tbuckley/cabot-search huggingface dataset:
Performance of classification criteria for peripheral spondyloarthritis and psoriatic arthritis in the Leiden early arthritis cohort
Authors: Rosaline van den Berg, Floris van Gaalen, Annette van der Helm-van Mil, Tom Huizinga, Désirée van der Heijde
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> The performance of spondyloarthritis (SpA) classification criteria is not well-established in general early arthritis cohorts. Therefore, the authors tested their performance in the Leiden Early Arthritis Clinic (EAC) cohort and assessed whether these criteria can assist rheumatologists in diagnosing patients. <h3>Methods</h3> The authors identified all SpA and psoriatic arthritis (PsA) patients in the EAC cohort according to the diagnosis of the treating rheumatologist. A control group consisting of arthritis patients with other diagnoses was matched to the SpA and PsA patients on gender, age and symptom duration. The authors assessed the fulfilment of SpA criteria in all three groups. <h3>Results</h3> Of the patients in the EAC cohort (n=2011), 7.5% was diagnosed with PsA and 3.8% with SpA. In the PsA group, the ClASsification criteria for Psoratic ARthritis (CASPAR) criteria had the highest sensitivity (88.7%). In the SpA group, the Assessment of SpondyloArthritis international Society (ASAS) peripheral SpA and European Spondylarthropathy Study Group (ESSG) criteria had the highest sensitivity (both 48.7%). Specificity of all criteria sets was good: ranging from 88.5% (ESSG) to 100% (Amor). <h3>Conclusions</h3> In early arthritis, sensitivity of SpA classification criteria is modest except for the CASPAR criteria in PsA. However, specificity of classification criteria, including the new ASAS-peripheral SpA criteria, is high.
All Gifts Large and Small: Toward an Understanding of the Ethics of Pharmaceutical Industry Gift-Giving
Authors: Dana Katz, Arthur L. Caplan, Jon F. Merz
Journal: The American Journal of Bioethics (2010)

Much attention has been focused in recent years on the ethical acceptability of physicians receiving gifts from drug companies. Professional guidelines recognize industry gifts as a conflict of interest and establish thresholds prohibiting the exchange of large gifts while expressly allowing for the exchange of small gifts such as pens, note pads, and coffee. Considerable evidence from the social sciences suggests that gifts of negligible value can influence the behavior of the recipient in ways the recipient does not always realize. Policies and guidelines that rely on arbitrary value limits for gift-giving or receipt should be reevaluated.
Cytisine improves smoking cessation
Authors: Wa'el Osman
Journal: Thorax (2011)

In this single-centre, randomised, double blind, placebo-controlled trial, the efficacy and safety of cytisine as an aid in smoking cessation was compared with placebo. Three hundred and seventy participants were randomly assigned to either the active drug or placebo in an equal ratio for 25 days. Participants in both groups received a minimal amount of counselling during the study.

The primary outcome measure was sustained biochemically-verified …
A Novel AKT1 Mutant Amplifies an Adaptive Melanoma Response to BRAF Inhibition
Authors: Hubing Shi, Aayoung Hong, Xiangju Kong, Richard C. Koya, Chunying Song, Gatien Moriceau, Willy Hugo, Clarissa C. Yu, Charles Ng, Thinle Chodon, Richard A. Scolyer, Richard F. Kefford, Antoni Ribas, Georgina V. Long, Roger S. Lo
Journal: Cancer Discovery (2013)

BRAF inhibitor (BRAFi) therapy leads to remarkable anti melanoma responses, but the initial tumor shrinkage is commonly incomplete, providing a nidus for subsequent disease progression. Adaptive signaling may underlie early BRAFi resistance and influence the selection pattern for genetic variants, causing late, acquired resistance. We show here that BRAFi (or BRAFi + MEKi) therapy in patients frequently led to rebound phosphorylated AKT (p-AKT) levels in their melanomas early on-treatment. In cell lines, BRAFi treatment led to rebound levels of receptor tyrosine kinases (RTK; including PDGFRβ), phosphatidyl (3,4,5)-triphosphate (PIP3), pleckstrin homology domain recruitment, and p-AKT. PTEN expression limited this BRAFi-elicited PI3K-AKT signaling, which could be rescued by the introduction of a mutant AKT1 (Q79K) known to confer acquired BRAFi resistance. Functionally, AKT1(Q79K) conferred BRAFi resistance via amplification of BRAFi-elicited PI3K-AKT signaling. In addition, mitogen-activated protein kinase pathway inhibition enhanced clonogenic growth dependency on PI3K or AKT. Thus, adaptive or genetic upregulation of AKT critically participates in melanoma survival during BRAFi therapy.
Discrete Role for Cytosolic Phospholipase A2α in Platelets
Authors: Dennis A. Wong, Yoshihiro Kita, Naonori Uozumi, Takao Shimizu
Journal: The Journal of Experimental Medicine (2002)

Among several different types of phospholipase A(2) (PLA(2)), cytosolic PLA(2) (cPLA(2))alpha and group IIA (IIA) secretory PLA(2) (sPLA(2)) have been studied intensively. To determine the discrete roles of cPLA(2)alpha in platelets, we generated two sets of genetically engineered mice (cPLA(2)alpha(-/-)/sPLA(2)-IIA(-/-) and cPLA(2)alpha(-/-)/sPLA(2)-IIA(+/+)) and compared their platelet function with their respective wild-type C57BL/6J mice (cPLA(2)alpha(+/+)/sPLA(2)-IIA(-/-)) and C3H/HeN (cPLA(2)alpha(+/+)/sPLA(2)-IIA(+/+)). We found that cPLA(2)alpha is needed for the production of the vast majority of thromboxane (TX)A(2) with collagen stimulation of platelets. In cPLA(2)alpha-deficient mice, however, platelet aggregation in vitro is only fractionally decreased because small amounts of TX produced by redundant phospholipase enzymes sufficiently preserve aggregation. In comparison, adenosine triphosphate activation of platelets appears wholly independent of cPLA(2)alpha and sPLA(2)-IIA for aggregation or the production of TX, indicating that these phospholipases are specifically linked to collagen receptors. However, the lack of high levels of TX limiting vasoconstriction explains the in vivo effects seen: increased bleeding times and protection from thromboembolism. Thus, cPLA(2)alpha plays a discrete role in the collagen-stimulated production of TX and its inhibition has a therapeutic potential against thromboembolism, with potentially limited bleeding expected.
Fiix-prothrombin time versus standard prothrombin time for monitoring of warfarin anticoagulation: a single centre, double-blind, randomised, non-inferiority trial
Authors: Páll T Onundarson, Charles W Francis, Olafur S Indridason, David O Arnar, Einar S Bjornsson, Magnus K Magnusson, Sigurdur J Juliusson, Hulda M Jensdottir, Brynjar Vidarsson, Petur S Gunnarsson, Sigrun H Lund, Brynja R Gudmundsdottir
Journal: The Lancet Haematology (2015)
Increased Insulin-Like Growth Factor I Receptor Expression and Signaling Are Components of Androgen-Independent Progression in a Lineage-Derived Prostate Cancer Progression Model
Authors: Sandra L. Krueckl, Robert A. Sikes, N. Magnus Edlund, Robert H. Bell, Antonio Hurtado-Coll, Ladan Fazli, Martin E. Gleave, Michael E. Cox
Journal: Cancer Research (2004)

Abstract Apoptosis and inhibition of mitosis are primary mechanisms mediating androgen ablation therapy-induced regression of prostate cancer (PCa). However, PCa readily becomes androgen independent, leading to fatal disease. Up-regulated growth and survival signaling is implicated in development of resistance to androgen ablation therapy. We are testing the hypothesis that insulin-like growth factor (IGF) responsiveness is required for androgen-independent (AI) progression. Using the LNCaP human PCa progression model, we have determined that IGF-I–mediated protection from apoptotic stress and enhanced mitotic activity is androgen dependent in LNCaP cells but is androgen independent in lineage-derived C4-2 cells. Both cell lines exhibit androgen-responsive patterns of IGF-I receptor (IGF-IR) expression, activation, and signaling to insulin receptor substrate-2 and AKT. However, C4-2 cells express higher levels of IGF-IR mRNA and protein and exhibit enhanced IGF-I–mediated phosphorylation and downstream signaling under androgen-deprived conditions. In comparisons of naïve and AI metastatic human PCa specimens, we have confirmed that IGF-IR levels are elevated in advanced disease. Together with our LNCaP/C4-2 AI progression model data, these results indicate that increased IGF-IR expression is associated with AI antiapoptotic and promitotic IGF signaling in PCa disease progression.
An Assessment of Prednisone, Salazopyrin, and Topical Hydrocortisone Hemisuccinate Used as Out-patient Treatment for Ulcerative Colitis
Authors: J. E. Lennard-Jones, A. J. Longmore, A. C. Newell, C. W. E. Wilson, F. A. Jones
Journal: Gut (1960)

Two consecutive trials of out-patient treatment for mild cases of active ulcerative colitis are described. In the first trial oral prednisone gave significantly better results than a placebo. In the second trial "salazopyrin" gave final results approaching those of prednisone, although over a longer time and with a higher incidence of unpleasant side-effects, but topical hydrocortisone gave disappointing results, probably because the technique of administration was not suitable for ordinary out-patient use.
Acquired Immunological Tolerance and Carcinogenesis by the Mammary Tumor Virus. II. Immune Responses Influencing Growth of Spontaneous Mammary Adenocarcinomas&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Donald L. Morton, Leon Goldman, David A. Wood
Journal: JNCI Journal of the National Cancer Institute (1969)

Adult hybrid (C3H × C57BL)F1 mice neonatally infectcd with the mammary tumor virus (MTV) are much more susceptible to the growth of transplanted mammary adenocarcinomas than MTV-free hybrids. Immune factors influencing the growth of mammary carcinomas were investigated in an attempt to relate the enhanced tumor growth in MTV+ mice and the resistance of MTV− mice to immunological events. Immunosuppression by total-body irradiation abolished the resistance against tumor growth in MTV− mice, but had little or no effect on tumor growth in MTV+ mice. The ability of lymphoid cells from MTV− mice to transfer resistance against tumor growth to MTV+ mice was tested in neutralization and adoptive immunity experiments. Neutralization experiments revealed that spleen cells from immune MTV− mice rejecting a mammary tumor transplant or spleen cells from normal MTV− mice could completely or partially inhibit tumor growth in MTV+ mice. However, spleen cells from MTV+ mice did not inhibit tumor growth. Inoculation of MTV-infected extracts of C3H lactating mammary tissue, as previously found to induce tolerance in newborn mice, elicited immunity against transplanted mammary adenocarcinomas in adult MTV− mice. These data are consistent with the hypothesis that all spontaneous mammary adenocarcinomas contain a common MTV-related tumor antigen which is antigenic in MTV− mice, but neonatal infection with the MTV induces acquired immunological tolerance to this antigen in MTV+ mice. The immunogenicity of this common tumor antigen in MTV− mice and the acquired immune tolerance to this antigen in MTV+ mice best explain the resistance and susceptibility of these mice to the growth of transplanted spontaneous mammary adenocarcinomas.
Molecular Changes in Lobular Breast Cancers in Response to Endocrine Therapy
Authors: Laura M. Arthur, Arran K. Turnbull, Victoria L. Webber, Alexey A. Larionov, Lorna Renshaw, Charlene Kay, Jeremy S. Thomas, J. Michael Dixon, Andrew H. Sims
Journal: Cancer Research (2014)

Invasive lobular carcinoma (ILC) accounts for approximately 10% to 15% of breast carcinomas, and although it responds poorly to neoadjuvant chemotherapy, it appears to respond well to endocrine therapy. Pre- and on-treatment (after 2 weeks and 3 months) biopsies and surgical samples were obtained from 14 postmenopausal women with estrogen receptor-positive (ER(+)) histologically confirmed ILC who responded to 3 months of neoadjuvant letrozole and were compared with a cohort of 14 responding invasive ductal carcinomas (IDC) matched on clinicopathologic features. RNA was extracted and processed for whole human genome expression microarray. Dynamic clinical response was assessed using periodic three-dimensional ultrasound measurements performed during treatment and defined as a reduction of >70% in tumor volume by 3 months. Pretreatment profiles of ILC and IDC tumors showed distinctive expression of genes associated with E-cadherin signaling, epithelial adhesion, and stromal rearrangement. The changes in gene expression in response to letrozole were highly similar between responding ILC and IDC tumors; genes involved in proliferation were downregulated and those involved with immune function and extracellular matrix remodeling were upregulated. However, molecular differences between the histologic subtypes were maintained upon treatment. This is the first study of molecular changes in ILC in response to endocrine therapy to date. The genes that change on letrozole are highly consistent between ILC and IDC. Differences in gene expression between ILC and IDC at diagnosis are maintained at each time point on treatment.
Autophagy as a therapeutic target for ischaemia /reperfusion injury? Concepts, controversies, and challenges
Authors: K. Przyklenk, Y. Dong, V. V. Undyala, P. Whittaker
Journal: Cardiovascular Research (2012)

Autophagy is the tightly orchestrated cellular 'housekeeping' process responsible for the degradation and disposal of damaged and dysfunctional organelles and protein aggregates. In addition to its established basal role in the maintenance of normal cellular phenotype and function, there is growing interest in the concept that targeted modulation of autophagy under conditions of stress (most notably, ischaemia/reperfusion) may represent an adaptive mechanism and render the myocardium resistant to ischaemia/reperfusion injury. Our aims in this review are to: (i) provide a balanced overview of the emerging hypothesis that perturbation of autophagy may serve as a novel, intriguing, and powerful cardioprotective treatment strategy and (ii) summarize the controversies and challenges in exploiting autophagy as a therapeutic target for ischaemia/reperfusion injury.
Pleiotrophin over-expression provides trophic support to dopaminergic neurons in parkinsonian rats
Authors: Irene RE Taravini, Mariela Chertoff, Eduardo G Cafferata, José Courty, Mario G Murer, Fernando J Pitossi, Oscar S Gershanik
Journal: Molecular Neurodegeneration (2011)

Pleiotrophin is known to promote the survival and differentiation of dopaminergic neurons in vitro and is up-regulated in the substantia nigra of Parkinson's disease patients. To establish whether pleiotrophin has a trophic effect on nigrostriatal dopaminergic neurons in vivo, we injected a recombinant adenovirus expressing pleiotrophin in the substantia nigra of 6-hydroxydopamine lesioned rats. The viral vector induced pleiotrophin over-expression by astrocytes in the substantia nigra pars compacta, without modifying endogenous neuronal expression. The percentage of tyrosine hydroxylase-immunoreactive cells as well as the area of their projections in the lesioned striatum was higher in pleiotrophin-treated animals than in controls. These results indicate that pleiotrophin over-expression partially rescues tyrosine hydroxylase-immunoreactive cell bodies and terminals of dopaminergic neurons undergoing 6-hydroxydopamine-induced degeneration.
Diabetic Retinopathy and Other Ocular Findings in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study
Authors: Lloyd Paul Aiello
Journal: Diabetes Care (2013)

OBJECTIVE To evaluate whether intensive treatment (INT) with the goal of achieving blood glucose levels as close to the nondiabetic range as safely possible reduced the risk of onset and progression of diabetic retinopathy (DR) in subjects with type 1 diabetes (T1D) compared with conventional therapy (CON). RESEARCH DESIGN AND METHODS The Diabetes Control and Complications Trial (DCCT) (1982–1993) was a multicenter, controlled clinical trial comparing INT with CON for onset and progression of DR. The Epidemiology of Diabetes Interventions and Complications (EDIC) study (1994–present) is an observational follow-up of the DCCT cohort. RESULTS Of the 1,441 DCCT subjects, 726 had no DR (primary prevention cohort) and 715 had mild DR (secondary intervention cohort) at baseline. Subjects were followed for a mean of 6.5 years. INT median HbA1c was 7% compared with CON median of 9%. INT reduced the adjusted mean risk for the development of DR by 76% and slowed progression of DR by 54% compared with CON. Following DCCT, the HbA1c levels in the original INT and CON groups converged (year 8, INT 7.98%; CON 8.07%); nevertheless, the groups continued to have a durable effect of initial assigned therapy with significantly lower incidence of further DR progression in the INT group (hazard reduction 53–56%). Severe retinal outcomes and procedures to treat them were reduced by 50% in the original INT group. CONCLUSIONS INT delays the onset and slows the progression of DR. Furthermore, the early effects of metabolic control continue to accrue over many years despite subsequent comparable glycemic control (metabolic memory). These results emphasize the need for optimizing glycemic control as early as possible in patients with diabetes.
Histone Deacetylase Inhibitor Panobinostat Induces Clinical Responses with Associated Alterations in Gene Expression Profiles in Cutaneous T-Cell Lymphoma
Authors: Leigh Ellis, Yan Pan, Gordon K. Smyth, Daniel J. George, Chris McCormack, Roxanne Williams-Truax, Monica Mita, Joachim Beck, Howard Burris, Gail Ryan, Peter Atadja, Dale Butterfoss, Margaret Dugan, Kenneth Culver, Ricky W. Johnstone, H. Miles Prince
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Histone deacetylase inhibitors can alter gene expression and mediate diverse antitumor activities. Herein, we report the safety and activity of the histone deacetylase inhibitor panobinostat (LBH589) in cutaneous T-cell lymphoma (CTCL) and identify genes commonly regulated by panobinostat. Experimental Design: Panobinostat was administered orally to patients with CTCL on Monday, Wednesday, and Friday of each week on a 28-day cycle. A dose of 30 mg was considered excessively toxic, and subsequent patients were treated at the expanded maximum tolerated dose of 20 mg. Biopsies from six patients taken 0, 4, 8, and 24 h after administration were subjected to microarray gene expression profiling and real-time quantitative PCR of selected genes. Results: Patients attained a complete response (n = 2), attained a partial response (n = 4), achieved stable disease with ongoing improvement (n = 1), and progressed on treatment (n = 2). Microarray data showed distinct gene expression response profiles over time following panobinostat treatment, with the majority of genes being repressed. Twenty-three genes were commonly regulated by panobinostat in all patients tested. Conclusions: Panobinostat is well tolerated and induces clinical responses in CTCL patients. Microarray analyses of tumor samples indicate that panobinostat induces rapid changes in gene expression, and surprisingly more genes are repressed than are activated. A unique set of genes that can mediate biological responses such as apoptosis, immune regulation, and angiogenesis were commonly regulated in response to panobinostat. These genes are potential molecular biomarkers for panobinostat activity and are strong candidates for the future assessment of their functional role(s) in mediating the antitumor responses of panobinostat.
Corticosteroid modulation of human, antigen-specific Th1 and Th2 responses
Authors: Christine M. Braun, Shau-Ku Huang, Gregory G. Bashian, Anne Kagey-Sobotka, Lawrence M. Lichtenstein, David M. Essayan
Journal: Journal of Allergy and Clinical Immunology (1997)

Corticosteroids are potent antiinflammatory agents that modulate human T-lymphocyte responses. Controversy remains as to their possible differential effects on Th1 and Th2 subsets. This study explores the kinetics and efficacy of these agents in human, antigen-driven peripheral blood mononuclear cells (PBMCs) and in nontransformed, antigen-specific Th1 and Th2 clones. Ragweed- and tetanus toxoid-driven proliferative responses of PBMCs from dually sensitized individuals were downregulated equally by dexamethasone (inhibitory concentration of 50% [IC(50)] = 3 x 10(-9) and 2 x 10(-9) mol/L, respectively). The addition of dexamethasone as late as 36 hours after ragweed stimulation still resulted in more than 75% inhibition of the proliferative response, whereas the efficacy of dexamethasone was less than 50% when added 24 hours after tetanus toxoid stimulation. Antigen-induced gene expression for proinflammatory cytokines (IL-4, IL-5, IL-13, and interferon-gamma) from PBMCs was also downregulated by dexamethasone. Proliferation of antigen-specific Th1 and Th2 clones was inhibited by several corticosteroids (hydrocortisone < budesonide < dexamethasone; IC(50) = 10(-6) to 10(-8) mol/L), but no significant differences between Th1 and Th2 clones were evident. IC(50) values in the clones were 10-fold greater than in PBMCs. Gene expression and protein secretion for IL-4, IL-13, and interferon-gamma were downregulated in a concentration-dependent manner by each of the corticosteroids in Th1 and Th2 clones. These data suggest that Th1 and Th2 responses are equally affected by corticosteroids.
A Wounded Healer
Authors: Elizabeth Lawrence
Journal: Annals of Internal Medicine (2014)

On Being a Doctor21 October 2014A Wounded HealerElizabeth Lawrence, MDElizabeth Lawrence, MDFrom La Familia Medical Center, Santa Fe, New Mexico.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M14-0690 Audio Reading - “A Wounded Healer” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "A Wounded Healer," by E. Lawrence. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail I devoured books as a young girl. I particularly loved stories of survivors: orphans, runaways, people who had overcome illnesses or lived through natural disasters. I imagined how I would subsist if I were to find myself alone on an island after a shipwreck. I plotted how I would respond upon surviving a plane crash in the Andes. I pictured myself alone in outer space, navigating my spaceship back to Earth.I memorized incantations that I thought might be useful if I met a sorcerer. I practiced map reading. Imaginary kingdoms blurred with foreign lands, and fairy godmothers were as ... Author, Article, and Disclosure InformationAffiliations: From La Familia Medical Center, Santa Fe, New Mexico.Corresponding Author: Elizabeth Lawrence, MD, La Familia Medical Center, PO Box 5395, Santa Fe, NM 87502; e-mail, [email protected]org. PreviousarticleNextarticle Advertisement Audio Reading - “A Wounded Healer” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "A Wounded Healer," by E. Lawrence. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 21 October 2014Volume 161, Issue 8Page: 611-612KeywordsForecastingHealth careHearingHospitalizationsMedical educationNatural disastersPatientsPrevention, policy, and public healthResidencyTaste ePublished: 21 October 2014 Issue Published: 21 October 2014 Copyright & PermissionsCopyright © 2014 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...