tbuckley/cabot-search huggingface dataset:
Bullous emphysema and severe COPD in acetylated opium users
Authors: Maria Sanzharovskaya, Ekaterina Budankova, Anna Fisenko, Evgeniy Kuzin, Elena Ustyuzhanina, Galina Chernyavskaya, Georgy Chernogoryuk
Journal: European Respiratory Journal (2013)

Background: Acetylated opium (opium extraction, chernyaga, hanka) - a means of hand-made, which contains up to 12% of heroin, which is widespread in Russia and other Eastern European countries, where there are wild poppies.  Aim: to describe cases of bullous emphysema and severe COPD in young drug addicts – acetylated opium users.  Methods: A total of 35 patients with history of intravenous abuse of acetylated opium hospitalized with exacerbation of severe COPD were included in the study.  The patients were from 21 to 39 years old. We analyzed clinical data, PFT data, chest radiographs, CT, alfa-1-antitripsin level.  Results: in the past 6 years in pulmonology department of Tomsk Clinical Regional Hospital there were 35 young drug addicts with severe COPD and bullous emphysema. Five of these patients died of progressive respiratory insufficiency and the others are clinically disabled. Severe bronchial obstruction was observed in all the subjects, mean FEV1 was 17.2±6.1%, mean FVC – 68.6±12.4%. On the CT scans panlobular bullous nonuniform emphysema was detected. Most of patients were Hepatitis C or C and B positive. All of them have had normal or even increased level of alfa-1-antitripsin.  Conclusion: In the literature the bullous emphysema in drug addicts was previously described in i.v. Ritalin users as well as in marihuana smokers. In case of acetylated opium users the lung damage may be due to high oxidation potential of the acetic anhydride used for the drug preparation.
Cervical assessment and preterm delivery
Authors: MichaelJ. Peek, Andrew Shennan, Joanna Girling, Christine Kurz, Norbert Vavra, Fitz Rudolf, Wolfgang Eppel, Paul Sevelda, A-R. Fuchs, F. Fuchs, Peter Husslein, JohnL. Bastien, W.R. Kiser
Journal: The Lancet (1994)
Significantly Higher Pathologic Complete Remission Rate After Neoadjuvant Therapy With Trastuzumab, Paclitaxel, and Epirubicin Chemotherapy: Results of a Randomized Trial in Human Epidermal Growth Factor Receptor 2–Positive Operable Breast Cancer
Authors: Aman U. Buzdar, Nuhad K. Ibrahim, Deborah Francis, Daniel J. Booser, Eva S. Thomas, Richard L. Theriault, Lajos Pusztai, Marjorie C. Green, Banu K. Arun, Sharon H. Giordano, Massimo Cristofanilli, Debra K. Frye, Terry L. Smith, Kelly K. Hunt, Sonja E. Singletary, Aysegul A. Sahin, Michael S. Ewer, Thomas A. Buchholz, Donald Berry, Gabriel N. Hortobagyi
Journal: Journal of Clinical Oncology (2005)

Purpose The objective of this study was to determine whether the addition of trastuzumab to chemotherapy in the neoadjuvant setting could increase pathologic complete response (pCR) rate in patients with human epidermal growth factor receptor 2 (HER2) –positive disease. Patients and Methods Forty-two patients with HER2-positive disease with operable breast cancer were randomly assigned to either four cycles of paclitaxel followed by four cycles of fluorouracil, epirubicin, and cyclophosphamide or to the same chemotherapy with simultaneous weekly trastuzumab for 24 weeks. The primary objective was to demonstrate a 20% improvement in pCR (assumed 21% to 41%) with the addition of trastuzumab to chemotherapy. The planned sample size was 164 patients. Results Prognostic factors were similar in the two groups. After 34 patients had completed therapy, the trial's Data Monitoring Committee stopped the trial because of superiority of trastuzumab plus chemotherapy. pCR rates were 25% and 66.7% for chemotherapy (n = 16) and trastuzumab plus chemotherapy (n = 18), respectively (P = .02). The decision was based on the calculation that, if study continued to 164 patients, there was a 95% probability that trastuzumab plus chemotherapy would be superior. Of the 42 randomized patients, 26% in the chemotherapy arm achieved pCR compared with 65.2% in the trastuzumab plus chemotherapy arm (P = .016). The safety of this approach is not established, although no clinical congestive heart failure was observed. A more than 10% decrease in the cardiac ejection fraction was observed in five and seven patients in the chemotherapy and trastuzumab plus chemotherapy arms, respectively. Conclusion Despite the small sample size, these data indicate that adding trastuzumab to chemotherapy, as used in this trial, significantly increased pCR without clinical congestive heart failure.
A Phase I Study of Intravenous LBH589, a Novel Cinnamic Hydroxamic Acid Analogue Histone Deacetylase Inhibitor, in Patients with Refractory Hematologic Malignancies
Authors: Francis Giles, Thomas Fischer, Jorge Cortes, Guillermo Garcia-Manero, Joachim Beck, Farhad Ravandi, Eric Masson, Patricia Rae, Glen Laird, Sunil Sharma, Hagop Kantarjian, Margaret Dugan, Maher Albitar, Kapil Bhalla
Journal: Clinical Cancer Research (2006)

Abstract Purpose: LBH589 is a novel histone deacetylase inhibitor that inhibits proliferation and induces apoptosis in tumor cell lines. In this phase I study, LBH589 was administered i.v. as a 30-minute infusion on days 1 to 7 of a 21-day cycle. Experimental Design: Fifteen patients (median age, 63 years; range, 42-87 years) with acute myeloid leukemia (13 patients), acute lymphocytic leukemia (1 patient), or myelodysplastic syndrome (1 patient) were treated with LBH589 at the following dose levels (mg/m2): 4.8 (3 patients), 7.2 (3 patients), 9.0 (1 patient), 11.5 (3 patient), and 14.0 (5 patients). The levels of histone acetylation were measured using quantitative flow cytometry and plasma LBH589 concentrations were assayed. Results: Four dose-limiting toxicities (grade 3 QTcF prolongation) were observed, four at 14.0 mg/m2 and one at 11.5 mg/m2. QTcF prolongation was asymptomatic and reversed on LBH589 discontinuation. Other potentially LBH589-related toxicities included nausea (40%), diarrhea (33%), vomiting (33%), hypokalemia (27%), loss of appetite (13%), and thrombocytopenia (13%). In 8 of 11 patients with peripheral blasts, transient reductions occurred with a rebound following the 7-day treatment period. H3 acetylation increase was significant in B-cells (CD19+; P = 0.02) and blasts (CD34+; P = 0.04). The increase in H2B acetylation was highest in CD19+ and CD34+ cells [3.8-fold (P = 0.01) and 4.4-fold (P = 0.03), respectively]. The median acetylation of histones H2B and H3 in CD34+ and CD19+ cells significantly increased on therapy as did apoptosis in CD14+ cells. Area under the curve increased proportionally with dose with a terminal half-life of ∼11 hours. Conclusion: Intravenous administration of LBH589 was well tolerated at doses &amp;lt;11.5 mg/m2 with consistent transient antileukemic and biological effects.
Blockade of Vascular Endothelial Growth Factor Suppresses Experimental Restenosis After Intraluminal Injury by Inhibiting Recruitment of Monocyte Lineage Cells
Authors: Kisho Ohtani, Kensuke Egashira, Ken-ichi Hiasa, Qingwei Zhao, Shiro Kitamoto, Minako Ishibashi, Makoto Usui, Shujiro Inoue, Yoshikazu Yonemitsu, Katsuo Sueishi, Masataka Sata, Masabumi Shibuya, Kenji Sunagawa
Journal: Circulation (2004)

Therapeutic angiogenesis by delivery of vascular endothelial growth factor (VEGF) has attracted attention. However, the role and function of VEGF in experimental restenosis (neointimal formation) after vascular intraluminal injury have not been addressed.We report herein that blockade of VEGF by soluble VEGF receptor 1 (sFlt-1) gene transfer attenuated neointimal formation after intraluminal injury in rabbits, rats, and mice. sFlt-1 gene transfer markedly attenuated the early vascular inflammation and proliferation and later neointimal formation. sFlt-1 gene transfer also inhibited increased expression of inflammatory factors such as monocyte chemoattractant protein-1 and VEGF. Intravascular VEGF gene transfer enhanced angiogenesis in the adventitia but did not reduce neointimal formation.Increased expression and activity of VEGF are essential in the development of experimental restenosis after intraluminal injury by recruiting monocyte-lineage cells.
Accelerated Telomere Shortening in Leukocyte Subpopulations of Patients With Coronary Heart Disease
Authors: Ioakim Spyridopoulos, Jedrzej Hoffmann, Alexandra Aicher, Tim H. Brümmendorf, Hans W. Doerr, Andreas M. Zeiher, Stefanie Dimmeler
Journal: Circulation (2009)

Background— Shortening of mean telomere length (TL) in white blood cells is correlated with the development of coronary heart disease (CHD) and with increased mortality due to infectious disease. The goal of the present study was to investigate whether telomere shortening in CHD is restricted to specific peripheral blood lymphocyte and/or myeloid cell subpopulations. Results were correlated to TL in CD34 + hematopoietic peripheral blood stem cells and progenitor cells obtained from the same individual patients. Methods and Results— TL was measured by multicolor flow cytometry–fluorescent in situ hybridization in 12 leukocyte subpopulations after immunomagnetic bead sorting. We investigated TL in 14 young (mean age 25 years) and 13 older (mean age 65 years) healthy male volunteers and in 25 age-matched patients with CHD (mean age 65 years). We show that TL in granulocytes and monocytes mirrors TL of CD34 + peripheral blood stem cells and progenitor cells extremely well ( r =0.95, P &lt;0.0001) in patients and in healthy adults. TL was ≈0.5 kilobases (kb) shorter in leukocytes from patients with CHD than in their age-matched control subjects. This difference was identical for CD34 + peripheral blood stem cells and progenitor cells, monocytes, granulocytes, B lymphocytes, and CD4 + T cells, including their memory and naïve subpopulations. Surprisingly, only in cytotoxic CD8 + T lymphocytes, we found a substantially increased TL deficit of 1.0 kb in CHD patients as opposed to control subjects. Further analysis revealed that TL shortening was particularly pronounced in CD8 + CD28 − T cells obtained from cytomegalovirus-seropositive CHD patients, whereas such a difference was not observed in healthy cytomegalovirus-positive as opposed to cytomegalovirus-negative control subjects. Finally, TL shortening of CD8 + CD45 RA+ T cells was correlated with the decrease in left ventricular function in CHD patients ( r =0.629, P =0.001). Conclusions— Telomere shortening in patients with CHD could potentially be attributed to either inherited TL shortening or acquired accelerated telomere shortening restricted to the hematopoietic system, which affects the baseline TL of all peripheral blood cell populations, including peripheral blood stem cells and progenitor cells. In addition, cytomegalovirus-seropositive patients but not healthy control subjects exhibited further shortening of their cytotoxic T lymphocytes. Surprisingly, TL shortening of CD8 + T lymphocytes in CHD patients demonstrated a very strong correlation with cardiac dysfunction, which suggests a mechanistic link between CHD and immunosenescence.
A novel system for the improvement of colonic cleansing during colonoscopy
Authors: J. Rigaux, I. Juriens, J. Devière
Journal: Endoscopy (2012)

Suboptimal bowel cleansing prior to colonoscopy impairs the efficacy and safety of the procedure. A new system for intracolonic cleansing has been developed, which includes a disposable catheter device that is inserted through the working channel of a standard colonoscope and an irrigation unit with predefined pressure and flow rate. The aim of the current study was to assess the safety and efficacy of this novel system for the improvement of bowel cleansing during colonoscopy. A total of 42 patients with suboptimal bowel preparation were systematically allocated, in a 1:1 ratio, to either the study group (JetPrep system, n = 21) or the control group (syringe irrigation, n = 21). The cleansing efficacy was evaluated using a segmental scoring scale to rate the bowel preparation level before and after irrigation. One patient from the study group was excluded from the efficacy analysis due to treatment with both techniques. The JetPrep system was significantly superior to syringe irrigation (P = 0.0001). No adverse events were reported. This study suggests that the safety profile of the JetPrep system is comparable to standard irrigation and shows that the device significantly improves suboptimal bowel preparation.
A multicentre phase I and pharmacokinetic study of BN80915 (diflomotecan) administered daily as a 20-min intravenous infusion for 5 days every 3 weeks to patients with advanced solid tumours
Authors: L. Scott, O. Soepenberg, J. Verweij, M.J.A. de Jonge, A.S. Th Planting, D. McGovern, P. Principe, R. Obach, C. Twelves
Journal: Annals of Oncology (2007)
c-Cbl–deficient mice have reduced adiposity, higher energy expenditure, and improved peripheral insulin action
Authors: Juan C. Molero, Thomas E. Jensen, Phil C. Withers, Michelle Couzens, Herbert Herzog, Christine B.F. Thien, Wallace Y. Langdon, Ken Walder, Maria A. Murphy, David D.L. Bowtell, David E. James, Gregory J. Cooney
Journal: Journal of Clinical Investigation (2004)

Casitas b-lineage lymphoma (c-Cbl) is an E3 ubiquitin ligase that has an important role in regulating the degradation of cell surface receptors. In the present study we have examined the role of c-Cbl in whole-body energy homeostasis. c-Cbl–/– mice exhibited a profound increase in whole-body energy expenditure as determined by increased core temperature and whole-body oxygen consumption. As a consequence, these mice displayed a decrease in adiposity, primarily due to a reduction in cell size despite an increase in food intake. These changes were accompanied by a significant increase in activity (2- to 3-fold). In addition, c-Cbl–/– mice displayed a marked improvement in whole-body insulin action, primarily due to changes in muscle metabolism. We observed increased protein levels of the insulin receptor (4-fold) and uncoupling protein-3 (2-fold) in skeletal muscle and a significant increase in the phosphorylation of AMP-activated protein kinase and acetyl-CoA carboxylase. These findings suggest that c-Cbl plays an integral role in whole-body fuel homeostasis by regulating whole-body energy expenditure and insulin action.
The diagnostic accuracy of the squeeze test to identify arthritis: a cross-sectional cohort study
Authors: W B van den Bosch, L Mangnus, M Reijnierse, T W J Huizinga, A H M van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objectives</h3> In daily practice, the squeeze test is used to screen for arthritis in metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joints. This cross-sectional cohort study determined the diagnostic accuracy of this test. <h3>Methods</h3> Patients referred with arthralgia of recent onset that had either a clinical suspicion for progression to arthritis or clinically apparent arthritis were studied. The main outcome was swelling at physical examination of ≥1 MCP or MTP joint. Joint inflammation detected at extremity MRI was the secondary outcome. <h3>Results</h3> Both at MCP and MTP joints, a positive squeeze test associated with swollen joints (p&lt;0.005). The sensitivity of the test at the MCP joints was 53%, specificity 82%, positive likelihood ratio (LR+) 3.0, negative likelihood ratio (LR−) 0.6 and area under the receiver operator characteristic curve (AUC) 0.68. At the MTP joints, the sensitivity was 54%, specificity 74%, LR+ 2.1, LR− 0.6 and AUC 0.64. With MRI-detected inflammation as outcome, the sensitivity and specificity were 39% and 86% and 31% and 69% for the test at the MCP and MTP joints, respectively. <h3>Conclusions</h3> A positive squeeze test is associated with local joint inflammation but the sensitivity is low, indicating a high percentage of swollen joints with a negative squeeze test. When the test is used on its own, it is insufficient to detect early arthritis.
Progression of coronary artery disease, vascular remodeling, and in-stent restenosis in humans as a function of endothelial shear stress: An In-Vivosix-month follow-up study
Authors: Peter H. Stone, Yerem Yeghiazarians, Ahmet U. Coskun, Scott Kinlay, Maureen E. Clark, Milan Sonka, Andreas Wahle, Olusegun J. Ilegbusi, Jeffrey J. Popma, John Orav, Richard E. Kuntz, Charles L. Feldman
Journal: Journal of the American College of Cardiology (2003)
Awareness and attitude of junior doctors towards BSG guidlines
Authors: I. Ahmed, A. Zaidee, C. Mitchell
Journal: Gut (2011)

<h3>Introduction</h3> Clinical guidelines are intended to improve quality of care and standardise the management of well-defined clinical situations. This also enables us to set standards against which clinical practice can be assessed. Clinical guidelines have proliferated but less effort is expended over their implementation. Junior doctors deal with a wide spectrum of clinical scenario and are exposed to these guidelines. Whether this is beneficial will depend upon knowledge of their existence, usage and perceived usefulness as quality assessment tools. This study assessed junior doctors9 awareness and compliance with the BSG guidelines for the management of ascites due to liver cirrhosis in a local NHS trust. <h3>Methods</h3> A survey was sent to 75 junior doctors (20 SpR and 55 SHO) during 2007–2008 who undertook therapeutic paracentesis for liver cirrhosis. This questionnaire assessed awareness and confidence in the BSG guidelines. To assess compliance objectively, case notes of patients admitted with ascites and underwent therapeutic paracentesis over the same period were studied. The documentation of the procedure was analysed against BSG guidelines. Information was also collected from hospital electronic resources for laboratory results. The parameters assessed were consent, technique, analysis of ascitic fluid, use of albumen, drain removal and diuretics use in accordance with BSG guidelines. <h3>Results</h3> Out of 75 doctors who were approached, 70 (93%) returned the questionnaire. All respondents perceived guidelines as effective educational tools and to improve quality of care. 88% have carried out the procedure in the last 2 years but only 55% were aware of the BSG guidelines. Out of these, only 68% claimed being compliant. Respondents had greater awareness and confidence in clinical guidelines endorsed by their hospital, but less in those by BSG. The most preferred methods for adoption were local availability, e-learning modules and education. From the case note study, a total of 50 procedures were recorded. Documentation of the procedure was available in 94% of cases. Compliance with BSG guidelines (&gt;80%) was achieved in only 40 % of the cases and 60% were only partially compliant. Analysis of ascitic fluid, use of albumen, and drain removal were poorly compliant areas. <h3>Conclusion</h3> This survey suggests that, although junior physicians felt that guidelines are valuable educational tools, awareness of their existence was poor as was compliance with the set standards. If clinical guidelines are to improve quality in clinical practice, they must be more effectively disseminated and implemented. To broaden junior physicians9 adoption of guidelines, clinical governance must be strengthened and supported by regular and fully resourced audit. Such actions must have the active support of NHS trusts.
Targeting of Transgene Expression to the Vascular Endothelium of Mice by Homologous Recombination at the Thrombomodulin Locus
Authors: Hartmut Weiler-Guettler, William C. Aird, Mansoor Husain, Helen Rayburn, Robert D. Rosenberg
Journal: Circulation Research (1996)

We describe a straightforward gene-targeting technique to achieve uniform, stable, and genetically invariant expression of a transgene in the vascular endothelium of mice. To demonstrate the feasibility of this approach, the reporter gene bacterial beta-galactosidase was inserted via homologous recombination into the intronless thrombomodulin locus of murine embryonic stem cells. In this fashion, the lacZ gene is placed under the regulatory control of the endogenous thrombomodulin promoter. The expression of the transgene in adult mice recapitulated the widespread, stable, and high-level expression of the thrombomodulin gene in vascular endothelium. These data indicate that targeting of cDNAs into the thrombomodulin locus serves as a viable strategy to express transgenes in endothelial cells. Analysis of reporter gene expression revealed a heterogeneous pattern of thrombomodulin gene activity in the endothelium of the aorta and its tributaries. We also show that embryonic stem cells with a targeted thrombomodulin locus contribute in a mosaic fashion to the vascular endothelium of chimeric mice. This method for generating animals with a functionally heterogeneous cardiovascular system should provide an experimental technique for studying how localized genetic abnormalities in endothelial cell function lead to the development of vascular diseases.
Insulin-like Growth Factor Receptor 1 (IGF1R) Gene Copy Number Is Associated With Survival in Operable Non–Small-Cell Lung Cancer: A Comparison Between IGF1R Fluorescent In Situ Hybridization, Protein Expression, and mRNA Expression
Authors: Rafal Dziadziuszko, Daniel T. Merrick, Samir E. Witta, Adelita D. Mendoza, Barbara Szostakiewicz, Amelia Szymanowska, Witold Rzyman, Katarzyna Dziadziuszko, Jacek Jassem, Paul A. Bunn, Marileila Varella-Garcia, Fred R. Hirsch
Journal: Journal of Clinical Oncology (2010)

Purpose The purpose of this study was to characterize insulin-like growth factor-1 receptor (IGF1R) protein expression, mRNA expression, and gene copy number in surgically resected non–small-cell lung cancers (NSCLC) in relation to epidermal growth factor receptor (EGFR) protein expression, patient characteristics, and prognosis. Patients and Methods One hundred eighty-nine patients with NSCLC who underwent curative pulmonary resection were studied (median follow-up, 5.3 years). IGF1R protein expression was evaluated by immunohistochemistry (IHC) with two anti-IGF1R antibodies (n = 179). EGFR protein expression was assessed with PharmDx kit. IGF1R gene expression was evaluated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) from 114 corresponding fresh-frozen samples. IGF1R gene copy number was assessed by fluorescent in situ hybridization using customized probes (n = 181). Results IGF1R IHC score was higher in squamous cell carcinomas versus other histologies (P &lt; .001) and associated with stage (P = .03) but not survival (P = .46). IGF1R and EGFR protein expression showed significant correlation (r = 0.30; P &lt; .001). IGF1R gene expression by qRT-PCR was higher in squamous cell versus other histologies (P = .006) and did not associate with other clinical features nor survival (P = .73). Employing criteria previously established for EGFR copy number, patients with IGF1R amplification/high polysomy (n = 48; 27%) had 3-year survival of 58%, patients with low polysomy (n = 87; 48%) had 3-year survival of 47% and patients with trisomy/disomy (n = 46; 25%) had 3-year survival of 35%, respectively (P = .024). Prognostic value of high IGF1R gene copy number was confirmed in multivariate analysis. Conclusion IGF1R protein expression is higher in squamous cell versus other histologies and correlates with EGFR expression. IGF1R protein and gene expression does not associate with survival, whereas high IGF1R gene copy number harbors positive prognostic value.