tbuckley/cabot-search huggingface dataset:
S31 Predicting Death Or Deterioration In Patients Admitted With Acute Exacerbation Of Copd Using Physiological And Blood Parameters
Authors: L. Hodgson, A. Borowska, A. Singer, P. Bernie, J. Potts, J. Congleton
Journal: Thorax (2014)

<h3>Introduction and objectives</h3> A number of clinical prediction rules have been described to predict adverse outcomes in patients admitted to hospital with an acute exacerbation of COPD (AECOPD).<sup>1</sup> None are used routinely, perhaps because of limitations including setting (confined to intensive care), use of subjectively defined or difficult to access clinical measurements and lack of external validation. None have undergone impact assessment. The National Early Warning Score (NEWS) in unselected medical admissions accurately predicts risk of in-patient mortality. The NEWS is less discriminating in patients with COPD. We hypothesised that patients admitted with an AECOPD could be more accurately risk stratified based on a combination of the NEWS and other parameters. <h3>Methods</h3> This was a twin site observational cohort study, over a two-year period (March 2012 – February 2014). 2361 admissions with COPD were identified (J40–44). <h3>Results</h3> 123 died during admission (5.2%) and a further 36 (1.5%) were escalated to Intensive Care (ICU) and survived to discharge. We analysed these 159 patients against a control group (n = 159) matched only for month of admission (to address seasonal fluctuations in disease severity). Major results of the study are summarised in Table 1. Those who died or had care escalated were older, had a higher NEWS and respiratory rate. Neutrophils, lymphocyte count, neutrophil-lymphocyte ratio, urea, albumin and CRP were significantly different between the two groups studied. On multivariable analysis lymphocyte count, urea, NEWS and age were independent predictors of adverse outcome. <h3>Conclusions</h3> Age, admission NEWS and blood parameters differed significantly between those who were managed on the ward with AECOPD and those who either died or whose care was escalated to ICU. This could form the basis for a prediction score, automatically calculable on admission to hospital using available technology to highlight those patients judged at greatest risk of deterioration. <h3>Reference</h3> Steer J, Gibson GJ, Bourke SC. Predicting outcomes following hospitalization for acute exacerbations of COPD.<i> QJM</i> 2010;103(11):817-29
Pulmonary overexpression of IL-9 induces Th2 cytokine expression, leading to immune pathology
Authors: Ulla-Angela Temann, Prabir Ray, Richard A. Flavell
Journal: Journal of Clinical Investigation (2002)

IL-9 is a pleiotropic cytokine with multiple functions on many cell types involved in the pathology of human asthma. The constitutive overexpression of IL-9 in the lungs of transgenic mice resulted in an asthma-like phenotype. To define the contribution of IL-9 to lung inflammation we generated transgenic mice in which lung-specific expression of the IL-9 transgene is inducible by doxycycline. Transgene induction resulted in lymphocytic and eosinophilic infiltration of the lung, airway epithelial cell hypertrophy with mucus production, and mast cell hyperplasia, similar to that seen in mice that constitutively expressed IL-9 in their lungs. Various cytokines, including IL-4, IL-5, and IL-13, were expressed in the lung in response to IL-9. Blockade of IL-4 or IL-5 following IL-9 induction reduced airway eosinophilia without affecting mucus production. In contrast, neutralization of IL-13 completely abolished both lung inflammation and mucus production. These findings suggest that pathologic changes in the lung require additional signals beyond IL-9, provided by IL-4, IL-5, and IL-13, to develop fully.
Oesophageal tuberculosis: four cases.
Authors: C J Dow
Journal: Gut (1981)

Four Asian patients presented with dysphagia. In each case the oesophagus was involved by adjacent tuberculous subcarinal glands. The lungs were clear and symptoms of systemic illness were minimal. Findings at oesophagoscopy were non-specific and early diagnosis rested on a high index of suspicion and a strongly positive Mantoux test. Bacteriological proof was obtained early in only two of the cases.
The role of pharmacokinetics/pharmacodynamics in setting clinical MIC breakpoints: the EUCAST approach
Authors: J.W. Mouton, D.F.J. Brown, P. Apfalter, R. Cantón, C.G. Giske, M. Ivanova, A.P. MacGowan, A. Rodloff, C.-J. Soussy, M. Steinbakk, G. Kahlmeter
Journal: Clinical Microbiology and Infection (2011)
Markedly inhibited 7-dehydrocholesterol-delta 7-reductase activity in liver microsomes from Smith-Lemli-Opitz homozygotes.
Authors: S Shefer, G Salen, A K Batta, A Honda, G S Tint, M Irons, E R Elias, T C Chen, M F Holick
Journal: Journal of Clinical Investigation (1995)

We investigated the enzyme defect in late cholesterol biosynthesis in the Smith-Lemli-Opitz syndrome, a recessively inherited developmental disorder characterized by facial dysmorphism, mental retardation, and multiple organ congenital anomalies. Reduced plasma and tissue cholesterol with increased 7-dehydrocholesterol concentrations are biochemical features diagnostic of the inherited enzyme defect. Using isotope incorporation assays, we measured the transformation of the precursors, [3 alpha- 3H]lathosterol and [1,2-3H]7-dehydrocholesterol into cholesterol by liver microsomes from seven controls and four Smith-Lemli-Opitz homozygous subjects. The introduction of the double bond in lathosterol at C-5[6] to form 7-dehydrocholesterol that is catalyzed by lathosterol-5-dehydrogenase was equally rapid in controls and homozygotes liver microsomes (120 +/- 8 vs 100 +/- 7 pmol/mg protein per min, P = NS). In distinction, the reduction of the double bond at C-7 [8] in 7-dehydrocholesterol to yield cholesterol catalyzed by 7-dehydrocholesterol-delta 7-reductase was nine times greater in controls than homozygotes microsomes (365 +/- 23 vs 40 +/- 4 pmol/mg protein per min, P < 0.0001). These results demonstrate that the pathway of lathosterol to cholesterol in human liver includes 7-dehydrocholesterol as a key intermediate. In Smith-Lemli-Opitz homozygotes, the transformation of 7-dehydrocholesterol to cholesterol by hepatic microsomes was blocked although 7-dehydrocholesterol was produced abundantly from lathosterol. Thus, lathosterol 5-dehydrogenase is equally active which indicates that homozygotes liver microsomes are viable. Accordingly, microsomal 7-dehydrocholesterol-delta 7-reductase is inherited abnormally in Smith-Lemli-Opitz homozygotes.
Chemotactic effect of prorenin on human aortic smooth muscle cells: a novel function of the (pro)renin receptor
Authors: Carolina M. Greco, Marina Camera, Laura Facchinetti, Marta Brambilla, Sara Pellegrino, Maria Luisa Gelmi, Elena Tremoli, Alberto Corsini, Nicola Ferri
Journal: Cardiovascular Research (2012)

The discovery of a specific prorenin receptor (PRR) suggests a biological function of prorenin that is independent of angiotensin I production. In the present study, we investigated the role of PRR on smooth muscle cell (SMC) migration. PRR was expressed in human mammary arteries and in cultured human aortic SMCs. Prorenin induced SMC migration in a dose-dependent manner, as assessed by Boyden chamber chemotaxis assay, and increased SMC random motility, as determined by video microscopy. The prorenin decoy peptide inhibited SMC migration in response to prorenin, and knockdown of PRR by small interfering RNA completely inhibited the migratory response to prorenin, demonstrating that the chemotactic action of prorenin is mediated by the PRR. Prorenin induced cytoskeleton reorganization and lamellipodia formation and increased the intracellular levels of both RhoA-GTP and Rac1-GTP through PRR. These effects were required for SMC migration, because the suppression by small interfering RNA of either Rac1 or RhoA GTP-bound forms completely blocked the PRR-mediated chemotactic effect. Prorenin also induced the formation of larger focal adhesions and cleavage of the focal adhesion kinase (pp125FAK) into two main fragments with molecular weights of 50 and 90 kDa. The generation of these two fragments of pp125FAK was reduced by the calpain inhibitor ALLN, which also inhibited SMC migration in response to prorenin. These results demonstrate that prorenin is a chemotactic factor for human aortic SMCs expressing PRR. This effect is elicited through reorganization of the cytoskeleton and focal adhesion, activation of RhoA and Rac1, and calpain-mediated cleavage of pp125FAK.
Ultrasound-detected musculoskeletal urate crystal deposition: which joints and what findings should be assessed for diagnosing gout?
Authors: Esperanza Naredo, Jacqueline Uson, Mercedes Jiménez-Palop, Agustín Martínez, Esther Vicente, Elia Brito, Ana Rodríguez, Francisco Javier Cornejo, Santos Castañeda, María Jesús Martínez, Jesús Sanz, Ingrid Möller, Enrique Batlle-Gualda, Jesús Garrido, Eliseo Pascual
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objective</h3> The primary objective of this prospective case-control study was to assess the diagnostic value of several intra-articular and periarticular ultrasound (US)-detected abnormalities in the upper and lower limbs in gout. The secondary objective was to test the concurrent validity of US abnormalities using as gold standard the microscopic demonstration of monosodium urate (MSU) crystals. <h3>Methods</h3> Ninety-one men with gout and 42 age-matched controls were prospectively recruited. All patients with gout and controls underwent US assessment of several US abnormalities in 26 joints, six bursae, eight tendons, 20 tendon compartments, four ligaments, and 18 articular cartilages by experts in US blinded to the patients' group. Patients with gout and controls with US abnormalities were asked to undergo US-guided aspiration for microscopic identification of MSU crystals. Interobserver and intraobserver reliability of the US assessment was evaluated in a web-based exercise. <h3>Results</h3> The assessment of one joint (ie, radiocarpal joint) for hyperechoic aggregates (HAGs), two tendons (ie, patellar tendon and triceps tendon) for HAGs and three articular cartilages (ie, first metatarsal, talar and second metacarpal/femoral) for double contour sign showed the best balance between sensitivity and specificity (84.6% and 83.3%, respectively). Intraobserver reliability was good (mean κ 0.75) and interobserver reliability was moderate (κ 0.52). The aspirated material from HAGs was positive for MSU crystals in 77.6% of patients with gout and negative in all controls. <h3>Conclusions</h3> Our results suggest that US bilateral assessment of one joint, three articular cartilages and two tendons may be valid for diagnosing gout with acceptable sensitivity and specificity.
Circulating cell-derived microparticles in patients with minimally symptomatic obstructive sleep apnoea
Authors: L. Ayers, B. Ferry, S. Craig, D. Nicoll, J. R. Stradling, M. Kohler
Journal: European Respiratory Journal (2008)

Moderate-severe obstructive sleep apnoea (OSA) has been associated with several pro-atherogenic mechanisms and increased cardiovascular risk, but it is not known if minimally symptomatic OSA has similar effects. Circulating cell-derived microparticles have been shown to have pro-inflammatory, pro-coagulant and endothelial function-impairing effects, as well as to predict subclinical atherosclerosis and cardiovascular risk. In 57 patients with minimally symptomatic OSA, and 15 closely matched control subjects without OSA, AnnexinV-positive, platelet-, leukocyte- and endothelial cell-derived microparticles were measured by flow cytometry. In patients with OSA, median (interquartile range) levels of AnnexinV-positive microparticles were significantly elevated compared with control subjects: 2,586 (1,566-3,964) microL(-1) versus 1,206 (474-2,501) microL(-1), respectively. Levels of platelet-derived and leukocyte-derived microparticles were also significantly higher in patients with OSA (2,267 (1,102-3,592) microL(-1) and 20 (14-31) microL(-1), respectively) compared with control subjects (925 (328-2,068) microL(-1) and 15 (5-23) microL(-1), respectively). Endothelial cell-derived microparticle levels were similar in patients with OSA compared with control subjects (13 (8-25) microL(-1) versus 11 (6-17) microL(-1)). In patients with minimally symptomatic obstructive sleep apnoea, levels of AnnexinV-positive, platelet- and leukocyte-derived microparticles are elevated when compared with closely matched control subjects without obstructive sleep apnoea. These findings suggest that these patients may be at increased cardiovascular risk, despite being minimally symptomatic.
Type D Personality as a Cardiovascular Risk Marker in the General Population: Results from the Gutenberg Health Study
Authors: M.E. Beutel, J. Wiltink, Y. Till, P.S. Wild, T. Münzel, F.M. Ojeda, T. Zeller, R.B. Schnabel, K. Lackner, M. Blettner, I. Zwiener, M. Michal
Journal: Psychotherapy and Psychosomatics (2012)

&lt;i&gt;Background:&lt;/i&gt; Type D personality is considered as an independent risk factor for morbidity and mortality in cardiovascular patients and a vulnerability factor for distress in the general population. Because representative community studies are rare, we sought to determine the prevalence of type D personality and its relationship with demographic characteristics, different features of mental disorders, cardiovascular risk factors, health behavior, endothelial function and cardiovascular biomarkers in the general population. &lt;i&gt;Methods:&lt;/i&gt; The prevalence of type D personality and its correlates were analyzed cross-sectionally in a population-based sample of 5,000 Mid-Europeans aged 35–74 years from the Gutenberg Health Study. &lt;i&gt;Results:&lt;/i&gt; The prevalence of type D personality was 22.2% without remarkable differences in sex distribution. Type D subjects were characterized by lower socioeconomic status, lack of a partnership, increased depression, anxiety, depersonalization and health care utilization. Despite its strong association with mental disorders, type D personality emerged as psychometrically distinct. Although type D personality was independently associated with coronary heart disease (OR = 1.54, p = 0.044), no associations with traditional cardiovascular risk factors were found independently from depression or anxiety. &lt;i&gt;Conclusions:&lt;/i&gt; Although type D personality is strongly associated with depression, anxiety, impaired mental and somatic health status, and increased health care utilization, the type D construct seems to comprise dysfunctional personality patterns not covered by depression and anxiety scales. Beyond these associations, the pathways of the cardiotoxic impact of type D personality remain to be elucidated. There is a need for prospective population studies on potential links between type D personality and cardiac disease.
Change in osmolarity of disodium cromoglycate solution and protection against exercise-induced bronchospasm in children with asthma
Authors: S Kano, T Hirose, S Nishima
Journal: European Respiratory Journal (1996)

It has been suggested that osmolarity and/or nebulizer output may affect the protective effects of disodium cromoglycate (DSCG) in asthma. The aim of this study was to evaluate the influence of osmolarity of the DSCG solution on exercise-induced bronchospasm (EIB) in children with bronchial asthma. A jet nebulizer was used for DSCG inhalation in Study 1 and an ultrasonic nebulizer in Study 2. Thirteen asthmatic children (7 males and 6 females, aged 6-14 yrs) were enrolled in Study 1, and nine asthmatic children (5 males and 4 females, aged 9-13 yrs) in Study 2. After pretreatment with saline (control), hypotonic DSCG or isotonic DSCG, children underwent exercise challenge with a cycle ergometer. The percentage fall in forced expiratory volume in one second (FEV1) was measured at 5 and 15 min postexercise. The data were compared by analysis of variance (ANOVA). Both in Study 1 and Study 2, there were no significant differences in minute ventilation volume or maximum heart rate during exercise between the different treatment groups. Both hypotonic and isotonic DSCG significantly reduced the maximum percentage fall in FEV1. There were no significant differences in protective effects between hypotonic and isotonic DSCG in either study. We conclude that the efficacy of hypotonic and isotonic disodium cromoglycate solutions is similar for protection against exercise-induced bronchospasm. Hypotonic disodium cromoglycate seems to be clinically effective for prevention of exercise-induced bronchospasm and treatment of asthmatic children.
Overview
Authors: Jennifer E. Van Eyk
Journal: Circulation Research (2011)

Proteomic technologies are used to study the complexity of proteins, their roles, and biological functions. It is based on the premise that the diversity of proteins, comprising their isoforms, and posttranslational modifications (PTMs) underlies biology. Based on an annotated human cardiac protein database, 62% have at least one PTM (phosphorylation currently dominating), whereas ≈25% have more than one type of modification. The field of proteomics strives to observe and quantify this protein diversity. It represents a broad group of technologies and methods arising from analytic protein biochemistry, analytic separation, mass spectrometry, and bioinformatics. Since the 1990s, the application of proteomic analysis has been increasingly used in cardiovascular research. Technology development and adaptation have been at the heart of this progress. Technology undergoes a maturation, becoming routine and ultimately obsolete, being replaced by newer methods. Because of extensive methodological improvements, many proteomic studies today observe 1000 to 5000 proteins. Only 5 years ago, this was not feasible. Even so, there are still road blocks. Nowadays, there is a focus on obtaining better characterization of protein isoforms and specific PTMs. Consequently, new techniques for identification and quantification of modified amino acid residues are required, as is the assessment of single-nucleotide polymorphisms in addition to determination of the structural and functional consequences. In this series, 4 articles provide concrete examples of how proteomics can be incorporated into cardiovascular research and address specific biological questions. They also illustrate how novel discoveries can be made and how proteomic technology has continued to evolve.
Long-term risks for kidney donors
Authors: Geir Mjøen, Stein Hallan, Anders Hartmann, Aksel Foss, Karsten Midtvedt, Ole Øyen, Anna Reisæter, Per Pfeffer, Trond Jenssen, Torbjørn Leivestad, Pål- Dag Line, Magnus Øvrehus, Dag Olav Dale, Hege Pihlstrøm, Ingar Holme, Friedo W. Dekker, Hallvard Holdaas
Journal: Kidney International (2013)
Identification of the Immunodominant Epitope Region in Phospholipase A2 Receptor-Mediating Autoantibody Binding in Idiopathic Membranous Nephropathy
Authors: Liyo Kao, Vinson Lam, Meryl Waldman, Richard J. Glassock, Quansheng Zhu
Journal: Journal of the American Society of Nephrology (2014)

Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults. Recent clinical studies established that >70% of patients with idiopathic (also called primary) MN (IMN) possess circulating autoantibodies targeting the M-type phospholipase A2 receptor-1 (PLA2R) on the surface of glomerular visceral epithelial cells (podocytes). In situ, these autoantibodies trigger the formation of immune complexes, which are hypothesized to cause enhanced glomerular permeability to plasma proteins. Indeed, the level of autoantibody in circulation correlates with the severity of proteinuria in patients. The autoantibody only recognizes the nonreduced form of PLA2R, suggesting that disulfide bonds determine the antigenic epitope conformation. Here, we identified the immunodominant epitope region in PLA2R by probing isolated truncated PLA2R extracellular domains with sera from patients with IMN that contain anti-PLA2R autoantibodies. Patient sera specifically recognized a protein complex consisting of the cysteine-rich (CysR), fibronectin-like type II (FnII), and C-type lectin-like domain 1 (CTLD1) domains of PLA2R only under nonreducing conditions. Moreover, absence of either the CysR or CTLD1 domain prevented autoantibody recognition of the remaining domains. Additional analysis suggested that this three-domain complex contains at least one disulfide bond required for conformational configuration and autoantibody binding. Notably, the three-domain complex completely blocked the reactivity of autoantibodies from patient sera with the full-length PLA2R, and the reactivity of patient sera with the three-domain complex on immunoblots equaled the reactivity with full-length PLA2R. These results indicate that the immunodominant epitope in PLA2R is exclusively located in the CysR-FnII-CTLD1 region.
Need for early recognition and multidisciplinary management of paediatric complex regional pain syndrome:
Authors: Christina Liossi, Jacqui Clinch, Richard Howard
Journal: BMJ (2015)

Complex regional pain syndrome (CRPS) in children and adolescents is often missed, with lengthy delays before appropriate treatment is started.1 This may be because of clinicians’ lack of awareness or the heterogeneity of the presenting signs and symptoms, although paediatric presentation has several unique features when compared with adults (table⇓). Whatever the underlying cause, …
Renin, Aldosterone, Body Fluid Volumes, and the Baroreceptor Reflex in the Development and Reversal of Goldblatt Hypertension in Conscious Dogs
Authors: JEAN-FRANCOIS LIARD, ALLEN W. COWLEY, ROBERT E. MCCAA, CONNIE S. MCCAA, ARTHUR C. GUYTON
Journal: Circulation Research (1974)

The renal artery to a sole remaining kidney was constricted in unanesthetized dogs while renal arterial pressure was recorded distal to the occluder. Following the constriction, mean arterial blood pressure, which was continuously monitored 24 hours a day for 1 week, exhibited a biphasic increase. The first peak in pressure correlated with a large increase in plasma renin activity; the second peak correlated with an increase in plasma volume brought about by positive sodium and water balances. Renin activity was returning to normal when the second peak occurred. Increased drinking played a major role in the positive water balance. Plasma aldosterone concentration was moderately and transiently increased for only a few hours following the constriction. The experiment was repeated in sinoaortic baroreceptor-denervated dogs; apparently, the baroreceptor reflex significantly slows the time course of the arterial blood pressure increase during the first few days of constriction but does not alter the magnitude of the pressure increase after 1 week. After release of renal artery constriction, mean arterial blood pressure decreased progressively over a 3-day period, during which time significant negative sodium and fluid balance occurred. The slow return of the pressure back to normal correlated highly with a decrease in plasma volume. In the baroreceptor-denervated dogs, the initial fall in arterial blood pressure apparently also resulted at least partly from a decrease in plasma renin activity, but this effect was not observed in the intact dogs because the renin activities in these dogs had already decreased to normal prior to constrictor release. The effects of the baroreceptor reflex on the time course of the pressure decrease did not seem to be as significant as those on the time course of the pressure increase.