tbuckley/cabot-search huggingface dataset:
One year period prevalence study of respiratory acidosis in acute exacerbations of COPD: implications for the provision of non-invasive ventilation and oxygen administration
Authors: P K Plant
Journal: Thorax (2000)

Non-invasive ventilation (NIV) reduces mortality and intubation rates in patients with chronic obstructive pulmonary disease (COPD) admitted to hospital with respiratory acidosis. This study aimed to determine the prevalence of respiratory acidosis in patients admitted with COPD, to draw inferences about oxygen therapy, and to determine the need for NIV services for acute COPD in typical UK hospitals.This one year prospective prevalence study identified patients with COPD aged 45-79 years inclusive who were admitted to Leeds General Infirmary, St James's University, and Killingbeck Hospitals, Leeds between 1 March 1997 and 28 February 1998. The prevalence of respiratory acidosis and the relationship with oxygenation are described. Other outcomes included intensive care use and in hospital mortality. From this data population prevalence estimates were determined for respiratory acidosis, from which the need for NIV in a typical district general hospital was modelled.983 patients were admitted, 11 of whom required immediate intubation. 20% of the remaining 972 had a respiratory acidosis. Acidosis was associated with subsequent admission to the intensive care unit (ICU): pH<7.25, OR 6.10 (95% confidence interval (CI) 1.19 to 31.11); pH 7.25-7.30, OR 8.73 (95% CI 2.11 to 36.06). pH was inversely correlated with arterial oxygen tension (PaO(2)) in the 47% of patients who were hypercapnic, with a PaO(2) of >10 kPa being associated with acidosis in most hypercapnic patients. 80% remained acidotic after initial treatment, giving an age/sex specific prevalence for England and Wales of 75 (95% CI 61 to 90)/100 000/year for men aged 45-79 years and 57 (95% CI 46 to 69)/100 000/year for women. Modelling the need for NIV for all COPD patients indicates that a typical UK hospital will admit 90 patients per year with acidosis of which 72 will require NIV.In patients with acute COPD the PaO(2) should be maintained at 7.3-10 kPa (SaO(2) 85-92%) to avoid the dangers of hypoxia and acidosis. If all COPD patients with a respiratory acidosis (pH<7.35) after initial treatment are offered NIV, a typical UK hospital will treat 72 patients per year.
Analysis of tau post-translational modifications in rTg4510 mice, a model of tau pathology
Authors: Lixin Song, Sherry X Lu, Xuesong Ouyang, Jerry Melchor, Julie Lee, Giuseppe Terracina, Xiaohai Wang, Lynn Hyde, J Fred Hess, Eric M Parker, Lili Zhang
Journal: Molecular Neurodegeneration (2015)

Microtubule associated protein tau is the major component of the neurofibrillary tangles (NFTs) found in the brains of patients with Alzheimer's disease and several other neurodegenerative diseases. Tau mutations are associated with frontotemperal dementia with parkinsonism on chromosome 17 (FTDP-17). rTg4510 mice overexpress human tau carrying the P301L FTDP-17 mutation and develop robust NFT-like pathology at 4-5 months of age. The current study is aimed at characterizing the rTg4510 mice to better understand the genesis of tau pathology and to better enable the use of this model in drug discovery efforts targeting tau pathology.
Hip joint disease in psoriatic arthritis: risk factors and natural history
Authors: C J Michet
Journal: Annals of the Rheumatic Diseases (2005)

To determine the natural history of hip joint disease in psoriatic arthritis (PsA) and identify clinical risk factors for its early identification.504 patients with PsA according to ESSG criteria were studied. Mean follow up was 5.7 years (range <1-45). Mean age at onset of psoriasis was 32 years and of PsA, 39 years. The most common pattern of PsA at onset was oligoarticular (49%) and at the latest examination, polyarticular (65%). Sacroiliitis or spondylitis was diagnosed in 94 (18.7%) patients.32 (6.3%) patients developed psoriatic hip arthropathy, and of these, 26 (81%) also had sacroiliitis or spondylitis. In 7/17 (41%) patients the hip became affected within 1 year after the onset of PsA. Hip disease occurred more often in younger patients. Sex, pattern of peripheral arthritis, duration of psoriasis before arthritis affected the distal interphalangeal joints, dactylitis, or enthesitis were not associated with the risk of hip disease. Seventeen patients were followed up and nine required hip arthroplasty. Sixteen (50%) first had arthroplasty within 5 years after the onset of hip pain.Psoriatic hip arthropathy occurs infrequently in PsA and is associated with earlier onset of arthritis and psoriatic spondylitis. Bilateral hip involvement and rapid progression to hip arthroplasty are common.
The population impact on incidence of suicide and non-fatal self harm of regulatory action against the use of selective serotonin reuptake inhibitors in under 18s in the United Kingdom: ecological study
Authors: Benedict W Wheeler, David Gunnell, Chris Metcalfe, Peter Stephens, Richard M Martin
Journal: BMJ (2008)

<b>Objective</b> To investigate the population impact on the incidence of suicide and non-fatal self harm of regulatory action in 2003 to restrict the use of selective serotonin reuptake inhibitors (SSRIs) in under 18s. <b>Design</b> Ecological time series study. <b>Setting</b> United Kingdom. <b>Populations</b> Young people in the UK aged 12-19 years (prescribing trends), in England and Wales aged 12-17 years (mortality), and in England aged 12-17 years (hospital admissions). <b>Main outcome measures</b> Deaths from suicide and hospital admissions for self harm. <b>Results</b> Antidepressant prescribing doubled between 1999 and 2003 but fell to the 1999 level between 2004 and 2005. These large changes in prescribing did not seem to be associated with temporal trends in suicide or self harm. In the years 1993 to 2005 the annual percentage reduction for suicide among 12-17 year olds was −3.9% (95% confidence interval −6.2% to −1.5%) in males and −3.0% (−6.6% to 0.6%) in females, with no indication of a substantial change in this rate of decrease during that period. Similarly, hospital admission rates for self harm in the years 1999 to 2005 indicated an annual percentage increase for males of 1.1% (−0.5% to 2.7%) and for females of 5.7% (3.6% to 7.8%), again with no statistical evidence of a change in rate after the regulatory action. <b>Conclusions</b> The noticeable reduction in prescribing of antidepressants since regulatory action in 2003 to restrict the use of SSRIs in under 18s does not seem to have been associated with changes in suicidal behaviour in young people. Specifically, these data for England do not indicate that reductions in antidepressant use have led to an increase in suicidal behaviour.
The Placebo Effect and Health: Combining Science and Compassionate Care
Authors: Anton J M de Craen
Journal: BMJ (2006)

E very doctor knows the word placebo, but how many have given serious thought to the subject? Misconceptions about the use of placebos and the placebo effect are common in medicine. For example, many believe that the placebo effect wears off after three months and that about 35% of people respond to placebos. Such misconceptions are unlikely to disappear in the near future, but The Placebo Effect and Health makes a good attempt at setting the …
Identifying patients with a high risk of relapse in quiescent Crohn's disease. The GETAID Group. The Groupe d'Etudes Therapeutiques des Affections Inflammatoires Digestives.
Authors: T Sahmoud, G Hoctin-Boes, R Modigliani, A Bitoun, J F Colombel, J C Soule, C Florent, J P Gendre, E Lerebours, R Sylvester
Journal: Gut (1995)

No reliable identification of quiescent Crohn9s disease (CD) patients with a high risk of relapse is available. The aim of this study was to develop a prognostic index to identify those patients. Untreated adult patients with quiescent disease (not induced by surgery) included in three phase III clinical trials were analysed retrospectively with respect to time to relapse. Nineteen factors related to biology, disease history, and topography were investigated. A relapse was defined as either a CD Activity Index (CDAI) &gt; or = 200, a CDAI &gt; or = 150 but over the baseline value by more than 100, or acute complications requiring surgery. The inclusion criteria were fulfilled by 178 patients. The median follow up was 23 months. The Cox model retained the following bad prognostic factors: age &lt; or = 25 years, interval since first symptoms &gt; 5 years, interval since previous relapse &lt; or = 6 months, and colonic involvement (p &lt; 0.001). Bootstrapping confirmed the variable selection. Patients were classified into three groups with an increasing risk of relapse (p &lt; 0.001). The worst risk group was composed of patients presenting at least three of the four bad prognostic factors. These results make possible the design of clinical trials in quiescent CD patients with a high risk of relapse.
Relation between severe malaria morbidity in children and level of Plasmodium falciparum transmission in Africa
Authors: Robert W Snow, Judy A Omumbo, Brett Lowe, Catherine S Molyneux, Jacktone-O Obiero, Ayo Palmer, Martin W Weber, Margaret Pinder, Bernard Nahlen, Charles Obonyo, Chris Newbold, Sunetra Gupta, Kevin Marsh
Journal: The Lancet (1997)
ACC/AHA 2002 guideline update for the management of patients with chronic stable angina—summary article
Authors: Raymond J Gibbons, Jonathan Abrams, Kanu Chatterjee, Jennifer Daley, Prakash C Deedwania, John S Douglas, T.Bruce Ferguson, Stephan D Fihn, Theodore D Fraker, Julius M Gardin, Robert A O’Rourke, Richard C Pasternak, Sankey V Williams, Raymond J Gibbons, Joseph S Alpert, Elliott M Antman, Loren F Hiratzka, Valentin Fuster, David P Faxon, Gabriel Gregoratos, Alice K Jacobs, Sidney C Smith
Journal: Journal of the American College of Cardiology (2002)
Randomised placebo-controlled trial of inhaled sodium cromoglycate in 1–4-year-old children with moderate asthma
Authors: MJA Tasche, JC van der Wouden, JHJM Uijen, BP Ponsioen, RMD Bernsen, LWA van Suijlekom-Smit, JC de Jongste
Journal: The Lancet (1997)
The Role of the Funny Current in Pacemaker Activity
Authors: Dario DiFrancesco
Journal: Circulation Research (2010)

Abstract : Pacemaking is a basic physiological process, and the cellular mechanisms involved in this function have always attracted the keen attention of investigators. The “funny” ( I f ) current, originally described in sinoatrial node myocytes as an inward current activated on hyperpolarization to the diastolic range of voltages, has properties suitable for generating repetitive activity and for modulating spontaneous rate. The degree of activation of the funny current determines, at the end of an action potential, the steepness of phase 4 depolarization; hence, the frequency of action potential firing. Because I f is controlled by intracellular cAMP and is thus activated and inhibited by β-adrenergic and muscarinic M2 receptor stimulation, respectively, it represents a basic physiological mechanism mediating autonomic regulation of heart rate. Given the complexity of the cellular processes involved in rhythmic activity, an exact quantification of the extent to which I f and other mechanisms contribute to pacemaking is still a debated issue; nonetheless, a wealth of information collected since the current was first described more than 30 years ago clearly agrees to identify I f as a major player in both generation of spontaneous activity and rate control. I f - dependent pacemaking has recently advanced from a basic, physiologically relevant concept, as originally described, to a practical concept that has several potentially useful clinical applications and can be valuable in therapeutically relevant conditions. Typically, given their exclusive role in pacemaking, f-channels are ideal targets of drugs aiming to pharmacological control of cardiac rate. Molecules able to bind specifically to and block f-channels can thus be used as pharmacological tools for heart rate reduction with little or no adverse cardiovascular side effects. Indeed a selective f-channel inhibitor, ivabradine, is today commercially available as a tool in the treatment of stable chronic angina. Also, several loss-of-function mutations of HCN4 (hyperpolarization-activated, cyclic-nucleotide gated 4), the major constitutive subunit of f-channels in pacemaker cells, are known today to cause rhythm disturbances, such as for example inherited sinus bradycardia. Finally, gene- or cell-based methods for in situ delivery of f-channels to silent or defective cardiac muscle represent novel approaches for the development of biological pacemakers eventually able to replace electronic devices.
Evaluation of a two dimensional analysis method as a screening and evaluation tool for anterior cruciate ligament injury
Authors: S G McLean, K Walker, K R Ford, G D Myer, T E Hewett, A J van den Bogert
Journal: British Journal of Sports Medicine (2005)

Background: Increased knee valgus predicts the risk of anterior cruciate ligament (ACL) injury, particularly in women. Reducing injury rates thus relies on detecting and continually evaluating people with relatively large valgus motions. Objectives: To examine the potential of a two dimensional (2D) video analysis method for screening for excessive valgus. Methods: Ten female and 10 male National Collegiate Athletic Association basketball players had three dimensional (3D) knee valgus and two dimensional (2D) frontal plane knee angle quantified during side step, side jump, and shuttle run tasks. 3D valgus was quantified from external marker coordinates using standard techniques, and 2D data were obtained from both the frontal plane projections of these coordinates (2D-Mot) and manual digitisation of digital video footage (2D-Cam). A root mean square (RMS) error was calculated between 2D-Mot and 2D-Cam data to evaluate the reliability of the latter. Correlations between 2D-Cam and 3D data (intersubject and intrasubject) were also conducted, and regression slope and r 2 values obtained. Results: 2D-Cam and 2D-Mot data were consistent for side step (RMS = 1.7°) and side jump (RMS = 1.5°) movements. Between subjects, 2D-Cam and 3D data correlated well for the side step ( r 2 = 0.58) and side jump ( r 2 = 0.64). Within subjects, 2D-Cam and 3D data correlated moderately for the side step ( r 2 = 0.25 (0.19)) and side jump ( r 2 = 0.36 (0.27)). Conclusions: The 2D-Cam method can be used to screen for excessive valgus in elite basketball players, particularly for movements occurring primarily in the frontal plane. This method may also be a useful training evaluation tool when large reductions in dynamic valgus motions are required.
Pancreatic beta cells are important targets for the diabetogenic effects of glucocorticoids.
Authors: F Delaunay, A Khan, A Cintra, B Davani, Z C Ling, A Andersson, C G Ostenson, J Gustafsson, S Efendic, S Okret
Journal: Journal of Clinical Investigation (1997)

Abnormalities contributing to the pathogenesis of non-insulin-dependent diabetes mellitus include impaired beta cell function, peripheral insulin resistance, and increased hepatic glucose production. Glucocorticoids are diabetogenic hormones because they decrease glucose uptake and increase hepatic glucose production. In addition, they may directly inhibit insulin release. To evaluate that possible role of glucocorticoids in beta cell function independent of their other effects, transgenic mice with an increased glucocorticoid sensitivity restricted to their beta cells were generated by overexpressing the glucocorticoid receptor (GR) under the control of the insulin promoter. Intravenous glucose tolerance tests showed that the GR transgenic mice had normal fasting and postabsorptive blood glucose levels but exhibited a reduced glucose tolerance compared with their control littermates. Measurement of plasma insulin levels 5 min after intravenous glucose load demonstrated a dramatic decrease in acute insulin response in the GR transgenic mice. These results show that glucocorticoids directly inhibit insulin release in vivo and identify the pancreatic beta cell as an important target for the diabetogenic action of glucocorticoids.
Antisense strategy shows that Mcl-1 rather than Bcl-2 or Bcl-xL is an essential survival protein of human myeloma cells
Authors: Sophie Derenne, Brett Monia, Nicholas M. Dean, Jennifer K. Taylor, Marie-Josée Rapp, Jean-Luc Harousseau, Régis Bataille, Martine Amiot
Journal: Blood (2002)
The 13C urea breath test in the diagnosis of Helicobacter pylori infection
Authors: V Savarino, S Vigneri, G Celle
Journal: Gut (1999)

The urea breath test (UBT) is one of the most important non-invasive methods for detecting Helicobacter pylori infection. The test exploits the hydrolysis of orally administered urea by the enzyme urease, which H pylori produces in large quantities. Urea is hydrolysed to ammonia and carbon dioxide, which diffuses into the blood and is excreted by the lungs. Isotopically labelled CO2 can be detected in breath using various methods. Labelling urea with 13C is becoming increasingly popular because this non-radioactive isotope is innocuous and can be safely used in children and women of childbearing age. Breath samples can also be sent by post or courier to remote analysis centres. The test is easy to perform and can be repeated as often as required in the same patient. A meal must be given to increase the contact time between the tracer and the H pylori urease inside the stomach. The test has been simplified to the point that two breath samples collected before and 30 minutes after the ingestion of urea in a liquid form suffice to provide reliable diagnostic information. The cost of producing 13C-urea is high, but it may be possible to reduce the dosage further by administering it in capsule form. An isotope ratio mass spectrometer (IRMS) is generally used to measure 13C enrichment in breath samples, but this machine is expensive. In order to reduce this cost, new and cheaper equipment based on non-dispersive, isotope selective, infrared spectroscopy (NDIRS) and laser assisted ratio analysis (LARA) have recently been developed. These are valid alternatives to IRMS although they cannot process the same large number of breath samples simultaneously. These promising advances will certainly promote the wider use of the 13C-UBT, which is especially useful for epidemiological studies in children and adults, for screening patients before endoscopy, and for assessing the efficacy of eradication regimens.
RESULTS OF 15 YEARS' EXPERIENCE WITH THE KETOGENIC DIET IN THE TREATMENT OF EPILEPSY IN CHILDREN
Authors: Henry F. Helmholz, Moe Goldstein
Journal: American Journal of Psychiatry (1938)

Thirty-one per cent of patients who had idiopathic epilepsy were rendered free of attacks and 16 per cent became definitely improved when the ketogenic diet was given an adequate trial. In all, 47 per cent were benefited. Approximately 11 per cent of patients who had symptomatic epilepsy became free of attacks following the use of the ketogenic diet. Eight per cent of patients with idiopathic epilepsy, whose seizures were controlled by the ketogenic diet, had recurrence of attacks within seven years following the last attack. No recurrence occurred after more than seven years.
Transnational Tobacco Company Interests in Smokeless Tobacco in Europe: Analysis of Internal Industry Documents and Contemporary Industry Materials
Authors: Silvy Peeters, Anna B. Gilmore
Journal: PLoS Medicine (2013)

European Union (EU) legislation bans the sale of snus, a smokeless tobacco (SLT) which is considerably less harmful than smoking, in all EU countries other than Sweden. To inform the current review of this legislation, this paper aims to explore transnational tobacco company (TTC) interests in SLT and pure nicotine in Europe from the 1970s to the present, comparing them with TTCs' public claims of support for harm reduction.Internal tobacco industry documents (in total 416 documents dating from 1971 to 2009), obtained via searching the online Legacy Tobacco Documents Library, were analysed using a hermeneutic approach. This library comprises documents obtained via litigation in the US and does not include documents from Imperial Tobacco, Japan Tobacco International, or Swedish Match. To help overcome this limitation and provide more recent data, we triangulated our documentary findings with contemporary documentation including TTC investor presentations. The analysis demonstrates that British American Tobacco explored SLT opportunities in Europe from 1971 driven by regulatory threats and health concerns, both likely to impact cigarette sales negatively, and the potential to create a new form of tobacco use among those no longer interested in taking up smoking. Young people were a key target. TTCs did not, however, make SLT investments until 2002, a time when EU cigarette volumes started declining, smoke-free legislation was being introduced, and public health became interested in harm reduction. All TTCs have now invested in snus (and recently in pure nicotine), yet both early and recent snus test markets appear to have failed, and little evidence was found in TTCs' corporate materials that snus is central to their business strategy.There is clear evidence that BAT's early interest in introducing SLT in Europe was based on the potential for creating an alternative form of tobacco use in light of declining cigarette sales and social restrictions on smoking, with young people a key target. We conclude that by investing in snus, and recently nicotine, TTCs have eliminated competition between cigarettes and lower-risk products, thus helping maintain the current market balance in favour of (highly profitable) cigarettes while ensuring TTCs' long-term future should cigarette sales decline further and profit margins be eroded. Please see later in the article for the Editors' Summary.
Loss of SNF5 Expression Correlates with Poor Patient Survival in Melanoma
Authors: Hanyang Lin, Ronald P.C. Wong, Magdalena Martinka, Gang Li
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Aberrant expression of SWI/SNF chromatin remodeling complex is involved in cancer development. The tumor suppressor SNF5, the core subunit of SWI/SNF complex, has been shown to regulate cell differentiation, cell cycle control, and apoptosis. To investigate the role of SNF5 in the development of melanoma, we examined the expression of SNF5 in melanocytic lesions at different stages and analyzed the correlation between SNF5 expression and clinicopathologic variables and patient survival. Experimental Design: Using tissue microarry and immunohistochemistry, we evaluated SNF5 staining in 51 dysplastic nevi, 88 primary melanomas, and 48 metastatic melanomas. We studied chemosensitivity of melanoma cells with reduced SNF5 expression by siRNA using cell survival and apoptosis assays. Results: SNF5 expression was reduced in metastatic melanoma compared with dysplastic nevi (P = 0.005), in advanced primary melanoma (Clark's level V) compared with low risk Clark's level II melanoma (P = 0.019), and in melanoma at sun-exposed sites compared with sun-protected sites (P = 0.044). Furthermore, we showed a strong correlation between negative SNF5 expression and a worse 5-year survival in melanoma patients (P = 0.016). Multivariate Cox regression analysis revealed that negative SNF5 expression is an independent prognostic factor to predict patient outcome in primary melanomas (P = 0.031). Finally, we showed that knockdown of SNF5 in melanoma cell lines resulted in significant chemoresistance. Conclusions: Our data indicate that SNF5 may be an important marker for human melanoma progression and prognosis as well as a potential therapeutic target. (Clin Cancer Res 2009;15(20):6404–11)