tbuckley/cabot-search huggingface dataset:
THU0268 Efficacy and Safety of a Combined Treatment Protocol for 2nd Degree Congenital Heart Block
Authors: A. Hoxha, V. Ottosson, S. Brauner, M. Wahren-Herlenius, M. Favaro, A. Calligaro, M. Facchinetti, A. Ruffatti, L. Punzi
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Congenital atrioventricular block (CHB) is the most frequent manifestation of neonatal lupus and depends on anti-Ro/SSA and/or anti-La/SSB-mediated inflammation and subsequent fibrosis of the atrioventricular node. No therapy has yet been found to be effective in treatment of second and third degree CHB induced by maternal autoantibodies, and due to the rarity of the disease controlled clinical trials and not possible to perform. <h3>Objectives</h3> To evaluate the clinical efficacy and safety of a combined therapy protocol utilizing plasmapheresis, intravenous immunoglobulin (IVIG) and betamethasone, and the effect of this treatment on anti-Ro52, anti-p200 and anti-La antibody levels. <h3>Methods</h3> Six consecutive women pregnant with fetuses diagnosed CHB (3 with 2nd degree and 3 with third degree CHB) underwent a combination therapy protocol composed of weekly plasmapheresis, fortnightly 1 g/Kg IVIG and daily 4 mg Betamethasone throughout pregnancy. IVIG (1 g/Kg) treatment in the neonates was begun at birth and administered every fifteen days until maternal autoantibodies became undetectable by ELISA in the circulation of the neonates. The anti-Ro52, anti-p200 and anti-La antibody levels were investigated by ELISA in serial sera of 4 mothers obtained before and after each plasmapheresis. <h3>Results</h3> The foetuses affected with second degree block (case 1, 2 and 3) reverted to a normal atrio-ventricular conduction during pregnancy, while those with a third degree block remained stable (case 4), showed a higher ventricular rate (case 5), or an improvement in cardiac function (case 6). These results improved the chances for survival and delayed the need for a pacemaker. No severe cardiac complications such as impaired ventricular function, hydrops or cardiomyopathy were observed in the foetuses with third degree CHB. We found that plasmapheresis significantly decreases the anti-Ro52, anti-p200 and anti-La antibody levels in all cases, except anti-Ro52 antibodies in the two patients with the highest autoantibody titers. Indeed, analysis by linear regression demonstrated that patients with high autoantibody levels had lesser decrease in anti-Ro52 antibody levels. <h3>Conclusions</h3> Overall, lessons learned from these case series are: A) an efficacy in treating second degree CHB, and b) the safety of plasmapheresis and IVIG therapies. The low number of treated cases, the relatively short follow-up (mean 22.7 months ± 10.4, range 12-42 months) and the high cost of the procedure can all be considered limits. Weekly plasmapheresis reduces the levels of anti-Ro52, anti-p200 and anti-La antibodies in patients with medium-high autoantibody titers. However, there is a limited effect on autoantibody levels in patients with very high autoantibody titers. <h3>Disclosure of Interest</h3> None Declared
Pay-for-Performance System for English Physicians
Authors: Rolf Stahl, El-Zoghby Zm, Grande Jp, Fraile Mg, Norby Sm
Journal: New England Journal of Medicine (2010)

from any cause), occurred in significantly fewer of the patients who received rivaroxaban as compared with those who received enoxaparin (P<0.001). We agree that the risk of fatal pulmonary embolism must be balanced against the risk of bleeding, but the likelihood of fatal bleeding events must also be considered. In the RECORD 3 trial, there were no deaths attributable to bleeding, but there were deaths due to venous thromboembolism. Furthermore, there was a clinically significant reduction in venous thromboembolism including death without increased bleeding, a finding of great interest for clinicians and patients. The RECORD 3 trial, like other phase 3 trials of anticoagulants, was neither designed nor intended to provide long-term data on the outcomes of knee arthroplasty. However, the study did provide results on end points that can affect longterm outcomes. The rivaroxaban and enoxaparin groups had similar incidences of major bleeding, hemorrhagic wound complications, blood transfusions, and postoperative wound infections. Only long-term studies of patients undergoing total knee replacement can assess the risks and benefits of various anticoagulants in regard to the surgical outcomes. The RECORD 3 trial was never intended to
Abstract 4541: Metabolomic diagnosis of prostate cancer from urine
Authors: Jonathan McDunn, Hayley Whitaker, Zhen Li, Klaus-Peter Adam, Michael Milburn, Bruce Neri, David Neal
Journal: Cancer Research (2012)

Abstract There is a critical unmet need for new diagnostic tests to both determine if a patient has prostate cancer and whether that cancer is aggressive and therefore requires aggressive management. In this study we performed global metabolomic profiling on the post-DRE urine sediments of twenty-four men referred to the urologist with concern of prostate cancer. Eight of these men presented with benign prostatic conditions leading to a raised PSA while the remaining sixteen patients had clinical T3 prostate cancer. Global metabolomic profiling was carried out on methanolic extracts of these urine sediments. The resulting data sets were found to contain 256 metabolites based on spectral comparison against an in-house chemical reference library of over 2500 authentic standards. A subset of prostate cancer patients, but no patients with benign prostatic conditions, had elevated sarcosine abundance in their urine sediments. Patients with elevated sarcosine had a distinct metabolic signature that included sixty-five other differentially abundant metabolites, predominantly amino acids and their catabolites, differentiating these patients from the rest. The remaining prostate cancer patients could be differentiated from the patients with benign prostatic conditions based on their abundance profiles of acyl carnitines (increased) and uridine (reduced). Stable isotope dilution assays for select analytes confirmed these results, and several multianalyte algorithms were found to have good performance for the diagnosis of prostate cancer (AUROC &amp;gt; 0.8). Both metabolic presentations of prostate cancer exhibited biochemical hallmarks of multiple acyl-coA dehydrogenase deficiency, an inborn error of metabolism that can be due to impaired activity of the mitochondrial electron transfer flavoprotein/quinone oxidase complex. These data indicate that post-DRE urine sediment profiling could provide valuable information regarding the need to refer the urologic patient for prostate biopsy and may hold additional insight into the molecular pathogenesis of prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4541. doi:1538-7445.AM2012-4541
Abstract 2101: <i>PMEPA1</i> co-operates with the androgen responsive gene, <i>NEDD4-1,</i> to control the androgen receptor levels in human prostate cancer cells
Authors: Hua Li, Juliet Chijioke, Shashwat Sharad, Albert Dobi, Shiv Srivastava
Journal: Cancer Research (2011)

Abstract Androgen receptor (AR) is a male hormone receptor and a nuclear transcriptional factor that plays central role in the differentiation and growth of the prostate gland and alterations of the AR network contribute to prostate tumorigenesis. The stability of the AR protein has been known to be regulated by the MDM2 E3 ubiquitin ligase. Recent investigations from our group suggest the role of PMEPA1-NEDD4-1 negative feedback loop in the regulation of AR protein levels in prostate cancer cells. In the PMEPA1-NEDD4-1 feedback loop, AR transcriptionally activates PMEPA1, which in turn provides a docking platform to recruit NEDD4-1 E3 ubiquitin ligase, to facilitate the proteasome dependent degradation of the AR. We hypothesize that decreased or absent PMPEA1 expression observed in more than 65% for prostate tumors may lead to the gain of AR functions which contribute to prostate tumorigenesis. Here we further investigate how PMEPA1 recruits NEDD4-1 to alter AR protein levels and AR signaling in prostate cancer cells. Androgen receptor positive prostate cancer cells lines, LNCaP and VCaP, were treated with synthetic androgen R1881 for 24 hours. The androgen receptor, PMEPA1 and NEDD4-1 were knocked down with specific small interfering RNA (siRNA) molecules. Wild-type AR and mt AR (T877A) were ectopically expressed in LNCaP cells with adenoviral expression vectors. Protein levels of AR, PMEPA1, NEDD4-1, as well as AR responsive gene PSA were assessed by immunoblot assays. Our new observations revealed that that NEDD4-1 was androgen inducible in both LNCaP and VCaP cells. Over-expression of wild-type and mutant AR (T877A) resulted in the upregulation of NEDD4-1 in LNCaP cells. Consistent with these findings, inhibition of AR by siRNA lead to down-regulation of NEDD4-1. As expected, loss of PMEPA1 in LNCaP cells induced up-regulation of AR and NEDD4-1 in an androgen dose-dependent manner. Knockdown of NEDD4-1, rather than NEDD4-2, resulted in elevation of androgen receptor levels and decreases of PMEPA1 expression in LNCaP cells. Our data suggest that NEDD4-1 is an androgen inducible gene and a complex inter-relationship between PMEPA1, NEDD4-1 and AR. Intriguingly, the AR degradation function of NEDD4-1 depends on the availability of PMEPA1. Thus PMEPA1-NEDD4-1 co-operation is critical for the regulation of androgen receptor protein levels. In conclusion, loss of PMEPA1 in human prostate cancer may also lead to the activation of NEDD4-1 through elevated AR signaling, representing a feed-forward event in tumorigenesis. 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 2101. doi:10.1158/1538-7445.AM2011-2101
AB1222 Subclinical atherosclerosis and oxidized LDL levels in familial mediterranean fever
Authors: S. Ugurlu, S.N. Karaca, Y. Demirel, E. Seyahi
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> To investigate markers of carotid atherosclerosis and oxidized low density lipoprotein(oxLDL) levels in patients with Familial Mediterranean Fever (FMF) who have no risk factors for cardiovascular disease. <h3>Methods</h3> We studied 44 patients (25 F/19 M; mean age: 33.5±7.5)with FMF in attack free period and gender and age matched 44 healthy subjects (25 F/19 M; mean age: 33.4±7.0). Exclusion criteria were clinical coronary artery disease, chronic renal disease, diabetes mellitus, hypertension, history of myocardial infarction, angina pectoris or cerebrovascular disease, dyslipidemia, metabolic syndrome or active infection. Those who were in postmenopausal status and using anti-lipid drugs were also excluded. We measured carotid artery intima- media thickness (IMT) and investigated presence or absence of atherosclerotic plaques in the carotids, using Doppler ultrasound. We also assessed serum lipid and OxLDL levels. <h3>Results</h3> Mean disease duration of the FMF patients was 20±9 years. The mean carotid IMT (C-IMT) did not differ between patients and controls (0.52±0.10 mm vs 0.53±0.06 mm, respectively, P=0.709). None of the patients or controls had atherosclerotic plaques. Total and LDL cholesterol levels were significantly lower among patients compared to controls (total cholesterol: 157.07±34.18 vs 181.05±36.79, respectively, P=0.002; LDL cholesterol: 100.48±30.13 vs 126.25±34.05, respectively, P=0.001). Whereas OxLDL levels were significantly higher in FMF patients (337.48±438.56 ng/dl) when compared to controls (156.19±383.24 ng/dl), (P=0.044). There was no correlation between CIMT and OxLDL levels among both patients (r= -0.156, p=0.324) and controls (r=-0.196, p=0.246). <h3>Conclusions</h3> Our study supports further evidence for no increased atherosclerosis in FMF. As previously shown patients with FMF have low cholesterol levels when compared to healthy controls [1,2]. On the other hand, increased OxLDL levels could be associated with increased sub-clinic inflammation. <h3>References</h3> Ugurlu S, Seyahi E, Cetinkaya F, Ozbakir F, Balci H, Ozdogan H. Intima-media thickening in patients with familial Mediterranean fever. Rheumatology (Oxford). 2009;48:911-5. Akdogan A, Calguneri M, Yavuz B, et al. Are familial Mediterranean fever (FMF) patients at increased risk for atherosclerosis? Impaired endothelial function and increased intima media thickness are found in FMF. J Am Coll Cardiol 2006;48:2351-3. <h3>Disclosure of Interest</h3> None Declared
18F-FDG Uptake in Intraductal Tubulopapillary Neoplasm of the Pancreas
Authors: Yuko Someya, Yuji Nakamoto, Koya Nakatani, Michiya Kawaguchi, Sachiko Minamiguchi, Kaori Togashi
Journal: Clinical Nuclear Medicine (2013)

We report a 74-year-old man with intraductal tubulopapillary neoplasm (ITPN), a rare primary intraductal neoplasm of the pancreas. Focal intense uptake of 18F-FDG was seen on the initial PET, corresponding to a pancreatic mass. Although the patient had no treatment, the uptake was mild to moderate on a second PET performed about 1 month later. The tumor was resected, with the final diagnosis of ITPN with an associated invasive carcinoma. Clinicians should be aware that decreased uptake of FDG during the follow-up period without treatment can occur even in malignant tumors.
Abstract LB-261: Cancer stem cell characteristics exhibited by doxorubicin-selected drug-resistant breast cancer cells
Authors: Anna Maria Calcagno, Crystal D. Salcido, Jean-Pierre Gillet, Chung-Pu Wu, Jennifer M. Fostel, Melanie Mumau, Michael M. Gottesman, Lyuba Varticovski, Suresh V. Ambudkar
Journal: Cancer Research (2010)

Abstract Background: Cancer stem cells (CSCs) are presumed to possess the virtually unlimited ability to proliferate while preserving self-renewal. These cells are also highly resistant to chemotherapeutics, a feature which correlates with overexpression of ATP-binding cassette (ABC) transporters. No reports to our knowledge have shown that prolonged continuous selection of cells for drug resistance enriches cancer stem-like cells. Methods: We examined parental and drug-selected breast cancer cell lines to determine whether there is a relationship between drug resistance and the presence of cells with a CSC phenotype. MCF-7/ADR cells, generated from weakly tumorigenic parental MCF7 cells by continuous exposure to increasing concentrations of doxorubicin, were examined by microarray analysis, flow cytometry, invasion, in vivo tumorigenicity and other CSC characteristics. The putative CSC population was also examined for expression of multidrug resistance (MDR) genes using TaqMan Low Density Arrays. Results: Pathway analysis showed that MCF-7/ADR cells express ABCB1 as well as genes with patterns similar to breast CSCs. MCF-7/ADR cells grow in 3D cultures as mammospheres, are highly invasive and tumorigenic. In contrast to parental cells, over 30% of MCF-7/ADR cells are CD44+/CD24-. The CD44+/CD24- cells have the ability to self-renew and overexpress many MDR genes when compared to the CD44+/CD24+ population. No enrichment in CD44+/CD24- or CD133+ populations was detected in MCF-7/MDR or other cells with forced expression of the ABCB1 transporter or MDR genes. Conclusions: Cells with characteristics of CSCs increased in number following selection for doxorubicin resistance. Based on our findings, we speculate that prolonged drug treatment in vivo may result in expansion of a CSC-like population. 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-261.
The enhanced in vitro hematopoietic activity of leridistim, a chimeric dual G-CSF and IL-3 receptor agonist
Authors: AL Abegg, LE Vickery, ME Bremer, AM Donnelly, PD Doshi, ML Evans, TL Thurman, SR Braford, MH Caparon, SC Bauer, JG Giri, JK Welply, JP McKearn, WG Smith
Journal: Leukemia (2002)
Reply to Mavrogenis et al.
Authors: R. Colaiacovo, A. de Castro, R. Ganc
Journal: Endoscopy (2011)

Histoplasmosis is an unusual fungal infection, most commonly occurring in cave explorers. Nonetheless it can affect immunosuppressed patients and the medical team must think of disseminated histoplasmosis when encountering multiple ulcers in the digestive tract of such patients.
Capsule endoscopy for acute upper gastrointestinal bleeding: is the cherry ripe yet?
Authors: Frederick Weber, Charles Wilcox, Shajan Peter
Journal: Endoscopy (2013)

We read with interest the prospective cohort study by Gralnek et al. [1], which used the PillCam ESO 2 (Given Imaging Ltd., Yoqneam, Israel) in the emergency department for patients presenting with acute upper gastrointestinal bleeding. This represents part of a limited emerging literature on the subject [2] [3] [4]. Although the feasibility and safety of video capsule endoscopy (VCE) in this clinical setting appear clear, there remain a number of obstacles to be overcome before VCE can become an integral part of the initial emergency department assessment of upper gastrointestinal bleeding.
Abstract 4001: SOX7 is a potential tumor suppressor in breast cancer
Authors: Daniel B. Stovall, Meimei Wan, Qiang Zhang, Gaifang Liu, Paul Cao, Lance D. Miller, Wennuan Liu, Jianfeng Xu, Guangchao Sui
Journal: Cancer Research (2012)

Abstract Among U.S. women, breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer-related deaths. Both epigenetic silencing and genetic deletion of tumor suppressors are critical for the development and progression of breast cancer. The SOX (Sex-determining region Y-box) genes encode a family of over 20 transcription factors, including SOX7. The SOX7 gene is located on chromosome arm 8p and is deleted in a number of human cancers, including breast cancer. Previously, SOX7 has been demonstrated to be down-regulated in human tissues of prostate and colon cancers and its ectopic expression inhibits proliferation and increase apoptosis in prostate and colon cancer cell lines. However, the functional role of SOX7 in breast cancer has not yet been reported. Our studies revealed a significant correlation between SOX7 transcript levels and clinical outcome in gene array data from an international meta-cohort of 674 breast cancer patients. Consistently, we observed that SOX7 mRNA levels and protein expression are down-regulated in multiple breast cancer tissues and breast cancer cell lines compared to adjacent normal tissue and non-tumorigenic cells, respectively. Further, we have observed that the SOX7 promoter is hyper-methylated in breast cancer cell lines compared to non-tumorigenic breast cells, and that inhibition of SOX7 methylation results in an increase in SOX7 mRNA. Importantly, shRNA-mediated silencing of SOX7 conferred a growth advantage to non-tumorigenic breast cells, while induced ectopic SOX7 expression inhibited proliferation and migration of breast cancer cells. Overall, our data suggest that SOX7 may act as a novel tumor suppressor in breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4001. doi:1538-7445.AM2012-4001
Sulfite Oxidase Deficiency
Authors: Vivian E. Shih, Israel F. Abroms, Jean L. Johnson, Miriam Carney, Roseann Mandell, Richard M. Robb, John P. Cloherty, K. V. Rajagopalan
Journal: New England Journal of Medicine (1977)

Study of a 4 1/2-year-old boy with the unusual combination of acute infantile hemiplegia, ectopia lentis and the absence of homocystinuria showed large amounts of abnormal sulfur-containing metabolites (sulfite, thiosulfate and S-sulfocysteine) in the urine. Sulfite and S-sulfocysteine were also present in the plasma. His inorganic sulfate excretion was only 50 per cent of total sulfur, as compared with 75 to 95 per cent by controls. Loading with L-cysteine hydrochloride and L-methionine further increased the excretion of sulfite and thiosulfate, but not inorganic sulfate excretion. Sulfite oxidase activity in skin fibroblasts average 1.07 nmol of cytochrome d reduced per milligram of protein per minute in control lines; it was not detectable (less than 5 per cent) in the patient. Activity was reduced in both parents (0.50 in the father and 0.32 in the mother)--compatible with autosomal recessive inheritance. Good biochemical responses to a low sulfur amino acid diet suggest that early treatment may benefit the patient.
Registration by the European Agency for the Evaluation of Medicinal products (EMEA) of oncology products approved by the Food and Drug Administration (FDA) under accelerated approval (AA) regulations
Authors: L. Talarico, F. Pignatti, R. Pazdur
Journal: Journal of Clinical Oncology (2005)

6054 Background: The FDA AA regulations, implemented in 1992, allow approval of drugs that appear to provide a benefit over available therapy for life-threatening diseases based on surrogate endpoints “reasonably likely” to predict clinical benefit. Confirmation of clinical benefit is expected from ongoing trials completed with “due diligence”. In the European Union (EU), since 1995 approval of new oncology drugs can be obtained for the entire EU based on recommendations by the EMEA Committee for Medical Products for Human Use (CHMP). In situations where it is impossible to produce comprehensive data at the time of submission, drugs in the EU may receive approval “under exceptional circumstances”, with regular approval pending submission of post-approval data from further studies, including clinical trials. Material: This review is to compare the approval process by EMEA of drugs approved by FDA under AA and to outline some aspect of the two regulatory mechanisms relevant to oncology. Results: From 1992 to 2004, 20 cancer drug have received AA by FDA for 24 indications. Six have been converted to regular approval. Twelve of the 20 drugs have been approved between 1995 and 2004 through the EMEA for 16 indications (alemtuzumab, bortezomib, capecitabine, celecoxib, cetuximab, docetaxel, ibritumomab, imatinib, liposomal cytarabine, liposomal doxorubicin, pemetrexed, temozolomide,). Of the 12 drugs approved by EMEA, 6 were approved under “exceptional circumstances” (alemtuzumab, bortezomaib, celecoxib, docetaxel, ibritumomab, imatinib). For the 6 remaining applications, the clinical data submitted were considered adequate to support approval through the EMEA. For most products, the submission of the application to the FDA and the FDA AA preceded the EMEA submission and approval. Conclusions: EMEA has granted approval of FDA AA oncology products based on positive benefit/risk assessment from surrogate endpoints or additional available data. The mechanisms of approval for each drug will be described and compared. *The views presented are those of the authors and do not represent those of the FDA and EMEA. No significant financial relationships to disclose.