tbuckley/cabot-search huggingface dataset:
Successful discontinuation of eltrombopag after complete remission in patients with primary immune thrombocytopenia
Authors: Tomás José González‐López, Cristina Pascual, María Teresa Álvarez‐Román, Fernando Fernández‐Fuertes, Blanca Sánchez‐González, Isabel Caparrós, Isidro Jarque, María Eva Mingot‐Castellano, José Angel Hernández‐Rivas, Mónica Martín‐Salces, Laura Solán, Paola Beneit, Reyes Jiménez, Silvia Bernat, Marcio M. Andrade, Montserrat Cortés, Maria José Cortti, Susana Pérez‐Crespo, Marta Gómez‐Núñez, Pavel E. Olivera, Gloria Pérez‐Rus, Violeta Martínez‐Robles, Rafael Alonso, Angeles Fernández‐Rodríguez, María Carmen Arratibel, María Perera, Carmen Fernández‐Miñano, Miguel Angel Fuertes‐Palacio, Juan Andrés Vázquez‐Paganini, Isabel Gutierrez‐Jomarrón, Inés Valcarce, Erik de Cabo, Adriana Sainz, Rosa Fisac, Carlos Aguilar, María Paz Martínez‐Badas, María Jesús Peñarrubia, María Calbacho, Carmen de Cos, Manuel González‐Silva, Erika Coria, Arancha Alonso, Alberto Casaus, Armando Luaña, Pilar Galán, Cristina Fernández‐Canal, Javier Garcia‐Frade, José Ramón González‐Porras
Journal: American Journal of Hematology (2014)

Eltrombopag is effective and safe in immune thrombocytopenia (ITP). Some patients may sustain their platelet response when treatment is withdrawn but the frequency of this phenomenon is unknown. We retrospectively evaluated 260 adult primary ITP patients (165 women and 95 men; median age, 62 years) treated with eltrombopag after a median time from diagnosis of 24 months. Among the 201 patients who achieved a complete remission (platelet count >100 × 10(9) /l), eltrombopag was discontinued in 80 patients. Reasons for eltrombopag discontinuation were: persistent response despite a reduction in dose over time (n = 33), platelet count >400 × 10(9) /l (n = 29), patient's request (n = 5), elevated aspartate aminotransferase (n = 3), diarrhea (n = 3), thrombosis (n = 3), and other reasons (n = 4). Of the 49 evaluable patients, 26 patients showed sustained response after discontinuing eltrombopag without additional ITP therapy, with a median follow-up of 9 (range, 6-25) months. These patients were characterized by a median time since ITP diagnosis of 46.5 months, with 4/26 having ITP < 1 year. Eleven patients were male and their median age was 59 years. They received a median of 4 previous treatment lines and 42% were splenectomized. No predictive factors of sustained response after eltrombopag withdrawal were identified. Platelet response following eltrombopag cessation may be sustained in an important percentage of adult primary ITP patients who achieved CR with eltrombopag. However, reliable markers for predicting which patients will have this response are needed.
Vitrectomy and Release of Presumed Epipapillary Vitreous Traction for Treatment of Nonarteritic Anterior Ischemic Optic Neuropathy Associated with Partial Posterior Vitreous Detachment
Authors: Mehdi Modarres, Mostafa Soltan Sanjari, Khalil Ghasemi Falavarjani
Journal: Ophthalmology (2007)
Effect of prophylactic paracetamol administration at time of vaccination on febrile reactions and antibody responses in children: two open-label, randomised controlled trials
Authors: Roman Prymula, Claire-Anne Siegrist, Roman Chlibek, Helena Zemlickova, Marie Vackova, Jan Smetana, Patricia Lommel, Eva Kaliskova, Dorota Borys, Lode Schuerman
Journal: The Lancet (2009)
Prominent Role of Tensile Stress in Propagation of a Dissection After Coronary Stenting
Authors: Attila Thury, Jolanda J. Wentzel, Johan C.H. Schuurbiers, Jurgen M.R. Ligthart, Rob Krams, Pim J. de Feyter, Patrick W. Serruys, Cornelis J. Slager
Journal: Circulation (2001)
Exercise capacity and muscle strength and risk of vascular disease and arrhythmia in 1.1 million young Swedish men: cohort study
Authors: Kasper Andersen, Finn Rasmussen, Claes Held, Martin Neovius, Per Tynelius, Johan Sundström
Journal: BMJ (2015)

To investigate the associations of exercise capacity and muscle strength in late adolescence with risk of vascular disease and arrhythmia.Cohort study.General population in Sweden.1.1 million men who participated in mandatory military conscription between 1 August 1972 and 31 December 1995, at a median age of 18.2 years. Participants were followed until 31 December 2010.Associations between exercise capacity and muscle strength with risk of vascular disease and subgroups (ischaemic heart disease, heart failure, stroke, and cardiovascular death) and risk of arrhythmia and subgroups (atrial fibrillation or flutter, bradyarrhythmia, supraventricular tachycardia, and ventricular arrhythmia or sudden cardiac death). Maximum exercise capacity was estimated by the ergometer bicycle test, and muscle strength was measured as handgrip strength by a hand dynamometer. High exercise capacity or muscle strength was deemed as above the median level.During a median follow-up of 26.3 years, 26 088 vascular disease events and 17 312 arrhythmia events were recorded. Exercise capacity was inversely associated with risk of vascular disease and its subgroups. Muscle strength was also inversely associated with vascular disease risk, driven by associations of higher muscle strength with lower risk of heart failure and cardiovascular death. Exercise capacity had a U shaped association with risk of arrhythmia, driven by a direct association with risk of atrial fibrillation and a U shaped association with bradyarrhythmia. Higher muscle strength was associated with lower risk of arrhythmia (specifically, lower risk of bradyarrhythmia and ventricular arrhythmia). The combination of high exercise capacity and high muscle strength was associated with a hazard ratio of 0.67 (95% confidence interval 0.65 to 0.70) for vascular events and 0.92 (0.88 to 0.97) for arrhythmia compared with the combination of low exercise capacity and low muscle strength.Exercise capacity and muscle strength in late adolescence are independently and jointly associated with long term risk of vascular disease and arrhythmia. The health benefit of lower risk of vascular events with higher exercise capacity was not outweighed by higher risk of arrhythmia.
Evaluation of Epigenetic Drug Targeting of Heterogenous Tumor Cell Fractions Using Potential Biomarkers of Response in Ovarian Cancer
Authors: Anand Kamal Singh, Nishi Chandra, Sharmila A. Bapat
Journal: Clinical Cancer Research (2015)

Resolution of aberrant epigenetic changes leading to altered gene expression during transformation and tumor progression is pertinent for mechanistic understanding of disrupted pathways in cancer. Such changes provide for biomarkers that can be applied in drug screening and improved disease management.Genome-wide profiling and analyses of promoter DNA methylation, histone modifications, and gene expression of an in vitro progression model of serous ovarian adenocarcinoma were carried out. Similar in silico analyses and comparison of methylation and gene expression of early- and late-grade ovarian cancer samples in The Cancer Genome Atlas assigned a clinical relevance to our study. Candidate biomarkers were evaluated for epigenetic drug treatments in experimental animal models on a background of differing tumor cell responses arising from intratumor heterogeneity.Differentially regulated genes during tumor progression were identified through the previously mentioned analyses as candidate biomarkers. In examining the tumor suppressor PTGIS as a potential biomarker for treatment with either 5-Aza-dC or TSA, 5-Aza-dC effectively stabilized cell cycling, restricted genetic instability, and derepressed PTGIS expression, while TSA led to emergence of drug-resistant progenitors lacking PTGIS expression. Profiling MEST and RXRγ for curcumin and CBB1007, respectively, indicated an inability of curcumin and CBB1007 in restricting residual tumor regenerative capabilities.Our study provides novel insights into epigenetic regulation in ovarian cancer progression and potential biomarkers for evaluating efficacy of epigenetic drugs in restricting residual tumor regeneration. Such approaches may assign a new functional interpretation of drug efficacy and cell tumor responses in ovarian cancer.
Investigation of Relationship Between Reduced, Oxidized, and Protein-Bound Homocysteine and Vascular Endothelial Function in Healthy Human Subjects
Authors: John C. Chambers, Per M. Ueland, Melissa Wright, Caroline J. Doré, Helga Refsum, Jaspal S. Kooner
Journal: Circulation Research (2001)

Previous studies investigating homocysteine and vascular disease have relied on total plasma homocysteine as the sole index of homocysteine status. We examined the dynamic relationship between vascular endothelial function and concentrations of total, protein-bound oxidized, free oxidized, and reduced homocysteine to identify the homocysteine form associated with endothelial dysfunction in humans. We investigated 14 healthy volunteers (10 men, 4 women). Brachial artery flow–mediated dilatation was measured at baseline and at 30, 60, 120, 240, and 360 minutes after oral (1) l -methionine (50 mg/kg), (2) l -homocysteine (5 mg/kg), and (3) placebo. Plasma concentrations of total, protein-bound oxidized, free oxidized, and reduced homocysteine were measured at each time point, and nitroglycerin-induced dilatation at was assessed at 0, 120, and 360 minutes. Flow-mediated dilatation fell, and concentrations of total, protein-bound oxidized, free oxidized, and reduced homocysteine increased after oral homocysteine and oral methionine (all P &lt;0.05 for difference in time course compared with placebo). Flow-mediated dilatation showed a reciprocal relationship with reduced homocysteine during both homocysteine and methionine loading. In both loading studies, peak reduction in flow-mediated dilatation coincided with maximal reduced homocysteine concentrations. In contrast, there was no consistent relationship between flow-mediated dilatation and free oxidized homocysteine, protein-bound oxidized homocysteine, or related species. Nitroglycerin-induced dilatation was unchanged by oral homocysteine and oral methionine ( P &gt;0.10 compared with placebo). Reduced homocysteine is closely associated with endothelial dysfunction during oral methionine and oral homocysteine loading. Our observations support the hypothesis that reduced homocysteine is the deleterious form of homocysteine for vascular function in vivo and suggest a less important role for other homocysteine species.
Investigation of hip abductor activation in subjects with clinical unilateral hip osteoarthritis
Authors: K J Sims
Journal: Annals of the Rheumatic Diseases (2002)

(a) To compare the magnitude of gluteus medius and tensor fascia lata activation between a group of subjects with clinical unilateral hip osteoarthritis and a group of healthy older adults. (b) To compare the magnitude of activation of the gluteus medius and tensor fascia lata between sides in a group of subjects with clinical unilateral hip osteoarthritis and a group of healthy older adults.19 subjects with clinical unilateral hip osteoarthritis and 19 healthy controls were investigated. The subjects performed a stepping task during which recordings were obtained using surface electromyograms from the hip abductors, and kinetic data were obtained from a dual force platform.Subjects with clinical hip osteoarthritis had higher gluteus medius activation than the healthy older adults (p=0.037). In addition, there were no differences in the magnitude of gluteus medius activation between the sides (p=0.733). There was no difference in the force platform data between the groups (p=0.078).The increased magnitude of gluteus medius activation in the group with hip osteoarthritis is evidence of a muscular dysfunction associated with hip disease. This has implications for the progressive nature of the disease and for its conservative management.
Common T cell receptor clonotype in lacrimal glands and labial salivary glands from patients with Sjögren's syndrome.
Authors: I Matsumoto, K Tsubota, Y Satake, Y Kita, R Matsumura, H Murata, T Namekawa, K Nishioka, I Iwamoto, Y Saitoh, T Sumida
Journal: Journal of Clinical Investigation (1996)

Sjogren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration into lacrimal and salivary glands leading to symptomatic dry eyes and mouth. Immunohistological studies have clarified that the majority of infiltrating lymphocytes around the lacrimal glands and labial salivary glands are CD4 positive alphabeta T cells. To analyze the pathogenesis of T cells infiltrating into lacrimal and labial salivary glands, we examined T cell clonotype of these cells in both glands from four SS patients using PCR-single-strand conformation polymorphism (SSCP) and a sequencing method. SSCP analysis showed that some infiltrating T cells in both glands expand clonally, suggesting that the cells proliferate by antigen-driven stimulation. Intriguingly, six to sixteen identical T cell receptor (TCR) Vbeta genes were commonly found in lacrimal glands and labial salivary glands from individual patients. This indicates that some T cells infiltrating into both glands recognize the shared epitopes on autoantigens. Moreover, highly conserved amino acid sequence motifs were found in the TCR CDR3 region bearing the same TCR Vbeta family gene from four SS patients, supporting the notion that the shared epitopes on antigens are limited. In conclusion, these findings suggest that some autoreactive T cells infiltrating into the lips and eyes recognized restricted epitopes of a common autoantigen in patients with SS.
Long-Term Effects of Protein-Restricted Diet on Albuminuria and Renal Function in IDDM Patients Without Clinical Nephropathy and Hypertension
Authors: Robin P F Dullaart, Berta J Beusekamp, Sytze Meijer, Jasper J Van Doormaal, William J Sluiter
Journal: Diabetes Care (1993)

OBJECTIVE To determine the long-term effects of an LPD on albuminuria and renal hemodynamics in IDDM patients without nephropathy. RESEARCH DESIGN AND METHODS We selected 31 patients with overnight albuminuria between 10 and 200 g/min and without hypertension from a referral-based diabetic clinic. One participant dropped out. A 2-yr randomized prospective study was conducted on 14 patients assigned to an LPD (0.6 g · kg−1 · day−1) and 16 patients assigned to continue their UPD. Protein intake was assessed by using urinary urea excretion. Albuminuria (three overnight collections) was measured at baseline and on seven occasions thereafter. GFR and ERPF were measured annually using [125I]iothalamate and [131I]hippuran, respectively. RESULTS In the LPD group, protein intake decreased from 1.05 ± 0.32 to 0.79 ± 0.16 g · kg−1 [ day−1 (P &amp;lt; 0.005), but only seven participants consumed &amp;lt; 0.8 g [ kg−1 [ day−1. Protein intake was unaltered in the UPD group (P &amp;lt; 0.001 vs. LPD). Baseline albuminuria and renal hemodynamics were not different in the groups. In the LPD group albuminuria decreased from 36 (95% CI, 16–83) to 30 μg/min (95' CI, 14–67) (P &amp;lt; 0.05). After adjustment for MAP and diabetes duration, the decrease in albuminuria in the LPD group was 26% (95% CI, 13–36) (P &amp;lt; 0.001), which was significantly different from the 5% (95% CI, −10–22) change in the UPD group (P &amp;lt; 0.005 vs. LPD). Multiple regression analysis showed the actual decrease in protein intake lessened (P &amp;lt; 0.005), whereas prevailing MAP accelerated albuminuria (P &amp;lt; 0.001). Low-protein intake independently reduced ERPF (P = 0.009) and GFR (indirectly via ERPF, P &amp;lt; 0.001) after 1 yr. Only minor changes in renal hemodynamics occurred in the second yr. CONCLUSIONS This study suggests that long-term dietary protein restriction beneficially reduces albuminuria and renal hemodynamics in IDDM patients with mildly elevated albuminuria. Systemic BP counteracts these effects even in the absence of hypertension. Suboptimal compliance limits diet efficacy.
Assessment of immediate and long-term functional results of percutaneous transluminal coronary angioplasty.
Authors: F Zijlstra, A den Boer, J H Reiber, G A van Es, J Lubsen, P W Serruys
Journal: Circulation (1988)

Assessment of the functional significance of coronary artery lesions during cardiac catheterization has recently become possible by calculating coronary flow reserve from both myocardial contrast appearance time and density in the resting and hyperemic states determined from digitized coronary cineangiograms. However, the interobserver and intraobserver variabilities, as well as the short-, medium-, and long-term variabilities of the coronary flow reserve measurements, have to be established before this technique becomes an acceptable means of assessing the immediate and long-term functional results of revascularization procedures such as percutaneous transluminal coronary angioplasty (PTCA). Variability was defined as the mean difference and standard deviation of the difference between duplicate determinations of coronary flow reserve. The intraobserver variability (mean difference +/- SD) in the measurement of coronary flow reserve was -0.01 +/- 0.07. Interobserver variability by two observers was +0.08 +/- 0.52. Short-term variability based on the analysis of two coronary cineangiograms taken 5 minutes apart was -0.02 +/- 0.26. Medium-term variability (coronary cineangiographies repeated 1-3 hours apart) was found to be -0.06 +/- 0.52. Long-term variability (coronary cineangiographies repeated 3-5 months apart) was 0.11 +/- 0.63. Having established the reproducibility of this radiographic method, we studied the prospective changes in coronary flow reserve in 25 patients undergoing PTCA for single vessel coronary artery disease. Coronary flow reserve measurements and quantitative coronary cineangiography were performed before, immediately after, and 3-5 months after PTCA. PTCA resulted in an immediate increase in coronary flow reserve from 1 +/- 0.3 to 2.3 +/- 0.6 with a concomitant increase in obstruction area from 0.9 +/- 0.3 to 3.3 +/- 0.7 mm2. Nine of the 25 patients developed restenosis defined as a diameter stenosis greater than 50% at follow-up. The other 16 patients had a coronary flow reserve of 3.3 +/- 0.6, which was measured 3-5 months after PTCA. Coronary flow reserve measurement from digitized coronary cineangiograms is a reproducible method for the assessment of the physiological importance of coronary artery obstructions. Short-, medium-, and long-term investigations of the functional results of interventions such as pharmacological therapy or revascularization can be performed reliably with this technique.
Randomized, Double-Blind, Placebo-Controlled Phase II Study of Single-Agent Oral Talactoferrin in Patients With Locally Advanced or Metastatic Non–Small-Cell Lung Cancer That Progressed After Chemotherapy
Authors: Purvish M. Parikh, Ashok Vaid, Suresh H. Advani, Raghunadharao Digumarti, Jayaprakash Madhavan, Shona Nag, Ajay Bapna, Jagdev S. Sekhon, Shekhar Patil, Preeti M. Ismail, Yenyun Wang, Atul Varadhachary, Junming Zhu, Rajesh Malik
Journal: Journal of Clinical Oncology (2011)

To investigate the activity and safety of oral talactoferrin (TLF) in patients with stages IIIB to IV non-small-cell lung cancer (NSCLC) for whom one or two prior lines of systemic anticancer therapy had failed.Patients (n = 100) were randomly assigned to receive either oral TLF (1.5 g in 15 mL phosphate-based buffer) or placebo (15 mL phosphate-based buffer) twice per day in addition to supportive care. Oral TLF or placebo was administered for a maximum of three 14-week cycles with dosing for 12 consecutive weeks followed by 2 weeks off. The primary objective was overall survival (OS) in the intent-to-treat (ITT) patient population. Secondary objectives included progression-free survival (PFS), disease control rate (DCR), and safety.TLF was associated with improvement in OS in the ITT patient population, meeting the protocol-specified level of significance of a one-tailed P = .05. Compared with the placebo group, median OS increased by 65% in the TLF group (3.7 to 6.1 months; hazard ratio, 0.68; 90% CI, 0.47 to 0.98; P = .04 with one-tailed log-rank test). Supportive trends were also observed for PFS and DCR. TLF was well tolerated and, generally, there were fewer adverse events (AEs) and grade ≥ 3 AEs reported in the TLF arm. AEs were consistent with those expected in late-stage NSCLC.TLF demonstrated an apparent improvement in OS in patients with stages IIIB to IV NSCLC for whom one or two prior lines of systemic anticancer therapy had failed and was well tolerated. These results should be confirmed in a global phase III trial.
Prednisolone inhibits phagocytosis by polymorphonuclear leucocytes via steroid receptor mediated events
Authors: C. J. P. Jones, K. J. Morris, M. I. V. Jayson
Journal: Annals of the Rheumatic Diseases (1983)

Prednisolone, at concentrations between 2·78 × 10<sup>−6</sup> M (1 μg/ml) and 1·39 × 10<sup>−8</sup> M (5 × 10<sup>−3</sup> μg/ml) exerts an inhibitory effect on the phagocytosis of latex particles by normal human polymorphonuclear leucocytes in vitro as assessed by electron microscopical analysis. This inhibition appears to be receptor-mediated, as it is dependent upon RNA and protein synthesis and is glucocorticoid specific.
Counterpoint: Are Insulin Pumps Underutilized in Type 1 Diabetes? No
Authors: David S. Schade, Virginia Valentine
Journal: Diabetes Care (2006)

One of the major goals in the treatment of diabetes is to achieve an HbA1c (A1C)  200,000 worldwide (3). This article will address one specific question, i.e., whether a major effort should be made to increase the number of patients on insulin pumps in order to achieve the above-stated A1C goal.

There are several factors that determine plasma glucose concentration. These include 1 ) the carbohydrate composition of food, 2 ) the rate of gastric emptying, 3 ) the rate of glucose absorption, 4 ) the concurrent magnitude of endogenous glucose production, 5 ) the concurrent rate of glucose disposal, 6 ) the diurnal change in insulin sensitivity, 7 ) the activity of counterregulatory hormones, 8 ) the change in the magnitude and type of exercise, and 9 ) the ambient insulin concentration. It is important to note that most of these factors are not directly under the patient’s control. Many of the factors are interrelated, so that altering one may affect the magnitude of the other. Thus, in attempting to normalize plasma …