tbuckley/cabot-search huggingface dataset:
Cerebral oxygenation in highlanders with high altitude pulmonary hypertension
Authors: Michael Furian, Tsogyal D Latshang, Sayaka Aeschbacher, Silvia Ulrich, Aizat K. Myrzaakmatova, Talant Sooronbaev, Almaz Aldashev, Konrad E. Bloch
Journal: European Respiratory Journal (2014)

Background High altitude pulmonary hypertension (HAPH), a chronic altitude related illness, is associated with exercise intolerance, hypoxemia and sleep apnea. We evaluated whether cerebral tissue oxygenation (CTO) and autoregulation are impaired in affected patients.

Methods We studied 36 patients with HAPH, mean pulmonary artery pressure (mPAP)=35±3mmHg, and 54 healthy highlanders (HH), mPAP=22±5mmHg, in Aksay, Kyrgyzstan at 3250m. 34 healthy lowlanders (HL), mPAP=16±4mmHg, were studied in Bishkek (700m). CTO was monitored by transcranial near-infrared spectroscopy (NIRS) along with pulse oximetry (SpO2) during quiet breathing and hyperventilation.

Results During quiet breathing mean (SD) SpO2 in HAPH, HH and HL was 88±4%, 92±2% and 95±2%, respectively (P<0.05 HAPH vs. others); corresponding CTO was 68±3%, 68±4%, 69±4% (p=NS, all comparisons). Hyperventilation increased SpO2 in HAPH, HH and HL by 9±4, 6±2, 3±1%, respectively, and changed CTO by 0±3, -2±2, -4±2% (P<0.05 HAPH vs. others, both instances). Hyperventilation reduced cerebral total hemoglobin concentration; the NIRS derived measure of cerebral blood volume, by 2% in all 3 groups.

Conclusions Although highlanders with HAPH were hypoxemic their CTO was not different from that in HH and HL. Moreover, hyperventilation was not associated with a reduction in CTO and cerebral total hemoglobin concentration in HAPH suggesting effective cerebrovascular compensatory mechanisms.

Grant:OPO Foundation, Zurich Lung League.
High resolution computed tomography (HRCT) can differentiate rapid from slow progressing Idiopathic pulmonary fibrosis (IPF)
Authors: Elisabetta Balestro, Graziella Turato, Roberta Polverosi, Giulio Barbiero, Silvia Zagallo, Ariel Floriani, Federico Rea, Fiorella Calabrese, Erica Bazzan, Marco Schiavon, Nazarena Nannini, Simonetta Baraldo, Marina Saetta, Manuel Cosio
Journal: European Respiratory Journal (2014)

INTRODUCTION:  HRCT has become the main diagnostic tool for IPF. A slow progressing (S) and a rapid progressing (R) behavior of IPF, with important prognostic consequences, have been identified. It is unknown if HRCT could differentiate these two patterns of progression.   AIM : to investigate 1) if functionally defined slow and rapid progressors could be differentiated by HRCT and 2) if different HRCT features are reflected by the pathology of the explanted lung.   METHODS : 26 patients, 15 (S) and 11 (R) (FVC decline/year l 10% or g10% predicted) with a HRCT or biopsy IPF diagnosis, were evaluated while clinically stable by HRCT at a median of 20 months after diagnosis. Each lobe was scored blindly by two radiologists using a semiquantitative scale (AJR 1997;169:977) assessing extension (0-100%) and score (0-5) of ground glass opacity and fibrotic changes. In a subgroup, in which an explanted lung was available, HRCT scores were correlated with the degree of lung inflammation.   RESULTS : in (R) ground glass opacity [(19%; 9-70); (score 1.6;1-3)] was significantly increased when compared with (S) [(4%,0-25); (score 0.8, 0-3) p=0.001]. The extension and score of fibrotic changes were similar in the two groups: (R) 51%, 14-69 Vs (S) 40%, 18-73. Ground glass extension significantly correlated with total leukocytes infiltration (CD45) (r=0.69, p=0.03) and the number of alveolar macrophages (r=0.67,p=0.04).   CONCLUSION : ground glass opacity in HRCT can differentiate rapid from slow progressing IPF and is correlated with the degree of inflammation in the explanted lung.
Platelet Fc Receptor
Authors: Anne Moore, Ralph L. Nachman
Journal: Journal of Clinical Investigation (1981)

The platelet Fc receptor, a membrane receptor for immune complexes or aggregated immunoglobulin (Ig)G, was compared in normal and myeloproliferative platelets. Washed platelets from 11 normal donors and 27 patients were incubated with fluorescein-conjugated ovalbumin-anti-ovalbumin complexes and examined by phase and fluorescence microscopy. Only 3.2+/-1% of the normal platelets stained, whereas 76+/-16% of the myeloproliferative platelets stained with the immune complex. The fluorescent staining was mediated by a platelet Fc receptor, as shown by the absence of platelet staining with immune complex containing antibody preincubated with Staphylococcal protein A to block the Fc region. In addition, no staining occurred with antigen or antibody alone or after preincubation of platelets with aggregated IgG. Platelets from normal or myeloproliferative donors did not stain with the immune complexes when the incubation was performed in plasma. The increased expression of Fc receptors on myeloproliferative platelets was corroborated by studies of [(14)C]serotonin release by immune complexes or aggregated IgG in 8 patients and 17 normal donors. Serotonin uptake was similar in both groups. Myeloproliferative platelets released significantly more serotonin than normal platelets at each concentration of immune complex or aggregated IgG; in addition, myeloproliferative platelets released serotonin in response to much smaller concentrations of immune complex or aggregated IgG. [(14)C]Serotonin release by myeloproliferative platelets was not increased above that of normal platelets when thrombin was used as the stimulus. The results were independent of patient age, sex, therapy, hematocrit, or platelet size. Interaction of circulating immune complexes with platelets bearing increased Fc receptors may contribute to the abnormal hemostasis associated with the myeloproliferative syndromes.
ABVD/MOPP and low-dose involved-field radiotherapy in pediatric Hodgkin's disease: the Stanford experience.
Authors: S P Hunger, M P Link, S S Donaldson
Journal: Journal of Clinical Oncology (1994)

PURPOSE We reported previously that treatment with six cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy and 15 to 25 Gy irradiation was effective in curing children with Hodgkin's disease, but was associated with a 6.5% 10-year risk of development of secondary leukemia. Based on the results of that study, a successor study was designed with the objective to maintain treatment efficacy while decreasing adverse effects, particularly the occurrence of secondary leukemia. PATIENTS AND METHODS Fifty-seven children with a chronologic and/or bone age less than 16 years were enrolled onto this study between May 1982 and October 1990. Treatment consisted of six cycles of combination chemotherapy--three of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and three of MOPP--and low-dose irradiation (15 Gy) of involved fields. Boosts of 10 Gy were given to areas of bulky disease and to those that did not respond completely after two cycles of chemotherapy. RESULTS With a median follow-up duration of 6.7 years, the projected 10-year survival and event-free survival (EFS) rates are 96% (SE 2.5%) and 93% (SE 3.5%) for the entire cohort of 57 patients, and 85% (SE 10%) and 69% (SE 12.8%), respectively, for 13 patients with stage IV disease. No patient has developed a second malignancy. Growth and development have progressed normally. No patients have symptomatic cardiac, pulmonary, or thyroid disease. Subclinical abnormalities of pulmonary function were detected in 32% and chemical hypothyroidism in 16%. CONCLUSION This therapy was highly efficacious in children with Hodgkin's disease without unacceptable toxicity. Future efforts should be directed toward further reducing therapy for favorable early-stage patients and improving treatment efficacy for those with stage IV disease.
Abstract 3472: The Prediction of Ischemic Events After Percutaneous Coronary Intervention by Platelet Reactivity to Adenosine Diphosphate: First Evidence for an Oral Antiplatelet Therapeutic Target Determined by an <i>Ex Vivo</i> Test of Platelet Function.
Authors: Paul Gurbel, Kevin P Bliden, Joseph Dichiara, Mark J Antonino, Thomas A Suarez, Lawal Lookman, Udaya S Tantry
Journal: Circulation (2007)

Background: High on-treatment platelet reactivity to adenosine diphosphate (HPR-ADP) may be a risk factor for ischemic events after percutaneous coronary intervention (PCI). We determined whether a cutpoint of HPR-ADP, similar to the INR used to guide anticoagulant therapy, could predict ischemic event occurrence after PCI. Methods : Post-procedural platelet reactivity to ADP was measured by conventional aggregometry in 352 consecutive patients undergoing non-emergent PCI followed for up to 2 years for post-discharge ischemic events. All patients had received clopidogrel and aspirin therapy at the time of aggregation measurements. Results: Eighty-two patients (23%) suffered ischemic events and had higher 5 and 20 μM ADP-induced aggregation compared to patients without ischemic events (46 ± 14% and 60 ± 13% versus 30 ± 17% and 43 ± 19%, respectively, p&lt;0.0001 for both measurements). Using a combined receiver operator curve analysis, HPR-ADP cutpoints of 46% aggregation following 5μM ADP stimulation and 59% aggregation following 20μM ADP stimulation were associated with 63% and 74% of ischemic events, respectively. Multivariate Cox regression demonstrated significance between events and post-procedural HPR-ADP cutpoints (20μM ADP, OR=8.6, p&lt;0.0001; and 5μM ADP, OR=2.9, p=0.01). Conclusions: High on-treatment platelet reactivity to ADP is an independent risk factor for ischemic events within 2 years of non-emergent PCI. These data are the first to support a therapeutic target for antiplatelet therapy based on an ex vivo platelet function test, similar to the INR used for anticoagulant therapy. The study is a step towards a personalized medicine approach to guide the intensity of antiplatelet therapy.
B2-adrenoceptor genotype16 influences airway calibre but not hyperresponsiveness in asthmatics using regular B2-agonist in addition to inhaled corticosteroids
Authors: William Anderson, Philip Short, Peter Williamson, Ashley Morrison, Colin Palmer, Roger Tavendale, Brian Lipworth
Journal: European Respiratory Journal (2013)

Background: Asthmatic patients receiving inhaled corticosteroids (ICS) may take frequent add-on short acting beta agonist (SABA) despite on-demand prescription. B2-adrenoceptor (B2ADR) genotype 16 may influence this.

Methods: A randomised double-blind triple crossover study comparing 2 weeks regular inhaled racemic salbutamol (200µg qid); levosalbutamol (100µg qid); or placebo on diurnal PEF and 6h trough methacholine PC20 in 30 persistent asthmatics (15 homozygous Arg16 and Gly16) all receiving ICS.

Results: Active SABAs improved evening PEF in both Gly16 (p<0.001) and Arg16 patients (p=0.006); morning PEF did not improve with either SABA in Arg16 patients (p=0.5) compared to improvement in Gly16 patients (p=0.04)

![Figure][1] 



There was no worsening of airway hyper-responsiveness (AHR) at trough to methacholine after 2 weeks regular exposure to either racemic (p=0.53) or levosalbutamol (p=0.84) compared to placebo; nor between genotypes as doubling dilution (dd) difference in methacholine PC20 from placebo.

Conclusion: B2ADR genotype 16 influenced differential improvements in morning pre-bronchodilator PEF when using regular SABA in addition to ICS. There was no worsening of trough AHR at 2 weeks by genotype or active SABA compared to placebo.

 [1]: pending:yes
Circulating Carcinoembryonic Antigen Levels and Serum Suppression of Phytohemagglutinin- Stimulated Lymphocyte DNA Synthesis: An Inverse Correlation in the Cancer Patient2
Authors: Antony M. Steward, Herbert Z. Kupchik, Norman Zamcheck
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Circulating Carcinoembryonic Antigen Levels and Serum Suppression of Phytohemagglutinin- Stimulated Lymphocyte DNA Synthesis: An Inverse Correlation in the Cancer Patient Get access Antony M. Steward, F.R.C.S., Antony M. Steward, F.R.C.S. 3Mallory Gastrointestinal Laboratory and Harvard Surgical Unit, Boston City Hospital, Boston, Mass. 02118 Search for other works by this author on: Oxford Academic PubMed Google Scholar Herbert Z. Kupchik, Ph.D., Herbert Z. Kupchik, Ph.D. 4Mallory Gastrointestinal Laboratory, Thorndike Memorial Laboratory, Harvard Medical Unit, Boston City Hospital, Department of Medicine, Harvard Medical School, Department of Pathology, Boston University School of Medicine, Boston, Mass. 02118 Search for other works by this author on: Oxford Academic PubMed Google Scholar Norman Zamcheck, M.D. Norman Zamcheck, M.D. 4Mallory Gastrointestinal Laboratory, Thorndike Memorial Laboratory, Harvard Medical Unit, Boston City Hospital, Department of Medicine, Harvard Medical School, Department of Pathology, Boston University School of Medicine, Boston, Mass. 02118 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 53, Issue 1, July 1974, Pages 3–9, https://doi.org/10.1093/jnci/53.1.3 Published: 01 July 1974 Article history Received: 06 November 1973 Accepted: 25 March 1974 Published: 01 July 1974
Phase III study of NEPA, a fixed-dose combination of netupitant (NETU) and palonosetron (PALO), versus PALO for prevention of chemotherapy-induced nausea and vomiting (CINV) following moderately emetogenic chemotherapy (MEC).
Authors: Matti S. Aapro, Giorgia Rossi, Giada Rizzi, Marco Palmas, Steven Grunberg
Journal: Journal of Clinical Oncology (2013)

LBA9514 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Saturday, June, 1, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Saturday edition of ASCO Daily News.
Etiologies of acute exacerbation of bronchial asthma in adults by real-time polymerase chain reaction
Authors: Kenichiro Shimizu, Yutaka Yoshii, Miyuki Morozumi, Naoko Chiba, Kimiko Ubukata, Hiromichi Hara, Takanori Numata, Makoto Kawaishi, Keisuke Saito, Jun Araya, Katsutoshi Nakayama, Kazuyoshi Kuwano
Journal: European Respiratory Journal (2013)

Background:  Most common microorganisms associated with acute exacerbation of bronchial asthma (AEBA) are respiratory viruses such as rhinovirus (RV) and atypical bacteria such as  Mycoplasma pneumoniae  ( M. p ). Causative organisms of AEBA in pediatric populations have been well documented; however, these have been rarely reported in adults. Recently multiplex polymerase chain reaction (PCR) has been applied to detect effectively both respiratory bacteria and viruses.  Aims:  To evaluate etiologies in adult AEBA, a rapid reliable process based on real-time PCR for respiratory samples was used.  Methods:  From September 2012 to January 2013, we prospectively enrolled adult AEBA patients who satisfied our criteria; 20 years of age or older, within 7 days of onset, and informed consent. Nasopharyngeal swab and sputum samples were collected from all patients and comprehensive real-time PCR was used to detect 6 bacteria and 11 respiratory viruses.  Results:  Among 36 patients who satisfied our criteria, 25 (69.4%) of them detected microorganisms both bacteria and/or viruses by PCR test. 7 (19.4%) were diagnosed with viral infection, 11 (30.6%) with bacterial infection, 3 (8.3%) with atypical bacterial infection, and 4 (11.1%) with viral/bacterial co-infection. The remaining 11 (30.6 %) had unknown pathogens. Most leading microorganisms were  Haemophilus influenzae  ( H.  i ),  M. p , and RV.  Conclusions:  Our results suggest usefulness of real-time PCR for nasopharyngeal swab and sputum sample in estimating etiologies in adult AEBA. Results of the detection of  M. p  and RV were as expected; however,  H. i  was unpredicted. Based on the results, we analyzed the association between microorganisms and AEBA.
Interaction of Sickle Erythrocytes With Endothelial Cells in the Presence of Endothelial Cell Conditioned Medium Induces Oxidant Stress Leading to Transendothelial Migration of Monocytes
Authors: Chand Sultana, Yamin Shen, Vinod Rattan, Cage Johnson, Vijay K. Kalra
Journal: Blood (1998)
DNA methylome analysis in Burkitt and follicular lymphomas identifies differentially methylated regions linked to somatic mutation and transcriptional control
Authors: Helene Kretzmer, Stephan H Bernhart, Wei Wang, Andrea Haake, Marc A Weniger, Anke K Bergmann, Matthew J Betts, Enrique Carrillo-de-Santa-Pau, Gero Doose, Jana Gutwein, Julia Richter, Volker Hovestadt, Bingding Huang, Daniel Rico, Frank Jühling, Julia Kolarova, Qianhao Lu, Christian Otto, Rabea Wagener, Judith Arnolds, Birgit Burkhardt, Alexander Claviez, Hans G Drexler, Sonja Eberth, Roland Eils, Paul Flicek, Siegfried Haas, Michael Humme, Dennis Karsch, Hinrik H D Kerstens, Wolfram Klapper, Markus Kreuz, Chris Lawerenz, Dido Lenzek, Markus Loeffler, Cristina López, Roderick A F MacLeod, Joost H A Martens, Marta Kulis, José Ignacio Martín-Subero, Peter Möller, Inga Nage, Simone Picelli, Inga Vater, Marius Rohde, Philip Rosenstiel, Maciej Rosolowski, Robert B Russell, Markus Schilhabel, Matthias Schlesner, Peter F Stadler, Monika Szczepanowski, Lorenz Trümper, Hendrik G Stunnenberg, Ralf Küppers, Ole Ammerpohl, Peter Lichter, Reiner Siebert, Steve Hoffmann, Bernhard Radlwimmer
Journal: Nature Genetics (2015)
Rostral and Orbital Prefrontal Cortex Dysfunction in the Manic State of Bipolar Disorder
Authors: Hilary P. Blumberg, Emily Stern, Sally Ricketts, Diana Martinez, Jose de Asis, Thomas White, Jane Epstein, Nancy Isenberg, P. Anne McBride, Ingrid Kemperman, Sylvia Emmerich, Vijay Dhawan, David Eidelberg, James H. Kocsis, David A. Silbersweig
Journal: American Journal of Psychiatry (1999)

This study investigated prefrontal cortex function in the manic state of bipolar disorder.High-sensitivity [15O]H2O positron emission tomography and a word generation activation paradigm were used to study regional cerebral blood flow in five manic and six euthymic individuals with bipolar disorder and in five healthy individuals.Decreased right rostral and orbital prefrontal cortex activation during word generation and decreased orbitofrontal activity during rest were associated with mania.The data support the presence of rostral and orbital prefrontal dysfunction in primary mania. These findings, when seen in the context of the human brain lesion and the behavioral neuroanatomic literatures, may help to explain some of the neurobehavioral abnormalities characteristic of the manic state.
Phase I Study of a Third-Generation Selective Estrogen Receptor Modulator, LY353381.HCl, in Metastatic Breast Cancer
Authors: Pamela N. Münster, Aman Buzdar, Kapil Dhingra, Nathan Enas, Lan Ni, Maureen Major, Allen Melemed, Andrew Seidman, Daniel Booser, Richard Theriault, Larry Norton, Clifford Hudis
Journal: Journal of Clinical Oncology (2001)

PURPOSE: We conducted this phase I trial to determine the safety and toxicity profile of LY353381.HCl—a novel, potent, third-generation selective estrogen receptor modulator (SERM)—because this benzothiophene derivative demonstrated an SERM profile in preclinical studies. PATIENTS AND METHODS: We studied 32 patients with recurrent or metastatic breast cancer. Patients were treated in four cohorts with oral daily doses of 10, 20, 50, and 100 mg. Pharmacokinetic sampling was performed during the first 72 hours following the first dose on day 1 and during the 24 hours after the day 57 dose. Eligibility criteria included Eastern Cooperative Oncology Group performance status of 0 to 2; no significant major organ dysfunction; and at least 3 weeks elapsed since most recent hormonal therapy, chemotherapy, and estrogen replacement therapy. RESULTS: The median patient age was 56 years (range, 30 years to 76 years). The median number of prior chemotherapies for metastatic disease was one (range, zero to four), while the median number of prior hormone regimens for metastatic disease was two (range, zero to five). Receptor status was estrogen receptor (ER) positive and progesterone receptor (PR) positive, 19 patients; ER positive and PR negative, eight patients; ER positive and PR unknown, two patients; and ER and PR unknown, three patients. Dose-limiting toxicity was not observed. Treatment was well tolerated with mild to moderate hot flashes in 18 of 32 patients (56%) at all dose levels. Transvaginal ultrasound performed at baseline and after 12 weeks of treatment showed no endometrial thickening. Of the 32 patients evaluable for response, six patients had stable disease for at least 6 months with a median duration of 7.7 months (range, 6.2 months to 33.8 months). The pharmacokinetics of LY353381.HCl were generally linear with respect to time and studied dose range. CONCLUSION: As predicted in preclinical testing, daily oral LY353381.HCl is safe, is well tolerated at all tested dose levels, and may be clinically beneficial in patients with extensively pretreated metastatic breast cancer. Further studies with LY353381 to evaluate the efficacy in patients with or without prior exposure to tamoxifen and fewer overall prior regimens are under way.
A Common Polymorphism in the Complement Factor H Gene Is Associated With Increased Risk of Myocardial Infarction
Authors: Isabella Kardys, Caroline C.W. Klaver, Dominiek D.G. Despriet, Arthur A.B. Bergen, André G. Uitterlinden, Albert Hofman, Ben A. Oostra, Cornelia M. Van Duijn, Paulus T.V.M. de Jong, Jacqueline C.M. Witteman
Journal: Journal of the American College of Cardiology (2006)
IP-10 is selectively produced in the airways upon respiratory virus infection
Authors: Marco P. Alves, Aline Schögler, Ricardo Muster, Marie-Noelle Kronig, Elisabeth Kieninger, Brigitte S. Kopf, Andrea Stokes, Nicolas Regamey
Journal: European Respiratory Journal (2013)

Acute respiratory infections (ARIs) represent a challenge in clinical practice. The symptoms of bacterial and viral infections are overlapping, and due to the lack of a specific reliable marker, the physician is left with diagnostic uncertainty. This often leads to an empirical antibiotic (over)treatment, although 60% of ARIs are associated with viral infections. It has been reported that IFN-gamma-inducible protein 10 (IP-10) is produced by the airway epithelium upon infection with respiratory viruses and is measurable in vivo in respiratory secretions and serum. This led us to evaluate the cytokine profile induced by primary airway epithelial cells upon viral and bacterial stimulation. We analysed IP-10, IL-6, and IL-8 responses of primary human nasal and bronchial epithelial cells after stimulation with rhinoviruses (RVs), poly(IC), and bacterial-derived products including LPS, flagellin, and lipopeptides. In addition, we measured IP-10 in nasopharyngeal aspirates (NPAs) obtained from three different groups of children hospitalized for lower respiratory tract infections: children with RV-wheezy bronchitis, RSV bronchiolitis and non-viral ARI. Bronchial and nasal cells produced similar amounts of IL-6 and IL-8 after viral and bacterial stimulation. In contrast, IP-10 was selectively produced upon stimulation with poly(IC) and infection with RVs. In accordance with the in vitro data, IP-10 was found at higher concentrations in NPAs from RV- and RSV-infected children compared to those with non-viral ARI. Our findings suggest a role of IP-10 during antiviral responses of the airways and its possible use as a tool to assist the physician in clinical decision-making when evaluating patients with ARI.