tbuckley/cabot-search huggingface dataset:
OP0184 Outcome of 205 Juvenile Onset SLE Patients: Single Center Experience from A Developing Country
Authors: A. Aggarwal, P. Srivastava, B. Abujam, A. Lawrence, V. Agarwal, R. Misra
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> About one fifth of SLE patients have onset before the age of 18 years. Long term outcome of these patients is difficult to assess as they are partly managed in pediatrics and then transition to adult services. Our clinic provides care to both pediatric and adult SLE patients. Further data from developing countries is scant <h3>Objectives</h3> Thus we decided to study the outcome of our cohort of juvenile onset SLE patients. <h3>Methods</h3> Medical records of patients attending the SLE clinic for the last 25 years were scanned and patients with onset of disease before age of 18 years (JSLE) were identified. In them demographic data, clinical and laboratory features, medications used, outcome and complications was retrieved. Overall outcome as well as actuarial survival was calculated <h3>Results</h3> There were 205 patients with JSLE among a total of 1015 SLE patients. Their median age at onset was 14 years (1-18 years) and mean duration of illness prior to presentation at this tertiary care hospital was 1 year (0.2-20 years). There were 292 girls and 13boys. Fever, alopecia, arthritis and renal involvement was present in more than two third of patients. One third had CNS disease with seizures being the commonest presentation. Among 130 patients with renal involvement kidney biopsy was done in Class I in 1, Class II in 13, class III in 24, class IV in 41 and class V in 12. Median follow up was 4 years (0-24 years). Flares were seen in nearly half the patients with 66 patients having 1 flare (41being major flares), 24 patients having 2 flares (28 being major flares), 9 patients having 3 flares (16 being major), 4 having 4 flares (9 being major) and 1 patient having 6 flares (all major). Acturial 5 year survival was 95% and 10 year survival was 89%. 55 patients had an infective episode during the follow up with almost half requiring hospitalization. Eleven patients died (5 during first admission due to uncontrolled disease activity, 2 with ESRD, 1 TB, 1 PAH with CAPS, 1 staph sepsis, 1 diabetic ketoacidosis). <h3>Conclusions</h3> JSLE in a developing country like India has good outcome but has significant morbidity due to disease flares and infections <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5601
Abstract 3095: The molecular, cellular, and physiological consequences of disrupting the HIF-1α interaction
Authors: Kelie M. Reece, Stephen T. Pisle, Emily D. Richardson, Kristina M. Cook, Douglas K. Price, William D. Figg
Journal: Cancer Research (2011)

Abstract Many cancers contain regions of hypoxia due to rapid cell proliferation and the presence of blood vessels within the tumor that are structurally and functionally abnormal, resulting in the heterogeneity of blood flow. This state of hypoxia is associated with increased risk of treatment failure, metastasis and patient mortality. A principal mechanism by which cancer cells adapt to the hypoxic microenvironment is through the activity of hypoxia-inducible factor 1 (HIF-1), a heterodimeric transcription factor composed of an O2-regulated HIF-1α subunit that dimerizes with a constitutively expressed HIF-1β subunit. HIF-1α expression under hypoxic conditions regulates hundreds of genes including those that play key roles in invasion/metastasis, angiogenesis, tumor cell immortalization, and resistance to chemotherapy and radiation. Therefore, the inhibition of transcription driven by HIF has the potential for cancer treatment. One way to reduce the activity of this protein is by disrupting the complex that HIF forms with p300, an essential transcriptional coactivator. Previous data from our laboratory showed that several members of the epidithiodiketopiperazine (ETP) family of natural products are able to block the interaction between HIF-1α and p300. Here, we extend these studies by examining the comprehensive effect that select ETPs have on the disruption of the HIF/p300 complex at the molecular, cellular, and physiological levels. We began our studies by performing a series of rat aortic ring assays to determine the antiangiogenic effect of selected ETPs, namely chetomin, chaetocin, and gliotoxin. Chetomin and chaetocin concentrations of 50 nM inhibited approximately 90% of outgrowth, while 500 nM of gliotoxin was needed to achieve a similar effect; these compounds had GI50 of 22, 11, and 175 nM, respectively. In ongoing work, we hope to determine if the antiangiogenic effects that were observed in our rat aortic ring assays, are due to disruption of the HIF/p300 complex. To this end we are immunoprecipitating the complex from cells in the absence or presence of the aforementioned ETPs. The molecular consequences of blocking the HIF/p300 interaction will be assayed by qRT-PCR for hypoxia-regulated genes such as VEGF and GLUT1; cell proliferation and migration assays will also be performed to monitor cellular effects. Together, these results will be key in determining the feasibility of targeting this interaction for cancer therapeutics. 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 3095. doi:10.1158/1538-7445.AM2011-3095
Abstract 3662: Absence of leukotriene B4 receptor-1 (BLT1) protects against lung cancer
Authors: Shuchismita R. Satpathy, Elangovan Krishnan, Rajesh K. Sharma, Venkatakrishna R. Jala, W. Glenn McGregor, Haribabu Bodduluri
Journal: Cancer Research (2011)

Abstract Chemokines direct leukocyte trafficking, which plays a major role in immune and inflammatory responses, thus contributing to (or) modulating a number of disease conditions. During carcinogenesis leukocytes infiltrate the site of the tumor microenvironment and could exert a major influence on promotion or suppression of cancer depending on their activation status. Leukotriene B4, a pro-inflammatory lipid chemokine, mediates many of its activities through BLT1, a high affinity G-protein coupled receptor. BLT1 is expressed on an array of immune cells and has been implicated to play a critical role in many inflammatory diseases. We investigated whether BLT1 also influences lung carcinogenesis, the leading cause of cancer-related deaths worldwide. In this study, we used BLT1-deficient mice (BLT1-/-) to determine their susceptibility to lung cancer development in a transgenic model expressing an oncogenic form of K-ras (K-ras LA1) as well as in carcinogen (3-Methylcholanthrene; 3MCA)-induced and inflammation (butylated hydroxy toluene; BHT) – promoted murine lung cancer model. We found that in the activated K-ras transgenic background the BLT1-/- mice showed fewer and smaller lung tumors as compared to the BLT1+/+ mice. In the MCA-BHT induced lung cancer model also the BLT1-/- mice showed fewer and smaller lung tumors than the BLT1+/+ mice. Lung lesions in BLT1-/- mice were more of adenomatous hyperplasia type and fewer adenomas when compared to those in BLT1+/+ mice. Moreover, the frequency of induced mutations in cells derived from the lungs of BLT1-/- mice was greatly reduced compared to BLT1+/+ mice. Pulmonary inflammation was assessed in bronchoalveolar lavage (BAL) fluids following one, three or six weekly injections of BHT. At one and three week time points macrophages, and at six weeks lymphocytes constituted the predominant leukocyte subtypes in the BAL fluids of BLT1+/+ mice. In BLT1-/- mice both of these responses were significantly attenuated leading to an overall reduction in pulmonary inflammation. Based on these results, we conclude that BLT1 mediated pulmonary inflammation has a promoting role in lung cancer. 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 3662. doi:10.1158/1538-7445.AM2011-3662
OP0019 Anti-citrullinated protein antibodies directly induce bone loss in rheumatoid arthritis
Authors: U. Harre, D. Georgess, R. Axmann, H. Bang, R. Toes, H.U. Scherer, A. Catrina, L. Klareskog, P. Jurdic, G. Schett
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Autoantibodies against citrullinated proteins (ACPA) are amongst the strongest risk factors for bone destruction in rheumatoid arthritis (RA) <h3>Objectives</h3> We therefore hypothesized that these autoantibodies directly influence bone metabolism. <h3>Methods</h3> A strong and specific association between autoantibodies against citrullinated proteins and serum markers for osteoclast-mediated bone resorption was found in the serum of RA patients. Moreover, human osteoclasts expressed enzymes eliciting protein citrullination such as PAD2 and revealed specific inducible N-terminal citrullination of vimentin during their differentiation process. Affinity purified human autoantibodies against mutated citrullinated vimentin (MCV) not only bound to the osteoclast surface, but also lead to a robust induction of osteoclastogenesis and bone resorptive activity. Adoptive transfer of human MCV antibodies into RAG1-/- mice was followed by induction of osteopenia and increased osteoclastogenesis in vivo. This effect was based on the inducible release of TNFa from osteoclast precursors and the subsequent increase of CD11b+ osteoclast precursor cell numbers with enhanced expression of RANK and CSF1 receptors <i>in vivo</i>. <h3>Conclusions</h3> Our data thus suggest that autoantibody formation to citrullinated vimentin directly induces bone loss and provides a novel link between the adaptive immune system and bone. <h3>Disclosure of Interest</h3> None Declared
Early Metabolic Defects in Persons at Increased Risk for Non-Insulin-Dependent Diabetes Mellitus
Authors: Johan Eriksson, Anja Franssila-Kallunki, Agneta Ekstrand, Carola Saloranta, Elisabeth Widén, Camilla Schalin, Leif Groop
Journal: New England Journal of Medicine (1989)

To identify early metabolic abnormalities in non-insulin-dependent diabetes mellitus (NIDDM), we measured sensitivity to insulin and insulin secretion in 26 first-degree relatives of patients with NIDDM and compared these subjects both with 14 healthy control subjects with no family history of NIDDM and with 19 patients with NIDDM. The euglycemic insulin-clamp technique, indirect calorimetry, and infusion of [3–3H]glucose were used to assess insulin sensitivity. Total-body glucose metabolism was impaired in the first-degree relatives as compared with the controls (P<0.01). The defect in glucose metabolism was almost completely accounted for by a defect in nonoxidative glucose metabolism (primarily the storage of glucose as glycogen). The relatives with normal rates of metabolism (mean±SEM, 1.81±0.27 mg per kilogram of body weight per minute) and impaired rates (1.40±0.22 mg per kilogram per minute) in oral glucose-tolerance tests had the same degree of impairment in glucose storage as compared with healthy control subjects (3.76±0.55 mg per kilogram per minute; P<0.01 for both comparisons). During hyperglycemic clamping, first-phase insulin secretion was lacking in patients with NIDDM (P<0.01) and severely impaired in their relatives with impaired glucose tolerance (P<0.05) as compared with control subjects; insulin secretion was normal in the relatives with normal glucose tolerance. We conclude that impaired glucose metabolism is common in the first-degree relatives of patients with NIDDM, despite their normal results on oral glucose-tolerance tests. Both insulin resistance and impaired insulin secretion are necessary for the development of impaired glucose tolerance in these subjects. (N Engl J Med 1989; 321:337–43.)
Atmospheric pollution and lung cancer.
Authors: R Doll
Journal: Environmental Health Perspectives (1978)

Lung cancer is consistently more common in urban areas than in rural. The excess cannot be accounted for by specific occupational hazards but some of it might be due to the presence of carcinogens in urban air. The excess cannot be wholly due to such agents, because the excess in nonsmokers is small and variable. Cigarette consumption has also been greater in urban areas, but it is difficult to estimate how much of the excess it can account for. Occupational studies confirm that pollutants present in town air are capable of causing lung cancer in man and suggest that the pollutants and cigarette smoke act synergistically. The trends in the mortality from lung cancer in young and middle-aged men in England and Wales provide uncertain evidence but support the belief that atmospheric pollution has contributed to the production of the disease. In the absence of cigarette smoking, the combined effect of all atmospheric carcinogens is not responsible for more than about 5 cases of lung cancer per 100,000 persons per year in European populations.
Abstract P2-14-08: Patient Perspectives on Information Communicated Regarding Effects of Treatment on Fertility
Authors: SB Goldfarb, JF Kelvin, B Thom, J Kaplan, S Corcoran, A Margolies, MS McCabe, L Norton, C Hudis, E Basch, MN. Dickler
Journal: Cancer Research (2010)

Abstract Background: Many breast cancer survivors diagnosed during their reproductive years desire to have children after treatment and are distressed about the possibility of treatment-induced infertility. Informing patients about fertility preservation options before therapy may optimize quality of life after treatment. This study was undertaken to evaluate the information patients received about effects of therapy on fertility, early menopause, and fertility preservation options. Methods: An IRB approved cross-sectional study was performed to evaluate patient perceptions of the impact of treatment on fertility and early menopause. The survey was developed at Memorial Sloan-Kettering Cancer Center (MSKCC) for patients ages 18-45, with items derived from existing surveys in the literature and input from a multidisciplinary committee. We evaluated two groups of patients, one who had completed treatment and the other who was currently undergoing therapy. Surveys were mailed to 395 women who began treatment (all modalities) for breast cancer at MSKCC between 7/1/07 and 6/30/08. A second cohort of patients (n=35) completed surveys during patient visits to breast cancer medicine ambulatory clinics between 3/22/2010 and 4/8/2010. Results: The survey was completed by 159 pts. (129/395 and 30/35). At the time of diagnosis, 69% (110/159) had children and 45% (70/156) were interested in having children. 79% (123/155) reported that the impact of treatment on fertility was discussed with them before initiating therapy. A healthcare provider initiated the discussion 54% (83/155) of the time. However, only 35% (54/152) and 47% (71/150) of women felt they received an adequate amount of information about the effect of cancer treatment on fertility and menopause, respectively. Based on their ranking, patients preferred to receive fertility information in person either from their physician or a fertility specialist, or through written material. After treatment, 5 patients attempted pregnancy (7 naturally, 1 with assisted technology), yielding 8 live births. Conclusions: Many breast cancer survivors wish to have children after treatment. To optimize success, patients should be adequately informed about the effects of therapy on fertility, early menopause, and options for fertility preservation. These findings are informing an institution-wide fertility program. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-14-08.
PWE-083 The Development of a Stratified Model of Follow up Care for Adult Patients with Inflammatory Bowel Disease
Authors: K Kemp, J Griffiths, S Campbell, K Lovell
Journal: Gut (2013)

<h3>Introduction</h3> There is concern in the UK that services for pts with long term conditions are not orgnised to promote independence with silo working in primary and secondary care with reactive services. These may be brought together formally through the development of model of care. Utilization of current out-pt spaces to regularly review stable pts is inappropriate and is challenged by commissioners. The question remains as to what models of follow up (FU) are we able to offer pts which are acceptable and feasible. The aim of this study was to develop an integrated, acceptable, modern model of FU care for pts with IBD. <h3>Methods</h3> Using the MRC Framework for complex interventions,24 IBDs (18 pts had CD, 6 UC, age range 27–72 years, disease duration range 2 – 40yr), 20 purposively selected GPs from NW England, and 3 IBD Nurses (specialist, advanced practitioner, consultant nurse) were interviewed. Participants were asked about the role of FU in IBD, experience of FU patterns, service delivery, other models of FU. Thematic analysis was undertaken using NVivo 9.0. Analysis of 3 groups of interviews were synthesised by a Cons Gastroenterologist, patient, GP, IBD Nurse, to develop the model of FU care. <h3>Results</h3> There were similarities between 3 groups of interviews. Pts did not want to be seen when well, GPs wanted more involvement in care and there is scope for an IBD outreach nurse at interface of primary/secondary care. Discharging quiescent pts into enhanced GP care, to ensure equitable treatment, was acceptable to all, as was the concept of ‘virtual’ clinics. Patients would initiate self referral within the virtual arm whilst pts under GP care would be referred by GP. Pts would be referred as a rapid FU &lt; 7days and not as a new pt tariff. Complex IBD patients would remain under secondary care. Patients will move across the 3 arms depending on disease. <h3>Conclusion</h3> This study provides an acceptable integrated model of FU for pts with IBD. It takes into account UK policy to reduce inappropriate FU, with emphasis on self management and integrating care, placing the pt closer to home, with secondary care emphasis on complex pt management. <h3>Disclosure of Interest</h3> None Declared.
AB0964 Dactylitis Ultrasonographic Features Correlation to Dermatological, Genetic and Activity Indices in Early Psoriatic Arthritis Patients
Authors: F. Bandinelli, F. Prignano, V. Denaro, L. Collaku, D. Melchiorre, S. Sladojevic, M. Matucci Cerinic
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> In early phase of Psoriatic arthritis (ePsA), US abnormalities might be sub-clinical and independent to psoriasis. <h3>Objectives</h3> To investigate the ultrasonography (US) dactylitis abnormalities in early PsA patients and to compare them to dermatological, genetic and activity indices. <h3>Methods</h3> 112 early PsA diagnosed with CASPAR criteria, were studied with MyLab70 Xview (linear probe 15 MHz) US examination of hand fingers. At US, were evaluated the Power Doppler positive synovitis (PS), the tenosynovitis-peritendinitis (TP) of flexors/extensors and the pseudotenosynovitis (PT) (PD subcutaneous signal around flexor tendons) and their correlation with dermatological (presence/absence of psoriasis, presence/absence of palmar psoriasis, presence/absence of nail dystrophy, PASI), genetic (positivity/negativity of HLAB27, B35, B38, CW6, CW7, DR1, DR4) and activity indices (BASDAI, HAQ modified for spondyloarthritis [SHAQ], normality or elevation of ESR, CRP). <h3>Results</h3> At US, in ePsA, US abnormalities at fingers were present in different percentage: 25,9% (29/112) PD positive synovitis (PS), 17,8% (20/112) tenosynovitis-peritendinitis (TP), 14,3% (16/112) pseudotenosynovitis (PT). At Yates X square test analysis, US parameters correlated to the presence of these three parameters: psoriasis (all p&lt;0,0001), palmar psoriasis (PS p&lt;0,005), nail dystrophy (PS p&lt;0,05, PT p&lt;0,0001), B27 (PS p&lt;0,0001, TP p&lt;0,01, PT p&lt;0,05), B35 (PS p&lt;0,05), B38 (PS p&lt;0,0001, TP p&lt;0,0001, PT p&lt;0,005), CW7 (PS p&lt;0,0001), DR4 (PS p&lt;0,0001, TP p&lt;0,0001, PT p&lt;0,005), CRP (all p&lt;0,0001), ESR (PS p&lt;0,0005, TP p&lt;0,0001, PT p&lt;0,0001). At Pearson correlation, US abnormalities are independent to PASI, BASDAI and SHAQ. <h3>Conclusions</h3> Dactylitis US abnormalities are correlated to the presence of psoriasis, HLA aplotypes B27-B35-B38-CW7-DR4 and CRP/ESR elevation, while are independent to severity of dermatologic involvement and clinical indices. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4283
Metabolic Differences between Obese Overweight and Muscular Overweight Men
Authors: Ronald Kalkhoff, Carlos Ferrou
Journal: New England Journal of Medicine (1971)

Exaggerated plasma insulin responses during glucose or tolbutamide tolerance tests and subnormal plasma growth-hormone increments after insulin-induced hypoglycemia were documented in 10 obese men as compared to 10 normal-weight men of the same age. Similar abnormalities did not exist in 10 extremely muscular weight lifters who were matched in age and degree of overweight to the obese group. Mean triceps skin-fold thicknesses of the obese subjects were approximately four and eight times greater than values of control and muscular men, respectively. These data suggest that metabolic changes in overweight persons are related more to degrees of body-fat accumulation than to deviations from ideal body weight or excessive lean tissue mass.
Post-Ebola Signs and Symptoms in U.S. Survivors
Authors: Lauren Epstein, Karen K Wong, Alexander J Kallen, Timothy M Uyeki
Journal: New England Journal of Medicine (2015)

The feasibility of the dilated-eye examination during routine office visits by nonophthalmologists was reported in 1987. 2 It is unclear why this practice has not been widely adopted.The importance of dilation was taught in our first-year course on physical diagnosis.A recommendation for nondilated retinal screening may miss potentially correctable signs of early retinal damage due to common systemic diseases (e.g., diabetes and hypertension).As an added benefit, the time and care of performing a dilated-eye examination builds patient-physician trust. 3
Case 26-2013
Authors: Margaret Seton, Carol C. Wu, Abner Louissaint
Journal: New England Journal of Medicine (2013)

A 46-year-old woman presented with pain and swelling in her arms and lower legs for 3 weeks. Examination showed swelling and tenderness of the left arm and tenderness in both calves. Chest imaging revealed a mediastinal mass. A diagnostic procedure was performed.