tbuckley/cabot-search huggingface dataset:
FRI0122 Long-term effects of etanercept and certolizumab pegol treatment on vascular function and lipid parameters in rheumatoid arthritis
Authors: E. Végh, G. Kerekes, A. Váncsa, F. Balázs, L. Pogácsás, I. Pál, S. Szántó, G. Szücs, Z. Szekanecz
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Cardiovascular (CV) morbidity and mortality are increased in patients with rheumatoid arthritis (RA). Biologics may influence vascular function and lipids in RA, however, most studies have been short-term and less information has become available on etanercept (ETN) and certolizumab pegol (CZP). <h3>Objectives</h3> We wished determine the effects of these TNF blockers on common carotid intima-media thickness (ccIMT), brachial artery flow-mediated, endothelium-dependent vasodilatation (FMD) and the arterial stiffness marker pulse wave velocity (PWV) in context with laboratory assessments in RA patients after 12 months of biological therapy. <h3>Methods</h3> Twenty-six patients (22 female, 4 male) were studied. They received either ETN or CZP for 12 months. Brachial and carotid ultrasonography was performed to determine FMD, ccIMT and PWV, respectively. We also assessed immunological, inflammatory and metabolic laboratory markers. <h3>Results</h3> At baseline, meanccIMT was 0.56 mm (normal range: 0.4-0.9 mm), mean FMD was 6,5% (normal: &gt;10%) and the mean PWV was 8.4 m/s (normal range: 4-20m/s). At baseline, ccIMT correlated with disease duration (R=0.446, p=0.015), while FMD and PWV did not. ccIMT (R=0.393, p=0.023) and PWV (R=0.511, p=0.005) also correlated with age at RA onset. PWV correlated with serum triglyceride levels. After 12 months of anti-TNF treatment, DAS28 (p&lt;0.001), CRP (p=0.004). FMD (p=0.04) and PWV (p=0.035) significantly improved. <h3>Conclusions</h3> In patients with RA, FMD, a marker of endothel dysfunction and PWV, a marker of arterial stiffness significantly improved after 12 months of anti-TNF treatment with ETN or CZP. ccIMT may require more time to improve. <h3>Disclosure of Interest</h3> None Declared
Serologic Studies in the Diagnosis and Management of Meningitis Due to<i>Sporothrix schenckii</i>
Authors: E. Nan Scott, Leo Kaufman, Aline C. Brown, Harold G. Muchmore
Journal: New England Journal of Medicine (1987)

Eight patients have previously been reported to have central nervous system infections caused by Sporothrix schenckii. In those patients the fungus proved quite difficult to culture, delaying correct diagnosis and treatment. We describe seven additional patients with sporotrichosis meningitis, all of whom had antibody to this fungus in cerebrospinal fluid and serum. The antibody in the cerebrospinal fluid was most likely produced locally, as evidenced by its oligoclonality and the relatively high ratio of immunoglobulin to albumin in the cerebrospinal fluid as compared with the serum. Only one of these seven patients, who had active sporotrichosis of the knee joint, had obvious extrameningeal infection. None of 130 patients with meningitis known to be caused by other agents and none of 170 patients with other neurologic disorders had antibody to S. schenckii in their cerebrospinal fluid. We suggest that cerebrospinal fluid should be tested for S. schenckii antibody (in addition to other fungal agents) in any patient with chronic meningitis for which no cause is discovered by the usual diagnostic tests.
AB0185 Increased Corticotropin-Releasing Hormone (CRH) Expression in Cutaneous Lupus Lesions
Authors: M. Schmitz, D.C. Botte, E. Bonfá, E.F. Borba, S.B. Mello
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Corticotropin-releasing hormone (CRH) and the pro-opiomelanocortin (POMC) axis activation leads to the production of several bioactive hormones such as adrenocorticotrophic hormone (ACTH) and the neuropeptide α-melanocyte stimulating hormone (α-MSH). In systemic lupus erythematosus (SLE), the prototype of autoimmune disease with a high frequency of skin involvement. There are no data concerning the possible role of CRH and MCs in the physiopathology of its cutaneous lesions. <h3>Objectives</h3> Thus, the aim of the present study was to evaluate if CRH and POMC axis activation underlies the cutaneous inflammatory response in SLE patients <h3>Methods</h3> Seventeen SLE patients were clinically evaluated and biopsies from affected and unaffected skin were compared to 17 healthy subjects. Immunohistochemical analysis for CRH, ACTH, a-MSH, and MC-1R were performed. Cytokine serum levels (IL-1, IL-1Ra, IL-6, IL-10, IL-12p70, IL-17, TNF-a, IFN-γ) was evaluated by multiplex bead-based immunoassay. <h3>Results</h3> Interestingly, affected skin of SLE patients exhibited higher CRH expression in the deep dermis compared to controls (figure, p=0.024), in contrast, no difference regarding CRH expression in the epidermis was observed comparing affected and unaffected skin of SLE patients and health skin (p=0.353). Tissue expression of ACTH, cortisol, a-MSH and its receptor MC-1R were comparable in SLE and controls. Significantly higher serum levels of IFN-g (p=0.041), TNF-a (p=0.001) and IL-6 (p=0.049) were observed in SLE while a-MSH serum levels were alike in both groups. <h3>Conclusions</h3> The novel finding of elevated CRH expression solely in affected skin deep dermis supports the notion of a cutaneous local dysfunction of CRH-POMC axis in the pathogenesis of cutaneous SLE lesions. <h3>Acknowledgements</h3> Supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP #09/54549-8) <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1492
Thyroid Function after Surgical Treatment of Thyrotoxicosis
Authors: Anthony D. Toft, W. James Irvine, Ian Sinclair, Donald McIntosh, John Seth, Euan H. D. Cameron
Journal: New England Journal of Medicine (1978)

We assessed thyroid function for 12 months after subtotal thyroidectomy in 100 tyrotoxic patients treated with propranolol alone before and immediately after operation. The operation proved safe, with low morbidity. Suppression of the hypothalamic-pituitary-thyroid axis, present in the majority one month after operation, was evidenced by normal or low levels of serum total tri-iodothyronine and thyroxine, but absent or subnormal serum thyrotropin response to thyrotropin-releasing hormone. Eighty patients were euthyroid at 12 months. Three patterns of thyroid function were observed in this group between the first and 12th months: normal serum total tri-iodothyronine, thyroxine and thyrotropin levels at all stages (20 patients); normal serum total tri-iodothyronine and thyroxine, but raised thyrotropin levels on one or more occasions (40 patients); and temporary hypothyroidism (20 patients). Of the remaining 20 patients, permanent hypothyroidism developed in 14, and six relapsed. Postoperative thyroid function was related to the estimated weight of the thyroid remnant.
AB0046 Serum S100A12 May be a Useful Biomarker of Disease Activity in Adult-Onset Still's Disease
Authors: H.-A. Kim, C.-H. Suh, C.-B. Bae, J.-Y. Jung, J.-Y. Nam, J.-Y. Jeon
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> S100A12 is a calcium binding protein of extracellular receptor for advance glycation end products-binding protein (EN-RAGE). S100A12 is secreted in inflamed tissues or in the bloodstream by activated neutrophils. S100A12 mediates the proinflammatory effects on lymphocytes, endothelial cells, and neutrophils. Soluble RAGE (sRAGE) acts as a naturally occurring inhibitor of RAGE by neutralizing proinflammatory ligands including S100A12. <h3>Objectives</h3> S100A12 and sRAGE have been suggested as biomarkers of disease activity in patients with systemic juvenile idiopathic arthritis. We investigated the clinical significance of these in adult onset Still9s disease (AOSD). <h3>Methods</h3> Blood samples were collected from 37 active AOSD patients and 38 normal controls (NC). Of the AOSD patients, follow-up samples were collected from 19 patients after resolution of disease activity. <h3>Results</h3> Serum S100A12 (547.9±148.4 ng/mL) in AOSD patients was higher than those of NC (272.3±133 ng/mL, <i>p</i>&lt;0.001). The sRAGE levels of AOSD (514.1±273.6 pg/mL) were lower than those of NC (850.3±405.8 pg/mL, <i>p</i>&lt;0.001). Serum S100A12 correlated with serum sRAGE (ρ=-0.228, p=0.049). Serum S100A12 correlated with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), ferritin, and systemic score, however the sRAGE did not correlate with any disease activity markers. In addition, S100A12 was decreased after disease activity was resolved in followed-up AOSD patients (505.7±161.3 ng/mL vs. 361.3±162.5 ng/mL, <i>p</i>=0.01). Furthermore, the change of S100A12 was well correlated with that of ESR, CRP, and systemic score. <h3>Conclusions</h3> The data suggest that serum S100A12 may be a useful biomarker for evaluating disease activity in AOSD patients. Furthermore, inverse regulation of both sRAGE and its proinflammatory ligand S100A12 could contribute to promoting systemic inflammation of AOSD. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2211
P385 MICROBIOTA PROFILING IN PSC AND CONTROL PATIENTS: A PILOT STUDY
Authors: N.G.M. Rossen, S. Fuentes, K. Boonstra, G.R.A.M. D'Haens, H.G.H.J. Heilig, E.G. Zoetendal, W.M. de Vos, C.Y. Ponsioen
Journal: Journal of Hepatology (2014)
Intramuscular Interferon Beta-1A Therapy Initiated during a First Demyelinating Event in Multiple Sclerosis
Authors: Lawrence D. Jacobs, Roy W. Beck, Jack H. Simon, R. Phillip Kinkel, Carol M. Brownscheidle, Thomas J. Murray, Nancy A. Simonian, Peter J. Slasor, Alfred W. Sandrock
Journal: New England Journal of Medicine (2000)

Treatment with interferon beta has been shown to help patients with established multiple sclerosis, but it is not known whether initiating treatment at the time of a first clinical demyelinating event is of value.
Rapid Loss of Vertebral Mineral Density after Renal Transplantation
Authors: Bruce A. Julian, David A. Laskow, Jiri Dubovsky, Eva V. Dubovsky, John J. Curtis, L. Darryl Quarles
Journal: New England Journal of Medicine (1991)

Osteopenia is a major complication of renal transplantation. Immunosuppressive regimens including cyclosporine, which permit the use of lower doses of glucocorticoids, may reduce glucocorticoid-induced osteopenia.
Open label, randomized, phase II study of pertuzumab (P) in patients (pts) with metastatic breast cancer (MBC) with low expression of HER2
Authors: J. Cortes, J. Baselga, P. Kellokumpu-Lehtinen, G. Bianchi, D. Cameron, D. Miles, S. Salvagni, A. Wardley, J.-C. Goeminne, L. Gianni
Journal: Journal of Clinical Oncology (2005)

3068 Background: P is the 1st of a new class of targeted therapeutics known as HER-dimerization inhibitors (HDI). It blocks ligand-associated heterodimerization of HER2 with other HER kinase family members, thereby inhibiting intracellular signaling. Preclinical activity of P in breast cancer has been shown to be independent of the HER2 expression level. In this study the primary endpoint was response rate according to RECIST. Secondary endpoints were: rate of stable disease (SD), toxicity profile, pharmacokinetics (PK). Methods: 79 pts in total were randomized to receive P every 3 weeks as an IV infusion either at 420 mg with a loading dose of 840 mg (arm A) or at 1050 mg (arm B). Selection criteria were: progressing MBC with low HER2 expression, anthracycline pretreatment, ≤ 2 chemotherapy regimens for MBC and LVEF ≥ 50%. Results: Out of 79 recruited pts, 78 were included in the intent to treat population. In arm A 2 partial responses (PR) and 18 SD were observed in 41 pts. In arm B 14 SD were observed in 37 pts. Overall, 6 out of 78 pts responded or had SD for > 6 months. Most frequent adverse events were: diarrhea grade (G) 1 & 2 51%, G3 8%, fatigue G 1 & 2 35%, G3 2%, nausea G 1 & 2 31%, G3 1% and vomiting G 1 & 2 23%, G3 4%. Drops in LVEF of ≥10% and to below 50% were observed in 3 pts (1 case of congestive heart failure) in arm A & 3 pts in arm B. PK data supports a fixed dose of P administered every 3 weeks. Conclusions: No obvious relationship between dose and activity or toxicity was observed. The monoclonal antibody P administered IV every 3 weeks is safe and well tolerated but there is evidence of limited activity in this BC study. A combination (either chemo or hormonal) or patient selection strategy may be investigated in the future. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis, Nordic, Roche Genentech, Roche Aventis, Lilly Oncology, Pierre Fabre, Roche Roche
INFLAMMATORY BIOMARKER IL-6 PREDICTS HEART FAILURE IN WOMEN WITH SIGNS AND SYMPTOMS OF ISCHEMIA AND NO OBSTRUCTIVE CORONARY ARTERY DISEASE: FINDINGS FROM THE NHLBI-SPONSORED WOMEN’S ISCHEMIC SYNDROME EVALUATION (WISE) STUDY
Authors: Ahmed AlBadri, Janet Wei, Puja Mehta, Sofy Landes, Quanlin Li, Delia Johnson, Steven E. Reis, Sheryl F. Kelsey, Diane Thompson, Vera Bittner, George Sopko, Leslee J. Shaw, Carl J. Pepine, C. Noel Bairey Merz
Journal: Journal of the American College of Cardiology (2016)
Abstract 3834: 3-ethynyl-1H-indazoles as inhibitors of PI3k signaling pathway
Authors: Elisa Barile, Surya De, Coby B. Carlson, Vida Chen, Christine Knutzen, Megan Riel-Mehan, Russell Dahl, Gary Chiang, Maurizio Pellecchia
Journal: Cancer Research (2011)

Abstract A new series of 3-ethynyl-1H-indazoles has been synthesized and evaluated in both biochemical and cell-based assays as potential kinase inhibitors. Interestingly, a selected group of compounds identified from this series exhibited low micromolar inhibition against critical components of the PI3K pathway, targeting PI3K, PDK1 and mTOR kinases. Combination of computational modeling and structure-activity relationships studies reveal a possible novel mode for PI3K inhibition, resulting in a PI3Kα isoform specific compound. Hence, by targeting the most oncogenic mutant isoform of PI3K, the compound displays anti-proliferative activity both in monolayer human cancer cell cultures and in three-dimensional tumor models. Because of its favorable physicochemical, in vitro ADME and drug-like properties, we propose that this novel ATP mimetic scaffold could result useful in deriving novel selecting and multi-kinase inhibitors for clinical use. 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 3834. doi:10.1158/1538-7445.AM2011-3834
AB0476 The Results of Total Hip Prosthesis in Rheumatoid Arthritis Patients
Authors: S. Lapshina, I. Akhtyamov, I. Gilmutdinov, L. Myasoutova
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To review the results of total hip prosthesis in rheumatoid arthritis patients according to baseline disease activity <h3>Methods</h3> Total hip prosthesis was used on 36 RA patients (32 women, 4 men) with a mean age of 49,5±15,82 years. Disease duration at the time of surgery was 12,45±5,53 years. High disease activity by DAS28 was observed in 10 patients (27.8%), moderate - in 19 (52.8%), low - in 7 (19.4%) patients, the mean DAS28 4,5±1,7. At the time of surgery (before and after), 24 (66.7%) of the patients continued to take basic anti-rheumatic drugs (DMARDs) - (methotrexate 7.5-15 mg per week -15, leflunomide - 7, sulfasalazine - 2). 6 (16.6%) patients received biological therapy: infliximab - 2, adalimumab -1, rituximab - 3, which were canceled before the operation in accordance with the terms specified in the national guidelines. 19 (52.8%) patients received steroids, of which, in combination with DMARDs - 7 (19.4%). Before the surgery, in the postoperative period and after 6 months joint pain on a visual analogue scale (VAS), the activity of the disease - DAS28, functional capacity index HAQ have been evaluated <h3>Results</h3> For 6 months after surgery VAS decreased by 2.5 times to 31,7±19,4 mm (p&lt;0.05), disease activity decreased (high - 4 (11.1%), moderate 17 (47.2%), low -15 (41,7%)), D DAS28 =1,1±0,7, HAQ index decreased from 1,63±0,91 to 1,04±0, 78 (p&lt;0.05). VAS in patients receiving steroids alone (n=12) was - 24,9±18,6 mm, steroids + DMARD (n=7) - 29,1±19,7 mm, only DMARDs (n=11) 34,8±18,9 mm, biological therapy + DMARD (n=6) 37,4±20,8 mm. Activity decreasing - D DAS28 – did not depend from treatment. Functional capacity in patients in the group (n=17), receiving DMARDs with or without biological therapy (D HAQ = -0,69±0,34) compared to patients receiving steroids without basic therapy (n=12) - D HAQ = -0,48±0,31 was significantly better improved (p&lt;0.05). Deep vein thrombosis complication was observed in one patient treated with steroids, the development of soft-tissue infection of the operated joint, required the use of antibiotics in one patient treated with steroids at the time of surgery. <h3>Conclusions</h3> Total hip prosthesis is an effective way to improve functional capacity, to relieve pain and to reduce the activity of RA. Functional ability after surgery is higher in patients using DMARDs continuously and receiving biological therapy compared to patients receiving steroids. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3547
Throat Clearing — A Novel Asthma Symptom in Children
Authors: Eva C. Mantzouranis, Sosipatros A. Boikos, Gregory Chlouverakis
Journal: New England Journal of Medicine (2003)

Throat Clearing -A Novel Asthma Symptom in Childrento the editor: The diagnosis of asthma in children is based largely on symptoms and physical findings, since tests of lung function are often difficult to obtain.Although wheeze and cough are commonly recognized as symptoms of asthma, other asthma symptoms may not be recognized.We report here on throat clearing as a lone, and previously underrecognized, symptom of asthma.We distributed 2690 questionnaires, based on those used in the International Study of Asthma and Allergies in Childhood, 1 to parents of children attending 70 day-care centers in 2 cities and 32 villages in Crete, Greece.The questionnaire was modified, on the basis of our experience, to include an additional question: "Does your child have a habit of clearing his or her throat often?"Parents of 2609 children (97.0 percent) returned completed questionnaires.The mean (±SD) age of the children was 4.3±1.2years.The prevalence of asthma diagnosed by a physician within the previ-
Tl-201 Imaging in a Malignant Peripheral Nerve Sheath Tumor
Authors: REIKO ITAGAKI, EIJI OHTAKE, SHO MATSUBARA, YASUHIRO KIDO
Journal: Clinical Nuclear Medicine (2000)

A 29-year-old man with neurofibromatosis type 1 (von Recklinghausen’s disease) had a large tumor in the left side of his back. A Tl-201 chloride SPECT early image showed abnormal uptake of Tl-201 corresponding to the back tumor. The delayed image showed decreased accumulation in the tumor compared with the early image. The tumor was excised and measured 6 × 5.5 × 3.5 cm. Pathologic examination indicated a malignant peripheral nerve sheath tumor with myxoid and necrotic changes, despite the rapid clearance of Tl-201.
Association between febrile neutropenia and use of G-CSF in chemotherapy of extensive-disease small-cell lung cancer
Authors: Takumi Fujiwara, Tetsuhiko Taira, Kazushige Wakuda, Akira Ono, Hirotsugu Kenmotsu, Tateaki Naitou, Haruyasu Murakami, Keita Mori, Masahiro Endou, Toshiaki Takahashi
Journal: Annals of Oncology (2015)
Abstract 3127: Protein kinase D1 downregulation facilities PMA-induced apoptosis in LNCaP prostate cancer cells
Authors: Jun Chen, Karthik V. Giridhar, Qiming Jane Wang
Journal: Cancer Research (2010)

Abstract Phorbol esters, analogs of diacylglycerol, induce apoptosis in androgen-sensitive LNCaP prostate cancer cells. Although the apoptotic pathways induced by PMA are well characterized, little is known of PMA-regulated pro-survival pathways such as ERK1/2 and Akt. We now provide experimental evidence to indicate that PKD1 promotes survival signals in LNCaP cells in response to PMA treatment. In turn, PMA induces dose- and time-dependent downregulation of PKD1 to facilitate apoptosis. This effect can be blocked by PKC inhibitor Ro 31-8220, indicating that PKC activation is required for PKD1 downregulation. Depletion of endogenous PKCδ and PKCε reveals that PKD1 activation and subsequent downregulation are mainly controlled by PKCδ. Knockdown of endogenous PKD1 and PKD2 decreases ERK1/2 and Akt activities and potentiates PMA-induced apoptosis as measured by cleaved PARP and sub-G0/G1 population, whereas overexpression of wild-type and constitutive-active PKD1 enhances ERK1/2 and Akt activities and suppresses PMA-induced apoptosis. Further analysis shows that the downregulation of PKD1 is mediated by ubiquitin/proteasome degradation pathway. In summary, our data indicate that PKD1 plays a pro-survival role in PMA-induced apoptosis by modulating downstream ERK1/2 and Akt activities. 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 3127.
Dense Breast Tissues May Hold Increased Cancer Risk for Some
Authors: S. Jenks
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Dense Breast Tissues May Hold Increased Cancer Risk for Some 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 86, Issue 8, 20 April 1994, Pages 578–580, https://doi.org/10.1093/jnci/86.8.578 Published: 20 April 1994
Changes in Bronchial Epithelium in Relation to Sex, Age, Residence, Smoking and Pneumonia
Authors: Oscar Auerbach, A. P. Stout, E. Cuyler Hammond, Lawrence Garfinkel
Journal: New England Journal of Medicine (1962)

IN previous investigations, we found a high degree of relation between cigarette smoking and certain changes in the bronchial epithelium of men who had died of causes other than lung cancer.1 2 3 These changes included hyperplasia, loss of cilia, metaplasia and the occurrence of cells with atypical nuclei. What impressed us most was the finding of many lesions composed entirely of cells with atypical nuclei in the bronchial epithelium of cigarette smokers, the number of such lesions increasing with amount of smoking. No such lesions were found in nonsmokers.3 Findings (other than invasive carcinoma) in the bronchial epithelium of men who . . .
COMPUTER-CONTROLLED RADIOCHEMICAL SYNTHESIS: AN AUTOMATED CHEMISTRY PROCESS CONTROL UNIT FOR THE PRODUCTION OF POSITRON-EMITTER LABELED RADIOCHEMICALS.
Authors: D. G. Schmidt, H. C. Padgett, E. Pekrul, F. Picker, P. Kretz, G. O. Hendry
Journal: Clinical Nuclear Medicine (1987)

Schmidt, D. G.; Padgett, H. C.; Pekrul, E.; Picker, F.; Kretz, P.; Hendry, G. O. Author Information