tbuckley/cabot-search huggingface dataset:
Percutaneous Left Atrial Appendage Transcatheter Occlusion (PLAATO System) to Prevent Stroke in High-Risk Patients With Non-Rheumatic Atrial Fibrillation
Authors: Stefan H. Ostermayer, Mark Reisman, Paul H. Kramer, Ray V. Matthews, William A. Gray, Peter C. Block, Heyder Omran, Antonio L. Bartorelli, Paolo Della Bella, Carlo Di Mario, Carlo Pappone, Paul N. Casale, Jeffrey W. Moses, Athena Poppas, David O. Williams, Bernhard Meier, Allan Skanes, Paul S. Teirstein, Michael D. Lesh, Toshiko Nakai, Yves Bayard, Kai Billinger, Thomas Trepels, Ulrike Krumsdorf, Horst Sievert
Journal: Journal of the American College of Cardiology (2005)
PRE-HOSPITAL NOTIFICATION OF STEMI (PNS): COLLABORATION BETWEEN THE VICTORIAN CARDIAC CLINICAL NETWORK, AMBULANCE VICTORIA AND PARTICIPATING HOSPITALS
Authors: Gishel New, Hatish Jangwal, Hella Parker, Louise Roberts, Bill Barger, Karen Smith, Geoffery Toogood, Kean Soon, Nicholas Cox, Yuvi Malaiapan, William van Gaal, Jenny Wilson, Robert Whitbourn, Andrew Maclsaac, Leeanne Grigg, Alexander Black, Archer Broughton, H. M. Omar Farouque, Karen Sanders, Ronald Dick, Esther Briganti, Jeffrey Lefkovits, Richard Harper
Journal: Journal of the American College of Cardiology (2013)
TCT-95 Outcomes of Transcatheter vs. Surgical Aortic Valve Replacement in Women: Insights from the Randomized PARTNER Trial
Authors: Mathew Williams, Susheel Kodali, Karin Humphries, Vuyisile Nkomo, Lars Svensson, Neil Weissman, David Cohen, Vinod Thourani, Michael Mack, E. Murat Tuzcu, Irene Hueter, Maria Alu, Ajay Kirtane, Martin Leon
Journal: Journal of the American College of Cardiology (2012)
A Study of Diffusion-Weighted Magnetic Resonance Imaging in Men with Untreated Localised Prostate Cancer on Active Surveillance
Authors: Nicholas J. van As, Nandita M. de Souza, Sophie F. Riches, Veronica A. Morgan, Sayid A. Sohaib, David P. Dearnaley, Chris C. Parker
Journal: European Urology (2008)
Advances in targeted therapy: safety of biological agents
Authors: E C Keystone
Journal: Annals of the Rheumatic Diseases (2003)

umour necrosis factor (TNF) antagonists have set a new therapeutic standard for rheumatoid arthritis (RA).The agents including infliximab (Remicade), etanercept (Enbrel), and adalimumab (Humira) have been shown to substantially improve the signs and symptoms, disability, and quality of life while significantly inhibiting joint damage in early and longstanding RA.As with any agent, safety issues in concert with efficacy determine a risk/benefit ratio and hence a position in the therapeutic algorithm.With TNF antagonists key safety considerations include (a) infection, both common and opportunistic; (b) cytopenias; (c) demyelinating disease; (d) lupus-like syndromes; (e) congestive heart failure (CHF) and malignancies, particularly lymphomas.In March 2003 the United States Federal Drug Administration (FDA) convened a meeting to update safety issues related to TNF antagonists, specifically focusing on solid tumours and lymphomas.Safety data from controlled clinical trials were presented for the three TNF antagonists with post-marketing safety data for etanercept and infliximab.All the data are available on the FDA website.The current review will focus on infection, CHF, and malignancy.Much of the information in this review was obtained from the FDA, Arthritis Adviser Committee, the National Databank for Rheumatic Disease (NDRD) of Dr Fred Wolfe, from data on file with Abbott Pharmaceuticals, Amgen Incorporated, and Centocor Incorporated.Safety data may be obtained from a variety of sources, including placebo controlled, randomised clinical trials, post-approval databases, particularly the USA FDA MedWatch spontaneous reporting programme, and long term registries such as the NDRD of Fred Wolfe as well as registries in Sweden and Germany and England.A number of factors significantly influence the interpretation of adverse event data.Within clinical trials issues of ascertainment bias in enrolling patients into trials, population homogeneity, lower comorbidities, restricted concomitant drugs, short trial duration, and a relatively small sample size may have substantial influences on the safety profile.Post-approval (post-marketing) adverse event reporting although influenced to a far lesser extent by population homogeneity, comorbidities, restricted concomitant drugs, duration of follow up, and sample size, still has significant limitations.Post-approval data are limited by substantial . . . . .
Arousal responses to added inspiratory resistance during REM and non-REM sleep in normal subjects.
Authors: M Gugger, S Bogershausen, L Schaffler
Journal: Thorax (1993)

BACKGROUND: Arousal in response to increased airflow resistance during sleep, especially rapid eye movement sleep (REM), could be an important protective mechanism against asphyxia. METHODS: The arousal response to the application of an external inspiratory resistance of 25 cm H2O/l/s was determined during REM and non-REM sleep in ten healthy men. RESULTS: The number of arousals occurring within two minutes of the load application was significantly higher during REM sleep than during either of the non-REM sleep stages 2 and 3/4, and was similar to that during stage 1. The proportion of arousals to non-arousals decreased significantly from stage 1 to stage 4. The mean time to arousal in REM was significantly shorter than in non-REM stages 1, 2 or 3/4 and increased significantly from stage 1 to stage 3/4. The duration of sleep (comparing the results of the first with the second half of the sleep period time) did not modify the arousal response in stages 2 and 3/4. CONCLUSIONS: The results show a significantly increased arousal response to an added inspiratory resistive load in REM sleep compared with non-REM sleep stages 2, 3 or 4 in normal men. In the context of previous studies these data could add support to the hypothesis that the decreased arousal response during REM sleep in patients with sleep apnoea might be due to an impairment of the normal "central processing" of this stimulus.
PTU-079 Prospective audit of readmission following emergency and elective cholecystectomy in a single health board
Authors: E J Barron, J P Blackmur, R McMurray, E M Harrison, T E Gillies, J Garden
Journal: Gut (2012)

<h3>Introduction</h3> Surgical outcome indicators, such as hospital stay, readmission and mortality rates, are increasingly being used to assess and compare hospital board performance and considerable variation exists between hospitals specifically in readmission rates. The aim of the study was to determine true readmission rates following cholecystectomy in a single large volume centre to determine whether readmission was potentially preventable. <h3>Methods</h3> All patients readmitted to one large teaching hospital surgical service within 28 days following elective or emergency cholecystectomy from September 2010 to June 2011 were audited prospectively. <h3>Results</h3> Of 979 cholecystectomies performed during the period, 57 (5.8%) patients were readmitted. 38 of the 57 (67%) readmissions followed emergency-admission with symptomatic gallstone disease and 51 of these (89.5%) had undergone a laparoscopic approach. 34/979 (3.5%) were considered to be secondary to demonstrable complications of surgery with the most common cause being retained stones (11). No patient presented with bile duct injury, and there were no deaths. Only 14 of the readmitted patients (25%) required intervention: one required sub-phrenic abscess drainage, nine endoscopic-retrograde-cholangiopancreatography and sphincterotomy (ERCP), two completion cholecystectomy, one laparoscopic assessment following ERCP for bile leak and one underwent hepatico-jejunostomy for definitive management of an irretrievable retained stone following ERCP and laparoscopic bile duct exploration. Of those readmitted, the most common cause of presentation was non-specific abdominal pain (15 (26.3%)) with no cause found. <h3>Conclusion</h3> Readmission rate in this large volume centre was low. Most patients readmitted following cholecystectomy have demonstrable surgically related complications but few require definitive surgical management. Further work is being conducted to define potential predictive factors for readmission. <h3>Competing interests</h3> None declared.
Immunologic properties of purified epidermal Langerhans cells. Distinct requirements for stimulation of unprimed and sensitized T lymphocytes.
Authors: K Inaba, G Schuler, M D Witmer, J Valinksy, B Atassi, R M Steinman
Journal: The Journal of Experimental Medicine (1986)

Langerhans cells (LC) are Ia+ leukocytes that account for less than 2% of the cells in murine epidermal isolates. We purified LC by cell sorting to study their capacity to stimulate antigen-specific responses from unprimed and sensitized T cells. Sorting was performed after 12 or 72 h of epidermal culture, since our earlier work had indicated that LC became immunologically active during that time interval. At 12 and 72 h, the LC were uniformly and equally rich in the Ia glycoproteins that are recognized by helper T cells. At both time points, LC were comparable in their capacity to stimulate sensitized helper T lymphocytes, and would cluster the T cells in an antigen-dependent fashion at 4 degrees C. However, 12-h LC did not sensitize T cells, as indicated by their inactivity in stimulating the primary MLR or antibody response, and they were unable to cluster T cells in an antigen-independent fashion at 37 degrees C. The latter properties were acquired during 72 h of culture. As a result, the function of 72-h LC fully resembled that of lymphoid dendritic cells. We propose that the maturation of stimulatory function within the dendritic cell lineage represents an important control point in the induction phase of cell-mediated immunity.
Improving Treatment of Depression Among Latinos With Diabetes Using Project Dulce and IMPACT
Authors: Todd P. Gilmer, Chris Walker, Elizabeth D. Johnson, Athena Philis-Tsimikas, Jürgen Unützer
Journal: Diabetes Care (2008)

To assess the feasibility and cost of integrating diabetes and depression care management in three community clinics serving a low-income and predominantly Spanish-speaking Latino population.We screened diabetes patients for depression, and for those with depressive symptoms, we provided depression care management. We assessed changes in depressive symptoms using the Patient Health Questionnaire-9 (PHQ-9), diabetes self-care activities (nutrition, exercise, and medication adherence), and costs.Thirty-three percent of patients with diabetes had symptoms of major depression. Among 99 patients completing the study, PHQ-9 scores declined by an average of 7.5 points from 14.8 to 7.3 (P < 0.001). Clients averaged 6.7 visits with the care manager during the study period. Costs of depression care management were estimated to be $512 per participant.Adding a depression care manager to an existing diabetes management team was effective at reducing depressive symptoms at a reasonable cost.
Reversing acute bronchoconstriction in asthma: the effect of bronchodilator tolerance after treatment with formoterol
Authors: S.L. Jones, J.O. Cowan, E.M. Flannery, R.J. Hancox, G.P. Herbison, D.R. Taylor
Journal: European Respiratory Journal (2001)

Continuous treatment with a short-acting β 2 ‐agonist can lead to reduced bronchodilator responsiveness during acute bronchoconstriction. This study evaluated bronchodilator tolerance to salbutamol following regular treatment with a long-acting β 2 ‐agonist, formoterol. The modifying effect of intravenous corticosteroid was also studied. Ten asthmatic subjects (using inhaled steroids) participated in a randomised, double-blind, placebo-controlled, cross-over study. Formoterol 12 μg b.i.d. or matching placebo was given for 10–14 days with &gt;2 weeks washout. Following each treatment, patients underwent a methacholine challenge to induce a fall in forced expired volume in one second (FEV 1 ) of at least 20%, then salbutamol 100 μg, 100 μg, and 200 μg was inhaled via a spacer at 5 min intervals, with a further 400 μg at 45 min. After a third single-blind formoterol treatment period, hydrocortisone 200 mg was given intravenously prior to salbutamol. Dose-response curves for change in FEV 1 with salbutamol were compared using analysis of covariance to take account ofmethacholine-induced changes in spirometry. Regular formoterol resulted in a significantly lower FEV 1 after salbutamol at each time point compared to placebo (p&lt;0.01). The area under the curves (AUCs) for 15 (AUC 0–15 ) and 45 (AUC 0–45 ) min were 28.8% and 29.5% lower following formoterol treatment (p&lt;0.001). Pretreatment with hydrocortisone had no significant modifying effect within 2 h of administration. It is concluded that significant tolerance to the bronchodilator effects of inhaled salbutamol occurs 36 h after stopping the regular administration of formoterol. This bronchodilator tolerance is evident in circumstances of acute bronchconstriction.
Lung angiotensin converting enzyme activity in chronically hypoxic rats.
Authors: J M Kay, P M Keane, K L Suyama, D Gauthier
Journal: Thorax (1985)

A study was carried out to test the hypothesis that the reduced lung angiotensin converting enzyme (ACE) activity which occurs in chronic hypoxia is related to the development of pulmonary hypertension rather than to hypoxia per se. Right ventricular mean systolic pressure (Prvs, mm Hg) and ACE activity (nmol/mg protein/min) in lung tissue homogenates were measured in seven groups of four rats placed in a hypobaric chamber (380 mm Hg; 51 kPa) for two to 24 days. Identical measurements were made on 11 groups of four rats, which were placed in the chamber for 24 days and then allowed to recover in room air for one to 153 days. After two days of hypoxia the mean Prvs (25.5 (SD 3.7] and the mean lung ACE activity (56 (4.6] did not differ significantly from control values. Exposure to hypoxia for four to 24 days caused a progressive increase in mean Prvs to 44.4 (5.9) and a progressive reduction in mean lung ACE activity to 34 (4.0). During recovery lung ACE activity increased and Prvs decreased, so that normal values were achieved by 15 and 56 days respectively. Decreased lung ACE activity may be related to haemodynamic factors associated with pulmonary hypertension rather than to hypoxia.
A multi-centre, randomised controlled trial of positive expiratory pressure mask therapy for inpatients with acute exacerbations of COPD and sputum expectoration
Authors: Christian Osadnik, Christine F. McDonald, Belinda R. Miller, Catherine Hill, Ben Tarrant, Ranjana Steward, Caroline Chao, Nicole Stodden, Cristino Oliveira, Nadia Gagliardi, Anne E. Holland
Journal: European Respiratory Journal (2013)

Background:  Positive expiratory pressure (PEP) is an airway clearance technique used to enhance sputum clearance during acute exacerbations of chronic obstructive pulmonary disease (AECOPDs). The impact of PEP therapy on clinically important outcomes during AECOPDs has not been established.    Aim:  To determine the effect of PEP therapy on symptoms, quality of life and future exacerbations in patients with AECOPDs.    Methods:  90 inpatients (58 male; mean age 68.6, FEV1 40.8% predicted) with AECOPDs and sputum expectoration were randomised to receive PEP therapy 3 times/day in addition to usual care, or usual care alone. Both groups underwent physical exercise. The Breathlessness, Cough and Sputum Scale (BCSS), St. George’s Respiratory Questionnaire (SGRQ), exacerbations, hospitalisations and BODE index (Body mass index, airflow Obstruction, Dyspnoea, Exercise tolerance) were measured at discharge, eight weeks and six months following discharge. Longitudinal data were analysed using linear mixed models.    Results:  There were no statistically significant between-group differences in BCSS scores (p = 0.98), SGRQ scores (p = 0.87), or incidence of exacerbations (p = 0.99) or hospitalisations (p = 0.36) at any time. The PEP group showed a more rapid improvement in dyspnoea (p = 0.01) and exercise tolerance (p = 0.052, ns) over the first eight weeks, however these benefits were not observed at six months.    Conclusion:  PEP therapy during AECOPDs does not affect important clinical outcomes at discharge or six months later. There does not appear to be a routine role for PEP therapy in the management of inpatients with AECOPDs.
Effectiveness of adenoidectomy in children with recurrent upper respiratory tract infections: open randomised controlled trial
Authors: M. T. A. van den Aardweg, C. W. B. Boonacker, M. M. Rovers, A. W. Hoes, A. G. M. Schilder
Journal: BMJ (2011)

<b>Objective</b> To assess the effectiveness of adenoidectomy in children with recurrent upper respiratory tract infections. <b>Design</b> Open randomised controlled trial. <b>Setting</b> 11 general hospitals and two academic centres. <b>Participants</b> 111 children aged 1-6 with recurrent upper respiratory tract infections selected for adenoidectomy. <b>Intervention</b> A strategy of immediate adenoidectomy with or without myringotomy or a strategy of initial watchful waiting. <b>Main</b><b>outcome</b><b>measure</b> Primary outcome measure: number of upper respiratory tract infections per person year calculated from data obtained during the total follow-up (maximum 24 months). Secondary outcome measures: days with upper respiratory tract infection per person year, middle ear complaints with fever in episodes and days, days with fever, prevalence of upper respiratory tract infections, and health related quality of life. <b>Results</b> During the median follow-up of 24 months, there were 7.91 episodes of upper respiratory tract infections per person year in the adenoidectomy group and 7.84 in the watchful waiting group (difference in incidence rate 0.07, 95% confidence interval −0.70 to 0.85). No relevant differences were found for days of upper respiratory tract infections and middle ear complaints with fever in episodes and days, nor for health related quality of life. The prevalence of upper respiratory tract infections decreased over time in both groups. Children in the adenoidectomy group had significantly more days with fever than the children in the watchful waiting group. Two children had complications related to surgery. <b>Conclusion</b> In children selected for adenoidectomy for recurrent upper respiratory tract infections, a strategy of immediate surgery confers no clinical benefits over a strategy of initial watchful waiting. <b>Trial registration</b> Dutch Trial Register NTR968: ISRCTN03720485.
Doctors' leaders back new guidance on using patients' records for research
Authors: A. O'Dowd
Journal: BMJ (2009)

Leading GP bodies have given their support to new guidance on how patients’ medical records should be used in medical research.

The guidance, published this week by the medical charity the Wellcome Trust, aims to make it clearer to GPs and researchers how they can ensure that medical records are used safely in research.

The report says that patients’ records in general practice are a unique source of information that can help medical researchers improve their understanding of disease, develop potential new treatments, and improve care.

Increasing use of electronic records should make it easier for researchers to use this information, but …
Expression of a mutant human fibrillin allele upon a normal human or murine genetic background recapitulates a Marfan cellular phenotype.
Authors: Z A Eldadah, T Brenn, H Furthmayr, H C Dietz
Journal: Journal of Clinical Investigation (1995)

The Marfan syndrome (MFS) is a connective tissue disorder inherited as an autosomal dominant trait and caused by mutations in the gene encoding fibrillin, a 350-kD glycoprotein that multimerizes to form extracellular microfibrils. It has been unclear whether disease results from a relative deficiency of wild-type fibrillin; from a dominant-negative effect, in which mutant fibrillin monomers disrupt the function of the wild-type protein encoded by the normal allele; or from a dynamic and variable interplay between these two pathogenetic mechanisms. We have now addressed this issue in a cell culture system. A mutant fibrillin allele from a patient with severe MFS was expressed in normal human and murine fibroblasts by stable transfection. Immunohistochemical analysis of the resultant cell lines revealed markedly diminished fibrillin deposition and disorganized microfibrillar architecture. Pulse-chase studies demonstrated normal levels of fibrillin synthesis but substantially reduced deposition into the extracellular matrix. These data illustrate that expression of a mutant fibrillin allele, on a background of two normal alleles, is sufficient to disrupt normal microfibrillar assembly and reproduce the MFS cellular phenotype. This underscores the importance of the fibrillin amino-terminus in normal microfibrillar assembly and suggests that expression of the human extreme 5' fibrillin coding sequence may be sufficient, in isolation, to produce an animal model of MFS. Lastly, this substantiation of a dominant-negative effect offers mutant allele knockout as a potential strategy for gene therapy.
Mutations in SMAD3 cause a syndromic form of aortic aneurysms and dissections with early-onset osteoarthritis
Authors: Ingrid M B H van de Laar, Rogier A Oldenburg, Gerard Pals, Jolien W Roos-Hesselink, Bianca M de Graaf, Judith M A Verhagen, Yvonne M Hoedemaekers, Rob Willemsen, Lies-Anne Severijnen, Hanka Venselaar, Gert Vriend, Peter M Pattynama, Margriet Collée, Danielle Majoor-Krakauer, Don Poldermans, Ingrid M E Frohn-Mulder, Dimitra Micha, Janneke Timmermans, Yvonne Hilhorst-Hofstee, Sita M Bierma-Zeinstra, Patrick J Willems, Johan M Kros, Edwin H G Oei, Ben A Oostra, Marja W Wessels, Aida M Bertoli-Avella
Journal: Nature Genetics (2011)
Blood Cholesterol and Hydrocortisone Production in Man: Quantitative Aspects of the Utilization of Circulating Cholesterol by the Adrenals at Rest and under Adrenocorticotropin Stimulation*
Authors: Abraham J. Borkowski, Sam Levin, Claude Delcroix, Antoinette Mahler, Vera Verhas
Journal: Journal of Clinical Investigation (1967)

A kinetic study of the conversion of blood cholesterol into hydrocortisone was carried out in two patients through prolonged infusions of cholesterol-4-(14)C. The following points appear to be established by our observations:1) The infused tracer behaved metabolically like endogenous cholesterol; it could therefore serve as a means of labeling plasma cholesterol for investigating its utilization by the adrenal cortex.2) At rest, about 80% of hydrocortisone derived from plasma cholesterol, the other 20% thus being synthesized in situ from acetate and other unlabeled precursors.3) Under ACTH stimulation the participation of plasma cholesterol in the synthesis of hydrocortisone was the same as at rest; the conversion of plasma cholesterol into hydrocortisone was thus proportional to the production of glucocorticosteroids by the adrenal glands.4) The specific activities of hydrocortisone allowed us to trace its adrenal precursors including adrenal cholesterol. The kinetics of the replacement of adrenal cholesterol by plasma cholesterol underlined the functional heterogeneity of the former. The experimental data were compatible with the following model: A fraction of plasma cholesterol entering the adrenal cell is immediately available for metabolism and conversion into steroid hormones, and another fraction turns over slowly, representing some form of storage.