tbuckley/cabot-search huggingface dataset:
AB0830-HPR Feelings of competence and relatedness during physical activity are related to well-being in rheumatoid arthritis patients: preliminary findings from a randomized control trial
Authors: P. C. Rouse, J. L. Duda, J. J. Veldhuijzen Van Zanten, G. S. Metsios, N. Ntoumanis, C.-A. Yu, G. D. Kitas
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic inflammatory disease that causes joint pain, swelling and stiffness with eventual structural damage leading to physical dysfunction. Consequently, people with RA tend to experience fatigue and psychological distress. As proposed by Self-determination Theory (SDT), feelings of ownership, competence and relatedness (basic human psychological needs) during physical activity (PA) are predicted to alleviate such disease-related symptoms and improve psychological well-being in RA patients. <h3>Objectives</h3> To examine whether a Self-determination Theory-based intervention fosters basic need satisfaction. In addition, to examine the relationships between need satisfaction and indicators of psychological well-being and disease related symptoms (i.e., fatigue, depression and subjective vitality) in patients with RA following a 3 month exercise programme. <h3>Methods</h3> A RCT compared two 3 month exercise programmes. The control arm participants received a standard exercise referral programme. Patients in the experimental arm received an additional psychological intervention that aimed to foster basic need satisfaction through contacts with a SDT trained PA advisor. Participants completed the following validated measures at the end of the 3 month exercise programme; Psychological Need Satisfaction in Exercise Scale, Multidimensional Assessment of Fatigue Scale, Hospital Anxiety and Depressions Scales, and Subjective Vitality Scale. <h3>Results</h3> Preliminary analyses (<i>N =</i> 41 patients; <i>M</i>age = 55.4 yrs) indicated that the intervention arm patients (<i>N</i> = 22) reported significantly greater competence need satisfaction [<i>F</i> (1,39) = 6.9, <i>p =</i> .01] than the control arm. Differences between arms for autonomy [<i>F</i> (1,39) = 3.63, <i>p =</i> .06] and relatedness [<i>F</i> (1,39) = .88, <i>p =</i> .36] favoured the intervention. Pearson correlation coefficients from all data revealed feelings of competence and relatedness after the exercise programme were significantly and negatively related to depressive symptoms (<i>r =</i> -.43, <i>p</i> = .006 and <i>r =</i> -.39, <i>p</i> = .02 respectively). Competence also demonstrated a significant positive relationship with subjective vitality (<i>r =</i> .42, <i>p</i> = .01) and a negative relationship with fatigue (<i>r =</i> -.49, <i>p</i> = .002) at the end of the 3 month exercise programme. <h3>Conclusions</h3> Results suggest that a SDT-grounded PA intervention promotes need satisfaction during exercise. In addition, need satisfaction is associated with reductions in fatigue and enhancements in psychological well-being in patients with RA. Subsequent work will examine follow-up effects at 6 and 12 months. <h3>Disclosure of Interest</h3> None Declared
Rosiglitazone in the UK: down but not out
Authors: Ike Iheanacho
Journal: BMJ (2010)

Go to the website of the Medicines and Healthcare products Regulatory Agency (MHRA; www.mhra.gov.uk) and you can find a statement released on 3 March 2010 about the drug rosiglitazone (Avandia). It’s essentially a brief summary of the view of the agency, and that of the European Medicines Agency (EMEA), on the safety of this diabetes medicine. Its presence and content, though, are a bit odd. The message is that EMEA completed a thorough review of the safety of the thiazolidinediones—the class from which the drug comes—in 2007, concluding that “the balance of risks and benefits of rosiglitazone remain favourable in its licensed indications.” Why does this conclusion need restating two-and-a-half years later?

First, a bit of background: rosiglitazone has been licensed in the European Union and marketed in the UK since July 2000. The licensed indications at launch included combination treatment …
Outbreak in Bristol of Conjunctivitis Caused by Adenovirus Type 8, and its Epidemiology and Control
Authors: D. L. Barnard, J. C. D. Hart, V. J. Marmion, S. K. R. Clarke
Journal: BMJ (1973)

In an investigation of an outbreak of adenovirus type 8 infection involving over 40 people it was found that the infection spread initially within the eye hospital, but subsequently involved several family contacts and two local hospitals for mentally subnormal patients. Presumptive diagnosis should be possible before subepithelial opacities have developed provided an adequate history is taken, and had that been done in this outbreak it is reasonable to suppose that many cases could have been prevented.
Evidence of a role for mesothelial cell-derived interleukin 8 in the pathogenesis of asbestos-induced pleurisy in rabbits.
Authors: A M Boylan, C Rüegg, K J Kim, C A Hébert, J M Hoeffel, R Pytela, D Sheppard, I M Goldstein, V C Broaddus
Journal: Journal of Clinical Investigation (1992)

Although acute asbestos-induced pleurisy is characterized by an influx of neutrophils, the identity of the factors that attract these cells to the pleural space and the source of the factors are unknown. We found that instillation of crocidolite asbestos into the pleural space of rabbits led to the appearance in pleural liquid of chemotactic activity for neutrophils, and that this chemotactic activity was inhibited significantly by a neutralizing antibody to human interleukin 8 (IL-8). Cultured rabbit pleural mesothelial cells incubated with crocidolite asbestos also released chemotactic activity for neutrophils, which was inhibited significantly by the anti-IL-8 antibody. To determine whether rabbit pleural mesothelial cells synthesize IL-8, we generated a probe for rabbit IL-8 mRNA by amplifying cDNA prepared from stimulated pleural mesothelial cells using the polymerase chain reaction (PCR) and primers based on homologous sequences in human and sheep IL-8 cDNAs. Homology-based PCR yielded a single cDNA fragment with a nucleotide sequence 88% identical to that of a corresponding region of human IL-8 cDNA. With the radiolabeled PCR product as a probe, we demonstrated rapid induction of IL-8 mRNA expression in pleural mesothelial cells exposed to asbestos. As expected, tumor necrosis factor-alpha also led to the appearance of IL-8 in the rabbit pleural space and stimulated cultured pleural mesothelial cells to synthesize and release IL-8. We conclude that asbestos directly stimulates pleural mesothelial cells to synthesize IL-8 and that mesothelial cell-derived IL-8 may play an important role in mediating asbestos-induced pleural inflammation.
The transcriptional regulators Id2 and Id3 control the formation of distinct memory CD8+ T cell subsets
Authors: Cliff Y Yang, J Adam Best, Jamie Knell, Edward Yang, Alison D Sheridan, Adam K Jesionek, Haiyan S Li, Richard R Rivera, Kristin Camfield Lind, Louise M D'Cruz, Stephanie S Watowich, Cornelis Murre, Ananda W Goldrath
Journal: Nature Immunology (2011)
Reimbursement for Unproven Therapies: The Case of Thermography
Authors: Thomas C. LaBorde
Journal: JAMA (1993)

<h3>To the Editor.</h3> —I feel compelled to comment on the misrepresentations and misinformation included in the article entitled "Court-Ordered Reimbursement for Unproven Medical Technology: Circumventing Technology Assessment" by Ferguson et al.<sup>1</sup>More important, the l Thermography is likened to Laetrile (amygdalin) and immunoaugmentive therapy as having "been assessed as not safe, not effective, or inadequately evaluated." Yet, thermography has been declared safe by the Food and Drug Administration (Victor Zafra, written communication, March 12,1982), considered as useful by the American Medical Association Council on Scientific Affairs<sup>2</sup>in the evaluation of certain neuromusculoskeletal conditions, and effective by the American Academy of Physical Medicine and Rehabilitation<sup>3</sup>in the evaluation of reflex sympathetic dystrophy. In contrast, similar support for Laetrile and immunoaugmentive therapy by organizations does not exist. Ferguson et al create the false perception that thermography is some type of unproven, fringe technology when in fact it is not.
Heart transplantation in children with congenital heart disease
Authors: Daphne T. Hsu, Jan M. Quaegebeur, Robert E. Michler, Craig R. Smith, Eric A. Rose, Maryanne R. Kichuk, Welton M. Gersony, Judith F. Douglas, Linda J. Addonizio
Journal: Journal of the American College of Cardiology (1995)

The aim of this study was to describe heart transplantation in children with congenital heart disease and to compare the results with those in children undergoing transplantation for other cardiac diseases. Reports describe decreased survival after heart transplantation in children with congenital heart disease compared with those with cardiomyopathy. However, transplantation is increasingly being considered in the surgical management of children with complex congenital heart disease. Present-day results from this group require reassessment. The diagnoses, previous operations and indications for transplantation were characterized in children with congenital heart disease. Pretransplant course, graft ischemia time, posttransplant survival and outcome (rejection frequency, infection rate, length of hospital stay) were compared with those in children undergoing transplantation for other reasons (n = 47). Thirty-seven children (mean [±SD] age 9 ± 6 years) with congenital heart disease underwent transplantation; 86% had undergone one or more previous operations. Repair of extracardiac defects at transplantation was necessary in 23 patients. Causes of death after transplantation were donor failure in two patients, surgical bleeding in two, pulmonary hemorrhage in one, infection in four, rejection in three and graft atherosclerosis in one. No difference in 1- and 5-year survival rates (70% vs. 77% and 64% vs. 65%, respectively), rejection frequency or length of hospital stay was seen between children with and without congenital heart disease. Cardiopulmonary bypass and donor ischemia time were significantly longer in patients with congenital heart disease. Serious infections were more common in children with than without congenital heart disease (13 of 37 vs. 6 of 47, respectively, p = 0.01). Despite the more complex cardiac surgery required at implantation and longer donor ischemic time, heart transplantation can be performed in children with complex congenital heart disease with success similar to that in patients with other cardiac diseases.
Vascular atrial natriuretic factor receptors in spontaneously hypertensive rats
Authors: E. L Schiffrin, A. Parent, J. S. Louis, J. Tremblay, R. Garcia, G. Thibault
Journal: Cardiovascular Research (1992)

Objective: The aim was to investigate vascular receptors for atrial natriuretic factor (ANF) in spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Wistar rats (WR) at different ages. Methods: Relaxation and guanylate cyclase responses of blood vessels to atrial natriuretic factor were investigated, as was the binding of 125 I-ANF to vascular membranes and ANF receptor subtypes, using sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) in reducing conditions, after solubilisation and irreversible binding of l25I-ANF. Results: Vascular relaxation responses of aorta showed an increased sensitivity to ANF in four week old SHR [pD2=8.9 (SEM 0.1) v 8.5(0.1) in WKY rats, p<0.05] while sensitivity was similar for the three strains at older ages. Production of cyclic GMP in mesenteric arteries in response to 100 nmol-litre-1 ANF was greater (p<0.05) in SHR than in WKY rats at four weeks of age, but was similar in older rats. The density of binding sites for ANF in mesenteric arteries, however, was lower in SHR at four weeks (p<0.01), and increased in older rats, becoming similar to that of normotensive rats at 12 weeks of age. Affinity of ANF sites was similar in all strains. The proportion of high and low molecular weight ANF binding peptides in solubilised blood vessel membranes on SDS-PAGE was similar in all strains except in four week old SHR, in which binding to the high molecular weight band (presumably the guanylate cyclase containing receptor) was increased relative to the low molecular weight band (non-cyclase-coupled receptor) in comparison to other strains and ages. Conclusions: Activity of guanylate cyclase in response to occupancy of ANF receptors may be increased in young SHR. Normal relaxation of blood vessels in response to ANF in older SHR could result in failure to counteract the increased vasoconstrictor activity present in these rats, which could play a role in the increase in blood pressure. Cardiovascular Research 1992;26:857–864
Beware extrapolation from ecological data
Authors: T. A. Hammad, A. D. Mosholder
Journal: BMJ (2010)

Identification of an association between antidepressant drugs and suicidal thinking and behaviour in adolescents in 2004, and the regulatory warnings that followed, sparked a debate on the potential for discouraging appropriate use of antidepressant drugs,1 2 3 with the unintended consequence of eventually exposing more patients to the suicide risk of untreated depression.4 These concerns were strengthened by …
Low Prevalence of <i>HNF1A</i> Mutations After Molecular Screening of Multiple MODY Genes in 58 Italian Families Recruited in the Pediatric or Adult Diabetes Clinic From a Single Italian Hospital
Authors: Maurizio Delvecchio, Ornella Ludovico, Claudia Menzaghi, Rosa Di Paola, Leopoldo Zelante, Antonella Marucci, Valeria Grasso, Vincenzo Trischitta, Massimo Carella, Fabrizio Barbetti
Journal: Diabetes Care (2014)

Maturity-onset diabetes of the young (MODY; MIM# 606391) is a genetically and clinically heterogeneous form of diabetes, accounting for 1–2% of all diabetes cases (1). MODY is characterized by mild hyperglycemia or overt diabetes usually detected in three consecutive generations, with onset before the age of 25 years and absence of type 1 diabetes autoantibodies. Among the thirteen MODY genes identified, two subtypes, GCK -MODY and HNF1A -MODY, account for most of cases (1). The prevalence of GCK -MODY has been reported higher in Southern Europe (2), while HNF1A -MODY is the most common MODY subtype in Northern Europe (3). This difference might be attributable to the clinical setting in which genetic screening is performed, especially when pediatric and adult diabetes clinics are distinct entities. We addressed this issue by investigating MODY patients identified in the pediatric or in the adult diabetes clinics of the same research-based …
Effect of enzyme digestion on the permeability barrier in keratinizing and non-keratinizing epithelia
Authors: C.A. SQUIER
Journal: British Journal of Dermatology (1984)

In an attempt to characterize the permeability barrier of the oral mucosa and skin, small pieces of keratinized and non‐keratinized oral epithelia and epidermis were digested with specific enzymes. These enzymes were selected for their effect on carbohydrate‐protein, or carbohydrate‐lipid compounds and phospholipids. The effect of the enzyme treatment was monitored by exposing the digested tissue to horseradish peroxidase. Electron microscopic examination of tissue treated with phospholipases revealed considerable damage to membrane structures but not to the integrity of the permeability barrier. Hyaluronidase and neuraminidase caused less structural damage but did not impair barrier function; this was only seen after treatment with chondroitinase ABC. This enzyme may degrade certain of the polar molecules thought to be necessary to stabilize the neutral lipid bilayers of the intercellular barrier and thus disrupt its barrier properties.
Soluble Intercellular Adhesion Molecule-1 (sICAM-1) and Interferon-Gamma in Bronchoalveolar Lavage Fluid from Children with Airway Diseases
Authors: CHRISTOPHE MARGUET, TARANEH P. DEAN, JOHN O. WARNER
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

We have previously described that in bronchoalveolar lavage fluid (BALF), eosinophils characterize asthma and neutrophils are more prominent in infantile wheeze. In this study, we hypothesized that intercellular adhesion molecule 1 (ICAM-1) and interferon-gamma (IFN-gamma) would have a role in promoting migration of both cell types into the airway. To investigate this, we measured soluble (s) ICAM-1 in 68 BALFs from infants and young children with various respiratory problems. Children with asthma were characterized by significantly raised sICAM compared with those with chronic cough without wheeze (p = 0.05) or control subjects with no lower airway pathology (p = 0.045). The levels correlated with disease severity (evaluated with a symptom score) and with lymphocyte numbers. IFN-gamma levels were also raised in children with asthma compared with those with chronic cough (p = 0.05), but there was no correlation with disease activity. Infantile wheeze was characterized by a linear correlation between sICAM-1 and IFN-gamma (r = 0.55; p = 0.002). sICAM-1 levels in infantile wheeze correlated with the severity of the disease and lymphocyte numbers. IFN-gamma levels were elevated in the wheezers treated with inhaled steroids compared with untreated infants (p = 0.03). Although sICAM-1 levels were increased in those with severe cough, no characteristic inflammatory profile was found in the group with chronic cough. Our study suggests that ICAM-1 and IFN-gamma play a role in the activity of the inflammatory process in asthma in childhood and possibly in some infant wheezers, in whom IFN-gamma may be one of the factors increasing the expression of ICAM-1. The role of IFN-gamma, a T helper-1 cytokine, in children with asthma remains to be fully understood.
Abstract 5764: Opposing roles of the COX-2 pathway receptors EP1 and EP4 in metastasis and contribution to disparities
Authors: Amy M. Fulton, Xinrong Ma, Namita Kundu, Olga Ioffe, Olga Goloubeva, Raymond Konger, Claudia Baquet, Jocelyn Reader
Journal: Cancer Research (2010)

Abstract Cyclooxygenase-2 is highly expressed in breast and other malignancies and contributes to a poor prognosis. Our goal is to identify novel approaches to target the COX-2 pathway in order to reduce metastatic potential and improve survival. The primary COX-2 product, prostaglandin E2, exerts cellular effects by binding to four distinct G-protein-coupled receptors designated EP1, EP2, EP3 and EP4. Using pharmacologic and genetic approaches and a preclinical model of metastatic, triple-negative (ER, PR, Her-2 negative) breast cancer, we have examined the role of EP4 and EP1 in malignant behavior. Inhibition of EP4 receptor signaling with selective EP4 antagonists limits breast cancer metastasis to the same degree as achieved with a COX-2 inhibitor. Likewise, gene silencing of EP4 with specific shRNA also limits metastatic capacity by a mechanism involving Natural Killer cells. Conversely, blocking EP1 with either pharmacologic antagonists or genetic ablation promotes tumor metastasis. The expansion of mammary-gland implanted tumors was not affected by changes in EP1 expression levels, indicating that EP1 functions selectively to suppress metastasis. In primary breast tumors or cell lines, EP1 protein is detected both on the plasma membrane and in the nucleus. Immunohistochemical examination of a tissue array containing primary breast tumors reveals that the absence of nuclear EP1 in malignant cells is associated with significantly worse long term survival. Levels of cytoplasmic EP1 were not correlated with differences in outcome. Interestingly, breast tumors from African-American women express significantly less EP1 mRNA than tumors from Caucasian women, suggesting that low EP1 could contribute to worse outcome in AA women. These data support the hypothesis that EP1 acts as a metastasis suppressor but EP4 promotes metastasis and that shifting the balance towards activation of EP1 could be a novel approach to reduce breast cancer metastasis and reduce disparities in outcome. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5764.
Eosinophil pathogenicity mechanisms and therapeutics in neuromyelitis optica
Authors: Hua Zhang, A.S. Verkman
Journal: Journal of Clinical Investigation (2013)

Eosinophils are abundant in inflammatory demyelinating lesions in neuromyelitis optica (NMO). We used cell culture, ex vivo spinal cord slices, and in vivo mouse models of NMO to investigate the role of eosinophils in NMO pathogenesis and the therapeutic potential of eosinophil inhibitors. Eosinophils cultured from mouse bone marrow produced antibody-dependent cell-mediated cytotoxicity (ADCC) in cell cultures expressing aquaporin-4 in the presence of NMO autoantibody (NMO-IgG). In the presence of complement, eosinophils greatly increased cell killing by a complement-dependent cell-mediated cytotoxicity (CDCC) mechanism. NMO pathology was produced in NMO-IgG–treated spinal cord slice cultures by inclusion of eosinophils or their granule toxins. The second-generation antihistamines cetirizine and ketotifen, which have eosinophil-stabilizing actions, greatly reduced NMO-IgG/eosinophil–dependent cytotoxicity and NMO pathology. In live mice, demyelinating NMO lesions produced by continuous intracerebral injection of NMO-IgG and complement showed marked eosinophil infiltration. Lesion severity was increased in transgenic hypereosinophilic mice. Lesion severity was reduced in mice made hypoeosinophilic by anti–IL-5 antibody or by gene deletion, and in normal mice receiving cetirizine orally. Our results implicate the involvement of eosinophils in NMO pathogenesis by ADCC and CDCC mechanisms and suggest the therapeutic utility of approved eosinophil-stabilizing drugs.
Mast Cell Degranulation, Hepatic Glycogen Depletion, and Hyperglycemia in Compound 48/80 or Pilocarpine-Treated Rats
Authors: Ruth V. W. Dimlich, Samuel F. Townsend, Frank D. Reilly
Journal: Hepatology (2007)

Blood glucose, hepatic glycogen, and mean carotid blood pressure were determined in anesthetized Sprague-Dawley rats receiving an i.v. infusion of Compound 48/80, pilocarpine, or Ringer's solution as a control. Histochemical determinations of the integrity and number of hepatic mast cells and hepatic glycogen content also were performed at the light microscopic level, and the results compared to those from rats whose livers were treated topically with each of these compounds. Compound 48/80 produced a marked decrease in mean carotid blood pressure, while pilocarpine produced a slight increase in this parameter. Injection of either Compound 48/80 or pilocarpine provoked an increase in blood glucose and a decrease in hepatic glycogen as well as in the number of hepatic mast cells. Infusion produced no change in glycogen within cardiac or skeletal muscle. The application of Compound 48/80 or pilocarpine to the surface of the liver evoked no alteration in the histochemical appearance of hepatic glycogen. However, the topical application of these substances elicited a significant decrease in the number of Falck-Hillarp-positive hepatic mast cells. Blood glucose was higher in rats that survived 30 min or more after injection of either compound. However, glucose levels were significantly higher in rats that survived 30 min or longer following Compound 48/80 infusion than in those surviving pilocarpine treatment. These results provide evidence that the i.v. injection of Compound 48/80 or pilocarpine causes: (a) hyperglycemia; (b) depletion of hepatic glycogen, and (c) a concomitant decrease in the number of Falck-Hillarp-positive mast cells. The degree of hyperglycemia appeared to correlate with the length of survival of the rats and to be independent of the hyper- or hypotensive effects elicited by either chemical.