tbuckley/cabot-search huggingface dataset:
Medication Use and the Risk of Stevens–Johnson Syndrome or Toxic Epidermal Necrolysis
Authors: Jean-Claude Roujeau, Judith P. Kelly, Luigi Naldi, Berthold Rzany, Robert S. Stern, Theresa Anderson, Ariane Auquier, Sylvie Bastuji-Garin, Osvaldo Correia, Francesco Locati, Maja Mockenhaupt, Catherine Paoletti, Samuel Shapiro, Neil Shear, Erwin Schöpf, David W. Kaufman
Journal: New England Journal of Medicine (1995)

Toxic epidermal necrolysis and Stevens-Johnson syndrome are rare, life-threatening, drug-induced cutaneous reactions. We conducted a case-control study to quantify the risks associated with the use of specific drugs.Data were obtained through surveillance networks in France, Germany, Italy, and Portugal. Drug use before the onset of disease was compared in 245 people who were hospitalized because of toxic epidermal necrolysis or Stevens-Johnson syndrome and 1147 patients hospitalized for other reasons (controls). Crude relative risks were calculated and adjusted for confounding by multivariate methods when numbers were large enough.Among drugs usually used for short periods, the risks were increased for trimethoprim-sulfamethoxazole and other sulfonamide antibiotics (crude relative risk, 172; 95 percent confidence interval, 75 to 396), chlormezanone (crude relative risk, 62; 21 to 188), aminopenicillins (multivariate relative risk, 6.7; 2.5 to 18), quinolones (multivariate relative risk, 10; 2.6 to 38), and cephalosporins (multivariate relative risk, 14; 3.2 to 59). For acetaminophen, the multivariate relative risk was 0.6 (95 percent confidence interval, 0.2 to 1.3) in France but 9.3 (3.9 to 22) in the other countries. Among drugs usually used for months or years, the increased risk was confined largely to the first two months of treatment, when crude relative risks were as follows: carbamazepine, 90 (95 percent confidence interval, 19 to infinity); phenobarbital, 45 (19 to 108); phenytoin, 53 (11 to infinity); valproic acid, 25 (4.3 to infinity); oxicam nonsteroidal antiinflammatory drugs (NSAIDs), 72 (25 to 209); allopurinol, 52 (16 to 167); and corticosteroids, 54 (23 to 124). For many drugs, including thiazide diuretics and oral hypoglycemic agents, there was no significant increase in risk.The use of antibacterial sulfonamides, anticonvulsant agents, oxicam NSAIDs, allopurinol, chlormezanone, and corticosteroids is associated with large increases in the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. But for none of the drugs does the excess risk exceed five cases per million users per week.
Plasma Lipoprotein (a) Levels in Patients with Slow Coronary Flow
Authors: Habil Yücel, Abdullah Doğan, Ahmet Altınbaş, Salaheddin Akçay, Atilla İçli, Hasan Aydın Baş, Betül Mermi Ceyhan, Akif Arslan
Journal: Journal of the American College of Cardiology (2013)
P1-08-07: Survival in US Women Following an Indication of Metastatic Breast Cancer Diagnosis and Chemotherapy Initiation: A SEER-Medicare Analysis.
Authors: H Rugo, D Taylor, M Sanon, K Clements, S Balu, C Faria, A Teitelbaum
Journal: Cancer Research (2011)

Abstract Objective: Use SEER-Medicare data to identify US women with metastatic breast cancer (MBC) treated (tx) with chemotherapy (CTX) and evaluate survival. Methods: Key inclusion criteria were women diagnosed (dx) with breast cancer (BC) in 2001–2005 with 1) Medicare enrollment 12 mo prior to dx through follow-up (2008) or death; 2) an indication of tx with CTX at any time after initial BC diagnosis (any stage). Dx of MBC between 2001–2006. MBC dx date was defined as the initial BC dx date if the patient had “distant” disease at entry into SEER or the date of first appearance of secondary malignancy in claims data (ICD9 codes 197.0−198.1, 198.3−198.7, 198.82−198.89) during follow up, at least 2 mo after initial dx. CTX date was defined as the date of first receipt of a CTX agent commonly used to treat BC after the MBC date. Data on oral medications (e.g., most hormone therapies, capecitabine) were not available. Kaplan-Meier survival analyses were performed to describe survival after MBC dx (patients were censored at end of follow-up). Survival was assessed both from the date of MBC and receipt of first intravenous (IV) chemo. Subgroup analyses were performed based on age, type of MBC dx and estrogen receptor (ER) status. Results: Patient demographics and survival are shown in the table. Conclusions: Despite recent advances in treatment options, median survival following a dx of MBC is less than two years, and is approximately 16 months after start of IV CTX. Survival is shorter for patients who develop MBC after an initial breast cancer dx compared to those with MBC at diagnosis, and for those with ERnegative tumors. In order to improve clinical outcomes, it is critical to pursue a better understanding of tumor biology and appropriate use of new agents. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-08-07.
Regions of juxtaposition in unbalanced 1q rearrangements of malignant hemopathies
Authors: R La Starza, A Aventin, D Falzetti, I Wlodarska, AM Fernandez Peralta, JJ Gonzalez-Aguilera, S Ciolli, MF Martelli, C Mecucci
Journal: Leukemia (2001)
THU0216 Down-Titration and Discontinuation of Infliximab, Adalimumab and Etanercept in Established Rheumatoid Arthritis
Authors: L. Lojo, G. Bonilla, D. Peiteado, A. Villalba, C. Plasencia, L. Nuño, A. Balsa, E. Martín-Mola
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The feasibility of down-titration or discontinuation of biological drugs has been demonstrated by several studies. However, there are limited data about the prevalence of successful down-titration in daily clinical practice. <h3>Objectives</h3> To Evaluate the prevalence of down-titration or discontinuation of infliximab (Ifx), adalimumab (Ada) and etanercept (Eta) in RA patients with low disease activity or remission and the effects on disease activity. <h3>Methods</h3> From January 2000 to December 2012, all RA patients who started treatment with Ifx, Ada and Eta as the first biologic drug, were included in the study. Patients who had stable low disease activity or remission for at least 6 months are treated according to our local protocol increasing the interval between doses. Prevalence of down-titration and discontinuation were described. Disease activity was assessed using disease activity score 28 (DAS28) and functional capacity was measured through the Health Assessment Questionnaire (HAQ). <h3>Results</h3> Of the 276 patients, 124 were treated with Ifx, 85 with Ada and 67 with Eta. The proportion of patients who were seropositive, the mean DAS28, mean HAQ and mean erythrocyte sedimentation rate (ESR) were different between groups. Baseline characteristics are depicted in the table bellow. <h3>Conclusions</h3> In our cohort down-titration of Ifx, Ada and Eta is possible in an important proportion of RA patients without a relevant change in clinical and functional outcomes. The proportion of Ifx-treated patients who could be down-titrated was significantly lower than in patients treated with Ada and Etn. <h3>Disclosure of Interest</h3> None Declared
A2.13 Ra-associated autoantibodies promote synovial fibroblast migration and adhesion through a peptidylarginine deiminases (pad) dependent pathway
Authors: M Sun, V Joshua, AH Hensvold, M Engström, SB Catrina, C Ospelt, V Malmström, K Amara, H Wähämaa, B Rethi, AI Catrina
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> We have recently demonstrated that anti-citrullinated proteins antibodies (ACPAs) promote IL-8 production and osteoclast activation. In a second step this might lead to chronic synovial inflammation characterised by activation of resident synovial fibroblasts (SF). We aimed to investigate the effect of ACPAs and IL-8 on SF. <h3>Methods and materials</h3> SFs were isolated from synovial tissue of RA patients by enzymatic digestion. Polyclonal ACPA and other non-ACPA IgGs were separated from plasma of RA patients by affinity purification on a CCP2 column. Monoclonal ACPAs were generated from synovial fluid single B-cells. Antibodies were tested in migration scratch assays and evaluated by NIH ImageJ software to calculate the migration index in the presence or absence of exogenous IL-8. SF adhesion was analysed by xCELLigence System Real-Time Cell Analyzer (ACEA bioscience). Impedance-based signals were monitored continuously during 36 h. Blocking experiments using phosphoinositide 3-kinase (PI3K), G-protein coupled receptors or focal adhesion kinase (FAK) inhibitors as well as a pan-peptidylarginine deiminases (PAD) inhibitor were performed in the migration scratch assays in the presence or absence of the antibodies. Phosphorylation signal pathways were detected by western blot. <h3>Results</h3> Polyclonal ACPAs but not other IgGs induced both SFs migration (a fold increase of 2.6 ± 0.5, mean±SD, p &lt; 0,05) and SFs adhesion (a fold increase of 1.3 ± 0.1 at 6 h, p &lt; 0.05). Similar effects were observed with two (D10 and B02) out of three tested monoclonal ACPAs, with 2.4 ± 0.4 fold increase of the migration index for D10 antibody and 2.2 ± 0.4 for B02 antibody (p &lt; 0.05 for both). Exogenous added IL-8 had minimal effect on SFs migration, but synergistically promote SF migration in presence of suboptimal ACPAs concentrations. GPCR and PI3K but not FAK blocking completely abolished ACPAs effects. Signalling pathway analysis revealed Akt phosphorylation in SFs in the presence of ACPA. No difference in either cytotoxicity or proliferation rate were observed between different treatments. <h3>Conclusion</h3> ACPAs increase SFs migration and adhesion acting synergistically with IL-8. Our findings suggest that SF might be important players in the ACPA-dependent disease propagation from the bone marrow to synovial tissue.
Abstract 241: Transcription factor RBP-J-mediated signaling regulates basal cell carcinoma growth
Authors: Mei Yu, David Zloty, Robert H. Bell, Anne Haegert, Nicholas Carr, Jerry Shapiro, Bryce Cowan, Larry Warshawski, Kevin J. McElwee
Journal: Cancer Research (2011)

Abstract Hair follicles (HF) and basal cell carcinomas (BCCs) can be regarded as ordered and disordered skin appendages respectively. They may utilize similar molecular mechanisms of growth. We examined the similarities and differences in gene expression between BCCs and HFs to define common and unique signaling pathways that distinguish an ordered skin appendage from a disordered skin growth. Nodular BCCs, non-follicular skin epithelium, and HF between the sebaceous gland and bulb region were microdissected and examined using microarrays. Selected genes were validated using quantitative PCR, immunohistochemistry and in vitro studies. Two differentially expressed gene sets were identified by significance analysis of microarray (SAM) in BCC and HF versus skin epithelium respectively. Subsequently, multiple signaling pathway analyses were conducted. The results indicated that Notch and Hedgehog signaling pathways were active in the growth of both HF and BCCs. However, Notch signaling, including tumor suppressor genes NOTCH1, NOTCH2, ligands JAG1, JAG2, signaling inhibitor NUMB, and downstream Notch pathway genes DTX1, DTX2, RBP-J, LFNG, HR, and HES7, all showed significant differential expression in BCCs compared to HF. The data suggests downstream gene expression in the Notch signaling pathway is suppressed in BCCs. We tested the effect of transcription factor RBP-J and found transcription factor RBP-J-mediated signaling suppresses BCC cell growth and induces cell apoptosis in vitro. Our data suggest that RBP-J serves as a tumor suppressor in BCC and BCCs deficient in RBP-J lose tumor repression activity. Modulation of the Notch pathway may be a focus for the development of BCC treatments. 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 241. doi:10.1158/1538-7445.AM2011-241
Paclitaxel-Induced Severe Neuropathy in Patients With Previous Radiotherapy to the Head and Neck Region
Authors: J. M. LIU, Y. M. CHEN, Y. CHAO, T. W. LIU, C. M. CHOU, L. T. CHEN, W. L. YU, J. WHANG-PENG
Journal: JNCI Journal of the National Cancer Institute (1996)
Abstract 1275: Expression of Nur77 induced by an <i>n</i>-butylidenephthalide derivative promotes apoptosis and inhibits cell growth in oral squamous cell carcinoma
Authors: Po-Yen Liu, Yi-Chang Su
Journal: Cancer Research (2010)

Abstract Background: In spite of numerous advances, the 5-year survival rate for head and neck squamous cell cancer has remained largely stagnant, and few new anti-tumor drugs have been developed for oral squamous cell carcinoma (OSCC). PCH4 ((Z)-N-(2-(dimethyl-amino) ethyl)-2-(3-((3-oxo-isobenzofuran-1(3H)-ylidene) methyl) phenoxy) acetamide), a derivative of n-butylidenephthalide (BP), was investigated for anti-tumor effects on OSCC. Aim: The aim of this study was to investigated the mechanism of Nur77 translocation induced by PCH4 Methods: OSCC cells were treated by PCH4 in vitro and in vivo. The Nur77 translocation was detection by western blotting, immunohistochemistry and immunocytochemistry. Results: PCH4 promoted Nur77 translocation from the nucleus to the cytoplasm and induced cell apoptosis in OSCC cells. When Nur77 translocation was prohibited by Nur77 short interfering RNAs, the degree of tumor apoptosis caused by PCH4 was significantly alleviated. Within the MAPK pathway, PCH4 induced only JNK phosphorylation. Furthermore, treatment with a JNK inhibitor significantly reduced PCH4-induced apoptosis (p&amp;lt;0.05) and decreased PCH4-induced Nur77 expression (p&amp;lt;0.05). In a xenograft animal model, administration of PCH4 showed similar anti-tumor effects in OSCC cells that were dose dependent. Immunohistological staining showed similar effects on Nur77 expression and apoptosis in xenografts. Conclusion: We have demonstrated that OCSS cells are sensitive to PCH4 and that Nur77 protein translocation from the nucleus to the cytoplasm might be associated with the induction of apoptosis by PCH4. These results, both in vitro and in vivo, indicate that PCH4 may serve as a potential anti-tumor drug for OSCC therapy. 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 1275.
Abstract 4229: Wound repair promotes ovarian cancer stem cell self-renewal
Authors: Ilana Chefetz-Menaker, Noah Lebowitz, Paolomi Aldo, Ayesha Alvero, Jennie Holmberg, Gil Mor
Journal: Cancer Research (2010)

Abstract Background: In normal tissues following injury, there is an expansion of tissue specific stem cells prior to their differentiation to initiate injury repair. Once the tissue is repaired, the stem cells return to a quiescent state. Tumor tissue, might follow similar characteristics as in normal tissues, but the control of the expansion process may be significantly altered. Recently, ovarian cancer stem cells (ovCSC) were isolated from ovarian cancer tissue and ascites using CD44/CK18 as markers. We hypothesize that these cells play a critical role in tumor repair and renewal. To test this hypothesis, we used an in vitro wound/healing system. Methods: Cells were plated in an Essen ImageLock plate and wounds were made using an Essen WoundMaker. This sytem allows the generation of consistent wound locations and widths and precise imaging of the wound area. The healing process is monitored using an insitu imaging system (IncuCyte, Essen Instruments, NH) that records and quantifies the repair process in real time. Levels of cancer stem cell markers, CD44, Oct-4, and β-catenin were determined by Western blot analysis or Real Time PCR. Levels of cytokines and chemokines were determined using Luminex Technology. Results: Initially we tested whether an in vitro wound/healing system can be used as a renewal model. Interestingly, ovCSCs showed a well coordinated and organized response to the wound. First, the cells created a “straight line” to replace the irregular edge of the wound. Afterwards, the cells proliferated towards the wound, repairing the wound until confluence was reached. Analysis of cancer stem cell markers by Western blot revealed that the cells which repaired the wound maintained CD44, CK18, Oct4, and β-catenin, previously shown as ovCSC markers. Additionally, the process of repair was characterized by significant and differential up-regulation in IL-6, GRO-α, and MCP-1 expression and secretion. Interestingly, the CD44 expression was increased in wounded wells when compared to control. Moreover, using specific primers for CD44 variant isoforms we found that wound healing promotes expression of different CD44 forms. Conclusions: In this study we demonstrate ovCSCs have the capacity to repair an in vitro wound and that this process is accompanied by increased CD44 expression and cytokine secretion. This increased capacity of self renewal can lead to the accumulation of a large pool of progenitor cells, which has the potential to individually spread to other areas of the body as metastatic 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 4229.
Detection of Human T-Cell Lymphoma/Leukemia Virus Type I DNA and Antigen in Spinal Fluid and Blood of Patients with Chronic Progressive Myelopathy
Authors: Satyakam Bhagavati, Garth Ehrlich, Roger W. Kula, Shirley Kwok, John Sninsky, Vrajesh Udani, Bernard J. Poiesz
Journal: New England Journal of Medicine (1988)

The presence of antibodies to human T-cell lymphoma/leukemia virus Type I (HTLV-I) has been associated with chronic progressive myelopathy. We attempted to isolate the virus from the blood and spinal fluid of patients with chronic progressive myelopathy and to define the clinical, radiologic, and electrophysiologic features of this disease. Ten of 13 patients from tropical countries and 2 of 8 from the United States had serum antibodies to HTLV-I. The virus was detected in cultures of peripheral-blood lymphocytes from three of seven patients by means of Southern blot hybridization. Using a sensitive in vitro enzymatic gene-amplification technique, we detected HTLV-I sequences in fresh peripheral-blood mononuclear cells of all of 11 patients tested who were positive for the antibody, and in cell cultures of the spinal fluid from 3 of the 11 tested. Magnetic resonance imaging of the cranium revealed periventricular lesions in the white matter of 3 of the 12 antibody-positive patients. Five of these patients had mild axonal sensorimotor polyneuropathy, and one had bilateral lumbar radiculopathy. Visual evoked potentials were abnormal in three seropositive patients, and brain-stem evoked responses were abnormal in two. The detection of the DNA and proteins of HTLV-I strengthens the proposition that this virus is involved in the pathogenesis of a subset of cases of chronic progressive myelopathy. (N Engl J Med 1988; 318:1141–7.)
Brain PET Metabolic Abnormalities in a Case of Varicella-Zoster Virus Encephalitis
Authors: Benjamin Coiffard, Eric Guedj, Aurélie Daumas, Pierre Leveque, Patrick Villani
Journal: Clinical Nuclear Medicine (2013)

The role of brain 18F-FDG PET in the diagnostic evaluation of encephalitis has been recently suggested, especially in limbic encephalitis, but descriptions are mainly limited to small case reports. However, the evaluation of cerebral metabolism by 18F-FDG PET has never been described for varicella-zoster virus encephalitis. We report the first case of varicella-zoster virus encephalitis in which 18F-FDG PET revealed brain metabolic abnormalities. Brain metabolic PET imaging was analyzed by comparing the patient's brain 18F-FDG PET scans to that of 12 healthy subjects. Compared with healthy subjects, significant hypometabolism and hypermetabolism were found and evolved over time with treatment.
PTH-043 Difficult Biliary Access: Early Experience with the New Double Wire Technique Compared to Conventional Precut at Ercp
Authors: R Rameshshanker, B Macfarlane, A King, A Leahy
Journal: Gut (2013)

<h3>Introduction</h3> Selective cannulation of the common bile duct (CBD) during endoscopic retrograde cholangiopancreatography (ERCP) can be technically challenging. The precut technique is a tried and tested method of gaining biliary access when standard cannulation with either contrast or guidewire has failed. However, it does have a recognised higher risk of causing pancreatitis and when used it is currently advised to place a prophylactic pancreatic stent. A new technique, termed double guidewire, involves leaving a wire in the pancreatic duct to provide a “roadmap” for subsequent biliary wire cannulation. <h3>Objectives</h3> To report our initial experience for the success and complication rate of the double guidewire technique. <h3>Methods</h3> Retrospective analysis of all patients who underwent ERCP between April 2010 to April 2012 at our institution. Observed differences were tested with the Fisher’s exact test. <h3>Results</h3> 484 ERCP procedures, all having initial cannulation with either a single guidewire or contrast. Overall successful biliary cannulation for first ever ERCP was achieved in 95%. Attempted CBD cannulation was facilitated by double guidewire in 20 patients and precut in 19 patients. CBD cannulation was successful in 19/20 (95%) double guidewire patients and 15/19 (79%) precut patients (p = NS). Post-ERCP pancreatitis occurred in all procedures were 11/484 (2.2%), double guidewire 3/20 (15%) (p &lt; 0.02), precut 1/19 (5.3%). Prophylactic pancreatic stents were placed in 2 double guidewire patients and no precut patients. In the double guidewire group, patients with pancreatitis stayed longer (mean 8 days) in the hospital when compared to precut group (mean 3 days). <h3>Conclusion</h3> Deep CBD cannulation could be equally achieved with the help of either the double guidewire or the precut technique. There was a significant increased risk of pancreatitis with the double guidewire technique presumably related to inadvertent and repeated wire cannulations of the pancreatic duct. We find that the double guidewire technique is technically easy and currently use it if pancreatic duct cannulation occurs on &gt; 3 occasions. However, when used we now also place a prophylactic pancreatic stent at the end of the procedure. Conflicts of interest none <h3>Disclosure of Interest</h3> None Declared.
Attack Rates of Streptococcal Pharyngitis, Rheumatic Fever and Glomerulonephritis in the General Population
Authors: W. R. O. Goslings, H. A. Valkenburg, A. W. Bots, J. C. Lorrier
Journal: New England Journal of Medicine (1963)

SINCE the attack rate of rheumatic fever and of acute hemorrhagic glomerulonephritis after untreated infection due to Group A streptococci has been estimated at between 1.5 and 5 per cent1 2 3 4 5 penicillin treatment has been widely recommended for the control of these late nonsuppurative sequelae. The attack rate of glomerulonephritis is even higher when related to Type 12 infections.6 The attack rate of both diseases has been determined primarily from epidemic studies conducted in more or less closed communities living under epidemiologic conditions not prevalent in the general population.Several recent reports7 8 9 10 11 12 13 14 have suggested that rheumatic fever and glomerulonephritis occur less . . .