tbuckley/cabot-search huggingface dataset:
FRI0374 Outcomes in Systemic Lupus Erythematosus Patients with High Disease Activity Treated with Belimumab: 18 Month Results from the US Observe Study: Table 1
Authors: C.E. Collins, M. Dall'Era, C. Macahilig, R. Pappu, C. Molta, H. Kan, V. Koscielny
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Certain baseline factors in the BLISS trials were associated with high disease activity and identified as predictors of improved belimumab response. <h3>Objectives</h3> We examined clinical effectiveness of belimumab 10 mg/kg plus standard therapy in systemic lupus erythematosus (SLE) patients with high disease activity in US clinical practice. <h3>Methods</h3> OBSErve US (BLM117295) is a multicentre, retrospective, medical chart review study. Rheumatologists (n=92) randomly identified SLE patients who had received ≥8 belimumab infusions as part of usual care. Clinical measures were assessed 6 months (m) before belimumab initiation (index date), and every 6 m after, up to 2 years. Primary outcome was physician impression of overall change in SLE disease manifestations every 6 m, relative to the previous timepoint. Post hoc analyses examined three patient subgroups with high disease activity at index date: high anti-dsDNA and low complement (C3/C4); steroid dose ≥7.5 mg/day; SELENA-SLEDAI (SS) &gt;10. Safety was not assessed. We present 18-m results. <h3>Results</h3> Of the 501 patient charts examined at 0–6 m, 121 were lost to follow-up/had outstanding data and 46 discontinued by 12 m (multiple reasons permitted: 16 patient request, 12 medication not effective, 9 lack of patient compliance, 8 disease progression, 3 insurance/reimbursement loss, 2 sepsis, 2 depression). 334 patients remained at 12–18 m; at index date 70.7% received steroid doses ≥7.5 mg/day; 53.0% had high anti-dsDNA and low C3/C4; 74.5% of 102 patients with available SS data scored &gt;10. Characteristics across groups at index date appear similar (Table). SLE disease manifestations improved from 12–18 m (Table 1); only changes in the high anti-dsDNA and low C3/C4 subgroup were significantly different vs the remaining sample. Since index date all groups had mean SS score reductions of ≥8.5 at 18 m (in patients with available data) and mean steroid dose reductions of ≥14.9 mg/day (Table 1). <h3>Conclusions</h3> Based on physician impression, overall clinical response improved from 12–18 m with belimumab plus standard therapy; high anti-dsDNA and low C3/C4 patients had better responses vs the remaining sample. <h3>Disclosure of Interest</h3> C. Collins Consultant for: GlaxoSmithKline, M. Dall9Era Consultant for: GlaxoSmithKline, C. Macahilig Grant/research support: GlaxoSmithKline, R. Pappu Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, C. Molta Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, H. Kan Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, V. Koscielny Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4968
Occurrence of Ophthalmopathy after Treatment for Graves' Hyperthyroidism
Authors: L Tallstedt, G Lundell, O Tørring, G Wallin, J G Ljunggren, H Blomgren, A Taube
Journal: New England Journal of Medicine (1992)

Ophthalmopathy caused by Graves' disease may first appear or worsen during or after treatment for hyperthyroidism. It is not known, however, whether choosing to treat hyperthyroidism with antithyroid drugs, iodine-131, or surgery affects the development or aggravation of Graves' ophthalmopathy.
18F-Fluoride PET/CT Scan for Quantification of Bone Metabolism in the Inner Ear in Patients With Otosclerosis—A Pilot Study
Authors: Jérôme J. Waterval, Maud Vallinga, Boudewijn Brans, Bjorn Winkens, Robert J. Stokroos
Journal: Clinical Nuclear Medicine (2013)

In otosclerosis, CT of the temporal bone is used to confirm the diagnosis. Whereas CT is a static diagnostic tool displaying the demineralization caused by otosclerosis, imaging of bone metabolism by (18)F-fluoride PET may provide quantitative information. This could be useful for prognosis and stratification of patients. The aim of this study was to assess (18)F-fluoride activity in patients with otosclerosis and to evaluate its use as a complementary diagnostic tool.All patients with otosclerosis underwent a PET/CT scan. Audiometric data were collected. The severity of otosclerosis was assessed using a recognized radiological classification. The control group consisted of patients who had undergone (18)F-fluoride PET/CT scan for orthopedic purpose. Regions of interest were drawn on PET scans which corresponded to standardized anatomical sites as defined on CT, to measure bone metabolism using standardized uptake values (SUV(max) and SUV(mean)).Group 1 consisted of 11 otosclerosis patients (16 eligible temporal bones) and group 2 consisted of 5 control patients (10 temporal bones). On PET scan, visual assessment of temporal bones with otosclerosis showed increased metabolic activity in the otic capsule in 11/16 cases. The SUV(max) in the entire otic capsule was significantly higher in otosclerosis patients compared to control subjects. Significant differences in SUV(mean) were found between otosclerosis and control subjects in the fenestral and saccule area. Moreover, metabolic activity in these regions significantly correlated with hearing loss and CT classification.(18)F-Fluoride PET scanning using SUV measurements has the potential to be a diagnostic tool in otosclerosis.
SAT0558 Vegf Promotes RANKL Expression and Osteoclastogenesis in Rheumatoid Arthritis
Authors: H.R. Kim, H.-H. Kim, S.-H. Lee
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Vascular endothelial growth factor (VEGF) is an angiogenic, inflammatory, and bony destructive molecule in the pathogenesis of rheumatoid arthritis (RA). <h3>Objectives</h3> This study was aimed to determine the specific role of VEGF on the osteoclastogenesis in RA. <h3>Methods</h3> The expression of VEGF, CD55, and receptor activator of nuclear factor kB ligand (RANKL) in RA synovial tissues was analyzed using confocal microscopy. VEGF-induced RANKL expression was determined in RA synovial fibroblasts using reverse transcription PCR, luciferase assays and ELISA. Osteoclastogenesis was assessed by counting tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells from the culture of isolated CD14+ monocytes with VEGF in the presence of signal inhibitors. Osteoclastogenesis was also determined after co-culture of monocytes with VEGF–pretreated synovial fibroblasts and CD4+ T cells. <h3>Results</h3> There was co-expression of VEGF, RANKL and CD55 in lining and sublining area of RA synovium. The RANKL level correlated with the VEGF level in synovial fluid from RA patients. VEGF stimulated the expression of RANKL mRNA in RA synovial fibroblasts and RANKL promoter activity was upregulated by VEGF in the synovial fibroblasts transfected with RANKL reporter plasmids. VEGF-induced RANKL expression was decreased by the inhibition of Src and PKC. VEGF induced osteoclast differentiation from peripheral blood monocytes in the absence of RANKL. When monocytes were co-cultured with VEGF-prestimulated RA synovial fibroblasts, monocytes were differentiated into osteoclasts and the osteoclastogenesis decreased with inhibition of Src and PKC signaling. <h3>Conclusions</h3> VEGF plays dual roles on osteoclastogenesis in RA: induction of osteoclastogenesis from the precursors and direct stimulation of RANKL production in synovial fibroblasts, mediated by Src and PKC pathways. The axis of VEGF and RANKL could be a potential therapeutic target for RA-associated bone destruction. <h3>References</h3> Lee SS, Joo YS, Kim WU, Min DJ, Min JK, Park SH, et al. Vascular endothelial growth factor levels in the serum and synovial fluid of patients with rheumatoid arthritis. Clinical and experimental rheumatology. 2001;19(3):321-4. Harada M, Mitsuyama K, Yoshida H, Sakisaka S, Taniguchi E, Kawaguchi T, et al. Vascular endothelial growth factor in patients with rheumatoid arthritis. Scandinavian journal of rheumatology. 1998;27(5):377-80. Koch AE. Review: angiogenesis: implications for rheumatoid arthritis. Arthritis and rheumatism. 1998;41(6):951-62. <h3>Acknowledgements</h3> This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (NRF-2011-R1A4A007-0026961) <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1254
Phase II trial of KOS-862 (epothilone D) in anthracycline and taxane pretreated metastatic breast cancer
Authors: B. Overmoyer, S. Waintraub, P. A. Kaufman, T. Doyle, H. Moore, M. Modiano, J. Kroener, X. Zhang, A. Buzdar, M. Demario
Journal: Journal of Clinical Oncology (2005)

778 Background: KOS-862 (K) is genetically-produced epothilone D, a naturally occurring macrolide. K has preclinical activity in multiple breast cancer models, including taxane-resistant cell lines. A phase II trial was implemented to determine antitumor activity of K in women with anthracycline (A) and taxane (T) pretreated metastatic breast cancer (MBC). Methods: Pts with MBC + A & T treatment failure are eligible. Treatment failure is defined as disease progression after receipt of both A and T (adjuvant or metastatic setting) or inability to tolerate these agents (toxicity). All pts are ECOG 0–1. Pts with baseline neuropathy > gr 1 or CNS metastases are excluded. K administered as 100 mg/m2 iv over 90 min wkly x 3 Q 4 wks. H1 + H2 antagonists & corticosteroids are given 30–60 min before K as infusion reaction prophylaxis. PK sampling for K + its seco-metabolite collected up to 48 hr post C1D1. Results: 12 women (10 evaluable) have received K. Mean number of K cycles 2.6 (1–6). Three pts had > 4 K cycles. Two pts have had confirmed PR, including 1 pt with hepatic-metastases who had > 50% tumor reduction & normalization of CA 27–29. This pt’s prior treatments include adjuvant AC+T and 6 mo. docetaxel for metastatic disease shortly before trial entry. K-related toxicities (event/grade-#pts) include: peripheral neuropathy (1–2, 2–4, 3–1), paresthesia/hypoesthesia (1–4, 2–1), ataxia (2–1, 3–1), cognitive disorder (2–1), dizziness (1–2), diarrhea (1–4), nausea (1–2), anorexia (2–1), flushing (1–1, 2–1), & fatigue (1–4). Several pts with neurotoxicity (including responders) have been successfully retreated with K dose reduction (75 mg/m2). PK: mean KOS-862 Cmax 4.6±3.0 μg/mL, AUCinf 26 ± 31 h•μg/mL, Vz 196 ± 137 L and T1/2 12 ± 5 hr. Seco-metabolite 39±25% of K. Conclusions: Initial phase II results demonstrate encouraging antitumor activity for K (2 of 10 eval pts) in A & T pretreated MBC. Pts with K toxicities have been successfully retreated with 25% dose reduction. Accrual is anticipated to 53 evaluable pts in order to determine the antitumor activity of K in MBC. Updated response & PK data will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Hoffmann-La Roche Hoffmann-La Roche
Prenatal Exposure to Phthalates and Childhood Body Size in an Urban Cohort
Authors: Michelle M. Maresca, Lori A. Hoepner, Abeer Hassoun, Sharon E. Oberfield, Stephen J. Mooney, Antonia M. Calafat, Judyth Ramirez, Greg Freyer, Frederica P. Perera, Robin M. Whyatt, Andrew G. Rundle
Journal: Environmental Health Perspectives (2015)

Phthalate exposures are hypothesized to increase obesity; however, prior research has been largely cross-sectional.We evaluated associations between prenatal phthalate exposures and body mass index (BMI) at child ages 5 and 7 years.Nine metabolites of six phthalates-di(2-ethylhexyl) phthalate (DEHP), di-n-octyl-, di-iso-butyl-, di-n-butyl-, butylbenzyl-, and diethyl phthalates-were measured in spot urine samples collected from pregnant African-American and Dominican women during their third trimester, and from their children at ages 3 and 5 years. To reduce multiple comparison issues, we initially used principal component analysis (PCA) to identify major patterns of natural log (ln)-transformed metabolite concentrations. Height and weight were assessed at ages 5 and 7 years, and fat mass and waist circumference at age 7. Linearized generalized estimating equation analyses related maternal component scores to child anthropometric outcomes at ages 5 (n = 326) and 7 (n = 330) years.PCA identified a DEHP component and a non-DEHP component. In boys, higher maternal non-DEHP, but not DEHP, component scores were associated with lower BMI z-score (β = -0.30; 95% CI: -0.50, -0.10, n = 156), lower fat percentage (β = -1.62; 95% CI: -2.91, -0.34, n = 142), and smaller waist circumference (β = -2.02; 95% CI: -3.71, -0.32, n = 124). No significant associations with anthropometric outcomes were seen in girls (for BMI z-score, β = 0.07; 95% CI: -0.18, 0.31, n = 181). Interactions between sex and non-DEHP component association with outcomes were statistically significant (p < 0.01).Contrary to hypotheses, prenatal non-DEHP phthalate exposures were associated with lower BMI z-score, waist circumference, and fat mass in boys during early childhood.Maresca MM, Hoepner LA, Hassoun A, Oberfield SE, Mooney SJ, Calafat AM, Ramirez J, Freyer G, Perera FP, Whyatt RM, Rundle AG. 2016. Prenatal exposure to phthalates and childhood body size in an urban cohort. Environ Health Perspect 124:514-520; http://dx.doi.org/10.1289/ehp.1408750.
FRI0089 Respiratory Morbidity and Mortality in Early Rheumatoid Arthritis: Table 1
Authors: S. Ramanujam, D. Symmons, T. Marshall, J. Chipping, I. Bruce, S. Verstappen
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Respiratory disease is the second commonest cause of death after cardiovascular disease in patients with inflammatory polyarthritis (IP) and its subset rheumatoid arthritis (RA). However, limited data are available on predictors of both respiratory morbidity and mortality. <h3>Objectives</h3> To identify predictors associated with respiratory morbidity and mortality in early IP. <h3>Methods</h3> 942 IP cases with symptom duration &lt;2 years recruited to the Norfolk Arthritis Register (NOAR) between January 1st 2000 and December 31st 2008 were included in this study. At baseline, demographic, clinical and disease activity markers (Table) were collected. Hospital admissions were retrieved from the Hospital Episode Statistics database. Primary and secondary diagnoses of a respiratory event were included and categorized into: i) lung cancer ii) Chronic Lung Disease [CLD] with lung infection iii) CLD without lung infection and iv) others. CLD comprised of COPD, asthma, interstitial lung disease (ILD) and bronchiectasis. Death certificates were provided by the Office of National Statistics. Separate survival analyses were performed for respiratory morbidity and mortality. Patients were followed until their first hospital admission for a respiratory event or death, embarkation date, June 2012 (morbidity analysis) or June 2013 (mortality analysis). The association between baseline predictors and respiratory morbidity or mortality was assessed using Cox proportional regression analysis (HR, 95%CI). <h3>Results</h3> The mean age was 57.8±14.8 years and 57% fulfilled the 2010 EULAR/ACR criteria for RA at baseline. Respiratory morbidity and mortality rates were 28.8 and 4.59 per 1000 person year respectively during 6569 and 8065 person-years follow-up. There were 189 respiratory admissions which included cancer (6.9%), CLD with infection (5.8%), CLD without infection (55.6%), and others (31.7%), comprising mainly of infections without underlying lung disease. There were 37 deaths due to pulmonary causes: lung cancer (43%), COPD (22%), lung infection (16%), ILD (8%), bronchiectasis (3%) and others (8%).Men, smoking status and increased functional disability were significant predictors of both morbidity and mortality. Positive RF and ACPA and high DAS28 score were associated with morbidity with a similar trend in mortality but was not significant due to the low death numbers. Low BMI predicted mortality. <h3>Conclusions</h3> Although traditional risk factors contributed to respiratory morbidity and deaths, markers of disease severity also significantly predicted respiratory morbidity in early IP. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5627
Kinetics of Peritoneal Fluid Absorption in Adult Man
Authors: Leroy Shear, Charles Swartz, James A. Shinaberger, Kevin G. Barry
Journal: New England Journal of Medicine (1965)

THE peritoneal membrane is used extensively as a dialyzing surface for the treatment of uremia, hyperkalemia, overhydration and poisoning with a variety of drugs.1 , 2 It has also been utilized therapeutically by pediatricians for administration of blood,3 , 4 fluid and electrolytes,4 5 6 particularly in areas of the world where nursing personnel are not available to monitor intravenous infusions.Rate of movement of water and solutes from blood to peritoneal fluid has been studied in detail.1 By contrast, little is known about kinetics of fluid absorption. In the present study absorption of isotonic saline solution from the peritoneal cavity was studied in adult human . . .
Intrauterine Growth Retardation and Postnatal Growth Failure Associated with Deletion of the Insulin-Like Growth Factor I Gene
Authors: Katie A. Woods, Cecilia Camacho-Hübner, Martin O. Savage, Adrian J.L. Clark
Journal: New England Journal of Medicine (1996)

Insulin-like growth factor I (IGF-I) mediates the majority of the growth-promoting effects of growth hormone (GH) after birth.1 In the prenatal period, GH does not appear to have a major influence on fetal growth, whereas IGF-I does. Infants with congenital GH deficiency and defects in the GH-receptor gene have only mild retardation of growth at birth,2–4 whereas transgenic mice with a homozygous defect of the IGF-I gene (IGF-I knockout mice) have profound embryonic and postnatal growth retardation.5–7 Although there is no direct evidence that IGF-I has a prominent role in human fetal growth, fetal tissues express IGF-I from . . .
Abstract LB-303: Metastasis suppression by MDM2 binding protein through inhibition of ACTN4 function
Authors: Tomoo Iwakuma
Journal: Cancer Research (2012)

Abstract MDM2 Binding Protein (MTBP) has been implicated in cancer progression. Our previous results demonstrate that MTBP haploinsufficiency in mice enhances cancer metastasis. Recently, loss of MTBP expression is shown to be associated with reduced survival of patients with head and neck carcinoma, and serves as an independent prognostic factor when p53 is mutated in tumors. Here we demonstrate one mechanism by which MTBP inhibits cancer metastasis. Overexpression of MTBP in human osteosarcoma cell lines lacking wild-type p53 did not alter primary tumor growth in mice but significantly inhibited metastases. MTBP downregulation increased the migratory potential of Mdm2-/-p53-/- mouse embryonic fibroblasts, suggesting that MTBP inhibited cell migration independently of the MDM2-p53 pathway. Co-immunoprecipitation and mass spectrometric analysis identified alpha-actinin-4 (ACTN4) as a MTBP-interacting protein. Endogenous MTBP interacted with and partially colocalized with ACTN4. MTBP overexpression inhibited cell migration and filopodia formation mediated by ACTN4. Increased cell migration by MTBP downregulation was inhibited by concomitant downregulation of ACTN4. MTBP also inhibited ACTN4-mediated F-actin bundling. We furthermore demonstrated that nuclear localization of MTBP was dispensable for inhibiting ACTN4-mediated cell migration and filopodia formation. Thus, MTBP suppresses cell migration, at least partially, by inhibiting ACTN4 function. Our study not only provides a mechanism of metastasis suppression by MTBP, but also suggests MTBP as a potential biomarker for cancer progression. 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 LB-303. doi:1538-7445.AM2012-LB-303
AB0861 Genetic Role of Serotonergic System on Pathogenesis of Primer Fibromyalgia
Authors: R.N. Sarıer Ülker, T. Çakır, M. Akyol, N.F. Toraman, I. Sezer, S. Koldaş Doğan, M. Bilgilisoy Filiz
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Fibromyalgia is a chronic pain syndrome, characterized by widespread pain and tenderness at spesific anatomical localizations. <h3>Objectives</h3> The purpose is investigating candidate genes related to the serotonergic system which is thought to be responsible for the pathophysiology of primer fibromyalgia and the validity of serotonin receptor gene polymorphisms for the Turkish society. <h3>Methods</h3> Ninety-six female patients diagnosed with fibromyalgia according to 1990 and 2010 ACR criteria and 96 healthy controls were included in the study. A detailed medical history of the patients were taken, the symptoms were questioned. Assessment of disease activity and functional status were performed with tender point examination and assessment of the severity of the pain, Fibromyalgia Impact Questionnaire. A total of 192 blood samples were taken from the patient and the control group and isolation of DNA was performed. Primer design for serotonin receptor gene was done, the products derived from polymerase chain reaction were cleaned. The analysis of sequence results after the sequence reaction and statistical evaluation were performed. <h3>Results</h3> The regions of serotonin receptor 2A gene were analyzed. According to the analysis, E318E mutation occurring at amino acid 318 which has not caused a change in any amino acid, and V143V mutation which has not caused a change at amino acid 143 were detected for the first time. A similar number of heterozygous polymorphic allele of rs35224115 single-nucleotide polymorphism were found in the patient and control groups. Although, Rs6305 was found as polymorphic heterozygous in 7 samples in the patient grup, it was found in 3 samples in the control group. Although, Rs6314 was found in 3 samples as polymorphic heterozygous in the control group, it was found in 16 samples in the patient group. The difference between the two groups in terms of the incidence of heterozygous allele was statistically significant according to chi-square test (p=0.002). <h3>Conclusions</h3> In our study that we investigate the relationship between fibromyalgia and the exons of serotonin receptor 2A gene which are the protein-coding regions, we found that rs6314 polymorphism associated with the disease. This relationship is a result which can be used and developed for diagnostic and treatment process. We also determined two new possible polymorphism single base change (E318E, V143V), but we did not find any relationship with the fibromyalgia syndrome. We determined that, there was no differce in terms of other known polymorphisms between patients and controls. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4187
Case 23-2007
Authors: Christopher P. Duggan, Sjirk J. Westra, Andrew E. Rosenberg
Journal: New England Journal of Medicine (2007)

A 9-year-old boy with autism was admitted to the hospital because of pain in the hip, rash, and swelling of the gingiva. Three months earlier, pain in his right hip developed, and he eventually refused to walk. Physical examination disclosed no joint swelling, and radiographs of the pelvis and spine were normal. Indomethacin was prescribed; the pain improved, but a petechial rash on the legs and gingival swelling developed.