tbuckley/cabot-search huggingface dataset:
Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial
Authors: Kai C Wollert, Gerd P Meyer, Joachim Lotz, Stefanie Ringes Lichtenberg, Peter Lippolt, Christiane Breidenbach, Stephanie Fichtner, Thomas Korte, Burkhard Hornig, Diethelm Messinger, Lubomir Arseniev, Bernd Hertenstein, Arnold Ganser, Helmut Drexler
Journal: The Lancet (2004)
Lipoxygenase Pathway in Islet Endocrine Cells. OXIDATIVE METABOLISM OF ARACHIDONIC ACID PROMOTES INSULIN RELEASE
Authors: Stewart Metz, Michael VanRollins, Robert Strife, Wilfred Fujimoto, R. Paul Robertson
Journal: Journal of Clinical Investigation (1983)

Metabolism of arachidonic acid (AA) via the cyclooxygenase pathway reduces glucose-stimulated insulin release. However, metabolism of AA by the lipoxygenase pathway and the consequent effects on insulin secretion have not been simultaneously assessed in the endocrine islet. Both dispersed endocrine cell-enriched pancreatic cells of the neonatal rat, as well as intact islets of the adult rat, metabolized [3H]AA not only to cyclooxygenase products (prostaglandins E2, F2α, and prostacyclin) but also to the lipoxygenase product 12-hydroxyeicosatetraenoic acid (12-HETE). 12-HETE was identified by coelution with authentic tritiated or unlabeled 12-HETE using four high performance liquid chromatographic systems under eight mobile-phase conditions and its identity was confirmed by gas chromatography/mass spectrometry using selected ion monitoring. The predominant effect of exogenous AA (5 μg/ml) was to stimulate insulin release from pancreatic cells grown in monolayer. This effect was concentration- and time-dependent, and reversible. The effect of AA upon insulin release was potentiated by a cyclooxygenase inhibitor (indomethacin) and was prevented by either of two lipoxygenase inhibitors (5,8,11,14-eicosatetraynoic acid [ETYA] and BW755c). In addition, glucose, as well as two structurally dissimilar agents (the calcium ionophore A23187 and bradykinin), which activate phospholipase(s) and thereby release endogenous AA in several cell systems, also stimulated insulin secretion. The effects of glucose, glucagon, bradykinin and high concentrations of A23187 (5 μg/ml) to augment insulin release were blocked or considerably reduced by lipoxygenase inhibitors. However, a lower concentration of the ionophore (0.25 μg/ml), which did not appear to activate phospholipase, was resistant to blockade. Exogenous 12-HETE (up to 2,000 ng/ml) did not alter glucose-induced insulin release. However, the labile intermediate 12-hydroperoxy-ETE increased insulin release. Furthermore, diethylmaleate (which binds intracellular glutathione and thereby impedes conversion of the lipoxygenase intermediates hydroperoxy-ETE and leukotriene A4 to HETE and leukotriene C4, respectively) potentiated the effect of glucose and of exogenous AA. Finally, 5,6-epoxy, 8,11,14-eicosatrienoic acid (a relatively stable epoxide analogue of leukotriene A4) as well as two other epoxy-analogues, potentiated glucose-induced insulin release. We conclude that dual pathways of AA metabolism exist in islet endocrine cells and have opposing regulatory effects on the beta cell—an inhibitory cyclooxygenase cascade and a stimulatory lipoxygenase cascade. Labile products of the latter pathway may play a pivotal role in stimulus-secretion coupling in the islet.
THE SYMPTOM OR CHARACTER TRAIT MAY BECOME "ORGANIC"
Authors: JOHN P. KEMPH
Journal: American Journal of Psychiatry (1964)

Occasionally a symptom or character trait may not change during an otherwise successful course of psychotherapy. It is postulated that this may result from the development of a multitude of intrapsychic associations, learned patterns of behavior, and at the organ level many nerve fiber synaptic connections between nerve cells and between neural systems which form an organic basis for the character trait or symptom. Prolonged therapy may nevertheless be successful in these "organic conditions through the patient's establishing new adaptational modes of behavior as a result of the ability of the human nerve cells to form new cellular processes. This development of nerve fibers occurs most rapidly in early childhood and there may be a second period of rapid growth in adolescence.
The Influence of Psychotic Parents on Their Children's Development
Authors: RITA LANDAU, PAULA HARTH, NAVA OTHNAY, CILA SHARFHERTZ
Journal: American Journal of Psychiatry (1972)

A comparison of the psychological and intellectual development of children whose parents were mentally ill and children of normal parents disclosed significant differences between the two groups. The authors believe the former group should be viewed as a population at risk; serious consideration should be given to their needs, and services—including the opportunity to develop long-term relationships with stable adults—should be provided for them.
Estrogen-Dependent Signaling in a Molecularly Distinct Subclass of Aggressive Prostate Cancer
Authors: Sunita R. Setlur, Kirsten D. Mertz, Yujin Hoshida, Francesca Demichelis, Mathieu Lupien, Sven Perner, Andrea Sboner, Yudi Pawitan, Ove Andrén, Laura A. Johnson, Jeff Tang, Hans-Olov Adami, Stefano Calza, Arul M. Chinnaiyan, Daniel Rhodes, Scott Tomlins, Katja Fall, Lorelei A. Mucci, Philip W. Kantoff, Meir J. Stampfer, Swen-Olof Andersson, Eberhard Varenhorst, Jan-Erik Johansson, Myles Brown, Todd R. Golub, Mark A. Rubin
Journal: JNCI Journal of the National Cancer Institute (2008)

BackgroundThe majority of prostate cancers harbor gene fusions of the 5′-untranslated region of the androgen-regulated transmembrane protease serine 2 (TMPRSS2) promoter with erythroblast transformation–specific transcription factor family members. The common fusion between TMPRESS2 and v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) is associated with a more aggressive clinical phenotype, implying the existence of a distinct subclass of prostate cancer defined by this fusion.
Detection of patients with sick sinus syndrome by use of low amplitude potentials early in filtered P wave
Authors: Takahisa Yamada, Masatake Fukunami, Kazuaki Kumagai, Yasushi Abe, Jiyoong Kim, Shoji Sanada, Masatsugu Hori, Takenobu Kamada, Noritake Hoki
Journal: Journal of the American College of Cardiology (1996)
Evaluation of lapatinib as a component of neoadjuvant therapy for HER2+ operable breast cancer: NSABP protocol B-41.
Authors: Andre Robidoux, Gong Tang, Priya Rastogi, Charles E. Geyer, Catherine A. Azar, James Norman Atkins, Louis Fehrenbacher, Harry Douglas Bear, Luis Baez-Diaz, J. Phillip Kuebler, Richard G. Margolese, William Blair Farrar, Adam Brufsky, Henry R. Shibata, Hanna Bandos, Soonmyung Paik, Joseph P. Costantino, Sandra M. Swain, Eleftherios P. Mamounas, Norman Wolmark
Journal: Journal of Clinical Oncology (2012)

LBA506 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Sunday, June 3, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News.
Face Agnosia and the Neural Substrates of Memory
Authors: A R Damasio, D Tranel, H Damasio
Journal: Annual Review of Neuroscience (1990)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Synergism of Epidermal Growth Factor Receptor–Targeted Immunotherapy With Photodynamic Treatment of Ovarian Cancer In Vivo
Authors: Marcela G del Carmen, Imran Rizvi, Yuchiao Chang, Anne C E Moor, Esther Oliva, Margaret Sherwood, Brian Pogue, Tayyaba Hasan
Journal: JNCI Journal of the National Cancer Institute (2005)

Epithelial ovarian cancer often develops resistance to standard treatments, which is a major reason for the high mortality associated with the disease. We examined the efficacy of a treatment regimen that combines immunotherapy to block the activity of epidermal growth factor receptor (EGFR), overexpression of which is associated with the development of resistant ovarian cancer, and photodynamic therapy (PDT), a mechanistically distinct photochemistry-based modality that is effective against chemo- and radioresistant ovarian tumors.We tested a combination regimen consisting of C225, a monoclonal antibody that inhibits the receptor tyrosine kinase activity of EGFR, and benzoporphyrin derivative monoacid A (BPD)-based PDT in a mouse model of human ovarian cancer. Therapeutic efficacy was evaluated in acute treatment response and survival studies that used 9-19 mice per group. Analysis of variance and Wilcoxon statistics were used to analyze the data. All statistical tests were two-sided.Mice treated with PDT + C225 had the lowest mean tumor burden compared with that in the no-treatment control mice (mean percent tumor burden = 9.8%, 95% confidence interval [CI] = 2.3% to 17.3%, P < .001). Mean percent tumor burden for mice treated with C225 only or PDT only was 66.6% (95% CI = 58.7% to 74.4%, P < .001) and 38.2% (95% CI = 29.3% to 47.0%, P < .001), respectively. When compared with PDT only or C225 only, PDT + C225 produced synergistic reductions in mean tumor burden (P < .001, analysis of variance) and improvements in survival (P = .0269, Wilcoxon test). Median survival was approximately threefold greater for mice in the PDT + C225 group than for mice in the no-treatment control group (80 days versus 28 days), and more mice in the PDT + C225 group were alive at 180 days (3/9; 33% [95% CI = 7% to 70%]) than mice in the C225-only (0/12; 0% [95% CI = 0% to 22%]) or PDT-only (1/10; 10% [95% CI = 0.2% to 44%]) groups.A mechanistically nonoverlapping combination modality consisting of receptor tyrosine kinase inhibition with C225 and BPD-PDT is well tolerated, effective, and synergistic in mice.
Pharmacokinetic/Pharmacodynamic Modeling in Drug Development
Authors: L. B. Sheiner, J.-L. Steimer
Journal: The Annual Review of Pharmacology and Toxicology (2000)

We propose a framework for considering the role of pharmacokinetic/ pharmacodynamic modeling in drug development and an appraisal of its current and potential impact on that activity. After some introduction, definitions, and background information on drug development, we discuss subject-matter models that underlie pharmacokinetic/pharmacodynamic modeling and show how they determine appropriate statistical models. We discuss the broad role modeling can play in drug development, enhancing primarily the “learning” steps, i.e. acquiring the information needed for the label and for planning efficient confirmatory clinical trials. Examples of past applications of modeling to drug development are presented in tabular form, followed by a discussion of some practical issues in application. Modeling will not reach its potential utility until it is manifest as a visible and separate work unit within a drug development program. We suggest that that work unit is the “in numero” study: a protocol-driven exercise designed to extract additional information, and/or answer a specific drug-development question, through an integrated model-based (meta-) analysis of existent raw data, often pooled across separate (clinical) studies.
Effects of Interleukin-1β Inhibition With Canakinumab on Hemoglobin A1c, Lipids, C-Reactive Protein, Interleukin-6, and Fibrinogen
Authors: Paul M Ridker, Campbell P. Howard, Verena Walter, Brendan Everett, Peter Libby, Johannes Hensen, Tom Thuren
Journal: Circulation (2012)

Background— To test formally the inflammatory hypothesis of atherothrombosis, an agent is needed that reduces inflammatory biomarkers such as C-reactive protein, interleukin-6, and fibrinogen but that does not have major effects on lipid pathways associated with disease progression. Methods and Results— We conducted a double-blind, multinational phase IIb trial of 556 men and women with well-controlled diabetes mellitus and high cardiovascular risk who were randomly allocated to subcutaneous placebo or to subcutaneous canakinumab at doses of 5, 15, 50, or 150 mg monthly and followed over 4 months. Compared with placebo, canakinumab had modest but nonsignificant effects on the change in hemoglobin A1c, glucose, and insulin levels. No effects were seen for low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or non–high-density lipoprotein cholesterol, although triglyceride levels increased ≈10% in the 50-mg ( P =0.02) and 150-mg ( P =0.03) groups. By contrast, the median reductions in C-reactive protein at 4 months were 36.4%, 53.0%, 64.6%, and 58.7% for the 5-, 15-, 50-, and 150-mg canakinumab doses, respectively, compared with 4.7% for placebo (all P values ≤0.02). Similarly, the median reductions in interleukin-6 at 4 months across the canakinumab dose range tested were 23.9%, 32.5%, 47.9%, and 44.5%, respectively, compared with 2.9% for placebo (all P ≤0.008), and the median reductions in fibrinogen at 4 months were 4.9%, 11.7%, 18.5%, and 14.8%, respectively, compared with 0.4% for placebo (all P values ≤0.0001). Effects were observed in women and men. Clinical adverse events were similar in the canakinumab and placebo groups. Conclusions— Canakinumab, a human monoclonal antibody that neutralizes interleukin-1β, significantly reduces inflammation without major effect on low-density lipoprotein cholesterol or high-density lipoprotein cholesterol. These phase II trial data support the use of canakinumab as a potential therapeutic method to test directly the inflammatory hypothesis of atherosclerosis. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00900146.
Methadone-Induced Pulmonary Edema
Authors: J. Mark Kjeldgaard
Journal: JAMA (1971)

A 19-year-old former heroin addict developed pulmonary edema within six hours after the oral ingestion of 80 mg of methadone hydrochloride and recovered rapidly and without sequalae, with vigorous ventilatory support. This complication has been observed following intravenous overdosage with morphine and heroin, but has not previously been recorded after methadone ingestion.
Surgery in Bleeding Peptic Ulcers
Authors: J. N. Ward-McQuaid, J. C. Pease, A. M. Smith, R. J. Twort
Journal: Gut (1960)

This paper records a study of 400 patients admitted for haematemesis and melaena. Emergency surgery was undertaken on selected patients but the overall mortality increased when more frequent emergency operations were performed in the latter half of the series.
Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival
Authors: James A Bonner, Paul M Harari, Jordi Giralt, Roger B Cohen, Christopher U Jones, Ranjan K Sur, David Raben, Jose Baselga, Sharon A Spencer, Junming Zhu, Hagop Youssoufian, Eric K Rowinsky, K Kian Ang
Journal: The Lancet Oncology (2009)
Laboratory tests for antithrombin deficiency
Authors: Bernard Khor, Elizabeth M. Van Cott
Journal: American Journal of Hematology (2010)

Hereditary antithrombin deficiency is a hypercoagulable state associated with an increased risk for venous thrombosis. The recommended initial test for antithrombin is an activity (functional) assay. The advantages and disadvantages of the various testing options are presented. The causes of acquired antithrombin deficiency are much more common than hereditary deficiency. Therefore, this article describes the appropriate steps to take when antithrombin activity is low, in order to confirm or exclude a hereditary deficiency. The causes of falsely normal results are also described, including direct thrombin inhibitors. Am. J. Hematol. 85:947-950, 2010. © 2010 Wiley-Liss, Inc.
Persistent airway eosinophilia after leukotriene (LT) D4 administration in the guinea pig: modulation by the LTD4 receptor antagonist, pranlukast, or an interleukin-5 monoclonal antibody.
Authors: D C Underwood, R R Osborn, S J Newsholme, T J Torphy, D W Hay
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Aerosolized cysteinyl leukotrienes (CysLTs) elicit migration of eosinophils into guinea pig lungs and the airways of patients with asthma. The present studies were designed to analyze the concentration-response relationship, time course, and pharmacologic and histologic characteristics of leukotriene D4 (LTD4)-induced eosinophil influx into the airways of conscious guinea pigs. Animals were exposed to aerosols of 0.3 to 30 microg/ml LTD4 for 1 min, during which specific airway conductance (sGaw) was monitored. Bronchoalveolar lavages (BALs) of guinea pig airways were conducted at selected times from 4 h to 4 wk after LTD4 challenge. LTD4 produced maximal decreases in sGaw (70 to 90% reduction) at all concentrations tested and concentration-related increases in eosinophil levels in BALs, assessed 24 h after challenge. Increased numbers of eosinophils in the bronchial epithelium and subepithelium were confirmed histologically. Significant eosinophilia was maintained for up to 4 wk postchallenge. Pretreatment with the LTD4 receptor antagonist, pranlukast (ONO-1078, SB 205312) (20 mg/kg, intragastrically), significantly inhibited both the bronchoconstriction and the eosinophilia at 24 h, whereas the cyclooxygenase inhibitor, meclofenamic acid (5 mg/kg, intragastrically), had no effect on either parameter. Histologic observations were consistent with BAL results. Pretreatment with the rat anti-mouse antibody to interleukin-5 (IL-5), TRFK-5 (10-300 microg, intraperitoneally), produced dose-related inhibition of LTD4-induced eosinophilia, measured in 24 h or 3 wk BAL, but did not affect the acute bronchoconstriction. These results indicate that LTD4 elicits airway eosinophil influx in guinea pigs which persists as long as 4 wk after a single exposure, and provide the first evidence that IL-5 may have a role in LTD4-induced airways inflammation. This and other previously reported proinflammatory effects of LTD4 may contribute significantly to its overall influential role in the pathophysiology of asthma, and may underlie the therapeutic benefit of CysLT receptor antagonists, such as pranlukast, in this disorder.
Influence of Acute Stimuli on Plasma Aldosterone Concentration in Anephric Man and Kidney Allograft Recipients
Authors: ROBERT E. McCAA, VIRGINIA H. READ, ALLEN W. COWLEY, JOHN D. BOWER, GEORGE V. SMITH, CONNIE S. McCAA
Journal: Circulation Research (1973)

The response of plasma aldosterone concentration to postural variation, adrenocorticotropic hormone (ACTH), and angiotensin II was studied in five kidney allograft recipients and compared with the response observed in the same five subjects during the anephric period. Normal subjects acted as intact controls. After 2 hours of normal ambulation, plasma aldosterone levels increased in normal subjects (6.7 ± 1.6 to 22.9 ± 2.7 ng/100 ml plasma), remained unchanged in anephric patients (4.5 ± 1.0 to 5.2 ± 1.1 ng/100 ml plasma), and increased in kidney allograft recipients (6.8 ± 1.5. to 25.6 ± 1.9 ng/100 ml plasma). After ACTH administration, plasma aldosterone levels increased in normal subjects (7.5 ± 1.8 to 24.3 ± 2.5 ng/100 ml plasma), anephric subjects studied immediately after hemodialysis (16.6 ± 1.6 to 30.0 ± 2.6 ng/100 ml plasma), and kidney allograft recipients (5.0 ± 1.6 to 22.3 ± 1.4 ng/100 ml plasma). After angiotensin II infusion, plasma aldosterone levels increased in normal subjects (7.2 ± 1.8 to 42.5 ± 3.6 ng/100 ml plasma), remained unchanged in anephric subjects (8.6 ± 2.1 to 7.4 ± 1.6 ng/100 ml plasma), and increased in kidney allograft recipients (6.3 ± 1.5 to 40.2 ± 3.1 ng/100 ml plasma). In anephric man after prolonged absence of the renal renin-angiotensin system ACTH increased the rate of aldosterone secretion but angiotensin II had little effect. An intact renal renin-angiotensin system was necessary for increased aldosterone secretion in response to postural variation.
The hand eczema severity index (HECSI): a scoring system for clinical assessment of hand eczema. A study of inter- and intraobserver reliability
Authors: E. Held, R. Skoet, J.D. Johansen, T. Agner
Journal: British Journal of Dermatology (2005)

Background There is a need for a standardized clinical grading system for a more objective and accurate assessment of the severity of hand eczema (HE). Objectives To develop and validate a scoring system called the hand eczema severity index (HECSI) designed for clinical assessment of HE. Methods Twelve dermatologists (observers) assessed 15 HE patients twice, with an interval of 30 min. The study was performed blinded for the observers, and only the hands and wrists of the patients were visible to the observers. Agreement between the observers was determined by using the intraclass correlation coefficient (ICC), which is the correlation between (single) ratings of the same patient. Results ICC for total HECSI score was 0·79 at the first assessment and 0·84 at the second assessment. ICC for intraobserver agreement was 0·90. Conclusions Overall excellent agreement existed for both inter‐ and intraobserver reliability and the scoring system is suggested for use in future clinical studies on HE. Because HECSI is an entirely objective assessment of clinical signs, in addition, inclusion of patient‐rated symptoms should be considered.
Surfing the Internet for Patient Information: The Personal Clinical Web Page
Authors: D. John Doyle
Journal: JAMA (1995)

To the Editor.  —Access to emergency medical information (allergies, summaries of past hospital admissions, old electrocardiograms, and the like) is often required when travelers are admitted to a hospital far from home. The need for such information is likely to be especially strong when a patient is unconscious at the time of hospital entry, such as might occur following a head injury or stroke. This problem has been addressed to some extent by the Medic Alert System, which provides a very limited amount of clinical information as an inscription on a bracelet (or other device), with a telephone number to call where further information is available.  Another possibility exists, however. As many readers with Internet experience know, home pages on the World Wide Web have become a common way to organize information on the Internet. Since many of these Web pages are private and require password access, this same approach