tbuckley/cabot-search huggingface dataset:
Right Ventricular Function in Respiratory Distress Syndrome and Subsequent Partial Liquid Ventilation
Authors: ROBBERT H. LOPES CARDOZO, PAUL STEENDIJK, JAN BAAN, HENS A. A. BROUWERS, MAARTJE DE VROOMEN, FRANK VAN BEL
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Infant respiratory distress syndrome (IRDS) and subsequent partial liquid ventilation (PLV) cause increased pulmonary vascular resistance, thus raising afterload. In nine newborn lambs the effects of IRDS and subsequent PLV on right (RV) and left ventricular (LV) contractility and systolic pump function were assessed using indices derived from RV and LV pressure-volume relations, obtained by micromanometric and conductance catheters during transient inferior vena cava occlusion. Pulmonary function deteriorated during IRDS with a significant decrease in the ratio of arterial oxygen pressure to fraction of inspired oxygen (Pa(O(2))/FI(O(2))) whereas pulmonary artery pressure (Ppa) showed a significant increase and pulmonary vascular resistance showed a substantial though not significant increase. Cardiac output (Q), stroke volume (SV), and end-diastolic volume (EDV) did not change. RV contractility showed a significant increase during IRDS: the slope of the end-systolic pressure-volume relation (RV-E (ES)) increased whereas its volume intercept at 5 kPa (RV-V(5)) decreased. The preload-corrected time derivative of ventricular pressure (RV-dP/dt(max)), however, did not change significantly. LV pump function and contractility were unchanged. During PLV pulmonary function showed a recovery but Ppa and pulmonary vascular resistance remained high; indices for RV contractility showed a sustained significant increase compared with baseline conditions whereas indices for LV pump function and contractility remained unchanged. These results show that the right ventricle of the newborn heart, in the face of increased pulmonary vascular resistance, is able to maintain cardiac output through homeometric autoregulation.
Abstract 748: Studying the significance of human p53-Sin3B interaction under the condition of DNA damage.
Authors: Rama Kadamb, Shilpi Mittal, Nidhi Bansal, Bilikere Srinivasa Rao Dwarakanath, Daman Saluja
Journal: Cancer Research (2013)

Abstract Sin3, a global regulator of transcription plays an important role in mediating gene regulation, by binding to various transcription factors through its highly conserved Paired Amphipathic Helices (PAH) domains. Physical association of Sin3 corepressor molecule with human p53, a tumour suppressor protein is now well established. In response to stimuli that activate p53, cells can undergo repair processes, cell cycle arrest or apoptosis. In order to combat the stress, p53 gets activated by posttranslational stabilization and modulate the expression levels of its target genes. There are number of genes which are negatively regulated by p53, but the mechanism of repression is not well characterized. We hereby show that p53 interacts with Sin3/HDAC corepressor complex in-vivo and expression of Sin3B is up regulated in response to DNA damaging stimuli in p53 dependent manner. Increase in the levels of Sin3B upon different kind of DNA damage suggests that Sin3B might be an important protein involved in DNA damage pathway. Sin3/HDAC corepressor complex is recruited by p53 onto the promoters of its target genes, resulting in the down regulation of p53 target genes. In our study we propose that the mechanism of repression of p53 target genes is through recruitment of Sin3/HDAC corepressor complex which leads to context specific chromatin modification. Such modifications results in enrichment of epigenetic marks like H3K9me3, H3K27me3, which are marker of repression under condition of DNA damage induced by Bleomycin. Knockdown of Sin3B using shRNA causes derepression of p53 target genes, suggesting that Sin3B is a key player in p53 mediated transrepression. Based on our studies we propose that Sin3B is an important corepressor molecule recruited by p53 in response to DNA damage and Increased Sin3B expression is an early event in DNA damage induced by Bleomycin. We further provide evidence that p53 regulate its target genes, namely HSPA8, MAD1, CRYZ, ANLN and CDC25c through its interaction with Sin3/HDAC corepressor complex which leads to chromatin modification by recruiting proteins involved in epigenetic modifications. Citation Format: Rama Kadamb, Shilpi Mittal, Nidhi Bansal, Bilikere Srinivasa Rao Dwarakanath, Daman Saluja. Studying the significance of human p53-Sin3B interaction under the condition of DNA damage. [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 748. doi:10.1158/1538-7445.AM2013-748
Neuronal inference must be local, selective, and coordinated
Authors: William A Phillips
Journal: Behavioral and Brain Sciences (2013)

Abstract Life is preserved and enhanced by coordinated selectivity in local neural circuits. Narrow receptive-field selectivity is necessary to avoid the curse-of-dimensionality, but local activities can be made coherent and relevant by guiding learning and processing using broad coordinating contextual gain-controlling interactions. Better understanding of the functions and mechanisms of those interactions is therefore crucial to the issues Clark examines.
Restarting Dabigatran Etexilate 24 h After Reversal With Idarucizumab and Redosing Idarucizumab in Healthy Volunteers
Authors: Stephan Glund, Joachim Stangier, Joanne van Ryn, Michael Schmohl, Viktoria Moschetti, Wouter Haazen, Marina De Smet, Dietmar Gansser, Stephen Norris, Benjamin Lang, Paul Reilly, Jörg Kreuzer
Journal: Journal of the American College of Cardiology (2016)
THU0343 No Upregulation of IL-6 at Different Sites in Facet Joints of Patients with Ankylosing Spondylitis Compared to Controls
Authors: J. Bleil, U. Syrbe, R. Maier, H. Appel, J. Sieper
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The analysis of interleukin-6 serum levels in patients with ankylosing spondylitis (AS) have indicated that IL-6 might be a proinflammatory cytokine in AS patients. However, a placebo-controlled trail using Tocilizumab (TCZ) has failed to demonstrate the efficacy of the monoclonal humanized anti-human IL-6 receptor antibody TCZ over placebo for the treatment of symptoms of AS (Sieper et al., 2012, EULAR abstract [OP0166]). <h3>Objectives</h3> An immunohistochemical analysis of IL-6 in facet joints from patients with AS in comparison to controls (CO) and osteoarthritis (OA) patients was performed to examine a possible reason for the missing efficacy of TCZ over placebo. <h3>Methods</h3> Facet joints from 13 AS, 11 OA patients and 12 controls (autopsies without spinal diseases) were analyzed. Immunohistochemistry was performed to detect IL-6+ cells at five different sites: within subchondral bone marrow, fibrous tissue replacing subchondral bone marrow, hyaline cartilage, subchondral bone plate and at the enthesial sites. <h3>Results</h3> The frequency of IL-6+ cells within subchondral bone marrow (p=0.0006), subchondral bone plates (p&lt;0.0001), entheses (p=0.0003) and fibrous tissue replacing subchondral bone marrow (p=0.0327) was significantly lower and within hyaline cartilage slightly lower (p=0.1689) in patients with AS compared to OA. Most interestingly, no significant differences were observed at all analyzed sites if AS patients and controls were compared, with the exception of the subchondral bone marrow. Only there, a significant decrease of the IL-6 expression was evident in AS patients compared to both, OA (p=0.0006) and CO (p=0.0043), while OA patients even showed a significant increase compared to CO (p=0.0095). In addition, AS patients also tended to have even lower percentages of IL-6+ cells than controls regarding subchondral bone plates (p=0.2131) and entheses (p=0.0806). <h3>Conclusions</h3> The comparable or even lower expression of IL-6 in facet joints of patients with AS compared to controls serves as a possible explanation for a lack of clinical benefit in the treatment of AS with anti-human IL-6 receptor antibody. <h3>References</h3> Sieper et al., 2012, EULAR abstract [OP0166] <h3>Disclosure of Interest</h3> None Declared
ABSTRACTS
Authors: PAUL W. DALE, HAROLD S. WRIGHT
Journal: American Journal of Psychiatry (1962)

Experience over a 3-year period demonstrates that a general hospital can admit, and successfully treat, a wide variety of psychiatric disorders using the facilities that ordinarily exist in such a general hospital designed and built for the care of patients with physical diseases. The advantages of this program are that it permits the patient to be treated in the community where he resides. There may be more ready acceptance of hospitalization by the patient and his family. Usually his health insurance plan provides some coverage for such care. It permits patients to have simultaneous psychiatric, medical and surgical study, and almost always in our experience, several physicians were involved in the treatment of each patient. Lastly, it is of educational value to members of the staff–interns, residents, nurses and student nurses. This method of care of psychiatric patients in a community general hospital is commended to others who are considering similar programs. We suspect that wherever the three ingredients of a good psychiatric staff, a progressive administration, and a willing nursing department co-exist, such a program will be successful. Psychiatric services in general hospitals will improve medical care throughout the hospital, will strengthen the medical staff, will advance teaching, and, most of all, will provide a needed service for a group of distressingly ill psychiatric patients. These problems and these patients occur in all communities throughout the land.
Abstract P2-07-01: Simvastatin Prevents Breast Cancer Skeletal Metastasis by Increasing p53 Levels To Increase PTEN and Inhibit CD44 Expression
Authors: CC Mandal, N Ghosh-Choudhury, T Yoneda, GG Choudhury, N. Ghosh-Choudhury
Journal: Cancer Research (2010)

Abstract Bone represents one of the main sites of metastatic spread of breast cancer. The prognosis for the breast cancer patients with bone metastasis is very poor with severely compromised life style associated with extreme bone pain and fracture prevalence. We used heart injection model to test the effect of simvastatin on breast cancer bone metastasis. Simvastatin prevented osteolytic lesions in mice injected with MDA-MB-231 (MDA) human breast cancer cells, indicating that statin attenuates breast cancer metastasis to bone. To investigate the mechanism, MDA cells were used in an in vitro wound-healing assay. Simvastatin significantly inhibited the migration of MDA cells. Transwell invasion assay using collagen-coated discs confirmed the inhibitory effect of simvastatin on breast cancer cell invasion. We have recently shown that simvastatin inhibits primary tumor growth in mice by upregulating the tumor suppressor PTEN. Overexpression of PTEN in MDA cells significantly blocked their ability to migrate and invade. To determine the mechanism of PTEN upregulation, we considered the tumor suppressor protein p53, which is known to regulate PTEN expression. Simvastatin-treated mice tumors showed significantly increased levels of p53. Similarly, simvastatin enhanced the expression of p53 in MDA cells. Additionally, simvastatin increased transcription of the reporter plasmids containing the consensus p53-binding element (p53-Luc) or the PTEN promoter (PTEN-Luc). Cotransfection of p53 with these reporter constructs resulted in similar increase in transcription, indicating a role of p53 in PTEN expression by simvastatin. Recent reports indicate a direct correlation between expression of CD44 in breast cancer and their metastasis to other organs including bone. Levels of CD44 were significantly reduced in the tumors of mice treated with simvastatin. In MDA cells, simvastatin decreased the expression of CD44 protein and its transcription, as determined by CD44 promoter-driven luciferase construct (CD44-Luc). p53 acts as transcriptional activator or transcriptional repressor in a cell-type and context-dependent manner. Presence of non-canonical p53-binding elements has been reported in the CD44 promoter. Cotransfection of p53 with CD44-Luc significantly suppressed the transcription of CD44. Furthermore, expression of p53 markedly reduced the expression of CD44 protein. Finally, downregulation of endogenous CD44 by specific shRNA decreased migration of MDA cells. Together these results uncover a novel action of simvastatin, which targets p53 expression to simultaneously increase PTEN and decrease CD44 thus blocking migration and preventing bone metastasis of the human breast cancer cells. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-07-01.
Upper gastrointestinal tumors
Authors: P. Siersema
Journal: Endoscopy (2012)

Nearly half of the worldwide esophageal squamous cell carcinoma (ESCC) cases occur in China [2]. In China, early esophageal squamous cell neoplasia (ESCN) is graded according to the proportion of the epithelial thickness containing neoplasia: 1/3 (low grade intraepithelial neoplasia [LGIN], mild dysplasia), 2/3 (moderate-grade [MGIN], moderate dysplasia), or 3/3 (high-grade [HGIN], severe dysplasia) [3]. The rate of progression to invasive ESCC varies according to the baseline grade of neoplasia: LGIN (5 % incident ESCC within 3.5 years, 24 % incident ESCC within 13.5 years), MGIN (27 % and 50 %, respectively), and HGIN (65 % and 74 %, respectively) [4] [5].
SP0014 Data collection for adolescents with arthritis: How to make it cool
Authors: K. Minden
Journal: Annals of the Rheumatic Diseases (2013)

Treatment strategies for patients with juvenile idiopathic arthritis (JIA) have tremendously changed during the past decade. Today, children and adolescents with JIA are treated earlier in the disease course with disease modifying antirheumatic drugs (DMARDs) and in particular increasingly more often with biologics. Their successful use in patients failing conventional DMARD therapy has led to a shift in the paradigm of arthritis treatment. More ambitious outcomes such as elimination of any inflammation, normalisation of short- and long-term function, and achievement of normal growth, physical and psychosocial development are new priorities for rheumatologists and patients. However, information on whether the new treatment strategies have actually resulted in better long-term outcomes of patients can only by gained by a follow-up of patients beyond adolescence. However, patient follow-up into adulthood, at least data collection of patients in their early adult years, is a challenge. Patients of this age have to cope with many developmental tasks. They move from school to work, move out from family home, move forward into an independent life, and have to move from paediatric to adult care. In these times, the rheumatic disease is understandably often not in the focus of patients. Thus, rheumatologists are attended not regularly or not at all, not to mention that about half of all JIA patients enter adulthood without active disease. The lecture will give an example on how to collect data for adolescents and young adults with arthritis. This will be exemplified by a biologic follow-up register. Therein about 700 adult patients have been meanwhile observed who were formerly included in the Biker register and ever treated with a biologic drug or methotrexate. The register differs in its monitoring from others because it is patient-oriented. Its advantages and disadvantages will be discussed. The primary aim of this register is to examine the long-term safety of anti-rheumatic drugs. In addition to serious adverse events/adverse event capture, the register shows actual drug exposure, medication switches and the reason(s) for drug change. Moreover, effectiveness parameters such as measures of quality of life, functional status, disease activity, co-morbidity, and employability are recorded. Selected outcomes will be presented. Summarizing, the methods and usability of a national adult JIA biologic register will be demonstrated. Such a register integrated with other national or international registers (e.g. Pharmachild) has the potential to provide effective mechanism for monitoring the long-term safety of therapies and to provide data for much needed clinical, cost-effectiveness, and health service research. <h3>Disclosure of Interest</h3> K. Minden Grant/Research support from: Pfizer
ED-13 * POSTTRAUMATIC GLIOMA: LITERATURE REVIEW
Authors: K. Kurako, V. Kurako, E. Salgado
Journal: Neuro-Oncology (2014)

BACKGROUND: Head injury's potential role as a factor in the development of brain tumors has often been a controversial subject. MATERIALS AND METHODS: We performed a systematic literature search in the PubMed database. Eight full-text articles including eleven case reports were selected for critical reading. RESULTS: Of the 11 case reports studied, 4 (36%) patients were female with a mean age of 51 and 7 (64%) patients were male with a mean age of 49. All patients previously experienced a motor-vehicle accident that resulted in severe brain trauma. Men usually reported their symptoms (an average of 13 years after the accident) later that women (an average of 7 years after the accident). The most commonly presented symptoms were headache in 5 (45%) cases, seizures in 4 (36%)cases, and speech disturbance in 3 (37%) cases. CONCLUSION: Evidently, a connection between head trauma and the formation of glioma may exist, but further evaluation and study is required for a more definitive
Acquired Esophagotracheal Fistula Secondary to a Foreign Body in the Esophagus
Authors: Yosh Maruyama, John R. Pettet, Charles R. Green
Journal: New England Journal of Medicine (1959)

ESOPHAGOTRACHEAL fistula resulting from a foreign body lodged in the esophagus is rare.1 One caused by a swallowed denture is reported below, and attention is called to the difficulties encountered in the demonstration of such plates by x-ray examination.Case ReportA 19-year-old soldier with epilepsy was admitted to the medical service of Tokyo Army Hospital on March 27, 1957. Three months previously, he had had an epileptic seizure, and after this he was unable to find his denture, a 4-tooth bridge. X-ray study of the chest (Fig. 1) had given no evidence of a radiopaque foreign body. Since that . . .
Treatment of Metastatic Malignant Melanoma with Dacarbazine plus Tamoxifen
Authors: Giorgio Cocconi, Mariangela Bella, Federico Calabresi, Maurizio Tonato, Rodolfo Canaletti, Corrado Boni, Franco Buzzi, Guido Ceci, Enrichetta Corgna, Paolo Costa, Renata Lottici, Franco Papadia, Maria Carla Sofra, Marisa Bacchi
Journal: New England Journal of Medicine (1992)

Endocrine factors may affect the clinical course of malignant melanoma and the response to the treatment of this disease. The presence of estrogen receptors in melanomas has been suggested, and occasional responses to antiestrogen therapy have been reported.We randomly assigned 117 patients with metastatic malignant melanoma to treatment with dacarbazine alone or dacarbazine in combination with tamoxifen. The overall rate of response, measured objectively, was higher (28 percent vs. 12 percent, P = 0.03) and survival was longer (median, 48 vs. 29 weeks, P = 0.02) among the patients who received dacarbazine plus tamoxifen than among those who received dacarbazine alone. Among women, both the response rate (38 percent vs. 10 percent, P = 0.04) and the median survival (69 vs. 30 weeks, P = 0.008) were better with dacarbazine plus tamoxifen than with dacarbazine alone, whereas among men the differences were smaller and not statistically significant. Among the patients given dacarbazine alone, there were no significant differences between women and men in response rate (10 percent vs. 13 percent) or survival (30 vs. 27 weeks), whereas among those given dacarbazine plus tamoxifen, women had better outcomes, as indicated by both response rate (38 percent vs. 19 percent, P = 0.15) and survival (69 vs. 31 weeks, P = 0.02). When we analyzed the Quetelet body-mass index (the weight in kilograms divided by the square of the height in meters) as an indirect indicator of the levels of endogenous estrogens in postmenopausal women and in men, survival was not affected by the body-mass index in the group given dacarbazine alone, whereas in the group given dacarbazine plus tamoxifen, survival was longer among patients whose Quetelet index was above the median value than among those with a Quetelet index lower than the median value (60 vs. 26 weeks, P less than 0.001).In the treatment of metastatic malignant melanoma, dacarbazine plus tamoxifen is more effective than dacarbazine alone, as indicated by both the response rate and the median survival; the difference in efficacy is among women.
SAT0121 Cardiovascular Risk Factors and Outcomes in Patients with Rheumatoid Arthritis across 7 Countries:
Authors: E. Arts
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular disease (CVD). CV risk factors and scoring algorithms vary by country but comparisons have not been performed for RA. <h3>Objectives</h3> To compare CV risk factors, scoring algorithms and outcomes in RA patients from 7 countries. <h3>Methods</h3> RA cohorts from 8 rheumatology centers in UK, Norway, Netherlands, USA, Sweden, Greece and South Africa were compared. Data on CV risk factors, algorithms (SCORE and Framingham) and RA characteristics were collected at baseline for each cohort; CV outcomes were collected prospectively using standardized definitions. Chi-square and rank sum tests were used to compare risk factors and algorithms; Kaplan-Meier methods were used to compare CV event rates between centers. <h3>Results</h3> 3176 RA patients without prior CVD were included (mean age: 55 [SD: 14] years, 73% female). During a mean follow-up of 7.8 years (24733 total person years), 314 patients developed CVD. Disease duration varied by center: 2 with early RA (&lt;1 year duration), 4 established (mean 9-13 years) RA and 1 with both. Mean age varied from 53 to 61 years (younger in the early RA cohorts - p&lt;0.001); females varied from 66% to 87% (p&lt;0.001). 1 cohort consisted of Hispanics, the rest Caucasians. All CV risk factors (smoking status, blood pressure, hypertension, lipids, diabetes mellitus, body mass index and use of antihypertensive or antilipemic medications), SCORE and Framingham algorithms and RA characteristics (rheumatoid factor and/or anti-citrullinated protein antibody seropositivity, disease activity scores [DAS28] and acute phase reactants) differed significantly across centers, p&lt;0.001 for each comparison. Mean risk scores were highest in Norway, UK, Netherlands, and Sweden. However, CV event rates were lowest in Norway and UK and highest in South Africa, Netherlands, US-Mayo and Sweden. <h3>Conclusions</h3> Statistically (but not necessarily clinically) significant differences in CV risk factors, algorithms and RA characteristics exist among RA cohorts from different countries. Misalignment between CV event rates and risk algorithms across RA cohorts illustrates the need for RA-specific and possibly country-specific risk algorithms. <h3>Acknowledgements</h3> Sherine Gabriel, Cynthia Crowson, George Kitas, Karen Douglas, Anne Grete Semb, Silvia Rollefstad, Eirik Ikdahl, Piet Van Riel, Elke Arts, Jaap Fransen, Solbritt Rantapää-Dahlqvist, Solveig Wållberg-Jonsson, Lena Innala, George Karpouzas, Petros P. Sfikakis, Evi Zampeli, Patrick H. Dessein, Linda Tsang, Miguel A. Gonzalez-Gay, Alfonso Corrales, Hani El-Gabalawy, Carol Hitchon, Virginia Pascual Ramos, Irazú Contreras Yáñez, Daniel Solomon, Katherine Liao. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1714