tbuckley/cabot-search huggingface dataset:
Fibrinolytic Variables and Cardiovascular Prognosisin Patients With Stable Angina Pectoris Treated With Verapamil or Metoprolol
Authors: Claes Held, Paul Hjemdahl, Nina Rehnqvist, N. Håkan Wallén, Inge Björkander, Sven V. Eriksson, Lennart Forslund, Björn Wiman
Journal: Circulation (1997)

Background Disturbed fibrinolytic function may influence the progression of coronary atherosclerosis and contribute to thrombotic cardiovascular (CV) events. Methods and Results In the Angina Prognosis Study In Stockholm (APSIS), patients with stable angina pectoris were studied prospectively during double-blind treatment with metoprolol or verapamil. Various measures of fibrinolytic function were studied in 631 (of 809) patients. During a median follow-up time of 3.2 years (2132 patient-years), 32 patients suffered a CV death, 21 had a nonfatal myocardial infarction (MI), and 77 underwent revascularization. Plasma levels of tissue plasminogen activator (TPA) activity and antigen (ag), plasminogen activator inhibitor (PAI-1) activity at rest, and TPA responses to exercise were determined at baseline and after 1 month's treatment and were related to subsequent fatal and nonfatal CV events. Univariate Cox regression analysis revealed that elevated levels of TPA-ag at rest ( P &lt;.05), high PAI-1 activity ( P &lt;.05), and low TPA-ag responses to exercise ( P &lt;.05) were associated with increased risk of subsequent CV death. After adjustment for baseline risk factors, TPA-ag independently predicted CV death or MI. In addition, PAI-1 activity independently predicted CV death or MI in male patients. Verapamil treatment was associated with a 10% decrease of TPA-ag levels and metoprolol treatment with a 2% increase ( P &lt;.001 for treatment difference). Conclusions Plasma TPA-ag levels at rest, and among male patients PAI-1 activity as well, independently predict subsequent CV death or MI in patients with stable angina pectoris. Impaired fibrinolytic reactivity to exercise is a novel factor related to CV prognosis. Effects of verapamil or metoprolol treatment on fibrinolytic function did not importantly influence CV prognosis.
Combined use of transoesophageal and transbronchial ultrasonography may lead to fewer unnecessary thoracotomies while staging NSCLC
Authors: S. Bose
Journal: Thorax (2011)

This study investigated the use of endosonography versus surgical staging in non-small cell lung cancer. Patients in the endosonography arm underwent transbronchial and transoesophageal ultrasonography to detect mediastinal involvement followed by surgical staging if no nodal involvement was found.

Two hundred and forty-one patients were …
New protease inhibitors and direct-acting antivirals for hepatitis C: interferon's long goodbye: Table 1
Authors: Geoffrey Dusheiko, Heiner Wedemeyer
Journal: Gut (2012)

The first-generation protease inhibitors (PIs) of hepatitis C virus (HCV), telaprevir and boceprevir, are the harbingers of important advances in the treatment of chronic HCV infection. Improved response rates have been observed in both previously untreated and previously treated patients who have failed pegylated interferon (PEG-IFN) and ribavirin (RBV) treatment.1–5 Sustained virological response (SVR) rates of >70% have been reported. Despite the side effects of the agents and their continued necessity for a PEG-IFN and RBV backbone, the high rates of early viral response translate into higher rates of cure than with PEG-IFN and RBV alone in genotype 1 infection. Their efficacy in the treatment of genotype 2–6 has not been fully tested.6 Activity in in vitro cell culture systems showed similar efficacy of PIs against genotypes 2a, 5a and 6a and comparatively low but varying efficacy against genotype 3a isolates.7 Replication-competent intergenotype chimaeras inserted into the JFH clone of HCV have shown susceptibility to telaprevir, with genotypes 1 and 2 being most susceptible and genotypes 4 and 5 most resistant.8

Previously untreated (naive) patients without severe fibrosis respond better to the first-generation PIs than those with advanced fibrosis or cirrhosis. Although response rates in patients with cirrhosis are improved compared with PEG-IFN and RBV treatment, they remain suboptimal. Patients with a prior null response (defined as a decline in HCV RNA of <2 log10 after 12 weeks of treatment) and cirrhosis are less likely to respond to retreatment with telaprevir or boceprevir.9 ,10 Approximately 15% of prior null responders and cirrhosis respond to first-generation PIs, and only 35% of those with a prior partial response and cirrhosis respond to retreatment. Inherited IL28b haplotypes continue to influence response rates.11 ,12 Response rates are slightly lower in subtype 1a compared with subtype 1b.

These …
Erythropoietin therapy in humans increases erythrocyte expression of complement receptor type 1 (CD35).
Authors: L A Hebert, D J Birmingham, J J Dillon, F G Cosio, X P Shen
Journal: Journal of the American Society of Nephrology (1994)

The expression of complement receptor Type 1 (CR1, CD35) on erythrocytes (E) is unique to humans and other primates. E-CR1, a C3b/C4b receptor that also acts as cofactor for Factor I, appears to be important in clearing C3/C4-opsonized immune complexes from the circulation, in controlling complement activation in the circulation, and in regulating antibody formation. This study was undertaken to determine whether therapy with recombinant human erythropoietin (rEPO) might increase E-CR1 expression in humans. The rationale is that young erythrocytes express more E-CR1 than old erythrocytes. Thus, conditions that stimulate erythropoiesis should increase E-CR1 expression. The hypothesis that stimulating erythropoiesis by rEPO therapy can increase E-CR1 expression was tested in six anemic chronic hemodialysis (ESRD) patients and five systemic lupus erythematosus (SLE) patients without renal failure. Before the rEPO therapy, three of the SLE patients were anemic and two were not. The ESRD patients were studied before and during 9 or 10 mo of rEPO therapy. The SLE patients were studied before, during, and after 7 mo of rEPO given by sc injection two or three times weekly. It was found that rEPO therapy was associated with a progressive increase in the average number of CR1/E in each of the ESRD patients and in the anemic SLE patients: mean baseline CR1/E was 210 +/- 50 (SE) for the ESRD patients and 125 +/- 35 for the SLE patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Inhibition of cardiac vagal effects by neurally released and exogenous neuropeptide Y.
Authors: M R Warner, M N Levy
Journal: Circulation Research (1989)

Neuropeptide Y (NPY) attenuates vagal effects on cardiac cycle length, presumably by inhibiting the release of acetylcholine from vagal nerve endings. We sought to determine if NPY inhibited the vagal effects on atrioventricular (AV) interval and atrial contraction in a manner similar to its inhibition of the vagal effects on cycle length. In 19 anesthetized dogs we measured the vagal effects on cycle length, AV interval, and atrial contraction before and after 3-minute trains of sympathetic stimulation or before and after exogenous NPY (20 micrograms/kg i.v.). Three minutes after 10-Hz sympathetic stimulation, the vagal effects on cycle length and AV interval were attenuated by 52 +/- 9% and 63 +/- 8%, respectively. Phentolamine significantly augmented this attenuation, but propranolol had no appreciable effect. In the control group of animals or in the group that received phentolamine, the vagal effects on atrial contraction measured before and after sympathetic stimulation were not significantly different. In these two groups, however, the basal atrial contraction was reduced substantially after the cessation of sympathetic stimulation. Propranolol prevented this reduction in atrial contraction. After propranolol, the vagal effects on atrial contraction 3 minutes after sympathetic stimulation were attenuated by 31 +/- 6%. Exogenous NPY had no direct effect on cycle length, AV interval, or atrial contraction, but exogenous NPY did persistently inhibit the vagal effects on each of these cardiac processes. Three minutes after NPY was given, the vagal effects on cycle length, AV interval, and atrial contraction were inhibited by 62 +/- 7%, 69 +/- 5%, and 68 +/- 5%, respectively. We conclude that NPY attenuates the vagal effects on the atrial myocardium and on the sinus and AV nodes. In the absence of beta-blockade, the inhibitory effect of neurally released NPY on the vagally induced decreases in atrial contraction may be masked by the reduction in the atrial contraction that occurs after sympathetic stimulation.
Position Paper for the Organization of Extracorporeal Membrane Oxygenation Programs for Acute Respiratory Failure in Adult Patients
Authors: Alain Combes, Daniel Brodie, Robert Bartlett, Laurent Brochard, Roy Brower, Steve Conrad, Daniel De Backer, Eddy Fan, Niall Ferguson, James Fortenberry, John Fraser, Luciano Gattinoni, William Lynch, Graeme MacLaren, Alain Mercat, Thomas Mueller, Mark Ogino, Giles Peek, Vince Pellegrino, Antonio Pesenti, Marco Ranieri, Arthur Slutsky, Alain Vuylsteke
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Section:ChooseTop of pageAbstract <<Purpose of this Position ...DefinitionsNationwide/Regional Organ...Mobile ECMO TeamIntrahospital Transport o...General Structure of an E...StaffingPhysical Facilities and E...Non-ICU Support ServicesStaff Training and Contin...Program Evaluation and Qu...Patient Follow-upResearchConclusionsReferencesCITING ARTICLES
Aligned Chitosan‐Polycaprolactone Polyblend Nanofibers Promote the Migration of Glioblastoma Cells
Authors: Forrest M. Kievit, Ashleigh Cooper, Soumen Jana, Matthew C. Leung, Kui Wang, Dennis Edmondson, David Wood, Jerry S. H. Lee, Richard G. Ellenbogen, Miqin Zhang
Journal: Advanced Healthcare Materials (2013)

Abstract In vitro models that accurately mimic the microenvironment of invading glioblastoma multiform (GBM) cells will provide a high‐throughput system for testing potential anti‐invasion therapies. Here, the ability of chitosan‐polycaprolactone polyblend nanofibers to promote a migratory phenotype in human GBM cells by altering the nanotopography of the nanofiber membranes is investigated. Fibers are prepared with diameters of 200 nm, 400 nm, and 1.1 μm, and are either randomly oriented or aligned to produce six distinct nanotopographies. Human U‐87 MG GBM cells, a model cell line commonly used for invasion assays, are cultured on the various nanofibrous substrates. Cells show elongation and alignment along the orientation of aligned fibers as early as 24 h and up to 120 h of culture. After 24 h of culture, human GBM cells cultured on aligned 200 nm and 400 nm fibers show marked upregulation of invasion‐related genes including β‐catenin, Snail, STAT3, TGF‐β, and Twist, suggesting a mesenchymal change in these migrating cells. Additionally, cells cultured on 400 nm aligned fibers show similar migration profiles as those reported in vivo, and thus these nanofibers should provide a unique high‐throughput in vitro culture substrate for developing anti‐migration therapies for the treatment of GBM.
Antepartum Dental Radiography and Infant Low Birth Weight
Authors: Philippe P. Hujoel, Anne Marie Bollen, Carolyn J. Noonan, Michael A. Del Aguila
Journal: JAMA (2004)

ContextBoth high- and low-dose radiation exposures in women have been associated with low-birth-weight offspring. It is unclear if radiation affects the hypothalamus-pituitary-thyroid axis and thereby indirectly birth weight, or if the radiation directly affects the reproductive organs.ObjectiveTo investigate whether antepartum dental radiography is associated with low-birth-weight offspring.DesignA population-based case-control study.Participants and SettingEnrollees of a dental insurance plan with live singleton births in Washington State between January 1993 and December 2000. Cases were 1117 women with low-birth-weight infants (<2500 g), of whom 336 were term low-birth-weight infants (1501-2499 g and gestation ≥37 weeks). Four control pregnancies resulting in normal-birth-weight infants (≥2500 g) were randomly selected for each case (n = 4468).Main Outcome MeasuresOdds of low birth weight and term low birth weight by dental radiographic dose during gestation.ResultsAn exposure higher than 0.4 milligray (mGy) during gestation occurred in 21 (1.9%) mothers of low-birth-weight infants and, when compared with women who had no known dental radiography, was associated with an adjusted odds ratio (OR) for a low-birth-weight infant of 2.27 (95% confidence interval [CI], 1.11-4.66, P = .03). Exposure higher than 0.4 mGy occurred in 10 (3%) term low-birth-weight pregnancies and was associated with an adjusted OR for a term low-birth-weight infant of 3.61 (95% CI, 1.46-8.92, P = .005).ConclusionDental radiography during pregnancy is associated with low birth weight, specifically with term low birth weight.
Canes for knee osteoarthritis: is a randomised trial necessary?
Authors: Kåre B Hagen
Journal: Annals of the Rheumatic Diseases (2011)

In this issue of the Annals , Jones et al 1 (pp 172) report the results of a randomised clinical trial (RCT) of canes for knee osteoarthritis. Current recommendations on the management of hip and knee osteoarthritis emphasise non-pharmacological interventions, with sticks or canes universally recommended in existing guidelines.2 According to the Osteoarthritis Research Society International (OARSI) recommendations for the management of hip and knee osteoarthritis one of 25 treatment propositions recommended is ‘Walking aids can reduce pain in patients with hip and knee OA. Patients should be given instruction in the optimal use of a cane or crutch in the contralateral hand. Frames or wheeled walkers are often preferable for those with bilateral disease.’3 In the National Institute for Health and Clinical Excellence (NICE) guideline for care and management of osteoarthritis in adults, assistive devices (such as walking sticks) are considered as adjunct treatments.4 While both the OARSI and the NICE recommendations acknowledge the paucity of well-designed clinical trials in this area, there appears to be a high degree of expert consensus that walking aids can reduce pain in patients with hip and knee osteoarthritis. One might then ponder the need for a randomised trial on canes for knee osteoarthritis.

RCT provide the most unbiased evidence about the benefits and harms of medical interventions. However, sometimes when there are clear indications from observational studies that an intervention has a dramatic beneficial effect, a RCT is considered unnecessary and unethical. For example, although the evidence for the effectiveness of joint replacement surgery for severe knee and hip osteoarthritis is based substantially on uncontrolled observational studies and cohort studies in which outcomes have been compared with standard medical care, most people will agree that a RCT comparing surgery with the standard medical care of the present is unethical …
Surrogate markers predicting overall survival for lung cancer: ELCWP recommendations
Authors: T. Berghmans, F. Pasleau, M. Paesmans, Y. Bonduelle, J. Cadranel, I. Cs Toth, C. Garcia, V. Giner, S. Holbrechts, J.J. Lafitte, J. Lecomte, I. Louviaux, E. Markiewicz, A.P. Meert, M. Richez, M. Roelandts, A. Scherpereel, Ch. Tulippe, P. Van Houtte, P. Van Schil, C. Wachters, V. Westeel, J.P. Sculier
Journal: European Respiratory Journal (2011)

The present systematic review was performed under the auspices of the European Lung Cancer Working Party (ELCWP) in order to determine the role of early intermediate criteria (surrogate markers), instead of survival, in determining treatment efficacy in patients with lung cancer. Initially, the level of evidence for the use of overall survival to evaluate treatment efficacy was reviewed. Nine questions were then formulated by the ELCWP. After reviewing the literature with experts on these questions, it can be concluded that overall survival is still the best criterion for predicting treatment efficacy in lung cancer. Some intermediate criteria can be early predictors, if not surrogates, for survival, despite limitations in their potential application: these include time to progression, progression-free survival, objective response, local control after radiotherapy, downstaging in locally advanced nonsmall cell lung cancer (NSCLC), complete resection and pathological TNM in resected NSCLC, and a few circulating markers. Other criteria assessed in these recommendations are not currently adequate surrogates of survival in lung cancer.
Capsaicin and menthol in the treatment of itch and pain: recently cloned receptors provide the key
Authors: P Anand
Journal: Gut (2003)

Topical capsaicin is reported to be an effective treatment for idiopathic intractable pruritus ani. While both capsaicin and menthol application produce a transient perianal burning sensation, only capsaicin relieves itching. Classical observations on functional desensitisation of nociceptors by capsaicin may explain the beneficial effects but the recent discovery of a range of receptors which respond to capsaicin, menthol, and temperature, and their expression in subsets of sensory nerve fibres, provides an exciting prospect towards advancing our understanding and treatment of sensory dysfunction.
Characterization of recombinant monoclonal IgA anti–PDC-E2 autoantibodies derived from patients with PBC
Authors: N Fukushima
Journal: Hepatology (2002)

Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by the presence of autoantibodies to mitochondria (AMA). Recent evidence suggests that PBC develops after a locally driven response in the mucosa, where immunoglobulin A (IgA) is the dominant antibody isotype. In this study, we produced recombinant pyruvate dehydrogenase complex (PDC-E2)-specific dimeric human IgA monoclonal antibodies (mAbs) in a baculovirus expression system. By using 2 anti-PDC-E2 IgG mAbs derived from patients with PBC, we constructed 2 recombinant baculoviruses, each containing heavy chains with the Calpha constant region. These were simultaneously co-infected into Sf9 insect cells with recombinant baculovirus containing the J chain. A sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) immunoblotting profile of the IgA using a 6% nonreducing gel verified the dimeric nature of the autoantibodies. Both recombinants retained their original specificity for PDC-E2. In addition, the antibody showed a mitochondrial staining pattern in HEp2 cells and apically stained the biliary epithelial cells (BECs) in the liver of a patient with PBC but not a normal patient. Transcytosis experiments performed using human polymeric immunoglobulin receptor (pIgR) expressing Madine-Darby canine kidney (MDCK) cells showed that one of the recombinants showed a high degree of colocalization with PDC-E2. In conclusion, these data provide further support of the hypothesis that PDC-E2-specific IgA may enter biliary epithelial cells of PBC patients via the pIgR and complex with PDC-E2, thereby potentially contributing to the pathology of BECs. Moreover, this recombinant PDC-E2-specific mAb provides a tool for further determination of the role of anti-PDC-E2 IgA in the pathogenesis of PBC.
Humming Greatly Increases Nasal Nitric Oxide
Authors: Eddie Weitzberg, Jon O. N. Lundberg
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

The paranasal sinuses are major producers of nitric oxide (NO). We hypothesized that oscillating airflow produced by humming would enhance sinus ventilation and thereby increase nasal NO levels. Ten healthy subjects took part in the study. Nasal NO was measured with a chemiluminescence technique during humming and quiet single-breath exhalations at a fixed flow rate. NO increased 15-fold during humming compared with quiet exhalation. In a two-compartment model of the nose and sinus, oscillating airflow caused a dramatic increase in gas exchange between the cavities. Obstruction of the sinus ostium is a central event in the pathogenesis of sinusitis. Nasal NO measurements during humming may be a useful noninvasive test of sinus NO production and ostial patency. In addition, any therapeutic effects of the improved sinus ventilation caused by humming should be investigated.
CHIR-258: A Potent Inhibitor of FLT3 Kinase in Experimental Tumor Xenograft Models of Human Acute Myelogenous Leukemia
Authors: Daniel E. Lopes de Menezes, Jing Peng, Evelyn N. Garrett, Sharianne G. Louie, Sang H. Lee, Marion Wiesmann, Yan Tang, Lee Shephard, Cheryl Goldbeck, Yoko Oei, Helen Ye, Sharon L. Aukerman, Carla Heise
Journal: Clinical Cancer Research (2005)

Fms-like tyrosine kinase 3 (FLT3) encodes a receptor tyrosine kinase (RTK) for which activating mutations have been identified in a proportion of acute myelogenous leukemia (AML) patients and associated with poor clinical prognosis. Given the relevance of FLT3 mutations in AML, we investigated the activity of CHIR-258, an orally active, multitargeted small molecule, with potent activity against FLT3 kinase and class III, IV, and V RTKs involved in endothelial and tumor cell proliferation in AML models.CHIR-258 was tested on two human leukemic cell lines in vitro and in vivo with differing FLT3 mutational status [MV4;11 cells express FLT3 internal tandem duplications (ITD) versus RS4;11 cells with wild-type (WT) FLT3].Antiproliferative activity of CHIR-258 against MV4;11 was approximately 24-fold greater compared with RS4;11, indicating more potent inhibition against cells with constitutively activated FLT3 ITD. Dose-dependent down modulation of receptor phosphorylation and downstream signaling [signal transducer and activator of transcription 5 (STAT5) and extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase] in MV4;11 cells with CHIR-258 confirmed the molecular mechanism of action. Target modulation of phospho-FLT3, phospho-STAT5, and phospho-ERK in MV4;11 tumors was achieved at biologically active doses of CHIR-258. Tumor regressions and eradication of AML cells from the bone marrow were shown in s.c. and bone marrow engraftment leukemic xenograft models. Tumor responses were characterized by decreased cellular proliferation and positive immunohistochemical staining for active caspase-3 and cleaved poly(ADP-ribose) polymerase, suggesting cell death was mediated in part via apoptosis.Our data indicate that CHIR-258 may be an effective therapy in FLT3-associated AML and warrants clinical trials.