tbuckley/cabot-search huggingface dataset:
AB0339 Safety of 23-Valent Pneumococcal Vaccine in Rheumatoid Arthritis Patients (Preliminary Results)
Authors: M.S. Naumtseva, B.S. Belov, G.M. Tarasova, D.E. Karateev, E. Luchikina, Y. Muravyev, E. Alexandrova, A. Novikov
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Comorbid infections have significant impact on morbidity and mortality, especially in autoimmune rheumatic diseases. Therefore, prevention of infection is an integral part of supervision of these patients. <h3>Objectives</h3> Safety study of 23-valent pneumococcal vaccine for patients with rheumatoid arthritis (RA), receiving therapy with disease modifying anti rheumatic drugs (DMARDs), and biological disease-modifying antirheumatic drugs (bDMARDs). <h3>Methods</h3> The research included 72 people (women - 57 men - 15, at the age of 24 to 73 years), including 39 RA patients and 33 control subjects with a history of near ≥2 cases of lower respiratory tract infections (bronchitis, pneumonia). 24 patients with RA receiving methotrexate (MTX), 6 – leflunomide, 9 - tumor necrosis factor alpha (TNF-α) + MTX. 23-valent pneumococcal vaccine at 1 dose (0.5 ml) were injected subcutaneous continued MTX/leflunomide or 28-30 days before use TNF-α. Length of observation period after vaccination was 12 months. <h3>Results</h3> In 49 cases (69% of observations) patients tolerated the vaccine without complications. In 19 cases (26%) pain, swelling and redness of the skin with a diameter of 2 cm was observed. In 4 cases (5%) the injection of vaccine resulted in low-grade fever. These reactions were not associated with the on-going antirheumatic therapy and they did not require changes in the treatment scheme. These reactions were fully resolved within 24 hours without additional treatment. Clinical and radiographic signs of pneumonia were not observed in any of the cases. Episodes of exacerbation of RA or the occurrence of any new autoimmune disorders during follow-up were not observed as well. <h3>Conclusions</h3> Thus, preliminary results indicate sufficient clinical efficacy and good tolerability of the 23-valent pneumococcal vaccine for the patients with RA. For a more complete assessment of the effectiveness and safety of vaccine further clinical studies are recommended. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1248
Lymphatic mapping of ductal carcinoma in situ diagnosed by stereotactic core needle biopsy
Authors: P. Meijnen, M. C. Van Rijk, H. S. Oldenburg, C. E. Loo, R. A. Valdés Olmos, O. E. Nieweg, J. L. Peterse, M. J. Van de Vijver, E. J. Rutgers
Journal: Journal of Clinical Oncology (2006)

10507 Background: About 20% of ductal carcinoma in situ (DCIS) lesions diagnosed by stereotactic core needle biopsy (SCNB) are shown to be invasive on postoperative pathology examination. Sentinel lymph node biopsy (SLNB) is an accurate method of evaluating axillary lymph nodes in patients with invasive breast cancer. The aim of this study was to review our experience with lymphatic mapping in patients with a SCNB diagnosis of pure DCIS, to evaluate the DCIS underestimation rate and consequently the risk of lymph node metastases. Methods: Files from 160 patients diagnosed with pure DCIS by SCNB between July 1999 and March 2005 were retrieved from our database. Patients with DCIS were selected for SLNB if there was concern for presence of an invasive component on the basis of size, palpability or imaging. Results: The median age of the study group was 55 years (range 29–85 years) and median DCIS size on mammography was 25 mm (range 4–96 mm). Thirty-six (23%) out of the 160 women underwent a SLNB. Macrometastases in the sentinel node were detected in seven (19%) patients and one (3%) patient was found to have a micrometastasis. Twenty (56%) of these 36 patients had invasive lesions on final pathology. Of the 124 women who did not receive SLNB, 29 (24%) turned out to have invasive lesions on postoperative evaluation. In total, 49/160 (31%) patients with pure DCIS diagnosed by SCNB had invasive breast cancer (range pT1mic-pT2) on final pathology. Finally, 88 patients underwent lymphatic staging by SLNB, basal node sampling or complete axillary lymph node dissection. Nodal involvement was present in 14 (16%) out of these 88 patients with initially diagnosed DCIS: 36% in patients with invasive breast cancer and 2% with pure DCIS on final pathology. Conclusion: Postoperative pathology examination of the specimen demonstrates DCIS underestimation in nearly one third of SCNB diagnosed DCIS patients. SLNB is of benefit for these patients as in 19% of the patients who undergo a SLNB macrometastatic disease in the sentinel node can be found. No significant financial relationships to disclose.
LEFT ATRIAL DYSFUNCTION IN PATIENTS WITH PRESSURE GRADIENT-AORTIC VALVE AREA MISMATCHED SEVERE AORTIC STENOSIS
Authors: Tomoko Tani, Takeshi Kitai, Kitae Kim, Takafumi Yamane, Atsushi Kobori, Natsuhiko Ehara, Makoto Kinoshita, Shuichiro Kaji, Yutaka Furukawa
Journal: Journal of the American College of Cardiology (2015)
Changes in Human Adeno virus 5 Propagated in Burkitt's Lymphoma Cells
Authors: N Faucon, G Ogier, Y Chardonnet
Journal: JNCI Journal of the National Cancer Institute (1982)

The effect of host cells on human adenovirus 5 properties was studied with the use of Burkitt's lymphoma cell lines (Raji and Jijoye) that poorly replicate the virus. Only a small fraction of the cell population was producing adenovirus 5. The major virus components were synthesized; however, the purified virus particles differed from those produced in HeLa cells by lower density in CsCl gradient, lower content in DNA, limited changes in DNA restriction enzyme pattern, and polypeptide composition. After one passage in HeLa cells, modifications of polypeptides reversed.
SC-22 * GLIOMA STEM CELLS INTERNALIZE BEVACIZUMAB FOUND IN THE PERIVASCULAR NICHE AND TARGET IT FOR RECYCLING OR DEGRADATION
Authors: G. Muller-Greven, C. Carlin, J. Lathia, J. Rich, P. Hamerlik, C. Gladson
Journal: Neuro-Oncology (2014)

Antiangiogenic therapy shows great promise for treatment of cancer. Bevacizumab is a humanized mAb that blocks VEGF-A, thereby inhibiting angiogenesis. It has received FDA approval for patients with recurrent glioblastoma (GBM); however, approximately 30% of patients are non-responsive and the underlying mechanism for the lack of response is not known. It has been assumed that Bevacizumab solely targets circulating VEGF-A; however, VEGF-A found in the perivascular space of GBM tumors could also be an important target. We hypothesized that Bevacizumab is transcytosed across brain endothelial cells (ECs), gains access to the perivascular niche containing glioma stem cells (GSCs), and that differences in GSC endocytosis and targeting of Bevacizumab for recycling or degradation determines a patients' response. We found that Bevacizumab is internalized by normal and tumor-isolated brain ECs in a time-dependent manner that is partially inhibited by amiloride and stimulated by EGF, suggesting Bevacizumab enters the cells by macropinocytosis. ECs transcytose 62% of Bevacizumab over two-hours. Importantly, we found that 95% of GSCs internalize Bevacizumab in 30 minutes. Internalized Bevacizumab in GSCs can be recycled to the extracellular space or degraded; at 5 minutes we found that Bevacizumab was localized to the Rab4+ fast recycling compartment (67%); whereas at 30 minutes only 7% localized to the Rab4+ compartment and 16% localized to the LAMP1+ compartment (late endosome/lysosome). Furthermore, in an orthotopic xenograft mouse model of GBM administered Bevacizumab, we found a gradient of Bevacizumab extending from the vessel into the tumor and it was readily detected within perivascular tumor cells. Our data indicate that the trafficking of Bevacizumab by perivascular GSCs in GBM may influence Bevacizumab effectiveness in patients. Understanding the mechanism of internalization and trafficking of Bevacizumab in GSCs from different molecular subtypes of GBM may help us understand which patients will be responsive to Bevacizumab therapy.
Abstract 5040: Aberrant DNA methylation of microRNAs in hepatocellular carcinoma
Authors: Jing Shen, Shuang Wang, Yu-Jing Zhang, Maya Kappil, Hui-Chen Wu, Muhammad G. Kibriya, Qiao Wang, Farzana Jasmine, Habib Ahsan, Po-Huang Lee, Ming-Whei Yu, Chien-Jen Chen, Regina M. Santella
Journal: Cancer Research (2012)

Abstract microRNAs (miRNAs) are a class of small non-coding RNAs involved in post-translational gene silencing by accelerating the degradation of mRNA and translational inhibition. miRNAs may regulate more than 60% of protein-coding genes’ translation. Previous studies have found that down-regulation of miRNAs is one of the most common features observed in solid tumors, including hepatocellular cancer (HCC). In the current study, we employed a genome-wide approach to test the hypothesis that methylation alteration in miRNA genes is an important mechanism causing deregulated miRNA expression in HCC. We analyzed tumor and adjacent non-tumor tissues from 62 Taiwanese HCC cases using the HumanMethylation27 DNA Analysis BeadChips that include 255 CpG sites relevant to 64 miRNA genes. A volcano plot was used to display mean DNA methylation differences of all CpG sites. The hierarchical clustering for the significant CpG sites was performed to differentiate tumor and non-tumor tissues. After Bonferroni adjustment, a total of 54 CpG sites (27 relevant genes) significantly differed in methylation levels, with 53 CpG sites significantly hypermethylated in tumor compared to non-tumor tissues. Among the significant CpG sites, 15 sites have more than 2 fold tumor/non-tumor differences, 17 sites have a difference between tumor and non-tumor tissues of &amp;gt;10%, and 10 sites have both features. PANTHER ontology analysis suggested several enriched biological pathways for these miRNAs, including Wnt signaling, Ras, oxidative stress response, glutamine/glutamate conversion and mannose metabolism. The miRNAs methylation profiles were also compared by viral status (HBV/HCV) and AFB1 exposures. No statistically significant miRNA was identified. Analysis of a panel of candidate miRNAs (miR-196, miR-10a, miR-10b and miR-170) is ongoing in the same HCC tissues to evaluate whether the aberrant DNA methylation significantly correlates with expression. 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 5040. doi:1538-7445.AM2012-5040
SP0208 Highlights from the health professionals in rheumatology at the 2012 eular congress
Authors: J. Verhoef, J. de la Torre-Aboki
Journal: Annals of the Rheumatic Diseases (2013)

The purpose of this session is to summarize and to highlight the most important advances in the field of the Health Professionals in Rheumatology, which were presented and discussed during the Health Professionals sessions at the 2012 EULAR Congress. The Health Professionals in Rheumatology programme consists of the following session topics that will be summarized and discussed from the perspective of new insights and future developments: Experiences with running an osteoarthritis clinic in daily practice; Crossing boundaries of primary to secondary care; Promotion of physical activity in rheumatology targeting patients, providers and the public; Challenges in health professionals’ practice regarding to develop and execute a treatment plan for a patient with rheumatic condition and multimorbidity; Clinical update in connective tissue diseases; Start of reviewing a guideline and Cardiovascular health in rheumatic diseases. <h3>Disclosure of Interest</h3> None Declared
Endoscopic ultrasound-guided ethanol ablation of a symptomatic sporadic insulinoma
Authors: F. Vleggaar, E. bij de Vaate, G. Valk, R. Leguit, P. Siersema
Journal: Endoscopy (2011)

An insulinoma is an insulin-secreting neuroendocrine tumor (NET) which may lead to symptomatic fasting hypoglycemia. These often small lesions are primarily located in the pancreas. Endoscopic ultrasonography (EUS) has been found to be the optimal diagnostic modality for NET identification.
ASCO Intensifies Efforts To Aid Cancer Survivors
Authors: S. Jenks
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article ASCO Intensifies Efforts To Aid Cancer Survivors Get access Susan Jenks Susan Jenks Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 16, August 1993, Page 1277, https://doi.org/10.1093/jnci/85.16.1277 Published: 01 August 1993
Intraosseous Catheter Placement in Children
Authors: Joshua Nagler, Baruch Krauss
Journal: New England Journal of Medicine (2011)

Obtaining vascular access in acutely ill or injured children can be challenging. Intraosseous access provides a means for delivery of medications, crystalloid fluids, colloids, and blood products during pediatric resuscitation. In addition, when intraosseous access is achieved, blood samples can be obtained for laboratory analysis. Numerous studies show that an intraosseous catheter can be placed more rapidly than a central venous catheter and that this technique is more reliable than venous cutdown. . . .
S51 Klotho is associated with skeletal muscle dysfunction and oxidative stress in COPD
Authors: MS Patel, AV Donaldson, SA Natanek, PLB Bruijnzeel, NS Hopkinson, W D-C Man, PR Kemp, MI Polkey
Journal: Thorax (2013)

<h3>Introduction</h3> Klotho is a transmembrane protein; klotho null mice develop sarcopenia and emphysema. We have previously found serum soluble klotho levels to be lower in COPD patients (ATS 2013). We hypothesised that klotho protects against muscle dysfunction by reducing oxidative stress which is a known feature of skeletal muscle dysfunction in COPD. <h3>Aims</h3> To relate quadriceps klotho levels to protein carbonylation and muscle strength in COPD patients. To determine the effect of smoking cessation on <i>vastus lateralis</i> protein carbonylation and klotho. <h3>Methods</h3> In 47 COPD patients (mean FEV<sub>1 </sub>53 (23)%pred), we measured fat-free mass index (FFMI) and quadriceps strength (as QMVC/BMI). Klotho and protein carbonylation were assessed in <i>vastus lateralis</i> protein extracts. 7 current smokers (3 with COPD) had measurements before and after successful smoking cessation. Differences were assessed by Mann-Whitney and relationships by Spearman’. Response to smoking cessation was determined by paired Wilcoxon. <h3>Results</h3> <i>Vastus lateralis</i> protein carbonyls were related to klotho levels (r = 0.34, p = 0.02). Patients with a low FFMI (n = 12) had increased klotho levels compared to those who did not, 14.0 (8.5, 30.0) v 9.2 (6.5, 13.2) pg/mg; p = 0.04, however, protein carbonyls were not different (p = 0.08). Conversely, patients with muscle weakness defined as a QMVC/BMI below 1.2 (n = 24) had higher protein carbonylation, 0.76 (0.52, 0.99) v 0.51 (0.40, 0.71) nmol/mg; p = 0.04, but no difference in klotho (see figure 1). Patients with both a low FFMI and QMVC/BMI (n = 6) had elevated levels of klotho and protein carbonyls (p = 0.02 and p = 0.03 respectively). In those completing smoking cessation, protein carbonyls, tended to fall, 0.75 (0.64, 1.24) to 0.61 (0.50, 0.71) nmol/mg; p = 0.08, however, klotho levels did not change (p = 0.38). <h3>Conclusions</h3> Klotho levels are related to oxidative stress within the quadriceps. Klotho levels are unexpectedly higher in those with reduced FFMI without increased oxidative stress. However, when there is loss of muscle mass and strength, increased klotho levels in muscle are accompanied by increased oxidative stress. Klotho may have a protective role against chronic oxidative stress in the skeletal muscle of patients with a reduced FFMI.
18F-FDG PET Detection of Unknown Primary Malignancy in Dermatomyositis
Authors: Syed Mahmood, Sofia Rodríguez Martínez de Llano
Journal: Clinical Nuclear Medicine (2012)

Dermatomyositis is an inflammatory myopathy that has an association with malignancy in adults. We present a patient who initially presented with adenopathy and progressive muscular weakness and was diagnosed with dermatomyositis and lung carcinoma on further investigation. Whole-body PET/CT scan revealed diffuse proximal muscle hypermetabolism representing the inflammatory nature of dermatomyositis, and an intensely FDG-avid primary right lower lung small cell lung carcinoma and metastatic thoracic lymphadenopathy. PET/CT imaging may offer an "all-in-one" procedure as an alternative to other diagnostic procedures, reducing the number of unnecessary investigations in patients presenting with paraneoplastic syndromes searching for underlying malignancy.
Risk of Localized and Widespread Endometrial Cancer in Relation to Recent and Discontinued Use of Conjugated Estrogens
Authors: Samuel Shapiro, Judith P. Kelly, Lynn Rosenberg, David W. Kaufman, Susan P. Helmrich, Neil B. Rosenshein, John L. Lewis, Robert C. Knapp, Paul D. Stolley, David Schottenfeld
Journal: New England Journal of Medicine (1985)

In a case-control study of the risk of adenocarcinoma of the endometrium in relation to conjugated-estrogen use, we found that 31 per cent of 425 women with endometrial cancer and 15 per cent of 792 controls reported having used conjugated estrogens; the rate-ratio estimate was 3.5 with a 95 per cent confidence interval of 2.6 to 4.7. For use that lasted at least one year, the rate-ratio estimate for Stage I or II cancer was 5.2 (95 per cent confidence interval, 3.7 to 7.2), and for Stages III and IV combined it was 3.1 (1.5 to 6.4). Among women who had used estrogen for at least one year and then discontinued it, the risk of endometrial cancer remained significantly elevated even after estrogen-free intervals of over 10 years. The findings suggest that long-term use of conjugated estrogen increases the risk of both localized and widespread endometrial cancer. The data also suggest that women who have taken conjugated estrogen for one or more years remain at increased risk for at least 10 years after they discontinue use. Such women should be considered for long-term gynecologic surveillance.
Uncertainty and Possible Subclinical Valve Leaflet Thrombosis
Authors: David R. Holmes, Michael J. Mack
Journal: New England Journal of Medicine (2015)

Transcatheter aortic-valve replacement (TAVR) has had a profound effect on the management of structural heart disease, as evidenced by the fact that since 2010 the Journal has featured six reports on pivotal registries or randomized TAVR trials.16 The effect can also be assessed by the incredible growth in the number of procedures. The Transcatheter Valve Therapy Registry, launched by the Society of Thoracic Surgeons and the American College of Cardiology, has enrolled approximately 35,000 patients who have been treated with commercially approved devices at 376 centers in 49 states in the United States alone. The rapid growth of this . . .
LONG-TERM ANTIHYPERTENSIVE TREATMENT LOWERING BLOOD PRESSURE IMPROVES LEFT VENTRICULAR TWISTING AND UNTWISTING IN HYPERTENSIVES: A 3 YEAR FOLLOW-UP STUDY
Authors: Ignatios Ikonomidis, Helen Trianatafyllidi, Paraskevi Trivilou, Stavros Tzortzis, George Pavlidis, Leonidas Palaiodimos, Ioannis Paraskevaidis, John Lekakis
Journal: Journal of the American College of Cardiology (2015)
The Pathogenesis of Insulin-Dependent Diabetes Mellitus
Authors: Franklin H. Epstein, Mark A. Atkinson, Noel K. Maclaren
Journal: New England Journal of Medicine (1994)

Insulin-dependent diabetes mellitus (IDDM) is a chronic disorder that results from autoimmune destruction of the insulin-producing pancreatic beta cells. Much has been learned during the past decade about the underlying genetics, natural history, and pathogenesis of IDDM. In this review, we shall describe some of this new information and discuss how it might be used to prevent the disease.EpidemiologyIDDM occurs most frequently in persons of northern European descent. Among other racial groups, such as blacks, Native Americans, and Asians, the disease is less common1. The incidence ranges from a low of 1 to 2 per 100,000 per . . .
Abstract 5360: Leptin-induced SIRT1 expression in human colon cancer cells: a potential link between obesity and cancer
Authors: Na-Young Song, Young-Joon Surh
Journal: Cancer Research (2010)

Abstract Recently, several epidemiological studies have shown that obesity is one of the prime factors in the etiology of some malignancies. The molecular mechanism underlying obesity-induced carcinogenesis, however, is not fully clarified yet. Leptin, a representative adipokine secreted from the white adipose tissue, is considered as a potential linker between obesity and cancer. Although leptin has been identified as an anorexic adipokine, obese subjects exhibit unexpectedly higher circulating levels of leptin than non-obese individuals. Increased serum levels of leptin may activate the pro-inflammatory signals and stimulate the tumor growth. In the present study, we have found that treatment with leptin (100 ng/ml) promotes migration and invasion of human colon cancer (HCT-116) cells, suggesting leptin as a molecular link between obesity and cancer. Interestingly, leptin induced expression as well as activity of SIRT1, a NAD+-dependent class III histone deacetylase, recognized as an important metabolic regulator. It has been reported that SIRT1 exerts an anti-aging effect. Paradoxically, SIRT1 gene is highly expressed in certain types of tumors, and is speculated to function as an oncogene. We found that leptin-induced HCT-116 cell migration and invasion were blocked by treatment with sirtinol (25 μM), an inhibitor of SIRT1. NF-E2-related factor 2 (Nrf2) is a redox-sensitive transcription factor responsible for regulating expression of a battery of stress-responsive genes. Considering that obesity is a state of chronic oxidative stress, Nrf2 might be involved in leptin-induced SIRT1 up-regulation. In line with this notion, several consensus antioxidant response elements (AREs) specified for Nrf2 binding are found within a promoter region of SIRT1. Treatment of HCT-116 cells with leptin provoked nuclear translocation and ARE binding of Nrf2. Moreover, siRNA knockdown of Nrf2 abrogated leptin-induced SIRT1 expression, lending further support to the notion that Nrf2 regulates SIRT1 expression in leptin-treated HCT-116 cells. We also found that treatment with leptin led to accumulation of reactive oxygene species (ROS) in HCT-116 cells. Pre-treatment with N-acetyl cysteine attenuated leptin-induced SIRT1 expression, indicating a possible involvement of ROS. In conclusion, leptin, a key adipokine in obesity, may mediate colon tumor progression via Nrf2-dependent SIRT1 expression. 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 5360.
Access to Patient-Level Trial Data
Authors: Hal Barron, Michael Rosenblatt
Journal: New England Journal of Medicine (2014)

To the Editor: The Chief Medical Officers Roundtable (CMOR), of which we are members, welcomes the Perspective article by Eichler et al. (Oct. 24 issue),1 who are representatives of the European Medicines Agency (EMA), on access to patient-level trial data. CMOR formulates positions on medical topics, and its members include chief medical officers of major biopharmaceutical companies. CMOR supports a transparent, harmonized process for access to patient-level clinical trial data. Any approach to clinical trial data sharing must be in the interest of patients. Data sharing should be based on two tenets. First, principles should apply uniformly to all who . . .
677 TERLIPRESSIN AND ALBUMIN FOR TYPE-2 HEPATORENAL SYNDROME. IS IT JUSTIFIED?
Authors: E. Rodríguez, G. Pereira, M. Guevara, C. Fagundes, E. Sola, R. Barreto, M. Pavesi, V. Arroyo, P. Gines
Journal: Journal of Hepatology (2012)