tbuckley/cabot-search huggingface dataset:
Upper airway shape: Is it important in the pathogenesis of obstructive sleep apnea?
Authors: J C Leiter
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

It is widely accepted that the size of the airway and the level of upper airway muscle activity contribute to the pathogenesis of obstructive sleep apnea (OSA). However, some individuals with normal airway size and apparently normal upper airway muscle activity nonetheless develop OSA. Recent data and analysis suggest that airway shape may also contribute to the development of OSA; patients with OSA tend to have elliptical airways, with the long axis of the ellipse oriented along the anteroposterior axis, and this orientation may adversely affect upper airway muscle function. By incorporating airway shape, airway size, and upper airway muscle activity into a unified hypothesis of the pathogenesis of OSA, it may be possible to reconcile discrepant anatomic and electromyographic findings in patients with OSA, to explain the difficulty of selecting appropriate surgical therapy for patients with OSA using currently available diagnostic tools, and to understand the often disappointing response to upper airway surgery in these patients.
Anti-tumour necrosis factor therapy in rheumatoid arthritis and risk of malignant lymphomas: relative risks and time trends in the Swedish Biologics Register
Authors: J Askling, E Baecklund, F Granath, P Geborek, M Fored, C Backlin, L Bertilsson, L Cöster, L T Jacobsson, S Lindblad, J Lysholm, S Rantapää-Dahlqvist, T Saxne, R van Vollenhoven, L Klareskog, N Feltelius
Journal: Annals of the Rheumatic Diseases (2008)

Tumour necrosis factor (TNF) antagonists have proved effective as treatment against rheumatoid arthritis (RA), but the unresolved issue of whether the use of anti-TNF therapy increases the already elevated risk of lymphoma in RA remains a concern.Using the Swedish Biologics Register (ARTIS), the Swedish Cancer Register, pre-existing RA cohorts and cross-linkage with other national health and census registers, a national RA cohort (n = 67,743) was assembled and patients who started anti-TNF therapy between 1998 and July 2006 (n = 6604) were identified. A general population comparator (n = 471,024) was also assembled and the incidence of lymphomas from 1999 to 31 December 2006 was assessed and compared in these individuals.Among the 6604 anti-TNF-treated RA patients, 26 malignant lymphomas were observed during 26,981 person-years of follow-up, which corresponded to a relative risk (RR) of 1.35 (95% CI 0.82 to 2.11) versus anti-TNF-naive RA patients (336 lymphomas during 365,026 person-years) and 2.72 (95% CI 1.82 to 4.08) versus the general population comparator (1568 lymphomas during 3,355,849 person-years). RA patients starting anti-TNF therapy in 1998-2001 accounted for the entire increase in lymphoma risk versus the two comparators. By contrast, RR did not vary significantly by time since start of first treatment or with the accumulated duration of treatment, nor with the type of anti-TNF agent.Overall and as used in routine care against RA, TNF antagonists are not associated with any major further increase in the already elevated lymphoma occurrence in RA. Changes in the selection of patients for treatment may influence the observed risk.
Quality of life and healthcare utilisation in cystic fibrosis: a multicentre study
Authors: Judy M. Bradley, Steven W. Blume, Maria-Magdalena Balp, David Honeybourne, J. Stuart Elborn
Journal: European Respiratory Journal (2012)

The aim of our study was to discover the health status and healthcare utilisation associated with pulmonary exacerbations in cystic fibrosis (CF) and chronic Pseudomonas aeruginosa infection. Patients with CF from five UK CF centres attended two visits, 8–12 weeks apart. They were classified at visit 1 as being in one of the three health states: no current pulmonary exacerbation; “mild” (no hospitalisation) pulmonary exacerbation; and “severe” (hospitalisation) pulmonary exacerbation. All patients completed the Cystic Fibrosis Questionnaire-Revised (CFQ-R) and EuroQol (EQ-5D) and a clinical form, and forced expiratory volume in 1 s (FEV 1 ) was measured at visits 1 and 2. Annual healthcare utilisation data were collected. 94 patients of mean± sd age 28.5±8.2 yrs and FEV 1 58.7±26.8% were recruited. 60 patients had no pulmonary exacerbation, 15 had a mild and 19 had a severe pulmonary exacerbation at visit 1. EQ-5D and CFQ-R data showed that the worse the exacerbation, the poorer the health-related quality of life (HRQoL). There were strong relationships between the CFQ-R and EQ-5D domain scores. The mean rate of pulmonary exacerbations per patient per year was 3.6 (1.5 in hospital and 2.2 at home). The mean length of stay per hospital pulmonary exacerbation was 9 days. As exacerbation status worsens, patients experience worse HRQoL. There is a significant healthcare burden associated with treatment of pulmonary exacerbation and long-term prophylaxis.
Interleukin-6 dimers produced by endothelial cells inhibit apoptosis of B-chronic lymphocytic leukemia cells
Authors: Ana Moreno, Marı́a Luisa Villar, Carmen Cámara, Rosario Luque, Constantino Cespón, Pedro González-Porqué, Garbiñe Roy, Javier López-Jiménez, Alfredo Bootello, Ernesto Roldán Santiago
Journal: Blood (2001)
Case Report: The University of Michigan Dioxin Exposure Study: A Follow-up Investigation of a Case with High Serum Concentration of 2,3,4,7,8-Pentachlorodibenzofuran
Authors: Alfred Franzblau, Elizabeth Hedgeman, Olivier Jolliet, Kristine Knutson, Tim Towey, Qixuan Chen, Biling Hong, Peter Adriaens, Avery Demond, David H. Garabrant, Brenda W. Gillespie, James Lepkowski
Journal: Environmental Health Perspectives (2010)

ContextPolychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and dioxin-like polychlorinated biphenyls that have toxic equivalency factors (TEFs) were measured in serum of 946 subjects in five Michigan counties. The study was motivated by concerns about human exposure to dioxin-contaminated sediments in the Tittabawassee River (TR). Most of the toxic equivalency in TR sediments is from two furan congeners, 2,3,7,8-tetrachlorodibenzofuran and 2,3,4,7,8-pentachlorodibenzofuran (2,3,4,7,8-pentaCDF).Case presentationThe individual with the highest adjusted (for age, age squared, and body mass index) serum level of 2,3,4,7,8-pentaCDF in the study (42.5 ppt) reported a unique history of raising cattle and vegetables in the floodplain of the TR. Interviews and serum samples were obtained from the index case and 15 other people who ate beef and vegetables raised by the index case. 2,3,4,7,8-pentaCDF in beef lipid was estimated to have been more than three orders of magnitude greater than background (1,780 vs. 1.1 ppt). The mean, median, and 95th percentile for serum 2,3,4,7,8-pentaCDF in the study control population were 6.0, 5.4, and 13.0 ppt, respectively, and were 9.9, 8.4, and 20.5 ppt among beef and vegetable consumers, respectively. Back extrapolation for the index case suggests that his increase in serum concentration of 2,3,4,7,8-pentaCDF above background may have been as high as 146 ppt.DiscussionConsumption of beef and/or vegetables raised on dioxin-contaminated soil may be an important completed pathway of exposure.Relevance to public health practiceAnimals and crops should not be raised for human consumption in areas contaminated with dioxins.
THE CONGRESS OF MEDICINE IN VIENNA
Authors: H. Head
Journal: BMJ (1923)

In the past three decades, mass casualty incidents have occurred worldwide at multiple sporting events and other mass gatherings. Organisational safety and healthcare provision can consequently be scrutinised post-event. Within the UK, such incidents in the 1980s provided incentives to improve medical services and subsequent high profile UK-based international sporting events (London Olympics and Paralympics 2012, Glasgow Commonwealth Games 2014, Rugby World Cup 2015) added a further catalyst for developing services. Furthermore in the aftermath of the abandoned France versus Germany association football match at the Stade de France (<i>Paris Terrorist Attacks,</i> November 2015) and the 2016 UK report from HM Coroner on the <i>Hillsborough Inquest</i>, medical cover at sporting events is being further reviewed. Doctors providing spectator cover therefore need to have an awareness of their likely roles at sporting venues. Formal guidance exists in many countries for the provision of such cover but remains generic even though Events Medicine is increasingly recognised as a necessary service. The current evidence base is limited with best practice examples often anecdotally cited by acute care specialists (eg, emergency medicine) who provide cover. This article is therefore intended to present an overview for doctors of the knowledge and skills required to treat ill and injured spectators and enable them to adequately risk-assess venues in cooperation with other health and safety providers, including preparation for a major incident. It also gives guidance on how activity can be adequately assessed and how doctors can have management roles in Events Medicine.
RECK modulates Notch signaling during cortical neurogenesis by regulating ADAM10 activity
Authors: Teruyuki Muraguchi, Yujiro Takegami, Toshiyuki Ohtsuka, Shunsuke Kitajima, Ediriweera P S Chandana, Akira Omura, Takao Miki, Rei Takahashi, Naoya Matsumoto, Andreas Ludwig, Makoto Noda, Chiaki Takahashi
Journal: Nature Neuroscience (2007)
Parametric v non-parametric methods for data analysis
Authors: D. G Altman, J M. Bland
Journal: BMJ (2009)

Continuous data arise in most areas of medicine. Familiar clinical examples include blood pressure, ejection fraction, forced expiratory volume in 1 second (FEV1), serum cholesterol, and anthropometric measurements. Methods for analysing continuous data fall into two classes, distinguished by whether or not they make assumptions about the distribution of the data.

Theoretical distributions are described by quantities called parameters, notably the mean and standard deviation.1 Methods that use distributional assumptions are called parametric methods, because we estimate the parameters of the distribution assumed for the data. Frequently used parametric methods include t tests and analysis of variance for comparing groups, and least squares regression and correlation for studying the relation between variables. All of the common parametric methods (“ t methods”) assume that …
Response of right ventricular myocardial function to endoscopic lung volume reduction in patients with advanced emphysema
Authors: Carmen Pizarro, Robert Schueler, Christoph Hammerstingl, Jens Kreuz, Uwe Juergens, Georg Nickenig, Dirk Skowasch
Journal: European Respiratory Journal (2014)

Introduction: 

Endoscopic lung volume reduction (ELVR) provides a minimally invasive, effective therapy for patients with severe, progressive lung emphysema. However, its impact on right ventricular (RV) function is unknown.

Objectives: 

The aim of this study was to assess, by use of speckle tracking based RV deformation analysis, the extent of global and regional RV dysfunction in patients undergoing ELVR, and to correlate the results with the clinical outcomes.

Methods: 

We enrolled 25 patients (62±9.8 yrs, 68% male) with severe emphysematous COPD scheduled for bronchoscopic LVR using endobronchial valves (Zephyr®, PulmonX, Inc.). Echocardiography was conducted one day prior to ELVR and at 6-week follow-up visit. Clinical responsiveness was defined by a pre- to post-procedural increase in 6-minute walk test (6MWT) distance of ≥26 m. 15/25 treated patients were clinically responders, with an improvement mean value in 6-MWT distance of 126.3±67.5 m.

Results: 

After ELVR, RV global longitudinal strain improved significantly in the responder group (-17.9±5.4% vs. -21.4±5.2%, p=0.049), whereas there was no significant differences in other parameters of RV function such as RV apical and medial longitudinal strain, TAPSE or mPAP; no significant effect was seen in non-responding patients. These results correlated with the Nt-proBNP-levels showing a statistical trend towards a relevant post-procedural Nt-proBNP decrease in the responder group (239.6±344.6 pg/ml vs. 90.3±69.3 pg/ml, p=0.07).

Conclusion: 

ELVR improved RV function in patients with advanced emphysema. RV global longitudinal strain appears to be the best index to detect RV alterations in these patients.
Cardiorespiratory Fitness Is Strongly Related to the Metabolic Syndrome in Adolescents
Authors: Ian Janssen, Wendy C. Cramp
Journal: Diabetes Care (2007)

The metabolic syndrome is a predecessor of type 2 diabetes and cardiovascular disease (1). In adults, physical activity is important for both preventing and treating metabolic syndrome (2). A limited number of studies have examined the impact of physical activity on metabolic syndrome in youth (3–7). The results from the few existing studies are conflicting, reporting no associations, weak effects, and strong effects of physical activity (3–7). These inconsistencies may reflect that most of these studies measured physical activity using self-report questionnaire measures, which have limited validity and reliability in youth (8,9). While one paper reported that the beneficial effects of physical activity on metabolic syndrome are limited to girls (3), published studies of physical activity and metabolic syndrome in youth have been limited to predominantly Caucasian samples and lack ethnic comparisons. Thus, it is unknown whether the effects of physical activity on metabolic syndrome are consistent in different population groups. The purpose of this study is to 1 ) examine the relation between objective measures of cardiorespiratory fitness (CRF) (the ability to perform endurance activities) and metabolic syndrome in adolescents and 2 ) determine whether the relationship is consistent by sex and ethnicity.

The study sample consisted of 1,561 adolescents, aged 12–19 years, who participated in the National Health and Nutrition Examination Survey (NHANES) 1999–2002, which is a nationally representative cross-sectional survey (10 …
Michelangelo and Medicine
Authors: Frank Jackson
Journal: Journal of the Royal Society of Medicine (2003)

John Seamer (December 2002 JRSM1) believes that the statue of David is left-handed as the sling is over the left shoulder. However, the pose of the statue is almost contemplative, as if he was studying Goliath, and does not suggest an imminent attack, in which case the position of the sling is immaterial and the larger size of the right hand should indicate right-handedness.
Oncolytic HSV-1 Infection of Tumors Induces Angiogenesis and Upregulates CYR61
Authors: Kazuhiko Kurozumi, Jayson Hardcastle, Roopa Thakur, Joshua Shroll, Michal Nowicki, Akihiro Otsuki, E Antonio Chiocca, Balveen Kaur
Journal: Molecular Therapy (2008)
Everolimus for subependymal giant cell astrocytoma in patients with tuberous sclerosis complex: 2-year open-label extension of the randomised EXIST-1 study
Authors: David Neal Franz, Elena Belousova, Steven Sparagana, E Martina Bebin, Michael Frost, Rachel Kuperman, Olaf Witt, Michael H Kohrman, J Robert Flamini, Joyce Y Wu, Paolo Curatolo, Petrus J de Vries, Noah Berkowitz, Oezlem Anak, Julie Niolat, Sergiusz Jozwiak
Journal: The Lancet Oncology (2014)
Impact of bariatric surgery on serum urate targets in people with morbid obesity and diabetes: a prospective longitudinal study
Authors: Nicola Dalbeth, Peggy Chen, Marie White, Gregory D Gamble, Caran Barratt-Boyes, Peter J Gow, Brandon Orr-Walker
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Weight loss leads to reduced serum urate (SU) in people with obesity. However, the clinical relevance of such reductions in SU is unknown. This study examined the impact of non-surgical weight loss and bariatric surgery on SU targets in people with morbid obesity and diabetes. <h3>Methods</h3> The study was a single-centre, prospective study of 60 people with type 2 diabetes and body mass index ≥35 kg/m<sup>2</sup>. Following 6 months of non-surgical weight loss, all participants had laparoscopic sleeve gastrectomy, with a further 1 year of follow-up. Serial SUs were measured throughout the study. <h3>Results</h3> Participants experienced mean (SD) weight loss of 5.5 (4.1) kg prior to surgery and 34.3 (11.1) kg following surgery. SU did not change following non-surgical weight loss (0.38 (0.09) mmol/L at baseline and 0.38 (0.10) mmol/L at follow-up), but increased to 0.44 (0.15) mmol/L in the immediate postoperative period and reduced to 0.30 (0.08) mmol/L 1 year after surgery (p&lt;0.05 for both compared with baseline). Baseline SU, cessation of diuretics, female sex and change in creatinine independently predicted change in SU at the final visit. In participants without gout, SU above saturation levels (≥0.41 mmol/L) were present in 19/48 (40%) at baseline and 1/48 (2%) 1 year after surgery (p&lt;0.0001). In participants with gout, SU above therapeutic target levels (≥0.36 mmol/L) were present in 10/12 (83%) at baseline and 4/12 (33%) 1 year after surgery (p=0.031). <h3>Conclusions</h3> Clinically relevant reductions in SU occur following bariatric surgery in people with diabetes and WHO class II or higher obesity.
Semaphorin 7a<sup>+</sup> Regulatory T Cells Are Associated with Progressive Idiopathic Pulmonary Fibrosis and Are Implicated in Transforming Growth Factor-β1–induced Pulmonary Fibrosis
Authors: Ronald A. Reilkoff, Hong Peng, Lynne A. Murray, Xueyan Peng, Thomas Russell, Ruth Montgomery, Carol Feghali-Bostwick, Albert Shaw, Robert J. Homer, Mridu Gulati, Aditi Mathur, Jack A. Elias, Erica L. Herzog
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Lymphocytes are increasingly associated with idiopathic pulmonary fibrosis (IPF). Semaphorin 7a (Sema 7a) participates in lymphocyte activation.To define the relationship between Sema 7a and lymphocytes in IPF.We characterized the significance of Sema 7a+ lymphocytes in humans with IPF and in a mouse model of lung fibrosis caused by lung-targeted, transgenic overexpression of TGF-β1. We determined the site of Sema 7a expression in human and murine lungs and circulation and used adoptive transfer approaches to define the relevance of lymphocytes coexpressing Sema7a and the markers CD19, CD4, or CD4+CD25+FoxP3+ in TGF-β1-induced murine lung fibrosis.Subjects with IPF show expression of Sema 7a on lung CD4+ cells and circulating CD4+ or CD19+ cells. Sema 7a expression is increased on CD4+ cells and CD4+CD25+FoxP3+ regulatory T cells, but not CD19+ cells, in subjects with progressive IPF. Sema 7a is expressed on lymphocytes expressing CD4 but not CD19 in the lungs and spleen of TGF-β1-transgenic mice. Sema 7a expressing bone marrow-derived cells induce lung fibrosis and alter the production of T-cell mediators, including IFN-γ, IL-4, IL-17A, and IL-10. These effects require CD4 but not CD19. In comparison to Sema 7a-CD4+CD25+FoxP3+ cells, Sema7a+CD4+CD25+FoxP3+ cells exhibit reduced expression of regulatory genes such as IL-10, and adoptive transfer of these cells induces fibrosis and remodeling in the TGF-β1-exposed murine lung.Sema 7a+CD4+CD25+FoxP3+ regulatory T cells are associated with disease progression in subjects with IPF and induce fibrosis in the TGF-β1-exposed murine lung.
Remarks on Dilatation of the Stomach and its Treatment
Authors: T. C. Allbutt
Journal: BMJ (1880)

IN the year i869, my attention was arrested, when reading the Archiv fur EIiinische 2lledicin, by a paper of Professor Kussmaul's on dilata- tion of the stomach and its treatment.The method described by the author seemed so reasonable and appropriate, that I at once formed hopes of its success, which, if they have dwindled somewhat in the following ten years, are by no means extinguished.But before I begin to speak of Professor Kussmaul's method of treating this malady, I must confess that the perusal of his paper in- structed me much concerning the nature of dilatation of the stomach, and indeed concerning the existence of dilatation of the stomach as a primary state.I have reason to know that many, even eminent physicians, are not familiar with the fact, that dilatation of the stomach may appear as a simple disease, apart from the well known secondary forms of it, which result from pyloric and other mechanical obstructions.
Inhibition of TNF receptor 1 internalization by adenovirus 14.7K as a novel immune escape mechanism
Authors: Wulf Schneider-Brachert, Vladimir Tchikov, Oliver Merkel, Marten Jakob, Cora Hallas, Marie-Luise Kruse, Peter Groitl, Alexander Lehn, Eberhard Hildt, Janka Held-Feindt, Thomas Dobner, Dieter Kabelitz, Martin Krönke, Stefan Schütze
Journal: Journal of Clinical Investigation (2006)

The adenoviral protein E3-14.7K (14.7K) is an inhibitor of TNF-induced apoptosis, but the molecular mechanism underlying this protective effect has not yet been explained exhaustively. TNF-mediated apoptosis is initiated by ligand-induced recruitment of TNF receptor-associated death domain (TRADD), Fas-associated death domain (FADD), and caspase-8 to the death domain of TNF receptor 1 (TNFR1), thereby establishing the death-inducing signaling complex (DISC). Here we report that adenovirus 14.7K protein inhibits ligand-induced TNFR1 internalization. Analysis of purified magnetically labeled TNFR1 complexes from murine and human cells stably transduced with 14.7K revealed that prevention of TNFR1 internalization resulted in inhibition of DISC formation. In contrast, 14.7K did not affect TNF-induced NF-kappaB activation via recruitment of receptor-interacting protein 1 (RIP-1) and TNF receptor-associated factor 2 (TRAF-2). Inhibition of endocytosis by 14.7K was effected by failure of coordinated temporal and spatial assembly of essential components of the endocytic machinery such as Rab5 and dynamin 2 at the site of the activated TNFR1. Furthermore, we found that the same TNF defense mechanisms were instrumental in protecting wild-type adenovirus-infected human cells expressing 14.7K. This study describes a new molecular mechanism implemented by a virus to escape immunosurveillance by selectively targeting TNFR1 endocytosis to prevent TNF-induced DISC formation.
Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma
Authors: Ravi K. Amaravadi, Duonan Yu, Julian J. Lum, Thi Bui, Maria A. Christophorou, Gerard I. Evan, Andrei Thomas-Tikhonenko, Craig B. Thompson
Journal: Journal of Clinical Investigation (2007)

Autophagy is a lysosome-dependent degradative pathway frequently activated in tumor cells treated with chemotherapy or radiation. Whether autophagy observed in treated cancer cells represents a mechanism that allows tumor cells to survive therapy or a mechanism for initiating a nonapoptotic form of programmed cell death remains controversial. To address this issue, the role of autophagy in a Myc-induced model of lymphoma generated from cells derived from p53ERTAM/p53ERTAM mice (with ER denoting estrogen receptor) was examined. Such tumors are resistant to apoptosis due to a lack of nuclear p53. Systemic administration of tamoxifen led to p53 activation and tumor regression followed by tumor recurrence. Activation of p53 was associated with the rapid appearance of apoptotic cells and the induction of autophagy in surviving cells. Inhibition of autophagy with either chloroquine or ATG5 short hairpin RNA (shRNA) enhanced the ability of either p53 activation or alkylating drug therapy to induce tumor cell death. These studies provide evidence that autophagy serves as a survival pathway in tumor cells treated with apoptosis activators and a rationale for the use of autophagy inhibitors such as chloroquine in combination with therapies designed to induce apoptosis in human cancers.
Phase IB study of the combination of docetaxel, gemcitabine, and bevacizumab in patients with advanced or recurrent soft tissue sarcoma: the Axtell regimen
Authors: C.F. Verschraegen, H. Arias-Pulido, S.-J. Lee, S. Movva, L.A. Cerilli, S. Eberhardt, B. Schmit, R. Quinn, C.Y. Muller, I. Rabinowitz, M. Purdy, D. Snyder, T. Bocklage
Journal: Annals of Oncology (2011)