3 months. Between-group comparisons of utility change and accumulated QALYs were performed, using last observation carried forward (LOCF) following protocol breach. Missing data were imputed by linear interpolation or LOCF. Sensitivity analyses applying baseline observation carried forward (BOCF) or restricted to completers were conducted. Results Of 487 patients initially enrolled, 128 and 130 were randomised to IFX or SSZ+HCQ, respectively. Mean utility in the IFX and SSZ+HCQ groups increased from 0.52 (SD 0.27) and 0.55 (SD 0.27) at randomisation to 0.66 (SD 0.25) and 0.63 (SD 0.27) at 21 months (adjusted mean difference favouring IFX 0.04; 95% CI −0.01, 0.09; p=0.15). Average accumulated QALYs were 1.10 (SD 0.37) and 1.07 (SD 0.42) in the IFX and SSZ+HCQ groups, respectively (adjusted mean difference favouring IFX 0.07; 95%CI −0.01, 0.14; p=0.07). BOCF analysis showed similar results, while differences were reversed, though remained statistically non-significant among completers. Dropout rates in the IFX/SSZ+HCQ groups were 30%/43% (p=0.01). Conclusions Comparing addition of IFX or SSZ+HCQ to MTX in active early RA, no statistically significant differences in utility or QALY gain could be detected over 21 months. Trial registration Registered in WHO database at the Karolinska University Hospital, number CT20080004.
Direct analysis of beta-adrenergic receptor subtypes on intact adult ventricular myocytes of the rat.
Authors: I L Buxton, L L Brunton
Journal: Circulation Research (1985)

beta 1- and beta 2-Adrenergic receptors co-exist in the adult rat ventricle. We have employed radioligand binding and cell purification techniques to determine the cellular origin of these receptors. The beta-adrenergic antagonist ligand (+/-)-[125I] iodocyanopindolol binds to 2 X 10(5) receptors per purified adult rat cardiomyocyte, with a dissociation constant of 70 pM. The subtype-selective antagonists betaxolol (beta 1), practolol (beta 1), and zinterol (beta 2) compete for [125I]iodocyanopindolol-binding sites on intact myocytes in monophasic manners with dissociation constants of 46, 845, and 923 nM, respectively. [125I]iodocyanopindolol binding to membranes prepared from nonmyocyte elements of rat ventricle occurs with a dissociation constant of 43 pM and a capacity of 88 fmol/mg membrane protein. Computer analysis of competition of [125I]iodocyanopindolol binding by betaxolol, practolol, and zinterol in nonmyocyte membranes demonstrates biphasic curves that comprise binding to both beta 1- and beta 2-receptors. These data demonstrate that purified adult ventricular myocytes possess only beta 1-receptors, and that the beta 2-receptors found in rat ventricle are located on nonmyocyte cell types.
Complete Responders to Chemotherapy in Metastatic Breast Cancer
Authors: David A. Decker
Journal: JAMA (1979)

Four hundred thirty-eight patients with metastatic breast cancer treated with nine prospective randomized trials were reviewed to analyze, characterize, and compare those with complete regression (CR) (N=49 [11%]) with those with noncomplete regression (non-CR) (N=389 [89%]). Site of dominant disease was identical in the CR and non-CR patients. However, CR was statistically more likely when the disease-free interval and the postmenopausal status was five years or less. Survival and time to progression occurred at sites of prior dominant disease, except that relapses occurred in the CNS in 14%. Six CR patients received prolonged chemotherapy and were believed to be "cured" when treatment was discontinued; however, all except one have had relapses.