tbuckley/cabot-search huggingface dataset:
Acute Profound Thrombocytopenia After c7E3 Fab (Abciximab) Therapy
Authors: Scott D. Berkowitz, Robert A. Harrington, Michele M. Rund, James E. Tcheng
Journal: Circulation (1997)

Background Platelets play a crucial role in the ischemic complications of percutaneous coronary procedures. The recent availability of c7E3 Fab (abciximab; ReoPro), a chimeric monoclonal antibody Fab fragment directed against the platelet glycoprotein IIb/IIIa receptor, has reduced abrupt closure and other adverse clinical events and lessened the need for revascularization procedures. As experience accrues, rare cases of acute profound thrombocytopenia have been revealed. Methods and Results From November 1991 to July 1996, patients at Duke University Medical Center who underwent percutaneous coronary revascularization and received their first exposure to c7E3 Fab were evaluated for the development of acute profound thrombocytopenia, defined as a platelet count &lt;20×10 9 /L occurring within 24 hours of initial treatment. Four patients (0.5%) developed acute profound thrombocytopenia within 11 to 21 hours of receiving the c7E3 Fab bolus. Nadir platelet counts ranged from 1 to 16×10 9 /L and occurred within 11 to 26 hours. No patient developed a significant hemorrhagic complication, and each patient's platelet count responded to platelet transfusion. Platelet counts remained depressed for at least 3 days but returned to baseline within 2 weeks. Conclusions Acute profound thrombocytopenia can occur after c7E3 Fab administration. Its development was not predictable, and it requires consideration in every patient treated. A platelet count 2 to 4 hours after the bolus would likely have detected these four cases. When indicated, platelet transfusion will raise the platelet count to safer levels without adverse effects. The differential diagnosis (including heparin-induced thrombocytopenia), a plan for management, and postulates as to the mechanism are discussed.
Pleurectomy for chylothorax associated with intestinal lymphangiectasia.
Authors: D S Barrett, S R Large, G M Rees
Journal: Thorax (1987)

a rarecondition characterised bydilated lymphatics inthesmall boweland associated with aprotein losing enteropathy. Bilateral pleurectomy inaddition tothoracic ductligation wasrequired to control this problem satisfactorily. Wehavebeenunable to find aprevious report ofpleurectomy performed tocontrol chylothorax. Acaseismadeforearly surgical intervention in this rarecondition. Casereport A 39yearoldwomanpresented inMarch1984complaining ofasixmonthhistory ofweight loss, weakness, andabdominal distension. Onexamination sheappeared anaemic and hadasymmetrical lymphoedema ofthelower limbs with abdominal proptosis. Fouryears previously chylous ascites hadbeennoted at hysterectomy forfibroids. After removal ofvaricose veins a lymphocele haddeveloped intheleft groin. Lymphangiography oftheleft leg atthat time showed apaucity of lymphatics. Intestinal lymphangiectasia wassuggested after abarium mealandconfirmed bysmall bowel biopsy. Overtheyearafter presentation achylous effusion developed, first ontheleft andthen ontheright side also. Control ofthesubsequent shortness ofbreath required frequent bilateral thoracocenteses. Overthis period about 19litres of chyle wereremoved. Despite afatfree, highprotein, high carbohydrate diet, thechylothorax wasnotcontrolled and theserumprotein concentration fell to45g/l. Inview ofherfailure torespond toconservative treatment over12months left thoractomy wasundertaken. Atoperation lymph wasnoted tobeoozing frommultiple pinpoints onanabnormally thickened pleura. Anapparently normal thoracic ductwasidentified. Pleurectomy wastherefore undertaken. Threelitres ofchyle drained fromtheintercostal drains during thefirst fourpostoperative daysbut nonesubsequently. After removal ofthechest drains there wasnorecurrence ofthechylous effusion ontheleft. Persistence oftheright chylothorax ledtoright thoracotomy onemonth later. Atoperation theright pleura was similar inmacroscopic appearance totheleft, butthe changes wereless noticeable. Thusinaddition toright pleurectomy thethoracic ductwasligated. Postoperative recoverywasuneventful after minimal lymphdrainage fromthe
Immortalization of Primary Endothelial Cells by the K1 Protein of Kaposi's Sarcoma–Associated Herpesvirus
Authors: Ling Wang, Dirk P. Dittmer, Christine C. Tomlinson, Farnaz D. Fakhari, Blossom Damania
Journal: Cancer Research (2006)

Abstract Kaposi's sarcoma–associated herpesvirus (KSHV) is linked to three different human cancers: Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. The Kaposi's sarcoma lesion expresses high levels of angiogenic factors and is comprised of a mixed cell population, including endothelial cells that are infected with KSHV. We find that the KSHV K1 protein is expressed in Kaposi's sarcoma lesions and can immortalize and extend the life span of primary human umbilical vein endothelial cells in culture. Vascular endothelial growth factor (VEGF) is critical for the survival of endothelial cells, and we show that expression of K1 in endothelial cells resulted in increased levels of secreted VEGF and the activation of key signaling pathways, including the VEGF/VEGF receptor and the phosphatidylinositol-3′-OH-kinase (PI3K) pathway. The SH2 binding motifs present in the cytoplasmic tail of K1 were critical for K1's ability to activate these pathways. Activation of PI3K by K1 results in activation of Akt kinase and mammalian target of rapamycin and inactivation of the proapoptotic proteins FKHR, glycogen synthase kinase-3, and Bad, which are events indicative of cell survival. Because activation of the PI3K pathway is critical for transformation of many human cells, we suggest that PI3K activation by K1 is involved in endothelial cell immortalization and contributes to KSHV-associated tumorigenesis. We also report that K1 enhances angiogenesis in vivo and increases tumor vasculature and tumor size. (Cancer Res 2006; 66(7): 3658-66)
A Robust ANOVA Approach to Estimating a Phylogeny from Multiple Genes
Authors: Ximing Xu, Katherine A. Dunn, Chris Field
Journal: Molecular Biology and Evolution (2015)

In this article, we address the issue of estimating the phylogenetic tree based on sequence data across a set of genes. Recognizing that the individual gene trees may not all share the same evolutionary history due to lateral gene transfer or differences in rates of evolution for instance, we develop a robust algorithm for tree estimation based on pairwise distances computed gene by gene. A robust analysis of variance (ANOVA) is used to combine the distances across all genes giving a summary distance for all genes. The tree can then be constructed using any distance method such as BIONJ. Using the weights from the robust ANOVA, we can then identify the outlying genes and taxa for further examination. As the method is based on distances, computation is much faster than maximum likelihood on the concatenated genes. It is also very straightforward to carry out a bootstrap analysis using standard methods for regression models. We test our methods in a comprehensive simulation study and apply them to three data sets recently analyzed in the literature.
Effects of Metergoline on Symptoms in Women With Premenstrual Dysphoric Disorder
Authors: Catherine A. Roca, Peter J. Schmidt, Mark J. Smith, Merry A. Danaceau, Dennis L. Murphy, David R. Rubinow
Journal: American Journal of Psychiatry (2002)

The authors investigated the role of acute serotonergic modulation in the efficacy of selective serotonin reuptake inhibitors (SSRIs) in women with premenstrual dysphoric disorder.Patients with premenstrual dysphoric disorder (whose symptoms had remitted during treatment with fluoxetine) and a group of unmedicated healthy comparison women received the serotonin receptor antagonist metergoline as part of a double-blind, placebo-controlled crossover study.The patients with premenstrual dysphoric disorder experienced a return of symptoms 24 hours after treatment with metergoline but not diphenhydramine (active placebo). The comparison women experienced no changes in mood.These data support the role of altered serotonergic transmission in the efficacy of SSRI treatment for premenstrual dysphoric disorder.
Parental education and guided self-management of asthma and wheezing in the pre-school child: a randomised controlled trial
Authors: C A Stevens
Journal: Thorax (2002)

Background: The effects on morbidity were examined of providing an educational intervention and a written guided self-management plan to the parents of pre-school children following a recent attendance at hospital for asthma or wheeze. Methods: A prospective, randomised, partially blinded, controlled trial was designed at two secondary care centres. Over a 13 month period 200 children aged 18 months to 5 years at the time of admission to a children9s ward or attendance at an accident and emergency department or children9s (emergency) assessment unit (A&amp;E/CAU) with a primary diagnosis of acute severe asthma or wheezing were recruited. 101 children were randomised into the control group and received usual care and 99 were assigned to the intervention group and received: (1) a pre-school asthma booklet; (2) a written guided self-management plan; and (3) two 20 minute structured educational sessions between a specialist respiratory nurse and the parent(s) and child. Subjects were assessed at 3, 6, and 12 months. The main outcomes were GP consultation rates, hospital re-admissions, and attendances at A&amp;E/CAU. Secondary outcomes included disability score, caregivers9 quality of life, and parental knowledge of asthma. Results: There were no statistically significant differences between the two groups during the 12 month follow up period for any of the main or secondary outcome measures. Conclusions: These results do not support the hypothesis that the introduction of an educational package and a written guided self-management plan to the parents of pre-school children with asthma who had recently attended hospital for troublesome asthma or wheeze reduces morbidity over the subsequent 12 months.
Risk of Bleeding With Dabigatran in Atrial Fibrillation
Authors: Inmaculada Hernandez, Seo Hyon Baik, Antonio Piñera, Yuting Zhang
Journal: JAMA Internal Medicine (2014)

It remains unclear whether dabigatran etexilate mesylate is associated with higher risk of bleeding than warfarin sodium in real-world clinical practice.To compare the risk of bleeding associated with dabigatran and warfarin using Medicare data.In this retrospective cohort study, we used pharmacy and medical claims in 2010 to 2011 from a 5% random sample of Medicare beneficiaries. We identified participants as those newly diagnosed as having atrial fibrillation from October 1, 2010, through October 31, 2011, and who initiated dabigatran or warfarin treatment within 60 days of initial diagnosis. We followed up patients until discontinued use or switch of anticoagulants, death, or December 31, 2011.Dabigatran users (n = 1302) and warfarin users (n = 8102).We identified any bleeding events and categorized them as major and minor bleeding by anatomical site. Major bleeding events included intracranial hemorrhage, hemoperitoneum, and inpatient or emergency department stays for hematuria, gastrointestinal, or other hemorrhage. We used a propensity score weighting mechanism to balance patient characteristics between 2 groups and Cox proportional hazards regression models to evaluate the risk of bleeding. We further examined the risk of bleeding for 4 subgroups of high-risk patients: those 75 years or older, African Americans, those with chronic kidney disease, and those with more than 7 concomitant comorbidities.Dabigatran was associated with a higher risk of bleeding relative to warfarin, with hazard ratios of 1.30 (95% CI, 1.20-1.41) for any bleeding event, 1.58 (95% CI, 1.36-1.83) for major bleeding, and 1.85 (95% CI, 1.64-2.07) for gastrointestinal bleeding. The risk of intracranial hemorrhage was higher among warfarin users, with a hazard ratio of 0.32 (95% CI, 0.20-0.50) for dabigatran compared with warfarin. Dabigatran was consistently associated with an increased risk of major bleeding and gastrointestinal hemorrhage for all subgroups analyzed. The risk of major bleeding among dabigatran users was especially high for African Americans and patients with chronic kidney disease.Dabigatran was associated with a higher incidence of major bleeding (regardless of the anatomical site), a higher risk of gastrointestinal bleeding, but a lower risk of intracranial hemorrhage. Thus, dabigatran should be prescribed with caution, especially among high-risk patients.
MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis
Authors: Jeffrey B Kopp, Michael W Smith, George W Nelson, Randall C Johnson, Barry I Freedman, Donald W Bowden, Taras Oleksyk, Louise M McKenzie, Hiroshi Kajiyama, Tejinder S Ahuja, Jeffrey S Berns, William Briggs, Monique E Cho, Richard A Dart, Paul L Kimmel, Stephen M Korbet, Donna M Michel, Michele H Mokrzycki, Jeffrey R Schelling, Eric Simon, Howard Trachtman, David Vlahov, Cheryl A Winkler
Journal: Nature Genetics (2008)
Club cells and CC16: another “smoking gun”? (With potential bullets against COPD)
Authors: Lucie Knabe, Aurélie Fort, Pascal Chanez, Arnaud Bourdin
Journal: European Respiratory Journal (2015)

Chronic obstructive pulmonary disease (COPD) remains a challenge for clinicians and scientists, as no currently available treatment can significantly change the natural history of the disease. Accelerated lung function decline and recurrent episodes of exacerbations are thought to play critical roles in precipitating patients towards comorbid conditions, long-term oxygen supplementation dependency, and finally death. Currently, the underlying paradigm counterbalances alveolar wall destruction with peribronchiolar fibrosis, the latter being hypothesised to precede the former [1]. Although small airways are now largely recognised as the critical zone of disease initiation and progression [2], very few histological and biological properties specific to this compartment in humans have been highlighted to explain this phenomenon. Greater susceptibility of knockout CC16 mice to cigarette smoking gives insight regarding a potential player in COPD <http://ow.ly/KhCMa>
Immunogenicity, safety, and tolerability of a recombinant measles-virus-based chikungunya vaccine: a randomised, double-blind, placebo-controlled, active-comparator, first-in-man trial
Authors: Katrin Ramsauer, Michael Schwameis, Christa Firbas, Matthias Müllner, Robert J Putnak, Stephen J Thomas, Philippe Desprès, Erich Tauber, Bernd Jilma, Frederic Tangy
Journal: The Lancet Infectious Diseases (2015)
Left ventricular systolic and diastolic dysfunction after infusion of tumor necrosis factor-alpha in conscious dogs.
Authors: F D Pagani, L S Baker, C Hsi, M Knox, M P Fink, M S Visner
Journal: Journal of Clinical Investigation (1992)

We used a load-insensitive index of systolic left ventricular (LV) function and an analysis of diastolic pressure-dimension relationships to test the hypothesis that recombinant human (rh) tumor necrosis factor-alpha (TNF alpha) impairs LV function in dogs. Animals were studied 7-10 d after aseptic implantation of instrumentation to monitor cardiac output, external anterior-posterior LV diameter, and LV and pleural pressures. Data were analyzed from seven dogs that received active rhTNF alpha (100 micrograms/kg over 60 min) and from five dogs that received heat-inactivated rhTNF alpha. At 24 h after infusion of active rhTNF alpha, the slope of the LV end-diastolic dimension-stroke work relationship decreased significantly, indicating a decrement in LV systolic contractility. Simultaneously, LV unstressed dimension increased significantly, suggesting diastolic myocardial creep. The end-diastolic relationship between LV transmural pressure and normalized LV dimension (strain) was markedly displaced to the left, suggesting increased diastolic elastic stiffness. Despite these changes in LV performance, cardiac index was maintained by tachycardia. The abnormalities in LV function were resolved by 72 h. We conclude that rhTNF alpha reversibly impairs LV systolic and diastolic function in unanesthetized dogs. Because dysfunction occurs greater than 6 h after the infusion of rhTNF alpha and persists for 24-48 h, the mechanism underlying this phenomenon may involve secondary mediators or a change in myocardial gene expression.
Does home based medication review keep older people out of hospital? The HOMER randomised controlled trial
Authors: Richard Holland, Elizabeth Lenaghan, Ian Harvey, Richard Smith, Lee Shepstone, Alistair Lipp, Maria Christou, David Evans, Christopher Hand
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To determine whether home based medication review by pharmacists affects hospital readmission rates among older people. <b>Design</b> Randomised controlled trial. <b>Setting</b> Home based medication review after discharge from acute or community hospitals in Norfolk and Suffolk. <b>Participants</b> 872 patients aged over 80 recruited during an emergency admission (any cause) if returning to own home or warden controlled accommodation and taking two or more drugs daily on discharge. <b>Intervention</b> Two home visits by a pharmacist within two weeks and eight weeks of discharge to educate patients and carers about their drugs, remove out of date drugs, inform general practitioners of drug reactions or interactions, and inform the local pharmacist if a compliance aid is needed. Control arm received usual care. <b>Main outcome measure</b> Total emergency readmissions to hospital at six months. Secondary outcomes included death and quality of life measured with the EQ-5D. <b>Results</b> By six months 178 readmissions had occurred in the control group and 234 in the intervention group (rate ratio = 1.30, 95% confidence interval 1.07 to 1.58; P = 0.009, Poisson model). 49 deaths occurred in the intervention group compared with 63 in the control group (hazard ratio = 0.75, 0.52 to 1.10; P = 0.14). EQ-5D scores decreased (worsened) by a mean of 0.14 in the control group and 0.13 in the intervention group (difference = 0.01, -0.05 to 0.06; P = 0.84, <i>t</i> test). <b>Conclusions</b> The intervention was associated with a significantly higher rate of hospital admissions and did not significantly improve quality of life or reduce deaths. Further research is needed to explain this counterintuitive finding and to identify more effective methods of medication review.
Inhibition of Vascular Smooth Muscle Cell Growth Through Antisense Transcription of a Rat Insulin-Like Growth Factor I Receptor cDNA
Authors: Jie Du, Patrick Delafontaine
Journal: Circulation Research (1995)

Insulin-like growth factor I (IGF I) is an autocrine/paracrine growth factor that is produced in multiple tissues and is essential for normal developmental growth. Its effects are mediated by activation of a membrane-bound tyrosine kinase receptor, IGF IR. On the basis of the partial rat IGF IR alpha-chain cDNA sequence previously reported, we cloned cDNA encoding the full-length rat IGF IR. The deduced amino acid sequence predicts a 1370-amino acid receptor precursor, which includes signal sequence, a 707-amino acid alpha-chain, a 4-Arg cleavage site, and a 629-amino acid beta-chain. Overall, similarity to human IGF IR is 89% and 98% at the nucleotide and amino acid levels, respectively. Antisense IGF IR expression constructs in vectors incorporating Epstein-Barr virus replicative signals and the cytomegalovirus promoter/enhancer or the inducible human metallothionein IIa promoter/enhancer were assembled and stably transfected into cultured rat aortic smooth muscle cells. Clone CA9 (constitutively expressing abundant antisense IGF IR transcripts), clones MA5 and MA7 (expressing antisense IGF IR transcripts inducibly), and clones ME8 and ME10 (expressing vector alone) were characterized. There was a 57% reduction in IGF IR mRNA levels in clone CA9 after confluence compared with clone ME10. This resulted in a 51% decrease in IGF I binding sites in clone CA9, without a change in binding affinity (Kd), and a 55% and 57% reduction in DNA synthesis rates, basally and in response to 10 ng/mL IGF I, respectively. Clones MA5/MA7 similarly showed a 54% reduction in IGF IR number after confluence following exposure to 100 mumol/L ZnSO4 and a 44% and 58% reduction in DNA synthesis, basally and in response to 10 ng/mL IGF I, respectively. Growth curves indicated that proliferation of clone CA9 in the presence of 10% serum was reduced by 60% compared with clone ME10. Thus, cloning of cDNA encoding the full-length rat IGF IR indicates that this receptor is highly conserved. Antisense targeting of this receptor in vascular smooth muscle cells (VSMCs) demonstrates that a decrease in IGF IR density results in marked inhibition of VSMC proliferation. These findings indicate an important role for this ligand-receptor system in regulating VSMC growth. Specifically, they suggest that modulation of VSMC IGF IR density may be an important mechanism whereby growth of these cells is controlled.
The Prognostic Impact of CD163-Positive Macrophages in Follicular Lymphoma: A Study from the BC Cancer Agency and the Lymphoma Study Association
Authors: Robert Kridel, Luc Xerri, Bénédicte Gelas-Dore, King Tan, Pierre Feugier, Ayesha Vawda, Danielle Canioni, Pedro Farinha, Sami Boussetta, Alden A. Moccia, Pauline Brice, Elizabeth A. Chavez, Alastair H. Kyle, David W. Scott, Ashley D. Sanders, Bettina Fabiani, Graham W. Slack, Andrew I. Minchinton, Corinne Haioun, Joseph M. Connors, Laurie H. Sehn, Christian Steidl, Randy D. Gascoyne, Gilles Salles
Journal: Clinical Cancer Research (2015)

We aimed to assess the prognostic significance of follicular lymphoma-associated macrophages in the era of rituximab treatment and maintenance.We applied immunohistochemistry for CD68 and CD163 to two large tissue microarrays (TMA). The first TMA included samples from 186 patients from the BC Cancer Agency (BCCA) who had been treated with first-line systemic treatment including rituximab, cyclophosphamide, vincristine, and prednisone. The second contained 395 samples from PRIMA trial patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, and randomized to rituximab maintenance or observation. Macrophage infiltration was assessed using Aperio image analysis. Each of the two cohorts was randomly split into training/validation sets.An increased CD163-positive pixel count was predictive of adverse outcome in the BCCA dataset [5-year progression-free survival (PFS) 38% vs. 72%, respectively, P = 0.004 in the training cohort and 5-year PFS 29% vs. 61%, respectively, P = 0.004 in the validation cohort]. In the PRIMA trial, an increased CD163 pixel count was associated with favorable outcome (5-year PFS 60% vs. 44%, respectively, P = 0.011 in the training cohort and 5-year PFS 55% vs. 37%, respectively, P = 0.030 in the validation cohort).CD163-positive macrophages predict outcome in follicular lymphoma, but their prognostic impact is highly dependent on treatment received.