tbuckley/cabot-search huggingface dataset:
Angiokeratoma: Decision Making Methodology for the Diagnosis of Fabry Disease
Authors: A. Zampetti, C.H. Orteu, D. Antuzzi, M.R. Bongiorno, S. Manco, M. Gnarra, A. Morrone, G. Cardinali, D. Kovacs, N. Aspite, D. Linder, R. Parini, C. Feliciani
Journal: British Journal of Dermatology (2011)

Background Isolated angiokeratomas are common benign cutaneous lesions, generally deemed unworthy of further investigation. In contrast, diffuse angiokeratomas should alert the physician to a possible diagnosis of Fabry disease, a rare X-linked lysosomal storage disorder, characterized by alpha-galactosidase deficiency. Glycosphingolipids accumulate in cells throughout the body resulting in progressive multiorgan failure. Difficulties are encountered when trying to interpret the significance of angiokeratomas since they may also occur in other lysosomal storage disorders and rarely in an isolated manner in Fabry disease. Objectives We present an algorithm for the classification of angiokeratomas which might prove useful for the diagnosis and management of Fabry disease. Methods. Assessment of clinical features and location of the lesions, personal and family history, skin biopsy, dermoscopy and electron microscopy imaging are sequential steps in the diagnostic process. Assessing the deficiency of α-galactosidase enzyme activity is essential to confirm the diagnosis in males, whilst mutation analysis is always needed in females. Results This algorithm can potentially change the current approach to patients when Fabry disease is suspected, thus improving the diagnostic strategy and management of this disorder. It remains to be ascertained whether the use of an algorithm may reduce the number of genetic consultations. Conclusion. Since evidences have shown the efficacy of enzyme replacement therapy in halting the progression of disease before the onset of irreversible organ damage, it is advisable to aim at an early diagnosis in order to achieve timely initiation of effective treatment with benefits for patients and appropriate use of medical resources.
S166 The role of clinical, metabolic and cardiac biomarkers in predicting outcome from COPD exacerbations requiring hospital admission: A prospective observational study
Authors: G. Tack, V. Osman-Hicks, A. Hicks, Y. Perry, R. M. Angus, P. M. A. Calverley, B. Chakrabarti
Journal: Thorax (2010)

<h3>Introduction</h3> Baseline hyperglycaemia along with Respiratory Rate has been shown to represent a marker for mortality and failure of Non Invasive Ventilation in COPD exacerbations complicated by decompensated respiratory failure. This study aims to determine whether the same association holds true for those COPD exacerbations admitted to hospital in the absence of respiratory acidosis and if other markers may predict outcomes in such a population. <h3>Methodology</h3> COPD patients admitted to University Hospital Aintree with an acute exacerbation were recruited within 48 h of admission with the primary end point being 3 month mortality. Patients presenting with respiratory acidosis were excluded. Subjects underwent clinical assessment at recruitment; blood samples were drawn for Random Blood glucose (RBG), Brain Natriuretic Peptide (BNP) level (Siemens Healthcare©). Admission ECGs were analysed in order to calculate Cardiac Infarction Injury Score (CIIS). <h3>Results</h3> 116 patients (mean age 70 years; 55% female; FEV1 0.98(predicted 2.49) litres; admission ABGS pH 7.40; PCO2 5.93kPA; PO2 9.04kPA) were recruited; 18 (16%) patients had died by 3 months. Hyperglycaemia (defined as RBG ≥7 mmol/l) was not associated with increased 3 month mortality (observed in 6/18 (33%) of deaths at 3 months vs 35/98(36%) of survivors; p=0.85).The Respiratory Rate (RR) measured during clinical assessment appeared to significantly higher in those who had died by 3 months (27 (SD 5) vs 24 (SD 5); p=0.048). No association was observed between those who had died by 3 months in terms of BNP levels (18.71 vs 24.22 pg/ml; p=0.48), CIIS (7.65 vs 6.25; p=0.37), age (71 vs 70 years; p=0.63), PaCO2 (6.29 vs 5.87 kPA) or serum Bicarbonate (25 vs 26 mmol/l; p=0.64). An inverse correlation was noted between BNP values and admission PaCO2 levels (Correlation coefficient −0.25; p=0.018) and Bicarbonate levels (Correlation coefficient −0.35; p=0.001); a positive correlation was observed between BNP levels and patient age (Correlation coefficient −0.35; p=0.002). <h3>Discussion</h3> In patients admitted to hospital with COPD exacerbations, hyperglycaemia, BNP level and CIIS were not found to be predictors of mortality in the absence of acute respiratory acidosis. Interestingly, Respiratory Rate measured whilst in hospital appears to predict outcome at 3 months.
A COST-EFFECTIVENESS ANALYSIS IN THE US OF LCZ696 (SACUBITRIL/VALSARTAN) VERSUS RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM INHIBITION FOR HEART FAILURE PATIENTS WITH REDUCED EJECTION FRACTION
Authors: Thomas A. Gaziano, Gregg Fonarow, Brian Claggett, Milton Packer, Michael Zile, Karl Swedberg, Jean Rouleau, John McMurray, Wing Chan, Stuart Turner, Celine Deschaseaux, Scott Solomon
Journal: Journal of the American College of Cardiology (2016)
THU0582 Health Related Quality of Life in Patients with Chronic Gout Compared to Patients with Rheumatoid Arthritis
Authors: E. Taal, P. M. ten Klooster, H. E. Vonkeman, M. A. van de Laar
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The Medical Outcomes Study Short-Form 36 (SF-36) has been endorsed as a valid instrument for measurement of health related quality of life (HRQoL) in gout at the International Consensus Conference on Outcome Measures in Rheumatology (OMERACT 9) [1] <h3>Objectives</h3> To compare HRQoL in patients with chronic gout and matched patients with rheumatoid arthritis (RA) as measured with the SF-36 version 2 (SF-36v2). <h3>Methods</h3> Consecutive patients with crystal deposition proven gout (n=102) or with RA (n=619) visiting the outpatient rheumatology clinic of the hospital in Enschede, the Netherlands completed the SF-36v2. Gout patients were matched to patients with RA on sex, age (± 5 years) and disease duration (±5 years). Ninety-three patients with gout could be successfully matched to 93 patients with RA. SF-36v2 measures eight aspects of HRQoL with a total of 36 items (Physical Functioning (PF), Role problems as a result of physical health (RP), Bodily Pain (BP), General health (GH), Vitality (VT), Social Functioning (SF), Mental Health (MH) and Role problems as a result of emotional problems (RE)), as well as two summary scores for physical health (Physical Component Summary, PCS) and mental health (Mental Component Summary, MCS). Differences in the eight aspects and two summary scores of HRQoL between patients with gout and RA were tested by t-tests. <h3>Results</h3> In both disease groups mean age was 59 (± 12) years, mean disease duration was 7 (±9) years and 86% of patients were male. HRQoL scores in matched groups of patients with gout and RA were highly similar (see table). Mean differences between patients with gout and RA were small and non-significant for all scales and both summary scores. <h3>Image/graph:</h3> <h3>Conclusions</h3> As measured with SF36, the impact of chronic gout is highly similar to the impact of RA on health related quality of life. <h3>References</h3> Grainger R, Taylor JW, Dalbeth N et al. Progress in Measurement Instruments for Acute and Chronic Gout Studies. J Rheumatol 2009; 36:2346–55 <h3>Disclosure of Interest</h3> None Declared
RHEUMATIC EPILEPSY
Authors: WALTER L. BRUETSCH
Journal: American Journal of Psychiatry (1942)

The term "rheumatic epilepsy" has been suggested for patients who develop convulsions following rheumatic fever or chorea, and for epileptic persons with chronic rheumatic cardiovalvular disease. The fundamental process in the brain of these patients consists of a recurrent, obliterating rheumatic arteritis with secondary changes in the cortex.
Final results of the gideon study according to patient etiology: The italian experience
Authors: S. D'Angelo, D. Germano, T. Zolfino, D. Sansonno, G. Montalto, A. Benedetti, V. Montesarchio, A.F. Attili, A. Buonadonna, S. Barni, A. Gasbarrini, M. Pirisi, U. Cillo, S. Marenco, E. Villa, P. Giovanis, G. Pinotti, C. Saitta, C. Erminero, M. de Giorgio, V. Lorusso
Journal: Annals of Oncology (2015)
Abstract 267: The effect of amphiregulin knockdown on the expression of transformed phenotypes in triple-negative breast cancer
Authors: Andrea J. Baillo, Stephen P. Ethier
Journal: Cancer Research (2010)

Abstract Amphiregulin (AREG) and epidermal growth factor receptor (EGFR) co-expression leads to aggressive growth phenotypes observed in some triple negative breast tumors. In SUM-149 cells, a triple negative breast cancer cell line with an AREG/EGFR autocrine loop, we have shown that these cells are more invasive and motile than MCF10A cells grown with EGF and that altered signaling occurs when AREG is the stimulating ligand. To provide additional insight into the role of AREG in the SUM-149 cells, we have successfully knocked down AREG expression in the SUM-149 cells. Q-RT-PCR analysis showed an approximately 40-fold knock-down of AREG mRNA following stable transduction of the most effective shRNA vector. In these knock-down cells, secreted AREG was undetectable by ELISA, and cellular AREG was undetectable by western blot. Knock-down of AREG in SUM-149 cells resulted in a dramatic decrease in the growth rate of these cells, resulting in a doubling time of about half that of the parental SUM149 cell line. Soft agar assays comparing the anchorage-independent growth potential of SUM-149 cells with AREG knock-down SUM-149 cells demonstrated an approximately 50% decrease in soft agar colony forming ability. To examine the migration and invasion capacity of the AREG knock-down cells relative to parental cells, Matrigel invasion assays were carried out and showed that knocking down AREG resulted in a 40-fold decrease in the cells ability to invade the matrix. Our lab has previously shown that in SUM-149 cells, NF-κB DNA binding activity is initiated as a result of AREG activation of EGFR. NF-κB activity in the AREG knock-down cells was altered suggesting that AREG affects cellular signaling by altering transcription factors. Addressing the continued proliferation of the AREG knock-down cells, we examined the requirement for EGFR activation for growth of these cells. Phosphotyrosine western blot analysis demonstrated detectable EGFR activation in the AREG knock-down cells. Growth assays where these cells were treated with an EGFR tyrosine kinase inhibitor or with a neutralizing EGFR antibody demonstrated the dependency of EGFR for growth of these cells. Q-RT-PCR analysis for expression of all seven EGFR family ligands suggested that epigen or EGF may be factors contributing to the continued growth of these cells, in the absence of AREG. In summary, knock-down of AREG expression in SUM-149 cells has a dramatic affect on the cells ability to proliferate, invade, and form colonies in soft agar, which links this growth factor with the aggressive properties associated with the SUM-149 cells. 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 267.
THU0473 The Present State of Diagnosis and Therapy for IgG4-Related Diseases in Our Hospital
Authors: M. Yamamura, N. Shibuto
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> IgG-related disease (IgG4RD) is a systemic lymphoproliferative disorder characterized by tissue infiltration with IgG4-secreting plasma cells, occasionally leading to organ dysfunction. The gold standard of IgG4RD diagnosis is based on the pathological finding, but in practical, tissue sampling could be often unavailable. <h3>Objectives</h3> To determine the state of diagnosis and therapy for IgG4RD in our hospital. <h3>Methods</h3> Since April 2011, we have prospectively followed up patients with IgG4RD who were diagnosed mostly by the physical and image findings highly specific for IgG4RD and serum IgG4 levels of &gt;135mg/dL. <h3>Results</h3> At present, 18 patients enrolled in the study. Their mean age at presentation was 66.7 years (range: 39 – 85 years) and male : female ratio was 12 : 6. Organs involvement at diagnosis were salivary glands in 8 cases, lymph nodes in 5 cases, thyroid glands in 4 cases, pancreas or retroperitoneum in 3 cases, aorta, kidneys, salivary glands, bile tracts in 2 cases, and lungs or joints in one case. 8 patients have been treated with glucocorticoids (GC) therapy for their retroperitoneal lesions (3 cases), renal dysfunction (3 cases), pancreatitis, periaortitis, and others, and in 6 of them, azathioprine (AZA) was added later because of insufficient GC efficacy and/or its adverse effects. They responded well to the treatment, and 8 other untreated patients have not yet developed any organ dysfunction. <h3>Conclusions</h3> These results indicate that IgG4RD principally shows a benign clinical course and GC therapy thus should be indicated for patients with progression or risk of organ damage. In our experience, AZA may be useful for patients GC-resistant or intolerant patients. <h3>Disclosure of Interest</h3> None Declared
Abstract 1455: Knock down of the aryl hydrocarbon receptor sensitizes human breast carcinoma cell lines to radio- and chemotherapy
Authors: Gennifer D. Goode, Sakina Eltom
Journal: Cancer Research (2012)

Abstract Breast cancer is the most common cancer in North American women and is the second leading cause of cancer deaths in women today. Despite recent advances in treatment of breast cancer the development of chemo- and radio-resistance remains a major obstacle in treating advanced breast cancer. The aryl hydrocarbon receptor (AhR) is overexpressed and constitutively activated in several human breast carcinoma cell lines and the expression levels showed strong correlation with the degree of the tumor malignancy. In the current study, we evaluated the effect of reducing AhR expression on the chemo- and radio-sensitization of the MDA-MB231 human breast cancer cell line. We stably knocked down (KD) AhR expression in MDA-MB231 by using retroviral vectors expressing AhR-specific shRNA. Results show that reducing AhR expression enhanced radiation-induced apoptosis as shown by FITC-annexin V assay as well as significantly reducing cell clonogenic survival of MDA-MB231 cell line. In addition, knockdown of AhR alone has significantly impacted expression of genes regulating apoptotic pathways in these cells; increasing the expression of a number of pro-apoptotic genes while anti-apoptotic genes were down-regulated. Furthermore, the AhR-KD MDA-MB231 cells were sensitized to paclitaxol treatment; seen as an increase in the dose-dependent cytotoxicity compared to control cells. Our results suggest that reduction of AhR expression increases the chemo- and radio-sensitivity of MDA-MB231 breast cancer cell line. Therefore, AhR could be a novel target for enhancing efficacy of chemo and radiotherapy of breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1455. doi:1538-7445.AM2012-1455
Postpolypectomy surveillance in patients with adenomas and serrated lesions: a proposal for risk stratification in the context of organized colorectal cancer-screening programs
Authors: Antoni Castells, Montserrat Andreu, Gemma Binefa, Anna Fité, Rebeca Font, Josep Espinàs
Journal: Endoscopy (2014)

In the past few years, a tremendous effort has been made by scientific societies, cooperative groups, and public institutions to rationalize colorectal cancer (CRC) screening and surveillance strategies, with the final goal of improving both effectiveness and efficiency of such strategies [1] [2] [3]. Although the European Guidelines [4] have represented a landmark toward the standardization of policies across Europe, their surveillance strategies have been focused mainly on conventional adenomas [4]. This drawback has recently been addressed by two expert groups, which have proposed two different postpolypectomy surveillance strategies for patients with serrated polyps [5] [6].
TEMPORAL TRENDS OF OUTCOMES FOR ACUTE KIDNEY INJURY IN ACUTE ISCHEMIC STROKE FROM 2002 TO 2012: AN ANALYSIS OF NATIONWIDE INPATIENT SAMPLE DATA
Authors: Achint Patel, Girish Nadkarni, Alexandre Benjo, Shiv Kumar Agarwal, Ioannis Konstantinidis, Priya Simoes, Narender Annapureddy, Krishna Chaitanya Pakanati, Charuhas Thakar
Journal: Journal of the American College of Cardiology (2015)
P860 NUCLEAR RECEPTOR FXR UPREGULATES GENE EXPRESSION OF BILE ACID TRANSPORTERS IN NONALCOHOLIC STEATOHEPATITIS
Authors: N. Méndez-Sánchez, V. Sánchez-Valle, J.A. López-Velázquez, F. Chablé-Montero, N.C. Chávez-Tapia, M. Uribe
Journal: Journal of Hepatology (2014)
Corticosteroid-Treated Chronic Active Hepatitis in Remission
Authors: Albert J. Czaja, Jurgen Ludwig, Archie H. Baggenstoss, Audrey Wolf
Journal: New England Journal of Medicine (1981)

To assess the prognosis of patients with severe chronic hepatitis after histologic examination had shown an improvement to chronic persistent hepatitis, we followed 52 such patients regularly for 54±4 months after the cessation of corticosteroid therapy. In 24 patients, the condition deteriorated 7±1 months after therapy and required further treatment with prednisone. Histologic features of chronic active hepatitis, including bridging and multilobular necrosis, were documented in all 14 patients in whom biopsies were performed. In 20 of 24 patients, the disease responded to retreatment, but 13 again had relapses, and cirrhosis developed in two. Of 28 patients who remained asymptomatic for 48±6 months, 17 retained features of chronic persistent hepatitis, and nine had improvement to normal histologic features. Cirrhosis developed in two patients without clinical manifestations of active inflammation. Findings before and after treatment did not predict outcome. We conclude that severe chronic active hepatitis that has been treated with prednisone and converted to chronic persistent hepatitis will often and unpredictably deteriorate after treatment has been stopped. Cirrhosis develops rarely but may occur with or without clinically overt chronic active hepatitis. (N Engl J Med. 1981; 304: 5–9.)
P52 Prisms: A Systematic Review Of The Mrc 'phase Iv' Evidence On Implementing Asthma Self-management
Authors: H. Pinnock, E. Epiphaniou, H. Parke, G. Pearce, S. Taylor
Journal: Thorax (2014)

<h3>Aim</h3> Asthma self-management is effective in clinical trials, widely recommended by guidelines but poorly implemented. We aimed to synthesise the evidence from implementation studies of asthma self-management support interventions to inform delivery in routine clinical practice. <h3>Methods</h3> Using systematic review methodology (Cochrane Handbook) we searched eight electronic databases, performed snowball and manual searches, and searched research databases for unpublished and on-going work. We included studies with a range of methodologies, and which evaluated the introduction of an asthma self-management support intervention in routine clinical practice. We assessed included papers for quality (Downs and Black), extracted and synthesised data on process (e.g. number of action plans issued) and clinical outcomes (e.g. measures of asthma control, unscheduled healthcare). Narrative synthesis used the whole systems approach as a framework. [PROSPERO registration: CRD42012002898]. <h3>Results</h3> We included 18 studies (7 randomised trials, 8 longitudinal database studies, 3 uncontrolled studies) from primary, secondary, community and managed care settings in six countries. Interventions which explicitly addressed patient, professional and organisational factors (n = 7 studies) showed the most consistent improvement in both process and clinical outcomes. Targeting professionals (n = 2 studies) improved process but not clinical outcomes. Targeting patients (n = 6 studies) had inconsistent impact on process/clinical outcomes. Targeting the organisation (n = 3 studies) improved process, and had a small effect on clinical outcomes. Authors highlighted the importance of a healthcare system committed to supporting self-management, skills training for professionals, patient education programmes supported by regular reviews, and on-going evaluation of the implementation process. <h3>Conclusion</h3> Effective interventions were complex: actively engaging patients, and training and motivating professionals within the context of an organisation which prioritised supported self-management. Commissioners and providers of services for people with asthma should consider how they can promote a culture of supporting self-management as a normal, expected, monitored and remunerated aspect of the provision of care. <h3>Funding</h3> NIHR HS&amp;DR programme (project number 11/1014/04). The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Hs and DR programme, NIHR, NHS or the Department of Health.
ADDITION OF ATRIAL ECTOPY AND NT-PROBNP TO FRAMINGHAM ATRIAL FIBRILLATION RISK ALGORITHM IMPROVES RISK PREDICTION
Authors: Preman Kumarathurai, Mette R. Mouridsen, Nick Mattsson, Bjorn Larsen, Olav Nielsen, Thomas Gerds, Ahmad Sajadieh
Journal: Journal of the American College of Cardiology (2015)
Abstract 3906: Design, synthesis and biological evaluation of 2nd generation ezrin inhibitors for metastatic osteosarcoma
Authors: George W. Kosturko, Gulay Bulut, Sung-Hyeok Hong, Veronica Rodriguez, Milton Brown, Jeffrey Toretsky, Chand Khanna, Mikell Paige, Aykut Uren
Journal: Cancer Research (2012)

Abstract Though advancements in chemotherapy and surgical techniques have ameliorated treatment of primary osteosarcoma (OS), the metastatic phenotype remains a clinical challenge. Overall five-year survival rates for patients with localized OS have improved to 60-70%, yet survival rates of patients with metastasis remains at 20-30% with mortality linked to metastatis-induced respiratory failure. Therefore, targeting fundamental molecular events that lead to metastasis may yield significant benefit to patients with OS. Accumulating evidence from clinical samples and pre-clinical animal models suggests that ezrin is a key regulator in the metastasis of OS cells. Ezrin is a multifunctional protein that connects the actin cytoskeleton to extracellular matrix through transmembrane proteins and a critical component for cell motility, adhesion and shape. We have recently identified that a small molecule, NSC 668394 acts as a potent and selective inhibitor of ezrin function and inhibits migration in both in-vitro and in-vivo models. Moreover, suppression of ezrin phosphorylation by NSC 668394 significantly reduced the metastatic behavior in cellular and animal models and has thus emerged as an important lead inhibitor. Consequently, we conducted a series of structure-activity-relationship (SAR) studies that monitored direct binding; OS cell migration and HUVEC monolayer invasion in ‘real-time’ with surface-plasmon resonance and electrical impedance technology. From our 2nd generation library, we have designed novel candidate inhibitors which feature enhanced ezrin-binding affinity, and improved anti-migration and anti-invasion activities. In addition to their potency against the different stages of OS metastasis, these compounds possess other desirable attributes for development including good druggable physical-chemical characteristics and are currently undergoing further preclinical evaluation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3906. doi:1538-7445.AM2012-3906