tbuckley/cabot-search huggingface dataset:
OC-052 Universal Screening For Alcohol Misuse In Acute Medical Admissions Is Feasible And Identifies Patients At High Risk Of Liver Disease
Authors: P Meredith, P Schmidt, S Atkins, P Greengross, G Westwood, R Aspinall
Journal: Gut (2014)

<h3>Introduction</h3> The 2013 NCEPOD report into deaths from Alcohol Related Liver Disease (ARLD) highlighted missed opportunities for detecting alcohol misuse in recurrent hospital admissions. Universal screening of medical patients was advised but little is known of the achievability of this or its efficiency at detecting high risk cases. In 2011, Portsmouth Hospitals NHS Trust introduced a 7-day Alcohol Specialist Nursing Service (ASNS) coupled with universal screening of medical patients using a novel electronic data capture system. We present data on the feasibility of unselected screening and the resulting alcohol profiles of over 28,000 medical admissions in a large acute hospital serving a catchment of 650,000. <h3>Methods</h3> From July 2011 to December 2012, all admissions via the Acute Medical Unit (AMU) were screened using the VitalPAC clinical observation system with a VitalPAC Alcohol Assesment Score (VPAAS) based on the Paddington Alcohol Test. At-risk patients (VPAAS of 6 or more) were referred to the ASNS and an Alcohol Use Disorders Identification Test (AUDIT) performed. Data analysis was performed on patient demographics, unit consumption, diagnosis, mortality and previous ED attendances and admissions. <h3>Results</h3> There were 29,361 admissions of whom 28,098 (96%) completed VPAAS alcohol screening. Mean AMU population age was 67.4 years, 52.3% female. Of 1,123 high risk cases, 770 were seen by the ASNS and 636 defined as dependent (AUDIT &gt;20). Compared to the general AMU cohort, the at-risk group had more ED attendances (7.8 vs. 2.9) and hospital admissions (4.8 vs. 3.1) in the previous 3 years and a lower age of death (58.3 vs. 81.5). Dependent women had fewer recurrent attendances and admissions than men but had a higher mortality rate and lower age of death (52.2 vs. 62.4). The maximum AUDIT score of 40 was recorded in 41% of cases seen by the ASNS and this subgroup had a mean age of death of 52.7 with 6.2 admissions and 10.8 ED attendances previously. The most frequent primary diagnoses in those with a VPAAS of 6+ were liver disease, mental health disorders and GI bleeding. <h3>Conclusion</h3> Our analysis of over 28,000 admissions demonstrates that screening of all medical patients for alcohol misuse is achievable. We successfully identified a cohort of high risk patients with recurrent admissions and ED attendances, high unit consumption and an elevated risk of liver disease and early death. This cohort can be targeted with interventions to reduce the burden of alcohol related harm. <h3>Disclosure of Interest</h3> P. Meredith: None Declared, P. Schmidt Conflict with: Unpaid research advisor to The Learning Clinic Ltd that created and licences use of VitalPAC, S. Atkins: None Declared, P. Greengross Conflict with: Part-time Medical Director of The Learning Clinic Ltd that created and licences the use of VitalPAC, G. Westwood: None Declared, R. Aspinall: None Declared.
Abstract 2758: Population pharmacokinetics of cyclophosphamide in infants and young children
Authors: Michael Tagen, John C. Panetta, Amar Gajjar, Clinton F. Stewart
Journal: Cancer Research (2010)

Abstract Cyclophosphamide (CTX) is an anticancer pro-drug used for induction therapy of brain tumors and other malignancies. An adequate pharmacokinetic study of CTX and its active metabolite, 4-hydroxy-cyclophosphamide (4OH-CTX), has never been performed in infants and young children. We are therefore examining the disposition of CTX, 4OH-CTX, and its inactivated metabolite, carboxyethylphosphoramide mustard (CEPM), in children &amp;lt; 3 years of age with brain tumors. CTX was administered during the first course of treatment (1.5 g/m2 infused over 1 h), and serial samples were collected prior to infusion, at the end of infusion, and 3, 6, and 24 h after the end of infusion. CTX and CEPM were quantitated in plasma with a validated LC-MS/MS method and 4OH-CTX was stabilized by addition of phenylhydrazine to whole blood and quantitated with a validated LC-MS/MS method. A nonlinear mixed-effects model was fit to the data using NONMEM software and covariates were added to the model based on reduction in objective function value and improvement in diagnostic plots. Pharmacokinetic studies were performed with 28 patients. The median (range) age was 17.3 months (0.87 − 35.9 months) and median (range) BSA was 0.49 m2 (0.24 − 0.71 m2). A model with one compartment for CTX and each of its metabolites adequately described the data. BSA normalization of the dose reduced the inter-individual variability (IIV) in the volume of distribution of CTX (VCTX) from 32% to 13% and reduced the IIV in the elimination of 4OH-CTX through non-CEPM pathways (k4OH-CTX) from 60% to 38%. The covariate analysis showed that the BSA-normalized clearance of CTX to 4OH-CTX (CLCTX) increased slightly with age, whereas k4OH-CTX increased rapidly with age. The net effect was that exposure to 4OH-CTX decreased with age in a nonlinear fashion. These results demonstrate the importance of studying the pharmacokinetics of anticancer drugs in infants and young children, and will provide the basis for the rational design of CTX dosing strategies for infants and young children with brain tumors. 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 2758.
Abstract 3095: JMJDX interacts with DEAH (Asp-Glu-Ala-His) box polypeptide 9 (DHX9)
Authors: Motoko Unoki, Yusuke Nakamura, Ryuji Hamamoto
Journal: Cancer Research (2010)

Abstract We identified JMJDX as a candidate oncogene. Expression of JMJDX was up-regulated in various cancers including bladder cancer. Knockdown of JMJDX suppressed cell growth, suggesting that the protein may be involved in cancer cell growth. The protein possesses a JmjC domain. The domain is often found in lysine demethylases. To identify substrates of JMJDX, we performed immunoprecipitation and subsequent mass spectrometric analysis. In the result, we found that JMJDX physically associated with DHX9, which is also known as RNA helicase A. DHX9 is a DNA helicase and also works as an RNA helicase. DHX9 has a nuclear transport domain (NTD), which is known to necessary and sufficient for its bi-directional nuclear trafficking. It was reported that arginine methylation at the NTD domain is required for the NTD-mediated nuclear import. Thus, JMJDX may demethylate the methylated arginines at the domain and control its transportation between nucleus and cytoplasm. If our hypothesis is true, JMJDX will be the first arginine demethylase, because JMJD6, which was reported as the first arginine demethylase, was recently turned out that it is actually a lysine hydroxylase. DHX9 is thought to have oncogenic functions in cancer cells. In addition, expression levels of JMJDX are very low in normal tissues. Therefore, we think that JMJDX can be an anti-drug target with less adverse reactions. 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 3095.
FRI0434 Anterior chest wall pain in recent inflammatory back pain. data from the desir cohort.
Authors: D. Wendling, C. Prati, C. Demattei, D. Loeuille, P. Richette, M. Dougados
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Anterior chest wall pain (ACW) may be suggestive of spondyloarthritis (SpA), but little is known about this clinical feature in recent inflammatory back pain (IBP). <h3>Objectives</h3> To determine the prevalence of ACW in patients with recent IBP suggestive of SpA, and to investigate the influence of ACW on the overall features of patients presenting with recent IBP. <h3>Methods</h3> The DESIR cohort is a prospective, multicenter French cohort of patients with early IBP (Calin or Berlin criteria) (&gt;3 months and &lt;3 years of duration) suggestive of SpA according to the investigator, including 708 patients (mean age 33.8 years, 53.8% female, 57.3% HLA B27 positive). ACW was defined by at least one episode of chest wall pain attributed to SpA by the rheumatologist, after ruling out other causes of chest pain. Data on the baseline demographic characteristics, functional status and quality of life, imaging features (standard X-Rays, MRI, Ultrasounds), BMD, and blood tests were compared in patients with and without ACW. Both the date of the first symptom of IBP and the symptoms of ACW were recorded, as well as the date of the visit. Factors associated with ACW were identified both by uni and multivariate analysis (logistic regression). <h3>Results</h3> The prevalence of ACW in the DESIR cohort was 44.6 % [95%CI 40.9-48.3] (n=316/708 patients). ACW occurred after the first symptoms of IBP in 62 %, before in 14 %, and simultaneously (±1month) in 24 % of the cases. Localization was diffuse in 41% of the positive cases, sterno costal (35%), manubrio sternal (29%) or sterno clavicular (26%). Presence of ACW was significantly associated in univariate analysis with pain in cervical and thoracic spine, buttock, peripheral arthritis and enthesitis, fulfilment of ASAS and ESSG criteria, associated reactive arthritis and SAPHO, increased BASDAI, ASDAS, BASFI, BASG, SF-36, BASMI, articular index, increased CRP, radiographic sacro iliac involvement and reduced BMD. ACW was not associated with HLA-B27, uveitis, psoriasis, smoking, age and MRI findings. A stepwise multivariate analysis found an association between ACW and (Table): the enthesitis score, involvement of the thoracic spine, diagnosis of ankylosing spondylitis and radiographic abnormality of the sacro iliac joints. <h3>Conclusions</h3> In recent IBP suggestive of SpA, presence of ACW is associated with enthesitis, thoracic spine involvement, radiographic sacro iliitis and the diagnosis of ankylosing spondylitis, and with a more severe disease. Since there are no differences in symptoms duration between ACW positive and ACW negative patients, ACW could be interpreted as an independent diagnosis feature for ankylosing spondylitis. <h3>Disclosure of Interest</h3> None Declared
Abstract 4043: Characterization of the enzymatic activity, biochemical requirements and inhibition of deubiquitinating enzymes, a novel oncology target class
Authors: Jonathan D. Wrigley, Kay Eckersley, Helen Plant, Marian Preston, Lindsey Millard, Ian Hardern, Thorsten Nowak, Peter B. Simpson, David Andrews, Kevin Hudson
Journal: Cancer Research (2011)

Abstract Deubiquitinating enzymes (DUBs) represent promising opportunities for therapeutic intervention in oncology, and this study reports key information about the catalytic activity, assaying and inhibition of this novel enzyme class. The DUBs are proteases responsible for the cleavage of Ubiquitin from substrate molecules, and the resulting effects on the levels or activity of the substrates has been shown to play key roles in a range of cellular processes. Here we have utilized a range of in vitro and cellular assays of DUB activity to characterize various DUB enzymes, generate high throughput screens and profile DUB inhibition by hit molecules, to further our understanding in this area. The characterization of different DUBs has enabled us to highlight both differences and similarities in their behavior and requirements, particularly with respect to protein subunits, reducing conditions, and activity against different substrates. Profiling of small-molecule hits targeting these enzymes, under various in vitro conditions, and also in a cellular environment, has not only yielded information on the compounds, but has also demonstrated key considerations about the inhibition of these cysteine proteases. Together these findings further our knowledge of this novel target class, as well as providing valuable information to aid the hunt for therapeutic agents modulating these enzymes in a range of oncology settings. 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 4043. doi:10.1158/1538-7445.AM2011-4043
Drug instrumentalization and evolution: Going even further
Authors: Daniel H. Lende
Journal: Behavioral and Brain Sciences (2011)

Abstract Müller &amp; Schumann (M&amp;S) deserve applause for their interdisciplinary examination of drug use, evolution, and learning. Further steps can deepen their evolutionary analysis: a focus on adaptive benefits, a distinction between approach and consummatory behaviors, an examination of how drugs can create adaptive lag through changing human niche construction, the importance of other neurobehavioral mechanisms in drug use besides instrumentalization, and the importance of sociocultural dynamics and neural plasticity in both human evolution and drug use.
Mediastinal Teratoma With Metastatic Lymph Node
Authors: Keita Terui, Hiromasa Kohno, Shugo Komatsu, Kiyoshi Shibuya
Journal: Clinical Nuclear Medicine (2011)

F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) typically demonstrates prominent thymus uptake in normal children and young adults. A 12-year-old girl presenting with back pain and respiratory discomfort underwent an FDG PET/CT examination that demonstrated an anterior mediastinal mass with relatively low FDG uptake and an apparently separate FDG-positive nodular lesion superior to the larger mass. Surgical excision demonstrated a larger mature teratoma mass with a smaller thymic tissue nodule connected to the tumor with hourglass bridging.
Zika virus infection in pregnant women in Barcelona, Spain
Authors: C. Bocanegra, E. Sulleiro, A. Soriano-Arandes, D. Pou, A. Suy, E. Llurba, C. Rodó, M. Espasa, M. Campins, A. Martín, C. Rodrigo, A. Vázquez, F. De Ory, M.P. Sánchez-Seco, T. Pumarola, E. Carreras, I. Molina
Journal: Clinical Microbiology and Infection (2016)
Renovascular Hypertension due to Takayasu's Arteritis Demonstrated by Tc-99m Ethylenedicysteine Captopril Scintigraphy
Authors: ÖMER UĞUR, [horizontal bar over]IRFAN PEKSOY, B[horizontal bar over]IRAY CANER, SARUHAN ÇEKIRGE, FERHUN BALKANCI, COSKUN BEKDIK
Journal: Clinical Nuclear Medicine (1996)

A 34-year-old woman with severe hypertension underwent Tc-99m ethylenedicycteine (Tc-99m EC) captopril renal scintigraphy. There was bilateral parenchymal retention of the tracer suggesting renal artery stenosis. Angiography confirmed bilateral renal artery stenosis and also demonstrated contour irregularities of the abdominal aorta, and stenosis in mesenteric and subclavian arteries with increased collateral circulation consistent with Takayasu's arteritis. In light of this case of renal artery stenosis, it was concluded that Tc-99m EC can be used successfully as a potential renal agent in the diagnosis of renal involvement in patients with Takayasu's arteritis.
Bilateral 3.0-Tesla MRI of the hand and wrist in early and very early inflammatory arthritis: tenosynovitis is associated with progression to rheumatoid arthritis
Authors: Márcio Navalho, Catarina Resende, Ana Maria Rodrigues, Filipa Ramos, Tiago Castela, Rúben Teixeira, Augusto Gaspar, J Alberto Pereira da Silva, João Eurico Fonseca, Helena Canhão
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> To identify bilateral hand and wrist high field strength 3.0 Tesla MRI (3-T MRI) findings of synovial inflammation that are associated with progression to rheumatoid arthritis (RA) in a very early arthritis cohort and in an early arthritis cohort. <h3>Materials and methods</h3> Thirty-five patients (32 women, three men; mean age 45 years) with untreated recent-onset inflammatory arthritis participated in this prospective study and were examined using a new MRI approach including both wrists and hands. MRI scoring included the quantification of synovitis in multiple joints and tendons of the hands and wrist. All of these territories were considered for symmetry evaluation. Possible associations between synovitis for each joint and tendon and for each group of joints and tendons and RA diagnosis at 12 months were tested by univariate logistic regression analysis. <h3>Results</h3> Tenosynovitis of the flexor tendons of the second finger (OR, 14.61) and of the extensor carpi ulnaris (OR, 3.21) in the very early RA group (VERA, disease duration &lt;3 months) and tenosynovitis of the flexor tendons of the second finger (OR, 9.60) and synovitis of the radioulnar joint (OR, 8.79) in the early RA group (ERA, disease duration &lt;12 months) were the MRI findings most significantly associated with progression to RA (p&lt;0.05). Joint and tendon analysis by group revealed that tenosynovitis of the flexor tendons (OR, 4.28) was the most significantly associated with progression to RA in the VERA group (p&lt;0.05). Asymmetry was found in 80.0% and 69.3% of joint or tendon pairs of VERA and ERA patients, respectively. <h3>Conclusion</h3> Tenosynovitis is a major pathological finding in early RA. Furthermore high-field-strength MRI identifies early RA as an asymmetrical disease, confirming the importance of a bilateral acquisition protocol.
Activation of Programmed Cell Death by Recombinant Human Tumor Necrosis Factor Plus Topoisomerase II - Targeted Drugs in L929 Tumor Cells
Authors: Natasha Kyprianou, Richard B. Alexander, John T. Isaacs
Journal: JNCI Journal of the National Cancer Institute (1991)

The mechanism of death induced by recombinant human tumor necrosis factor (rHuTNF) in L929 tumor cells of C3H mice was investigated. Treatment with rHuTNF led to fragmentation of DNA into nucleosomal oligomers and to induction of the expression of TRPM-2, a programmed cell death-associated gene. Both events preceded cell death by several hours. Treatment with DNA topoisomerase II inhibitors accelerated both the rHuTNF-mediated DNA fragmentation and the elevation in TRPM-2 messenger RNA levels. These results suggest that rHuTNF exerts its cytotoxicity on L929 cells by activating programmed cell death, leading to apoptosis, and that topoisomerase II inhibitors enhance rHuTNF-mediated cytotoxicity by accelerating this process.
Measurement of adherence to sepsis guidelines in emergency general surgery admissions: A multicentre study
Authors: S. Hallam, L. Merker
Journal: International Journal of Surgery (2015)

s / International Journal of Surgery 23 (2015) S15eS134 S75 Other factors were unimportant to prospective patients. Conclusion: This data helps clarify what information surgeons should emphasize and what is irrelevant. 0849: MEASUREMENT OF ADHERENCE TO SEPSIS GUIDELINES IN EMERGENCY GENERAL SURGERY ADMISSIONS: A MULTICENTRE STUDY S. Hallam, L. Merker. Severn and Peninsula Deaneries, UK Aim: The aim of this audit was ascertain compliance with the sepsis six guidelines in acute general surgical admissions. Methods: This was a prospective, protocol driven, multi-centre trainee led audit. Data was extracted on all patients presenting as emergencies within seven day period (21/10/13 to 28/10/13). All patients meeting diagnostic criteria for sepsis, as defined by the surviving sepsis campaign, within the first 24 h following admission were further investigated using paper and electronic records to determine adherence to the surviving sepsis guidelines. Results: 97 hospitals in five countries participated in this audit, with 5078 patients admitted as general surgical emergencies during the study period. In total 895 (17.6%) patients (141 male, median age 67.7 years) met the diagnostic criteria for sepsis with 282 (5.6%) presenting with severe sepsis. Adherence with the Sepsis Six Bundle was poor with less than a third of patients treated in compliance with four of the six guidelines. Conclusion: This multi-centre audit has demonstrated that sepsis amongst emergency general surgical patients is common. Worryingly however the majority of patients admitted with sepsis are not receiving basic interventions proposed by the surviving sepsis campaign. 0871: DO WE OPTIMIZE OLDER SURGICAL PATIENTS APPROPRIATELY PRIOR TO ELECTIVE OPERATIONS? e THE NEED FOR GERIATRIC PREOPERATIVE ASSESSMENT AT UNIVERSITY COLLEGE HOSPITAL S. Dilke , E. Farrow, J. Oldman , G. Ramsden , J. Hardwick , C. Bond . University College Hospital NHS Foundation Trust, UK; University
Tc-99m MIBI SPECT in a Patient with Congenitally Corrected Transposition of the Great Arteries and Situs Solitus
Authors: Paulo S Duarte, Alfonso Y Matsumoto, Valdir A Moises, Antonio S Tebexreni, Luiz E Mastrocolla
Journal: Clinical Nuclear Medicine (2002)

DUARTE, PAULO S. M.D.; MATSUMOTO, ALFONSO Y. M.D.; MOISÉS, VALDIR A. M.D.; TEBEXRENI, ANTÔNIO S. M.D.; MASTROCOLLA, LUIZ E. M.D. Author Information
Abstract LB-33: Selective inhibition of Histone Deacetylase 6 enhances transformed cell sensitivity to anti-cancer agents
Authors: Mandana Namdar, Gisela Venta-Perez, Lang Ngo, Paul A Marks
Journal: Cancer Research (2010)

Abstract Histone deacetylase (HDAC) inhibitors have emerged as promising targeted anti-cancer agents when used both in monotherapies and in combination with other anti-cancer agents. Histone deacetylase 6 (HDAC6) is a structurally and functionally unique member of the histone deacetylase family. HDAC6 has two catalytic sites, a ubiquitin binding site, cytoplasmic localization and deacetylates a number of non-histone proteins such as tubulin, HSP90 and peroxiredoxins. This study aims to unravel HDAC6-mediated anti-cancer effects and explore the therapeutic potential of HDAC6-specific inhibition in combination with other anti-cancer therapies. We found that chemical inhibition with the HDAC6 specific inhibitor tubacin, reduces cell proliferation but does not effect cell viability in transformed cells. Tubacin significantly enhances cell death induced by anti-cancer agents such as the topoisomerase II inhibitors, etoposide and doxorubicin, as well as the pan-HDAC inhibitor SAHA in transformed cells (LNCaP, MCF-7), an effect not observed in normal cells (HFS). The inactive analog of tubacin, nil-tubacin, does not sensitize transformed cells to these anti-cancer agents. Furthermore, downregulation of HDAC6 expression by shRNA in LNCaP cells enhances cell death induced by SAHA, etoposide and doxorubicin. To explore the mechanisms of tubacin sensitization of transformed cells to anti-cancer agents, we have demonstrated that the combination treatments increases PARP cleavage and that the pan-caspase inhibitor Z-VAD-fmk, partially inhibits cell death induced by combination therapy. Thus, HDAC6 inhibition can significantly increase transformed cell sensitivity to anti-cancer agents and highlights the importance of HDAC6 as a target for cancer 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 LB-33.