tbuckley/cabot-search huggingface dataset:
Postal consent for upper gastrointestinal endoscopy
Authors: H A Shepherd
Journal: Gut (2000)

Standards for good practice in clinical risk management issued by the Clinical Negligence Scheme for Trusts indicate that "appropriate information is provided to patients on the risks and benefits of proposed treatment, and of the alternatives available before a signature on a consent form is sought".To investigate the practicability and patient acceptability of a postal information and consent booklet for patients undergoing outpatient gastroscopy.Information about gastroscopy procedure, personalised appointment details, and a carbonised consent form were compiled into a single booklet. This was mailed to patients well in advance of their endoscopic procedure. Patient satisfaction for this new process was assessed by questionnaire.275 patients received a patient information booklet. Of these, 150 (54.5%) returned the consent form by post when they confirmed their attendance; 141 (94%) had signed the form, and the other nine requested further information. Of the remaining 125 booklets sent out, 115 (92%) forms were brought back on the day of the investigation having been previously signed. The remaining 10 (8%) required further information before signing the form. An audit of 168 patients was used to test reaction to the booklet and the idea of filling in the form before coming to hospital; 155 patients (92. 2%) reported the information given in the booklet to be "very useful", and all reported it to be "clear and understandable".A specifically designed patient information booklet with integral consent form is accepted by patients, and improves the level of understanding prior to the investigation being carried out.
A Hospital-Based School Mental Health Project
Authors: EMILY MUMFORD, FRED BROWN, M. RALPH KAUFMAN
Journal: American Journal of Psychiatry (1971)

The authors describe a pilot project designed to provide the wide range of services of a hospital-based team to a group of elementary school children and their families. The team found numerous physical and mental problems as well as serious social problems that had interfered with the ability of the target families to avail themselves of health services. The authors conclude that the use of hospital-based teams working in the schools may offer the best approach to providing truly comprehensive, coordinated, and continuous help.
Use of phosphate-binding agents is associated with a lower risk of mortality
Authors: Jorge B. Cannata-Andía, José L. Fernández-Martín, Francesco Locatelli, Gérard London, José L. Gorriz, Jürgen Floege, Markus Ketteler, Aníbal Ferreira, Adrian Covic, Boleslaw Rutkowski, Dimitrios Memmos, Willem-Jan Bos, Vladimir Teplan, Judit Nagy, Christian Tielemans, Dierik Verbeelen, David Goldsmith, Reinhard Kramar, Pierre-Yves Martin, Rudolf P. Wüthrich, Drasko Pavlovic, Miha Benedik, José Emilio Sánchez, Pablo Martínez-Camblor, Manuel Naves-Díaz, Juan J. Carrero, Carmine Zoccali
Journal: Kidney International (2013)
Recovery of coronary function and morphology during regression of left ventricular hypertrophy
Authors: Martyn Kingsbury, Almut Mahnke, Mark Turner, Desmond Sheridan
Journal: Cardiovascular Research (2002)

Objectives: To investigate changes in coronary morphology and haemodynamic function during regression of established left ventricular hypertrophy (LVH) following surgical unloading. Methods: LVH was induced in guinea-pigs by aortic banding and sham operated animals served as controls. We examined the degree of LVH, coronary haemodynamic function and contemporaneous vessel morphology 42 days post-operation. Identically treated animals were debanded and the same parameters measured after 1, 3 and 6 weeks to assess haemodynamic and morphological changes as hypertrophy regressed. Results: Banding resulted in an aortic pressure gradient of 41±9 mmHg and increases in heart/body weight ratio (46%), myocyte size (26%) and a doubling of arteriolar wall thickness, all P<0.01. These changes were accompanied by a reduction in coronary reserve (38%) and significantly (P<0.01) decreased maximal response to acetylcholine (70%), sodium nitroprusside (87%), adenosine (70%) and reactive hyperaemia (52%). Surgical debanding normalised the systemic haemodynamics and removed the aortic gradient after 7 days. There was some limited improvement in coronary structure and, to a lesser extent, function despite the continued presence of significant LVH. This had completely regressed to normal levels 23 days after debanding and was accompanied by normalisation of coronary structure and function, although systolic impedance to flow remained significantly increased. After 44 days, debanding resulted in complete cardiac morphological and functional recovery. Conclusion: Left ventricular haemodynamic unloading can result in complete normalisation of LVH, coronary morphology and haemodynamic function. Although morphological and functional recovery were closely correlated, recovery of coronary morphology and function slightly preceded that of the myocardium in this aortic banded/debanded model.
Asthma exacerbations {middle dot} 2: Aetiology
Authors: A M Singh, W W Busse
Journal: Thorax (2006)

The natural history of asthma involves relatively stable periods that are often punctuated by significant exacerbations of symptoms. There are many aetiologies that may lead to an increase in asthma severity including respiratory infection (bacterial/viral), allergens, irritants, and occupational exposures. Each trigger probably acts through different mechanisms, but a final common pathway of multicellular inflammation, enhanced bronchial responsiveness, and airflow obstruction is a likely consequence. This review discusses the most common causes of asthma exacerbations with a focus on their microbiology and immunopathogenesis. Through an understanding of underlying causes of asthma exacerbations, treatments with increased effectiveness may be developed, and it is these future developments that may directly influence the morbidity and mortality of the disease.
Fast track lung cancer service in a tertiary care centre
Authors: R. Naseer, M.E.J. Callister, P.K. Plant
Journal: European Respiratory Journal (2011)

Background: Leeds is one of the largest Lung Cancer Centres in the UK

Aim: Audit our practice against Department of Health (DoH) & local standards.

Methods: Retrospective audit of patients (pts) referred to the Fast Track cancer clinic from 03.10 to 04.10.

Results: 153 pts attended. 51% were fast track referrals (C02). 37% were diagnosed with lung cancer of which 32% received best supportive care, 12% had radical surgery & 51% had oncological treatment. 50% had a benign diagnosis, 8% were enrolled into monitoring. 8 pts breached the 62 day target of which 63% required more than 1 diagnostic test. Analysis of breaches identified 29% surgical delays & 35% radiological delays (CT biopsy &/or PET).

View this table:

Table 1. Summary of results





Conclusion: 14 day & 31 day targets are achieved, however to achieve the 62 day target requires close liason between specialities and pts requiring tests delivered by non pulmonologists are more likely to breach.
Human mast cells express receptors for IL‐3, IL‐5 and GM‐CSF; a partial map of receptors on human mast cells cultured <i>in vitro</i>
Authors: C. Dahl, H. J. Hoffmann, H. Saito, P. O. Schiøtz
Journal: Allergy (2004)

Background: Mast cells have long been recognized as the principal cell type that initiates the inflammatory response characteristic of acute allergic type 1 reactions. Our goal has been to further characterize maturation of progenitors to mast cells. Methods: Mast cells were cultured from human cord blood derived CD133 + progenitors. Mast cell function was tested using histamine release. During differentiation mast cells surface marker expression was monitored by flow cytometry. Results: CD133 + progenitors expressed the early haematopoietic and myeloid lineage markers CD34, CD117, CD13 and CD33. Mature mast cells expressed CD117, CD13 and CD33, and expression of the high affinity immunoglobulin E recpetor Fc ɛ RI increased during culture. Cytokine receptors interleukin (IL)‐5R, IL‐3R, granulocyte‐macrophage‐colony stimulating factor (GM‐CSF)R and IL‐18R were expressed at high levels during maturation. Chemokine receptors CXCR4 and CXCR2 were highly expressed on both newly purified CD133 + cells and mature cells. Conclusion: Human mast cells can be cultured from a CD34 + /CD117 + /CD13 + /CD33 + progenitor cell population in cord blood that is tryptase and chymase negative. Developing and mature mast cells express a wide range of chemokine and cytokine receptors. We found high levels of expression of CD123, IL‐5R and GM‐CSF receptors, also found on eosinophils and basophils, and high levels of expression of the receptor for the inflammatory cytokine IL‐18.
Cardiac Alpha<sub>1</sub>-Adrenergic Receptors: Novel Aspects of Expression, Signaling Mechanisms, Physiologic Function, and Clinical Importance
Authors: Timothy D. O’Connell, Brian C. Jensen, Anthony J. Baker, Paul C. Simpson
Journal: Pharmacological Reviews (2013)

Adrenergic receptors (AR) are G-protein-coupled receptors (GPCRs) that have a crucial role in cardiac physiology in health and disease. Alpha<sub>1</sub>-ARs signal through G<i>α</i><sub>q</sub>, and signaling through G<sub>q</sub>, for example, by endothelin and angiotensin receptors, is thought to be detrimental to the heart. In contrast, cardiac alpha<sub>1</sub>-ARs mediate important protective and adaptive functions in the heart, although alpha<sub>1</sub>-ARs are only a minor fraction of total cardiac ARs. Cardiac alpha<sub>1</sub>-ARs activate pleiotropic downstream signaling to prevent pathologic remodeling in heart failure. Mechanisms defined in animal and cell models include activation of adaptive hypertrophy, prevention of cardiac myocyte death, augmentation of contractility, and induction of ischemic preconditioning. Surprisingly, at the molecular level, alpha<sub>1</sub>-ARs localize to and signal at the nucleus in cardiac myocytes, and, unlike most GPCRs, activate "inside-out" signaling to cause cardioprotection. Contrary to past opinion, human cardiac alpha<sub>1</sub>-AR expression is similar to that in the mouse, where alpha<sub>1</sub>-AR effects are seen most convincingly in knockout models. Human clinical studies show that alpha<sub>1</sub>-blockade worsens heart failure in hypertension and does not improve outcomes in heart failure, implying a cardioprotective role for human alpha<sub>1</sub>-ARs. In summary, these findings identify novel functional and mechanistic aspects of cardiac alpha<sub>1</sub>-AR function and suggest that activation of cardiac alpha<sub>1</sub>-AR might be a viable therapeutic strategy in heart failure.
Spontaneous improvement in a patient with the hepatopulmonary syndrome assessed by serial exercise tests.
Authors: K B Saunders, S S Fernando, H R Dalton, A Joseph
Journal: Thorax (1994)

A 37 year old patient with chronic active hepatitis progressing to cirrhosis presented with increasing breathlessness and was found to be hypoxic with finger clubbing. A progressive exercise study with measurement of oxygen saturation (SaO2) showed abnormally high ventilation and desaturation to 81% at 100 W. Serial studies over nearly two years showed, first, deterioration, then improvement with lower ventilation and higher saturation levels at all work loads. This could not be correlated with any change in treatment with azathioprine, prednisolone, or propranolol.
Amelioration of hepatic fibrosis by NK cell activation
Authors: N. Muhanna, L. A. Tair, S. Doron, J. Amer, M. Azzeh, M. Mahamid, S. Friedman, R. Safadi
Journal: Gut (2010)

Background and aims Interactions between hepatic stellate cells (HSCs) and immune cell subsets have emerged as important determinants of liver fibrosis progression and regression. Natural killer (NK) cells have an antifibrotic activity through killing of activated HSCs. In liver injury NK cell expression of activating/inhibitory killer immunoglobulin-related receptors (aKIR/iKIR) and their ratio are significantly increased, while class I major histocompatibilty (MHC) expression by activated HSCs is decreased. The aim of this study was to amplify the antifibrotic activity of NK cells and ameliorate hepatic fibrosis by iKIR silencing. Methods Human lymphocytes from patients with hepatitis C virus (HCV) infection were transfected with specific iKIR small interfering RNAs (siRNAs) or non-silencing control siRNAs, then co-cultured with a human HSC line and assessed for fibrogenic activity. To induce hepatic fibrosis, carbon tetrachloride was administrated to BALBc SCID-Beige male mice (lacking B/T/NK cells) for 4 weeks. Splenocytes from naive SCID donors (lacking B/T cells but with preserved NK cells) were transfected in vitro with either iKIR siRNA or non-silencing control siRNA, and then were transferred to the fibrotic SCID-Beige recipients. Results Transfection with iKIR or positive control siRNAs (mice and human) decreased mRNA expression of iKIR and mitogen-acivated protein kinase 1 (MAPK1). Consequently, total NK cells and NK cell degranulation were increased (p=0.01), consistent with NK cell stimulation. Compared with healthy lymphocytes, when HCV lymphocytes were transfected with non-silencing control siRNA and co-cultured with HSCs there was increased α-smooth muscle actin (αSMA) expression, reflecting HSC activation. Expression of αSMA in co-cultures was attenuated when HCV lymphocytes were transfected with iKIR siRNA. In SCID-Beige recipients, hepatic fibrosis and serum alanine aminotransferase (ALT) levels were significantly attenuated as a result of receiving iKIR siRNA. Conclusions iKIR knockdown stimulates NK cells and promotes their antifibrogenic activity in mice and human co-cultures. These findings have implications for possible immune therapeutic strategies in patients with advanced liver disease.
Concentration of l-Thyroxine and l-Triiodothyronine Specifically Bound to Nuclear Receptors in Rat Liver and Kidney
Authors: Martin I. Surks, Jack H. Oppenheimer
Journal: Journal of Clinical Investigation (1977)

To estimate the relative contribution of l-triiodothyronine (T3) and l-thyroxine (T4) to thyroidal effects, we have measured the concentration of iodothyronine bound to specific hepatic nuclear receptor sites by three different techniques: (a) specific radioimmunoassay after separation of T3 and T4 by preparative paper chromatography; (b) in vivo kinetic approaches as reported previously; and (c) isotopic equilibration. By these three methods, receptor concentration of T3 and T4 in liver was 0.51±0.19 (SD) and 0.08±0.06; 0.52±0.12 and 0.08±0.02; and 0.50±0.13 and 0.10±0.03 pmol/mg DNA, respectively. The percentage contribution of T3 and T4 to total receptor iodothyronine was thus 86.8±9.0 and 13.2±9.4; 86.3±3.5 and 13.7±3.5; and 83.7±5.6 and 16.3±5.6%, respectively. In kidney, specifically bound nuclear T3 and T4 were estimated both by isotopic equilibration and by in vivo kinetic techniques to be 0.28±0.11 and 0.03±0.01 pmol/mg DNA, respectively. Thus, T3 constituted 89.4±3.2% of total receptor iodothyronine in this tissue. No other iodothyronines or analogs were bound to the nuclear sites in either tissue. Kidney and liver nuclear T3 concentrations also were identical to values previously reported with in vivo kinetic techniques. Other studies from this laboratory have suggested that thyroid effect is related to the molar concentration of iodothyronine bound to specific nuclear sites, that the sites are similar in various tissues, and that iodothyronine in plasma is in equilibrium with nuclear T3. If these relationships are assumed, T3 contributes between 85 and 90% of thyroidal effects in the euthyroid rat. The remaining 10-15% of thyroidal effect appears to result from the intrinsic activity of T4.
What's new in respiratory infections and tuberculosis 2008–2010
Authors: Jeremy S Brown, Marc C I Lipman, Heather J Zar
Journal: Thorax (2011)

Over the past few years there have been an increasing number of research articles published in Thorax on respiratory tract infections (including tuberculosis) affecting children and adults. Although these articles cover a wide variety of areas, several broad themes can be discerned. These include greater interest in viral respiratory infections (partially stimulated by the recent influenza A pandemic), improved characterisation of who is at risk of community-acquired pneumonia and mycobacterial infection, research into better diagnostics and attempts to develop new or improved scoring scales for a range of respiratory infection syndromes. There have also been a limited number of articles on how to manage patients with respiratory infection, including describing the efficacy of prevention by vaccination. Overall, there has been a discernible emphasis on transferring advances in clinical science to actual clinical practice, with several papers using molecular methodologies or measuring levels of cytokines or other potential biomarkers to improve diagnostic accuracy in patients with lung infection. There have also been manuscripts linking specific pathogen genotypes to infection phenotype, an area that is likely to be increasingly important in explaining some of the variations in severity between patients with respiratory infection. However, many questions remain on the optimum strategies for the management and prevention of pneumonia, bronchiectasis and tuberculosis, and there remains a strong need for further clinical research in order to make substantial improvements in the management of patients with lung infection.
Pharmacological Rescue of Mitochondrial Deficits in iPSC-Derived Neural Cells from Patients with Familial Parkinson’s Disease
Authors: Oliver Cooper, Hyemyung Seo, Shaida Andrabi, Cristina Guardia-Laguarta, John Graziotto, Maria Sundberg, Jesse R. McLean, Luis Carrillo-Reid, Zhong Xie, Teresia Osborn, Gunnar Hargus, Michela Deleidi, Tristan Lawson, Helle Bogetofte, Eduardo Perez-Torres, Lorraine Clark, Carol Moskowitz, Joseph Mazzulli, Li Chen, Laura Volpicelli-Daley, Norma Romero, Houbo Jiang, Ryan J. Uitti, Zhigao Huang, Grzegorz Opala, Leslie A. Scarffe, Valina L. Dawson, Christine Klein, Jian Feng, Owen A. Ross, John Q. Trojanowski, Virginia M.-Y. Lee, Karen Marder, D. James Surmeier, Zbigniew K. Wszolek, Serge Przedborski, Dimitri Krainc, Ted M. Dawson, Ole Isacson
Journal: Science Translational Medicine (2012)

Neural cells derived from induced pluripotent stem cells from patients with genetic forms of Parkinson’s disease provide insights into disease pathogenesis.
Enhancement of goblet cell hyperplasia and airway hyperresponsiveness by salbutamol in a rat model of atopic asthma
Authors: A Kamachi
Journal: Thorax (2001)

Goblet cell hyperplasia (GCH) is a prominent feature in animal models of atopic asthma produced by immunisation and following multiple challenges with antigens. The aim of this study was to examine the effect of a beta(2) agonist on the development of GCH induced by the immune response.Brown Norway rats were immunised and challenged with an aerosol of ovalbumin for four weeks. Salbutamol (0.5 mg/kg/day) or vehicle was continuously delivered for the four weeks using a subcutaneously implanted osmotic minipump. The density of goblet cells, other morphological changes, and airway responsiveness to methacholine were evaluated 24 hours after the final challenge.Treatment with salbutamol induced a more than twofold increase in the mean (SE) number of goblet cells (53.7 (7.3) vs 114.5 (11.8) cells/10(3) epithelial cells, p<0.01) while it did not significantly influence airway wall thickening and eosinophilic infiltration. Airway responsiveness to methacholine expressed as the logarithmic value of the concentration of methacholine required to generate a 50% increase in airway pressure (logPC(150)Mch) was also enhanced by the beta(2) agonist (-0.56 (0. 21) vs -0.95 (0.05), p<0.05). Additional experiments revealed that the same dose of the beta(2) agonist alone did not cause GCH in non-immunised rats and that the enhancement of GCH by salbutamol was completely abolished by simultaneous treatment with methylprednisolone (0.5 mg/kg/day).These data suggest that salbutamol enhances goblet cell hyperplasia and airway hyperresponsiveness in this rat model of atopic asthma.
Crohn's disease: NOD2, autophagy and ER stress converge
Authors: T. Fritz, L. Niederreiter, T. Adolph, R. S. Blumberg, A. Kaser
Journal: Gut (2011)

Polymorphisms in <i>NOD2</i>, encoding an intracellular pattern recognition receptor, contribute the largest fraction of genetic risk for Crohn9s disease among the &gt;40 risk loci identified so far. Autophagy plays a prominent role in the innate immune response towards intracellular bacteria. The discovery of the autophagy genes <i>ATG16L1</i> and <i>IRGM</i> as risk factors for Crohn9s disease turned autophagy into the spotlight in inflammatory bowel disease (IBD). Remarkably, NOD2 has recently been identified as a potent autophagy inducer. A physical interaction of NOD2 and ATG16L1 appears to be required for autophagic clearance of intracellular pathogens. Moreover, Crohn9s disease-associated NOD2 and ATG16L1 variants exhibit a defect in the induction of an autophagic response and hence predict autophagy as a key converging mechanism that leads to Crohn9s disease. Another pathway that is closely intertwined with autophagy and mutually cross-regulated is the unfolded protein response (UPR), which is induced by endoplasmic reticulum (ER) stress. Genes involved in the UPR (<i>XBP1, ORMDL3</i>) have also been genetically associated with Crohn9s disease and ulcerative colitis. Moreover, the intestinal epithelium at the interface between host and microbe appears particularly affected by IBD-associated hypomorphic function of autophagy and the UPR. The functional convergence of main genetic risk factors for IBD on these innate immune pathways has hence important implications for the host9s interaction with the microbiota. Moreover, the genetic convergence on these molecular mechanisms may open novel therapeutic options for IBD that deserve further exploration.
Prostate Cancer (PCa) Risk Variants and Risk of Fatal PCa in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium
Authors: Irene M. Shui, Sara Lindström, Adam S. Kibel, Sonja I. Berndt, Daniele Campa, Travis Gerke, Kathryn L. Penney, Demetrius Albanes, Christine Berg, H. Bas Bueno-de-Mesquita, Stephen Chanock, E. David Crawford, W. Ryan Diver, Susan M. Gapstur, J. Michael Gaziano, Graham G. Giles, Brian Henderson, Robert Hoover, Mattias Johansson, Loic Le Marchand, Jing Ma, Carmen Navarro, Kim Overvad, Fredrick R. Schumacher, Gianluca Severi, Afshan Siddiq, Meir Stampfer, Victoria L. Stevens, Ruth C. Travis, Dimitrios Trichopoulos, Paolo Vineis, Lorelei A. Mucci, Meredith Yeager, Edward Giovannucci, Peter Kraft
Journal: European Urology (2014)
Does Lapatinib Work against HER2-negative Breast Cancers?
Authors: Ingrid A. Mayer, Carlos L. Arteaga
Journal: Clinical Cancer Research (2010)

Abstract Aberrant growth factor receptor signaling can augment or suppress estrogen receptor (ER) function in hormone-dependent breast cancer cells and lead to escape from anti-estrogen therapy. Interruption of HER2/ER cross-talk with lapatinib can restore sensitivity to anti-estrogens and thus, should be investigated in combination with endocrine therapy in patients with ER+/HER2-negative breast cancers. Clin Cancer Res; 16(5); 1355–7