tbuckley/cabot-search huggingface dataset:
FRI0331 Reasons and Risk Factors for Discontinuation of Biologic Agents in Rheumatoid Arthritis Patients
Authors: K. Terabe, T. Kojima, N. Takahashi, K. Funahashi, A. Kaneko, Y. Hirano, N. Ishiguro
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Rheumatoid arthritis (RA) patients who failed a first biologic agent due to any reasons have the option of switching to a second one along with the strategy of biologic agent treatment. Patients go over switching to the next one at failing their biologic agent. On the other hand, there are some patients who discontinue any biologic agent treatment due to various reasons such as tolerability concern, complications, economic issue, remission and so on. The impact of this concern has been less studied. <h3>Objectives</h3> The objective of this study was to investigate the reasons and the risk factors for discontinuation any biologic agent in RA patients. <h3>Methods</h3> In total patients (n=2179) who underwent biologic agent treatment between 2003 and 2011 at Nagoya University Hospital and 12 other institutes (Tsurumai Biologics Communication Study Group), 1966 patients who were confirmed continuation or discontinuation of biologic agent treatment were enrolled. We analyzed the retention rate of biologic agent treatment and the reasons for discontinuation. To identify the risks for discontinuation, baseline demographics were compared between the continuing group and the disc continuing group using cox hazard regression analysis. <h3>Results</h3> In total 1966 patients, 1479 patients were administered biologics continuously, 487 patients were withdrew. Table 1 showed the demographic date in total patients. The retention rate was 72% (n=1563) at least 1 year from starting biologics treatment, 68.7% (n=866) at 3 years, 65.6% (n=360) at 5 years. In 327 patients who were confirmed the reasons of discontinuation, the reasons were adverse events in 191 patients, lack of effectiveness in 66 patients, others in 70 patients. Comparison of incidence for discontinuation using cumulative hazard function, the reason of adverse events was significantly higher than others reasons (Fig. 1). To identify o the risks of discontinuation, we used cox hazard model regression in patients who discontinued treatment due to adverse events and lack of effectiveness, the risk factors were over 70 years of age (OR 1.80 [1.31-2.46]), male (OR 1.79 [1.27-2.52]), over 3 of steinblocker class (OR 1.51 [1.12-2.04]). Non concomitant with methotrexate (OR 1.47 [1.06-2.04]) (Fig. 2). <h3>Conclusions</h3> The most common reason for discontinuation was adverse events. In a numerically greater proportion of patients who discontinued any biologic agent treatment, timing of discontinuation was within a first year from starting treatment. In addition, the risk factors for discontinuation were similar with those of adverse events. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5503
Characterization of hepatitis C virus intergenotypic recombinant strains and associated virological response to sofosbuvir/ribavirin
Authors: Charlotte Hedskog, Brian Doehle, Krishna Chodavarapu, Viktoria Gontcharova, Javier Crespo Garcia, Robert De Knegt, Joost P.H Drenth, John G. McHutchison, Diana Brainard, Luisa M. Stamm, Michael D. Miller, Evguenia Svarovskaia, Hongmei Mo
Journal: Hepatology (2014)

To date, intergenotypic recombinant hepatitis C viruses (HCVs) and their treatment outcomes have not been well characterized. This study characterized 12 novel HCV recombinant strains and their response to sofosbuvir in combination with ribavirin (SOF/RBV) treatment. Across the phase II/III studies of SOF, HCV samples were genotyped using both the Siemens VERSANT HCV Genotype INNO‐LiPA 2.0 Assay (Innogenetics, Ghent, Belgium) and nonstructural (NS)5B sequencing. Among these patient samples, genotype assignment discordance between the two methods was found in 0.5% of all cases (12 of 2,363), of which all were identified as genotype 2 by INNO‐LiPA (12 of 487; 2.5%). HCV full‐genome sequences were obtained for these 12 samples by a sequence‐independent amplification method coupled with next‐generation sequencing. HCV full‐genome sequencing revealed that these viruses were recombinant HCV strains, with the 5' part corresponding to genotype 2 and the 3' part corresponding to genotype 1. The recombination breakpoint between genotypes 2 and 1 was consistently located within 80 amino acids of the NS2/NS3 junction. Interestingly, one of the recombinant viruses had a 34‐amino‐acid duplication at the location of the recombination breakpoint. Eleven of these twelve patients were treated with a regimen for genotype 2 HCV infection, but responded as if they had genotype 1 infection; 1 patient had received placebo. Conclusion : Twelve new HCV intergenotypic recombinant genotype 2/1 viruses have been characterized. The antiviral response to a 12‐ to 16‐week course of SOF/RBV treatment in these patients was more similar to responses among genotype 1 patients than genotype 2 patients, consistent with their genotype 1 NS5B gene (H epatology 2015;61:471‐480)
Propranolol-resistant infantile haemangiomas
Authors: S. Caussé, H. Aubert, M. Saint-Jean, E. Puzenat, A.-C. Bursztejn, C. Eschard, E. Mahé, A. Maruani, J. Mazereeuw-Hautier, I. Dreyfus, J. Miquel, C. Chiaverini, O. Boccara, S. Hadj-Rabia, J.-F. Stalder, S. Barbarot
Journal: British Journal of Dermatology (2013)

Propranolol is now widely used to treat severe infantile haemangiomas (IHs). Very few cases of propranolol-resistant IH (PRIH) are mentioned in the literature.To describe the characteristics of PRIHs.A national, multicentre, retrospective, observational study was conducted from February 2011 to December 2011. All patients with PRIH evaluated by the members of the Groupe de Recherche Clinique en Dermatologie Pédiatrique from 1 January 2007 to 1 December 2011 were eligible.Among 1130 patients treated with propranolol for infantile haemangioma, 10 (0.9%) had PRIHs. Haemangioma propranolol resistance was observed at all ages during early childhood and at any proliferation stage.PRIH is a rare phenomenon that raises questions and merits further investigation.
Toxic shock syndrome. Evidence of a broad clinical spectrum
Authors: R. W. Tofte
Journal: JAMA (1981)

We evaluated various clinical and laboratory manifestations of toxic shock syndrome (TSS) in 17 menstruating females to define the spectrum of illness. Ten women had definite TSS, while seven who satisfied modified case definition criteria had probable TSS. Patients with definite TSS were younger, and symptoms developed later after onset of menstruation than in those with probable TSS. Overall, 16 (94%) had a rash with subsequent desquamation; 15 (88%), myalgias and orthostatic dizziness; 11 (79%), temperature of 38.9 °C or higher; 13 (76%), vomiting; 11 (65%), diarrhea; and 7 (54%), hypotension. All patients survived, and acute respiratory or oliguric renal failure possibly related to the absence of shock did not develop in any of them. None had a recurrent episode of TSS after treatment with an antistaphylococcal antibiotic, discontinuing tampon use, or both. Early recognition and treatment of less severely ill women may obviate potentially serious or fatal recurrences of TSS. (<i>JAMA</i>1981;246:2163-2167)
CNS Effects of Mitral Commissurotomy
Authors: Charlyne T. Herbert
Journal: JAMA (1964)

<h3>To the Editor:—</h3> We feel that we were very careful in our experiment and did not need to compare control groups with our experimental group. We do not believe it has been established that the tests definitely have a<i>practice effect</i>. Drs. Klein and Pollack mention their study on psychiatric patients using chlorpromazine. We know of no similarity between the effects of the drug chlorpromazine and the possible effects of blocking, or disturbing directly, circulation of blood to the brain. For these reasons, we do not feel that their point of view applies to our study.
The AMA and Torture
Authors: Howard S. Rubenstein
Journal: JAMA (1986)

To the Editor.—  The editorial, Toward the Prevention of Torture, by Dr Lundberg and Ms Knoll1has confounded the appropriate condemnation of physician participation in torture with the inappropriate defense of  quasi-historical, quasi-scientific religious article published in  major medical and scientific journal.2  The editorial says that the article was published, in part, because the editor considered it a pathological analysis (apparently no pun intended). This explanation lacks credibility because the article was by no means analytic (it was, if anything, synthetic) and because no amount of history, even when it is factual, can take the place of an authentic autopsy3—a position the editor himself has championed in the past.4Had he said that he published the article because it supported his religious beliefs, he would at least have had credibility.  In the editorial, the death of Jesus was placed in juxtaposition with physician participation
Leaky severe combined immunodeficiency and aberrant DNA rearrangements due to a hypomorphic RAG1 mutation
Authors: William Giblin, Monalisa Chatterji, Gerwin Westfield, Tehmina Masud, Brian Theisen, Hwei-Ling Cheng, Jeffrey DeVido, Frederick W. Alt, David O. Ferguson, David G. Schatz, JoAnn Sekiguchi
Journal: Blood (2009)
The Metabolic Theory of Pulmonary Arterial Hypertension
Authors: Roxane Paulin, Evangelos D. Michelakis
Journal: Circulation Research (2014)

Numerous molecular abnormalities have been described in pulmonary arterial hypertension (PAH), complicating the translation of candidate therapies to patients because, typically, 1 treatment addresses only 1 abnormality. The realization that in addition to pulmonary artery vascular cells, other tissues and cells are involved in the syndrome of PAH (eg, immune cells, right ventricular cardiomyocytes, skeletal muscle) further complicates the identification of optimal therapeutic targets. Here, we describe a metabolic theory that proposes that many apparently unrelated molecular abnormalities in PAH do have a common denominator; they either cause or promote a mitochondrial suppression (inhibition of glucose oxidation) in pulmonary vascular cells; in turn, the signaling downstream from this mitochondrial suppression can also explain numerous molecular events previously not connected. This integration of signals upstream and downstream of mitochondria has similarities to cancer and can explain many features of the PAH vascular phenotype, including proliferation and apoptosis resistance. This suppression of glucose oxidation (with secondary upregulation of glycolysis) also underlies the abnormalities in extrapulmonary tissues, suggesting a global metabolic disturbance. The metabolic theory places mitochondria at the center stage for our understanding of PAH pathogenesis and for the development of novel diagnostic and therapeutic tools. Current PAH therapies are each addressing 1 abnormality (eg, upregulation of endothelin-1) and were not developed specifically for PAH but for systemic vascular diseases. Compared with the available therapies, mitochondria-targeting therapies have the advantage of addressing multiple molecular abnormalities simultaneously (thus being potentially more effective) and achieving higher specificity because they address PAH-specific biology.
The t(7;11)(p15;p15) translocation in acute myeloid leukaemia fuses the genes for nucleoporin NUP96 and class I homeoprotein HOXA9
Authors: Julian Borrow, Amanda M. Shearman, Vincent P. Stanton, Reinhard Becher, Tucker Collins, Amy J. Williams, Ian Dubé, Fay Katz, Yok L. Kwong, Christine Morris, Kazuma Ohyashiki, Keisuke Toyama, Janet Rowley, David E. Housman
Journal: Nature Genetics (1996)
BELL'S PALSY
Authors: Harold Stevens
Journal: JAMA (1960)

<h3>To the Editor:—</h3> Dr. David Cohen's breezy essay inThe Journal, Aug. 6, page 1563, entitled "Bell's Palsy—a Medical Emergency," deserves a more receptive audience than subscribers toThe Journal. Science fiction readers might appreciate his picturesque notions more than the jaded A. M. A. members. The reader is grandly informed that "an eventful revolution has occurred in the management of Bell's palsy,... yet generations of practitioners have treated Bell's palsy as a condition demanding no immediate active measures, because they did not understand its pathogenesis." After a series of<i>non sequiturs</i>and unfounded speculations, the author urges a vigorous therapeutic attack which could leave a trail of iatrogenic cripples from here to old Olympus' towering tops. And all this for a benign, self-limiting affliction from which about 90% of the patients recover completely. In the experience of most neurologists, the remainder have only minor sequellae. Severe residuals are rare.
RAC Conditionally Approves Lung Cancer Gene Therapy
Authors: S. Jenks
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article RAC Conditionally Approves Lung Cancer Gene Therapy Get access Susan Jenks Susan Jenks Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 13, 6 July 1994, Pages 964–965, https://doi.org/10.1093/jnci/86.13.964 Published: 06 July 1994
Ethical Problems in Human Experimentation
Authors: Paul A. Freund
Journal: New England Journal of Medicine (1965)

I HAVE asked myself what a mere lawyer can contribute to a discussion of the ethics of medical experimentation. I feel like the hapless first-year law student in Professor "Bull" Warren's class to whom, as he was floundering, the Bull said, "You are in very shallow water, but you are sinking fast!"If you expect an exposition of rules of law regarding medical experiments, I am afraid you will be sorely disappointed, for this is not an area where the law has crystallized into firm, neat rules. To look for such rules would be to emulate the figures of the . . .
A prospective randomised multicentre study comparing continuous and intermittent treatment with celecoxib in patients with osteoarthritis of the knee or hip
Authors: F P Luyten, P Geusens, M Malaise, L De Clerck, R Westhovens, F Raeman, D Vander Mijnsbrugge, L Mathy, J P Hauzeur, F De Keyser, F Van den Bosch
Journal: Annals of the Rheumatic Diseases (2006)

To compare the effects of continuous and intermittent celecoxib treatment in patients with knee or hip osteoarthritis in flare.In this 24-week, prospective, randomised, double-blind, placebo-controlled study, patients were randomly assigned to receive continuous (n = 62) or intermittent (n = 61) treatment with celecoxib 200 mg once daily. The primary efficacy end point was the area under the curve (AUC) of the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total scores between baseline and week 24 divided by the time interval. Secondary end points included the percentage of days with intake of the flare drug, the AUC of the change in the WOMAC total scores, the mean change from baseline in the WOMAC scores, and the patient's and physician's global assessment of osteoarthritis.There were no significant differences between patients randomised to continuous or intermittent treatment in the primary end point or most of the secondary end points, although a consistent trend supporting continuous treatment was observed. The percentage of days with intake of the flare drug was significantly lower (p = 0.031) in the group receiving continuous versus intermittent celecoxib. Both treatment regimens were well tolerated.The results of this pilot study indicate a potential clinical difference between continuous and intermittent treatment with celecoxib, and may be useful in designing future trials. A larger trial on both efficacy and safety outcomes is required for conclusive evidence in favour of either continuous or intermittent treatment.
ACP1 genotype, glutathione reductase activity, and riboflavin uptake affect cardiovascular risk in the obese
Authors: Nadja Apelt, Alda Pereira da Silva, Joana Ferreira, Irina Alho, Cristina Monteiro, Cláudia Marinho, Pedro Teixeira, Luís Sardinha, Ma José Laires, Mário Rui Mascarenhas, Manuel Pires Bicho
Journal: Metabolism (2009)
The acute-phase response in (NZB X NZW)F1 and MRL/l MICE.
Authors: C Rordorf, H P Schnebli, M L Baltz, G A Tennent, M B Pepys
Journal: The Journal of Experimental Medicine (1982)

The acute-phase plasma protein response to disease activity in murine models of autoimmune lupus-like disease was investigated by measurement of the concentration of serum amyloid P component (SAP) in NZB X W and MRL/l mice. The levels of SAP, which is a major acute-phase protein in mice, did not rise at all in response to progression of disease in NZB X W mice between the ages of 1 and 9 mo. This resembles the behavior of acute-phase proteins such as C-reactive protein and serum amyloid A protein in human systemic lupus erythematosus, and just as in human lupus, where the occurrence of intercurrent microbial infection can stimulate an acute-phase response, so injection of bacterial lipopolysaccharide or casein into the NZB X W mice stimulated "normal" acute-phase SAP production. In marked contrast, MRL/l mice developed greatly increased levels of SAP, which correlated closely with progression of their pathology as they aged. The disease profile of the MRL/l strain includes rheumatoid factors and spontaneous polyarthritis and their SAP response resembles the behavior of acute phase proteins in human rheumatoid arthritis. Different patterns of acute-phase response in different autoimmune disorders may thus be a reflection of the genetic predisposition to particular diseases and/or contribute to their pathogenesis. The existence of animal counterparts for the various clinical patterns of human acute-phase protein production will assist in experimental investigation of the underlying mechanisms and of the biological role of the acute-phase response.
1049-104 Correlation between brain natriuretic peptide and cardiopulmonary exercise test parameters in patients with chronic heart failure
Authors: Angela Beatrice Scardovi, Nadia Aspromonte, Claudio Coletta, Elena Cerquetani, Mauro Romano, Tiziana Di Giacomo, Manuela Greggi, Vincenzo Ceci
Journal: Journal of the American College of Cardiology (2004)
Cytolysis by Ca-permeable transmembrane channels. Pore formation causes extensive DNA degradation and cell lysis.
Authors: A Hameed, K J Olsen, M K Lee, M G Lichtenheld, E R Podack
Journal: The Journal of Experimental Medicine (1989)

This study investigates the effect of the purified membrane pore formers, staphylococcal alpha-toxin and CTL perforin, on target cell lysis as measured by 51Cr release and on nuclear damage as measured by DNA degradation and 125IUdR release. Both pore formers cause dose-dependent cell lysis, which is accompanied by DNA release. The ratio of DNA/Cr release depends on the nature of target cell and shows the same pattern as the ratio of release of the two markers reported for CTL-mediated lysis of the same targets. DNA degradation is dependent on the presence of intracellular Ca in the target cell and is totally blocked if Ca is chelated by Quin 2 intracellularly and EGTA extracellularly. DNA degradation, in addition, is inhibited by the lysosomotropic agents NH4Cl, chloroquine, and monensin. rTNF doubles the degree of DNA degradation mediated by alpha-toxin in 3-h assays. We conclude that pore formers alone can mediate DNA degradation. In addition, they may promote the uptake of other factors and thereby accelerate their time course of action. DNA degradation by pore formers requires active target participation in a pathway that is dependent on intracellular Ca and lysosomes. These aspects of target lysis resemble CTL- and NK cell-mediated cytolysis.
Heart Transplantation in Man
Authors: James D. Hardy, Carlos M. Chavez, Fred D. Kurrus, William A. Neely, Sadan Eraslan, M. Don Turner, Leonard W. Fabian, Thaddeus D. Labecki
Journal: JAMA (1964)

HEART TRANSPLANTATION has interested many investigators.<sup>1-5</sup>Studies of related problems were begun in our laboratory in 1956. Webb and his associates studied such factors as practical methods for homologous cardiac transplantation,<sup>6</sup>cardiopulmonary transplantation,<sup>7-8</sup>restoration of function of the refrigerated heart,<sup>9</sup>and cardiac metabolism as influenced by ischemia and refrigeration.<sup>10</sup>The operative mortality was high, but extended survival of some dogs with orthotopic homotransplants was achieved. Collateral studies were conducted by other members of the department.<sup>11-14</sup>Thus, in the spring of 1963, Webb and the senior author (J.D.H. ) considered that the laboratory and clinical heart work justified a planned approach directed toward eventual heart transplantation in man. This objective, a natural outgrowth of transplantation research, was cleared with the administrative officials of the University Medical Center. It remained for us to evaluate further the methods available for preservation of the heart during its transplantation. While
GONOCOCCAL BACTEREMIA IN A WOMAN, WITH APPARENT CURE BY SURGICAL INTERVENTION
Authors: GEORGE W. WHEELER
Journal: JAMA (1930)

The case described in this article was one of intermittent gonococcal bacteremia in a woman, in which positive cultures were obtained from the genital organs (cervix, uterine cavity and tubes) without any evidence, either gross or microscopic, of a local acute inflammatory reaction. A thorough search of the literature failed to reveal a similar case treated surgically. In the majority of the cases in the literature, the bacteremia had followed an acute gonorrhea. The treatment of this case by surgical means apparently opens up a new field in the therapy of this disease. The history of the case in detail is as follows: <h3>REPORT OF CASE</h3> N. H., a woman, aged 19, single, born in the United States and employed as a bottle filler, was admitted to the New York Hospital, first medical division,<sup>1</sup>June 6, 1928. Her chief complaints were of pains in the left arm and left
Slaging of Sézary syndrome with somatostatin receptor scintigraphy
Authors: F. Heule, P. M. Vanhagen, J. J. M. van
           Dongen, E. P. Krenning, J. C. Reubi, T. van
           Joost
Journal: British Journal of Dermatology (1996)

Journal Article Slaging of Sézary syndrome with somatostatin receptor scintigraphy Get access F. Heule, F. Heule Department of Dermato‐Venereology, University Hospital Rotterdam‐Dijkzigt and Erasmus University. 3015GD Rotterdam, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar P. M. Vanhagen, P. M. Vanhagen Department of Internal Medicine III, University Hospital Rotterdam‐Dijkzigt and Erasmus University, 3015GD Rotterdam, the NetherlandsDepartment of Immunology, University Hospital Rotterdam‐Dijkzigt and Erasmus University, 3015GD Rotterdam, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar J. J. M. van Dongen, J. J. M. van Dongen Department of Immunology, University Hospital Rotterdam‐Dijkzigt and Erasmus University, 3015GD Rotterdam, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar E. P. Krenning, E. P. Krenning Department of Nuclear Medicine, University Hospital Rotterdam‐Dijkzigt and Erasmus University, 3015GD Rotterdam, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar J. C. Reubi, J. C. Reubi Department of Institute of Pathology, University of Berne, Switzerland Search for other works by this author on: Oxford Academic Google Scholar T. van Joost T. van Joost Department of Dermato‐Venereology, University Hospital Rotterdam‐Dijkzigt and Erasmus University. 3015GD Rotterdam, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 134, Issue 1, 1 January 1996, Pages 178–179, https://doi.org/10.1111/j.1365-2133.1996.tb07864.x Published: 01 January 1996