tbuckley/cabot-search huggingface dataset:
AB0699 Contribution of Extra-Articular Manifestations to the Burden of Disease in Ankylosing Spondylitis. A Longitudinal Study
Authors: I. Essers, S. Ramiro, C. Stolwijk, M. Blaauw, R. Landewé, D. van der Heijde, F. van den Bosch, M. Dougados, A. van Tubergen
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Extra-articular manifestations (EAMs), such as acute anterior uveitis (AAU), inflammatory bowel disease (IBD), and psoriasis contribute to the burden of the disease in patients with ankylosing spondylitis (AS). <h3>Objectives</h3> To assess whether the presence of EAM is associated with more functional disability, quality of life (QoL), and radiographic damage in patients with AS over time. <h3>Methods</h3> Twelve-year follow-up data from all patients included in the Outcome in Ankylosing Spondylitis International Study (OASIS) were used. The presence of EAMs was extracted from medical charts by two independent extractors. Function was assessed by the Bath AS Functional Index (BASFI). QoL was assessed by the Short Form-36 (SF-36), ASQoL and the EuroQoL. Radiographic damage was assessed by the modified Stoke AS Spinal Score (mSASSS). Univariable and multivariable generalized estimating equations (GEE) analyses were performed to assess whether prevalent and incident EAMs, respectively, were associated with function, QoL, and radiographic damage over time. Patients with a prevalent EAM were excluded from the analysis involving incident EAMs. <h3>Results</h3> 216 Patients were included (154 (71%) men, mean age 43.6 years (SD 12.7), mean symptom duration 20.5 years (SD 11.7), and mean follow-up 8.3 years (SD 4.3). At baseline, 39 (18%) patients had AAU, 15 (7%) IBD, and 9 (4%) psoriasis (prevalent cases). During follow up, 19 patients developed AAU, 9 IBD, and 5 psoriasis (incident cases). Psoriasis was not taken into account in further analyses, because of a low prevalence and incidence in this cohort. Prevalent AAU was univariably associated with worse mSASSS (B=7.19, 95% Confidence Interval [95% CI] 0.19 to 14.19, p=0.04), and worse SF-36 mental component (B=3.45, 95% CI 0.23 to 6.77, p=0.04) over time, but in a multivariable model these associations disappeared (B=1.22, 95% CI -3.81 to 6.26, p=0.64; and B=2.94, 95% CI -0.63 to 6.61, p=0.11, respectively). Prevalent IBD was not associated with clinical outcomes over time. Incident AAU also was not associated with the clinical outcomes over time. Incident IBD showed a trend towards worse function (BASFI) over time in a univariable model (B=1.84, 95% CI -0.10 to 3.78, p=0.06), and also in a multivariable model (B=1.40, 95% CI 0.05 to 3.60, p=0.06). <h3>Conclusions</h3> The presence of AAU and IBD at baseline was not associated with a worse course of QoL or radiographic damage over time. However, patients with new-onset IBD tended to have more functional disability over time in comparison with patients who do not develop IBD. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1873
Repeated Bleeding Scintigraphy May Reveal That Stationary Foci of Activity Represent Sites of Active Hemorrhage
Authors: Borys R Krynyckyi, Lionel S Zuckier, Rozet Tatlidil, Wen-Te T Chen, Chun K Kim, Leonard M Freeman
Journal: Clinical Nuclear Medicine (2002)

The goal of bleeding scintigraphy is to localize the site of origin of a hemorrhage to within general regions of the large or small bowel. Activity is typically seen to extravasate from the blood pool into the lumen, and the collection of activity then moves on sequential images, as a result of the cathartic action of blood. Sometimes, bleeding studies show a stationary focus of activity without subsequent movement. It is generally assumed that these foci represent fixed structures, such as the urinary tract or prominent vasculature, rather than acute extravasation of labeled blood into the bowel. The authors report three cases in which repeated studies showed that fixed foci of activity were, in fact, related to gastrointestinal bleeding. In two instances, the fixed foci represented extravasated blood that, for unexplained reasons, did not move during the study. In an additional case, the fixed activity visualized was ultimately shown to be prominent varices, which were implicated in the bleeding. Recognition of these possibilities, and consideration of possible strategies to localize the bleeding site further, should facilitate optimal patient treatment.
CO2 insufflation during single-balloon enteroscopy: a multicenter randomized controlled trial
Authors: Philipp Lenz, Tobias Meister, Mauro Manno, Marco Pennazio, Rita Conigliaro, Sven Lebkücher, Hansjoerg Ullerich, Andre Schmedt, Martin Floer, Torsten Beyna, Frank Lenze, Dirk Domagk
Journal: Endoscopy (2013)

Carbon dioxide (CO2) insufflation has previously been shown to have advantages over air insufflation in terms of procedure-related pain and oral insertion depth during double-balloon enteroscopy. The aim of this prospective study was to evaluate the performance of CO2 vs. air insufflation during single-balloon enteroscopy.This study was a randomized European multicenter trial (ClinicalTrials.gov: NCT01524055). Patients and endoscopists were blinded to the type of insufflation gas used. Patient discomfort during and after the procedure was scored using a visual analog scale.A total of 107 patients were enrolled in the study (52 in the CO2 group and 55 in the air group). Patient characteristics were comparable in both groups. The mean (±SD) oral intubation depth was not significantly deeper in the CO2 group vs. the air group (254±80 vs. 238±55 cm; P=0.726). However, in patients with previous abdominal surgery, oral intubation depth was significantly higher in the CO2 group compared with the air group (258±84 vs. 192±42 cm; P<0.05). In patients undergoing SBE via the anal approach, CO2 showed no significant difference in intubation depth compared with air insufflation (86±67 vs. 110±68 cm; P=0.155). The diagnostic yield was comparable (CO2 67%; air 73%). Procedure times, dosage of sedation, and therapeutic interventions did not differ between the two groups. Patients in the CO2 group reported less pain than those in the air group.This study demonstrated an advantage of using CO2 insufflation during single-balloon enteroscopy in patients with a history of previous abdominal surgery. Overall, single-balloon enteroscopy was a well-tolerated procedure that may benefit from the use of CO2 insufflation to reduce post-procedural pain.
THE MYOCARDIAL CONTRACTION FRACTION IS SUPERIOR TO THE VOLTAGE TO MASS RATIO FOR IDENTIFYING TTR CARDIAC AMYLOID IN PATIENTS UNDERGOING TAVR
Authors: Adam Castano, David Narotsky, Susheel Kodali, Tamim Nazif, Isaac George, Torsten Vahl, Nadira Hamid, Rebecca Hahn, Rachelle Morgenstern, Sabahat Bokhari, Mathew Maurer
Journal: Journal of the American College of Cardiology (2016)
Abstract 2670: Decreased expression of miR-302 contributes radioresistance of breast cancer cells
Authors: Zhongxing Liang, Donna Guo, John R. Votaw, Ya Wang, Hyunsuk Shim
Journal: Cancer Research (2011)

Abstract Radiotherapy is a common treatment strategy for many solid tumors, including breast cancer. Unfortunately, solid tumors can be resistant or develop resistance to radiotherapy. Though many studies have been conducted to further elucidate the mechanisms of radioresistance, they remain largely obscure due to the complex genetic cellular response to radiation and involvement of a large number of genes. MicroRNA, a recently discovered class of small, functional, non-coding RNA, is one of such class of potential regulators. A single microRNA can target a large number of genes and regulate several signal pathways simultaneously. Thus, miRNAs may be involved in the complex radioresistance of tumor cells. In the present study, we characterized miR-302 family members (miR-302s) pre-clinically as novel biomarkers for radiotherapy resistance. Our results showed that miR-302s were downregulated in irradiated breast cancer cells. Furthermore, we found, with a bioinformatic analysis, that AKT and RAD52, two critical regulators of radioresistance, are the predicted targets of miR-302s. Additionally, the expression levels of miR-302a were inversely consistently with those of AKT and RAD52. More promisingly, our data have demonstrated that miR-302a mimics sensitized breast cancer MDA-MB-231 cells to radiation therapy and reduced the expression of AKT and RAD52. Collectively, loss of miR-302s may be involved in the radioresistance of breast cancer cells, mainly through the release of repression of AKT and RAD52. Thus, our findings suggest that decreased expression of miR-302s contributes to radiotherapy-resistance and restoration of miR-302 baseline expression sensitizes breast cancer cells to radiotherapy. These data suggest that miR-302s may be potential sensitizers to radiotherapy and represent a novel strategy for radiotherapy of breast cancer. 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 2670. doi:10.1158/1538-7445.AM2011-2670
S22 Lung clearance index, FEV1 and CT findings in cystic fibrosis: data from the UK CF Gene Therapy Consortium run-in study
Authors: H. S. Sheridan, N. J. Bell, K. A. Macleod, P. A. Reid, A. R. Horsley, G. Davies, C. Saunders, S. Cunningham, J. A. Innes, J. C. Davies, E. W. Alton
Journal: Thorax (2010)

<h3>Introduction</h3> Lung Clearance Index (LCI) is a measure of lung gas mixing derived from the Multiple Breath Washout (MBW) test. We present LCI, FEV<sub>1</sub> and CT data from the Run-In Study, a longitudinal study in preparation for a multi-dose trial of nebulised gene therapy for CF. <h3>Methods</h3> MBW, spirometry and low-dose HRCT chest were performed as part of the first Run-In Study visit. LCI was reported as the mean result from at least two technically acceptable sulphur hexafluoride MBW tests performed using a modified Innocor gas analyser. Spirometry was performed to ERS standards. CT scans were assessed by two independent radiologists for extent and severity of bronchiectasis, wall thickening, presence of small and large airway plugs, and gas trapping. <h3>Results</h3> 191 patients attended visit 1, mean (range) age 22.6 (10–59.1) years. Validated LCI, FEV<sub>1</sub> and CT results were available for 167, 191 and 150 patients, respectively. Mean (SD) FEV<sub>1</sub> was 72(19)% predicted. Mean (SD) LCI was 10.7 (2.7), with mean intravisit coefficient of variation of 4.9%. LCI correlated negatively with FEV<sub>1</sub> (r=−0.68, p&lt;0.001), but was abnormally elevated in 72% of participants with normal FEV<sub>1</sub> (see Abstract S22 Figure 1; triangles indicate FEV<sub>1</sub> &gt;80% and LCI &gt;7.5). 95% CI for LCI in normal subjects 5.9 to 7.5. Both FEV<sub>1</sub> and LCI correlated with all CT measures (p&lt;0.001), most strongly with extent of bronchiectasis. LCI correlated better than FEV<sub>1</sub> with extent of bronchiectasis, r=0.72 (p&lt;0.001) vs r=−0.61 (p&lt;0.001), respectively. <h3>Conclusions</h3> Results from this large cohort suggests that LCI is a more sensitive test of early CF lung disease, and correlates better with extent of bronchiectasis seen on CT, than FEV<sub>1</sub>. Validation of data from subsequent study visits is in progress and will be reported at a future date.
Engineering novel ThioFab/Mabs for site specific conjugation of cytotoxic drugs
Authors: Jagath Reddy Junutula, Helga Raab, Karen E. Ervin, Jennifer L. Speer, Debra Dugger, Charles Eigenbrot, Richard Vandlen, Mark X. Sliwkowski, Henry B. Lowman, Richard H. Scheller
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

1993 

Antibody therapy has been established for the targeted treatment across spectrum of several diseases, including cancer, immunological and angiogenic disorders. The identification of tumor associated antigens (TAAs) that specifically expressed in tumor cells but not in normal tissues, has given the ability to specifically target cancer cells via antibody based therapies. Although there are few examples (eg. trastuzumab) of naked antibodies showing therapeutic potency but many antibodies that raised against these TAAs often do not show efficacy in animal xenograft models. Therefore, the focus is turned on arming these antibodies, thereby specifically targeting cytotoxic and cytostatic agents to inhibit or kill the tumor cells in the treatment of cancer. One of the challenges in the use of Antibody Drug Conjugates (ADCs) is the preparation of homogenous mixture of ADC. The current protocols involve the usage of either lysines (antibody surface) or reduced cysteines, involved in disulfide bonds, often result in the heterogeneous population of antibody drug conjugate and inconsistent preparation. Towards this objective, we have developed a novel Phage derived biochemical assay (PHESELECTOR) to rapidly screen and identify the reactive Thiol groups on antibody surface by combining Phage display and protein engineering methods. Using this method, we successfully engineered reactive Cys residues on antibody surface (light or heavy chains), thereby conjugating cytotoxic drugs in a site-specific manner with defined number of drugs per antibody. These sites are transferable to any given antibody and we tested the activity of these ADCs using in vitro cell proliferation as well as in vivo tumor xenograft models. The results will be discussed and presented during the meeting.
Abstract 5428: Rewiring of glucose metabolism in cancer.
Authors: Jason W. Locasale
Journal: Cancer Research (2013)

Abstract This seminar topic focuses on the role glucose metabolism in cancer biology. A common theme within this biology is a rewiring of metabolism to support and drive these processes. I will discuss how changes in the metabolism of cancer cells alters the physic-chemical properties of the metabolic network. At the core of this effort lies the utilization of computational modeling and mass spectrometry. Using these tools, we have studied the effects of an alternative glycolytic pathway observed in proliferating cells that we recently identified. These efforts have enumerated several principles of glycolytic regulation in growing cells. We have also defined and characterized a metabolic pathway that is genetically selected for and drives the development of human cancer. This pathway involves the diversion of glycolytic flux into de novo serine metabolism through phosphoglycerate dehydrogenase (PHGDH). This direction has also led us to the study of how metabolism can regulate pluripotency and cell fate determination. Together, these findings define a systems biology approach through combining these mathematical tools with an integration of genetics, biochemistry, cell biology, and metabolomics. Citation Format: Jason W. Locasale. Rewiring of glucose metabolism in cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5428. doi:10.1158/1538-7445.AM2013-5428
ANÁLISIS RETROSPECTIVO DE LA EVOLUCIÓN A LARGO PLAZO DE LOS PACIENTES CON COLEDOCOLITIASIS TRATADOS CON DILATACIÓN PAPILAR CON BALON HIDRÓSTATICO DE GRAN DIÁMETRO
Authors: G Rascarachi, M García, L Vaquero, L Arias, E Del Pozo, A Miguel, R Diez, J Espinel
Journal: Endoscopy (2010)

Objetivo: Analizar características y la evolución a largo plazo de los pacientes que se someten a dilatación papilar con balón hidrostático de gran diámetro en el tratamiento de la coledocolitiasis
US health organizations call for Congress to end bans on research into gun violence
Authors: Michael McCarthy
Journal: BMJ (2016)

Nearly 150 US medical associations, public health organizations, and advocacy groups have called on Congress to end federal legislation that restricts funding of research into gun violence.

In a 6 April letter to leaders of the House and Senate Committees on Appropriation, organizations representing more than a million US health professionals, including the American Medical Association, the American Public Health Association, and the American Association …
FRI0403 Arhalofenate, a novel uricosuric agent, is an inhibitor of human URIC acid transporters
Authors: B.E. Lavan, C. McWherter, Y.-J. Choi
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> It is estimated that the hyperuricemia in 80- 90% of gout patients is due to under excretion of uric acid. Uricouric drugs decrease serum uric acid by causing a reciprocal increase in uric acid excretion into urine. This occurs by inhibition of apical organic anion transporters/exchangers, including URAT1, OAT4 and OAT10, which are responsible for reabsoprtion of uric acid from the proximal renal tubule. Arhalofenate is a novel uricosuric agent in development for the treatment of hyperuricemia in patients with gout. <i>In vitro</i> profiling of the biologically active form of arhalofenate (arhalofenate acid) established that it is an inhibitor of uric acid transport mediated by URAT1, OAT4 and OAT10. Arhalofenate acid was found to be 8-20 fold more potent than probenecid. In addition, arhalofenate acid did not inhibit xanthine oxidase, another mechanism by which drugs can lower serum uric acid. <h3>Objectives</h3> To evaluate the basis for the uricosuric action of arhalofenate acid by assessing its inhibition of human renal urate transporters in vitro and to compare its effects with the currently available uricosuric agents. <h3>Methods</h3> The inhibition of the human urate transporters URAT1, OAT4 and OAT10 was determined by measuring the uptake of <sup>14</sup>C-uric acid into human HEK293 cells transiently expressing the relevant transporter relative to the uptake into parental HEK293 cells. <h3>Results</h3> Arhalofenate acid inhibited urate transport by all three transporters tested with IC<sub>50</sub>values of 92 μM for URAT1, 2.6 μM for OAT4 and 53 μM for OAT10. Probenecid showed much weaker inhibition of these same transporters with IC<sub>50</sub> values of 750 μM, 29 μM and 1.0 mM being observed with URAT1, OAT4 and OAT10, respectively. In contrast, benzbromarone was found to be an inhibitor of both URAT1 and OAT4 with IC<sub>50</sub> values of 0.30 μM and 1.5 μM, respectively, but was somewhat less potent against OAT10 (IC<sub>50</sub> of &gt;3 μM). Arhalofenate was also found to be inactive toward xanthine oxidase. <h3>Conclusions</h3> Arhalofenate is a novel uricosuric agent that is converted <i>in vivo</i> to an inhibitor of multiple uric acid transporters which lacks xanthine oxidase activity. At doses studied in clinical trials the levels of arhalofenate acid found in human urine match or exceed the <i>in vitro</i> IC<sub>50</sub> value against these transporters. These results confirm the mode of action of arhalofenate as a uricosuric agent <h3>Disclosure of Interest</h3> None Declared
Case 19-2003
Authors: Lawrence C. Wolfe, Howard J. Weinstein, Judith A. Ferry
Journal: New England Journal of Medicine (2003)

Presentation of CaseA five-day-old girl was admitted to the hospital because of a worsening rash from birth and leukocytosis with blasts.The infant was delivered at 40 weeks' gestation by a 24-year-old woman (gravida 2, para 2), who had immigrated from Central America to the United States two months earlier. The pregnancy had been complicated by a urinary tract infection and by a vaginal discharge, which had been treated with topical medication.The mother had no history of oral or genital herpes, sexually transmitted diseases, or varicella during the pregnancy. Ultrasonographic examinations of the fetus, reportedly performed at four . . .
Proposals of population solutions are beset by lack of knowledge
Authors: H. Hemingway, G. Feder
Journal: BMJ (1995)

Low back painChiropractic manipulation is superior EDITOR,-J R Jenner and M Barry state that "the most effective method [of spinal manipulation] is unknown, but physiotherapists, chiropractors, and osteopaths, who use a variety of techniques, all seem effective."'This is not true.The benchmark study by Meade et al showed that spinal manipu- lation performed by a chiropractor was more effective for low back pain than manipulation performed by a physiotherapist.2More impor- tantly, the selection of the most suitable candidates for spinal manipulation is at least as important an indicator of the outcome as the technique that is applied.3Not all randomly selected patients with low back pain require spinal manipulation.The authors also state that "pathology in organs in the posterior part of the abdominal cavity may refer pain to the back-for example, aortic aneurysm or enlarged lymph nodes."In over 40 years of practising spinal manipulation one of us (PB) did not see any patient who presented with low back pain secondary to an aortic aneurysm or enlarged lymph nodes but did see many patients with prostatic disease, metastases to the spine, a retroflexed uterus, or kidney disease who presented with low back pain.
Abstract 2839: Effects of CDKN2A genetic polymorphisms on DNA methylation in head and neck cancer
Authors: Leslimar Rios, Arianexys Aquino-Lopez, Germán L. Velez, Bianca Rivera-Pena, Adriana Baez
Journal: Cancer Research (2010)

Abstract Gene polymorphism has been found to be associated with the susceptibility to cancer or its severity as exemplified in the CDKN2A gene. CDKN2A regulates G1 arrest and plays an important role in head and neck cancer (HNSCC) carcinogenesis. Deregulated tumor expression of CDKN2A has previously been described in association with HNSCC clinical progression. Aberrant methylation of CDKN2A is common gene silencing mechanism in HNSCC. CDKN2A is polymorphic, with variant alleles G/A442, C/T 540, and C/G 500 associated with cancer. Previously we have shown that in the Puerto Rican population the G/A 442, GG variant is associated with an increased head and neck cancer risk (OR, 4.09). In the present study, we examined the CDKN2A G/A442, C/T 540 and C/G 500 polymorphisms using PCR-RFLP and the pattern of methylation of the CDKN2A gene by methylation-specific PCR or Methylight assay in 152 HNSCC. The allelic frequencies were compared to a control group of 69 age - matched healthy blood donors. CpG island methylation for CDKN2A was found in 45% HNSCCs. The G/A 442, GG variant was more common in tumors of the larynx (63%). A significant correlation between CDKN2A G/A442 and head and neck cancer was indicated (r = 0.24, P = 0.02). We found no association between CDKN2A gene hypermethylation and CDKN2A C/T 540 and C/G 500 polymorphisms, However, we confirmed that individuals carrying the AG variant in G/A 442 gene had a higher frequency of hypermethylation in HNSCCs. Our results suggest that G/A 442 polymorphisms of CDKN2A gene may affect the methylation status. Functional and bioinformatic studies to clarify these results are underway. 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 2839.