tbuckley/cabot-search huggingface dataset:
AB0261 Profile of an under-studied rheumatoid arthritis (RA) population: characteristics of patients with moderately active rheumatoid arthritis despite methotrexate use:
Authors: A. Koenig, A. Szumski, S. Kotak, M. Stewart
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> RA progression is difficult to predict and rheumatologists need to rely on a combination of subjective and objective measurements to assess RA disease activity and severity, as reliance on one measurement is not recommended due to variability.[1] The majority of findings from treatment trials have been derived from patients with predominately severe RA; less is known about patients with moderately active disease, who represent a larger group that may benefit from early effective treatment. <h3>Objectives</h3> To help understand and characterize the moderate RA patient, demographic and baseline disease characteristics of subjects participating in the PRESERVE trial are presented. <h3>Methods</h3> Enrolled subjects with DAS28 &gt;3.2 and ≤5.1 despite stable doses of oral methotrexate (MTX) received open-label etanercept (ETN) 50 mg QW plus MTX for 36 weeks. Descriptive summary statistics for demographics and clinical disease characteristics are provided for subjects who received ≥1 dose of treatment (N=834); radiographic characteristics are provided for subjects who received ≥1 dose of treatment and had both a baseline and a post-baseline radiographic assessment (N=709). <h3>Results</h3> At baseline, most subjects were female (83%), Caucasian (74%), RF+ (73%), and aCCP+ (78%); mean age was 48.4 y (SD 11.9; median 50.0; min/max 18.0/70.0), with a mean MTX dose of 16.5 mg (SD 2.7; median 15.0; min/max 2.5/25.0) and disease duration, 6.9 y (SD 7.0; median 4.5; min/max 0.1/45.1). Overall 18% of subjects had a normal HAQ score (≤0.5) and 45% had paid employment. A majority used NSAIDs (74%) or corticosteroids (59%) within 1 month of screening; a minority used DMARDs (27% after excluding MTX use) within 6 months of screening. <h3>Conclusions</h3> The baseline characteristics of subjects who participated in the PRESERVE trial displayed wide variability in disease measures, highlighting the heterogeneity in clinical presentation, structural damage and burden of disease that can be found in moderate RA patients who are not well controlled on MTX alone and may benefit from effective intervention. These results from PRESERVE suggest the moderate RA population is distinct from other more extensively studied RA populations (eg, early severe and established severe disease) and warrants further investigation. <h3>References</h3> Wolfe F, et al. Arthritis Rheum 2005;52:3873–9. <h3>Disclosure of Interest</h3> A. Koenig Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., A. Szumski Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., S. Kotak Employee of: Pfizer Inc., M. Stewart Shareholder of: Pfizer Inc., Employee of: Pfizer Inc.
Spontaneous Coronary Artery Spasm Documented in a Young Woman
Authors: RICHARD J. CAMPEAU, JOHN G. SPELLMAN, ALAN N. TENAGLIA
Journal: Clinical Nuclear Medicine (1996)

A 35-year-old woman with coronary risk factors presented with nonexertional atypical burning chest pain of 1 week's duration. A myocardial perfusion study with Tc-99m MIBI revealed a severe stress induced anteroseptal perfusion defect that completely reperfused on a subsequent resting Tc-99m MIBI study. Coronary angiography showed mild nonobstructive coronary artery disease. At the termination of the procedure, a spontaneous episode of burning chest pain occurred. Left main coronary artery reinjection of contrast revealed proximal diffuse left anterior descending coronary artery spasm. The patient was followed for 2 years with no further episodes of chest pain, while on calcium channel-blocker medication. The phenomenon of vasospastic angina and the role of myocardial perfusion scintigraphy is discussed.
P575Functional characterization of novel PITX2 homeodomain mutations in AF patients
Authors: E Lozano-Velasco, F Hernandez-Torres, H Daimi, E Vazquez Ruiz De Castroviejo, C Lozano, A Aranega Jimenez, D Franco Jaime
Journal: Cardiovascular Research (2014)

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the human population, with an estimated incidence of 1-2% in young adults but increasing to more that 10% in 80+ years patients. Albeit AF is a frequent electrophysiological disorder, to date, the genetic bases of AF remain rather elusive. Point mutations in a large variety of ion channels have been described in familial cases of AF, yet explaining a minority of cases. Recently, genome wide association studies (GWAS) have unraveled risk SNPs highly associated with AF, among which the most significant are located in 4q25 locus. Surprisingly these risk alleles are located in a gene desert, being the closest gene PITX2. Experimental evidences of Pitx2 loss-of-function in mice revealed that this homeodomain (HD)-containing transcription factors plays a pivotal role in atrial electrophysiology. Therefore these data, underscore PITX2 as a candidate gene for AF. In this context, we have recruited 31 AF patients from the Regional Hospital for genetic analyses of both the risk alleles and PITX2 ORF re-sequencing. Among those patients, we have found two point mutations in the HD of PITX2 and three other mutations in the 5'untranslated region. A 65 years male patient with recurrent AF displayed two distinct HD-mutations, G947A (Q103H) and G1008A (E124Q), which both resulted in a change within a highly conserved amino acid position. Curiously, no 4q25 risk variants were present in this subject. Both PITX2 HD mutations were further followed for functional studies. We generated plasmid constructs with mutated version of each nucleotide variant (MD4 and MD5, respectively) as well as a dominant negative control construct in which the PITX2 HD was lacking (DN). Functional analyses demonstrated PITX2 MD4 and PITX2 MD5 decreased Nppa-luciferase transactivation by 50% and 40%, respectively, in a similar range as PITX2 DN (50%). Co-transactivation with other cardiac-enriched transcription factors, such as Gata4 and Nkx2.5, was similarly impaired, further supporting the pivotal role of these mutations for correct PITX2 function. We are currently evaluating the functional consequence of these mutations in a cardiomyocyte context. Preliminary data suggest that distinct AF-related genes are similarly impaired. In summary, we have identified novel PITX2 mutations in an AF patient, which functionally impairs the transactivating capacity of PITX2.
SP0211 Effects of Hypoxia on Immune Cells
Authors: T. Gaber
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Hypoxia is a feature of several pathological but also non-pathological areas. Hypoxia can be defined as a state where oxygen availability to cells, tissues or organs is decreased as compared to the physiological situation. But also physiological oxygen concentrations vary among the body compartments. Immune cells patrolling the whole body therefore face different oxygen levels and have to adapt properly in order to fulfil their functions. Moreover, the variety of different oxygen levels in primary and secondary lymphoid organs as well as in the tissue of immune action influence immune cell function, specification and fate. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6344
725 FOOD INTAKE DRAMATICALLY INCREASES LIVER STIFFNESS MEASUREMENTS AND HAMPERS RELIABLE VALUES: RESULTS FROM A LARGE COHORT OF HBV INFECTED AND NON INFECTED AFRICAN SUBJECTS
Authors: M. Lemoine, Y. Shimakawa, H. Njai, S. Tamba, T. Corrah, U. D'Alessandro, R. Njie, M. Thursz
Journal: Journal of Hepatology (2013)
ADECUACIÓN Y DEMORA DE LAS EXPLORACIONES ENDOSCÓPICAS EN UN PROGRAMA DE „ENDOSCOPIA ABIERTA“ EN ATENCION PRIMARIA
Authors: A Dacal Rivas, P Quintas Lorenzo, E Sánchez Hdez, M Francisco, J Cubiella Fernández, I Castro Novo, P Vega Villamil, J Fernández Seara
Journal: Endoscopy (2010)

Introducción: La rectorragia y la dispepsia son dos motivos de consulta frecuentes tanto en Atención Primaria (AP), como en las Consultas Especializadas de Aparato Digestivo (AE). En su proceso diagnóstico se incluyen exploraciones endoscópicas. Hemos procedido a la implementación de las Guías de Práctica Clínica (GPC) para estas dos entidades, con protocolos de derivación y solicitud de exploraciones endoscópicas desde AP.
Impact of BRCA mutation status on the clinical phenotype and survival of hereditary breast cancer.
Authors: M Kiechle, C Engel, U Schwarz-Boeger, D Grund, S Preisler-Adams, C Crohns, S Stark, D Gadzicki, K Strunz, I Schoenbuchner, C Nestle-Kräemeling, K Kast, N Ditsch, B Schlehe, R Schmutzler
Journal: Cancer Research (2009)

Abstract Abstract #3091 Background : In a multidisciplinary program supported by the German Cancer Aid in 1996-2006 a total of 3.408 women with a family history for breast and/or ovarian cancer were genetically counselled and tested for BRCA-1 and BRCA-2 mutations.&amp;#x2028; Methods: The mutations were detected using DHPLC and direct sequencing. The family history of breast and/or ovarian cancer was proven by collecting medical reports of family members. The statistical analysis was done using standard procedures (Kaplan-Meier-analysis, t-test, chi-square-test).&amp;#x2028; Results: Among the women with breast cancer 566 showed a deleterious BRCA1 and 313 a BRCA2 mutation. Four women were found to have mutations in both genes and 2.525 were BRCA-1/2 negative. In accordance with the literature we found the phenotype “hormone receptor negative and grade 3” as well as the medullary subtype significantly more often in BRCA1 associated breast cancers (74% vs. 24%, 63% vs. 42% and 10% vs. 5%). The median age of onset was significantly lower in BRCA1 mutation carriers (38 yrs) compared to BRCA2 mutation carriers (45 yrs) and women tested negative for BRCA1 and BRCA2 mutations (46 yrs) as well as sporadic breast cancer cases within these families (52 yrs). The median age of the 4 women with mutations in both genes was even lower (median age 33.5 yrs). Although BRCA2 associated breast carcinomas presented in more advanced stages (N+ in 44%[118/257] compared to BRCA-1 positive in 31%[166/519], p&amp;lt;0.01) there was no difference in overall survival between BRCA1 and BRCA2 mutation carriers. However, BRCA1 and BRCA2 negative cases showed a significantly better survival rate compared to the women with mutations (p&amp;lt;0.0001). Women from families with early onset breast cancer (&amp;lt;35 yrs) or bilateral breast cancer (&amp;lt;40 yrs) had a significantly better survival (p&amp;lt;0.0001) than women from families with a later age of onset.&amp;#x2028; Conclusions: The BRCA mutation status has a significant impact on the clinical phenotype of hereditary breast cancer which is important for the clinical management, counselling and prevention. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3091.
The 3-Year Medical School — Change or Shortchange?
Authors: Stanley Goldfarb, Gail Morrison
Journal: New England Journal of Medicine (2013)

Interview with Dr. Richard Schwartzstein on the pros and cons of three-year medical school programs. (00:00)Download Shortening medical school to 3 years, some observers argue, would increase the supply of physicians and reduce the cost of medical training. Data from many years of experiments in shortening medical education, however, suggest that doing so is unwise.
TOLERANCIA A LA COLONOSCOPIA AMBULATORIA BAJO SEDACIÓN CONSCIENTE Y FACTORES RELACIONADOS
Authors: I Grilo, L Gómez, E Gómez, V Aguado, M Cañas, I Ruz, R Navarro
Journal: Endoscopy (2014)

Introducción: La colonoscopia es una exploración potencialmente dolorosa. La detección de factores relacionados con una mala tolerancia bajo sedación consciente permitiría seleccionar a los pacientes para sedación profunda.
Abstract P6-09-02: Risk of Breast Cancer Associated with Hormone Replacement Therapy Use Differs by Age, Race, and Breast Density
Authors: S Hong, W Wang, D Huo, J Siddique, JJ. Dignam
Journal: Cancer Research (2010)

Abstract Background: Observational studies and randomized trials have demonstrated an association between hormone replacement therapy (HRT) use and increased risk for breast cancer. However, this risk may vary by age and other factors, including breast density and race/ethnicity. Using data from the Breast Cancer Surveillance Consortium (BCSC), we investigate whether self-reported HRT use in the peri-menopausal and immediate post-menopausal age groups is associated with breast cancer, and also whether risk associated with HRT use differs by breast density and race. Subjects and Methods: The BCSC is a longitudinal registry of mammography screening in seven U.S. centers. In the breast cancer risk prediction model developed by Barlow et al (J Natl Cancer Inst 2006 98:1204-14), HRT use and ten other features were identified as risk factorsfor breast cancer. Data for our study consists of 1,642,824 screens and 9,300 breast cancers among the post-menopausal women aged &amp;gt; 44 in this cohort. Logistic regression models were used to estimate odds ratios for breast cancer associated with HRT use within race, age, and density strata, adjusting for other variables from the Barlow model. Multiple imputation methods were used to accommodate missing data for HRT (14%) and other predictors. Results: Breast cancer risk for HRT use varied by age, with no risk excess among women aged 45-49 and risk excess of 20% or greater for women aged 50-64 (Table 1). Women &amp;gt;64 had a smaller excess risk with HRT use. There was no significant excess risk at any age for Black women, while White women age 50-64 had &amp;gt; 20% excess risk for HRT use. White women with higher breast density had increased risk with HRT use, while Black women did not. Table 1: Odds ratios (95% confidence interval) for HRT use (yes/no) Conclusions: In this large cohort of mammography-screened women, HRT use did not increase breast cancer risk in the peri-menopausal period (age 45-49). Women with low breast density had smaller risk increments associated with HRT than those with high density. For Black women, increased breast cancer risk due to HRT was not apparent at any age or breast density category. Data collection for the BCSC was supported by a NCI-funded Breast Cancer Surveillance Consortium co-operative agreement (U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976, U01CA63731, U01CA70040). Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-09-02.
Cytotoxins in Disease
Authors: Paul I. Terasaki, Vilma D. Mottironi, Eugene V. Barnett
Journal: New England Journal of Medicine (1970)

Lymphocytotoxic antibodies were found in 56 of 64 serum specimens from patients with systemic lupus erythematosus and 30 of 53 patients with rheumatoid arthritis. These cytotoxic antibodies characteristically reacted with a temperature optimum of 15°C as was found earlier with serums from patients with infectious mononucleosis, rubella and rubeola. The lymphotoxin found in systemic lupus was cytotoxic to autologous lymphocytes in 24 of 32 specimens tested. No correlation was found to the antibodies detected by radioactive labeled deoxyribonucleic acid (DNA) immunoelectrophoresis, antibodies against single-strand DNA and DNA. However, a definite association with antinuclear-factor activity and a weak association with latex-fixation tests were found. Association of specificity was tested against 18 different HL-A specificities, and antibodies against HL-A11, Te54, Te56 and Te59 were frequently observed.
Influence of Tumor Necrosis Factor-Alpha-Thymosin-Alpha1 on the Humoral and Cellular Immunity of Patients with Locally Advanced Breast Cancer
Authors: L.Y. Vladimirova, N. Podzorova, E. Zlatnik, G. Zakora, A. Bakhtin, V. Myagkova
Journal: Annals of Oncology (2014)
ECHOCARDIOGRAPHIC PROGNOSTIC MARKERS IN CONNECTIVE TISSUE DISEASE ASSOCIATED PULMONARY HYPERTENSION DIFFER FROM IDIOPATHIC PULMONARY HYPERTENSION
Authors: Srinivas Vunnam, Rishin Handa, Masataka Sugahara, Akiko Goda, Omar Batal, Michael Mathier, John Gorcsan
Journal: Journal of the American College of Cardiology (2016)
Abstract 5177: Primary tumor induces lymphangiogenesis and immune suppression in sentinel lymph nodes
Authors: Kazuaki Chikamatsu, Hiroki Ishii, Koichi Sakakura, Masanori Miyata, Keisuke Masuyama
Journal: Cancer Research (2011)

Abstract The main factor that affects the prognosis of patients with squamous cell carcinoma of the head and neck (SCCHN) is regional lymph node metastases, which usually spreads first to the sentinel lymph nodes (SLNs). Recent studies using animal models have demonstrated that tumor cells can induce lymphangiogenesis in SLNs before metastasizing. In this study, we investigated the association of SLN lymphangiogenesis with the status of primary tumors. Moreover, the immunological status of SLNs was also examined. The expression of lymphatic-specific markers, including VEGFR-3, Prox-1, and LYVE-1 in 23 metastasis-negative SLNs obtained from 10 patients with SCCHN was investigated using quantitative real-time RT-PCR. Moreover, primary tumors obtained from patients were evaluated for the expression of VEGF-A, -C, and -D by immunohistochemistry. The level of LYVE-1 expression in SLNs was significantly higher than in control lymph nodes from patients with non-cancerous diseases. Moreover, SLNs from patients with VEGF-C-positive tumor showed a significantly higher expression of VEGFR-3 than those from patients with VEGF-C-negative tumor. VEGFR-3 is expressed mainly in lymphatic endothelium but also in a subset of antigen-presenting cells including immature dendritic cells (DCs), therefore; we furthermore examined the infiltration of DCs into SLN by immunohistochemistry. Interestingly, S-100+ and CD1a+ immature DCs infiltrated significantly into SLNs compared to non-SLNs in patients with SCCHN, suggesting that predominant migration of immature DCs, which suppress T-cell activation and support regulatory T cell development, would contribute to inhibit rather than develop anti-tumor immunity. Our findings suggest that primary tumor actively induces lymphangiogenesis in SLNs prior to the onset of metastases, and where tumor-derived VEGF-C plays an important role. Moreover, active lymphangiogenesis may concomitantly lead to down-regulation of SLN immunity. Thus, both lymphangiogenesis and immune suppression in SLNs are likely the basis of its susceptibility to tumor metastases. 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 5177. doi:10.1158/1538-7445.AM2011-5177
Dexamethasone in the Treatment of Acute Mountain Sickness
Authors: Benjamin D. Levine, Kazuhiko Yoshimura, Toshio Kobayashi, Masao Fukushima, Toshishige Shibamoto, Gou Ueda
Journal: New England Journal of Medicine (1989)

Cerebral edema occurs in fatal cases of acute mountain sickness. Dexamethasone, commonly used to treat cerebral edema due to other causes, also reduces the symptoms of acute mountain sickness when given prophylactically. However, the efficacy of dexamethasone in the treatment of established acute mountain sickness remains uncertain. To investigate this question, we exposed six men in a hypobaric chamber to a simulated altitude of 3700 m (barometric pressure, 64 kPa [481 mm Hg]) for 48 hours on two occasions. Acute mountain sickness was diagnosed with use of a symptoms questionnaire, and dexamethasone (4 mg every six hours) or placebo was then given in a randomized, double-blind, cross-over fashion. Dexamethasone reduced the symptoms of acute mountain sickness by 63 percent (P<0.05), whereas placebo had a minimal effect (reduction by 23 percent; P not significant). In spite of this response, one subject had mild cerebral edema on brain CT after both placebo and dexamethasone. Dexamethasone had no effect on fluid shifts, oxygenation, sleep apnea, urinary catecholamine levels, the appearance of chest radiographs or perfusion scans, serum electrolyte levels, hematologic profiles, or the results of psychometric tests. Dexamethasone treatment was complicated by mild hyperglycemia in all subjects (mean [±SE] glucose level, 7.3±1.3 mmol per liter [132±23 mg per deciliter]). We conclude that dexamethasone effectively reduces the symptoms of acute mountain sickness. However, it did not improve objective physiologic abnormalities related to exposure to high altitudes. We therefore recommend that dexamethasone be used only when descent is impossible, or to facilitate cooperation in evacuation efforts. (N Engl J Med 1989; 321:1707–13.)
Abstract P1-14-19: Breast-Conserving Surgery after Neoadjuvant Chemotherapy is Oncologically Safe for Stage III Breast Cancer Patients
Authors: H-C Shin, W Han, H-G Moon, S-A Im, S-J Park, D-Y Noh
Journal: Cancer Research (2012)

Abstract Background The use of breast-conserving surgery (BCS) in patients with large breast tumors downstaged by neoadjuvant chemotherapy (NCT) remains controversial in clinical stage III breast cancer patients because of the possibility of residual tumor and resistance to NCT. The aims of this study were 1) to evaluate the local recurrence (LR) rate depending on the use of NCT and 2) to determine the oncologic safety of BCS after NCT by comparing LR between patients treated with preplanned/downstaged BCS and patients treated with NCT and mastectomy in clinical stage III breast cancer patients. Patients and Methods Between 2000 and 2007, 166 patients with clinical stage III breast cancer received BCS or mastectomy after NCT (NCT group) and 193 patients with clinical stage III breast cancer who underwent surgery first (Surgery group). Among 166 patients of the NCT group, 94 patients (56.6%) received mastectomy after NCT (mastectomy after NCT group), 39 patients (23.5%) received preplanned BCS (preplanned BCS group) and 33 patients (19.9%) received downstaged BCS (downstaged BCS group). The LR rates between the groups were compared. Results At a median follow-up period of 66.9 months (range, 6.5 to 104.1 months), 11 patients in the NCT group and 7 patients in the Surgery group had developed LR. The 5-year LR-free survival rates were 93.6% in the NCT group and 95.9% in the Surgery group and the LR rates were not significantly different between the groups (p = 0.196). In the NCT group, LRs were observed in 6 patients in the mastectomy after NCT group, 3 patients in the preplanned BCS group and 2 patients in the downstaged BCS group. The 5-year LR-free survival rates were 94.4% in the mastectomy after NCT group, 92.0% in the preplanned BCS group and 93.9% in the downstaged BCS group, respectively (p = 0.953). Conclusions Our study demonstrated that the LR was not different depending on the use of NCT in the clinical stage III breast cancer patients. Also, clinical stage III breast cancer patients who received preplanned or downstaged BCS after NCT showed similar LR-free survival rates compared to patients who received mastectomy after NCT. This result supports that BCS after NCT in clinical stage III patients is oncologically safe in terms of LR if primary breast tumor size has became 5cm or less after NCT. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-14-19.