tbuckley/cabot-search huggingface dataset:
A1.74 Serum levels of CXCL13 are increased in untreated patients with rheumatoid arthritis from the first weeks of disease development
Authors: Rita A Moura, Helena Canhão, Joaquim Polido-Pereira, Márcio Navalho, Maria J Leandro, Geraldine Cambridge, João Eurico Fonseca
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> CXCL13 (C-X-C motif ligand 13), also known as B-cell chemo-attractant, is an important B-cell chemokine that directly affects the migration and organization of B cells within follicles of lymphoid tissues. CXCL13 plays an important role as a major regulator of B-cell recruitment towards secondary lymphoid organs and inflammatory sites and it has recently been proposed as a serum biomarker of synovitis in patients with rheumatoid arthritis (RA). The aim of this study was to quantify CXCL13 serum levels in untreated very early polyarthritis patients to understand the dynamics of B-cell trafficking since early disease onset. <h3>Materials and Methods</h3> CXCL13 levels were measured by ELISA in serum samples from untreated very early RA (VERA) with &lt;6 weeks of disease duration, and compared with arthritis due to other conditions of the same duration (non-RA) (VENRA), untreated early RA (ERA) (&lt;1 year), other early arthritis patients (non-RA) (ENRA) (&lt;1 year), established treated RA and healthy controls (HC). Statistical analysis was performed with Mann-Whitney, Kruskal-Wallis and Spearman tests (p &lt; 0.05). <h3>Results</h3> We found that untreated polyarthritis patients with &lt;6 weeks of disease duration (VERA and VENRA) had significantly higher CXCL13 serum levels in comparison with HC (p = 0.01 and p = 0.02, respectively). ERA and established RA patients also had significantly higher circulating levels of CXCL13 when compared to HC (p = 0.04 and p = 0.003, respectively), but no significant differences were observed in comparison with VERA. Moreover, no significant differences were found in ENRA patients when compared to HC. However, all patients diagnosed with RA (VERA, ERA and established RA) had significantly higher levels of CXCL13 when compared to ENRA (p &lt; 0.05). VENRA also had significantly higher CXCL13 levels when compared to ENRA. Furthermore, no correlation was observed between CXCL13 serum levels with age, DAS28, ESR, VAS, tender and swollen joint counts. <h3>Conclusions</h3> CXCL13 serum levels were significantly increased in untreated polyarthritis patients who subsequently resolved into a clinical diagnosis of RA. This was found in both early RA cohorts (VERA and ERA). Although VERA and VENRA (&lt;6 weeks of disease duration) had similar CXCL13 levels, only ERA and not ENRA had significantly higher levels suggesting that chronicity was strongly associated with CXCL13 in RA patients. Overall, our results might reflect an interaction between CXCL13-producing cells (activated macrophages, follicular dendritic cells, or Th17-cells) with B-cells in secondary lymphoid tissues such as the spleen, lymph nodes and possibly in inflammatory sites i.e., joints.
Abstract 1274: Heterotrimeric stimulatory GTP-binding proteins inhibit cisplatin-induced apoptosis by inducing XIAP in cervical cancer cells
Authors: Eun Ah Cho, Yong-Sung Juhnn
Journal: Cancer Research (2010)

Abstract Cisplatin (cis-dichlorodiammineplatinum (II)) induces DNA double-strand breaks (DSBs), which are considered as the main cytotoxic damage that induces apoptosis of human cancer cells. Cisplatin was also known to found to inhibit DNA-synthesis and DNA-repair in HeLa cervical carcinoma cells. Recently, we observed that heterotrimeric G proteins modulate apoptosis signaling in several cancer cell lines. In this study, we attempted to investigate the effect of Gαs on apoptosis triggered by cisplatin and its molecular mechanism in HeLa cells. Expression of constitutively active Gαs (GαsQL) decreased the cleavage of caspase-3 and PARP at 24 hr after treatment of HeLa cells with 30 µM cisplatin, indicating that Gαs inhibited cisplatin-induced apoptosis of HeLa cells. Expression of GαsQL increased the expression of XIAP (inhibitor of apoptosis protein), and partially recovered the cisplatin-induced decrease in XIAP. Knock down of Gαs expression by shRNA reduced the expression of XIAP and augmented cisplatin-induced apoptosis. This study shows that Gαs can protect apoptosis triggered by cisplatin by up-regulation of XIAP in HeLa cervical cancer cells. These results suggest that Gαs signaling may contribute carcinogenesis and progression of cervical cancer. 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 1274.
Aberrations of Suppressor T Cells in Human Graft-versus-Host Disease
Authors: Ellis L. Reinherz, Robertson Parkman, Joel Rappeport, Fred S. Rosen, Stuart F. Schlossman
Journal: New England Journal of Medicine (1979)

To determine whether imbalances in immunoregulatory T-cell subsets exist in patients with graft-versus-host disease, we analyzed T cells in three patients with acute and in six patients with chronic graft-versus-host disease after bone-marrow transplantation. The normal human peripheral-blood T-cell compartment is composed of 80 per cent TH2-and 20 per cent TH2+ T cells, and defined by reactivity with subset-specific heteroantiserums. Human suppressor cells are TH2+, whereas helper cells are TH2-. Patients with acute and chronic graft-versus-host disease had abnormalities in these populations, and their T cells frequently bore la-like antigens. Patients with acute disease lacked TH2+ cells, and the reappearance of this subset preceded the cessation of disease activity. Chronic disease, in contrast, was more heterogeneous. Suppressor cells were lacking in two patients but increased in the other four. Two of these four patients had TH2+, la+ T cells, suggesting in vivo activation of suppressor cells. Studies showing that these TH2+, la+ cells actively suppressed the in vitro immune response support this hypothesis and suggest that the immunoregulatory cells may profoundly affect the overall immune response.
P66 * AN INVESTIGATION INTO SUBSTRATE EFFECTS AND TISSUE PRE-PROCESSING IN SPECTRAL HISTOPATHOLOGY USING RAMAN SPECTROSCOPY
Authors: T. Mudariki, R. W. Lea, D. Griffiths, G. Clemens, M. J. Baker
Journal: Neuro-Oncology (2014)

INTRODUCTION: Raman spectroscopy is a low cost non-destructive and non-invasive technique showing great potential for the diagnosis of cancer. Biobanks are generally comprised of formalin fixed paraffin preserved (FFPP) tissue used in spectroscopic investigations. In order to carry out spectroscopic investigations the tissue needs to undergo a dewaxing process which removes and reduces paraffin contributions in the spectra. The ineffective removal of paraffin from the tissue and substrate contributions can affect the results and quality of the spectra. The aim of this study was to investigate the efficacy of tissue pre-processing steps used in spectral histopathology and the influence of commonly used substrates. METHOD: Nitrocellulose membrane filters of varying density, 8.0 µM, 5.0 µM and 1.2 µM were used to model human tissue. Filters underwent histological processing as clinical biopsies. Sections from each filter were cut at 10 microns and placed on three substrates, CaF2, Low-E and Glass which were subsequently dewaxed using two clearing agents, Histoclear and Xylene in three different bath times, 5 min, 10 min and 15 min. Spectra was collected from three biological replicates of each filter using Raman Spectroscopy with a 785 nm laser. RESULTS: CaF2 had the least background noise; however Glass and Low-E retained the least amount of paraffin whilst Xylene completely removed paraffin under the same bath conditions as Histoclear. CONCLUSION:Glass and Low-E are relatively cheaper and also provide reproducible results. These substrates can allow us to use standard clinical preparation procedures. Whilst Xylene is more effective in paraffin removal it is a hazardous chemical.
Case 19-2013
Authors: Erik K. Alexander, Gayun Chan-Smutko, Mansi A. Saksena, Ion Popa
Journal: New England Journal of Medicine (2013)

A 35-year-old woman was seen in the endocrinology clinic because of recurrent goiter and breast cancer. Micronodular lesions on the gingiva and tongue were observed. Diagnostic testing was performed.
SP0078 Self-management in osteoarthitis: What is the evidence ?
Authors: F. Berenbaum
Journal: Annals of the Rheumatic Diseases (2013)

Because of aging of the population, epidemic of obesity and irreversibility of the disease process, osteoarthritis is going to be one of the main public health concerns in the next few years all around the world. Since no curative treatment is available, chronicity of the disease is inevitable. Thus, the role of the patient in the management of pain and loss of function becomes critical on a day-to-day basis. For this aim, quite all the national and international organizations/societies recommend encouraging self-management in OA. Self-management can be defined as the control of pain and dysfunction by the patient him(her)self. It is usually based on programs developed by health professionals but it can also be implemented by the patient alone independently of any medical supports. The usual objectives of such programs can target maladjusted behaviours, inappropriate self medication, non-adherence to pharmacological therapies or to diet programs, and sedentarity. This lecture will review the level of evidence according to the main outcomes: time for exercise, decrease in pain, weight loss. Taken together the evaluation of the evidence for efficacy of such programs is a challenge since the content of these programs differs from one study to another one. <h3>Disclosure of Interest</h3> None Declared
AB0442 Short courses of steroids do not induce HBV reactivation in rheumatologic patients
Authors: Y. Braun-Moscovici, M. Braun, D. Markovits, A.M. Nahir, A. Balbir-Gurman
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Hepatitis B Virus (HBV) infection is widespread. Immunosuppressive agents may precipitate an increase in HBV replication followed by a flare of hepatitis B that may be severe and even fatal. There is no consensus about the minimal steroids dose or duration of therapy leading to HBV reactivation. There are no guidelines regarding the need for antiviral prophylactic treatment in steroid or DMARD's treated HBV carriers. <h3>Objectives</h3> To assess whether short courses of steroids induce HBV reactivation in patients (pts) with immunosuppressive therapy. <h3>Methods</h3> A database search was performed for HBsAg positive or anti HB core positive, anti HBs negative pts hospitalized in our Rheumatology department during the years 2001-2010 and treated with steroids. Liver function tests (LFT), HBV serologic tests and serum HBV DNA at baseline and 1-3 months after discharge were recorded. A supervised treatment course was defined as intravenous methylprednisolone treatment for 7 days. <h3>Results</h3> Complete data were found for 23 pts with a total of 73 supervised treatment courses (all anti-HBcore positive, anti-HBs negative, 18 pts HBsAg positive). The study group comprised pts with rheumatoid arthritis (11), psoriatic arthritis (3), ankylosing spondylitis (1), Behcet disease (1), idiopathic inflammatory myositis (1), SLE (1), systemic sclerosis (2), gout (2) and interstitial lung disease (1). All pts received intravenous methylprednisolone (mean dose 33.9±24mg/d, range 12.5-500) for 7 days. The concomitant medications included DMARDs in 15 pts (methotrexate -3, imuran -7, cyclophospamide-5, cellcept-1, cyclosporine-2), biologicals (7 pts-antiTNFα, 3-rituximab). Ten pts were on chronic steroid therapy, besides DMARDs (10.3±4.7mg, range 5-20mg). HBV DNA was positive at baseline in 7 pts. LFT (ALT) were elevated at baseline in 4 pts, (HBV DNA was positive in one of them) and returned to normal in all pts. Steroid therapy by itself did not trigger exacerbation of HBV hepatitis. Seroconversion to positive HBV DNA occurred in 3 pts, in one of them, accompanied by elevation of transaminases (ALTx4-7). The etiology was exposure to anti TNFα (1 pt), rituximab and cyclophosphamide (1pt) and azathioprine (1pt). ALT elevation (&gt;3ULN) occurred in 2 pts, after cyclophosphamide treatment. Lamivudine therapy reduced the viral load and the LFT in all pts and even below detection in 2 pts. Six pts treated with lamivudine received 14 supervised treatment courses, No HBV reactivation occurred in lamivudine treated pts following recurrent biological or cyclophosphamide exposure. <h3>Conclusions</h3> Short courses of steroids seem to be safe in HBV carriers, even in the presence of DMARDs. Lamivudine prophylaxis should be considered not only in pts exposed to biologicals, but also to cyclophosphamide. Larger prospective trials are needed to establish guidelines. <h3>Disclosure of Interest</h3> None Declared
FRI0366 Gender differences in health-related quality of life in poymyalgia rheumatica
Authors: J. Hollywood, A. Hutchings, B. Dasgupta
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The limited evidence on gender differences in outcomes in PMR suggests females experience a more severe and protracted course of disease. Females have longer duration of symptoms, higher relapse rate, higher cumulative steroid dose, and more steroid complications. <h3>Objectives</h3> To determine gender outcome differences in the first two years of PMR by analysing an existing database. <h3>Methods</h3> The analyses use data from a UK multi-centre prospective cohort study (2000-2005) of 129 patients (77 females, 52 males). Patients received standard care of, tapering oral prednisolone treatment in-line with current BSR guidelines. Clinical and patient-reported outcomes were assessed prior to starting treatment and at five assessments during two year follow-up. Health-related quality of life was measured using mental and physical component scores of the SF-36. Statistical analysis was done using multivariable linear and logistic regression to examine differences in outcomes by gender. Analyses were adjusted for socio-economic status, age, co-morbidities, and pre-treatment differences in the relevant outcome measure. <h3>Results</h3> At presentation females had worse mental quality of life (p=0.01.) There was no evidence of a difference in physical quality of life (p=0.54.) During follow-up females had significantly less improvement in physical quality of life (p=0.04 at 12 months, p=0.01 at 24 months). There were no statistically significant differences between females and males in improvement in mental quality of life (p=0.38 at 12 months, p=0.65 at 24 months.) The percentage of females who relapsed in the first two years was higher but non-significant (57% versus 44%). The cumulative steroid dose was higher in females despite their mean 13% lower body weight (3930mg versus 3548mg). Females had twice as many steroid related adverse events as males. <h3>Conclusions</h3> Females with PMR have worse mental quality of life at initial presentation, a difference that remains during follow-up. Although relapse rates were not significantly different in females and males, there were significant differences in outcome in terms of physical quality of life. Cumulative steroid dose was higher in females despite lower body weight and steroid related adverse events were double those of males. Our findings add to existing evidence of worse outcomes in females and suggest the need to consider alternative approaches to treatment. <b>Disclosure of Interest</b>: None Declared
Neurodevelopment of Children Exposed in Utero to Antidepressant Drugs
Authors: Irena Nulman, Joanne Rovet, Donna E. Stewart, Jacob Wolpin, H. Allan Gardner, Jochen G.W. Theis, Nathalie Kulin, Gideon Koren
Journal: New England Journal of Medicine (1997)

Many women of reproductive age have depression, necessitating therapy with either a tricyclic antidepressant drug or a drug, such as fluoxetine, that inhibits the reuptake of serotonin. Whether these drugs affect fetal neurodevelopment is not known.We studied the children of 80 mothers who had received a tricyclic antidepressant drug during pregnancy, 55 children whose mothers had received fluoxetine during pregnancy, and 84 children whose mothers had not been exposed during pregnancy to any agent known to affect the fetus adversely. The children's global IQ and language development were assessed between 16 and 86 months of postnatal age by age-appropriate Bayley Scales of Infant Development or the McCarthy Scales of Children's Abilities (for IQ) and the Reynell Developmental Language Scales.The mean (+/-SD) global IQ scores were 118+/-17 in the children of mothers who received a tricyclic antidepressant drug, 117+/-17 in those whose mothers received fluoxetine, and 115+/-14 in those in the control group. The language scores were similar in all three groups. The results were similar in children exposed to a tricyclic antidepressant drug or fluoxetine during the first trimester and those exposed throughout pregnancy. There were also no significant differences in temperament, mood, arousability, activity level, distractibility, or behavior problems in the three groups of children.In utero exposure to either tricyclic antidepressant drugs or fluoxetine does not affect global IQ, language development, or behavioral development in preschool children.
Defining active sacroiliitis on MRI for classification of axial spondyloarthritis: update by the ASAS MRI working group
Authors: Robert G W Lambert, Pauline A C Bakker, Désirée van der Heijde, Ulrich Weber, Martin Rudwaleit, Kay-Geert A Hermann, Joachim Sieper, Xenofon Baraliakos, Alex Bennett, Jürgen Braun, Rubén Burgos-Vargas, Maxime Dougados, Susanne Juhl Pedersen, Anne Grethe Jurik, Walter P Maksymowych, Helena Marzo-Ortega, Mikkel Østergaard, Denis Poddubnyy, Monique Reijnierse, Filip van den Bosch, Irene van der Horst-Bruinsma, Robert Landewé
Journal: Annals of the Rheumatic Diseases (2016)

Objectives To review and update the existing definition of a positive MRI for classification of axial spondyloarthritis (SpA). Methods The Assessment in SpondyloArthritis International Society (ASAS) MRI working group conducted a consensus exercise to review the definition of a positive MRI for inclusion in the ASAS classification criteria of axial SpA. Existing definitions and new data relevant to the MRI diagnosis and classification of sacroiliitis and spondylitis in axial SpA, published since the ASAS definition first appeared in print in 2009, were reviewed and discussed. The precise wording of the existing definition was examined in detail and the data and a draft proposal were presented to and voted on by the ASAS membership. Results The clear presence of bone marrow oedema on MRI in subchondral bone is still considered to be the defining observation that determines the presence of active sacroiliitis. Structural damage lesions seen on MRI may contribute to a decision by the observer that inflammatory lesions are genuinely due to SpA but are not required to meet the definition. The existing definition was clarified adding guidelines and images to assist in the application of the definition. Conclusion The definition of a positive MRI for classification of axial SpA should continue to primarily depend on the imaging features of ‘active sacroiliitis’ until more data are available regarding MRI features of structural damage in the sacroiliac joint and MRI features in the spine and their utility when used for classification purposes.
Abstract 5092: Variants at 6q21 implicate PRDM1 in the etiology of therapy-induced second malignancies after Hodgkin's lymphoma
Authors: Kenan Onel, Timothy Best, Andrew D. Skol, Dalin Li, Tomas Kirchhoff, Yutaka Yasui, Smita Bhatia, Louise C. Strong, Susan M. Domchek, Katherine L. Nathanson, Olufunmilayo Olopade, Thomas M. Mack, David V. Conti, Kenneth Offit, Wendy Cozen, Leslie L. Robison
Journal: Cancer Research (2011)

Abstract Survivors of Hodgkin's lymphoma (HL) are at increased risk for second malignant neoplasms (SMNs) induced by exposure to radiation therapy (RT). Although SMNs are a leading cause of death in survivors of HL, it is not possible to identify those patients at greatest risk. We performed a genome-wide association study (GWAS) of 99 HL survivors who developed SMNs and 86 who did not, all of whom were treated for HL with RT. We then tested three SNPs in a replication set of 120 RT-treated HL patients with SMNs and 112 without SMNs. The functional effects of risk-associated variants on gene expression were assessed in lymphoblastoid cell lines before and after exposure to radiation. Two variants at 6q21 between PRDM1 and ATG5 were associated with SMNs in younger but not older HL patients treated with RT [rs4946728: P = 1.26×10-9, and rs1040411: P = 4.68×10-8]; individuals homozygous for the rs4946728 risk allele comprise 50% of the general population and were found to be at an eleven-fold increased risk for SMNs as compared to those homozygous for the protective allele. The risk variants comprise a haplotype that was associated with decreased PRDM1 expression (p=0.03) and protein levels. Furthermore, the risk variants were associated with a marked attenuation in the induction of PRDM1 following radiation exposure (p=0.002). Thus, we identified a new risk locus for SMNs following radiation treatment for HL at 6q21. This locus is associated with both basal and radiation-induced expression of PRDM1. These findings demonstrate a novel gene-exposure interaction associated with radiation-induced carcinogenesis and suggest that patients homozygous for the risk variants may benefit from early cancer screening. 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 5092. doi:10.1158/1538-7445.AM2011-5092
Medical Malpractice — The Canadian Experience
Authors: Peter C. Coyte, Donald N. Dewees, Michael J. Trebilcock
Journal: New England Journal of Medicine (1991)

IN this paper we describe the legal system for dealing with malpractice claims in Canada, contrasting it with that in the United States and suggesting reasons for the dramatically different liability costs imposed on physicians. Despite a lower frequency of litigation and cost of insurance in Canada, growth rates in both frequency of claims and size of awards are similar in the two countries, and average awards are not very different. We have explored the factors contributing to the upward trend of liability in Canada, some of which appear also to influence malpractice liability in the United States. This study . . .
Long-term Variability in Glycemic Control Is Associated With White Matter Hyperintensities in APOE4 Genotype Carriers With Type 2 Diabetes
Authors: Abigail Livny, Ramit Ravona-Springer, Anthony Heymann, Rachel Priess, Tammar Kushnir, Galia Tsarfaty, Leeron Rabinov, Reut Moran, Hadass Hoffman, Itzik Cooper, Lior Greenbaum, Jeremy Silverman, Mary Sano, Sterling C. Johnson, Barbara B. Bendlin, Michal Schnaider Beeri
Journal: Diabetes Care (2016)

We assessed whether the apolipoprotein ε4 (APOE4) genotype affects the relationship of variability in long-term glycemic control (measured by HbA1c SD of multiple measurements) with white matter hyperintensities (WMHs) in elderly patients with type 2 diabetes (T2D).WMH volume was generated from structural T1 and fluid-attenuated inversion recovery MRI in each subject. The analysis included 124 subjects; 27 (21.8%) had one or more APOE4 alleles.HbA1c variability was associated with significantly higher WMH in APOE4 carriers (r = 0.47, P = 0.03), controlling for age, sex, mean HbA1c, number of follow-up years, and a composite of cardiovascular risk factors, but not in noncarriers (r = -0.04, P = 0.71; P for interaction = 0.050).The results suggest that the APOE4 genotype affects the relationship of long-term glycemic control with WMH load so that APOE4 carriers may be more vulnerable to the insults of poor control.