tbuckley/cabot-search huggingface dataset:
Seronegative Lyme Disease
Journal: New England Journal of Medicine (1989)

Abstract The diagnosis of Lyme disease often depends on the measurement of serum antibodies to Borrelia burgdorferi, the spirochete that causes this disorder. Although prompt treatment with antibiotics may abrogate the antibody response to the infection, symptoms persist in some patients. We studied 17 patients who had presented with acute Lyme disease and received prompt treatment with oral antibiotics, but in whom chronic Lyme disease subsequently developed. Although these patients had clinically active disease, none had diagnostic levels of antibodies to B. burgdorferi on either a standard enzyme-linked immunosorbent assay or immunofluorescence assay. On Western blot analysis, the level of immunoglobulin reactivity against B. burgdorferi in serum from these patients was no greater than that in serum from normal controls. The patients had a vigorous T-cell proliferative response to whole B. burgdorferi, with a mean (±SEM) stimulation index of 17.8±3.3, similar to that (15.8±3.2) in 18 patients with chro...
AB1259 Comparison of two assays for the determination of anti-citrullinated peptide antibodies (ACPA) using a routine patient cohort
Authors: A. Swart, G. Lakos, J. Wu, I. Gürtler, M. Mahler
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Anti-citrullinated peptide antibodies (ACPA) are an important serological marker in the diagnosis of rheumatoid arthritis (RA). A variety of different test systems are available for ACPA detection. <h3>Objectives</h3> This study compares two ACPA assays in samples sent for routine testing in a clinic specialized in rheumatology. Special objective is to compare the two assays in Rheumatoid factor (RF) negative and early RA. <h3>Methods</h3> 295 sera were collected from patients for whom a CCP test was ordered. Samples were tested for ACPA by QUANTA Lite® CCP 3 (INOVA Diagnostics, Inc., San Diego, CA, USA) and EliA® CCP (Phadia, Germany). RF was determined using turbidimetry and RF(II) (Biokit, Spain). <h3>Results</h3> Good qualitative (96.6%, <i>kappa=</i> 0.93) and quantitative agreements (Spearman rho=0.77; <i>p</i>&lt;0.0001) were observed between the two tests. Seven samples were CCP3+/CCP2- and one sample was CCP2+/CCP3-. Of the 9 CCP3+/CCP2- patients, 6 (66.7%) had RA, one patient had ankylosing spondylitis, one osteoarthritis and one psoriasis arthritis. The CCP3-/CCP2+ patient had juvenile RA. At the manufacturer’s cut-offs, the sensitivities and specificities were 77.3/98.1% (CCP2), 81.6%/96.8% (CCP3) and 65.2%/89.6% (RF), respectively. At a cut-off which yields 99% specificity, the sensitivities were 59.6% (CCP2) and 69.5% (CCP3). 49/141 (34.8%) RA patients were RF negative. The mean age and the average disease duration were 62.3 years (standard deviation, SD=12.0) and 8.5 years (SD=8.8), respectively. The sensitivities were 49.0% (CCP2) and 57.1% (CCP3) in the RF negative group and 38.7% (CCP2) and 51.6% (CCP3) in the RF negative and early RA (disease duration &lt;5 years; n=31). <h3>Conclusions</h3> A good overall agreement between CCP2 and CCP3 was observed. Discrimination between RA and non-RA cases was better using CCP3, especially in early and RF negative RA. Both ACPA assays outperformed RF. Further studies, preferrentially in a uniform multi-center design, are needed to confirm the higher sensitivity of CCP3 in early and RF negative RA. <h3>Disclosure of Interest</h3> A. Swart: None Declared, G. Lakos Employee of: INOVA, J. Wu Employee of: INOVA, I. Gürtler: None Declared, M. Mahler Employee of: INOVA
Abstract LB-42: Inducible mouse models for studying liver stem cell activation and tumor development
Authors: Yoko Endo, Mingjun Zhang, Sachie Yamaji, YONG CANG
Journal: Cancer Research (2011)

Abstract In contrast to skin and intestine, liver does not undergo constant renewal, but it can regenerate itself after massive damage or volume loss. Liver regeneration is driven by proliferation of parenchymal hepatocytes, but when hepatocyte proliferation is compromised, quiescent liver stem cells (LSCs) can be activated to differentiate to transit-amplifying oval cells and eventually to hepatocytes and cholangiocytes. Currently no specific biomarkers have been defined for LSCs, making it difficult to characterize this rare population of cells. Conventional rodent models, i.e., mice or rats treated with liver damaging chemicals followed by partial hepatectomy, are not ideal for studying LSCs due to the promiscuous toxicity of the chemicals and the lack of distinguishing damaged and non-damaged cells. Here we demonstrate that hepatocyte-specific deletion of Damaged DNA Binding protein 1 (DDB1), an E3 ubiqutin ligase required for cell cycle progression targeted by oncogenic hepatic B virus X protein, abolishes self-renewal capacity of hepatocytes. This defect leads to compensatory activation of DDB1-expressing and EpCam-positive oval cells. These DDB1 mutant mice exhibit very minor liver damage, compared with mice that are treated with diethyldithiocarbamate (DDC). These EpCam-positive oval cells, purified by fluorescent-activated cell sorting, express both hepatotcyte and cholangiocyte markers, can form colonies in vitro, and differentiate to hepatocytes after transplantation. Microarray analysis was performed to compare gene expression profiles in EpCam-positive cells isolated from DDB1 mutant mice and from DDC-treated mice. Several previously unrecognized genes are found to be specifically upregulated in DDB1 mutant mice. LGR5, a stem cell marker found in intestine, colon, stomach, and hair follicles, is demonstrated to be not expressed in facultative LSCs or oval cells in both our genetic models and DDC models. Interestingly, DDB1 mutant mice develop liver tumors in an age-dependent manner, and the onset of tumorigenesis is positively correlated to the extent of LSC activation. We are currently investigating the possible origin of these tumors from activated LSCs. 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 LB-42. doi:10.1158/1538-7445.AM2011-LB-42
Attorneys general from 29 US states urge tougher e-cigarette regulations
Authors: M. McCarthy
Journal: BMJ (2014)

Attorneys general from 29 states have called on the US Food and Drug Administration to impose tougher regulations on electronic cigarettes (e-cigarettes).

These E-cigarettes are battery powered devices that generate a vapor containing nicotine and have become increasingly popular among smokers and nonsmokers seeking the psychoactive effects of nicotine without smoking traditional cigarettes.

Supporters of e-cigarettes argue that the devices provide a safer alternative to cigarettes and can help smokers wean themselves off traditional tobacco products. But …
Abstract 3484: Murine and human lymphatic endothelial cells show similar marker profiles and migratory properties
Authors: Sanja Coso, Elizabeth D. Williams
Journal: Cancer Research (2011)

Abstract Introduction: Lymphangiogenesis (growth of nascent lymphatic vessels in vivo and proliferation, migration and tube formation of lymphatic endothelial cells (LECs) in vitro) plays a key role in lymph node metastasis in a number of tumour types (1), including prostate cancer. Mechanisms underlying tumor cell-lymphatic vessel interactions are critical to understand. Thus determining the molecular basis of LEC motility and its relationship to lymphangiogenesis and subsequent metastasis will play an important part in developing novel strategies to prevent metastasis. We have previously shown that members of the vascular endothelial growth factor (VEGF) family regulate migration of human LECs (2). As the effect of stimulation with VEGF family ligands has not been reported in murine LECs, this study aims to isolate and characterize murine LECs and to compare their migratory profiles to human LECs. This data will be important in determining the relevance of experiments utilizing LECs derived from transgenic and/or human tumor-bearing mice to the study of lymphangiogenesis in human cancers. Results: Murine LECs were successfully isolated from prostate and skin using a CD34 depletion, CD31 positive selection strategy. Murine LECs expressed lymphatic endothelial cell markers Prox-1 and LYVE-1. The migratory profile of murine LECs was compared to human LECs using a panel of extracellular substrates and VEGF family ligands. VEGF-C and VEGF-D potently stimulated murine LEC migration in vitro. Stimulation of murine LECs with VEGF-C caused activation of pAKT(Ser347), Erk1/2 and JNK signalling pathways, consistent with observations in human LECs. Conclusions: This study describes a successful, robust protocol for isolation of murine LECs. Murine LECs derived from transgenic and knock-out mouse models will provide important insights into the molecular mechanisms of lymphangiogenesis and allow the study of LECs in the context of cancer metastasis and other disease associated with altered lymphatic vessel architecture or function. (1) Mumprecht V, Detmar M (2009) J Cell Mol Med, 13: 1405-16 (2) Zeng Y, Opeskin K, Goad J, Williams ED (2006) Cancer Res, 66: 9566-75 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 3484. doi:10.1158/1538-7445.AM2011-3484
S120 Right Ventricular Dysfunction In Pulmonary Hypertension With Combined Pulmonary Fibrosis And Emphysema Syndrome
Authors: A. Swift, S. Rajaram, D. Capener, C. Elliot, R. Condliffe, J. Hurdman, D. Kiely, J. Wild
Journal: Thorax (2014)

<h3>Introduction</h3> Recent studies have suggested that the coexistence of emphysema and fibrosis alters clinical outcome. The aim of this study was to investigate the comparative clinical characteristics, pulmonary function, haemodynamics and right ventricular (RV) function and outcome in patients with pulmonary hypertension associated with combined pulmonary fibrosis and emphysema (PH-CPFE), chronic obstructive pulmonary disease (PH-COPD) and interstitial lung disease (PH-ILD). <h3>Methods</h3> In 79, incident patients with pulmonary hypertension associated with respiratory disease, cardiovascular magnetic resonance imaging was performed at 1.5T. Emphysema and fibrosis were scored on high resolution computed tomography scans. Demographic data, lung function tests and right heart catheterisation were also performed. <h3>Results</h3> Patients with pulmonary hypertension associated with combined pulmonary fibrosis and emphysema syndrome had lower right ventricular ejection fraction when compared to both patients with PH-COPD and PH –ILD (p &lt; 0.05). At Kaplan-Meier analysis, patients with PH-CPFE patients had significantly worse outcome than those with PH-COPD (p = 0.015), and borderline worse outcome than patients with PH-ILD (p = 0.050), <b>Figure</b>. 48 of 94 patients were diagnosed with severe PH-RESP, defined at mPAP≥40 mmHg. WHO functional class (p = 0.036), TLCO (p = 0.019), RVEF (p = 0.033) were significant independent predictors of outcome in patients with severe PH-RESP. <h3>Conclusion</h3> Patients with severe PH-RESP have a dire clinical outcome. RVEF is an independent predictor of adverse outcome in these patients and may be a powerful biomarker for use in clinical trials of targeted therapy in patients with pulmonary hypertension associated with lung disease, particularly given the unreliable performance of echocardiography in patients with advanced lung disease.
AB0421 Outcomes of infliximab treatment in canadian rheumatoid arthritis patients of different age groups
Authors: R. Faraawi, M. Baker, W. Bensen, E. Rampakakis, J. Sampalis, S. Otawa
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Rheumatoid Arthritis (RA) is a chronic inflammatory disease with an average age of onset of ∼55 years. Given that aging affects many biological processes, including immunological, the patient profile and response to anti-TNF treatment may differ with age. The objective of this real-life observational Canadian study was to assess the influence of age on baseline characteristics as well as on response to treatment with Infliximab. <h3>Methods</h3> Data for this analysis were obtained from BioTRAC, an observational prospective registry of adult RA patients initiated on treatment with Infliximab since 2002 and managed as per routine care. Patients enrolled were biologic-naïve or had initiated treatment with a biologic for a period of &lt;6 months prior to enrolment. In this analysis, 545 RA patients were included who were enrolled by June, 2011 and had at least one follow-up assessment. Patients were divided into 5 subgroups based on age at time of enrollment: ≤40, 41-50, 51-60, 61-70, and &gt;70 years. <h3>Results</h3> Among the 545 patients comprising the study cohort, 14% were ≤40 years of age, 18% were 41-50 years-old, 31% were 61-70 years of age, while 23%, and 14% of patients belonged to the 61-70, &gt;70 age subgroups, respectively. At baseline, a significantly higher proportion in the older subgroups were RF+ (60%, 68%, 79%, 77%, and 79% of patients, respectively) and of female gender (74%, 69%, 71%, 83%, 84% of patients, respectively). Furthermore, significant between-group differences were observed in disease duration (P&lt;0.001), HAQ (P&lt;0.001), ESR (P&lt;0.001), CRP (P=0.021), and DAS28-ESR (P=0.003) with disease duration and severity increasing with age. However, morning stiffness, TJC, SJC, SGA, PGA and DAS28-CRP were comparable between-groups. Upon 6-months of treatment, remission achievement was significantly higher in younger subgroups with 41%/27%/15%/17%/13% of patients achieving DAS28-ESR remission, 31%/36%/16%/17%/17% achieving DAS28-CRP remission, 20%/27%/5.4%/11%/13% achieving SDAI remission, and 15%/13%/4%/6%/5% of patients achieving ACR/EULAR remission in the ≤40, 41-50, 51-60, 61-70, and &gt;70 patient subgroups, respectively. However, regardless of age group, all parameters studied (morning stiffness, HAQ, ESR, CRP, TJC, SJC, SGA, PGA, SDAI, DAS28-ESR, and DAS28-CRP) significantly (P&lt;0.05) improved over time upon treatment with Infliximab for 36-months, with the exception of ESR in the &gt;70 years-of-age subgroup. <h3>Conclusions</h3> The results of this observational study have shown that Infliximab is effective in improving outcomes in rheumatoid arthritis over a three year period, regardless of age. However, significant variation in patient baseline characteristics and remission rates within various age groups is observed. <h3>Disclosure of Interest</h3> None Declared
PTU-183 Ineffectiveness of 18F-Fluorodeoxyglucose positron emission tomography in the evaluation of tumour response after completion of neoadjuvant chemoradiation in oesophageal cancer
Authors: G Piessen, W B Robb, G Petyt, A Duhamel, X Mirabel, D Huglo, C Mariette
Journal: Gut (2012)

<h3>Introduction</h3> After primary CRT, a non-invasive evaluation of the tumour response could help in the treatment decision to identify patients who may benefit from surgery. Whether FDG-PET provides clinically relevant information remains questionable. The objective of this prospective trial was to evaluate the role of 18F-Fluorodeoxyglucose-positron emission tomography (FDG-PET) in the assessment of tumour response after the completion of neoadjuvant chemoradiation (CRT) in patients with locally advanced resectable oesophageal cancer. <h3>Methods</h3> Operable patients with locally advanced oesophageal cancer (clinically staged T3 N0-1 M0) were enrolled. The complete treatment plan included neoadjuvant CRT (cisplatin + 5-Fluorouracil/45 Gy) followed 6–8 weeks later by a transthoracic en bloc oesophagectomy. Morphological evaluations combined with FDG-PET results were performed 2 weeks before and 4–6 weeks after the completion of CRT. Intratumoural pre- and post-treatment FDG-standardised uptake values were assessed (SUV1, SUV2, percentage change). These variables were correlated with pathologic and morphologic responses and survival. Investigators were blinded to the FDG-PET results unless metastatic disease was suspected. <h3>Results</h3> Out of 60 total patients, 46 underwent the complete treatment plan (median age: 60.1 years; adenocarcinoma: 25 patients; squamous cell cancer: 21 patients). A major pathological response occurred in 19.6% of patients and was associated with a favourable outcome (p<i>=</i>0.057). Neoadjuvant CRT led to a significant reduction in intratumoral FDG-uptake (p<i>&lt;</i>0.001). No significant association was seen between a pathologic response (either complete or major) and the FDG-PET results (p<i>&gt;</i>0.280). The SUV2 value was correlated with a morphological response and the possibility to perform an R0 resection (p<i>&lt;</i>0.018; ROC analysis: SUV2 threshold = 5.5). No significant association was found between metabolic imaging and recurrence or survival. <h3>Conclusion</h3> FDG-PET does not effectively correlate with pathologic response and long-term survival in patients with locally advanced oesophageal cancer undergoing neoadjuvant CRT followed by surgery (registered on http://www.e-cancer.fr website, RECF0350, 2002-1936R). <h3>Funding</h3> Funded by the French ministry of Health – Programme Hospitalier de Recherche Clinique 2002. <h3>Competing interests</h3> None declared.
Lymph Node Evaluation for Colon Cancer
Authors: K. Soreide
Journal: JAMA (2011)

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Variability of Metal Levels in Spot, First Morning, and 24-Hour Urine Samples over a 3-Month Period in Healthy Adult Chinese Men
Authors: Yi-Xin Wang, Wei Feng, Qiang Zeng, Yang Sun, Peng Wang, Ling You, Pan Yang, Zhen Huang, Song-Lin Yu, Wen-Qing Lu
Journal: Environmental Health Perspectives (2015)

Metals in single spot urine samples are often used to estimate individual exposure in human studies. However, measurements in urine could vary greatly over time due to variable exposure, potentially leading to exposure misclassification.We examined the variability of metal levels in the urine of 11 men who provided 529 samples on 8 days during a 3-month period, which corresponds to the duration of spermatogenesis.The urinary levels of arsenic (As), cadmium (Cd), cobalt (Co), copper (Cu), lead (Pb), molybdenum (Mo), and nickel (Ni) were measured using inductively coupled plasma-mass spectrometry. We calculated the intraclass correlation coefficients (ICCs) to assess the reproducibility of metal measures and computed the sensitivity and specificity to evaluate how well spot urine samples determined the individuals' 3-month average exposure.Fair to good reproducibility was observed for the serial measurements of Cd (ICC = 0.53) in spot samples collected during the 3-month period, whereas the serial measurements of As, Co, Cu, Pb, Mo, and Ni showed poor reproducibility (ICCs = 0.01-0.29). Use of single spot urine samples to classify the high (top 33%) 3-month average metal levels had uniformly high specificities (0.70-0.84) but relatively low sensitivities (0.40-0.57), except for Cd (0.77). The minimum number of specimens (k) required to estimate the participant-specific mean for the seven metals within 20% of the "true" values ranged from 3 for Cd to 27 for Ni.The high variability observed in the urinary levels of As, Co, Cu, Pb, Mo, and Ni suggests that a single measurement provides only a brief snapshot in time of the exposure levels of an individual, which can result in a moderate degree of exposure misclassification.Wang YX, Feng W, Zeng Q, Sun Y, Wang P, You L, Yang P, Huang Z, Yu SL, Lu WQ. 2016. Variability of metal levels in spot, first morning, and 24-hour urine samples over a 3-month period in healthy adult Chinese men. Environ Health Perspect 124:468-476; http://dx.doi.org/10.1289/ehp.1409551.
Transmission of Idiopathic (Autoimmune) Thrombocytopenic Purpura by Liver Transplantation
Authors: Peter J. Friend, Leo J. McCarthy, Ronald S. Filo, Steven B. Leapman, Mark D. Pescovitz, Laurence Lumeng, David Pound, Konstance Arnold, Ronald Hoffman, Janice G. McFarland, Richard H. Aster
Journal: New England Journal of Medicine (1990)

Chronic idiopathic thrombocytopenic purpura is an autoimmune disorder in which the destruction of autologous platelets is mediated by autoantibodies directed against platelet-surface constituents.1 Glycoproteins IIb and IIIa, which exist in the platelet membrane in a 1:1 complex (IIb-IIIa), appear to be the main target molecules for these autoantibodies.2 3 4 The destruction of autologous platelets is thought to result from the ingestion of autoantibody-coated platelets by phagocytic cells in the spleen and other organs.1 The functional state of the reticuloendothelial system may influence the rate of cell destruction in individual patients.5 We recently encountered a patient who had severe, life-threatening thrombocytopenia after . . .
Ketoacidosis in Pancreatectomized Man
Authors: Adrian J. Barnes, Stephen R. Bloom, K. George M. M. Alberti, Patricia Smythe, Frank P. Alford, Don J. Chisholm
Journal: New England Journal of Medicine (1977)

We investigated the importance of glucagon in the development of diabetic ketoacidosis by withholding insulin from six patients with juvenile-type diabetes and four totally pancreatectomized subjects. Patients were fasting and had previously been maintained on intravenous insulin for 24 hours. In diabetic patients plasma glucagon concentrations rose sharply after withdrawal of insulin, and the increases were accompanied by a rise in blood ketone concentration of 4.1+/-0.7 (S.E.M.) and blood glucose concentration of 12.5+/-1.8 mmol per liter by 12 hours. In the pancreatectomized patients, despite the absence of measurable glucagon, blood ketones rose by 1.8+/-0.8 and blood glucose by 7.7+/-1.5 mmol per liter. Thus, glucagon is not essential for the development of ketoacidosis in diabetes, as has previously been suggested, but it may accelerate the onset of ketonemia and hyperglycemia in situations of insulin deficiency.
Bilateral Diffuse Hypoperfusion of Posterior Temporoparietals and Occipitals in Tc-99m HMPAO Brain SPECT in a Patient With Noncommunicating Hydrocephalus
Authors: WEI-JEN SHIH, C. H. TSAI, VICKIE STIPP, GANG LU
Journal: Clinical Nuclear Medicine (1996)

Tc-99m HMPAO brain SPECT of a patient with dementia showed diffuse cortical hypoperfusion especially in the posterior temporoparietal and occipital regions. These findings are delineated easily by volume and surface three-dimensional displays. CTs of the brain showed enlargement of the lateral ventricles especially in both posterior horns. Concurrent In-111 DTPA cisternography showed no radiotracer reflux to the lateral ventricles, consistent with noncommunicating hydrocephalus. Three-dimensional displays that simplify scan interpretation can apply in a patient with hydrocephalus to evaluate extension of cerebral cortical involvement.