tbuckley/cabot-search huggingface dataset:
Observational study of effect of patient centredness and positive approach on outcomes of general practice consultations
Authors: P. Little, H. Everitt, I. Williamson, G. Warner, M. Moore, C. Gould, K. Ferrier, S. Payne
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objective:</b> To measure patients9 perceptions of patient centredness and the relation of these perceptions to outcomes. <b>Design:</b> Observational study using questionnaires. <b>Setting:</b> Three general practices. <b>Participants:</b> 865 consecutive patients attending the practices. <b>Main outcome measures:</b> Patients9 enablement, satisfaction, and burden of symptoms. <b>Results:</b> Factor analysis identified five components. These were communication and partnership (a sympathetic doctor interested in patients9 worries and expectations and who discusses and agrees the problem and treatment, Cronbach9s α=0.96); personal relationship (a doctor who knows the patient and their emotional needs, α=0.89); health promotion (α=0.87); positive approach (being definite about the problem and when it would settle, α=0.84); and interest in effect on patient9s life (α=0.89). Satisfaction was related to communication and partnership (adjusted β=19.1; 95% confidence interval 17.7 to 20.7) and a positive approach (4.28; 2.96 to 5.60). Enablement was greater with interest in the effect on life (0.55; 0.25 to 0.86), health promotion (0.57; 0.30 to 0.85), and a positive approach (0.82; 0.52 to 1.11). A positive approach was also associated with reduced symptom burden at one month (β=−0.25; −0.41 to −0.10). Referrals were fewer if patients felt they had a personal relationship with their doctor (odds ratio 0.70; 0.54 to 0.90). <b>Conclusions:</b> Components of patients9 perceptions can be measured reliably and predict different outcomes. If doctors don9t provide a positive, patient centred approach patients will be less satisfied, less enabled, and may have greater symptom burden and higher rates of referral. <h3>What is already known on this topic</h3> Preliminary evidence suggests that patients9 perceptions of patient centredness predict outcomes better than analysing what the doctor says in a consultation <h3>What this study adds</h3> There are five distinct components of patients9 perceptions that can be measured reliably: communication and partnership, personal relationship, health promotion, positive approach to diagnosis and prognosis, and interest in the effect on life Each component predicts different consultation outcomes If doctors don9t provide a positive, patient centred approach patients will be less satisfied, less enabled, and may have greater symptom burden and use more health service resources
Global trends and projections for tobacco use, 1990–2025: an analysis of smoking indicators from the WHO Comprehensive Information Systems for Tobacco Control
Authors: Ver Bilano, Stuart Gilmour, Trevor Moffiet, Edouard Tursan d'Espaignet, Gretchen A Stevens, Alison Commar, Frank Tuyl, Irene Hudson, Kenji Shibuya
Journal: The Lancet (2015)
Club Cell Protein 16 and Disease Progression in Chronic Obstructive Pulmonary Disease
Authors: Hye Yun Park, Andrew Churg, Joanne L. Wright, Yuexin Li, Sheena Tam, S. F. Paul Man, Donald Tashkin, Robert A. Wise, John E. Connett, Don D. Sin
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Club (Clara) cell protein 16 (CC-16) is a protein that is synthesized predominantly in the lungs and is detectable in serum. Its expression decreases with lung injury and smoking, and is thus a marker of bronchial cell dysfunction.To evaluate the possibility of using serum CC-16 as a biomarker for disease progression in chronic obstructive pulmonary disease (COPD).We measured serum CC-16 levels from 4,724 subjects with mild-to-moderate airflow limitation in the Lung Health Study. Using a linear regression model, we determined the relationship of serum CC-16 concentrations to decline in lung function over 9 years. In addition, to determine whether CC-16 plays a major role in the pathogenesis of mild COPD, we exposed CC-16-deficient (-/-) mice to 6 months of cigarette smoke.Reduced serum concentrations of CC-16 were associated with accelerated decline in FEV1 over 9 years (P < 0.0001), and this association persisted after adjustments for age, sex, race, smoking status, airway reactivity, body mass index, and baseline FEV1 (P = 0.0002). However, CC-16(-/-) mice did not demonstrate an enhanced risk of emphysema or small airway remodeling in response to cigarette smoke.Serum CC-16 is associated with disease progression, and may assist in the identification of "rapid progressors." However, the absence of CC-16 does not appear to modify the risk of cigarette-related COPD in mice.
Effect of β-Blocking Therapy on Outcome in the Multicenter UnSustained Tachycardia Trial (MUSTT)
Authors: Kristin E. Ellison, Gail E. Hafley, Kathleen Hickey, Joyce Kellen, James Coromilas, Kenneth M. Stein, Kerry L. Lee, Alfred E. Buxton
Journal: Circulation (2002)

Background— β-Blockers are known to reduce total mortality and sudden death in survivors of recent myocardial infarction. The effects of these agents in patients at high risk for sudden death with remote infarction are not clear. Methods and Results— We analyzed the effect of β-blockers on outcomes in 2096 patients with coronary artery disease, ejection fraction ≤40%, and spontaneous nonsustained ventricular tachycardia enrolled in the Multicenter UnSustained Tachycardia Trial (MUSTT). Forty-five percent of 702 patients with inducible sustained ventricular tachyarrhythmia and 35% of 1394 patients without inducible tachycardia were discharged from hospital receiving β-blockers. Patients treated with β-blockers were younger and had higher ejection fractions, higher rates of recent angina, and more recent infarction. β-Blockers were associated with decreased total mortality for the entire study population (5-year mortality 50% with β-blockers versus 66% without β-blockers; adjusted P =0.0001). The mortality benefit associated with β-blockers was present in patients with and without inducible tachycardia, except those treated with implantable defibrillators. There was no significant effect of β-blocker therapy on the rate of arrhythmic death or cardiac arrest (adjusted P =0.2344). Conclusions— β-Blocking agents have beneficial effects on survival of patients having characteristics of those enrolled in the MUSTT trial. These effects do not appear to be due to a specific antiarrhythmic effect of β-blockers. The beneficial effects of β-blockers were demonstrable in all patients except those treated with implantable defibrillators.
Specialized DNA Arrays for the Differentiation of Pancreatic Tumors
Authors: Malte Buchholz, Hans A. Kestler, Andrea Bauer, Wolfgang Böck, Bettina Rau, Gerhard Leder, Wolfgang Kratzer, Martin Bommer, Aldo Scarpa, Martin K. Schilling, Guido Adler, Jörg D. Hoheisel, Thomas M. Gress
Journal: Clinical Cancer Research (2005)

Malignant tumors of the pancreas are frequently indistinguishable from inflammatory tumors arising in the context of a chronic pancreatitis with the use of conventional imaging techniques. Thus, cytologic analysis of cells obtained by abdominal ultrasound, computed tomography, or endoscopic ultrasound-guided fine needle aspiration biopsy is required for diagnosis. However, the reliability of cytologic analyses of pancreatic fine needle aspirates remains unsatisfactory, with a diagnostic accuracy of < or =80%. The purpose of the current study was therefore to develop a novel diagnostic approach based on expression profiling of biopsy material using a specialized diagnostic cDNA array.Previous gene expression profiling studies were reevaluated to design a 558-feature diagnostic array. Minimal amounts of residual material from pancreatic cytology samples as well as surgically resected tumor and control tissue specimens were analyzed using the diagnostic array and a newly developed statistical classification system.Our diagnostic approach resulted in 95% accurate differentiation between ductal adenocarcinomas and nonmalignant tumors of the pancreas. The diagnostic array, in conjunction with conventional diagnostic procedures, is thus suitable to significantly improve the reliability of pancreatic cancer diagnostics and can be expected to become a valuable new tool in the routine workup of suspect masses in the pancreas.
Resistance Training Prevents Deterioration in Quadriceps Muscle Function During Acute Exacerbations of Chronic Obstructive Pulmonary Disease
Authors: Thierry Troosters, Vanessa Suziane Probst, Tim Crul, Fabio Pitta, Ghislaine Gayan-Ramirez, Marc Decramer, Rik Gosselink
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Exacerbations of chronic obstructive pulmonary disease (COPD) acutely reduce skeletal muscle strength and result in long-term loss of functional capacity.To investigate whether resistance training is feasible and safe and can prevent deteriorating muscle function during exacerbations of COPD.Forty patients (FEV(1) 49 +/- 17% predicted) hospitalized with a severe COPD exacerbation were randomized to receive usual care or an additional resistance training program during the hospital admission. Patients were followed up for 1 month after discharge. Primary outcomes were quadriceps force and systemic inflammation. A muscle biopsy was taken in a subgroup of patients to assess anabolic and catabolic pathways.Resistance training did not yield higher systemic inflammation as indicated by C-reactive protein levels and could be completed uneventfully. Enhanced quadriceps force was seen at discharge (+9.7 +/- 16% in the training group; -1 +/- 13% in control subjects; P = 0.05) and at 1 month follow-up in the patients who trained. The 6-minute walking distance improved after discharge only in the group who received resistance training (median 34; interquartile range, 14-61 m; P = 0.002). In a subgroup of patients a muscle biopsy showed a more anabolic status of skeletal muscle in patients who followed training. Myostatin was lower (P = 0.03) and the myogenin/MyoD ratio tended to be higher (P = 0.08) in the training group compared with control subjects.Resistance training is safe, successfully counteracts skeletal muscle dysfunction during acute exacerbations of COPD, and may up-regulate the anabolic milieu in the skeletal muscle. Clinical trial registered with www.clinicaltrials.gov (NCT00877084).
Localization of atrial natriuretic peptide in caveolae of in situ atrial myocytes.
Authors: E Page, J Upshaw-Earley, G E Goings
Journal: Circulation Research (1994)

The plasma membrane-associated non-clathrin-coated vesicles called caveolae are multifunctional organelles thought to be implicated in the sequestration and transport of small molecules (potocytosis) as well as in the binding of Ca2+ ions, signal transduction, and processing of hormonal and mechanosensitive signals. We have previously suggested that the apparent contiguity of caveolar and atrial granule membranes observed in electron micrographs of in situ mouse atrial myocytes might reflect externalization of atrial natriuretic peptide through caveolae. Using Tokuyasu's classic technique, we now show by immunoelectron microscopy of glutaraldehyde-fixed and cryosectioned mouse and rat atria that antibody against atrial natriuretic peptide prohormone is present within caveolae of in situ atrial myocytes. We confirm this intracaveolar localization by stereoimaging colloidal gold-labeled antibody to the prohormone in electron micrographs of glutaraldehyde/osmium tetroxide-fixed positively stained atrial thin sections. Because profiles of caveolae were rarely immunolabeled with antibody against atrial peptide unless there was a profile of an immunolabeled atrial granule nearby in the subjacent cytoplasm, we concluded that the intracaveolar hormone was derived predominantly from a direct interaction of atrial granules with caveolae. Perturbations that markedly increase the rate of natriuretic peptide secretion via the regulated pathway, including atrial stretch, contractions, and increased external Ca2+ concentration, failed to alter caveolar immunostaining. These results suggest that atrial peptide can pass from atrial granules into caveolae by transiently open pathways between the interiors of granules and caveolae. The results are interpreted as suggesting the presence of a second pathway for externalization of atrial natriuretic peptide through caveolae in addition to the classic pathway for regulated atrial peptide secretion at noncaveolar plasmalemma.
Effects of Methylprednisolone on Hydrogen Ion Absorption in the Canine Stomach
Authors: Raphael S. K. Chung, Michael Field, William Silen
Journal: Journal of Clinical Investigation (1978)

The effect of methylprednisolone (2 mg/kg per day given parenterally for 3 doses, 2 wk or 12 wk) on the permeability of mammalian gastric mucosa to hydrogen ion (H+) was examined with denervated fundic pouches in dogs with antrectomies. Transmucosal electric potential difference (PD) and net fluxes of H+ and Na+ were determined for luminal [H+] from 20 to 160 mM and [Na+] from 1 to 140 mM ([H+] and [Na+] were varied reciprocally). The PD was 50-60 mV lumen negative and was constant over the entire range of Na+ and H+ concentration tested. Net H+ flux varied linearly with [H+]. Extrapolation indicated apparent H+ loss at zero luminal concentration, suggesting a basal HCO3− secretion. Addition of acetylsalicylic acid (ASA) or taurocholate decreased the PD to 30-40 mV and increased threefold the slope of the relation between net H+ flux and [H+] (kH). Calculation of PD-independent permeability constants for H+ (PH) with the Goldman constant field equation indicated that this increase in kH could not be attributed solely to the associated decrease in PD. Prednisolone administered for 3 doses had no effect on either the basal mucosal permeability to H+ or the altered permeability induced by ASA or taurocholate. Chronic administration induced a low rate of basal acid secretion (at 12 wk) but had no effect on either PD or kH. However, the increase in kH and PH that developed upon addition of ASA or taurocholate in chronically treated dogs was more than one and a half times that of controls. These data suggest that prolonged treatment with glucocorticoids increases susceptibility of the gastric mucosa to damage by agents that increase permeability to H+.
Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis
Authors: Heather R. Conti, Fang Shen, Namrata Nayyar, Eileen Stocum, Jianing N. Sun, Matthew J. Lindemann, Allen W. Ho, Justine Hoda Hai, Jeffrey J. Yu, Ji Won Jung, Scott G. Filler, Patricia Masso-Welch, Mira Edgerton, Sarah L. Gaffen
Journal: The Journal of Experimental Medicine (2009)

The commensal fungus Candida albicans causes oropharyngeal candidiasis (OPC; thrush) in settings of immunodeficiency. Although disseminated, vaginal, and oral candidiasis are all caused by C. albicans species, host defense against C. albicans varies by anatomical location. T helper 1 (Th1) cells have long been implicated in defense against candidiasis, whereas the role of Th17 cells remains controversial. IL-17 mediates inflammatory pathology in a gastric model of mucosal candidiasis, but is host protective in disseminated disease. Here, we directly compared Th1 and Th17 function in a model of OPC. Th17-deficient (IL-23p19(-/-)) and IL-17R-deficient (IL-17RA(-/-)) mice experienced severe OPC, whereas Th1-deficient (IL-12p35(-/-)) mice showed low fungal burdens and no overt disease. Neutrophil recruitment was impaired in IL-23p19(-/-) and IL-17RA(-/-), but not IL-12(-/-), mice, and TCR-alphabeta cells were more important than TCR-gammadelta cells. Surprisingly, mice deficient in the Th17 cytokine IL-22 were only mildly susceptible to OPC, indicating that IL-17 rather than IL-22 is vital in defense against oral candidiasis. Gene profiling of oral mucosal tissue showed strong induction of Th17 signature genes, including CXC chemokines and beta defensin-3. Saliva from Th17-deficient, but not Th1-deficient, mice exhibited reduced candidacidal activity. Thus, the Th17 lineage, acting largely through IL-17, confers the dominant response to oral candidiasis through neutrophils and antimicrobial factors.
Mechanisms of vitamin D3 metabolite repression of IgE-dependent mast cell activation
Authors: Kwok-Ho Yip, Natasha Kolesnikoff, Chunping Yu, Nicholas Hauschild, Houng Taing, Lisa Biggs, David Goltzman, Philip A. Gregory, Paul H. Anderson, Michael S. Samuel, Stephen J. Galli, Angel F. Lopez, Michele A. Grimbaldeston
Journal: Journal of Allergy and Clinical Immunology (2014)
Biochemical analyses of eight NKX2.5 homeodomain missense mutations causing atrioventricular block and cardiac anomalies
Authors: H KASAHARA
Journal: Cardiovascular Research (2004)

Objective: There has been considerable interest in understanding determinants of the diverse cardiac phenotypes associated with heterozygous NKX2.5 mutations. We hypothesized that analysis of functional properties of NKX2.5 mutant proteins would result in the ability to classify mutations according to function in a scheme that would help to clarify genotype–phenotype correlations. We analyzed missense mutations in the conserved homeodomain. Methods: We studied in vitro biochemical characteristics, including nuclear localization, DNA binding, transcriptional activation and protein–protein interaction with transcriptional partners (GATA4, TBX5 and NKX2.5 itself), of eight homeodomain missense mutations. Associated phenotypes include atrioventricular (AV) block (98% penetrance), atrial septal defect (83% penetrance), and additional varied heart malformations. Results: Mutations were present at varied homeodomain locations in the putative nuclear localizing signal (1), helix 2 (1), a turn between helix 2 and 3 (1) and helix 3 (5); a spectrum of biochemical phenotypes was observed. All mutants localized to the nuclei but some exhibited anomalous nuclear distribution. While all mutants exhibited markedly decreased DNA binding and reduced transcriptional activation, interaction with transcriptional partners was varied. Conclusion: Each mutant protein had a unique spectrum of observed properties, but our data show that while dominant negative properties could be demonstrated in vitro, the best correlation with clinical phenotypes resulted from the markedly reduced DNA binding shared by all eight homeodomain mutations. This suggests that the principle determinant of the two most common phenotypes associated with homeodomain missense mutations is the total dose of NKX2.5 capable of binding to DNA.
Ordering and Administration of Sedatives and Analgesics During the Withholding and Withdrawal of Life Support From Critically III Patients
Authors: William C. Wilson
Journal: JAMA (1992)

<h3>Objective.</h3> —To determine why and how sedatives and analgesics are ordered and administered during the withholding and withdrawal of life support from critically ill patients. <h3>Design.</h3> —Prospective case series. <h3>Setting.</h3> —Medical-surgical intensive care units at a county hospital and a university hospital. <h3>Patients.</h3> —Consecutive 1-year sample of 22 patients from whom life support was withheld or withdrawn in one intensive care unit at a county hospital and a random sample of 22 similar patients in the intensive care unit in the university hospital over the same period. <h3>Main Outcome Measures.</h3> —Physicians and nurses were interviewed to determine their reasons for ordering and administering drugs, and medical records were reviewed to document amounts of drugs ordered and administered. <h3>Results.</h3> —Drugs were given to 75% of patients during withholding and withdrawal of life support. Patients who did not receive medication were comatose and considered incapable of benefiting from sedation and analgesia. The median time until death following the initiation of the withholding or withdrawal of life support was 3.5 hours in the patients who received drugs and 1.3 hours in those patients who did not (P, not significant). Physicians ordered drugs to decrease pain in 88% of patients, to decrease anxiety in 85%, to decrease air hunger in 76%, to comfort families in 82%, and to hasten death in 39%; in no instance was hastening death the only reason cited. The amounts of benzodiazepines and opiates averaged 2.2 mg/h of diazepam and 3.3 mg/h of morphine sulfate in the 24 hours before withholding and withdrawal of life support and 9.8 mg/h and 11.2 mg/h in the 24 hours thereafter (<i>P</i>&lt;.025 and<i>P</i>&lt;.001, respectively). <h3>Conclusions.</h3> —Large doses of sedatives and analgesics were ordered primarily to relieve pain and suffering during the withholding and withdrawal of life support, and death was not hastened by drug administration. (<i>JAMA</i>. 1992;267:949-953)
Stereotypies in Sows during Chronic Stress
Authors: Piet R. Wiepkema, Willem G.P. Schouten
Journal: Psychotherapy and Psychosomatics (1992)

In pig husbandry sows are fixed in such a way that they undergo a chronic loss of control over their environment. In these conditions sows develop stereotypies that are associated with a specific activation of brain endorphins. Stereotyping itself reduces some neuroendocrine stress symptoms. During stress at least two coping styles can be distinguished in many mammals and birds. These types are found again in the stressed sows which either maintain a high or a low level of stereotypies. The low stereotyping sows show the strongest signs of uneasiness.
Alteration of Adenosine Receptors in Patients with Chronic Obstructive Pulmonary Disease
Authors: Katia Varani, Gaetano Caramori, Fabrizio Vincenzi, Ian Adcock, Paolo Casolari, Edward Leung, Stephen MacLennan, Stefania Gessi, Silvana Morello, Peter J. Barnes, Kazuhiro Ito, Kian Fan Chung, Giorgio Cavallesco, Gianfranco Azzena, Alberto Papi, Pier Andrea Borea
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of mortality worldwide. Adenosine is an inflammatory regulator that acts through four distinct receptors to mediate pro- and antiinflammatory effects.The primary aim of this study was to investigate the expression, affinity, and density of adenosine receptors in peripheral lung parenchyma from age-matched smokers with COPD (n = 14) and smokers with normal lung function (control group; n = 20).Adenosine receptors were analyzed by immunohistochemistry and saturation binding assays using typical antagonist radioligands.A(1), A(2A), A(2B), and A(3) receptors were expressed in different cells in peripheral lung parenchyma. The affinity of A(1), A(2A), and A(3) receptors was significantly decreased in patients with COPD compared with the control group (K(D)[A(1)] = 3.15 +/- 0.19 vs. 1.70 +/- 0.14 nM; K(D)[A(2A)] = 7.88 +/- 0.68 vs. 1.87 +/- 0.09 nM; K(D)[A(3)] = 9.34 +/- 0.27 vs. 4.41 +/- 0.25 nM; p < 0.01), whereas their density was increased (Bmax[A(1)] = 53 +/- 4 vs. 32 +/- 3 fmol/mg protein; Bmax[A(2A)] = 852 +/- 50 vs. 302 +/- 12 fmol/mg protein; Bmax[A(3)] = 2,078 +/- 108 vs. 770 +/- 34 fmol/mg protein; p < 0.01). The affinity of A(2B) receptors was not altered, but the density was significantly decreased in patients with COPD compared with the control group (Bmax = 66 +/- 5 vs. 189 +/- 16 fmol/mg protein; p < 0.01). A significant correlation was found between the affinity and density of the adenosine receptors and the FEV(1)/FVC ratio.This is the first report showing the presence of adenosine receptors in lung parenchyma in subjects with COPD compared with control smokers. These novel findings strengthen the hypothesis of a potential role played by adenosine receptors in the pathogenesis of COPD.