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Full-Text Articles in Internal Medicine

Target-Specific Oral Anticoagulants-New Approaches In The Field Of Oral Anticoagulation, H. Mani, J. Douxfils, J. Ansell Jan 2015

Target-Specific Oral Anticoagulants-New Approaches In The Field Of Oral Anticoagulation, H. Mani, J. Douxfils, J. Ansell

Journal Articles

No abstract provided.


A Novel Engineered Vegf Blocker With An Excellent Pharmacokinetic Profile And Robust Anti-Tumor Activity, L. Liu, H. Yu, X. Huang, H. Tan, S. Li, Y. Luo, L. Zhang, S. Jiang, C. C. Chu, W. Tian, +4 Additional Authors Jan 2015

A Novel Engineered Vegf Blocker With An Excellent Pharmacokinetic Profile And Robust Anti-Tumor Activity, L. Liu, H. Yu, X. Huang, H. Tan, S. Li, Y. Luo, L. Zhang, S. Jiang, C. C. Chu, W. Tian, +4 Additional Authors

Journal Articles

BACKGROUND: Relatively poor penetration and retention in tumor tissue has been documented for large molecule drugs including therapeutic antibodies and recombinant immunoglobulin constant region (Fc)-fusion proteins due to their large size, positive charge, and strong target binding affinity. Therefore, when designing a large molecular drug candidate, smaller size, neutral charge, and optimal affinity should be considered. METHODS: We engineered a recombinant protein by molecular engineering the second domain of VEGFR1 and a few flanking residues fused with the Fc fragment of human IgG1, which we named HB-002.1. This recombinant protein was extensively characterized both in vitro and in vivo for …


Reply To: Nasal Endoscopy To Characterize Sinonasal Disease, A. E. Dixon, M. Castro, R. I. Cohen, L. B. Gerald, J. T. Holbrook, C. G. Irvin, S. Mohapatra, S. P. Peters, S. Rayapudi, R. A. Wise, +1 Additional Author Jan 2015

Reply To: Nasal Endoscopy To Characterize Sinonasal Disease, A. E. Dixon, M. Castro, R. I. Cohen, L. B. Gerald, J. T. Holbrook, C. G. Irvin, S. Mohapatra, S. P. Peters, S. Rayapudi, R. A. Wise, +1 Additional Author

Journal Articles

No abstract provided.


Relationship Between Alcohol Use Categories And Noninvasive Markers Of Advanced Hepatic Fibrosis In Hiv-Infected, Chronic Hepatitis C Virus-Infected, And Uninfected Patients, J. K. Lim, J. P. Tate, S. L. Fultz, J. L. Goulet, J. Conigliaro, K. J. Bryant, A. J. Gordon, C. Gibert, D. Rimland, V. Lo Re, +4 Additional Authors Jan 2014

Relationship Between Alcohol Use Categories And Noninvasive Markers Of Advanced Hepatic Fibrosis In Hiv-Infected, Chronic Hepatitis C Virus-Infected, And Uninfected Patients, J. K. Lim, J. P. Tate, S. L. Fultz, J. L. Goulet, J. Conigliaro, K. J. Bryant, A. J. Gordon, C. Gibert, D. Rimland, V. Lo Re, +4 Additional Authors

Journal Articles

Background. It is unclear if the risk of liver disease associated with different levels of alcohol consumption is higher for patients infected with human immunodeficiency virus (HIV) or chronic hepatitis C virus (HCV). We evaluated associations between alcohol use categories and advanced hepatic fibrosis, by HIV and chronic HCV status. Methods. We performed a cross-sectional study among participants in the Veterans Aging Cohort Study who reported alcohol consumption at enrollment (701 HIV/HCV-coinfected; 1410 HIV-monoinfected; 296 HCV-monoinfected; 1158 HIV/HCV-uninfected). Alcohol use category was determined by the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire and alcohol-related diagnoses and was classified as nonhazardous …


Reply: To Pmid 23929808, J. Karkhanis, E. C. Verna, M. S. Chang, R. T. Stravitz, M. L. Schilsky, W. M. Lee, R. S., Jr. Brown Jan 2014

Reply: To Pmid 23929808, J. Karkhanis, E. C. Verna, M. S. Chang, R. T. Stravitz, M. L. Schilsky, W. M. Lee, R. S., Jr. Brown

Journal Articles

No abstract provided.


Steroid Use In Acute Liver Failure, J. Karkhanis, E. C. Verna, M. S. Chang, R. T. Stravitz, M. Schilsky, W. M. Lee, R. S., Jr. Brown Jan 2014

Steroid Use In Acute Liver Failure, J. Karkhanis, E. C. Verna, M. S. Chang, R. T. Stravitz, M. Schilsky, W. M. Lee, R. S., Jr. Brown

Journal Articles

Drug-induced and indeterminate acute liver failure (ALF) might be due to an autoimmune-like hepatitis that is responsive to corticosteroid therapy. The aim of this study was to evaluate whether corticosteroids improve survival in fulminant autoimmune hepatitis, drug-induced, or indeterminate ALF, and whether this benefit varies according to the severity of illness. We conducted a retrospective analysis of autoimmune, indeterminate, and drug-induced ALF patients in the Acute Liver Failure Study Group from 1998-2007. The primary endpoints were overall and spontaneous survival (SS, survival without transplant). In all, 361 ALF patients were studied, 66 with autoimmune (25 steroids, 41 no steroids), 164 …


Brief Motivational Enhancement Intervention To Prevent Or Reduce Postpartum Alcohol Use: A Single-Blinded, Randomized Controlled Effectiveness Trial, D. M. Rubio, N. L. Day, J. Conigliaro, B. H. Hanusa, C. Larkby, M. Mcneil, E. Cohen, B. Jones, M. Watt-Morse, K. L. Kraemer, +2 Additional Authors Jan 2014

Brief Motivational Enhancement Intervention To Prevent Or Reduce Postpartum Alcohol Use: A Single-Blinded, Randomized Controlled Effectiveness Trial, D. M. Rubio, N. L. Day, J. Conigliaro, B. H. Hanusa, C. Larkby, M. Mcneil, E. Cohen, B. Jones, M. Watt-Morse, K. L. Kraemer, +2 Additional Authors

Journal Articles

AIMS: The aim of this study is to assess the effect of brief motivational enhancement intervention postpartum alcohol use. DESIGN: This study is a single-blinded, randomized controlled effectiveness trial in which pregnant women were assigned to receive usual care or up to 5 face-to-face brief motivational enhancement sessions lasting 10-30 minutes each and occurring at study enrollment, 4 and 8 weeks after enrollment, 32 weeks of gestation, and 6 weeks postpartum. SETTING: The setting is in a large, urban, obstetrics clinic. PARTICIPANTS: Participants were women who were >/= 18 years old,gestation, and consumed alcohol during pregnancy. Of 3438 women screened, …


D-Dimer And Risk Of Thromboembolic And Bleeding Events In Patients With Atrial Fibrillation - Observations From The Aristotle Trial, C. Christersson, L. Wallentin, U. Andersson, J. H. Alexander, J. Ansell, R. De Caterina, B. J. Gersh, C. B. Granger, M. Hanna, A. Siegbahn, +5 Additional Authors Jan 2014

D-Dimer And Risk Of Thromboembolic And Bleeding Events In Patients With Atrial Fibrillation - Observations From The Aristotle Trial, C. Christersson, L. Wallentin, U. Andersson, J. H. Alexander, J. Ansell, R. De Caterina, B. J. Gersh, C. B. Granger, M. Hanna, A. Siegbahn, +5 Additional Authors

Journal Articles

BackgroundD-dimer is related to adverse outcomes in arterial and venous thromboembolic diseases. ObjectivesTo evaluate the predictive value of D-dimer level for stroke, other cardiovascular events, and bleeds, in patients with atrial fibrillation (AF) treated with oral anticoagulation with apixaban or warfarin; and to evaluate the relationship between the D-dimer levels at baseline and the treatment effect of apixaban vs. warfarin. MethodsIn the ARISTOTLE trial, 18201 patients with AF were randomized to apixaban or warfarin. D-dimer was analyzed in 14878 patients at randomization. The cohort was separated into two groups; not receiving vitaminK antagonist (VKA) treatment and receiving VKA treatment at …


Direct Oral Anticoagulants New Drugs And New Concepts, J. H. Levy, A. C. Spyropoulos, C. M. Samama, J. Douketis Jan 2014

Direct Oral Anticoagulants New Drugs And New Concepts, J. H. Levy, A. C. Spyropoulos, C. M. Samama, J. Douketis

Journal Articles

Direct oral anticoagulants (DOACs) are approved for multiple thromboembolic disorders and provide advantages over existing agents. As with all anticoagulants, management protocols for the eventuality of bleeding are important. Randomized phase III studies generally show that DOACs have a similar risk of clinically relevant bleeding compared with standard anticoagulants, with reductions in major bleeding in some cases. This may be particularly important in patients with atrial fibrillation, for whom the rate of intracranial hemorrhage was approximately halved with DOACs compared with warfarin. Conversely, the risk of gastrointestinal bleeding may be increased. Specific patient characteristics, such as renal impairment, comedications, and …


Factors Associated With Inconsistent Condom Use In Adolescents With Negative Or Unknown Hiv Status In Northwest Cameroon, L. Morris, F. Kouya, R. Kwalar, M. Pilapil, K. Saito, N. Palmer, R. Posada, P. M. Tih, T. Welty, J. Jao Jan 2014

Factors Associated With Inconsistent Condom Use In Adolescents With Negative Or Unknown Hiv Status In Northwest Cameroon, L. Morris, F. Kouya, R. Kwalar, M. Pilapil, K. Saito, N. Palmer, R. Posada, P. M. Tih, T. Welty, J. Jao

Journal Articles

The purpose of this study is to evaluate the association between utilization of HIV testing and condom use amongst Cameroonian youths/adolescents who are not known to be HIV-infected. Worldwide, HIV is spreading most quickly amongst youths/adolescents. Between 44% and 82% of sexually active youths in Cameroon report inconsistent condom use. Data regarding utilization of HIV testing and condom use are lacking. A cross-sectional survey was administered to 431 youths ages 12-26 years in Cameroon from September 2011 to December 2011. Data on sociodemographics, sexual risk behaviors, self-reported HIV status, and condom use were collected. We compared rates of inconsistent condom …


Hla-Drb1-Associated Rheumatoid Arthritis Risk At Multiple Levels In African Americans Hierarchical Classification Systems, Amino Acid Positions, And Residues, R. J. Reynolds, A. F. Ahmed, M. I. Danila, L. B. Hughes, P. K. Gregersen, S. Raychaudhuri, R. M. Plenge, S. L. Bridges, Af Consortium Longitudinal Evaluat Jan 2014

Hla-Drb1-Associated Rheumatoid Arthritis Risk At Multiple Levels In African Americans Hierarchical Classification Systems, Amino Acid Positions, And Residues, R. J. Reynolds, A. F. Ahmed, M. I. Danila, L. B. Hughes, P. K. Gregersen, S. Raychaudhuri, R. M. Plenge, S. L. Bridges, Af Consortium Longitudinal Evaluat

Journal Articles

Objective. To evaluate HLA-DRB1 genetic risk of rheumatoid arthritis (RA) in African Americans by 3 validated allele classification systems and by amino acid position and residue, and to compare genetic risk between African American and European ancestries. Methods. Four-digit HLA-DRB1 genotyping was performed on 561 autoantibody-positive African American cases and 776 African American controls. Associa-tion analysis was performed on Tezenas du Montcel (TdM), de Vries (DV), and Mattey classification system alleles and separately by amino acid position and individual residues. Results. TdM S2 and S3P alleles were associated with RA (odds ratio [95% confidence interval] 2.8 [2.0-3.9] and 2.1 [1.7-2.7], …


The Influence Of Polygenic Risk Scores On Heritability Of Anti-Ccp Level In Ra, J. Cui, K. E. Taylor, Y. C. Lee, H. Kallberg, M. E. Weinblatt, J. S. Coblyn, L. Klareskog, L. A. Criswell, P. K. Gregersen, E. W. Karlson, +2 Additional Authors Jan 2014

The Influence Of Polygenic Risk Scores On Heritability Of Anti-Ccp Level In Ra, J. Cui, K. E. Taylor, Y. C. Lee, H. Kallberg, M. E. Weinblatt, J. S. Coblyn, L. Klareskog, L. A. Criswell, P. K. Gregersen, E. W. Karlson, +2 Additional Authors

Journal Articles

The objective of this study was to study genetic factors that influence quantitative anticyclic citrullinated peptide (anti-CCP) antibody levels in RA patients. We carried out a genome-wide association study (GWAS) meta-analysis using 1975 anti-CCP + RA patients from three large cohorts, the Brigham Rheumatoid Arthritis Sequential Study (BRASS), North American Rheumatoid Arthritis Consortium (NARAC) and the Epidemiological Investigation of RA (EIRA). We also carried out a genome-wide complex trait analysis (GCTA) to estimate the heritability of anti-CCP levels. GWAS-meta-analysis showed that anti-CCP levels were most strongly associated with the human leukocyte antigen (HLA) region with a P-value of 2 x …


Lymphoma Risk In Systemic Lupus: Effects Of Disease Activity Versus Treatment, S. Bernatsky, R. Ramsey-Goldman, L. Joseph, J. F. Boivin, K. H. Costenbader, M. B. Urowitz, D. D. Gladman, P. R. Fortin, C. Aranow, A. E. Clarke, +27 Additional Authors Jan 2014

Lymphoma Risk In Systemic Lupus: Effects Of Disease Activity Versus Treatment, S. Bernatsky, R. Ramsey-Goldman, L. Joseph, J. F. Boivin, K. H. Costenbader, M. B. Urowitz, D. D. Gladman, P. R. Fortin, C. Aranow, A. E. Clarke, +27 Additional Authors

Journal Articles

Objective To examine disease activity versus treatment as lymphoma risk factors in systemic lupus erythematosus (SLE). Methods We performed case-cohort analyses within a multisite SLE cohort. Cancers were ascertained by regional registry linkages. Adjusted HRs for lymphoma were generated in regression models, for time-dependent exposures to immunomodulators (cyclophosphamide, azathioprine, methotrexate, mycophenolate, antimalarial drugs, glucocorticoids) demographics, calendar year, Sjogren's syndrome, SLE duration and disease activity. We used adjusted mean SLE Disease Activity Index scores (SLEDAI-2K) over time, and drugs were treated both categorically (ever/never) and as estimated cumulative doses. Results We studied 75 patients with lymphoma (72 non-Hodgkin, three Hodgkin) and …


Mhc Associations With Clinical And Autoantibody Manifestations In European Sle, D. L. Morris, M. M. A. Fernando, K. E. Taylor, S. A. Chung, J. Nititham, M. E. Alarcon-Riquelme, L. F. Barcelloss, T. W. Behrens, P. K. Gregersen, Con Syst Lupus Erythematosus Genet, +13 Additional Authors Jan 2014

Mhc Associations With Clinical And Autoantibody Manifestations In European Sle, D. L. Morris, M. M. A. Fernando, K. E. Taylor, S. A. Chung, J. Nititham, M. E. Alarcon-Riquelme, L. F. Barcelloss, T. W. Behrens, P. K. Gregersen, Con Syst Lupus Erythematosus Genet, +13 Additional Authors

Journal Articles

Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease affecting multiple organ systems and characterized by autoantibody formation to nuclear components. Although genetic variation within the major histocompatibility complex (MHC) is associated with SLE, its role in the development of clinical manifestations and autoantibody production is not well defined. We conducted a meta-analysis- of four independent European SLE case collections for associations between SLE sub-phenotypes and MHC single-nucleotide polymorphism genotypes, human leukocyte antigen (HLA) alleles and variant HLA amino acids. Of the 11 American College of Rheumatology criteria and 7 autoantibody sub-phenotypes examined, anti-Ro/SSA and anti-La/SSB antibody subsets exhibited the …


Acute Mesenteric Ischemia: A Sequela Of Abdominal Aortography, S. Kedia, V. R. Bhatt, A. Koirala, S. Murukutla, J. Rijal, S. Pant, M. A. Wrzolek, A. Gottesman Jan 2014

Acute Mesenteric Ischemia: A Sequela Of Abdominal Aortography, S. Kedia, V. R. Bhatt, A. Koirala, S. Murukutla, J. Rijal, S. Pant, M. A. Wrzolek, A. Gottesman

Journal Articles

The use of abdominal angiography and transcatheter embolization has increased rapidly in the last few decades. Although improvement in angiographic techniques has made the procedure safe, ischemic colitis is a rare but potentially dreadful complication. We report a case of a 51-year-old woman who developed ischemic colitis following aortography, demonstrating that such angiographic studies may produce substantial morbidity.


Acute St-Segment Elevation Myocardial Infarction In A Young Patient With Essential Thrombocythemia: A Case With Long-Term Follow-Up Report, T. Bhat, M. Ahmed, H. Baydoun, Z. Ghandour, A. Bhat, D. Mccord Jan 2014

Acute St-Segment Elevation Myocardial Infarction In A Young Patient With Essential Thrombocythemia: A Case With Long-Term Follow-Up Report, T. Bhat, M. Ahmed, H. Baydoun, Z. Ghandour, A. Bhat, D. Mccord

Journal Articles

Essential thrombocythemia (ET) is a neoplastic proliferation of mature myeloid cells - in particular, megakaryocytes - leading to persistently elevated platelet count. Usual clinical presentation is related to an increase in the risk of hemorrhage and/or thrombosis. Management of ET consists of antiplatelet therapies - mainly aspirin and cytoreductive therapies. Coronary involvement in patients with ET is rare. The optimal treatment strategies for ET patients presenting with acute myocardial infarction remains unclear. Acute interventions like intracoronary thrombolytic therapy, angioplasty, and coronary-artery bypass grafting have been reported in such patients. However, several questions remain unanswered about the acute and long-term management …


Angiopoietin-2: A Key To Understanding Sepsis And Its Pulmonary Sequelae?, J. Y. Lee, E. J. Miller Jan 2014

Angiopoietin-2: A Key To Understanding Sepsis And Its Pulmonary Sequelae?, J. Y. Lee, E. J. Miller

Journal Articles

No abstract provided.


B-1a Cell Diversity: Nontemplated Addition In B-1a Cell Ig Is Determined By Progenitor Population And Developmental Location, N. E. Holodick, T. Vizconde, T. L. Rothstein Jan 2014

B-1a Cell Diversity: Nontemplated Addition In B-1a Cell Ig Is Determined By Progenitor Population And Developmental Location, N. E. Holodick, T. Vizconde, T. L. Rothstein

Journal Articles

Natural Abs produced by B-1a cells are required for immediate protection against infection. The protective capacity of natural Abs is attributed to germline-like structure, which includes the relative absence of N-region addition. Previous studies have shown B-1a cell Ig from aged mice contains abundant nontemplated (N)-additions. B-1a cells have been shown to derive from a specific lineage-negative (Lin(-)) CD45R(low/-) CD19(+) progenitor found both in fetal liver and adult bone marrow. In this study, we report identification of a fetal liver population characterized phenotypically as Lin(-)CD45R(-)CD19(-), which gives rise to IgM(+)IgD(low)CD45R(low)CD5(+)Mac-1(+)CD19(high)CD43(+)CD23(low) B-1a cells upon adoptive transfer to SCID recipients. These B-1a …


Breast Cancer And Aging: Results Of The U13 Conference Breast Cancer Panel, M. F. Barginear, H. Muss, G. Kimmick, C. Owusu, E. Mrozek, A. Shahrokni, K. Ballman, A. Hurria Jan 2014

Breast Cancer And Aging: Results Of The U13 Conference Breast Cancer Panel, M. F. Barginear, H. Muss, G. Kimmick, C. Owusu, E. Mrozek, A. Shahrokni, K. Ballman, A. Hurria

Journal Articles

Breast cancer is predominantly a disease of older women, yet there is a knowledge gap due to the persisting misalignment between the age distribution of women with breast cancer and the age distribution of participants in clinical trials. The purpose of this report is to state the U13 conference breast cancer panel's recommendations regarding therapeutic clinical trials that will fill gaps in knowledge regarding the care of older patients with breast cancer. The U13 conference was a collaboration between the Cancer and Aging Research Group and the National Institute on Aging and the National Cancer Institute (NCI). Clinical trials should …


C1q-Mediated Repression Of Human Monocytes Is Regulated By Lair-1, M. Son, B. Diamond Jan 2014

C1q-Mediated Repression Of Human Monocytes Is Regulated By Lair-1, M. Son, B. Diamond

Journal Articles

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by abnormal function of both the innate and the adaptive immune system, leading to a loss of tolerance to self-antigens. Monocytes are a key component of the innate immune system and are efficient producers of multiple cytokines. In SLE, inappropriate activation of monocytes is thought to contribute to the loss of self-tolerance. In this study, we demonstrate that type 1 interferon (IFN) production by CpG-challenged monocytes can be suppressed by C1q through activate leukocyte-associated Ig-like receptor-1 (LAIR-1), which contains ITIM motifs. The phosphorylation of LAIR-1 and the interaction of LAIR-1 …


Coupling To A Glioblastoma-Directed Antibody Potentiates Antitumor Activity Of Curcumin, P. Langone, P. R. Debata, J. D. Inigo, S. Dolai, S. Mukherjee, P. Halat, K. Mastroianni, G. M. Curcio, M. R. Castellanos, K. Raja, P. Banerjee Jan 2014

Coupling To A Glioblastoma-Directed Antibody Potentiates Antitumor Activity Of Curcumin, P. Langone, P. R. Debata, J. D. Inigo, S. Dolai, S. Mukherjee, P. Halat, K. Mastroianni, G. M. Curcio, M. R. Castellanos, K. Raja, P. Banerjee

Journal Articles

Current therapies for glioblastoma are largely palliative, involving surgical resection followed by chemotherapy and radiation therapy, which yield serious side effects and very rarely produce complete recovery. Curcumin, a food component, blocked brain tumor formation but failed to eliminate established brain tumors in vivo, probably because of its poor bioavailability. In the glioblastoma GL261 cells, it suppressed the tumor-promoting proteins NF-kappa B, P-Akt1, vascular endothelial growth factor, cyclin D1 and BClXL and triggered cell death. Expression of exogenous p50 and p65 subunits of NF-kappa B conferred partial protection on transfected GL261 cells against curcumin insult, indicating that NF-kappa B played …


Effects Of Prostaglandin E-2 On P53 Mrna Transcription And P53 Mutagenesis During T-Cell-Independent Human B-Cell Clonal Expansion, S. Haque, X. J. Yan, L. Rosen, S. Mccormick, N. Chiorazzi, P. K. A. Mongini Jan 2014

Effects Of Prostaglandin E-2 On P53 Mrna Transcription And P53 Mutagenesis During T-Cell-Independent Human B-Cell Clonal Expansion, S. Haque, X. J. Yan, L. Rosen, S. Mccormick, N. Chiorazzi, P. K. A. Mongini

Journal Articles

Within T-cell-dependent germinal centers, p53 gene transcription is repressed by Bcl-6 and is thus less vulnerable to mutation. Malignant lymphomas within inflamed extranodal sites exhibit a relatively high incidence of p53 mutations. The latter might originate from normal B-cell clones manifesting activation-induced cytosine deaminase (AID) and up-regulated p53 following T-cell-independent (TI) stimulation. We here examine p53 gene transcription in such TI clones, with a focus on modulatory effects of prostaglandin E-2 (PGE(2)), and evaluate progeny for p53 mutations. Resting IgM(+)IgD(+)CD27(-) B cells from human tonsils were labeled with CFSE and stimulated in vitro with complement-coated antigen surrogate, IL-4, and BAFF …


Endobronchial Ultrasound As A Confirmatory Tool For The Diagnosis Of Pulmonary Embolism, K. Harris, M. Chalhoub Jan 2014

Endobronchial Ultrasound As A Confirmatory Tool For The Diagnosis Of Pulmonary Embolism, K. Harris, M. Chalhoub

Journal Articles

No abstract provided.


External Validation Of The Risk Assessment Model Of The International Medical Prevention Registry On Venous Thromboembolism (Improve) For Medical Patients In A Tertiary Health System, D. Rosenberg, A. Eichorn, M. Alarcon, L. Mccullagh, T. Mcginn, A. Spyropoulos Jan 2014

External Validation Of The Risk Assessment Model Of The International Medical Prevention Registry On Venous Thromboembolism (Improve) For Medical Patients In A Tertiary Health System, D. Rosenberg, A. Eichorn, M. Alarcon, L. Mccullagh, T. Mcginn, A. Spyropoulos

Journal Articles

Background-Hospitalized medical patients are at risk for venous thromboembolism (VTE). Universal application of pharmacological thromboprophylaxis has the potential to place a large number of patients at increased bleeding risk. In this study, we aimed to externally validate the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) VTE risk assessment model in a hospitalized general medical population. Methods and Results-We identified medical discharges that met the IMPROVE protocol. Cases were defined as hospital-acquired VTE and confirmed by diagnostic study within 90 days of index hospitalization; matched controls were also identified. Risk factors for VTE were based on the IMPROVE risk assessment …


The Gut Microbiota Influences Blood-Brain Barrier Permeability In Mice, V. Braniste, M. Al-Asmakh, C. Kowal, F. Anuar, A. Abbaspour, M. Toth, A. Korecka, B. T. Volpe, B. Diamond, S. Pettersson, +8 Additional Authors Jan 2014

The Gut Microbiota Influences Blood-Brain Barrier Permeability In Mice, V. Braniste, M. Al-Asmakh, C. Kowal, F. Anuar, A. Abbaspour, M. Toth, A. Korecka, B. T. Volpe, B. Diamond, S. Pettersson, +8 Additional Authors

Journal Articles

Pivotal to brain development and function is an intact blood-brain barrier (BBB), which acts as a gatekeeper to control the passage and exchange of molecules and nutrients between the circulatory system and the brain parenchyma. The BBB also ensures homeostasis of the central nervous system (CNS). We report that germ-free mice, beginning with intrauterine life, displayed increased BBB permeability compared to pathogen-free mice with a normal gut flora. The increased BBB permeability was maintained in germ-free mice after birth and during adulthood and was associated with reduced expression of the tight junction proteins occludin and claudin-5, which are known to …


Hormonal Milieu At Time Of B Cell Activation Controls Duration Of Autoantibody Response, V. Jeganathan, E. Peeva, B. Diamond Jan 2014

Hormonal Milieu At Time Of B Cell Activation Controls Duration Of Autoantibody Response, V. Jeganathan, E. Peeva, B. Diamond

Journal Articles

A strong gender bias is seen in many autoimmune diseases including systemic lupus erythematosus (SLE). To investigate the basis for the female preponderance in SLE, we have been studying BALB/c mice in which B cells express the R4A heavy chain of an anti-DNA antibody in association with an endogenous light chain repertoire (R4Atg mice). In unmanipulated mice, approximately 5% of B cells express the R4A transgene. R4Atg mice do not spontaneously develop elevated serum titers of anti-DNA antibodies. Administration of either estradiol (E2) or prolactin (Pr) results in escape from tolerance of autoreactive B cells, expressed as an increase in …


Identification Of Stage-Specific Genes Associated With Lupus Nephritis And Response To Remission Induction In (Nzb X Nzw)F1 And Nzm2410 Mice, R. Bethunaickan, C. C. Berthier, W. J. Zhang, R. Eksi, H. D. Li, Y. F. Guan, M. Kretzler, A. Davidson Jan 2014

Identification Of Stage-Specific Genes Associated With Lupus Nephritis And Response To Remission Induction In (Nzb X Nzw)F1 And Nzm2410 Mice, R. Bethunaickan, C. C. Berthier, W. J. Zhang, R. Eksi, H. D. Li, Y. F. Guan, M. Kretzler, A. Davidson

Journal Articles

Objective. To elucidate the molecular mechanisms involved in renal inflammation during the progression, remission, and relapse of nephritis in murine lupus models using transcriptome analysis. Methods. Kidneys from (NZB x NZW)F1 (NZB/NZW) and NZM2410 mice were harvested at intervals during the disease course or after remission induction. Genome-wide expression profiles were obtained from microarray analysis of perfused kidneys. Real-time polymerase chain reaction (PCR) analysis for selected genes was used to validate the microarray data. Comparisons between groups using SAM, and unbiased analysis of the entire data set using singular value decomposition and self-organizing maps were performed. Results. Few changes in …


Impact On House Staff Evaluation Scores When Changing From A Dreyfus- To A Milestone-Based Evaluation Model: One Internal Medicine Residency Program's Findings, K. A. Friedman, S. Balwan, F. Cacace, K. Katona, S. Sunday, S. Chaudhry Jan 2014

Impact On House Staff Evaluation Scores When Changing From A Dreyfus- To A Milestone-Based Evaluation Model: One Internal Medicine Residency Program's Findings, K. A. Friedman, S. Balwan, F. Cacace, K. Katona, S. Sunday, S. Chaudhry

Journal Articles

Purpose: As graduate medical education (GME) moves into the Next Accreditation System (NAS), programs must take a critical look at their current models of evaluation and assess how well they align with reporting outcomes. Our objective was to assess the impact on house staff evaluation scores when transitioning from a Dreyfus-based model of evaluation to a Milestone-based model of evaluation. Milestones are a key component of the NAS. Method: We analyzed all end of rotation evaluations of house staff completed by faculty for academic years 2010-2011 (pre-Dreyfus model) and 2011-2012 (post-Milestone model) in one large university-based internal medicine residency training …


Iso-66, A Novel Inhibitor Of Macrophage Migration Inhibitory Factor, Shows Efficacy In Melanoma And Colon Cancer Models, K. Ioannou, K. F. Cheng, G. V. Crichlow, A. I. Birmpilis, E. J. Lolis, O. E. Tsitsilonis, Y. Al-Abed Jan 2014

Iso-66, A Novel Inhibitor Of Macrophage Migration Inhibitory Factor, Shows Efficacy In Melanoma And Colon Cancer Models, K. Ioannou, K. F. Cheng, G. V. Crichlow, A. I. Birmpilis, E. J. Lolis, O. E. Tsitsilonis, Y. Al-Abed

Journal Articles

Macrophage migration inhibitory factor (MIF) is a pleiotropic pro-inflammatory cytokine, which possesses a contributing role in cancer progression and metastasis and, thus, is now considered a promising anticancer drug target. Many MIF-inactivating strategies have proven successful in delaying cancer growth. Here, we report on the synthesis of ISO-66, a novel, highly stable, small-molecule MIF inhibitor, an analog of ISO-1 with improved characteristics. The MIF:ISO-66 co-crystal structure demonstrated that ISO-66 ligates the tautomerase active site of MIF, which has previously been shown to play an important role in its biological functions. In vitro, ISO-66 enhanced specific and non-specific anticancer immune responses, …


Measures Of User Experience In A Streptococcal Pharyngitis And Pneumonia Clinical Decision Support Tools, D. Mann, M. Knaus, L. Mccullagh, A. Sofianou, L. Rosen, T. Mcginn, J. Kannry Jan 2014

Measures Of User Experience In A Streptococcal Pharyngitis And Pneumonia Clinical Decision Support Tools, D. Mann, M. Knaus, L. Mccullagh, A. Sofianou, L. Rosen, T. Mcginn, J. Kannry

Journal Articles

Objective: To understand clinician adoption of CDS tools as this may provide important insights for the implementation and dissemination of future CDS tools. Materials and Methods: Clinicians (n=168) at a large academic center were randomized into intervention and control arms to assess the impact of strep and pneumonia CDS tools. Intervention arm data were analyzed to examine provider adoption and clinical workflow. Electronic health record data were collected on trigger location, the use of each component and whether an antibiotic, other medication or test was ordered. Frequencies were tabulated and regression analyses were used to determine the association of tool …