tbuckley/cabot-search huggingface dataset:
FRI0474 Association of serum vascular endothelial growth factor and angiopoietin-2 levels with clinical manifestations and nailfold capillaroscopic changes in patients with raynaud’s phenomenon
Authors: A. Kuryliszyn-Moskal, J. Kita, S. Chwieśko-Minarowska
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Raynaud's phenomenon (RP) is an exaggerated vasospastic response to cold and emotion, which can be primary (idiopathic) or secondary to a number of different conditions, including rheumatological diseases. Functional and/or structural vascular involvement is a key feature of RP. Nailfold capillary microscopy (NC) is the best technique to investigate microvascular abnormalities and to differentiate between primary and secondary RP. <h3>Objectives</h3> Based on the findings, suggesting an important role of microvascular involvement in the pathogenesis of RP, we evaluated whether the vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang2) serum levels are associated with clinical manifestations and microvascular changes in NC in patients with RP. <h3>Methods</h3> Serum levels of VEGF and Ang2 were determined by an enzyme-linked immunosorbent assay (ELISA) in 78 patients with RP (38 with primary and 40 with secondary RP) and in 30 healthy controls. <h3>Results</h3> Morphological changes in nailfold capillaroscopy were seen in 56 out of 76 (73.7%) patients with RP. A normal capillaroscopic pattern or mild changes were found in 36 (47.3%) and moderate/severe abnormalities - in 40 (52.6%) of all RP patients. In all patients with secondary RP, severe or moderate changes in capillaroscopy were found. The severity of microvascular abnormalities were associated with the frequency and severity of vasospastic episodes as well as with the duration of RP. In the control group no pathological changes in nailfold capillaroscopy were observed. Patients with severe changes in nailfold capillaroscopy showed significantly higher serum levels of VEGF and Ang2 than those without or with mild changes and in the control group. Moreover, there was a significant positive correlation between Ang2 serum levels and the duration of RP as well as the pain severity rating on the VAS scale. <h3>Conclusions</h3> Our findings confirm the usefulness of NC as a non-invasive technique in the evaluation of microvascular involvement in RP patients. Moreover, a relationships between the changes in nailfold capillaroscopy and serum levels of VEGF and Ang2 point to a pathogenic role of these molecules in the clinical manifestation of RP. <h3>Disclosure of Interest</h3> None Declared
AB0138 Mice lacking the alpha 7 nicotinic acetylcholine receptor have increased bone mass
Authors: P. Mandl, S. Hayer, S. Huck, B. Niederreiter, P. Scholze, D. Sykoutri, J.S. Smolen, K. Redlich
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Cholinergic receptors, discovered on bone cells suggest that the cholinergic nervous system may play a regulatory role also in bone metabolism. Our previous experiments have confirmed the presence of nicotinic acetylcholine receptor subunits on osteoclasts, and have revealed that the α<sub>7</sub> nicotinic acetylcholine receptor plays a key role in the regulation of osteoclastogenesis <i>in vitro</i>. <h3>Objectives</h3> To evaluate the role of the α<sub>7</sub> nicotinic acetylcholine receptor in bone homeostasis <i>in vivo</i>. <h3>Methods</h3> We analyzed the bone phenotype of α<sub>7</sub> nicotinic acetylcholine receptor knockout mice (α<sub>7</sub> nAChR<sup>-/-</sup> mice). We investigated the bone phenotype of C57/BL6 α<sub>7</sub> nAChR<sup>-/-</sup> mice as well as sex- and age-matched littermates. For bone mineral density (BMD) measurements we evaluated the proximal tibia and BMD values were calculated by using dual energy X-ray absorptiometry (DEXA). Bone phenotype was further evaluated by histomorphometrical analysis using 2-μm decalcified paraffin-embedded sections stained with hematoxylin and eosin, toluidine blue, and TRAP. Histomorphometry of metaphyses was performed using an Axioskop 2 microscope and OsteoMeasure Analysis System (OsteoMetrics) according to international standards. <h3>Results</h3> We observed no marked macroscopic alterations suggestive of a severe osteopetrotic phenotype (disturbed teeth eruption, shortened limbs) in α<sub>7</sub> nAChR<sup>-/-</sup> mice. However, DEXA revealed a significantly increased trabecular density (+26%) in 16 week old male α<sub>7</sub> nAChR<sup>-/-</sup> mice compared to wild-type littermates. In line with this finding, histomorphometry of α<sub>7</sub> nAChR<sup>-/-</sup> mice also showed increased bone volume/tissuevolume (p≤0.001) as well as increased trabecular thickness (p≤0.001), coupled with reduced trabecular separation (p≤0.001). To further evaluate the pathomechanisms involved, we elaborated the effects of α<sub>7</sub> nAChR on both osteoclasts and osteoblasts. In α<sub>7</sub> nAChR<sup>-/-</sup> mice we found a reduced number of osteoclasts/bone perimeter (p≤0.001) and reduced osteoclast surface/bone surface (p≤0.05), whereas osteoblasts were not affected. <h3>Conclusions</h3> Our investigations have revealed increased bone mass coupled with reduced osteoclastogenesis in mice lacking the α<sub>7</sub> nicotinic acetylcholine receptor subunit. These findings confirm the significance of these receptors in osteoclastogenesis and highlight the important regulatory role of the cholinergic nervous system in bone turnover. <h3>Disclosure of Interest</h3> None Declared
PTU-242 Can endoscopic ultrasound and ERCP be performed safely in the same patient during the same session?
Authors: J S Leeds
Journal: Gut (2012)

<h3>Introduction</h3> ERCP should be considered as a therapeutic modality in the vast majority of cases but some patients may have to wait for the appropriate diagnostic test. Endoscopic ultrasound (EUS) can be used to detect pancreaticobiliary pathology especially in situations where cross sectional imaging techniques have reduced accuracy (eg, &lt;10 mm bile duct stones). When such pathology is identified, same session ERCP theoretically could be performed but there is limited data on safety, patient comfort and complications. The aim of this study was to evaluate a recent service development whereby EUS can be immediately followed by ERCP. <h3>Methods</h3> Our unit performs around 350 ERCP9s and 250 EUS procedures per annum. Since April 2011, there has been facility to perform EUS on the ERCP lists. All referrals are vetted and if deemed appropriate are listed for EUS ± ERCP on the same list. All patients listed for both procedures had their notes reviewed and demographics, indication, sedation requirements, comfort scores, need for ERCP and final diagnosis recorded. Median pethidine dose, midazolam dose and comfort scores were compared in those who EUS and ERCP vs EUS alone. <h3>Results</h3> During the period April 2011–December 2011, 34 patients (median age 72 years) were listed for EUS ± ERCP. Indications for EUS prior to ERCP included dilated ducts (n=13), abnormal enzymes (n=10), other imaging unclear (n=4), possible sphincter of Oddi dysfunction (n=3), fine needle aspiration (n=4). 10/34 (29.4%) patients did not undergo subsequent ERCP as the EUS showed no indication. 16 were found to have bile duct stones, 4 had a neoplasm, 3 had sphincter of Oddi dysfunction and 1 a pancreatic duct stone (all confirmed at ERCP). There were no differences in demographics or indication in patients undergoing EUS and ERCP vs EUS alone. Median midazolam doses were significantly higher in those undergoing both procedures (4 mg vs 3 mg, p=0.002) not median pethidine dose (25 mg vs 25 mg, p=0.12) or comfort scores (1.0 vs 1.0, p=0.25). At ERCP, 18 patients underwent sphincterotomy and duct trawl, five patients had a stent inserted and one patient underwent choledochoscopy. No complications occurred in either group. <h3>Conclusion</h3> EUS and ERCP can be performed safely in the same session but patients often need extra sedation for the second procedure. This does not appear to be detrimental to patients comfort or associated with an increased complication rate. A larger cohort should be examined prospectively and include analysis of list dynamics, cost effectiveness and patient preference. <h3>Competing interests</h3> None declared.
Abstract 3124: Tetraspanin CD151-mediated signaling network between cell-matrix and cell-cell adhesions
Authors: In-Kee Hong, Hansoo Lee, Hee-Jung Byun, Iha Park, Young-Myeong Kim
Journal: Cancer Research (2011)

Abstract CD151 has been suggested to promote cancer invasion and metastasis by regulating adhesion-dependent signaling events through its association with laminin-binding α3β1/α6β1 integrins. Previously, we have demonstrated that homophilic interactions of CD151 stimulate integrin-dependent signaling to c-Jun through the FAK-Src-MAPKs pathways in human melanoma cells. In this study, we found that CD151 plays a role in recruiting Ras, Rac1, and Cdc42, but not Rho, to the membrane region, leading to formation of α3β1/α6β1 integrins-CD151-small GTPases complexes. Adhesion receptor complexes-associated small GTPases were found to be activated by β1 integrins-CD151 complexes-stimulating adhesion events such as interactions of integrins with laminin and homophilic interactions of CD151 on two contacting cells, implicating CD151-mediated signaling network between cell-matrix and cell-cell adhesions. Adhesion-dependent activation of small GTPases appeared to be mediated by the FAK-Src pathways. Meanwhile, EGF and phorbol ester treatment further enhanced CD151-β1 integrin complexes-induced cell motility and MMP-9 expression, along with activation of p38 MAPK and JNK, indicating a positive signaling cross-talk between CD151-β1 integrin adhesion receptor, EGF receptor, and PKC. Using siRNAs and dominant-inhibitory mutant expression constructs for various intracellular signaling mediators, we found that integrin-linked kinase (ILK), PAK1-interacting exchange factor beta (β-PIX), and p21-activated protein kinase 1 (PAK1) were involved in CD151-β1 integrin adhesion receptor complex signaling pathways. Also, MEK3/6 and MEK7 were found to participate in CD151-β1 integrin signaling cascades, upstream of p38 MAPK and JNK, respectively. Taken together, our data strongly suggest that β1 integrin-CD151 adhesion receptor complexes activate c-Jun AP-1 factor via the signaling cascades involving the FAK-Src, ILK-β-Pix, small GTPases-PAK1, MEK3/6-p38 MAPK, and MEK7-JNK pathways, leading to increased cell motility and MMP-9 expression in human melanoma cells. Key words: tetraspanin, CD151, integrin, adhesion receptor, cell signaling 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 3124. doi:10.1158/1538-7445.AM2011-3124
OP0023 Germinal and Somatic Genetic Variants of TNFAIP3 Promote Lymphomagenesis Process Complicating Primary Sjögren’s Syndrome
Authors: G. Nocturne, S. Boudaoud, C. Miceli Richard, S. Viengchareun, T. Lazure, J. Nititham, K. E. Taylor, L. A. Criswell, A. Ma, F. Busato, J. Melki, J. J. Dubost, E. Hachulla, J. E. Gottenberg, M. Lombes, J. Tost, X. Mariette
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The pathophysiology of lymphomas in auto immune disease (AID) involves persistent inflammation and activation of autoimmune B cells leading to NF-kB activation. The <i>TNFAIP3</i> gene encodes the A20 protein, a central gatekeeper of NF-kB activation. Germinal abnormalities in <i>TNFAIP3</i> have been associated with different AID and somatic mutations of the gene have been observed in several lymphoma subtypes, particularly MALT lymphoma, the lymphoma subtype most frequently associated with pSS. <h3>Objectives</h3> To investigate whether <i>TNFAIP3</i> abnormalities are involved in the lymphomagenesis process in pSS. <h3>Methods</h3> The discovery set was constituted by 584 pSS patients including 25 patients with lymphoma and 451 controls of Caucasian ancestry, addressed by 48 Ancestry Informative Markers. Three SNPs encompassing the <i>TNFAIP3</i> locus located on 6q23 (rs13192841, rs2230926 and rs6922466) and known to be associated with SLE and RA were genotyped. 19 additional patients with pSS and lymphoma were used for extension and replication. We sequenced all <i>TNFAIP3</i> exons in germinal and lymphoma DNA from 20 pSS patients with lymphoma. Functional abnormalities of A20 were assessed by gene reporter assays. <h3>Results</h3> The 3 <i>TNFAIP3</i> SNPs were not significantly associated with risk of pSS. But multivariate analysis demonstrated a significant association between the rs2230926 SNP (coding for an amino acid substitution in exon 3) and pSS complicated by lymphoma: OR vs controls = 3.36 (95%CI 1.34 - 8.42) p= 0.0097, OR vs pSS without lymphoma = 3.26 [95%CI 1.31 – 8.12], p=0.011. <i>TNFAIP3</i> gene sequencing of germinal DNA from 43 patients with pSS and lymphoma confirmed the more frequent presence of the rs2230926G risk variant in 11/43 patients (25.6%, versus 11% in controls, p=0.018). Twelve of the 20 (60%) patients with paired germinal and lymphoma <i>TNFAIP3</i> sequence data had functional abnormalities of A20. The frequency was even higher (77%) among pSS patients with MALT lymphoma (n=28). Mutated A20 variants (rs2230926G and GG insertion) were both less effective than the wild type A20 in inhibiting NF-kB-dependent activation (p&lt; 0.0001). <h3>Conclusions</h3> This study demonstrates that A20 inactivation plays a key role in lymphomagenesis in the context of autoimmunity. It supports a scenario in which the presence of germinal and/or somatic abnormalities of genes leading to impaired control of NF-kB activation in B cells continuously stimulated by autoimmunity enhances the risk of lymphoma. <h3>Disclosure of Interest</h3> None Declared
Thyroid Crisis Associated with Diabetic Coma
Authors: Philip Troen, Robert C. Taymor, Bernard I. Goldberg
Journal: New England Journal of Medicine (1951)

THAT the coexistence of two metabolic disturbances such as thyrotoxicosis and diabetes mellitus can cause an increased severity in both conditions has long been recognized.1 These two conditions reach their most extreme states in the form of thyroid crisis and diabetic coma. The recent treatment of a case combining these two extremes has prompted the writing of this report.Joslin and his co-workers have emphasized the high incidence of glycosuria and hyperglycemia in patients with hyperthyroidism.2 In a large number of thyrotoxic patients they found that one third had fasting blood-sugar levels of over 130 mg. per 100 cc. Because . . .
Oral Treatment of Pernicious Anemia with Vitamin B<sub>12</sub>without Intrinsic Factor
Authors: Edward H. Reisner, Leo Weiner, Marilyn T. Schittone, Edwin A. Henck
Journal: New England Journal of Medicine (1955)

THE absorption of ordinary amounts of vitamin B12 from the gastrointestinal tract is normally dependent on the presence of the intrinsic factor of Castle in the gastric secretions. A lack of intrinsic factor results in deficient absorption of vitamin B12 and the clinical picture of pernicious anemia. In the treatment of this condition it has been necessary either to administer vitamin B12 parenterally or to add intrinsic factor to the vitamin B12 given by mouth to ensure proper absorption. If, however, the oral dose of vitamin B12 is increased to more than 1 mg. enough . . .
Abstract 3715: EP-100 syndergizes with paclitaxel in ovarian, breast and prostate cancer cell lines
Authors: Carola Leuschner, Cody Giardina, Hector W. Alila
Journal: Cancer Research (2012)

Abstract EP-100 is a targeted anti-cancer drug comprised of Luteinizing Hormone Releasing Hormone (LHRH) fused to a lytic peptide. EP-100 is currently being investigated in human clinical trials. EP-100 seeks and destroys LHRH receptor positive cancer cells via a novel mechanism of action involving direct membrane disruption. Studies were conducted to determine the cytotoxic effects of combining EP-100 with paclitaxel using multi-drug resistant LHRH receptor positive ovarian (OVCAR-3), breast (MDA-MB-231), uterine sarcoma (MES-SA-Dx5), prostate (PC-3) and LHRH receptor negative ovarian (SKOV-3) cancer cells. Cells were cultured in the presence of EP-100 (0.005 nM-50µM, N=8) or paclitaxel (0.0025-500 nM, N=8) alone or in combination for 48 to 72 hours in non-constant and constant ratio formats (N=6). Cell viability was measured by luminometric assays. Data for IC50 values were obtained using the GraphPad Prism and GraphPad Software for the Hill Equation. The synergistic effects of EP-100 and paclitaxel were expressed as Combination Index (CI) using the CompuSyn Software analysis program. EP-100 alone killed LHRH receptor positive OVCAR-3, MDA-MB-231, MES-SA-Dx5 and PC-3 cells at low micromolar concentrations after 48 to 72 h incubation(IC50 values 2.189 ± 0.027 µM, 2.092 ± 0.114 µM, 1.419 ± 0.133 µM and 1.9 ± 0.071 µM respectively). As expected, SKOV-3 cells did not respond well to EP-100 (IC50= 10.3 ±0.36 µM) because they lack LHRH receptors on their surfaces. OVCAR-3, MDA-MB-231, MES-SA-Dx5 and SKOV-3 cells were resistant to paclitaxel (IC50 values = 13.6 ± 0.7 nM 86.2 ± 5.9 nM, 94.1 ± 0.3 nM and 48.52 ± 4.5 nM, for OVCAR-3, MDA-MB-231, MES-SA-Dx5 and SKOV-3, respectively) and PC-3 cells were very sensitive to paclitaxel with IC50 of 5.2 ± 1.1 nM. The combination of EP-100 at 50 nM and paclitaxel at 500 nM resulted in 3620 and 6720- fold increased sensitivity when compared to paclitaxel alone. The median CI values were 0.18, 0.05, 0.25, and 0.6 for for MES-SA-Dx5, OVCAR-3, MDA-MB-231 and PC-3, respectively indicating synergistic responses in the cell lines. No synergy was observed in the LHRH receptor negative SKOV-3 cell line (CI=8.4). These results indicate that a combination of EP-100 and paclitaxel results synergistic responses in LHRH-receptor positive and multi-drug resistant cancer cells. 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 3715. doi:1538-7445.AM2012-3715
AB0958 Tendon's Involvement in Marfan Syndrome: Ultrasound Evaluation
Authors: D. Melchiorre, E. Pratelli, E. Torricelli, F. Sofi, R. Abbate, M. Matucci-Cerinic, G. Gensini, G. Pepe
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Hypermobility, dislocations and contractures of joints represent overlapping clinical manifestations between rheumatological diseases, neuromuscular disorders and inherited connective tissue disorders such as Marfan Syndrome. Some Authors (1) focused on the muscle alterations responsible for joint hypermobility and dislocations. Ultrasound (US) imaging, and more recently Power Doppler (PD) technology, are regarded as a helpful method to detect myopathic muscle highlights as muscle atrophy, intramuscular fibrosis and fatty infiltration; and tendon structure as tendon abnormalities with a good reproducibility. <h3>Objectives</h3> The involvement of the musculoskeletal system with other mild pleiotropic manifestations represents a major criterion in Marfan Syndrome. We aim to investigate by US, the nature, muscular or tendineous, of the contractures present in the hands and feet of a group of Marfan patients. <h3>Methods</h3> In 13 Marfan patients previously investigated, an accurate clinical examination was performed. In particular it involved the characterization of muscle skeleton system by visual analogic scale to measure muscle pain (VAS) and muscle strength (MRC system); Beighton scale score to evaluate articular hypermobility; tendon ultrasound to detect deep-superficial flexor and extensor tendon structures of both hands and feet fingers in static and dynamic positions. US exam was carried out by equipments Esaote myLab 70 with linear probe (10-18 MHz; Esaote Genoa - Italy). The probe was oriented perpendicular to its longitudinal axis. <h3>Results</h3> Our results showed a reduction of the thickness of all tendons in pts <i>vs</i> controls (p&lt;0.02 for long and short flexor tendons of feet and p&lt;0.0001 for the other tendons). A severe hypoechointensity of these tendons was also detected. The mean value of the area of all tendons was 1 mm<sup>2</sup> among patients and 4 mm<sup>2</sup> among controls. PD was negative in all tendons. No tears of tendon fibers were present. The intra-observed (kappa=0.97) agreement was assessed at baseline and after 1 month. <h3>Conclusions</h3> This study reveals the involvement of tendons, unsuspected until now, in the finger contractures alterations observed in all patients. In our patients, all tendons showed hypoechointensity and decreased tendon thickness that can correlate with the alterations in patients with inherited connective tissue disorders. Our original findings suggest an overlapping with chronic inflammatory diseases; the evaluation of biochemical markers are required to address this question. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5950
AB0165 Association between neutrophil to lymhocyte ratio with disase activity in rheumatoid arthritis and ankylosing spondylitis
Authors: R. Mercan, A. Tufan, B. Bitik, M. E. Tezcan, A. Kaya, B. Goker, M. A. Ozturk, S. Haznedaroglu
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Blood neutrophil-to-lymphocyte ratio (NLR) is a new inflammatory index which has been shown to be associated with prognosis of many disorders including cardiovascular diseases and neoplastic conditions. Its role in acute inflammation was also studied with a good discriminative value from those noninflammatory conditions. The value of NLR in the assessment of activity of inflammatory arthritides is not studied. <h3>Objectives</h3> To investigate correlation of NLR with disease activity indices in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). <h3>Methods</h3> One hundred eighteen RA (76% female, mean age 46.8±10.1 years) and 138 AS (43% female, mean age 36.7±9.3 years) patients were enrolled. Control group constituted 117 healthy subjects (34% female, mean age 36.1±12.0 years). Disease activities were evaluated with DAS28 and BASDAI indices in RA and AS patients, respectively. Hemoglobin, white blood cell (WBC) counts; erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) levels were measured. WBC differential was obtained from complete blood counts. <h3>Results</h3> RA and AS patients had remarkably higher ESR, CRP and WBC measurements and significantly lower hemoglobin levels compared to control subjects (p&lt;0.001 for each parameter). NLR was significantly higher in RA patients compared to healthy subjects (2.59±1.2 vs 2.15±1.1, p=0.023). NLR is moderately correlated with DAS 28 and CRP in patients with RA (r:0.37 p=0.002, r:0.30 p&lt;0.001, respectively). However NLR was not correlated with BASDAI in AS patients. <h3>Conclusions</h3> NLR could be used as a marker of activity in patients with RA and showed a moderate correlation with DAS 28. However such a correlation was not observed in AS patients. <h3>Disclosure of Interest</h3> None Declared
IBUPROFEN PROPHYLAXIS IS ASSOCIATED WITH IMPROVED HOMOGRAFT LONGEVITY IN THE RIGHT VENTRICULAR OUTFLOW TRACT IN CHILDREN
Authors: Frances Chen Travelli, Andrew S. Haynes, Pamela M. Faire, Vaughn A. Starnes, Ram Kumar Subramanyan, Winfield Wells, Jondavid Menteer
Journal: Journal of the American College of Cardiology (2015)