tbuckley/cabot-search huggingface dataset:
Clinical decision rules in rheumatoid arthritis: do they identify patients at high risk for osteoporosis? Testing clinical criteria in a population based cohort of patients with rheumatoid arthritis recruited from the Oslo Rheumatoid Arthritis Register
Authors: G Haugeberg
Journal: Annals of the Rheumatic Diseases (2002)

Preliminary clinical criteria based on age, inflammation, and immobility have been proposed to identify which patients with rheumatoid arthritis (RA) should be examined by dual energy x ray absorptiometry (DXA) to diagnose osteoporosis. The three item criteria have not been evaluated in male patients with RA or in the entire female RA population.(1) To test the proposed criteria in a cohort of men and women thought to be representative of the entire underlying RA population. (2) To develop clinical decision rules, which could be applied to all patients with RA irrespective of corticosteroid use.Clinical and demographic data were collected from a total of 287 representative patients with RA (235 (82%) women, 52 (18%) men, age range 25.3-73.1 years) from the Oslo RA register (completeness 85%). Bone mineral density (BMD) was measured in spine L2-4 (anterior-posterior view) and femoral neck by DXA. The criteria were applied and sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated.Mean age (SD) for the women and men with RA was 56.8 (11.0) years and 61.5 (10.2) years; disease duration was 15.5 (9.5) years and 14.7 (8.6) years. Of the women 163 (69%) were postmenopausal. One hundred and seventeen (50%) women and 28 (54%) men fulfilled the three item criteria. For the diagnosis of osteoporosis (T score <or=-2.5) using the original three item criteria sensitivity in women and men was 74% and 67%, specificity 57% and 50%, PPV 32% and 29% and NPV 89% and 83%, and including weight and ever use of corticosteroids in a five item criteria sensitivity increased to 82% and 83%, specificity decreased to 45% and 45%, PPV was 29% and 31%, and NPV was 90% and 90% respectively.The novel five item criteria (age, weight, inflammation, immobility, and ever use of corticosteroids) are a more accurate tool to identify patients with RA and osteoporosis than the original three item criteria (age, inflammation, and immobility). The clinical decision rules have an acceptable sensitivity and provide a practical tool for the doctor to identify patients with RA who should have a DXA measurement performed.
Depressive Symptoms as Predictors of Medical Outcomes in HIV Infection
Authors: Constantine G. Lyketsos
Journal: JAMA (1993)

<h3>Objective.</h3> —To ascertain whether depressive symptoms as determined by the Center for Epidemiologic Studies—Depression scale (CES-D) predict accelerated mortality and worse medical outcomes in patients infected with human immunodeficiency virus (HIV). <h3>Design.</h3> —Eight-year cohort study with semiannual follow-up. <h3>Setting.</h3> —Community volunteers. <h3>Participants.</h3> —A total of 1809 HIV-seropositive homosexual men without the acquired immunodeficiency syndrome (AIDS) who entered the Multicenter AIDS Cohort Study in 1984 or 1985. Eight-year follow-up data were available on 75% of eligible participants. <h3>Outcome Measures.</h3> —Times to AIDS, death, and prophylactic treatment, and slopes describing the decline in CD4 count for each individual participant. <h3>Results.</h3> —Using a conventional definition of depression (CES-D ≥16 at the first study visit), 21.3% of participants were classified as depressed. Depressed participants had lower CD4 counts and reported more AIDS-related symptoms. There were no significant differences between depressed and nondepressed participants on any of the outcome measures (<i>P</i>&gt;.05 in all cases). In contrast, men reporting AIDS-related symptoms had shorter times to AIDS and to death even after adjusting for CD4 counts (<i>P</i>&lt;.01). The analyses were repeated, with similar results, using different definitions of depression based on the CES-D. <h3>Conclusions.</h3> —We find no evidence that depressive symptoms independently prognosticate worse outcomes in HIV infection. Because of associations of depression with symptom reports, CD4 counts, and indicators of socioeconomic status, future studies of the relationship between depression and HIV outcome should consider these variables as confounders. (<i>JAMA</i>. 1993;270:2563-2567)
An epigenomic mechanism in retinoblastoma: the end of the story?
Authors: A Linn Murphree, Timothy J Triche
Journal: Genome Medicine (2012)

The role that retinoblastoma has played in our understanding of cancer biology could hardly have been imagined 40 years ago when this disease was a rare curiosity, of interest primarily because of its variable laterality, occasional dominant inheritance, frequent lethality and embyronal origin. The discovery of its cause (biallelic loss of RB1) did not offer insight to improved management. However, the recent discovery of aberrant expression of the gene encoding spleen tyrosine kinase (SYK) subsequent to widespread methylation abnormalities in retinoblastoma suggests a potential new therapy for the disease. There is more to the story, however.
Radical Duodenopancreatectomy for Papilloma of the Pancreatic Duct
Authors: W. G. Hendry
Journal: BMJ (1952)

TREATMENT OF NON-SPECIFIC CERVICITIS Biusn 815The average number of treatments required in the satisfactory cases was 4.5.Forty cases of monilial infection in pregnancy treated with the same preparation were all regarded as cured.We thank Messrs. Camden Chemical Co. for liberal supplies of this compound, which is marketed under the name of " pruvagol.
Transplantation of cardiac-committed mouse embryonic stem cells to infarcted sheep myocardium: a preclinical study
Authors: Claudine Ménard, Albert A Hagège, Onnik Agbulut, Marietta Barro, Miguel Cortes Morichetti, Camille Brasselet, Alain Bel, Emmanuel Messas, Alvine Bissery, Patrick Bruneval, Michel Desnos, Michel Pucéat, Philippe Menasché
Journal: The Lancet (2005)
Monoclonal Antibody Targeting of the Cell Surface Molecule TM4SF5 Inhibits the Growth of Hepatocellular Carcinoma
Authors: Sanghoon Kwon, Kyung-Chan Choi, Young-Eun Kim, Yang-Wha Ha, Dongbum Kim, Byoung Kwon Park, Guang Wu, Doo-Sik Kim, Younghee Lee, Hyung-Joo Kwon
Journal: Cancer Research (2014)

The cell surface transmembrane receptor TM4SF5 has been implicated in hepatocellular carcinoma (HCC), but its candidacy as a therapeutic target has not been evaluated. Building on findings that immunization with a peptide vaccine targeting human TM4SF5 can exert prophylactic and therapeutic effects in a murine model of HCC, we developed a monoclonal antibody to characterize expression of TM4SF5 in HCC and to target its function there as an anticancer strategy. We found that the antibody modulated cell signaling in HCC cells in vitro, reducing cell motility, modulating E-cadherin expression, altering p27(kip1) localization, and increasing RhoA activity. Using a mouse xenograft model of human HCC, we documented the in vivo efficacy of the antibody, which suppressed tumor growth in either tumor prevention or treatment designs. Our work offers a preclinical proof of concept for TM4SF5 as a promising target for antibody therapeutics to treat HCC. Cancer Res; 74(14); 3844-56. ©2014 AACR.
Design of the Revascularization With Open Bypass vs Angioplasty and Stenting of the Lower Extremity Trial (ROBUST)
Authors: Mahmoud B. Malas, Umair Qazi, Natalia Glebova, Isibor Arhuidese, Thomas Reifsnyder, James Black, Bruce A. Perler, Julie A. Freischlag
Journal: JAMA Surgery (2014)

<h3>Importance</h3> To our knowledge, there is no level 1 evidence comparing open bypass with angioplasty and stenting in TransAtlantic Inter-Society Consensus (TASC II) B and C superficial femoral artery lesions. The Revascularization With Open Bypass vs Angioplasty and Stenting of the Lower Extremity Trial (ROBUST) is the first prospective randomized clinical trial comparing both treatments. <h3>Objectives</h3> To report the design of the ROBUST trial. The primary aim of the trial is to compare (1) the patency rate (primary, primary assisted, and secondary patency at 6 and 12 months), (2) improvement of quality of life, (3) clinical improvement (at least 1 Rutherford category), and (4) wound healing and limb salvage in patients presenting with critical limb ischemia; secondary aims include (1) cost-effectiveness by factoring procedure and hospital admission costs including rehabilitation, readmission, and reintervention costs, (2) amputation-free survival, (3) reintervention rate, and (4) 30-day operative mortality, morbidity, and wound and access complications. <h3>Design, Setting, and Participants</h3> ROBUST is a prospective randomized clinical trial with the aim to enroll 320 patients with intermittent claudication that does not respond to medical management and patients with critical limb ischemia. The maximum level of medical therapy will be administered using antiplatelet agents and statins, as well as measures to control hypertension and diabetes mellitus. <h3>Interventions</h3> Patients with TASC II B or C lesions are prospectively randomized to receive either femoropopliteal bypass or percutaneous transluminal angioplasty and stenting; patients with TASC II A and D lesions are not randomized and receive percutaneous transluminal angioplasty and stenting or femoropopliteal bypass, respectively. All patients will be evaluated at 1, 6, and 12 months postoperatively with physical examination, ankle brachial index, duplex, and a quality-of-life questionnaire. <h3>Results</h3> The trial is actively enrolling participants. At the time of writing, 29 patients have been enrolled; most are male (60%) and white (65%). <h3>Conclusions and Relevance</h3> Providing level 1 evidence, ROBUST may help to establish guidelines for the treatment of superficial femoral artery lesions, eliminate unnecessary procedures, and reduce health care costs. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT01602159
THE LESIONS IN THE SKELETAL MUSCLES IN EXPERIMENTAL SCORBUTUS
Authors: Gilbert Dalldorf
Journal: The Journal of Experimental Medicine (1929)

1. Muscle degeneration was constantly found in the intercostal muscles of scorbutic guinea pigs. 2. It has likewise been found in the masseter and diaphragmatic muscles. 3. Exercise will produce an identical lesion in other skeletal muscles in scorbutic animals. 4. The lesions appear to be an intrinsic part of the scorbutic process. 5. It is suggested that the tenderness over muscles in scorbutic animals and in man may be due to this myopathy.
Prospective Comparison of Clinical and Genomic Multivariate Predictors of Response to Neoadjuvant Chemotherapy in Breast Cancer
Authors: Jae K. Lee, Charles Coutant, Young-Chul Kim, Yuan Qi, Dan Theodorescu, W. Fraser Symmans, Keith Baggerly, Roman Rouzier, Lajos Pusztai
Journal: Clinical Cancer Research (2010)

Several different multivariate prediction models using routine clinical variables or multigene signatures have been proposed to predict pathologic complete response to combination chemotherapy in breast cancer. Our goal was to compare the performance of four conceptually different predictors in an independent cohort of patients.Gene expression profiling was done on fine-needle aspirations of 100 stage I to III breast cancers before preoperative paclitaxel, 5-fluorouracil, doxorubicin, and cyclophosphamide combination chemotherapy. Pathologic response was correlated with prediction results from a clinical nomogram, a human cancer-derived genomic predictor (DLDA30), a cell line-based genomic predictor [in vitro coexpression extrapolation (COXEN)], and an optimized cell line-derived (in vivo COXEN) predictor. None of the 100 test cases were used in the development of these predictors.The in vitro COXEN using a combination of four individual drug sensitivity predictions derived from cell lines was not predictive [area under the receiver operator characteristic curve (AUC), 0.5; 95% confidence interval, (95% CI), 0.41-0.59]. The clinical nomogram (AUC, 0.73; 95% CI, 0.65-0.80) and the DLDA30 (AUC, 0.73; 95% CI, 0.66-0.80) genomic predictor had similar performances. The in vivo COXEN that used informative genes from cell lines but was trained on a separate human data set also showed significant predictive value (AUC, 0.67; 95% CI, 0.60-0.74). These three different prediction scores correlated with each other and were significant in univariate but not in multivariate analysis.Three conceptually different predictors performed similarly in this validation study and tended to identify the same patients as responders. A genomic predictor that relied solely on a composite of individual drug sensitivity predictions from cell lines did not show any predictive value.
Fyn Is Downstream of the HGF/MET Signaling Axis and Affects Cellular Shape and Tropism in PC3 Cells
Authors: Ana R. Jensen, Saito Y. David, Chuanhong Liao, Jinlu Dai, Evan T. Keller, Hikmat Al-Ahmadie, Kelly Dakin-Haché, Peter Usatyuk, Margarit F. Sievert, Gladell P. Paner, Soheil Yala, Gustavo M. Cervantes, Viswanathan Natarajan, Ravi Salgia, Edwin M. Posadas
Journal: Clinical Cancer Research (2011)

Fyn is a member of the Src family of kinases that we have previously shown to be overexpressed in prostate cancer. This study defines the biological impact of Fyn inhibition in cancer using a PC3 prostate cancer model.Fyn expression was suppressed in PC3 cells using an shRNA against Fyn (PC3/FYN-). Knockdown cells were characterized using standard growth curves and time-lapse video microscopy of wound assays and Dunn Chamber assays. Tissue microarray analysis was used to verify the physiologic relevance of the HGF/MET axis in human samples. Flank injections of nude mice were performed to assess in vivo growth characteristics.HGF was found to be sufficient to drive Fyn-mediated events. Compared to control transductants (PC3/Ctrl), PC3/FYN- showed a 21% decrease in growth at 4 days (P = 0.05). PC3/FYN- cells were 34% longer than control cells (P = 0.018) with 50% increase in overall surface area (P < 0.001). Furthermore, when placed in a gradient of HGF, PC3/FYN- cells showed impaired directed chemotaxis down an HGF gradient in comparison to PC3/Ctrl (P = 0.001) despite a 41% increase in cellular movement speed. In vivo studies showed 66% difference of PC3/FYN- cell growth at 8 weeks using bidimensional measurements (P = 0.002).Fyn plays an important role in prostate cancer biology by facilitating cellular growth and by regulating directed chemotaxis-a key component of metastasis. This finding bears particular translational importance when studying the effect of Fyn inhibition in human subjects.
EBV-Related Lymphoproliferative Disease Complicating Therapy with the Anti-CD2 Monoclonal Antibody, Siplizumab, in Patients with T-Cell Malignancies
Authors: Deirdre O'Mahony, John C. Morris, Maryalice Stetler-Stevenson, Helen Matthews, Margaret R. Brown, Thomas Fleisher, Stefania Pittaluga, Mark Raffeld, Paul S. Albert, Dirk Reitsma, Karen Kaucic, Luz Hammershaimb, Thomas A. Waldmann, John E. Janik
Journal: Clinical Cancer Research (2009)

We report an increased incidence of EBV-induced B-cell lymphoproliferative disease (LPD) in patients treated with siplizumab, an anti-CD2 antibody. The development of EBV-LPD has been associated with the use of immunosuppressive agents used in solid organ, bone marrow, and stem cell transplantation and in certain congenital immunodeficiencies.We conducted a single-institution phase I dose-escalation trial of siplizumab, a humanized monoclonal antibody to CD2, in 29 patients with T-cell malignancies.Although initial responses were encouraging, 4 (13.7%) patients developed EBV-LPD and the trial was stopped. Reductions in CD4(+) and CD8(+) cell count numbers in response to therapy were seen in all patients, but in those patients developing EBV-LPD a significantly greater reduction in natural killer (NK) cell number and CD2 expression on T cells was seen. These findings highlight the importance of NK-cell depletion and CD2 expression in addition to T-cell depletion in the etiology of EBV-LPD.The emergence of EBV-LPD may be associated with the ability of siplizumab to deplete both T and NK cells without affecting B cells. Agents that deplete T- and NK-cell populations without affecting B cell number should be screened for this potentially serious adverse event.
Loss of Phosphatase and Tensin Homologue Increases Transforming Growth Factor β–Mediated Invasion with Enhanced SMAD3 Transcriptional Activity
Authors: Anita B. Hjelmeland, Mark D. Hjelmeland, Qing Shi, Janet L. Hart, Darell D. Bigner, Xiao-Fan Wang, Christopher D. Kontos, Jeremy N. Rich
Journal: Cancer Research (2005)

Abstract In normal epithelial tissues, the multifunctional cytokine transforming growth factor-β (TGF-β) acts as a tumor suppressor through growth inhibition and induction of differentiation whereas in advanced cancers, TGF-β promotes tumor progression through induction of tumor invasion, neoangiogenesis, and immunosuppression. The molecular mechanisms through which TGF-β shifts from a tumor suppressor to a tumor enhancer are poorly understood. We now show a role for the tumor suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN) in repressing the protumorigenic effects of TGF-β. The TGF-β effector SMAD3 inducibly interacts with PTEN on TGF-β treatment under endogenous conditions. RNA interference (RNAi) suppression of PTEN expression enhances SMAD3 transcriptional activity and TGF-β–mediated induction of SMAD3 target genes whereas reconstitution of PTEN in a null cancer cell line represses the expression of TGF-β–regulated target genes. Targeting PTEN expression through RNAi in a PTEN wild-type cell line increases TGF-β–mediated invasion but does not affect TGF-β–mediated growth inhibition. Reconstitution of PTEN expression in a PTEN-null cell line blocks TGF-β–induced invasion but does not modulate TGF-β–mediated growth regulation. These effects are distinct from Akt and Forkhead family members that also interact with SMAD3 to regulate apoptosis or proliferation, respectively. Pharmacologic inhibitors targeting TGF-β receptors and phosphatidylinositol 3-kinase signaling downstream from PTEN cooperate to block TGF-β–mediated invasion. Thus, the loss of PTEN expression in human cancers may contribute to a role for TGF-β as a tumor enhancer with specific effects on cellular motility and invasion. (Cancer Res 2005; 65(24): 11276-81)
Idiopathic pulmonary fibrosis fibroblasts migrate and proliferate to CC chemokine ligand 21
Authors: E. M. Pierce, K. Carpenter, C. Jakubzick, S. L. Kunkel, H. Evanoff, K. R. Flaherty, F. J. Martinez, G. B. Toews, C. M. Hogaboam
Journal: European Respiratory Journal (2007)

Idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP) is the severest form of idiopathic interstitial pneumonia for which therapeutic targets are needed. Surgical lung biopsy specimens from IPF/UIP patients exhibit focal expression of CC chemokine receptor (CCR) 7, but the identity of these CCR7-positive cells is unknown. The purpose of the present study was to examine the functional and signalling significance of CCR7 expression of primary fibroblasts grown from IPF/UIP and normal surgical lung biopsy specimens. Primary fibroblasts were cultured from surgical lung biopsy specimens from IPF/UIP and normal patients. Fibroblasts treated with or without CC chemokine ligand (CCL) 21 were analysed for functional, transcriptional and proteomic differences using immunocytochemical analysis, gene arrays, Taqman real-time PCR, and migration, proliferation and Western blot assays. CCR7 was expressed by IPF/UIP fibroblasts, but not normal fibroblasts. IPF/UIP fibroblasts, but not normal fibroblasts, showed significant migratory and proliferative responses when exposed to CCL21, which were inhibited by pertussis toxin or neutralising antibodies to CCR7. Exposure of IPF/UIP fibroblasts to CCL21 altered the phosphorylation status of mitogen-activated protein kinase kinase 1/2, extracellular signal-regulated kinase 1/2 and ribosomal S6 kinase (90 kDa) in these cells; this was abrogated by pertussis toxin or CCR7-specific small interfering RNA. Together, these data demonstrate that CC chemokine ligand 21 modulates the functional properties of idiopathic pulmonary fibrosis/usual interstitial pneumonia fibroblasts, but not normal fibroblasts.
The Calcimimetic Agent AMG 073 Lowers Plasma Parathyroid Hormone Levels in Hemodialysis Patients with Secondary Hyperparathyroidism
Authors: William G. Goodman, Gerald A. Hladik, Stewart A. Turner, Peter W. Blaisdell, David A. Goodkin, Wei Liu, Yousri M. Barri, Raphael M. Cohen, Jack W. Coburn
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Treatment with vitamin D sterols can lower plasma parathyroid hormone (PTH) in many patients with secondary hyperparathyroidism due to end-stage renal disease, but hypercalcemia, hyperphosphatemia, or both often develop during treatment. As such, alternative therapeutic approaches to managing excess PTH secretion are needed. Calcimimetic agents directly inhibit PTH secretion by activating the calcium-sensing receptor in the parathyroid glands, but clinical experience with them is limited. Fifty-two hemodialysis patients with secondary hyperparathyroidism were given single orally administered doses of the calcimimetic agent AMG 073 ranging from 5 to 100 mg, or placebo. Plasma PTH levels decreased 2 h after 25-, 50-, 75-, or 100-mg doses, falling by a maximum of 43 ± 29%, 40 ± 36%, 54 ± 28%, or 55 ± 39%, respectively. Plasma PTH levels decreased in all patients given doses of ≥25 mg but did not change in those who received placebo. In patients treated with daily doses of 25 or 50 mg of AMG 073 for 8 d, plasma PTH levels declined for the first 3 to 4 d and remained below baseline values after 8 d of treatment. Serum calcium concentrations also decreased by 5 to 10% from pretreatment levels in patients given 50 mg of AMG 073 for 8 d, but values were unchanged in those who received lower doses. Serum phosphorus levels and values for the calcium-phosphorus ion product both decreased after treatment with AMG 073. Thus, 8 d of treatment with AMG 073 effectively lowers plasma PTH levels and improves several disturbances in mineral metabolism that have been associated with soft tissue and vascular calcification and with adverse cardiovascular outcomes in patients with end-stage renal disease.