tbuckley/cabot-search huggingface dataset:
OC-001 Anti-tnf Withdrawal In Ibd: Initial Results From A Pan-uk Study
Authors: NA Kennedy, B Warner, E Johnston, C Basquill, R Harris, CA Lamb, A Singh, AS Fadra, F Cameron, U Basavaraju, J Mason, K Lithgo, L Penez, C Stansfield, S Lal, F Cummings, A Hart, M Johnson, R Russell, D Wilson, I Gooding, J Thomson, D Gaya, J Lindsay, T Ahmad, J Mansfield, J Gordon, J Satsangi, P Irving, CW Lees
Journal: Gut (2014)

<h3>Introduction</h3> Infliximab and adalimumab have established roles in IBD therapy. NICE and SMC guidelines mandate reassessment of disease activity after 12 months. Therapy should ordinarily be discontinued where clinical remission and mucosal healing has been achieved. However, there are presently few data about outcomes of anti-TNF withdrawal. <h3>Methods</h3> We conducted a retrospective clinical audit of outcomes following withdrawal of anti-TNF therapy. Inclusion criteria were confirmed diagnosis of IBD; ≥12 m continuous anti-TNF therapy; primary withdrawal reason sustained clinical remission (no corticosteroids for 6 m); ≥12 m follow-up post-withdrawal. Relapse was defined as moderate (oral steroids, immunomodulators, recommencement of anti-TNF agent) or severe (hospitalisation, iv steroids, surgical resection). All UK centres were invited to participate. Demographic and phenotypic data plus clinical, laboratory and endoscopic parameters were recorded. <h3>Results</h3> 80 cases (62 infliximab; 18 adalimumab) with a median follow-up time of 26 m post drug withdrawal were included in this analysis (59% female; median age at drug withdrawal 32y). All were in clinical remission at withdrawal; 47/80 had normal laboratory parameters (Hb, WCC, plts, Albumin, CRP, FC) prior to withdrawal. 49/80 had endoscopic re-evaluation with mild disease noted on 9/50 and moderate on 1. 23/70 (33%; 2/23 severe) of patients with Crohn’s disease relapsed by 12 months and 49% relapse (3/35 severe) by 24 months (Fig 1, median time to relapse 10.4 m). Younger age at diagnosis (p = 0.017) and elevated WCC (p = 0.025), but not CRP or faecal calprotectin, were predictive of relapse. 4/10 (none severe) with UC/IBDU had relapsed by 12 and 24 months. Anti-TNF therapy was re-introduced in 30 patients following relapse and was successful in 93%. <h3>Conclusion</h3> Planned withdrawal of anti-TNF therapy for sustained clinical remission is associated with a moderate relapse of Crohn’s disease in up to half of patients by 2 years. Data collection of an expanded cohort is ongoing around the UK to improve power to dissect predictive factors at time of drug withdrawal. <h3>Disclosure of Interest</h3> None Declared.
Is the science of positive intentional change a science of objective moral values?
Authors: William Andrew Rottschaefer
Journal: Behavioral and Brain Sciences (2014)

Abstract I examine whether Wilson et al.'s argument for a science of positive intentional change constitutes an argument for a science of objective moral values. Drawing from their discussion, I present four reasons for thinking that it may be and some considerations on why it may not be. Concluding, I seek help from the authors.
OC-042 The burden of malnutrition in general practice
Authors: P McGurk, A Cawood, E Walters, R J Stratton, M Elia
Journal: Gut (2012)

<h3>Introduction</h3> Although most malnutrition exists in the community, there is a lack of information about its burden in General Practice (GP). The aim of this survey was to establish the prevalence of malnutrition in GP and its relationship to use of nutrition support, health outcomes and healthcare use (infections requiring antibiotics, frequency of wounds and GP visits). The dataset represents an extension of information obtained from a preliminary study.<sup>1</sup> <h3>Methods</h3> Of a total of 1130 consecutive individuals attending nine GPs in the Southampton area (November 2010–December 2011), 65% (<i>n</i> 738) agreed to participate (main reason for non-participation was fear of missing their appointment). After excluding 160 people who were accompanying friends/relatives or carers, 578 patients visiting the GP or nurse formed the survey population. Subjects had their height and weight measured and provided information about unintentional weight loss, infections requiring antibiotics, wounds, GP visits, dietetic input, and use of any form of oral nutritional support, during the preceding 6 months. The risk of malnutrition according to the “Malnutrition Universal Screening Tool” (“MUST”) was established. <h3>Results</h3> Patients had a mean age, weight and Body Mass Index (BMI) of 43.1 (SD±18.7) years, 73.6 (SD±17.0) kg, and 26.2 (SD±5.3) kg/m<sup>2</sup> respectively. The overall prevalence of malnutrition was 11.1% (95% CI 8.8% to 13.9%), comprising of 6.7% at medium risk and 4.4% at high risk. Compared to people at low risk of malnutrition, those “at risk” (medium + high risk) had significantly more infections requiring antibiotics (17.1% vs 28.1%, RR 1.643 (95% CI 1.063 to 2.539); p=0.025), a significantly higher frequency of wounds (2.1% vs 9.4%, RR 4.381 (95%CI 1.667 to 11.443); p=0.003) and more GP visits in the previous 6 months (59.3% vs 68.8%, RR 1.159 (95% CI 0.968 to 1.387); p=0.109). None of the subjects identified as “at risk” of malnutrition were receiving dietetic input or any form of oral nutritional support. <h3>Conclusion</h3> This survey has established that the prevalence of malnutrition among people visiting their GP in the Southampton area is 11.1% (95% CI 8.8% to 13.9%). The results indicate that those “at risk” of malnutrition have more infections, wounds, and tend to visit their GP more frequently. Furthermore, malnutrition is under-detected and under-treated in this setting. <h3>Competing interests</h3> None declared. <h3>Reference</h3> 1. <b>McGurk P</b>, Cawood A, Walters E, <i>et al.</i> Proceedings of the Nutrition Society. 2012. In press.
Diagnostic amino acids in actin genes: an idea whose time has gone
Authors: M. E. White, B. I. Crother
Journal: Molecular Biology and Evolution (1999)

In 1978, Vanderkerckhove and Weber wrote an important paper detailing differences between mammalian actins.They found that, although the protein was conserved overall, actins from mammalian muscle and cytoplasmic sources differed by a characteristic set of at least 25 amino acids.Impressive for its breadth of information in the early days of sequencing, this publication unfortunately started a trend that has yet to be overturned: typing actin genes based on ''diagnostic'' amino acids.While these amino acids may be useful for characterizing mammalian actins, their utility for classifying other actins is questionable.Vanderkerckhove and Weber (1978) used tryptic mapping to obtain partial (62%-98%) protein sequences for mammalian actins, and their analysis considered all available data.The ''diagnostic'' amino acids were the only positions that showed variation among the actins they analyzed.In later works, Vanderkerckhove andWeber (1979, 1984) obtained complete sequences of the mammalian forms, as well as amino-terminal sequences from a variety of other actins.Again, they used all available data to arrive at conclusions about actin evolution.As methods for obtaining protein (or more commonly, nucleotide) sequences have improved, the complete sequences of a wide array of actin genes have been obtained.In many cases, investigators have plugged the appropriate amino acid positions into a chart containing the mammalian diagnostic amino acids in order to determine the type: beta-or gammacytoplasmic, enteric or vascular smooth muscle, cardiac or skeletal striated muscle.Adherence to the concept of diagnostic amino acids in determining gene relationships suggests that other characters have no phylogenetic value.Using 25-27 amino acids from a sequence of 375 results in an effective weight of 0 for over 90% of the characters.This reprises compatibility methods (Le Quesne 1974;Estabrook and Anderson 1978;Meacham 1981) that have been resoundingly criticized (Farris and Kluge 1979;Farris 1983).Swofford et al. (1996, p. 500) noted that such methods are ''no longer in widespread use, probably because of their implicit adherence to an unrealistic model that asserts that once a character has been excluded from the largest clique, it no longer conveys any useful information whatsoever.''
EFICACIA A LARGO PLAZO DE LA DILATACION ASOCIADA A INYECCIÓN INTRALESIONAL DE ESTEROIDES EN LAS ESTENOSIS ESOFÁGICAS BENIGNAS REFRACTARIAS.
Authors: A Alcalde Vargas, S Sobrino Rodríguez, A Araujo Míguez, I Gutiérrez Domingo, T López, JM Bozada García, JL Márquez Galán
Journal: Endoscopy (2012)

Introduccion y objetivos: La dilatación endoscópica es una modalidad eficaz para el tratamiento de las estenosis esofágicas benignas, aunque un número significativo de pacientes experimentan recurrencia, precisando nuevas dilataciones. Nuestro objetivo es determinar la eficacia a largo plazo del tratamiento con inyección intra-lesional de esteroides (IIE) como alternativa. Material y método: Estudio retrospectivo de 18 pacientes con estenosis esofágicas benignas refractarias desde 2008 a 2012.Tratados inicialmente con dilataciones endoscópicas intermitentes, y tras su fracaso, con dilatación endoscópica asociada a la inyección intra-lesional de triamcinolona en los 4 cuadrantes en dosis alícuotas de 0,5cc en 3 o 4 sesiones consecutivas. Calculamos el índice de dilatación periódica (IDP), definido como número de dilataciones por mes, tanto antes como después de la IIE. Resultados: 13 varones (72.2%) y 5 mujeres (27.8%), con edad media de 56,7±12 (38–74). Etiología: anastomosis quirúrgica (n=11), caustica (n=3), radioterápica (n=3) y péptica (n=1).El tipo de dilatación mas usado fue la neumática (42,8%) El numero de dilataciones, antes de pasar al programa de tratamiento combinado (dilatación mas IIE), fue de 8,29±12,5 (2–44), durante 10,1±11,8 meses (1–40).La terapia endoscópica combinada se inició tras 11.9 meses (2–40) del inicio de las dilataciones. El numero medio de sesiones con tratamiento combinado fue de 3,7±1,4 (2–7) Al comparar las dos líneas de tratamiento, observamos que hay una reducción significativa del IDP con el tratamiento combinado (0,92 vs. 0,22; p=0,002), así como del diámetro esofágico máximo conseguido (7,8 vs. 13,2,con una p=0,001) Seguimiento global de 23,3±11 meses (5–36) Tiempo medio libre de terapéutica endoscópica tras el tratamiento combinado de 18±11,6 meses (5–35) No hubo ninguna complicación grave asociada. Conclusiones: Con la terapia combinada, reducimos claramente la necesidad de sesiones endoscópicas para dilatación de las estenosis refractarias, lo que supone una reducción del coste económico y de la carga de trabajo para las unidades de endoscopia, así como un gran beneficio para el paciente, por lo que podríamos plantearlo incluso como primera opción en estenosis refractarias.
Stat Bite: AIDS Deaths Among Male Cancer Patients Under Age 45
Authors: C. Kosary
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Stat Bite : AIDS Deaths Among Male Cancer Patients Under Age 45 Get access Carol Kosary Carol Kosary Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 2, 19 January 1994, Page 86, https://doi.org/10.1093/jnci/86.2.86 Published: 19 January 1994
Correlation Between 123I-FP-CIT Brain SPECT and Parkinsonism in Dementia With Lewy Bodies
Authors: Angelo Del Sole, Giulia Perini, Michela Lecchi, Claudio Mariani, Giovanni Lucignani, Francesca Clerici
Journal: Clinical Nuclear Medicine (2014)

Although parkinsonism is considered a core feature of dementia with Lewy bodies (DLB), it is occasionally mild or even absent. I-FP-CIT SPECT has been accepted as a diagnostic support tool in this context, given that low striatal uptake is associated with neuronal loss. The aim of this retrospective study was to look for correlations between I-FP-CIT uptake in the striatum and clinical extrapyramidal signs (EPSs) in patients with a diagnosis of probable DLB to clarify the extent to which the supporting role of I-FP-CIT is related to motor impairment.Semiquantitative I-FP-CIT uptake was analyzed and correlated with Unified Parkinson Disease Rating Scale Part III scores in a sample of 22 patients with a diagnosis of probable DLB and a wide range of EPSs.A significant negative linear correlation between I-FP-CIT uptake and Unified Parkinson Disease Rating Scale Part III score was found both in the caudate and the putamen (r = -0.69 and -0.72, respectively, P < 0.001). Striatal uptake in patients with no or questionable EPS was comparable to that recorded in normal age-matched subjects (99% [22%] in the putamen) but significantly reduced in those with mild and severe EPS (43% [35%] and 30% [17%], respectively, P < 0.0001, but P = nonsignificant between mild and severe EPS).SPECT may be redundant when there are no doubts about the parkinsonism (ie, when it is absent or unequivocally present), but it may be helpful in identifying presynaptic nigrostriatal degeneration in patients with mild EPSs.
68Ga DOTATATE Uptake in Vertebral Hemangioma
Authors: Claudia Brogsitter, Thomas Hofmockel, Jörg Kotzerke
Journal: Clinical Nuclear Medicine (2013)

Somatostatin receptor scintigraphy is an established modality for imaging well-differentiated neuroendocrine tumors. It is known that inflammatory diseases (eg, tuberculosis) may also accumulate somatostatin receptor analogs. Here, we present the case of a 69-year-old patient with a neuroendocrine tumor of the rectum showing uptake of Ga DOTATATE in 2 vertebrae that was caused by vertebral hemangiomas. This could be clearly demonstrated on the CT scan. Although studies outlining the normal distribution of Ga DOTATATE exist, uptake in vertebral hemangiomas has not been described yet. As the case shows, vertebral hemangiomas should be kept in mind as a benign differential diagnosis.
Abstract 1437: Laminin-1 confers Bleomycin-resistance through poly(ADP-ribose) polymerase activation in 3D culture
Authors: Gabriel Benton, Hai Xu
Journal: Cancer Research (2010)

Abstract The purpose of this study is to examine the role of extracellular matrix proteins in regulating Bleomycin resistance and to evaluate the potential role of poly(ADP-ribose) polymerase (PARP) in modulating drug resistance in MDA-MB-231 breast cancer cells. These phenomenons were investigated using a 3D culture model where the MDA-MB-231 cells were cultured on either collagen I or laminin-1. Cells were evaluated for viability as a dose-response to the chemotherapeutic agent, Bleomycin. Cell lysates were also evaluated for PARP expression as a consequence of the 3D culture environment. Cells were then treated with the PARP inhibitor, PJ-34, and evaluated for viability as a dose-response to Bleomycin in the 3D cultures. PARP activity was assessed using a pharmacodynamic ELISA. For the first time, this study presents evidence that the basement membrane protein, laminin-1, induces Bleomycin resistance, that laminini-1 induces PARP expression and activity, and that PARP inhibition sensitizes breast cancer cells to Bleomycin treatment. In conclusion, this data provides a mechanism for ECM-mediated Bleomycin-resistance and the potential therapeutic application for PARP inhibitors to sensitize tumors to Bleomycin treatment. 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 1437.
1104 ANALYSIS OF VIRAL FACTORS, CLINICAL PARAMETERS AND IL28B ASSOCIATED WITH OUTCOME OF PATIENTS WITH ACUTE HEPATITIS C AND HIV COINFECTION
Authors: J. Dietz, T. Lutz, G. Knecht, P. Gute, A. Carlebach, G. Grammatikos, C. Füller, B. Raziorrouh, H. Diepolder, W.P. Hofmann, C. Stephan, H.R. Brodt, S. Zeuzem, C. Sarrazin
Journal: Journal of Hepatology (2012)
Clostridial Gas Gangrene and Septicemia in Four Patients with Leukemia
Authors: Dane R. Boggs, Emil Frei, Louis B. Thomas
Journal: New England Journal of Medicine (1958)

FOUR cases of leukemia in which gas gangrene of the bowel and clostridial septicemia developed are reported. Ante-mortem blood cultures were positive in all, but 3 patients died before the diagnosis was established or therapy instituted. The fourth patient survived for four weeks after the positive blood culture, and in this case the clinical diagnosis of septicemia, possibly due to clostridium, was made and antibiotic therapy instituted. Similar cases in malignant neoplastic disease have recently been described.1 Case ReportsCase 1. A.S. (N.I.H. 01 02 84), a 36-year-old man with Schilling-type monocytic leukemia, was admitted to the Clinical Center on . . .
Abstract 3319: <i>Salmonella typhimurium</i> A1-R inhibits aggressive pancreatic tumor growth and prolongs survival.
Authors: Ali Maawy, Yong Zhang, Michael Bouvet, Robert M. Hoffman, Ming Zhao
Journal: Cancer Research (2013)

Abstract Salmonella typhimurium (A1-R) has been previously shown to target multiple tumor types. A1-R has been shown to prevent metastasis of the XPA-1 human pancreatic cancer cell line in nude mice. The aim of this study is the anti-tumor efficacy of A1-R against a more aggressive pancreatic cell line. Human MiaPaCa2 pancreatic cancer cells, expressing RFP, were cultured in vitro and subsequently infected with A1-R. Efficacy of infection was noted by intracellular bacteria with subsequent cell lysis and apoptosis. MiaPaCa2-RFP was implanted subcutaneously in nude mice. After tumor engraftment, the mice were subjected to intravenous therapy with A1-R (5×107 CFU) once a week for 3 weeks. The tumors were harvested and weighed after the treatment period. MiaPaCA2-RFP were subsequently surgically implanted orthotopically. Treatment was initiated 2 weeks later. Mice were treated with intravenous A1-R (5×107 CFU) once a week for 6 weeks, after which survival and tumor growth were recorded. In the subcutaneous tumor model, significant decreases in the rate of tumor growth (p = 0.049) and tumor size (p =0.004) were observed upon termination. In the orthotopic model, a significant decrease in the rate of tumor growth (p = 0.01) and increased survival was observed (p = 0.014). The mean survival of the treatment group and the control group was 49 days and 35 days, respectively. None of the mice showed any adverse events or weight loss from bacterial therapy. Further investigation will be expanded to other pancreatic cancer cell lines and human patient tumorgrafts in combination with chemotherapy with the goal of cure of pancreatic cancer. Citation Format: Ali Maawy, Yong Zhang, Michael Bouvet, Robert M. Hoffman, Ming Zhao. Salmonella typhimurium A1-R inhibits aggressive pancreatic tumor growth and prolongs survival. [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 3319. doi:10.1158/1538-7445.AM2013-3319
Chemoradiation: an Integrated Approach to Cancer Treatment
Authors: L. R. COIA
Journal: JNCI Journal of the National Cancer Institute (1994)

Chemoradiation: an Integrated Approach to Cancer Treatment Get access Chemoradiation: an Integrated Approach to Cancer Treatment Madhu J. John , Marshall S. Flam , Sewa S. Legha , Theodore L. Phillips eds. Philadelphia: Lea & Febiger 1993 688 pp., illus. $110. ISBN 0-8121-1482-5 LAWRENCE R. COIA LAWRENCE R. COIA M.D. Department of Radiation Oncology Fox Chase Cancer Center7701 Burholme Ave. Philadelphia, PA 19111 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 6, 16 March 1994, Pages 461–462, https://doi.org/10.1093/jnci/86.6.461 Published: 16 March 1994
Case 4-2007
Authors: Josep Dalmau, R. Gilberto Gonzalez, Melinda F. Lerwill
Journal: New England Journal of Medicine (2007)

A 56-year-old woman had dizziness and nausea, followed by slurred speech and ataxia; 2 months later she was unable to walk. Neurologic examination disclosed severe ataxia. Imaging studies of the brain did not show discrete parenchymal lesions or vascular occlusion; there was cerebellar atrophy. A diagnostic procedure was performed.
OP0092 Differential systemic and synovial TH1 cell reactivity towards escherichia coli antigens in patients with ankylosing spondylitis and rheumatoid arthritis
Authors: U. Syrbe, R. Scheer, P. Wu, J. Sieper
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Ankylosing spondylitis (AS) is associated with clinical and subclinical mucosal inflammation suggesting that commensal bacteria contribute to the pathogenesis of the disease [1,2]. <h3>Objectives</h3> We determined the frequency of Th1 cells reacting towards conserved Escherichia coli (E. coli) proteins and pathogenicity factors in peripheral blood mononuclear cells (PBMNC) and synovial fluid mononuclear cells (SFMNC) of patients with AS and patients with rheumatoid arthritis (RA). As control, PBMNC of healthy individuals (HI) were included in the study. <h3>Methods</h3> All AS patients fulfilled the modified New York criteria. Peripheral blood or synovial fluid mononuclear cells were isolated by Ficoll density gradient centrifugation. For stimulation conserved proteins of E. coli were expressed and purified as described previously in detail [3]. PBMNC or SFMNC were stimulated with anti-CD28 in the presence or absence of the E. coli protein pool (10 proteins at 5 μg/ml) or pathogenicity factors espB and cesT. For polyclonal stimulation staphylococcus enterotoxin B (SEB) was used. CMV pp65 protein was used as a gut-unrelated protein antigen. Stimulation was performed for 6 hours with Brefeldin A added for the last 4 hours. Antigen-reactive Th1 cells were determined according to CD40L upregulation and IFNγ co-expression. <h3>Results</h3> In PBMNC and in particular in SFMNC of AS patients we detected higher frequencies of Th1 cells reacting to conserved E. coli proteins than in RA patients (PBMNC: p&lt;0.05, SFMNC p&lt;0.01). In contrast, the frequencies of CMV- and SEB-induced Th1 cells did not differ between AS and RA patients in SFMNC, and SEB-induced Th1 cell frequencies in PBMNCs were even higher in RA patients compared to AS patients (p&lt;0.05). <h3>Conclusions</h3> The high frequency of E. coli-specific CD4+ T cells in the blood and in particular their enrichment in the inflamed joints of AS patients but not of RA patients suggests that commensal bacteria are relevant antigens in AS that might trigger the disease. <h3>References</h3> [1]Mielants H, Veys EM, Cuvelier C, de Vos M. Ileocolonoscopic findings in seronegative spondylarthropathies. Br J Rheumatol. 1988; 27 Suppl 2:95-105. [2]Mielants H, Veys EM, Cuvelier C, De Vos M, Goemaere S, De Clercq L, et al. The evolution of spondyloarthropathies in relation to gut histology. II. Histological aspects. J Rheumatol. 1995 Dec; 22(12):2273-2278. [3]Ergin A, Bussow K, Sieper J, Thiel A, Duchmann R, Adam T. Homologous high-throughput expression and purification of highly conserved E coli proteins. Microb Cell Fact. 2007; 6:18. <h3>Disclosure of Interest</h3> None Declared
TGFβ-induced SMAD2 phosphorylation predicts inhibition of thymidine incorporation in CD34+ cells from healthy donors, but not from patients with AML after MDS
Authors: S Koschmieder, W-K Hofmann, J Kunert, S Wagner, K Ballas, G Seipelt, D Hoelzer, OG Ottmann, U Kalina
Journal: Leukemia (2001)