tbuckley/cabot-search huggingface dataset:
FRI0250 Anca positivity in scleroderma patients identifies a poor prognosis: Myocarditis and survival
Authors: G. Berardi, G. De Luca, A. Laria, M. Bocci, M. Rucco, A. Capacci, M. Correra, M.R. Gigante, N. Galiano, S.L. Bosello, G. Ferraccioli
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Previous studies have shown that about 7% of unselected systemic sclerosis (SSc) patients are positive for ANCA<sup>1</sup>. Some case reports have also described an ANCA–associated vasculitis in SSc patients with progressive renal and lung function deterioration and poor outcome. <h3>Objectives</h3> To evaluate the prevalence of ANCA positivity in a SSc cohort and to study its association with clinical characteristics, major organ involvement and risk of mortality. <h3>Methods</h3> We evaluated the positivity and the levels of p- and c-ANCA in our cohort of 294 SSc patients according with age, immunological characteristics, disease duration and clinical manifestations. Only patients with almost two positive ANCA assessments have been considered ANCA positive. Specifically we evaluated the presence of digital ulcers, glomerulonephritis, myositis and myocarditis. Myocarditis was defined as the presence of increasedcardiac enzymes associated with the presence of enhancement at late gadolinium-enhanced cardiac magnetic resonance imaging and/or myocarditis on myocardial biopsy. The mortality in the last 12 years was also recorded. <h3>Results</h3> 17 patients out of 294 (5.8%) of the entire SSc cohort were identified as ANCA-positive. Six patients (35.3%) were c-ANCA positive with a mean level of 70.4±50.7 U/ml, while 11 patients (64.7%) were p-ANCA positive with a mean level of 65.8±47.7 U/ml. Out of the 17 ANCA positive patients, 58.8% presented anti-topoisomerase antibodies, 41.2% anticentromere antibodies. Sixteen patients (5.4%) presented myocarditis which was more frequent in patients with ANCA positivity than in ANCA negative patients (41.7% vs 3.2%, p&lt;0.0001). Overall mortality was 6.8%. Mortality in ANCA positive patients was higher than in ANCA negative patients (29.4% vs 5.4%, p=0.003). There was no association between ANCA positivity and complement consumption, glomerulonephritis, myositis and digital ulcers. <h3>Conclusions</h3> The prevalence of ANCA positivity in our cohort was 5.8% and, as previously reported, the majority of patients was positive for anti-topoisomerase antibodies. ANCA positivity was associated with myocarditis and with an increased risk of mortality. Considering the high mortality associated with cardiac involvement in SSc patients, our preliminary data suggest that ANCA positivity in SSc patients should be a warning biomarker to identify patients at risk of myocarditis and of a poor survival. <h3>References</h3> Akimoto S, Ishikawa O, Tamura T, Miyachi Y. Antineutrophil cytoplasmic autoantibodies in patients with systemic sclerosis. Br J Dermatol 1996;134(3):407-10. <h3>Disclosure of Interest</h3> None Declared
Mary Nicol Finlay
Authors: A. F. E. Edwards
Journal: BMJ (2013)

Mary Nicol Finlay (nee Peggie; known as “Ray”) was born in Borrowstounness and educated in Bathgate, where she was dux of her year. She studied medicine after her wish to be a vet was vetoed by her father. As a house officer at Edinburgh’s Southern General Hospital, she encountered wounded German prisoners of war and always recalled their poignant singing of …
Proton beam therapy benefits relatively few cancers, US guideline says
Authors: M. McCarthy
Journal: BMJ (2014)

Although proton beam therapy is appropriate in situations where it is not possible to spare surrounding normal tissue using standard photon based radiotherapy, routine insurance coverage should be reserved for treating relatively rare malignancies such as ocular tumors and pediatric brain tumors, says a new policy document from the American Society for Radiation Oncology (ASTRO).1

In its “model policy” document the society detailed which diagnoses met ASTRO’s evidence based standards and when they should be covered by private and government insurance. In a statement Colleen Lawton, chairwoman of ASTRO’s board of directors, …
Case 38-2001
Authors: A A Amato, P C Sanelli, M P Anderson
Journal: New England Journal of Medicine (2001)

Presentation of CaseA 51-year-old woman was admitted to the hospital because of paresthesias, ataxic gait, and hallucinations.The patient had been well until 9 or 10 months earlier, when tingling and numbness developed in all her fingers, with weakness of her hands and a burning sensation in her feet. A tentative diagnosis of bilateral carpal tunnel syndrome was made, but no neurophysiological studies were undertaken. Six months before admission, “asthmatic bronchitis” developed, with a cough that became productive, accompanied by mild hemoptysis. At about the same time, she began to have difficulty finding words and remembering the names of . . .
Improvement in Cardiac Function in the Cardiac Variant of Fabry's Disease with Galactose-Infusion Therapy
Authors: Andrea Frustaci, Cristina Chimenti, Roberta Ricci, Luigi Natale, Matteo A. Russo, Maurizio Pieroni, Christine M. Eng, Robert J. Desnick
Journal: New England Journal of Medicine (2001)

Fabry's disease is an X-linked inborn error of glycosphingolipid catabolism caused by deficient activity of α-galactosidase A, a lysosomal exoglycosidase.1,2 In males with the classic form of the disease, there is little if any α-galactosidase A activity. As a result, undegraded glycosphingolipids accumulate, particularly in the vascular endothelium. These deposits cause the characteristic angiokeratomas, acroparesthesias, hypohidrosis, and corneal opacities of Fabry's disease. Death in early adulthood in affected persons may be due to vascular disease of the heart, kidney, or brain. These abnormalities are absent in males with the cardiac variant of the disease. Those with the cardiac variant . . .
Abstract 61: Use of two-color fluorometric real-time PCR to develop molecular diagnostic tests with intrinsic quality control that augment cytomorphologic diagnosis of lung cancer.
Authors: Jiyoun Yeo, Erin L. Crawford, Thomas M. Blomquist, Lauren M. Stanoszek, Rachel E. Dannemiller, Laura Jordan, Jill Zyrek, Luis de la Casas, James C. Willey
Journal: Cancer Research (2013)

Abstract Quantitative RT-PCR tests that measure transcript abundance of selected genes in clinical specimens promise to improve cancer diagnostic accuracy and enable “personalized medicine” through selection of the most effective treatment for each cancer. However, most clinical samples are Formalin-Fixed, Paraffin-Embedded (FFPE) and these yield sub-optimal RNA integrity. Thus, there is a need for qPCR tests with increased robustness that also have intrinsic quality control and low cost. To address this need, we developed qPCR methods that enable simultaneous measurement of each target gene and reference gene transcript relative to a known number of gene-specific internal standard (IS) molecules using two-color fluorometric analysis on real-time platform. For each gene, a competitive template IS was synthesized containing 4-6 nucleotide changes relative to the native template (NT). During PCR, NT or IS signal was quantified with sequence-specific FAM-labeled probe or Quasar 670-labeled probe, respectively. To optimize measurement sensitivity for analysis of highly degraded FFPE samples; a) each RNA sample was reverse transcribed (RT) with gene-specific primer and b) cDNA was pre-amplified with 18 PCR cycles in the presence of internal standards. Results obtained with pre-amp or no pre-amp conditions were highly correspondent. We conducted a validation study of this assay in 38 samples (10 malignant and 10 benign surgical FFPE tissues and 13 malignant and 5 benign fine needle aspirate (FNA) samples. Consistent with previous results in fresh frozen surgical samples, the lung cancer diagnostic test (LCDT) optimal cut-off value discriminated malignant from non-malignant tissues (p = 0.0009), had 92.9% specificity and 75.0% sensitivity, and a receiver operator characteristic area under the curve of 0.87 (95% confidence interval 0.74-0.99). Based on these data, we expect that this quality-controlled two color fluorometric qPCR approach will enable reliable analysis of the LCDT and other promising qPCR-based molecular diagnostic tests in small degraded RNA extracted from clinical FFPE and FNA cell block FFPE samples. Citation Format: Jiyoun Yeo, Erin L. Crawford, Thomas M. Blomquist, Lauren M. Stanoszek, Rachel E. Dannemiller, Laura Jordan, Jill Zyrek, Luis de la Casas, James C. Willey. Use of two-color fluorometric real-time PCR to develop molecular diagnostic tests with intrinsic quality control that augment cytomorphologic diagnosis of lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 61. doi:10.1158/1538-7445.AM2013-61
EFFECT OF LOWER LIMB REMOTE ISCHEMIC CONDITIONING ON INFARCT SIZE IN PATIENTS WITH ANTERIOR ST-ELEVATION MYOCARDIAL INFARCTION
Authors: Dinos Verouhis, Peder Sörensson, Andrey Gourine, Loghman Henareh, Jonas Persson, Nawzad Saleh, Martin Sundqvist, Per Tornvall, Nils Witt, Felix Böhm, John Pernow
Journal: Journal of the American College of Cardiology (2016)
279 AUTOPHAGY NEGATIVELY REGULATES THE MESENCHYMAL PROGRAM IN HEPATOCYTES BY PROMOTING Snail DEGRADATION
Authors: G. Grassi, L. Santangelo, G. Di Caprio, M. Komatsu, M. Piacentini, G.M. Fimia, M. Tripodi, T. Alonzi
Journal: Journal of Hepatology (2013)
Recombinant Human Interleukin-2, Recombinant Human Interferon Alfa-2a, or Both in Metastatic Renal-Cell Carcinoma
Authors: Sylvie Negrier, Bernard Escudier, Christine Lasset, Jean-Yves Douillard, Jacqueline Savary, Christine Chevreau, Alain Ravaud, Alain Mercatello, Jean Peny, Mireille Mousseau, Thierry Philip, Thomas Tursz
Journal: New England Journal of Medicine (1998)

Recombinant human interleukin-2 (aldesleukin) and recombinant human interferon alfa can induce notable tumor regression in a limited number of patients with metastatic renal-cell carcinoma. We conducted a multicenter, randomized trial to determine the effect of each cytokine independently and in combination, and to identify patients who are best suited for this treatment.
PTH-081 Unearthing The True Prevalence of Anxiety within a Typical District General Cohort of Inflammatory Bowel Disease Patients: Is it Time we Considered Routinely Screening for Anxiety?
Authors: N Swart, D Wellsted, K Lithgo, T Price, M W Johnson
Journal: Gut (2013)

<h3>Introduction</h3> Previous studies have suggested that 15 to 30% of inflammatory bowel disease (IBD) patients also suffer from anxiety. Whilst most gastroenterologists would feel confident in recognising and diagnosing florid steroid induced psychosis, much of the associated anxiety experienced by IBD patients goes undiagnosed and untreated. Disease severity, recurrent flares, poor treatment adherence, disability, unemployment status, and socio-economic deprivation are all believed to be associated with anxiety in these patients. The severity of anxiety also appears to be directly correlated to the physical morbidity and malnutrition risk. <h3>Objectives</h3> To assess the true prevalence of anxiety within our IBD patients. <h3>Methods</h3> 2400 patients with IBD in the Luton &amp; Dunstable catchment were invited to participate in a web-based quality of life assessment, with the option to request a paper copy. Eligibility criteria required patients to be between 18 and 90 years of age, with no serious learning difficulties or pre-existing serious mental disorders. The well validated 7-item self-report “Generalised Anxiety Disorder (GAD) Questionnaire” was used. The GAD-7 has a minimum possible score of 0 and a maximum possible score of 21. Scores of 5, 10, and 15 represent cut-off scores for mild, moderate, and severe anxiety. <h3>Results</h3> 245 patients completed the assessment (43% male; mean age = 53, SD = 17). 45% had Ulcerative Colitis, 45% had Crohn’s Disease and 10% had an alternative form of IBD (e.g. Proctitis, Lymphocytic Colitis, or Collagenous Colitis). The ethnic mix in the responding cohort was 91% Caucasian, 6% Asian, 2% Mixed and 1% was not stated. The sample had a mean score of 6.6 (CI = 5.9 – 7.4). 72% of patients’ scores reflected no anxiety or “mild anxiety”; 15% reflected “moderate anxiety”; and 13% reflected “severe anxiety”. <h3>Conclusion</h3> 29% of our responding IBD patients were shown to have significant anxiety scores (moderate + severe), with 14% demonstrating severe anxiety levels. Despite the severity, few of these patients were receiving treatment or therapy for their condition. The GAD score is a simple and quick tool that can be used in clinic. Given that anxiety is believed to directly affect the clinical course of IBD, both the screening and treatment of this condition should be considered part of standard IBD medical care. <h3>Disclosure of Interest</h3> None Declared.
OP0099 Somatic Comorbidity in Patients with Chronic Widespread Pain in an Outpatient Secondary Care Center for Rheumatology and Rehabilitation in the Netherlands
Authors: M. Crins, L. D. Roorda, W. Beuving, H. C. Boshuizen, J. Dekker
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Comorbidity, defined as one or more additional disease(s) among patients with an index-disease, can affect the treatment and the prognosis of the index disease.<sup>1,2</sup> Although numerous studies address the prevalence of somatic complaints in patients with chronic widespread pain (CWP), the prevalence of somatic comorbidity has not been studied in detail in these patients and, more specifically, this prevalence has not been compared to the prevalence in the general population.<sup>2</sup> <h3>Objectives</h3> First aim was to describe the prevalence of somatic comorbidity in patients with CWP. Second aim was to compare this prevalence with the prevalence rates in the general Dutch population and to describe the risk factor of these comorbidities for patients with CWP. <h3>Methods</h3> A cohort study on somatic comorbidity was conducted among 1238 patients with CWP referred to an outpatient secondary care center for rheumatology and rehabilitation in the Netherlands. Data on comorbidity were collected by means of a questionnaire including 15 chronic somatic conditions, adapted from the Health Interview Survey of the Statistics Netherlands.<sup>3</sup> Statistical analyses included descriptive statistics, Chi-square tests and Standardized Mortality Ratios (SMR). SMR quantifies the disease risk of a study population compared to the general population. <h3>Results</h3> 84% of the subjects reported one or more somatic comorbidities. The most frequently reported comorbidities were migraine (52%), dizziness with falling (24%), hypertension (23%), incontinence (19%) and chronic pulmonary disease (15%). In comparison with the Dutch population, 13 of the 15 somatic comorbidities were significantly (P&lt;0.05) more prevalent in the CWP patients than expected. The SMR was for 12 of the 15 comorbidities greater in the study population compared to the Dutch population, including higher risk for migraine (SMR 2.5), dizziness with falling (SMR 7.6), hypertension (SMR 1.4), incontinence (SMR 2.8) and chronic pulmonary disease (SMR 1.8). <h3>Conclusions</h3> The results show substantial somatic comorbidities in patients with CWP and an increased risk factor in comparison to the general population. <h3>References</h3> Feinstein AR. The pre-therapeutic classification of co-morbidity in chronic disease. J Chron Dis 1970;23:455-69. Fishbain DA. Polypharmacy treatment approaches to the psychiatric and somatic comorbidities found in patients with chronic pain. Am J Phys Med Rehabil 2005;84(suppl):S56–S63. Health Interview Survey. Voorburg/Heerlen: Statistics Netherlands; 1994 <h3>Disclosure of Interest</h3> None Declared
Case 3-1994
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Jeffrey S. Hyams, Fiona Graeme-Cook
Journal: New England Journal of Medicine (1994)

Presentation of CaseAn 11-year-old boy was admitted to the hospital because of recurrent abdominal pain.The child was born of a full-term normal pregnancy and delivery, weighing 3.5 kg. His early growth and development were normal. He was well until one month before entry, when he experienced the onset of periumbilical, nonradiating, “squeezing” pain that occurred as frequently as every two or three hours. The pain began without relation to food intake, sometimes awakened him during the night, and was relieved by nothing but improved temporarily after defecation. He began to pass one soft stool every day or two, . . .
Acute Hypothalamic–Pituitary–Adrenal Responses to the Stress of Treadmill Exercise
Authors: Anton Luger, Patricia A. Deuster, Susan B. Kyle, William T. Gallucci, Lesley C. Montgomery, Philip W. Gold, D. Lynn Loriaux, George P. Chrousos
Journal: New England Journal of Medicine (1987)

To study the effects of physical conditioning on the hypothalamic–pituitary–adrenal axis, we examined the plasma ACTH, cortisol, and lactate responses in sedentary subjects, moderately trained runners, and highly trained runners to graded levels of treadmill exercise (50, 70, and 90 percent of maximal oxygen uptake) and to intravenous ovine corticotropin-releasing hormone (1 μg per kilogram of body weight). Basal evening concentrations of ACTH and cortisol, but not of lactate, were elevated in highly trained runners as compared with sedentary subjects and moderately trained runners. Exercise-stimulated ACTH, cortisol, and lactate responses were similar in all groups and were proportional to the exercise intensity employed. These responses, however, were attenuated in the trained subjects when plotted against applied absolute workload. Only the highly trained group had diminished responses of ACTH and cortisol to ovine corticotropin-releasing hormone, consistent with sustained hypercortisolism. We conclude that physical conditioning is associated with a reduction in pituitary–adrenal activation in response to a given workload. Alterations of the hypothalamic–pituitary–adrenal axis consistent with mild hypercortisolism and similar to findings in depression and anorexia nervosa were found only in highly trained runners. Whether these alterations represent an adaptive change to the daily stress of strenuous exercise or a marker of a specific personality profile in highly trained athletes is unknown. (N Engl J Med 1987; 316:1309–15.)
Abstract 2082: ERK activation mediated by Duox2 expression and reactive oxygen production is responsible for HIF-1α accumulation and VEGF induction in IFN-γ-treated BxPC-3 pancreatic cancer cells
Authors: Yongzhong Wu, Smitha Antony, Jiamo Lu, Agnes Juhasz, Han Liu, Guojian Jiang, Krishnendu Roy, James H. Doroshow
Journal: Cancer Research (2011)

Abstract Reactive oxygen species (ROS) play an important role in tumor angiogenesis by up-regulating pro-angiogenic effectors such as HIF-1alpha and vascular endothelial growth factor (VEGF). However, the sources of ROS and the pro-angiogenic signaling pathways they target in tumor cells remain incompletely understood. We recently found that several members of the NADPH Oxidase (Nox) gene family are expressed in many human tumors; of these, Duox (Dual oxidase) 2 is highly expressed in tumors of the gastrointestinal tract. Recently, we demonstrated that IFN-gamma treatment of Bx-PC-3 cells upregulates the expression of Duox2 (and its maturation factor DuoxA2; but no other Nox isoform) leading to long-lived production of H2O2. Using this system, we investigated the role of Duox2-mediated ROS in the regulation of HIF-1alpha and VEGF expression. In BxPC-3 cells, IFN-gamma induction of Duox2/A2 expression was accompanied by both intra- and extracellular ROS accumulation, and by the simultaneous upregulation of HIF-1alpha and VEGF. However, in the MIA-PaCa-2 and PANC-1 lines that do not upregulate Duox2 following IFN-gamma exposure, no HIF-1alpha or VEGF induction was observed. In BxPC-3 cells, both the Nox inhibitor diphenylene iodonium and the ROS scavenger N-acetyl-L-cysteine suppressed IFN-gamma-induced HIF-1alpha accumulation and VEGF upregulation, suggesting that Duox2-derived ROS are involved in VEGF induction. Further experiments revealed that IFN-gamma induced a sustained activation of ERK1/2, which subsequently activated p90 ribosomal S6 kinases (RSKs) and the regulator of protein translation, ribosomal protein S6, resulting in enhanced synthesis of HIF-1alpha. ERK activation was required for IFN-gamma-induced HIF-1alpha and VEGF expression, since treatment with the MEK inhibitor U0126 completely abrogated IFN-gamma-induced HIF-1alpha and VEGF expression. Duox2-specific siRNA experiments showed that IFN-gamma-induced ROS, ERK activation, and HIF-1alpha accumulation were significantly attenuated following silencing of Duox2 expression. However, IFN-gamma-induced expression of VEGF was unchanged following Duox2 knockdown. Ongoing studies are evaluating the role of residual Duox2 or Duox2-independent pathways for VEGF activation following IFN-gamma exposure as well as other downstream, pro-angiogenic targets of Duox2-mediated HIF-1alpha expression under normoxic conditions. 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 2082. doi:10.1158/1538-7445.AM2011-2082
SC-05 * DOPAMINE RECEPTOR ANTAGONISTS ARE SELECTIVE INHIBITORS OF GLIOBLASTOMA STEM CELLS THROUGH IMPAIRMENT OF AUTOPHAGY
Authors: S. Dolma, M. So, V. Voisin, X. Zhu, R. Head, I. Clarke, G. Bader, M. Tyers, P. Dirks
Journal: Neuro-Oncology (2014)

Glioblastoma is an incurable cancer. The tumorigenic potential of glioblastoma resides within cells with a stem cell phenotype called glioblastoma stem cells. In order to identify novel glioblastoma drugs, we interrogated a library of 680 neuromodulatory compounds for their activity on glioblastoma derived neural stem cells (GNS), normal human fetal neural stem (NS) cells and normal fibroblasts to identify selective inhibitors. Compounds modulating dopaminergics, serotonergics and cholinergics pathways are enriched in the hits. In particular, two dopamine receptor antagonists demonstrated great selectivity for GNS cells and were synergistic with the chemotherapeutic drug temozolomide. These compounds reduced the clonogenic potential of primary glioblastoma cells and the growth of glioblastoma xenografts. Primary glioblastoma tumor and GNS cells expressed dopamine receptor. Mechanistic studies by pharmalogical inhibition and genetic knockdown of dopamine receptor suppressed glioblastoma stem cells growth and the ERK1/2 pathway. Furthermore, genome wide expression array showed downregulation of genes involved in cell cycle progression and upregulation of genes involved in autophagy. Further investigation revealed accumulations of autophagic vacuole with increased p62 suggesting a block in autophagy leading to cell death. This study identified new candidates for glioblastoma therapy and suggests neurochemical modifications should be focus for further drug development.
P1091 : One year effectiveness of Baclofen treatment in 100 alcohol-dependent patients
Authors: C. Barrault, H. Lison, F. Roudot-Thoraval, A. Garioud, V. Béhar, I. Rosa-Hézode, D. Belloula, M. Medmoun, C. Fourny, G. Pulwermacher, H. Hagège, J.-F. Cadranel
Journal: Journal of Hepatology (2015)