tbuckley/cabot-search huggingface dataset:
SAT0361 Short Term Efficacy of Tumor Necrosis Factor Inhibitors in Patients with Non–Radiographic Axial Spondylarthritis and Ankylosing Spondylitis; Results from TURKBIO Registry: Table 1.
Authors: P. Cetin, U. Kalyoncu, D. Solmaz, I. Sari, O. Karadag, L. Kilic, M. Birlik, S. Kiraz, F. Onen, I. Ertenli, N. Akkoc
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Axial spondylarthritis (AxSpA) has been proposed as an umbrella term for ankylosing spondylitis (AS) and non-radiographic (nr) AxSpA. This new concept makes diagnosis of AS possible at an early stage in the absence of radiographic sacroiliitis. Disease burden in AxSpA patients with or without radiographic sacroiliitis have been shown to be similar in different cohorts, which suggest that both diseases should be treated with the same strategy. Recent randomized clinical trials showed that TNF inhibitors (TNFi) are effective also in treating signs and symptoms of nr-AxSpA. However, the efficacy of anti-TNF agents in patients with nr-AxSpA remains to be shown in daily rheumatology practice. <h3>Objectives</h3> To compare the efficacy of TNF inhibitors in patients with AS and nr-AXSpA in daily clinical setting <h3>Methods</h3> A total of 174 patients with AxSpA (107 M; 40.8±10.0) from two centers, who contribute to TURKBIO, a biological database in Turkey, and who could provide detailed data on imaging for patients with AxSpA, were included in this study. Of these patients 115 had AS according to the modified New York criteria, 59 patients fulfilled the ASAS classification criteria for AxSpA (78% fulfilling the imaging arm). <h3>Results</h3> Baseline demographics and clinical characteristics are summarized in the table below. Patients with nr-AxSpA were significantly younger, had a shorter disease duration and had a higher female predominance than patients with AS. After treatment with TNF inhibitors mean BASDAI score decreased significantly from 6.15±1.76 at baseline to 3.28±2.1 at 3 months (p=0.049) in patients with nr-AxSpA; from 5.99±1.69 to 3.05±1.7 (p:0.008) in patients with AS and from 6.05±1.71 to 3.12±1.85 (p=0.001) in the whole group. Minimal clinical response (a decrease of 2 units in BASDAI) was observed in 63% of the patients with nr-AxSpA and in 68% of the patients with AS. Major clinical response (BASDAI 50) was achieved in 49% and 51% of the patients with nr-AxSpA and AS, respectively. Other efficacy measures such as ASAS20 and ASAS40 response were also similar in both groups, but could be performed in only a small number of patients due to missing data. <h3>Conclusions</h3> The results of our study suggest that TNFi, which have been clearly shown to be effective in treating signs and symptoms of AS, seem to be equally effective in the treatment of nr-AxSPA. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5754
Defective Reticuloendothelial System Fc-Receptor Function in Systemic Lupus Erythematosus
Authors: Michael M. Frank, Max I. Hamburger, Thomas J. Lawley, Robert P. Kimberly, Paul H. Plotz
Journal: New England Journal of Medicine (1979)

To determine whether reticuloendothelial-system immunospecific Fc-receptor function is abnormal in patients with systemic lupus erythematosus, we studied the clearance of IgG-sensitized 51Cr-labeled erythrocytes by these splenic macrophage membrane receptors in 15 untreated patients. Fc-specific clearance rates were strikingly abnormal in 13 of 15 patients (half-times ranging from 80 to 2256 minutes, P less than 0.001 as compared to controls). Abnormal clearances correlated with immune-complex levels (as measured by the C1q-binding assay) and with disease activity. C1q-binding activity and anti-DNA titers also correlated with disease activity. The correlations of C3, C4, CH50 and factor B with abnormal clearance and disease activity were weaker or nonexistent. The significant correlations among clearance, disease activity and C1q-binding activity suggest that the defect in Fc-receptor function may lead to the prolonged circulation of immune complexes, thereby contributing to tissue deposition and damage.
PWE-016 Can the Response to Posterior Tibial Nerve Stimulation for Faecal Incontinence Predict the Response to Sacral Nerve Stimulation?
Authors: G Thomas, T Dudding, R J Nicholls, C Vaizey
Journal: Gut (2013)

<h3>Introduction</h3> Sacral nerve stimulation (SNS) is an established treatment for faecal incontinence (FI). Posterior tibial nerve stimulation (PTNS) is a more recent and increasingly popular treatment for FI. PTNS is cheaper, safer and as effective as SNS in the short term. PTNS can be used as an initial therapy, with SNS reserved for those who have failed to improve. The aim of this study was to see if the response to PTNS can be used to predict the response to SNS. <h3>Methods</h3> Prospectively collected data for all patients who had undergone transcutaneous PTNS followed by SNS were analysed. A good clinical response to PTNS and to SNS was defined as a ≥50% reduction in frequency of FI episodes per week. <h3>Results</h3> Ten patients underwent PTNS followed by SNS for FI. Three patients had a poor response to PTNS. Two of these had a subsequently had a poor response to SNS. Seven patients had a good response to PTNS. Five of these had a good response to SNS. <h3>Conclusion</h3> This small study suggests that the response to PTNS may predict the response to SNS. Much larger studies are needed to explore this further. <h3>Disclosure of Interest</h3> None Declared.
Umbilical Hernia Simulating Recurrent Carcinoid on Octreoscan
Authors: David A. Hirschl, Yi Li, K. J. Chun, Leonard M. Freeman
Journal: Clinical Nuclear Medicine (2011)

Physiologic bowel activity on In-111 octreotide imaging is commonly seen. However, on occasion, normal bowel activity may mimic lesions in the abdomen, which can be very difficult to differentiate, particularly after surgical intervention. We report a case of focal bowel activity simulating a lesion in a patient who had an In-111 octreotide scan (Octreoscan), postoperatively, looking for recurrent carcinoid. SPECT/CT demonstrated that the uptake was localized in the anterior abdomen, and corresponded to a loop of bowel within a ventral hernia at the site of surgical incision. The correlation with CT as well as the precise localization made possible by the fusion images helped avoid misinterpretation of this finding as possible recurrent carcinoid.
Laminin Expression by Human Pancreatic Carcinoma Cells in the Nude Mouse and in Culture<xref ref-type="fn" rid="FN1">2</xref><xref ref-type="author-notes" rid="FN2">3</xref>
Authors: C Haberern-Blood, L A Liotta, C N Rao, H Z Kupchik
Journal: JNCI Journal of the National Cancer Institute (1987)

The abilities of 4 established human pancreatic tumor cell lines (PANC-1, CAPAN-1, AsPc-1, and BxPc-3) to synthesize and to maintain laminin-containing basement membranes when grown in the nude mouse have been examined and compared with synthesis of the glycoprotein laminin by these tumor cells when grown in culture. Immunohistochemical visualization of basement membrane integrity within the transplanted tumors employed a monoclonal antibody specific for human laminin to clearly distinguish between human tumor-produced laminin and murine basement membranes. This technique demonstrated strikingly different degrees of basement membrane formation and laminin distribution for the 4 biologically diverse pancreatic tumors. Basement membranes were present within the differentiated, less invasive tumors, whereas structure basement membranes were absent in the poorly differentiated, invasive tumors. Regardless of their propensity to produce basement membranes in vivo, all 4 pancreatic tumor cell lines continued to synthesize laminin in culture, as was determined by immunologic assays. The most invasive cell line, AsPc-1, released large quantities of soluble laminin into conditioned culture medium. The less invasive, well-differentiated tumor cells did not release laminin into the medium, but they retained the laminin produced by them within the cell layer. The combination of in vivo and in vitro studies indicates that the extent of basement membrane loss by these human pancreatic tumors is not due to an inherent inability of the tumor cells to synthesize the structural component laminin.
Prospective Evaluation of Circulating Vegf in Patients with Advanced Non-Small Cell Lung Cancer Treated with Bevacizumab, Pemetrexed and Cisplatin in the Trial Sakk19/09
Authors: S.I. Rothschild, O. Gautschi, B. Huegli, Q. Li, L. Stalder, A. Zippelius, R. Cathomas, S. Peters, M. Frueh, N. Mach, A. Ochsenbein, E. Oppliger Leibundgut
Journal: Annals of Oncology (2014)
AB0868 Results of Early Intervention in Patients Being off Work Due to Musculoskeletal Causes in the HUP LA FE Area
Authors: C. Molina Almela, I. Martinez Cordellat, J.L. Valero Sanz, J. Ivorra Cortes, I. Chalmeta Verdejo, E. Grau Garcia, C. Feced Olmos, R. Negueroles Albuixech, L. Gonzalez Puig, M.L. Muñoz Guillen, C. Nuñez-Cornejo Piquer, C. Alcañiz Escandell, J.A. Roman Ivorra
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> In March 2012, a new project was started at HUP La Fe following the pilot project carried out at San Carlos Clinical Hospital in Madrid, where patients who were off work for musculoskeletal causes were referred to us from Primary Care. <h3>Objectives</h3> The aim of the study is to analyze the variation in days off work in those individuals included in this program with respect to the normal average of days off. <h3>Methods</h3> Cohort, observational, cross-sectional study from April 2012 to December 2013, which included patients from the HUP La Fe area, referred for the first time to the Rheumatology Early Intervention consultation program because of temporary disability due to musculoskeletal problems. These patients are referred to a medical appointment with a maximum waiting time of one week and were provided medical treatment, ultrasound, joint injections and directed exercises if needed. The patient is reviewed continuously until discharge. We excluded patients whose disabilities were due to trauma or surgery or if their situation could cause permanent disability. <h3>Results</h3> We included a total of 250 patients with a mean age of 48 years and 53% were women. The most frequently reported diseases were: back pain (33%), neck pain (16%), shoulder pain syndrome (13%) and other tendinopathies (10%). 100% of patients received medical treatment, 39% underwent articular ultrasound, 35% of them underwent injections and 82% were trained to perform physical therapy exercises at home. The pathology that had a higher average number of days from the first visit to the medical discharge was lumbar/sciatic pain (38 days), neck pain (30 days), and painful shoulder syndrome (34 days). Comparing our data with the control population in the San Carlos Hospital study, there was a decrease of the days off, being in the control group lumbociatalgia (57.6 days), neck (37.4 days) and neck pain (37.4 days). <h3>Conclusions</h3> Results obtained in our study show that early intervention by rheumatologists in patients with temporary disability of musculoskeletal origin decreases the number of days off work compared to patients who receive routine treatment and they can be incorporated in work early. Consequently, it saves all costs resulting from such temporary disability. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5060
A Randomized Trial of Nonoperative Treatment for Perforated Peptic Ulcer
Authors: Trevor J. Crofts, Kenneth G.M. Park, Robert J.C. Steele, Sydney S.C. Chung, Arthur K.C. Li
Journal: New England Journal of Medicine (1989)

To determine whether surgery could be avoided in some patients with perforated peptic ulcer, we conducted a prospective randomized trial comparing the outcome of nonoperative treatment with that of emergency surgery in patients with a clinical diagnosis of perforated peptic ulcer. Of the 83 patients entered in the study over a 13-month period, 40 were randomly assigned to conservative treatment, which consisted of resuscitation with intravenous fluids, institution of nasogastric suction, and intravenous administration of antibiotics (cefuroxime, ampicillin, and metronidazole) and ranitidine. Eleven of these patients (28 percent) had no clinical Improvement after 12 hours and required an operation. Two of the 11 had a perforated gastric carcinoma, and 1 had a perforated sigmoid carcinoma. The other 43 patients were assigned to immediate laparotomy and repair of the perforation. One of these patients was found to have a perforated gastric carcinoma. The overall mortality rates in the two groups were similar (two deaths in each, 5 percent), and did not differ significantly in the morbidity (infection, cardiac failure, or renal failure) rates (40 percent in the surgical group and 50 percent in the nonsurgical group). The hospital stay was 35 percent longer in the group treated conservatively. Patients over 70 years old were less likely to respond to conservative treatment than younger patients (P<0.05). We conclude that in patients with perforated peptic ulcer, an initial period of nonoperative treatment with careful observation may be safely allowed except in patients over 70 years old, and that the use of such an observation period can obviate the need for emergency surgery in more than 70 percent of patients. (N Engl J Med 1989; 320:970–3.)
First Human Gene Transfer Trial
Authors: F. S. Antoine
Journal: JNCI Journal of the National Cancer Institute (1988)

Journal Article First Human Gene Transfer Trial Get access Florence S. Antoine Florence S. Antoine Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 17, 2 November 1988, Pages 1364–1365, https://doi.org/10.1093/jnci/80.17.1364 Published: 02 November 1988
Abstract 1108: Ferritin binds breast cancer cells and tissue, and promotes proliferation independently of iron content
Authors: Ahmed Alkhateeb, James Connor
Journal: Cancer Research (2011)

Abstract A connection between iron and breast tumorigenesis has been convincingly argued over the years. Several in vivo studies have demonstrated that iron-rich diets increase tumor incidence rate in carcinogen-induced mammary tumor models. Moreover, a large cohort study has recently associated mutations in the hemochromatosis (HFE) gene (promoting iron overload) with breast cancer risk in females. Individuals with mutations in the HFE protein can exhibit iron accumulation in the liver, high transferrin saturation levels, and elevated serum ferritin levels, but not have clinical hemochromatosis. Cells store iron in ferritin, but this protein is also secreted and is detected circulating in serum. Although serum ferritin has been used as an indicator of total body iron, a specific functional role has not been proposed thus far other than perhaps recycling iron to the bone marrow. Interestingly, serum ferritin levels have been shown to be increased in breast cancer patients, and higher levels seem to be associated with poorer prognosis. Furthermore, comparisons between pre- and post-surgery ferritin levels suggested that the tumor itself is responsible for the high levels of serum ferritin possibly through secretion. We have demonstrated that ferritin binds to breast tumor sections obtained from biopsy. Based on these observations, we hypothesized that serum ferritin interacts directly with breast cancer cells enhancing their growth. In this study we report that ferritin exposure will increase proliferation and DNA synthesis in the breast cancer cell lines, MCF-7 and T47D. These effects were not dependent on the iron content of ferritin, as both apo- and holo-ferritin had comparable effects. Because extra-cellular ferritin has been speculated to play an iron delivery role in some cells, we examined changes in transferrin receptor levels, and the quenching of the fluorescent metal-sensitive dye calcein following ferritin treatments. Our data, suggests that ferritin does not deliver iron to cells, and might have an iron-independent signaling function. Taken together, these findings encourage a new perspective on serum ferritin in cancer biology, and raise several possibilities for novel therapeutic and diagnostic strategies. 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 1108. doi:10.1158/1538-7445.AM2011-1108
Modulation of the Function of p-glycoprotein by Estramustine
Authors: C.-P. H. Yang, H.-J. Shen, S. B. Horwitz
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Modulation of the Function of p-glycoprotein by Estramustine Get access Chia-Ping Huang Yang, Chia-Ping Huang Yang Search for other works by this author on: Oxford Academic PubMed Google Scholar Heng-Jia Shen, Heng-Jia Shen Search for other works by this author on: Oxford Academic PubMed Google Scholar Susan Band Horwitz Susan Band Horwitz *Department of Molecular Pharmacology, Albert Einstein College of MedicineBronx, N. Y. Correspondence to : Susan Band Horwitz, Ph.D., Department of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 9, 4 May 1994, Pages 723–725, https://doi.org/10.1093/jnci/86.9.723 Published: 04 May 1994 Article history Received: 08 December 1993 Revision received: 08 March 1994 Accepted: 05 April 1994 Published: 04 May 1994
A9.3 Hydrogen sulfide and MEK1 inhibition reduce IL-1β-induced activation of fibroblast-like synoviocytes
Authors: D Sieghart, H P Kiener, B Kloesch, G Steiner
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> In the pathophysiology of osteoarthritis (OA) the secretion of the pro-inflammatory cytokine interleukin (IL)-1β is among the critical steps mediating the aberrant degenerative processes in which activated fibroblast-like synoviocytes (FLS) play a pivotal role. The major goal of this study was to investigate the molecular mechanisms underlying this activation and how treatment with hydrogen sulfide (which is applied for treatment of OA in the form of sulfur spa therapy), or various mitogen-activated protein kinase (MAPK) inhibitors influences them. <h3>Methods</h3> FLS derived from OA patients were used throughout this study. The effect of IL-1β and NaHS treatment on the phosphorylation of 26 MAPkinases and other serine / threonine kinases was analysed by proteome profiler array. The secretion of IL-6 was monitored by ELISA in cell culture supernatants from conventional cultured FLS treated with NaHS or MAPK inhibitors. In addition, FLS were grown in 3-dimensional extracellular matrix micromass cultures, stimulated with IL-1β and treated with NaHS or the MAPK inhibitors PD98059 (MEK1), SB203580 (p38) and SP600125 (JNK). <h3>Results</h3> Data gained from human phospho-MAPK proteome profiler array revealed that IL-1β as well as NaHS increased the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 (68 ± 16% and 90 ± 27%), mitogen- and stress activated protein kinase (MSK)2 (37 ± 5%), p38 subunits α (232 ± 51%), β (125 ± 38%) and γ (417 ± 216%) as well as c-Jun-N-terminal (JNK) 1/2 (33 ± 7% and 89 ± 3%). Interestingly, NaHS treatment inhibited the IL-1β-induced activation of ERK1/2, MSK2, p38δ and JNK2 between 10 up to 30%. Furthermore, treatment with NaHS or MEK1 inhibitor completely abolished the IL-1β-induced secretion of IL-6, whereas inhibitors of p38 and JNK did not show this effect. FLS micromass cultures stimulated with IL-1β developed a hyperplastic lining layer structure and treatment with NaHS or the MEK1 inhibitor was found to almost completely inhibit this process. <h3>Conclusion</h3> These experiments demonstrate that hydrogen sulfide decreases the IL-1β-induced phosphorylation of ERK1/2 and MSK2, which signal downstream of MEK1/2. This suggests a direct effect of hydrogen sulfide on MEK1/2 activation leading to decreased IL-6 secretion and inhibition of formation of hyperplastic lining layer structures, which might explain some of the beneficial effects of sulfur spa therapy. Gene expression studies will help to elucidate the molecular mechanisms of the inhibitory effects exerted by hydrogen sulfide.
Abstract 916: Functional significance of sulfotransferase 1A1 polymorphisms in the 3’ untranslated region in determination of enzymatic activity
Authors: Xinfeng Yu, Marjorie L. Beggs, Ishwori B. Dhakal, Xuemei Zhang, Vineetha Koroth Edavana, Suzanne Williams, Kelly E. Mercer, Fred F. Kadlubar, Susan Kadlubar
Journal: Cancer Research (2010)

Abstract SULT1A1 is the most highly expressed hepatic sulfotransferase and is involved in the biotransformation of a wide variety of endo-and xenobiotics. The inter-individual variation of SULT1A1 enzyme activity can markedly influence drug toxicity and/or treatment efficacy in the clinical setting. We and others have examined a common SNP in the coding region of SULT1A1 (Arg213His, SULT1A1*1/2), as well as several SNPs in the proximal promoter that were associated with altered enzymatic activity. However, the SNPs account for only a small proportion of variation of SULT1A1 activity in human populations. In order to identify SNPs that markedly affect SULT1A1 activity, we resequenced the 3’UTR of SULT1A1 in 97 liver samples. Direct sequencing revealed 2 SNPs (902A&amp;gt;G, 973C&amp;gt;T) in the 3’UTR and 1 SNP (1307G&amp;gt;A) in the 3’ flanking region. Interestingly, we found these SNPs are in absolute linkage disequilibrium and are closely associated with SULT1A1 expression and enzymatic activity. To further elucidate the important role of SNPs in 3’UTR, we performed haplotype analysis to predict the collective effects of functional genetic variants in the 3’ UTR regions, the SULT1A1*1/2 polymorphism and copy number variation on SULT1A1 enzymatic activity. Notably, two major haplotypes (ACGG and GTAA) were significantly correlated with SULT1A1 activity, Copy number did not influence on SULT1A1 activity in liver samples. 3’UTR SNPs are in linkage disequilibrium with SULT1A1*1/2 polymorphism, so to examine the effect of the SULT1A1*1/2 polymorphism, we performed haplotype-activity assay in 499 Caucasian and 129 African American subjects. Haplotype and regression analysis both strongly suggest that the 3’UTR SNPs are the pivotal predictor of SULT1A1 activity. MicroInspector predicts 3116C&amp;gt;T influences the binding of miR-631 to SULT1A1 3’UTR. Furthermore, in vitro luciferase reporter assays and overexpression of miRNA mimics and inhibitors indicated that SULT1A1 is a direct target of miR-631 and miR-631 differentially regulates the C and T alleles of rs1042157. The results suggest, for the first time, that allele-specific regulation of SULT1A1 by miR-631 contributes to the activity variation of SULT1A1 in population. 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 916.
Chlorpropamide in Patients on High Insulin Dosage
Authors: David L. Singer, Robert C. Stewart, David Hurwitz
Journal: New England Journal of Medicine (1961)

A RECENT review of patients from the Diabetes Clinic of the Boston City Hospital revealed a substantial number doing well on chlorpropamide¶ whose insulin requirement had exceeded 50 units. Because it has become almost axiomatic that these patients should not be expected to do well on the sulfonylurea type of agent, the subject was pursued further. Additional patients receiving 50 units of insulin or more a day were transferred to chlorpropamide, and their response tabulated. The results in 28 patients constitute the basis of this report.Methods and MaterialsCriteria for inclusion in the study were as follows: the diabetes . . .