tbuckley/cabot-search huggingface dataset:
THU0206 Clinical Usefulness of Serum Level of Adalimumab, in Patients with Rheumatoid Arthritis
Authors: J. Rosas, F. LLinares, I. de la Torre, L. Valor, X. Barber, C. Santos-Ramírez, D. Hernández, J. M. Senabre, L. Carreño, G. Santos-Soler, E. Salas, M. Sánchez-BArrioluengo, J. Molina-García
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To analyze the clinical relevance, in clinical practice, of adalimumab (ADA) serum levels (SL) and anti-ADA antibodies (anti-ADA-Abs). 2. To evaluate if there is correlation between SL of ADA and result of DAS28. 3. To determine the minimum appropriate SL of ADA to keep the patients in remission or in low clinical activity. <h3>Methods</h3> Serum levels of ADA and anti-ADA-Abs (ELISA kit. Promonitor®-ADA. Proteomika, Derio. Vizcaya. Spain) were analyzed in patients with rheumatoid arthritis (RA) receiving ADA &gt;6 months. Cut-off level for serum Abs anti-ADA was &gt;32 U/mL and for serum level of ADA &lt;0.004 mg/L. Clinical characteristics, clinical activity index (DAS in 28 joints), using ESR, were recorded. All the patients were receiving DMARD (methotrexate, leflunomide or hydroxychloroquine). Serum samples were collected before injection of ADA (same day), and stored frozen until analysis. Patients were considered on clinical remission if they had at the same time of extraction, DAS28≤2,6, and low clinical activity if DAS28 between 2,7-3,2. The patients was distributed in tertiles groups from serum levels of ADA: &lt;2,8 mg/L; 2,9-7,3 mg/L; &gt;7,3 mg/L. ROC curvewas used to select optimus cut-off level of ADA to keep the patients on remission or low activity level of disease. Finally, correlation between DAS28 and SL of ADA was evaluated. <h3>Results</h3> We included 63 determinations from 56 patients with RA. 75% were women; mean age: 62 years. The average time of evolution of RA was 156±122 months, and for the treatment of ADA 32,26±18,31months. ADA was the first anti-TNF received in 80% of patients. The distribution of DMARDs: methotrexate: 65% (mean dose: 15 mg), leflunomide: 21% (18 mg) and hydroxychloroquine: 14% (200 mg). In 4 (7%) patients anti-ADA Abs was detected; all in the group of SL of ADA &lt;2,8 mg/L. We obtained a negative relation between SL of ADA and DAS28 (r: -0.46. CI 95%: -0.66,-0.21). The cut-off of SL of ADA in ROC curves was, for DAS28≤2,6: 3,01 (AUC: 65,77%; sensitivity: 50% y specificity: 77,77%); for DAS28 2,7-3,2: 3,48 (AUC: 83,18%; sensitivity: 83,33% y specificity: 77,80%). Table show the relation of SL of ADA anti-ADA Abs and DAS28-ESR, according ADA tertiles. <h3>Conclusions</h3> The cut-off of ROC curve for serum level of ADA, to keep the patients in low activity of disease is 3,45 mg/L. 2. There is a negative correlation between the serum level of ADA and DAS28. 3. Serum level of ADA &gt;7,3 mg/L does not increase the improvement of DAS28. In these patients, we can consider to decrease the ADA dose or its delay. 4. The prevalence of anti-ADA Abs in patients with RA treated with ADA and DMARD is 7%. <h3>Disclosure of Interest</h3> None Declared
Troponin I and risk stratification of patients with acute nonmassive pulmonary embolism
Authors: D. Jimenez, G. Diaz, J. Molina, D. Marti, J. Del Rey, S. Garcia-Rull, C. Escobar, R. Vidal, A. Sueiro, R. D. Yusen
Journal: European Respiratory Journal (2007)

The assessment of risk and appropriate treatment of patients with acute pulmonary embolism (PE) remains a challenge. The prognostic performance of cardiac troponin I (cTnI) in predicting 30-day all-cause mortality was prospectively assessed in consecutive haemodynamically stable patients with PE. The present study included 318 haemodynamically stable patients with PE. During the 30-day study period, 23 (7%) patients died. cTnI was elevated (>or=0.1 ng x mL(-1)) in 102 (32%) patients. An age >65 yrs, systolic blood pressure <120 mmHg and severity of illness assessed using the PE severity index (PESI) were significantly associated with an increased risk for mortality, but no significant association was found between elevation of cTnI and 30-day mortality in a logistic regression analysis. When only fatal PE was considered, multivariate analysis showed that severity of illness using the PESI and an elevated cTnI (odds ratio 3.7, 95% confidence interval (CI) 1.1-12.8) were associated with a significant increase in the risk for death. The negative predictive value (95% CI) of a negative cTnI for mortality was 93 (90-97)%. In conclusion, in haemodynamically stable patients with acute pulmonary embolism, cardiac troponin I was not an independent predictor of 30-day all-cause mortality, although it did predict fatal pulmonary embolism.
Anti–Tumor Necrosis Factor-α Antibody Limits Heart Failure in a Transgenic Model
Authors: Toshiaki Kadokami, Carole Frye, Bonnie Lemster, Carrie L. Wagner, Arthur M. Feldman, Charles F. McTiernan
Journal: Circulation (2001)

Background — Tumor necrosis factor (TNF)-α has been implicated in the pathophysiology of congestive heart failure. A strain of transgenic mice (TNF1.6) with cardiac-specific overexpression of TNF-α develop congestive heart failure. Methods and Results — To determine the effect of anti-TNF-α therapy in this model, we studied 3 groups: TNF1.6 mice treated with saline, wild-type mice treated with saline, and TNF1.6 mice treated with TNF-α neutralizing antibody (cV1q) from 6 to 12 weeks of age. We used echocardiography to compare cardiac hypertrophy, function, and catecholamine response at 12 weeks of age versus baseline (6 weeks). cV1q treatment did not limit cardiac hypertrophy, but it significantly improved basal fractional shortening and responsiveness to β-adrenergic stimulation, and it limited development of cardiac dilation. Conclusions — Blockade of TNF-α bioactivity by antibody therapy may both preserve cardiac function and partially reverse pathological changes in congestive heart failure.
Expression of endothelin 3 by mesenchymal cells of embryonic mouse caecum
Authors: M A Leibl, T Ota, M N Woodward, S E Kenny, D A Lloyd, C R Vaillant, D H Edgar
Journal: Gut (1999)

Mutations in endothelin 3 (EDN3) and endothelin B receptor (EDNRB) genes cause terminal colonic aganglionosis in mice, and mutations in these genes have also been linked to the terminal aganglionosis seen in human Hirschsprung's disease. However, details of EDN3 expression during embryogenesis are lacking, and consequently the cellular mechanism by which EDN3 regulates innervation of the terminal gut is unclear.To localise the expression of EDN3 and EDNRB in the embryonic mouse gut.Expression of EDN3 and EDNRB mRNA was analysed by reverse transcription polymerase chain reaction and in situ hybridisation.High levels of EDN3 mRNA expression were restricted to mesenchymal cells of the caecum before and after the arrival of neural crest cells. In contrast, EDNRB expression along the gut displayed a time dependent pattern similar to those of the protein tyrosine kinase ret and the neural crest cell marker PGP9.5.Mesenchymal cells of the caecum express high levels of EDN3 mRNA during embryogenesis and hence the production of EDN3 at the caecum is likely to act on neural crest cells as a paracrine factor necessary for subsequent innervation of the terminal gut.
Are asymptomatic ultrasound abnormalities in the achilles tendon of elite soccer players risk factors for symptoms one year later? a longitudinal cohort study
Authors: S Jhingan, M Perry, G O'Driscoll, M Ahmad, N Maffulli, D Morrissey
Journal: British Journal of Sports Medicine (2011)

Background Achilles tendinopathy is common and can bring a sports career to a premature end. Identifying players at an increased risk of this debilitating condition could lead to better prevention. Objectives The primary aim was to compare asymptomatic elite soccer players with and without baseline ultrasound changes in terms of development of Achilles tendinopathy symptoms at one year follow-up. This study also investigated the effect that baseline tendon thickness had on development of symptoms. Method Using ultrasonography of the Achilles tendon, 18 initially asymptomatic elite soccer players in the top English league were examined in April 2009 and in May 2010. Symptom development during the 12 month follow-up period was assessed with an Achilles tendinopathy questionnaire on follow-up. Any Achilles pain during the follow-up period, of any duration or severity, was deemed to represent symptom development. Results No association between the existence of baseline asymptomatic ultrasound signs and development of Achilles tendinopathy symptoms in the following year was observed (χ 2 , 1.180 p=0.277). Baseline calcaneal insertion thickness was greater in tendons that experienced symptoms (p=0.035) in the following year compared to those that remained asymptomatic. Conclusion Baseline calcaneal insertion thickness was identified as a risk factor in the development of Achilles tendinopathy in elite soccer players. However, follow-up studies should aim to establish whether abnormal ultrasound signs and thickness measures over a longer period of time are significant markers of a presymptomatic stage.
A Comprehensive Lifestyle Peer Group–Based Intervention on Cardiovascular Risk Factors
Authors: Emilia Gómez-Pardo, Juan Miguel Fernández-Alvira, Marta Vilanova, Domingo Haro, Ramona Martínez, Isabel Carvajal, Vanesa Carral, Carla Rodríguez, Mercedes de Miguel, Patricia Bodega, Gloria Santos-Beneit, Jose Luis Peñalvo, Iñaki Marina, Napoleón Pérez-Farinós, Marian Dal Re, Carmen Villar, Teresa Robledo, Rajesh Vedanthan, Sameer Bansilal, Valentin Fuster
Journal: Journal of the American College of Cardiology (2015)
Nurse-coordinated multidisciplinary, family-based cardiovascular disease prevention programme (EUROACTION) for patients with coronary heart disease and asymptomatic individuals at high risk of cardiovascular disease: a paired, cluster-randomised controlled trial
Authors: DA Wood, K Kotseva, S Connolly, C Jennings, A Mead, J Jones, A Holden, D De Bacquer, T Collier, G De Backer, O Faergeman
Journal: The Lancet (2008)
PWE-162 An Audit Of Testing For Coeliac Disease In Patients Diagnosed With The Irritable Bowel Syndrome At A Large Primary Care Centre
Authors: J Cooke, P Clamp, D Haigney, K Rostami, D Aldulaimi
Journal: Gut (2014)

<h3>Introduction</h3> NICE guidance recommends that patients presenting with symptoms suggestive of the irritable bowel syndrome (IBS) should be tested for coeliac disease (CD). This study reviewed the symptoms, demographics and investigation of pateints diagnosed with IBS at a large semi-rural general practice. <h3>Methods</h3> Patients diagnosed with the IBS were identified from a computer database of 11,250 patients at St Johns Surgery. 250 casenotes were randomly selected for analysis. Patient demographics, symptoms recorded and investigations performed were recorded. a history of depression was recorded. Census and postcode data was used as a surogate marker of poverty. <h3>Results</h3> 499 patients had a diagnosis of IBS (110 male and 389 females). The records of 48 male and 202 female patients were reviewed. 186 patients were diagnosed with IBS within 6 months of their initial consultation. 180 began treatment for IBS within 6 months of diagnosis. 65 patients were tested for CD (13 males and 52 females). 34 (52%) of those tested for CD went on to have further investigations such as a barium enema or colonoscopy.185 patients were not tested for CD. 137 had no further investigations. Symptoms of those tested for CD were a change in bowel habit (90.8%), abdominal pain (90.8%), chronic diarrhoea (73.8%) and bloating (67.7%). Symptoms of those not tested for CD were the most common symptoms where abdominal pain (91.9%), change in bowel habit (73.5%) and bloating (69.2%) and chronic diarrhoea (52.4%). There was no significant difference in poverty or history of depression between those tested and not tested for CD. <h3>Conclusion</h3> This study suggests that patients diagnosed with the IBS in primary care are not routinely tested for CD. Explanations include a pragmatic approach to investigation of common gastrointestinal symptoms and a likely difference between patients diagnosed with the IBS in primary care and those referred onto secondary care and academic centres. <h3>References</h3> National Institute for Health and Clinical Excellence. 2009. <i>Recognition and Assessment of Coeliac Disease</i> National Institute for Health and Clinical Excellence. 2008. Irritable bowel syndrome in adults <h3>Disclosure of Interest</h3> None Declared.
Transplantation of a multipotent cell population from human adipose tissue induces dystrophin expression in the immunocompetent mdx mouse
Authors: Anne-Marie Rodriguez, Didier Pisani, Claude A. Dechesne, Claude Turc-Carel, Jean-Yves Kurzenne, Brigitte Wdziekonski, Albert Villageois, Claude Bagnis, Jean-Philippe Breittmayer, Hervé Groux, Gérard Ailhaud, Christian Dani
Journal: The Journal of Experimental Medicine (2005)

Here, we report the isolation of a human multipotent adipose-derived stem (hMADS) cell population from adipose tissue of young donors. hMADS cells display normal karyotype; have active telomerase; proliferate &amp;gt;200 population doublings; and differentiate into adipocytes, osteoblasts, and myoblasts. Flow cytometry analysis indicates that hMADS cells are CD44+, CD49b+, CD105+, CD90+, CD13+, Stro-1−, CD34−, CD15−, CD117−, Flk-1−, gly-A−, CD133−, HLA-DR−, and HLA-Ilow. Transplantation of hMADS cells into the mdx mouse, an animal model of Duchenne muscular dystrophy, results in substantial expression of human dystrophin in the injected tibialis anterior and the adjacent gastrocnemius muscle. Long-term engraftment of hMADS cells takes place in nonimmunocompromised animals. Based on the small amounts of an easily available tissue source, their strong capacity for expansion ex vivo, their multipotent differentiation, and their immune-privileged behavior, our results suggest that hMADS cells will be an important tool for muscle cell–mediated therapy.
Sex and NO — beyond regulation of vasomotor tone
Authors: M Barton
Journal: Cardiovascular Research (2000)

See article by Fraser et al. [43] ( pages 111 -118) indemonstrated that 'neuronal NOS'(NOS1) [18], 'macrothis issue.phage NOS' (NOS2) [19], and 'endothelial cell NOS' (NOS3) [20] or splice variants of the respective enzymes The mechanisms contributing to sex differences in are expressed in a variety of tissues [26][27][28][29], including susceptibility to and mortality from cardiovascular and macrophages [19], kidney, [27,30] skeletal muscle [28], renal disease are still unknown.Sexual dimorphisms of and myocardium [31,32].The terminology formerly used coronary artery disease were first suggested by Heberden to indicate calcium-dependency has also been abandoned in 1802 [1], and researchers have described vascular as NOS3 also exhibits calcium-independent activity under actions of estrogens since the late 19th century [2][3][4].certain conditions [33][34][35].In addition, induction of Subsequently, several studies provided indirect and direct 'constitutive' isoforms has been observed (i.e.induction of evidence for an involvement of estrogens in the regulation NOS3 by estrogen) [20,36], and the 'inducible' isoform of vascular tone [5][6][7][8][9].Most of the mechanisms were only NOS2 is constitutively expressed in certain organs (i.e. the ?discovered in the past two decades (reviewed in Refs.kidney) [27,30].Interestingly, inhibition of NO synthases [10,11]), following the observation by Furchgott and may exert detrimental as well as beneficial effects on tissue Zawadzki that vascular smooth muscle tone is regulated by and organ injury [25,37], which may be related to differenan endothelium-derived relaxing factor [12], later iden-tial generation of NOS-derived free radicals [21][22][23][24].
Ultrasonographic scoring system score versus liver stiffness measurement in prediction of cirrhosis
Authors: Kyoung Min Moon, Gaeun Kim, Soon Koo Baik, Eunhee Choi, Moon Young Kim, Hyoun A Kim, Mee Yon Cho, Seung Yong Shin, Jung Min Kim, Hong Jun Park, Sang Ok Kwon, Young Woo Eom
Journal: Clinical and Molecular Hepatology (2013)

Background/Aims We compared the cirrhosis-prediction accuracy of an ultrasonographic scoring system (USSS) combining six representative sonographic indices with that of liver stiffness measurement (LSM) by transient elastography, and prospectively investigated the correlation between the USSS score and LSM in predicting cirrhosis. Methods Two hundred and thirty patients with chronic liver diseases (187 men, 43 women; age, 50.4±9.5 y, mean±SD) were enrolled in this prospective study. The USSS produces a combined score for nodularity of the liver surface and edge, parenchyma echogenicity, presence of right-lobe atrophy, spleen size, splenic vein diameter, and abnormality of the hepatic vein waveform. The correlations of the USSS score and LSM with that of a pathological liver biopsy (METAVIR scoring system: F0-F4) were evaluated. Results The mean USSS score and LSM were 7.2 and 38.0 kPa, respectively, in patients with histologically overt cirrhosis (F4, P=0.017) and 4.3 and 22.1 kPa in patients with fibrotic change without overt cirrhosis (F0-F3) (P=0.025). The areas under the receiver operating characteristic (ROC) curves of the USSS score and LSM for F4 patients were 0.849 and 0.729, respectively. On the basis of ROC curves, criteria of USSS ≥6: LSM ≥17.4 had a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 89.2%:77.6%, 69.4%:61.4%, 86.5%:83.7%, 74.6%:51.9% and 0.83:0.73, respectively, in predicting F4. Conclusions The results indicate that this USSS has comparable efficacy to LSM in the diagnosis of cirrhosis. Keywords: Ultrasonography; Elastography; Cirrhosis; Biopsy
The Antitumor and Immunoadjuvant Effects of IFN-α in Combination with Recombinant Poxvirus Vaccines
Authors: Kenneth W. Hance, Connie J. Rogers, David A. Zaharoff, Daniel Canter, Jeffrey Schlom, John W. Greiner
Journal: Clinical Cancer Research (2009)

Abstract Purpose: IFN-α is a pleiotropic cytokine possessing immunomodulatory properties that may improve the efficacy of therapeutic cancer vaccines. The aim of this study was to evaluate the effectiveness and compatibility of combining recombinant IFN-α with poxvirus vaccines targeting the human carcinoembryonic antigen (CEA) in murine models of colorectal and pancreatic adenocarcinomas, where CEA is a self-antigen. Experimental Design: The phenotypic and functional effects of IFN-α were evaluated in the draining inguinal lymph nodes of tumor-free mice. We studied the effect of the site of IFN-α administration (local versus distal) on antigen-specific immune responses to poxvirus vaccination. Mechanistic studies were conducted to assess the efficacy of IFN-α and CEA-directed poxvirus vaccines in tumor-bearing CEA transgenic mice. Results: We identified a dose and schedule of IFN-α that induced a locoregional expansion of the draining inguinal lymph nodes and improved cellular cytotoxicity (natural killer and CD8+) and antigen presentation. Suppression of the vaccinia virus was avoided by administering IFN-α distal to the site of vaccination. The combination of IFN-α and vaccine inhibited tumor growth, improved survival, and elicited CEA-specific CTL responses in mice with CEA+ adenocarcinomas. In mice with pancreatic tumors, IFN-α slowed tumor growth, induced CTL activity, and increased CD8+ tumor-infiltrating lymphocytes. Conclusions: These data suggest that IFN-α can be used as a biological response modifier with antigen-directed poxvirus vaccines to yield significant therapeutic antitumor immune responses. This study provides the rationale and mechanistic insights to support a clinical trial of this immunotherapeutic strategy in patients with CEA-expressing carcinomas.
Effect of d-sotalol on mortality in patients with left ventricular dysfunction after recent and remote myocardial infarction
Authors: Albert L Waldo, A John Camm, Hans deRuyter, Peter L Friedman, Daniel J MacNeil, John F Pauls, Bertram Pitt, Craig M Pratt, Peter J Schwartz, Enrico P Veltri
Journal: The Lancet (1996)
Tough antigens trigger immunity
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2006)

The harder a protein is to chop up, say Delamarre and colleagues on page 2049, the more vigorous an immune response it will trigger. This suggests that the most durable antigens—or those attached to degradation-resistant carrier proteins—might make the best vaccines.






Figure 1

Protease-resistant proteins (HRP) induce more robust T cell proliferation than their degradation-sensitive counterparts (apo-HRP).




The correlation between stability and immunogenicity may seem counterintuitive, given that the very products of lysosomal degradation—antigenic peptides or epitopes—bind to class II MHC molecules for presentation to CD4+ T cells. And many (but not all) in vitro studies show that blocking lysosomal function in vitro inhibits antigen presentation.

To determine which kind of antigen elicits the strongest immune response, Delamarre et al. stuck identical T or B cell epitopes into lysosomal degradation-resistant and degradation-sensitive versions of the same protein. Mice immunized with the more durable versions of the proteins generated more robust T cell and antibody responses than those immunized with the more degradable forms. Stabilizing the degradation-prone antigens using aldehyde fixation boosted their immunogenicity.

Antigen-presenting cells did not simply have a bigger appetite for the more stable form of the protein, as both forms were taken up equally well by dendritic cells (DCs). Rather, the more stable antigens were better retained in DCs as they transited from peripheral sites of antigen capture to lymph nodes, where they present their antigenic cargo to T cells.

This group previously showed that DCs express a paucity of proteases compared with macrophages, allowing them to degrade internalized proteins more slowly and thus retain them longer—perhaps explaining why DCs are so good at disseminating antigens and initiating immunity. Thus, both the nature of a protein and the cell type it ends up in help determine how immune provoking that protein will be.