tbuckley/cabot-search huggingface dataset:
Assessment of Quality of Life in the Supportive Care Setting of the Big Lung Trial in Non–Small-Cell Lung Cancer
Authors: J. Brown, H. Thorpe, V. Napp, D.J. Fairlamb, N.H. Gower, R. Milroy, M.K.B. Parmar, R.M. Rudd, S.G. Spiro, R.J. Stephens, D. Waller, P. West, M.D. Peake
Journal: Journal of Clinical Oncology (2005)

The Big Lung Trial (BLT) was a large, pragmatic trial to evaluate the addition of chemotherapy to primary treatment (ie, surgery, radical radiotherapy, or supportive care) in non-small-cell lung cancer (NSCLC). In the supportive care group, there was a small but significant survival benefit in patients treated with chemotherapy compared with supportive care alone (no chemotherapy). A substudy was undertaken to evaluate the quality of life (QoL) implications of the treatment options. QoL was assessed using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires C30 (QLQ-C30) and LC17, and daily diary cards.EORTC QLQ-C30 and LC17 were collected at 0, 6 to 8, 12, 18, and 24 weeks. Diary cards were completed during the first 12 weeks of the study. The primary end point was global QoL at 12 weeks.A total of 273 patients were randomly assigned: 138 to no chemotherapy and 135 to chemotherapy. There was no evidence of a large detrimental effect on QoL of chemotherapy. No statistically significant differences in global QoL or physical/emotional functioning, fatigue and dyspnea, and pain were detected at 12 weeks. Higher rates of palliative radiotherapy in the no chemotherapy arm may have lessened differences in QoL. Global QoL, role functioning, fatigue, appetite loss, and constipation were prognostic indicators of survival at 12 weeks.There were no important adverse effects of chemotherapy on QoL.
A longitudinal study of lung function from 1 month to 18 years of age
Authors: Steve Turner, Shona Fielding, Dave Mullane, Des W Cox, Jack Goldblatt, Lou Landau, Peter le Souef
Journal: Thorax (2014)

<h3>Background</h3> Our hypothesis was that factors associated with wheeze will be associated with changes in lung function trajectory between 1 month and 18 years of age. <h3>Methods</h3> Measurements of lung function were made in individuals aged 1, 6 and 12 months (V9maxFRC), and also at ages 6, 12 and 18 years (FEF<sub>25–75</sub>). Changes in lung function over time relative to sex, a history of asthma, maternal asthma and other factors were explored using random coefficient models. <h3>Results</h3> Lung function (maximal flow at functional residual capacity in infants and FEF<sub>25–75</sub> in children) was determined in 241 individuals at 1 month, 192 at 6 months, 164 at 12 months, 106 at 6 years, 183 at 12 years and 141 at 18 years. In the multivariable model, maternal asthma (mean reduction in lung function 9.8%), flow limitation (mean reduction 17.4%), infant atopy (mean reduction 12.6%) and maternal smoking (mean reduction in lung function 8.1%) were acting independently. When interactions with time were sought, the reduction in lung function associated with maternal asthma and infant atopy were consistent over time, but % lung function increased in boys by a mean of 1%/year compared with girls, in flow-limited individuals by 3.0%/year and by 0.9%/year for those exposed to maternal smoking during pregnancy compared to other cohort members. <h3>Conclusions</h3> Decrements in lung function in 18-year-olds associated with maternal asthma and early onset atopy may be determined by 1 month of age. Low initial lung function in some individuals can ‘recover’ in some settings.
Biological changes associated with healthy versus pathological aging: A symposium review
Authors: M.N. Rajah, S. Bastianetto, K. Bromley-Brits, R. Cools, M. D’Esposito, C.L. Grady, J. Poirier, R. Quirion, N. Raz, E. Rogaeva, W. Song, J. Pruessner
Journal: Ageing Research Reviews (2009)
Angiotensin-converting Enzyme Inhibition Delays Pulmonary Vascular Neointimal Formation
Authors: KAZUSHIGE OKADA, MATTHEW L. BERNSTEIN, WEI ZHANG, DANIEL P. SCHUSTER, MITCHELL D. BOTNEY
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Primary pulmonary hypertension (PPH) is a disease characterized pathologically by pulmonary artery medial hypertrophy, adventitial thickening, and neointimal proliferation. Increasing recognition of the importance of remodeling to the pathogenesis of PPH suggests new therapeutic possibilities, but it will be necessary to (1) identify essential mediators of remodeling, and (2) demonstrate that inhibiting those mediators suppresses remodeling before new antiremodeling therapies can be considered feasible. The effect of angiotensin-converting enzyme (ACE) inhibition on pulmonary vascular remodeling was studied in a newly developed rat model in which neointimal lesions develop between 3 and 5 wk after monocrotaline injury is coupled with increased pulmonary artery blood flow after contralateral pneumonectomy. Neointimal formation was significantly suppressed at 5 wk by ACE inhibition whether it was started 10 d before or 3 wk after remodeling was initiated, although medial hypertrophy and adventitial thickening still developed. By 11 wk, the extent of neointimal formation in rats treated with ACE inhibition was similar to rats without ACE inhibition at 5 wk. Pulmonary artery pressures and right ventricular weights correlated with the extent of neointimal formation. Northern blot analysis and in situ hybridization demonstrated marked suppression of lung tropoelastin and type I procollagen gene expression in the presence of ACE inhibition. An angiotensin II type I receptor antagonist partially, but not completely, replicated the effects of ACE inhibition. These data suggest that the tissue angiotensin system may be a target for therapeutic efforts to suppress the vascular remodeling that is characteristic of primary pulmonary hypertension.
Relationship of Blood Transfusion and Clinical Outcomes in Patients With Acute Coronary Syndromes
Authors: Sunil V. Rao
Journal: JAMA (2004)

It is unclear if blood transfusion in anemic patients with acute coronary syndromes is associated with improved survival.To determine the association between blood transfusion and mortality among patients with acute coronary syndromes who develop bleeding, anemia, or both during their hospital course.We analyzed 24,112 enrollees in 3 large international trials of patients with acute coronary syndromes (the GUSTO IIb, PURSUIT, and PARAGON B trials). Patients were grouped according to whether they received a blood transfusion during the hospitalization. The association between transfusion and outcome was assessed using Cox proportional hazards modeling that incorporated transfusion as a time-dependent covariate and the propensity to receive blood, and a landmark analysis.Thirty-day mortality.Of the patients included, 2401 (10.0%) underwent at least 1 blood transfusion during their hospitalization. Patients who underwent transfusion were older and had more comorbid illness at presentation and also had a significantly higher unadjusted rate of 30-day death (8.00% vs 3.08%; P<.001), myocardial infarction (MI) (25.16% vs 8.16%; P<.001), and death/MI (29.24% vs 10.02%; P<.001) compared with patients who did not undergo transfusion. Using Cox proportional hazards modeling that incorporated transfusion as a time-dependent covariate, transfusion was associated with an increased hazard for 30-day death (adjusted hazard ratio [HR], 3.94; 95% confidence interval [CI], 3.26-4.75) and 30-day death/MI (HR, 2.92; 95% CI, 2.55-3.35). In the landmark analysis that included procedures and bleeding events, transfusion was associated with a trend toward increased mortality. The predicted probability of 30-day death was higher with transfusion at nadir hematocrit values above 25%.Blood transfusion in the setting of acute coronary syndromes is associated with higher mortality, and this relationship persists after adjustment for other predictive factors and timing of events. Given the limitations of post hoc analysis of clinical trials data, a randomized trial of transfusion strategies is warranted to resolve the disparity in results between our study and other observational studies. We suggest caution regarding the routine use of blood transfusion to maintain arbitrary hematocrit levels in stable patients with ischemic heart disease.
Morphology of the Cerebral Cortex in Preclinical Huntington’s Disease
Authors: Peg Nopoulos, Vincent A. Magnotta, Ania Mikos, Henry Paulson, Nancy C. Andreasen, Jane S. Paulsen
Journal: American Journal of Psychiatry (2007)

Objective: Cortical morphology was evaluated in subjects with known gene expansion for Huntington's disease and no manifest disease. Method: Magnetic resonance imaging scans were obtained for 24 subjects with preclinical Huntington's disease and were compared to those for 24 matched healthy subjects by means of novel imaging methods to quantify aspects of cortical structure. Results: In relation to the comparison subjects, those with preclinical Huntington's disease showed altered cortex morphology with enlargement of gyral crowns and abnormally thin sulci. These changes were manifested in global alterations of gyral and sulcal shape. Conclusion: These findings lend support to the notion that, in addition to the degenerative process, abnormal neural development may also be an important process in the pathoetiology of Huntington's disease.
PWE-047 When Should I Take Terminal Ileal Biopsies? Experience From A Single Unit: Abstract PWE-047 Table 1
Authors: LJ Neilson, R Bevan, CJ Rees
Journal: Gut (2014)

<h3>Introduction</h3> Terminal ileum (TI) intubation at colonoscopy may be useful in the investigation of patients with diarrhoea or possible inflammatory bowel disease (IBD).<sup>1,2 </sup>The yield of TI biopsies is variable and there are no standards for current practice.<sup>2,3</sup> Furthermore, in the UK concerns remain regarding the potential for prion transmission. <h3>Methods</h3> We aim to establish the yield of TI biopsies in a single unit. All TI biopsies recorded on the pathology system in a 3-year period were reviewed. Colonoscopy reports and case notes were reviewed to establish if biopsy results were clinically relevant (defined as altering management). Statistical analysis was performed using SPSS. P values were calculated using Fisher’s exact test to show any difference in biopsy yield between normal and abnormal looking mucosa for each indication. The values were calculated for all abnormal biopsy results and clinically relevant biopsy results. <h3>Results</h3> 129 TI biopsies were taken between September 2010 and September 2013, 49 (38%) male and 80 (62%) female. Mean age 44 years (s.d. 17.2). There were 29 (22.5%) cases of known IBD. 5 (3.9%) cases were completion colonoscopies after colorectal cancer surgery where TI biopsies are taken to prove a complete examination. <h3>Conclusion</h3> We demonstrate that when investigating patients with diarrhoea, abdominal pain or IBD, if the terminal ileum is visually normal, biopsies do not add to the clinical picture. There is a higher yield of relevant biopsy abnormalities when the TI appears abnormal. We can recommend within our practice that visual assessment of a normal terminal ileum is adequate, thereby reducing unnecessary biopsies. This reduces the workload for pathology laboratories, reduces risk from biopsies and improves patient care as normal results can be communicated sooner to the patient. <h3>References</h3> 1 Morini S, <i><i>et al</i></i>. Retrograde ileoscopy in chronic nonbloody diarrhea: a porspective, case-control study. <i>Am J Gastroenterol</i> 2003;98(7):1512–15 2 Geboes K, <i><i>et al</i>. </i>Is ileoscopy with biopsy worthwhile in patients presenting with symptoms of inflammatory bowel disease? <i>Am J Gastroenterol</i> 1998;93(2):201–206 3 Melton SD, <i><i>et al</i>. </i>Ileal biopsy:Clinical indications, endoscopic and histopathologic findings in 10,000 patients. <i>Dig Liver Dis</i> 2011;43(3):199–203 <h3>Disclosure of Interest</h3> None Declared.
S6 The FENOtype Trial: Inhaled Corticosteroid Dose-Response Using Domiciliary Exhaled Nitric Oxide in Persistent Asthma
Authors: WJ Anderson, PM Short, PA Williamson, BJ Lipworth
Journal: Thorax (2012)

<h3>Background</h3> International guidelines advocate a standard approach to asthma management for all despite its heterogeneity. ‘Personalised’ treatment for inflammatory asthma phenotypes confers superior benefits. We wished to evaluate dose-response to inhaled corticosteroids (ICS) in asthmatics with an elevated exhaled nitric oxide (FeNO) phenotype using domiciliary measurements. <h3>Methods</h3> We performed a randomised, cross-over trial in 21 mild-to-moderate persistent asthmatics receiving ICS with elevated FeNO (&gt;30ppb) that increased further (&gt;10ppb) after ICS washout. Patients were randomised to 2 weeks of either fluticasone propionate 50µg twice-daily (FP100) or 250µg twice-daily (FP500). The primary outcome was response in diurnal domiciliary FeNO levels. Secondary outcomes included: mannitol challenge; serum eosinophilic cationic protein (ECP); blood eosinophil count; and asthma control questionnaire (ACQ). <h3>Results</h3> We found significant dose-related reductions of diurnal FeNO compared to baseline - morning FeNO: baseline=71ppb (95%CI:61–83ppb); FP100=34ppb (95%CI:29–40ppb), p&lt;0.001; FP500=27ppb (95%CI:22–33ppb), p&lt;0.001; and significant dose separation for morning, p&lt;0.05, and evening, p&lt;0.001. Time series FeNO displayed exponential decay (Figure 1): FP100 R2=0.913, half-life=69hrs (95%CI:50–114hrs); FP500 R2=0.966, half-life=55hrs (95%CI:45–69hrs); as well as diurnal variation. ACQ showed significant improvements exceeding the minimal important difference (&gt;0.5) with values in keeping with controlled asthma (&lt;0.75) after each dose: FP100=0.48 (95%CI:0.24–0.71), p=0.004; FP500=0.37 (95%CI:0.18–0.57), p=0.001. All other secondary inflammatory related outcomes (mannitol, ECP and eosinophils) showed significant improvements from baseline but no dose separation. <h3>Conclusions</h3> There is a significant dose-response of diurnal FeNO to ICS in asthmatics with an elevated FeNO phenotype, which translates into well-controlled asthma. Further interventional studies are warranted using domiciliary FeNO in this specific phenotype.
α-Cells of the Endocrine Pancreas: 35 Years of Research but the Enigma Remains
Authors: Jesper Gromada, Isobel Franklin, Claes B. Wollheim
Journal: Endocrine Reviews (2007)

Glucagon, a hormone secreted from the α-cells of the endocrine pancreas, is critical for blood glucose homeostasis. It is the major counterpart to insulin and is released during hypoglycemia to induce hepatic glucose output. The control of glucagon secretion is multifactorial and involves direct effects of nutrients on α-cell stimulus-secretion coupling as well as paracrine regulation by insulin and zinc and other factors secreted from neighboring β- and δ-cells within the islet of Langerhans. Glucagon secretion is also regulated by circulating hormones and the autonomic nervous system. In this review, we describe the components of the α-cell stimulus secretion coupling and how nutrient metabolism in the α-cell leads to changes in glucagon secretion. The islet cell composition and organization are described in different species and serve as a basis for understanding how the numerous paracrine, hormonal, and nervous signals fine-tune glucagon secretion under different physiological conditions. We also highlight the pathophysiology of the α-cell and how hyperglucagonemia represents an important component of the metabolic abnormalities associated with diabetes mellitus. Therapeutic inhibition of glucagon action in patients with type 2 diabetes remains an exciting prospect.
Nuclear Accumulation of Globular Actin as a Cellular Senescence Marker
Authors: In Hae Kwak, Hong Seok Kim, Ok Ran Choi, Min Sook Ryu, In Kyoung Lim
Journal: Cancer Research (2004)

Abstract We evaluated the nuclear actin accumulation as a new marker of cellular senescence, using human diploid fibroblast (HDF), chondrocyte primary cultures, Mv1Lu epithelial cells, and Huh7 cancer cells. Nuclear accumulation of globular actin (G-actin) and dephosphorylated cofilin was highly significant in the senescent HDF cells, accompanied with inhibition of LIM kinase (LIMK) -1 activity. When nuclear export of the actin was induced by 12-O-tetradecanoylphorbol-13-acetate, DNA synthesis of the senescent cells increased significantly, accompanied with changes of morphologic and biochemical profiles, such as increased RB protein phosphorylation and decreased expressions of p21WAF1, cytoplasmic p-extracellular signal-regulated kinase 1/2, and caveolins 1 and 2. Significance of these findings was strengthened additionally by the fact that nuclear actin export of young HDF cells was inhibited by the treatment with leptomycin B and mutant cofilin transfection, whose LIMK-1 phosphorylation site was lost, and the old cell phenotypes were duplicated with nuclear actin accumulation, suggesting that nuclear actin accumulation was accompanied with G1 arrest during cellular senescence. The aforementioned changes were observed not only in the replicative senescence but also in the senescence induced by treatment of HDF cells, Mv1Lu, primary culture of human chondrocytes, or Huh7 cells with H-ras virus infection, hydroxyurea, deferoxamine, or H2O2. Nuclear actin accumulation was much more sensitive and an earlier event than the well-known, senescence-associated β-galactosidase activity.
Activation of RhoA by Thrombin in Endothelial Hyperpermeability
Authors: Geerten P. van Nieuw Amerongen, Sanne van Delft, Mario A. Vermeer, John G. Collard, Victor W. M. van Hinsbergh
Journal: Circulation Research (2000)

Endothelial cells (ECs) actively regulate the extravasation of blood constituents. On stimulation by vasoactive agents and thrombin, ECs change their cytoskeletal architecture and small gaps are formed between neighboring cells. These changes partly depend on a rise in [Ca(2+)](i) and activation of the Ca(2+)/calmodulin-dependent myosin light chain kinase. In this study, mechanisms that contribute to the thrombin-enhanced endothelial permeability were further investigated. We provide direct evidence that thrombin induces a rapid and transient activation of RhoA in human umbilical vein ECs. Under the same conditions, the activity of the related protein Rac was not affected. This was accompanied by an increase in myosin light chain phosphorylation, the generation of F-actin stress fibers, and a prolonged increase in endothelial permeability. Inhibition of the RhoA target Rho kinase with the specific inhibitor Y-27632 reduced all of these effects markedly. In the presence of Y-27632, the thrombin-enhanced permeability was additionally reduced by chelation of [Ca(2+)](i) by BAPTA. These data indicate that RhoA/Rho kinase and Ca(2+) represent 2 pathways that act on endothelial permeability. In addition, the protein tyrosine kinase inhibitor genistein reduced thrombin-induced endothelial permeability without affecting activation of RhoA by thrombin. Our data support a model of thrombin-induced endothelial permeability that is regulated by 3 cellular signal transduction pathways.
The Plight of Academic Health Centers
Authors: Catherine D. DeAngelis
Journal: JAMA (2000)

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The relationship between patellar tendinopathy risk factors and ground reaction forces during cross-over block jump landings
Authors: I Janssen, J R Steele, B J Munro, N A T Brown
Journal: British Journal of Sports Medicine (2011)

Background Overuse knee injuries, such as patellar tendinopathy, are one of the most prevalent and frequent injuries in volleyball with up to 50% of male indoor volleyball players sustaining this injury in their careers. Objective The aim of this research was to examine the intrinsic and extrinsic risk factors associated with patellar tendinopathy including muscle flexibility, muscle strength, vertical jump, and their relationship to vertical ground reaction forces (vGRF) during cross-over block jump landings. Design Structural alignment, lower limb flexibility, and muscle strength assessed were measured for each participant who then performed five trials of a cross-over step block. vGRF (vGRF: 1500 Hz; Kistler) were collected for takeoff and landing. Setting A portable volleyball net was used to simulate a typical and realistic volleyball condition in a biomechanics laboratory. A standard volleyball was mounted on a post and used as a target. Participants Elite male (EM) (N=10), sub-elite male (SEM) (N=10), and sub-elite female (N=10) volleyball players with no existing knee joint injury or history of lower limb surgery participated in this study. Main outcome measurements Magnitudes of and correlations among risk factor measures and peak vGRF. Results Gender differences were observed with SEM displaying significantly smaller Q-angle (p=0.04), greater strength (p=0.00), and maximal jump height (p=0.00) than SEF. EM displayed passive greater hip extension (p=0.01) and trunk flexion (p=0.05), and significantly greater strength in their non-dominant quadriceps (p=0.01) than SEM. SEM generated significantly higher vGRF compared to SEF. Significant negative correlations were found between vGRF and Q-angle and gastrocnemius flexibility for SEF but not SEM or EM. Conclusions The results of this study may provide further insight why and which volleyball athletes may be prone to developing overuse knee injuries.
Acetylcholinesterase Activity, Cohabitation with Floricultural Workers, and Blood Pressure in Ecuadorian Children
Authors: Jose R. Suarez-Lopez, David R. Jacobs, John H. Himes, Bruce H. Alexander
Journal: Environmental Health Perspectives (2013)

Acetylcholinesterase (AChE) inhibitors are commonly used pesticides that can effect hemodynamic changes through increased cholinergic stimulation. Children of agricultural workers are likely to have paraoccupational exposures to pesticides, but the potential physiological impact of such exposures is unclear.
Peutz-Jeghers syndrome: 78-year follow-up of the original family
Authors: Anne Marie Westerman, Mark M Entius, Ellen de Baar, Patrick PC Boor, Rita Koole, M Loes F van Velthuysen, G Johan A Offerhaus, Dick Lindhout, Felix WM de Rooij, JH Paul Wilson
Journal: The Lancet (1999)
Microvascular hyperpermeability in COPD airways
Authors: Y Minakata
Journal: Thorax (2005)

Chronic obstructive pulmonary disease (COPD) is characterised by an abnormal inflammatory response of the lungs. An increase in the albumin concentration in the sputum of COPD patients has previously been reported.1 This may suggest that the airway microvascular permeability is increased in COPD airways because the albumin comes from the vasculature via endothelial contraction at post-capillary venule lesions. However, measurement of sputum samples has some limitations such as contamination by saliva. We have measured the albumin concentration of the airway lumen in patients with COPD using a new direct …