tbuckley/cabot-search huggingface dataset:
Iodine-131 Uptake in Thymic Hyperplasia With Atypical Computed Tomographic Features
Authors: EUGENE C. LIN
Journal: Clinical Nuclear Medicine (2000)

A 24-year-old woman with a history of papillary thyroid carcinoma presented with increased thyroglobulin. A whole-body scan performed after I-131 treatment showed uptake in the anterior mediastinum and the neck. A computed tomographic scan showed a prominent thymus with slightly lobulated borders. This computed tomographic appearance is atypical for thymic hyperplasia, so the possibility of metastatic disease was raised. A right neck dissection, mediastinal exploration, and thymectomy were performed. Pathologic analysis revealed metastatic carcinoma of the right cervical nodes, minimal residual thyroid, and true thymic hyperplasia with no evidence of metastatic carcinoma to the thymus. False-positive anterior mediastinal uptake of radioiodine can be caused by thymic hyperplasia, and thus should be considered even if the thymus has lobulated borders.
FRI0375 A Delphi Exercise for Treatment Algorithms for Systemic Lupus Erythematosus: Table 1
Authors: C. Muangchan, J.E. Pope
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Treatment for SLE is often organ based. The literature lacks trials and consensus for treatment in SLE when standard first or second line care is ineffective. <h3>Objectives</h3> To determine expert consensus for SLE treatment using case scenarios and especially for treatment beyond first line therapy. <h3>Methods</h3> SLE experts (n=69) were sent three surveys; writing therapies for SLE organ complications assuming inadequate response to each choice and providing a list of secondary choices. <h3>Results</h3> The response rate for the first survey where all treatment options were written by the experts was 54%. For each subsequent survey, the response rate decreased. For widespread DLE, first-line: topical steroids or tacrolimus+hydroxychloroquine (HCQ) ± glucocorticoids, then azathioprine (AZA) and switching to mycophenolate mofetil (MMF). For cutaneous vasculitis, first-line was GC ± HCQ ± methotrexate (MTX), followed by adding either AZA or MMF and then IV cyclophosphamide (CYC). For gangrenous vasculitis, first-line was glucocorticoids+CYC, then rituximab (RTX) or plasmapheresis and maintenance with AZA or MMF. For arthritis, first-line therapy was HCQ ± glucocorticoids; adding MTX and then RTX. For pericarditis refractory to NSAIDs, first-line was glucocorticoids ± HCQ, then adding AZA, MMF or MTX and then Belimumab (BLM) or RTX; and if needed pericardial window and/or aspiration. For ILD, induction was glucocorticoids+MMF or CYC, then RTX or IVIG; maintenance with AZA or MMF. For PAH, glucocorticoids+CYC or MMF+endothelin receptor antagonist, adding phosphodiesterase-5 inhibitor and then prostanoid and RTX. First-line therapy was anticoagulation ± HCQ for lupus associated antiphospholipid antibody syndrome. A direct thrombin inhibitor was second-line therapy for venous thrombosis, and adding low dose aspirin or another platelet aggregation inhibitor was a second-line option for arterial thrombosis. For mononeuritis multiplex, and CNS vasculitis, first-line induction was glucocorticoids+CYC followed by maintenance with AZA, or MMF and then RTX, IVIG or plasmapheresis. For LN type III/IV and V first-line was glucocorticoids+MMF, then adding RTX for LN type III/IV or switching to AZA, CYC or RTX for LN type V. Treatment algorithm for organ system involvements by systemic lupus erythematosus: <h3>Conclusions</h3> Consensus for SLE treatment had variable agreement but some treatment consensus beyond first line therapy was obtained. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2541
Abstract LB-203: Mathematical modeling of the dynamic interaction between cancers stem cells and non-stem cancer cells and its potential clinical implication
Authors: Xinfeng Liu, Deepak Kanojia, Pang-Kuo Lo, Hexin Chen
Journal: Cancer Research (2012)

Abstract Cancer stem cells (CSCs) have been identified in primary breast cancer tissues and cell lines. The size of CSC population varies a lot among cancer tissues and cell lines but is associated with aggressiveness of breast cancer. Despite of the high tumor heterogeneity among different samples, CSCs isolated from either primary tissues or cell lines can rapidly regenerate the original heterogeneity and maintain a relatively constant proportion of CSCs. It remains largely unknown how the CSC population is maintained within a tumor. In this study, we develop a mathematical model to explore the key factors which control the size of CSC population during tumor cell growth both in vitro and in vivo. Our mathematic modeling and experimental data suggest that there is a negative feedback mechanism to control the balance between CSC and non-stem cancer cells. We further calculated how feedback sensitivities and robustness can be regulated by different intrinsic and extrinsic factors. As an example, our mathematical model predicts that overexpression of oncogeneHER2 leads to increase in the proportion of CSC via regulating the division mode or proliferation rate of CSCs. The prediction is supported by both in vitro cell culture results and the clinical data. We also show that enrichment of CSCs in suspension culture is due to both depletion of differentiated cancer cells and partial relieve of negative feedback. Mathematical modeling this culture condition reveals that the majority of tumporspheres are derived from progenitor cancer cells but not CSCs. Overall, these findings contribute to our understanding of cancer heterogeneity and may have significant implications in development and selection of anti-cancer therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-203. doi:1538-7445.AM2012-LB-203
INFLAMMATION, BUT NOT RECRUITMENT, OF ADIPOSE TISSUE MACROPHAGES REQUIRES SIGNALING THROUGH MAC-1 IN DIET-INDUCED OBESITY (DIO)
Authors: Dennis Wolf, Nathaly Anto Michel, Bukosza Nora, David Engel, Marjorie Poggi, Christian Weber, Christoph Bode, Karlheinz Peter, Esther Lutgens, Andreas Zirlik
Journal: Journal of the American College of Cardiology (2015)
P634Myocardial connein-43 in the antiarrhythmic mechanism of antioxidant-rich red palm oil in rats with altered thyroid status.
Authors: B Bacova, C Viczenczova, T Benova, J Radosinska, J Zurmanova, S Pavelka, T Soukup, N Tribulova
Journal: Cardiovascular Research (2014)

Background and purpose: The cardiovascular system is modulated by thyroid hormones and their deficiency or excess in hypo- (HY) or hyperthyroid (TH) status may affect both cardiac function and arrhythmogenesis. We hypothesized that intercellular communication via connexin-43 (Cx43) channels might be implicated. The goal of this study was to explore myocardial Cx43 and PKC signalling in rats with altered thyroid status as well as the effects of antioxidant-rich red palm oil (RPO) intake. Design and Methods: Male, Wistar euthyroid rats (EU); HY rats (treated with 0.05% methimazole); TH rats (treated with T3/T4, 5/25μg/100g b.w./day) fed RPO (100 microL/100g b.w./day) for six weeks were compared with untreated rats. Left ventricular tissue was taken for Cx43 and PKC-epsilon mRNA and protein analysis using real-time PCR and immunoblotting. Heart function and inducible ventricular fibrillation (VF) were examined using isolated heart preparation. Key Results: Heart and left ventricular mass was increased in TH but decreased in HYrats compared to EU rats. The threshold for sustained VF was significantly lower in TH comparing to EU rats (14.17±1.5 vs 31.25±4.8 mA) but increased in both groups due to RPO (25.0±3.1. and 45.0±3.9 respectively). VF was not induced in HY and HY+RPO rats even by highest stimulus strengths (50mA). Cx43 mRNA level was increased in TH and decreased in HY rats. In contrast, Cx43 protein and its functional phosphorylated (P) forms were increased in HY, but decreased in TH rats. PKC epsilon gene transcription did not change but its protein expression was decreased in TH and increased in HY rats. RPO intake partially normalized Cx43 mRNA as well as protein expression and its P forms as well as PKC epsilon protein expression in TH rats. In addition, RPO reduced heart rate in all treated groups. In conclusion, our findings indicate that down-regulation of myocardial Cx43due to hyperthyroidism is associated with increased, while up-regulation in hypothyroidism with decreased susceptibility of the heart to VF. RPO intake increased threshold for induction of VF in eu- and hyperthyroid rats in part due to up-regulation of Cx43.
Influence of Intrauterine Relations on the Intelligence of Twins
Authors: Charles T. Kaelber, Thomas F. Pugh
Journal: New England Journal of Medicine (1969)

An association of a higher IQ for the member of twin sets with the heavier birth weight, already described for highly selected groups of twins, is reported for a numerically larger and more representative sample. For the 374 twin sets studied a higher IQ for the heavier twin is found for like-sex pairs with large birth-weight differences (300 gm or more). When information on zygosity is considered, an association is shown for monozygous sets with large birth-weight differences, but none is demonstrated for like-sex dizygous pairs. Unequal intrauterine relations, perhaps of a circulatory nature, are proposed as an explanation for the IQ differences observed among the monozygous sets.
What predicts failed cannulation and therapy at ERCP? Results of a large-scale multicenter analysis
Authors: E. Williams, R. Ogollah, P. Thomas, R. Logan, D. Martin, M. Wilkinson, M. Lombard
Journal: Endoscopy (2012)

<b>Study background and aims:</b> Predicting outcome at endoscopic retrograde cholangiopancreatography (ERCP) remains difficult. Our aim was to identify the risk factors for failed ERCP. <b>Patients and methods:</b> A prospective multicenter study of ERCP was performed in 66 hospitals across England. Data on 4561 patients were collected using a structured questionnaire completed at the time of ERCP. <b>Results:</b> In total 3209 patients had not had an ERCP prior to the study period. Considering their first ever ERCP, 2683 (84 %) were successfully cannulated, 2241(70 %) had all intended therapy completed, 360 (11 %) had some intended therapy completed, and 608 (19 %) were considered to have had a failed procedure. For first ever ERCP, factors associated with incomplete procedure (odds ratio and 95 % confidence interval) were: Billroth surgery (9.2, 3.2 – 26.7), precutting (2.0, 1.6 – 2.7), common bile duct (CBD) stone size and number (3.2, 2.1 – 4.8 for multiple, large stones), interventions in the pancreatic duct (3.4, 1.6 – 7.0), and CBD stenting (2.8, 2.2 – 3.5). Analysis of the 1352 patients who had undergone an ERCP prior to the study period indicated previous failed ERCP was also predictive of incomplete therapy (1.5, 1.1 – 2.1). The modified Schutz score correlated with ERCP completion, as did the Morriston score, even when modified to include only variables measurable before the procedure. <b>Conclusion:</b> This study confirms that patient- and procedure-based variables are key predictors of technical success and validates current methods of rating ERCP difficulty. Of note, a correlation between outcome and institutional factors, such as unit and endoscopist caseload, was not demonstrated.
Book: Parkinson's Disease: The Treatment Options
Authors: H. Allain
Journal: BMJ (1999)

Wolfgang Oertel, Peter LeWitt Martin Dunitz, £65, pp 272 ISBN 1 85317 379 7 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> It was a pleasure to read this authoritative text on the treatment of Parkinson's disease. Oertel and LeWitt are well known for their contribution to the struggle against this particularly common neurodegenerative disease, and, with the help of distinguished colleagues from north America and Europe, they have perfectly summarised both the established regimens and new developments in … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
OP0207 Inhibitory effect of tacrolimus on the progression of joint damage in patients with rheumatoid arthritis
Authors: H. Motomura, I. Matsushita, E. Seki, T. Kimura
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Tacrolimus is an immunosuppressive drug widely used for the prevention and treatment of allograft rejection in organ transplantation. In Japan it was approved of rheumatoid arthritis (RA) in 2005. Tacrolimus prevents differentiation and maturation of osteoclasts by inhibiting the activation of NFATc induced by RANKL in osteoclasts [1]. Therefore, it is expected that tacrolimus directly suppress the activation of osteoclast as well as the production of cytokines related to RA inflammation. These effects of tacrolimus may achieve the inhibition of joint destruction. Recently, an excellent clinical response of tacrolimus has been demonstrated in RA patients that were resistant to disease-modifying anti-rheumatic drugs (DMARDs) including methotrexate (MTX). However, its inhibitory effect on the joint destruction remains to be clarified. <h3>Objectives</h3> The aim of this study is to examine the inhibitory effect of tacrolimus on the progression of joint damage in patients with RA. <h3>Methods</h3> We have retrospectively examined 27 patients with RA that failed to respond to non-biologic DMARDs and administered tacrolimus for one year or more with periodical X-ray examination of both hands and feet. Expert readers analyzed the photographs and recorded modified total Sharp scores (mTSS). Progression of joint destruction was evaluated with an estimated yearly change in mTSS (ΔmTSS). Disease activity was assessed with DAS28-ESR. Treatment responses were determined by using EULAR response criteria <h3>Results</h3> The mean age was 68.2±10.5 years old, and the duration of RA was 12.5±8.5 years. The mean DAS28-ESR in the patients was 4.99 at baseline and gradually improved to 3.65 at one year. Good and moderate response rate according to EULAR improvement criteria was 22.2% and 59.3% at one year, respectively. The mean ΔmTSS before tacrolimus administration was 11.1. Mean ΔmTSS then decreased to a value of 2.98 one year after tacrolimus treatment, indicating the inhibition of the progression of joint damage. We also examined the effect of tacrolimus on the radiographic joint damage at 2 years in 19 patients who were administered tacrolimus for two years or more. In these patients, ΔmTSS during the second year was significantly lower than that in the first year, although DAS28-ESR at two years was almost same as that at one year. Furthermore, the rate of patients with 0 or less ΔmTSS, indicating complete inhibition or repair of joint damage, significantly increased to 36.8% at two years, compared with 21.1% at one year. <h3>Conclusions</h3> These findings suggest that tacrolimus has a potential to inhibit the progression of joint damage in RA patients. <h3>References</h3> Takayanagi H et al. Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. Developmental Cell 2002. <h3>Disclosure of Interest</h3> None Declared
France and Japan increase support for Global Fund; a new leader is appointed
Authors: R. Watson
Journal: BMJ (2012)

Just six weeks into his new role as general manager of the Global Fund to Fight AIDS, Tuberculosis and Malaria, Gabriel Jaramillo is using his financial and administrative expertise to transform the public-private partnership, which has disbursed over $22.6bn (£14.3bn; €17bn) of aid since it was founded in 2002.

A former chairman and chief executive officer of Sovereign Bank, Mr Jaramillo’s appointment reflected the concerns of many donors that insufficient attention was being paid to the way the funds were being used on the ground. He has been given one year to implement the …
Phase I study of the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of the histone deacetylase inhibitor (HDACi) PCI-24781
Authors: S. D. Undevia, L. Janisch, R. L. Schilsky, D. Loury, S. Balasubramanian, C. Mani, M. Sirisawad, J. J. Buggy, R. A. Miller, M. J. Ratain
Journal: Journal of Clinical Oncology (2008)

14514 Background: Histone deacetylases catalyze the removal of acetyl groups from nucleosomal histones, tubulin and other proteins and thereby play an important role in the regulation of gene expression. PCI-24781 is a broad-spectrum HDACi with potent preclinical anti-tumor activity (Buggy JJ, et al. Mol Cancer Ther 2006; 5:1309–17). Methods: Eligible patients (pts) had refractory advanced solid tumors. The trial design consisted of 2 phases. In the accelerated phase (ACC), PCI-24781 was administered as a 2-hour IV infusion daily×3 every 3 weeks with dose escalation in successive pts. In the standard phase (STD), the PCI-24781 dose was escalated using cohorts of 3–6 pts until pts received drug daily×3 for 3 of 4 weeks. In this phase, pts also received a single oral dose (via solution or capsule) 7 days prior to the first IV dose to determine oral bioavailability. Blood samples were obtained to evaluate PK. Tubulin and histone acetylation were measured in peripheral blood mononuclear cells (PBMCs). Results: 15 pts (12 male/3 female, median age 59 y) completed treatment at 5 dose levels in the ACC (0.25 - 3 mg/kg) and 3 dose levels in the STD (2.0 - 2.4 mg/kg). EKG monitoring revealed grade ≤1 QTcF prolongation at all dose levels; 1 pt in the final STD cohort had asymptomatic non-specific ST and T wave changes and was discontinued. Adverse events included grade ≤ 2 anemia, thrombocytopenia, diarrhea, nausea, fatigue, and vomiting. These were not dose-related. In the STD, the mean (CV) elimination half life was 5.9 h (16.5%), systemic clearance was 0.98 L/h/kg (37.4%), and steady state volume of distribution was 2.6 L/kg (23.5%). Clearance was independent of dose. At 2 mg/kg, mean AUC values for the inactive carboxylic and amide metabolites were 59% and 58% of the parent. Mean oral bioavailability was 0.28 (34%) with no difference between solution and capsule. Acetylation levels increased at 1.5 h post dose and were sustained through 4 h (IV and oral) in all pts and up to 24 h (oral) in 60% of pts. Stable disease up to 8 cycles was seen in 5 of 13 evaluable pts. Conclusions: PCI-24781 was well tolerated following IV administration. Tubulin and histone acetylation were documented in PBMCs. The drug is orally bioavailable and further studies are ongoing using the capsule formulation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pharmacyclics Pharmacyclics
Intervention to Prevent Major Depression in Primary Care
Authors: Juan Ángel Bellón, Sonia Conejo-Cerón, Patricia Moreno-Peral, Michael King, Irwin Nazareth, Carlos Martín-Pérez, Carmen Fernández-Alonso, Antonina Rodríguez-Bayón, Anna Fernández, José María Aiarzaguena, Carmen Montón-Franco, Inmaculada Ibanez-Casas, Emiliano Rodríguez-Sánchez, María Isabel Ballesta-Rodríguez, Antoni Serrano-Blanco, María Cruz Gómez, Pilar LaFuente, María del Mar Muñoz-García, Pilar Mínguez-Gonzalo, Luz Araujo, Diego Palao, Paola Bully, Fernando Zubiaga, Desirée Navas-Campaña, Juan Mendive, Jose Manuel Aranda-Regules, Alberto Rodriguez-Morejón, Luis Salvador-Carulla, Juan de Dios Luna
Journal: Annals of Internal Medicine (2016)

Not enough is known about universal prevention of depression in adults.To evaluate the effectiveness of an intervention to prevent major depression.Multicenter, cluster randomized trial with sites randomly assigned to usual care or an intervention. (ClinicalTrials.gov: NCT01151982).10 primary care centers in each of 7 cities in Spain.Two primary care physicians (PCPs) and 5236 nondepressed adult patients were randomly sampled from each center; 3326 patients consented and were eligible to participate.For each patient, PCPs communicated individual risk for depression and personal predictors of risk and developed a psychosocial program tailored to prevent depression.New cases of major depression, assessed every 6 months for 18 months.At 18 months, 7.39% of patients in the intervention group (95% CI, 5.85% to 8.95%) developed major depression compared with 9.40% in the control (usual care) group (CI, 7.89% to 10.92%) (absolute difference, -2.01 percentage points [CI, -4.18 to 0.16 percentage points]; P = 0.070). Depression incidence was lower in the intervention centers in 5 cities and similar between intervention and control centers in 2 cities.Potential self-selection bias due to nonconsenting patients.Compared with usual care, an intervention based on personal predictors of risk for depression implemented by PCPs provided a modest but nonsignificant reduction in the incidence of major depression. Additional study of this approach may be warranted.Institute of Health Carlos III.
Altered intestinal microbiota as a major driving force in alcoholic steatohepatitis
Authors: Herbert Tilg, Philippe Mathurin
Journal: Gut (2016)

Alcoholic hepatitis (AH) covers a spectrum of disease severities from subclinical liver inflammation to acute liver failure. Among the histological features of alcoholic liver disease (ALD), AH is associated with the highest risk of fibrosis progression, leading to development of cirrhosis in 40% of cases. Patients hospitalised for severe forms of AH show 1-month mortality rates of 40–50%.1 Patients with AH form a heterogeneous population, in severity, and probably in disease pathogenesis. This diverse clinical picture might be caused by various factors including host factors, immunity and as recently suggested, intestinal microbiota (IM).2 

Patients with ALD present with an altered IM, a condition that is commonly called ‘dysbiosis’, and an increased intestinal permeability, even at an early stage of alcoholic liver injury; this leads to elevated endotoxin levels, with the highest levels in patients with cirrhosis.3 It has been shown that gut microbiota play an important role in experimental ALD. Mice treated with certain antibiotics are resistant to experimental ALD4 and alcohol-induced liver injury was largely blocked in mice lacking CD14 or TLR4 receptors.5 Administration of certain probiotics such as Lactobacillus rhamnosus GG to alcohol-fed mice improves the GI barrier and liver disease.6 Mutlu et al investigated the mucosa-associated colonic microbiome in subjects with and without …