tbuckley/cabot-search huggingface dataset:
Evaluation of Tamoxifen and Anastrozole in the Prevention of Gynecomastia and Breast Pain Induced by Bicalutamide Monotherapy of Prostate Cancer
Authors: F. Boccardo, A. Rubagotti, M. Battaglia, P. Di Tonno, F.P. Selvaggi, G. Conti, G. Comeri, A. Bertaccini, G. Martorana, P. Galassi, F. Zattoni, A. Macchiarella, A. Siragusa, G. Muscas, F. Durand, D. Potenzoni, A. Manganelli, V. Ferraris, F. Montefiore
Journal: Journal of Clinical Oncology (2005)

To determine whether tamoxifen or anastrozole prevents gynecomastia and breast pain caused by bicalutamide (150 mg) without compromising efficacy, safety, or sexual functioning.A double-blind, placebo-controlled trial was performed in patients with localized, locally advanced, or biochemically recurrent prostate cancer. Patients (N = 114) were randomly assigned to either bicalutamide (150 mg/d) plus placebo or in combination with tamoxifen (20 mg/d) or anastrozole (1 mg/d) for 48 weeks. Gynecomastia, breast pain, prostate-specific antigen (PSA), sexual functioning, and serum levels of hormones were assessed.Gynecomastia developed in 73% of patients in the bicalutamide group, 10% of patients in the bicalutamide-tamoxifen group, and 51% of patients in the bicalutamide-anastrozole group (P < .001); breast pain developed in 39%, 6%, and 27% of patients, respectively (P = .006). Baseline PSA level decreased by > or = 50% in 97%, 97%, and 83% of patients in the bicalutamide, bicalutamide-tamoxifen, and bicalutamide-anastrozole groups, respectively (P = .07); and adverse events were reported in 37%, 35%, and 69% of patients, respectively (P = .004). There were no major differences among treatments in sexual functioning parameters from baseline to month 6. Elevated testosterone levels occurred in each group; however, free testosterone levels remained unchanged in the bicalutamide-tamoxifen group because of increased sex hormone-binding globulin levels.Anastrozole did not significantly reduce the incidence of bicalutamide-induced gynecomastia and breast pain. In contrast, tamoxifen was effective, without increasing adverse events, at least in the short-term follow-up. These data support the need for a larger study to determine any effect on mortality.
Lower respiratory tract infection caused by respiratory syncytial virus: current management and new therapeutics
Authors: Natalie I Mazur, Federico Martinón-Torres, Eugenio Baraldi, Brigitte Fauroux, Anne Greenough, Terho Heikkinen, Paolo Manzoni, Asuncion Mejias, Harish Nair, Nikolaos G Papadopoulos, Fernando P Polack, Octavio Ramilo, Mike Sharland, Renato Stein, Shabir A Madhi, Louis Bont
Journal: The Lancet Respiratory Medicine (2015)
Induction of labour versus expectant management for large-for-date fetuses: a randomised controlled trial
Authors: Michel Boulvain, Marie-Victoire Senat, Franck Perrotin, Norbert Winer, Gael Beucher, Damien Subtil, Florence Bretelle, Elie Azria, Dominique Hejaiej, Françoise Vendittelli, Marianne Capelle, Bruno Langer, Richard Matis, Laure Connan, Philippe Gillard, Christine Kirkpatrick, Gilles Ceysens, Gilles Faron, Olivier Irion, Patrick Rozenberg
Journal: The Lancet (2015)
Cervical collar or physiotherapy versus wait and see policy for recent onset cervical radiculopathy: randomised trial
Authors: B. Kuijper, J. T. J Tans, A. Beelen, F. Nollet, M. d. Visser
Journal: BMJ (2009)

<b>Objective</b> To evaluate the effectiveness of treatment with collar or physiotherapy compared with a wait and see policy in recent onset cervical radiculopathy. <b>Design</b> Randomised controlled trial. <b>Setting</b> Neurology outpatient clinics in three Dutch hospitals. <b>Participants</b> 205 patients with symptoms and signs of cervical radiculopathy of less than one month's duration <b>Interventions</b> Treatment with a semi-hard collar and taking rest for three to six weeks; 12 twice weekly sessions of physiotherapy and home exercises for six weeks; or continuation of daily activities as much as possible without specific treatment (control group). <b>Main outcome measures</b> Time course of changes in pain scores for arm and neck pain on a 100 mm visual analogue scale and in the neck disability index during the first six weeks. <b>Results</b> In the wait and see group, arm pain diminished by 3 mm/week on the visual analogue scale (β=−3.1 mm, 95% confidence interval −4.0 to −2.2 mm) and by 19 mm in total over six weeks. Patients who were treated with cervical collar or physiotherapy achieved additional pain reduction (collar: β=−1.9 mm, −3.3 to −0.5 mm; physiotherapy: β=−1.9, −3.3 to −0.8), resulting in an extra pain reduction compared with the control group of 12 mm after six weeks. In the wait and see group, neck pain did not decrease significantly in the first six weeks (β=−0.9 mm, −2.0 to 0.3). Treatment with the collar resulted in a weekly reduction on the visual analogue scale of 2.8 mm (−4.2 to −1.3), amounting to 17 mm in six weeks, whereas physiotherapy gave a weekly reduction of 2.4 mm (−3.9 to −0.8) resulting in a decrease of 14 mm after six weeks. Compared with a wait and see policy, the neck disability index showed a significant change with the use of the collar and rest (β=−0.9 mm, −1.6 to −0.1) and a non-significant effect with physiotherapy and home exercises. <b>Conclusion</b> A semi-hard cervical collar and rest for three to six weeks or physiotherapy accompanied by home exercises for six weeks reduced neck and arm pain substantially compared with a wait and see policy in the early phase of cervical radiculopathy. <b>Trial registration</b> Clinical trials NCT00129714.
Sequential Influences of Leukemia-Specific and Genetic Factors on P-Glycoprotein Expression in Blasts from 817 Patients Entered into the National Cancer Research Network Acute Myeloid Leukemia 14 and 15 Trials
Authors: Claire H. Seedhouse, Martin Grundy, Paul White, Yun Li, Janet Fisher, Darya Yakunina, Anthony V. Moorman, Terence Hoy, Nigel Russell, Alan Burnett, Monica Pallis
Journal: Clinical Cancer Research (2007)

P-glycoprotein (Pgp) is a major prognostic factor for chemotherapy failure in acute myeloid leukemia (AML). This study compared the influence of genetic and leukemia-specific factors on Pgp.Eight hundred and seventeen samples were studied prospectively for Pgp protein expression and function and G1199A, G2677T, and C3435T polymorphisms in the encoding gene ABCB1.Age, low WBC count, high bcl-2, secondary AML and myelodysplastic syndrome, and adverse cytogenetics all correlated strongly with high Pgp (MRK16) protein expression. However, ABCB1 3435TT homozygosity was negatively correlated with Pgp. Pgp protein is only expressed in 41% of samples such that the negative effect of the polymorphism was not seen at baseline Pgp levels but was marked in the upper 41% of samples (MRK16 Deltamean fluorescence intensity of 75th centile sample = 9 units for TT variant samples and 26 units for CC/CT; P = 0.003). However, no association was found between genetic factors and Pgp function using rhodamine 123 accumulation.The genetic polymorphism 3435TT (which results in unstable mRNA) has a significant effect on Pgp expression, but this is only seen in approximately 40% of cases in which mRNA and protein are detectable. Moreover, leukemia-specific factors, such as low WBC count and poor risk cytogenetics, have a much greater effect than genetic polymorphisms on Pgp expression in AML blasts.
NY-ESO-1 DNA Vaccine Induces T-Cell Responses That Are Suppressed by Regulatory T Cells
Authors: Sacha Gnjatic, Nasser K. Altorki, Derek Ng Tang, Shi-Ming Tu, Vikas Kundra, Gerd Ritter, Lloyd J. Old, Christopher J. Logothetis, Padmanee Sharma
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Different vaccination strategies against the NY-ESO-1 antigen have been employed in an attempt to induce antitumor immune responses. Antigen-specific effector T-cell responses have been reported in a subset of vaccinated patients; however, these responses have not consistently correlated with disease regression. Here, we report for the first time clinical and immune responses generated by the NY-ESO-1 DNA vaccine administered by particle-mediated epidermal delivery to cancer patients. Experimental Design: Eligible patients received treatment with the NY-ESO-1 DNA vaccine. Clinical outcomes and immune responses were assessed. Results: The NY-ESO-1 DNA vaccine was safely administered and induced both antigen-specific effector CD4 and/or CD8 T-cell responses in 93% (14 of 15) of patients who did not have detectable pre-vaccine immune responses. Despite the induction of antigen-specific T-cell responses, clinical outcomes consisted predominantly of progressive disease. Detectable effector T-cell responses were inconsistent and did not persist in all patients after completion of the scheduled vaccinations. However, high-avidity CD4 T-cell responses that were either undetectable pre-vaccine or found to be diminished at a later time during the clinical trial were detected in certain patients' samples after in vitro depletion of regulatory T cells. Conclusions: Regulatory T cells play a role in diminishing vaccine-induced antigen-specific effector T-cell responses in cancer patients. The NY-ESO-1 DNA vaccine represents a feasible immunotherapeutic strategy to induce antigen-specific T-cell responses. Counteracting regulatory T-cell activity before vaccination may lead to prolonged effector T-cell responses and possibly antitumor responses in cancer patients.
Predictors of radiographic joint damage in patients with early rheumatoid arthritis
Authors: L M A Jansen
Journal: Annals of the Rheumatic Diseases (2001)

To determine factors at diagnosis, associated with radiographic damage at diagnosis and after one year, in patients with early rheumatoid arthritis (RA).New patients with early RA were followed up for one year. Possible prognostic factors were duration of complaints, morning stiffness, disease activity score (DAS28), functional status (Health Assessment Questionnaire (HAQ) score), rheumatoid factor (IgM RF), and C reactive protein (CRP). Outcome was defined as radiographic damage of the hands and feet (Sharp/van der Heijde score). For the statistical analysis, one way analysis of variance and a forward stepwise logistic regression model was used.130 patients with RA (68% female; median age 64 years, range 21-86) were included. Despite the fact that the median duration of complaints was short (15 weeks, range 2-106) the radiographic damage at diagnosis was significantly correlated with the duration of complaints (p<0.05). Patients with a duration of complaints of >34 weeks had significantly more radiographic joint damage at diagnosis than patients with a shorter duration of complaints. Radiographic progression at one year was correlated with high radiographic joint damage, high CRP level, and a positive IgM RF at entry.In early RA, the number of radiographic lesions was correlated with a longer duration of complaints at the first visit. Progression of these lesions was predicted by a high baseline joint damage, high CRP level, and a positive IgM RF. Further reduction of the delay in referral and early treatment may further decrease joint damage in patients with recent onset polyarthritis.
Dendritic cells are functionally defective in multiple myeloma: the role of interleukin-6
Authors: Marina Ratta, Francesco Fagnoni, Antonio Curti, Rosanna Vescovini, Paolo Sansoni, Barbara Oliviero, Miriam Fogli, Elisa Ferri, Gioacchino Robustelli Della Cuna, Sante Tura, Michele Baccarani, Roberto M. Lemoli
Journal: Blood (2002)
Glucocorticoid-induced Changes in Gene Expression of Airway Smooth Muscle in Patients with Asthma
Authors: Ching Yong Yick, Aeilko H. Zwinderman, Peter W. Kunst, Katrien Grünberg, Thais Mauad, Kees Fluiter, Elisabeth H. Bel, René Lutter, Frank Baas, Peter J. Sterk
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Glucocorticoids are the mainstay of asthma therapy. However, it is unclear whether the benefits of glucocorticoids in asthma are merely based on antiinflammatory properties. Glucocorticoids may also alter gene expression of airway smooth muscle (ASM). We hypothesized that the gene expression profile of the ASM layer in endobronchial biopsies of patients with asthma is altered by oral glucocorticoid therapy as compared with placebo.First, we investigated the change in ASM transcriptomic profile in endobronchial biopsies after 14 days of oral glucocorticoid therapy. Second, we investigated the association between changes in ASM transcriptomic profile and lung function.Twelve steroid-free patients with atopic asthma were included in this double-blind intervention study. Endobronchial biopsies were taken before and after 14 days of oral prednisolone (n = 6) or placebo (n = 6). RNA of laser-dissected ASM was sequenced (RNA-Seq) using GS FLX+ (454/Roche). Gene networks were identified by Ingenuity Pathway Analysis. RNA-Seq reads were assumed to follow a negative binomial distribution. At the current sample size the estimated false discovery rate was approximately 3%.Fifteen genes were significantly changed by 14 days of oral prednisolone. Two of these genes (FAM129A, SYNPO2) were associated with airway hyperresponsiveness (provocative concentration of methacholine causing a 20% drop in FEV1: r = -0.740, P < 0.01; r = -0.746, P < 0.01). Pathway analysis revealed three gene networks that were associated with cellular functions including cellular growth, proliferation, and development.Oral prednisolone changes the transcriptomic profile of the ASM layer in asthma. This indicates that in parallel to antiinflammatory properties, glucocorticoids also exert effects on gene expression of ASM, which is correlated with improved airway function.
Dose-escalated CHOEP for the treatment of young patients with aggressive non-Hodgkin’s lymphoma: II. Results of the randomized high-CHOEP trial of the German High-Grade Non-Hodgkin’s Lymphoma Study Group (DSHNHL)
Authors: M. Pfreundschuh, C. Zwick, S. Zeynalova, U. Dührsen, K.-H. Pflüger, T. Vrieling, R. Mesters, H.-G. Mergenthaler, H. Einsele, M. Bentz, E. Lengfelder, L. Trümper, C. Rübe, N. Schmitz, M. Loeffler
Journal: Annals of Oncology (2007)
Reduction of inflammation, tissue damage, and mortality in bacterial meningitis in rabbits treated with monoclonal antibodies against adhesion-promoting receptors of leukocytes.
Authors: E I Tuomanen, K Saukkonen, S Sande, C Cioffe, S D Wright
Journal: The Journal of Experimental Medicine (1989)

We tested if specific inhibition of recruitment of leukocytes across the blood brain barrier from the vascular compartment to the cerebrospinal fluid (CSF) space reduced tissue damage and improved the outcome of infection in a rabbit model of experimental meningitis. The CD11/CD18 complex of receptors on leukocytes promotes adhesion of these cells to endothelia, a process required for egress of cells into the extravascular space. Intravenous injection of the anti-CD18 mAb IB4 effectively blocked the development of leukocytosis in the CSF of animals challenged intracisternally with living bacteria, bacterial endotoxin, or bacterial cell wall. This effect was associated with protection from blood brain barrier injury as measured by exclusion of serum proteins from CSF in mAb-treated animals. The densities of bacteria in CSF and the degrees of bacterial killing due to ampicillin were not affected by the antibody. Animals receiving the antibody experienced a delay in the development of bacteremia and a significantly reduced inflammatory response during ampicillin-induced bacterial killing. Therapy with mAb IB4 prevented development of brain edema and death in animals challenged with lethal doses of Streptococcus pneumoniae. These studies indicate that the major mechanism of leukocyte migration across the blood brain barrier involves the CD11/CD18 receptors and that inflammatory leukocytes recruited by this mechanism are a major cause of blood brain barrier injury and cerebral edema during meningitis.
Excessive Urinary Albumin Levels Are Associated With Future Cardiovascular Mortality in Postmenopausal Women
Authors: Mark Roest, Jan Dirk Banga, Wilbert M. T. Janssen, Diederick E. Grobbee, Jan J. Sixma, Paul E. de Jong, Dick de Zeeuw, Yvonne T. van der Schouw
Journal: Circulation (2001)

Background —Microalbuminuria is an early predictor of cardiovascular morbidity and mortality, in both diabetic patients and hypertensive patients. Little is known about the relation of microalbuminuria to cardiovascular disease in women of the general population. Methods and Results —We have studied the relation of urinary albumin levels to cardiovascular mortality in a cohort study of 12 239 postmenopausal women living in Utrecht, the Netherlands. The initial age was between 52 and 67 years. Women were followed on vital status between 1976 and 1995 (168 513 women-years). Albumin was determined in the urine of 561 cases and 557 controls. Data were analyzed by using a nested case-control design. The cardiovascular mortality rate (95% CI) for women who were in the highest quintile of urinary albumin levels was 13.2/1000 years (8.1 to 20.9) compared with 2.6/1000 years (2.3 to 3.1) in women without detectable urinary albumin. The age-adjusted rate ratio (95% CI) between these groups was 4.4 (2.6 to 7.6). Conclusions —This is the first large cohort study that confirms a predictive role of urinary albumin for the risk of future cardiovascular mortality independent of hypertension and diabetes. Our findings support the hypothesis that microalbuminuria is a reflection of vascular damage and a marker of early arterial disease in women from the general population.
IgE to recombinant allergens <scp>A</scp>pi m 1, <scp>V</scp>es v 1, and <scp>V</scp>es v 5 distinguish double sensitization from crossreaction in venom allergy
Authors: U. Müller, P. Schmid‐Grendelmeier, O. Hausmann, A. Helbling
Journal: Allergy (2012)

Abstract Background Diagnostic tests in patients with H ymenoptera venom allergy are frequently positive to venoms of both honey bee and wasp ( V espula ). Component‐resolved analysis with recombinant species‐specific major allergens (r SSMA ) may help to distinguish true double sensitization from crossreactivity. Methods Included were 121 patients with systemic allergic reactions to H ymenoptera stings, 76 with double positivity of serum‐specific I g E (s I g E ) to both venoms, 45 with single positivity to bee or wasp venom, and 32 controls without history of systemic reactions to H ymenoptera stings and no s I g E to whole venoms. In venom‐allergic patients and controls, s I g E to r SSMA A pi m 1 of bee venom and to V es v 1 and V es v 5 of wasp venom were tested by I mmuno CAP . Results Only 47% of 76 patients with double positivity to whole venoms reacted also to r SSMA of both species. Specificity of s I g E to the 3 r SSMA was very high, with no s I g E to r SSMA of the other species in single‐positive venom‐allergic patients and only one control with low s I g E to V es v 1. All wasp‐allergic single‐positive patients had s I g E to V es v 5 and/or V es v 1, and 78.3% of single‐positive bee venom–allergic patients had s I g E to A pi m 1. Conclusion Specificity of s I g E to r SSMA of both species is excellent. Sensitivity of s I g E to r SSMA was optimal for wasp venom. Sensitivity of bee venom A pi m 1 could be increased by adding r SSMA of other important bee venom allergens.
Are Biochemical Recurrence Outcomes Similar After Radical Prostatectomy and Radiation Therapy? Analysis of Prostate Cancer–Specific Mortality by Nomogram-predicted Risks of Biochemical Recurrence
Authors: Byron H. Lee, Adam S. Kibel, Jay P. Ciezki, Eric A. Klein, Chandana A. Reddy, Changhong Yu, Michael W. Kattan, Andrew J. Stephenson
Journal: European Urology (2014)
T-independent and T-dependent steps in the murine B cell response to antiimmunoglobulin.
Authors: M L Birkeland, L Simpson, P C Isakson, E Pure
Journal: The Journal of Experimental Medicine (1987)

Sepharose-anti-Ig and purified populations of small, high-density B cells have been used to study the formation and function of B lymphoblasts. Sepharose-anti-Ig converts small, Ia-poor B cells with a high-buoyant density to large, Ia-rich, B blasts with a low-buoyant density. We find that this response proceeds efficiently in the absence of IL-4 (BSF-1) as well as most T cells, macrophages, and dendritic cells. Further development of the blasts requires an additional stimulus, such as LPS or the conditioned medium of stimulated EL-4 thymoma cells. Within 6 h, blasts begin to enter S phase and within 24 h most divide. At later times (48-72 h) most of the blasts are actively secreting IgM. Recombinant IL-1, -2, -3, and -4 have little or no effect on the B blasts, and a neutralizing mAb to IL-4 does not block the response to EL-4 Sn. We conclude that Sepharose-anti-Ig induces B cell blastogenesis in a T-independent fashion and that these blasts represent a highly enriched population of cells that respond to distinct, T cell-derived lymphokines.
Antimicrobial peptides in the real world: implications for cystic fibrosis
Authors: P. S. Hiemstra
Journal: European Respiratory Journal (2007)

The continuous cycle of respiratory infections and lung inflammation is a hallmark of cystic fibrosis (CF) lung disease and plays a central role in respiratory failure that develops in end-stage disease. Effective mucociliary clearance is an essential mechanism in host defence against infection and requires a functional “two-layer” mucus clearance system composed of a periciliary liquid layer and an overlying mucus layer in which inhaled substances are trapped 1. Together these two separate layers constitute airway surface liquid (ASL). Adequate hydration is essential for an optimal function of the mucociliary clearance system. Dehydration of the mucosal surface in CF may not only hamper effective mucus clearance but also causes adhesion of mucus to the epithelial surface. This results in airway flow obstruction, inflammation and favouring infections.

In addition to this defect in mucociliary clearance, an inadequate function of the secreted effector molecules of the innate immune system in the lung has been suggested to contribute to increased susceptibility to infection in CF 2. Antimicrobial peptides and proteins are an essential element of this innate immune system, and the airway epithelium forms a range of these compounds 3. The main classes of antimicrobial peptides produced by airway epithelial cells are the β-defensins and the cathelicidins (LL-37 in humans). The antimicrobial activity of most of these peptides is markedly restricted in isotonic and hypertonic conditions, and optimal activity under laboratory conditions is …
Dulanermin with rituximab in patients with relapsed indolent B-cell lymphoma: an open-label phase 1b/2 randomised study
Authors: Chan Yoon Cheah, David Belada, Michelle A Fanale, Andrea Janikova, Myron S Czucman, Ian W Flinn, Amy V Kapp, Avi Ashkenazi, Sean Kelley, Gordon L Bray, Scott Holden, John F Seymour
Journal: The Lancet Haematology (2015)