tbuckley/cabot-search huggingface dataset:
P45 Outcomes following pulmonary rehabilitation for patients with restrictive lung diseases with or without oxygen therapy
Authors: V. L. Warrington, J. Scullion, L. Sewell, J. Williams, S. Singh.
Journal: Thorax (2010)

<h3>Introduction</h3> To review the outcome of pulmonary rehabilitation (PR) for patients with restrictive lung diseases who do or not have oxygen therapy. <h3>Methods</h3> 10 years of PR data were searched for patients with Interstitial Lung Disease (ILD), Pulmonary Fibrosis (PF) or Cryptogenic Fibrosing Alveolitis (CFA) who had completed PR. PR classes were twice weekly for 7 weeks which consisted of training based on a walking programme, static bike and strength exercises. Exercise capacity measured by Incremental Shuttle Walk Test (ISWT) and Endurance Shuttle Walk Test (ESWT), health status measured by Hospital Anxiety and Depression Scale (HADS) and Chronic Respiratory Questionnaire – self-reported (CRQ) results were analysed. <h3>Results</h3> 25/81 patients who had completed PR were oxygen users: 16 male, mean(SD) age 69.8 (7.7) years; FEV<sub>1</sub> 1.95(0.63) l; FVC 2.52 (0.8) l; FEV<sub>1</sub>/FVC 81.83 (8.43)%; BMI 28.6 (5.97). 10 had ambulatory, 5 had long term and 10 used short-burst oxygen therapy with a median flow rate of 4 l/min. Patients without oxygen were 72.3 (9.5) years with a FEV<sub>1</sub> 1.84(0.61) l; FVC 2.41 (0.68) l; FEV<sub>1</sub>/FVC 78.58 (7.3)%; BMI 27.65(5.05); 33 male. Independent T-Tests revealed the only significant baseline difference between the groups was resting oxygen saturation (SaO<sub>2</sub>) with oxygen users having a mean SaO<sub>2</sub> of 90.5% compared to non-oxygen users′ SaO<sub>2</sub> being 94.8% (p=0.001). Paired T-Tests were performed between baseline and discharge scores for both groups (Abstract P45 Table 1). Those not using oxygen improved their mean change in ISWT (p=0.026) and ESWT (p=0.039) scores between baseline and discharge significantly more than those using oxygen. Oxygen users had significantly (p&lt;0.001) lower SaO<sub>2</sub> levels after performing ISWT (78% compared to 89%) and ESWT (78% compared to 87%) than those not using oxygen. <h3>Conclusion</h3> PR produces positive outcomes for patients with ILD, CFA or PF. Improvements in exercise capacity and health status for non-oxygen users were statistically and clinically significant, more so than for oxygen users. Those using oxygen de-saturated more than those not using oxygen after performing the SWTs. As both groups of patients benefited, PR should be offered to all patients with restrictive lung diseases irrespective of oxygen use, although the typical PR programme may need some adjustment for oxygen users to gain more benefit.
The epidemiology of rock-climbing injuries
Authors: G Jones, A Asghar, D J Llewellyn
Journal: British Journal of Sports Medicine (2007)

To determine the prevalence and nature of rock-climbing injuries, and the factors associated with these injuries.A retrospective cross-sectional study.Rock climbers were recruited at five outdoor and six indoor climbing venues in the UK.201 active rock climbers (163 male, 38 female climbers) aged 16-62 years.Rock climbing behaviours and key demographics.Injuries requiring medical attention or withdrawal from participation for > or = 1 day.Around 50% of climbers had sustained > or = 1 injury in the past 12 months, causing a total of 275 distinct anatomical injuries. 21 climbers (10%) had sustained acute climbing injuries as a result of a fall, 67 (33%) had chronic overuse injuries, and 57 (28%) had acute injuries caused by strenuous climbing moves. Dedicated climbers participating in different forms of rock climbing more often and at a higher level of technical difficulty may be more prone to injury, particularly overuse injuries of the finger and shoulder. The principal sources of treatment or advice sought by climbers were physiotherapists (18%), other climbers (14%) and doctors (11%).Climbing frequency and technical difficulty are associated with climbing injuries occurring at both indoor and outdoor venues, particularly cumulative trauma to the upper extremities.
The 'SMSA' Scoring System for Determining the Complexity of a Polyp
Authors: S. Gupta, D. Miskovic, P. Bhandari, S. Dolwani, B. McKaig, R. Pullan, B. Rembacken, M. D. Rutter, S. Riley, R. Valori, M. E. Vance, O. D. Faiz, B. P. Saunders, S. Thomas-Gibson
Journal: Gut (2011)

<h3>Introduction</h3> It may be possible to identify several 'levels' of polypectomy service within the UK, each requiring a different range of polypectomy skills: flexible sigmoidoscopy screening, non-screening colonoscopy, screening colonoscopy and the specialist endoscopy service. This requires a definition of 'complexity levels' of polyps, to reflect the four levels of service, each with clearly defined parameters that represent the bare minimum that an endoscopist operating at a particular level should be able to deal with competently. <h3>Methods</h3> The aim of this study was to define polyp levels to reflect the four levels of competency required to deliver a particular service, based on polyp characteristics. Consensus by nine experienced endoscopists regarding the parameters that determine the complexity of a polyp, was achieved using group meetings and the Delphi method. The same group of experts then assigned a polyp complexity level to each possible combination of factors. <h3>Results</h3> The group identified four factors to be most relevant for determining the complexity of a polypectomy: size (S), morphology (M), site (S) and access (A). In two Delphi rounds the benchmarks for each factor were evaluated (see table). After analysing the expected complexity for each polyp type as proposed by the experts, a scoring system was established, based on size (1–9 points), morphology (1–3 points), site (1–2 points) and access (1–3 points). Four polyp levels (with increasing level of complexity) were identified based on the range of expert scores obtained: Level 1 (4–5), Level 2 (6–9), Level 3 (10–12) and Level 4 (&gt;12). <h3>Conclusion</h3> Defining polyp complexity levels may be useful for planning training, competency assessment and certification in colonoscopic polypectomy. In turn this may allow for more efficient service delivery and referral onto specialist centres where appropriate. <h3>Competing interests</h3> None.
Orthostatic Factors in Pulsus Alternans
Authors: BEN FRIEDMAN, WILLIAM M. DAILY, ROY S. SHEFFIELD
Journal: Circulation (1953)

Ventricular alternans was present in three cardiac patients only in the erect or semierect position and disappeared with recumbency. The phenomenon which was regularly reproduced in the standing posture was prevented or minimized by exercise, digitalis, infusions of blood and norepinephrine and by application of external vascular support. Ventricular alternation in the supine patient was noted only after phlebotomy, or venous pooling combined with Valsalva maneuvers. The observations suggest that in the mechanism of this type of pulsus alternans there is an important peripheral hemodynamic factor which exerts its effect by changes in diastolic length of an injured ventricular muscle.
Obliteration of the leftatrial appendage forprevention of thromboembolism**Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Jonathan L Halperin, Mardi Gomberg-Maitland
Journal: Journal of the American College of Cardiology (2003)
Xanthine Oxidase–Dependent Regulation of Hypoxia-Inducible Factor in Cancer Cells
Authors: Corinne E. Griguer, Claudia R. Oliva, Eric E. Kelley, Gregory I. Giles, Jack R. Lancaster, G. Yancey Gillespie
Journal: Cancer Research (2006)

During chemical hypoxia induced by cobalt chloride (CoCl2), hypoxia-inducible factor 1alpha (HIF1-alpha) mediates the induction of a variety of genes including erythropoietin and vascular endothelial growth factor. We used glioma cells with oxidative phosphorylation-dependent (D54-MG) and glycolytic-dependent (U251-MG) phenotypes to monitor HIF1-alpha regulation in association with redox responsiveness to CoCl2 treatment. We showed that CoCl2 increased xanthine oxidase (XO)-derived reactive oxygen species (ROS), which causes accumulation of HIF1-alpha protein in U251-MG cells. Under these conditions, blockade of XO activity by pharmacologic (N-acetyl-L-cysteine or allopurinol) or molecular (by small interfering RNA) approaches significantly attenuated HIF1-alpha expression. Exogenous H2O2 stabilizes HIF1-alpha protein. XO was present in these cells and was the primary source of free radicals. We also showed higher XO activity in cells exposed to CoCl2 compared with cells grown in normoxia. From the experiments shown here, we concluded that ROS were indeed generated in D54-MG cells exposed to CoCl2 but it was unlikely that ROS participated in the hypoxic signal transduction pathways in this cell type. Possibly, cell type-dependent and stimulus-dependent factors may control ROS dependency or redox sensitivity of HIF1-alpha and thus HIF1-alpha activation either directly or by induction of specific signaling cascades. Our findings reveal that XO-derived ROS is a novel and critical component of HIF1-alpha regulation in U251-MG cells, pointing toward a more general role of this transcription factor in tumor progression.
The FLT3 Internal Tandem Duplication Mutation Prevents Apoptosis in Interleukin-3-Deprived BaF3 Cells Due to Protein Kinase A and Ribosomal S6 Kinase 1–Mediated BAD Phosphorylation at Serine 112
Authors: Xinping Yang, Liyun Liu, David Sternberg, Liren Tang, Ilene Galinsky, Daniel DeAngelo, Richard Stone
Journal: Cancer Research (2005)

Abstract Internal tandem duplication (ITD) mutations in the FLT3 tyrosine kinase have been detected in ∼20% of acute myeloid leukemia (AML) patients. Patients harboring FLT3/ITD mutations have a relatively poor prognosis. FLT3/ITD results in constitutive autophosphorylation of the receptor and factor-independent survival. Previous studies have shown that FLT3/ITD activates the signal transducers and activators of transcription 5 (STAT5), p42/p44 mitogen-activated protein kinase [MAPK; extracellular signal-regulated kinase (ERK) 1/2], and phosphatidylinositol 3-kinase/Akt pathways. We herein provide biochemical and biological evidence that ribosomal S6 kinase 1 (RSK1) and protein kinase A (PKA) are the two principal kinases that mediate the antiapoptotic function of FLT3/ITD via phosphorylation of BAD at Ser112. Inhibiting both MAPK kinase (MEK)/ERK and PKA pathways by a combination of U0126 (10 μmol/L) and H-89 (5 μmol/L) reduced most of BAD phosphorylation at Ser112 and induced apoptosis to a level comparable with that induced by FLT3 inhibitor AG1296 (5 μmol/L) in BaF3/FLT3/ITD cells. RNA interference of RSK1 or PKA catalytic subunit reduced BAD phosphorylation and induced apoptosis. The MEK inhibitor U0126 and/or the PKA inhibitor H-89 greatly enhanced the efficacy of the FLT3 inhibitor AG1296, suggesting that combining FLT3/ITD downstream pathway inhibition with FLT3 inhibitors may be a viable therapeutic strategy for AML caused by a FLT3/ITD mutation.
Does Detection of Merkel Cell Polyomavirus in Merkel Cell Carcinoma Provide Prognostic Information?
Authors: James A. DeCaprio
Journal: JNCI Journal of the National Cancer Institute (2009)

JNCI | Editorials 905 Awareness of Merkel cell carcinoma (MCC) is increasing within the scientific and medical communities. MCC is a highly lethal skin cancer: Approximately 30% of all MCC patients die from metastatic disease within 2 years of diagnosis ( 1 ). The incidence of this relatively rare skin cancer has increased threefold over the past 20 years ( 2 ). Approximately 1500 new cases of MCC were diagnosed in the United States in 2008 ( 1 ). Remarkably, a new human polyomavirus (later named Merkel cell polyomavirus [MCPyV]) was discovered last year when viral DNA was found to be integrated into the tumor chromosomal DNA from eight of 10 cases of MCC ( 3 ). In one of these cases, DNA from the virus was integrated at the same site in the primary tumor and in a metastasis, indicating that clonal integration of the virus occurred in the primary tumor before Does Detection of Merkel Cell Polyomavirus in Merkel Cell Carcinoma Provide Prognostic Information?
US drug agency is slow to exclude doctors who commit research crimes from further trials
Authors: J. Hopkins Tanne
Journal: BMJ (2009)

The US Food and Drug Administration has taken up to 11 years to debar doctors who engage in misconduct or crimes from participating in research involving new drugs, biologics, and medical devices, shows a report from the US Government Accountability Office.

Among the types of “alleged misconduct” cited by the FDA in its disqualification proceedings are submitting false information to the sponsor or to the FDA; failing to comply with requirements for obtaining informed consent from trial participants; failing to obtain approval from institutional review boards; failing to comply with the clinical trial’s research plan; failing to keep records about the use and disposal of investigational drugs, biologics, or devices; and failing …
Is the European Pediatric Medicine Regulation Working for Children and Adolescents with Cancer?
Authors: Gilles Vassal, Birgit Geoerger, Bruce Morland
Journal: Clinical Cancer Research (2013)

The European Pediatric Medicine Regulation was launched in 2007 to provide better medicines for children. Five years later, the number of new anticancer drugs in early development in the pediatric population remains low, and most children with cancer are still largely denied access to innovative drugs in Europe, as compared with the United States. We analyzed individual pediatric investigation plan (PIP) and waiver decisions for oncology drugs and all oncology drugs that have been approved for marketing authorization since 2007 in Europe. Among the 45 approved PIPs, 33% concern leukemias and lymphomas, 29% solid tumors, 13% brain tumors, and 20% a drug for supportive care. No specific PIP exists for life-threatening diseases such as high-risk neuroblastoma, whereas there are several PIPs in extremely rare malignancies in children and adolescents such as gastrointestinal stromal tumor, melanoma, thyroid cancer, and chronic myeloid leukemia. This paradoxical situation is due to approval of a PIP being driven by the adult indication. Twenty-six of 28 authorized new oncology drugs have a potentially relevant mechanism of action for pediatric malignancies, but 50% have been waived because the adult condition does not occur in children. The most striking example is crizotinib. Implementation of the pediatric regulation should no longer be driven by the adult indication but should be guided instead by the biology of pediatric tumors and the mechanism of action of a drug. This change will be achievable through voluntary PIPs submitted by Pharma or revocation of the oncology class waiver list.
A History of Clinical Psychology as a Profession in America (and a Glimpse at Its Future)
Authors: Ludy T. Benjamin
Journal: Annual Review of Clinical Psychology (2004)

Clinical psychology emerged as a profession in the United States in the 1890s with studies conducted by psychologists with patients in the mental asylums of that time, and with the founding of Witmer's psychological clinic, where he treated children with learning and behavioral problems. This chapter traces the history of clinical psychology as a profession, from the focus on assessment at the turn of the twentieth century to the provision of psychotherapy that would come to dominate the field after World War II. It concludes with a discussion of some of the contemporary concerns in the profession and how those might impact the future practice of clinical psychologists.
Relationship Between Plasma LDL Concentrations During Treatment With Pravastatin and Recurrent Coronary Events in the Cholesterol and Recurrent Events Trial
Authors: Frank M. Sacks, Lemuel A. Moyé, Barry R. Davis, Thomas G. Cole, Jean L. Rouleau, David T. Nash, Marc A. Pfeffer, Eugene Braunwald
Journal: Circulation (1998)

Although LDL lowering has been shown to reduce recurrent coronary events in patients with coronary heart disease, little direct information is available on the extent of LDL lowering required to achieve this outcome.The Cholesterol and Recurrent Events (CARE) trial compared pravastatin and placebo in patients who had experienced myocardial infarction (MI) who had average concentrations of total cholesterol <240 mg/dL (baseline mean, 209 mg/dL) and LDL cholesterol (LDL) 115 to 174 mg/dL (mean, 139 mg/dL). Pravastatin reduced coronary death or recurrent MI by 24%. In multivariate analysis, the LDL concentration achieved during follow-up was a significant, although nonlinear, predictor of the coronary event rate (P=.007), whereas the extent of LDL reduction was not significant, whether expressed as an absolute amount (P=.97) or a percentage (P=.76). The coronary event rate declined as LDL decreased during follow-up from 174 to approximately 125 mg/dL, but no further decline was seen in the LDL range from 125 to 71 mg/dL. In multivariate analysis, triglyceride but not HDL concentrations during follow-up were weakly but significantly associated with the coronary event rate.The LDL concentrations achieved during treatment with pravastatin or placebo were associated with reduction in coronary events down to an LDL concentration of approximately 125 mg/dL. LDL concentrations <125 mg/dL during treatment were not associated with further benefit. Absolute or percentage reduction in LDL had little relationship to coronary events.
Effects of interleukin-10 on monocyte/endothelial cell adhesion and MMP-9/TIMP-1 secretion
Authors: El Mostafa Mtairag, Sylvie Chollet-Martin, Mounia Oudghiri, Nathalie Laquay, Marie-Paule Jacob, Jean-Baptiste Michel, Laurent J. Feldman
Journal: Cardiovascular Research (2001)

Objective: Monocyte adhesion to endothelial cells and subsequent secretion of matrix metalloproteinases (MMPs) by activated macrophages are key events in arteriosclerosis and restenosis. We tested the hypothesis that interleukin-10 (IL-10), a potent anti-inflammatory cytokine, inhibits monocyte-endothelial cell interactions. Methods: The effect of IL-10 on monocyte/endothelial cell adhesion, as well as on the expression of MMP-9 and the tissue inhibitor of MMP-9, TIMP-1, were first tested in vitro in coculture systems. In addition, we used an ex vivo binding assay to study the inhibitory effect of IL-10 on monocyte adhesion to carotid arteries obtained from either normal, or l-nitro arginine-methyl ester (l-NAME)-treated rats. The effect of IL-10 on the expression of monocyte adhesion molecules (CD18 and CD62-L) was studied by flow cytometry. Results: IL-10 (150 ng/ml) inhibits monocyte adhesion to endothelial cells (by 35%) and to carotid arteries (by 40 and 50%, in normal and l-NAME-treated rats, respectively), via direct modulation of the expression of CD18 and CD62-L. Moreover, IL-10 dose-dependently decreases MMP-9 activity and increases TIMP-1 levels in coculture systems, both at the transcriptional level. Conclusions: Our results suggest that IL-10 is an important modulator of monocyte–endothelial cell interactions.
The Liverpool Statement 2005: Priorities for the European Union/United States Spiral Computed Tomography Collaborative Group
Authors: J.K. Field, R.A. Smith, S.W. Duffy, C.D. Berg, R van Klaveren, C.I. Henschke, D Carbone, P.E. Postmus, E Paci, F.R. Hirsch, J.L. Mulshine
Journal: Journal of Thoracic Oncology (2006)
Inhalation of cold air increases the number of inflammatory cells in the lungs in healthy subjects
Authors: K Larsson, G Tornling, D Gavhed, C Muller-Suur, L Palmberg
Journal: European Respiratory Journal (1998)

Prolonged exposure to cold air may induce a chronic asthma-like condition in healthy subjects as has been demonstrated in cross-country skiers. In the present controlled study, our aim was to elucidate further the link between cold air exposure and airway inflammation by assessing the cellular influx and mediator levels within the airways following acute exposure to cold air. Bronchoalveolar (BAL) and nasal lavages were performed after exposure to cold air (-23 degrees C) and normal indoor air (+22 degrees C) during a light, intermittent work for 2 h in a cross-over design in eight healthy, nonsmoking, subjects. Analyses of inflammatory cell number, cell activation markers, pro-inflammatory cytokines, albumin and interleukin (IL)-8 in lavage fluids were performed. The number of granulocytes and of alveolar macrophages in BAL fluid was significantly higher after cold air exposure (p&lt;0.05). No increase in BAL fluid lymphocytes and no signs of lymphocyte activation in BAL fluid were found. The concentration of IL-8 was unchanged. There were no signs of granulocyte activation (myeloperoxidase, eosinphilic cationic protein) in BAL fluid. Cold air did not influence the number of inflammatory cells or the concentration of albumin and IL-8 in nasal lavage fluid. In conclusion, exposure to cold air induces an increased number of granulocytes and macrophages in the lower airways in healthy subjects without influencing other inflammatory indices such as cellular activation, plasma leakage and pro-inflammatory cytokines. These findings support the hypothesis that cold air could be of pathogenetic importance in the asthma-like condition previously found in cross-country skiers.
DELETION OF HAPTEN-BINDING CELLS BY A HIGHLY RADIOACTIVE 125I CONJUGATE
Authors: Dov Theo Golan, Yves Borel
Journal: The Journal of Experimental Medicine (1972)

Exposure of normal mouse spleen cells in vitro to highly 125I-labeled dinitrophenyl (DNP)-protein carrier conjugates specifically inactivated cells able to mount an immune response to that hapten after in vivo challenge. The deletion was hapten specific and independent of the radioactive carrier to which the hapten was bound. DNP-binding cells were inactivated by radioactivity that was not part of the hapten, but was solely confined to the carrier moiety. The deletion of the anti-DNP response lasted 2–3 wk and could be specifically inhibited.
Prognostic Significance of MTOR Pathway Component Expression in Neuroendocrine Tumors
Authors: Zhi Rong Qian, Monica Ter-Minassian, Jennifer A. Chan, Yu Imamura, Susanne M. Hooshmand, Aya Kuchiba, Teppei Morikawa, Lauren K. Brais, Anastassia Daskalova, Rachel Heafield, Xihong Lin, David C. Christiani, Charles S. Fuchs, Shuji Ogino, Matthew H. Kulke
Journal: Journal of Clinical Oncology (2013)

Clinical studies have implicated the mechanistic target of rapamycin (serine/threonine kinase; MTOR) pathway in the regulation of neuroendocrine tumor (NET) growth. We explored whether expression of MTOR pathway components has prognostic significance in NET patients.We evaluated immunohistochemical expression of MTOR and phospho (p) -MTOR; its downstream targets RPS6KB1, RPS6, and EIF4EBP1; and its upstream regulators, in a cohort of 195 archival neuroendocrine tumors. We correlated expression levels with clinical outcomes, after adjusting for other prognostic variables.We observed anticipated correlations between expression of upstream components of the MTOR pathway and their downstream targets. Expression of PIK3CA, MTOR, or p-EIF4EBP1 was associated with high MKI67 (Ki-67) labeling index. We failed to identify clinical correlations associated with expression of the upstream regulators TSC1, TSC2, AKT, p-AKT, PDPK1, PTEN, PIK3R1, or PIK3CA. In contrast, high expression of MTOR or its activated downstream targets p-RPS6KB1, p-RPS6, or p-EIF4EBP1 was associated with adverse clinical outcomes.Our observations suggest that expression of MTOR or its downstream targets may be adverse prognostic factors in neuroendocrine tumors.
Stable remission after administration of the receptor tyrosine kinase inhibitor SU5416 in a patient with refractory acute myeloid leukemia
Authors: Rolf M. Mesters, Teresa Padró, Ralf Bieker, Martin Steins, Michael Kreuter, Michael Göner, Stephen Kelsey, Paul Scigalla, Walter Fiedler, Thomas Büchner, Wolfgang E. Berdel
Journal: Blood (2001)