tbuckley/cabot-search huggingface dataset:
Do responses to exercise training in cystic fibrosis depend on initial fitness level?
Authors: W. Gruber, D.M. Orenstein, K.M. Braumann
Journal: European Respiratory Journal (2011)

The aim of our study was to evaluate the responses to an exercise programme with respect to initial fitness in subjects with cystic fibrosis (CF). 72 subjects (42 female) aged 10–43 yrs (forced expiratory volume in 1 s of 62.0±26.7% predicted) were included. Participants were divided into three groups based on peak oxygen uptake expressed as % predicted. Subjects participated in a multifaceted rehabilitation programme, including five-times-a-week exercise training, for 6 weeks. Exercise and ventilatory capacity were determined by a maximal incremental cycling test. Oxygen uptake, workload and peak cardiac frequency at peak and submaximal workload were used as parameters for exercise capacity and responsiveness to training. Lung function values were significantly different between groups (p&lt;0.05), and increased after training (p&lt;0.05) only in groups with a lower initial fitness level. Responsiveness to training showed differences between groups (p&lt;0.05) at peak and ventilatory anaerobic threshold (VAT; p&lt;0.05), with higher improvements in subjects with lower initial fitness level. The improvements in exercise parameters in CF at peak and VAT depended on the fitness level at baseline, independent of lung function. These improvements seen after training were comparable with those seen in healthy subjects, suggesting that responsiveness to exercise is similar in CF and in healthy untrained persons.
Toll/IL-1 Signaling Is Critical for House Dust Mite–specific Th1 and Th2 Responses
Authors: Simon Phipps, Chuan En Lam, Gerard E Kaiko, Shen Yun Foo, Adam Collison, Joerg Mattes, Jessica Barry, Sophia Davidson, Kevin Oreo, Lauren Smith, Ashley Mansell, Klaus I Matthaei, Paul S Foster
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

One of the immunopathological features of allergic inflammation is the infiltration of helper T type 2 (Th2) cells to the site of disease. Activation of innate pattern recognition receptors such as Toll-like receptors (TLRs) plays a critical role in helper T type 1 cell differentiation, yet their contribution to the generation of Th2 responses to clinically relevant aeroallergens remains poorly defined.To determine the requirement for TLR2, TLR4, and the Toll/IL-1 receptor domain adaptor protein MyD88 in a murine model of allergic asthma.Wild-type and factor-deficient ((-/-)) mice were sensitized intranasally to the common allergen house dust mite (HDM) and challenged 2 weeks later on four consecutive days. Measurements of allergic airway inflammation, T-cell cytokine production, and airway hyperreactivity were performed 24 hours later.Mice deficient in MyD88 were protected from the cardinal features of allergic asthma, including granulocytic inflammation, Th2 cytokine production and airway hyperreactivity. Although HDM activated NF-kappaB in TLR2- or TLR4-expressing HEK cells, only in TLR4(-/-) mice was the magnitude of allergic airway inflammation and hyperreactivity attenuated. The diminished Th2 response present in MyD88(-/-) and TLR4(-/-) mice was associated with fewer OX40 ligand-expressing myeloid dendritic cells in the draining lymph nodes during allergic sensitization. Finally, HDM-specific IL-17 production and airway neutrophilia were attenuated in MyD88(-/-) but not TLR4(-/-) mice.Together, these data suggest that Th2- and Th17-mediated inflammation generated on inhalational HDM exposure is differentially regulated by the presence of microbial products and the activation of distinct MyD88-dependent pattern recognition receptors.
Reply to D. Braun et al
Authors: Molly S. Daniels, Karen H. Lu
Journal: Journal of Clinical Oncology (2014)

We thank Braun et al for their thoughtful comments regarding our recent publication. In particular, we look forward to the possibility that ovarian cancer histology will be included in future versions of BRCAPRO, given that our results do suggest that this would improve model calibration. In addition, they are correct in their assumption that we did not verify family history with medical record review but rather relied on the patient’s self-reported family history, and we appreciate their recognition that this is the reality of clinical practice. It is therefore exciting to see their proposed correction to the model to account for the possibility of misreporting of cancer family history in the clinical setting. We would also like to emphasize again that, given the exceptionally high prevalence of germline BRCA1 and BRCA2 mutations in women with high-grade serous ovarian cancer, BRCA1/BRCA2 genetic testing is recommended for all women with high-grade serous ovarian cancer, regardless of family history. Molly S. Daniels and Karen H. Lu The University of Texas MD Anderson Cancer Center, Houston, TX
Development and validation of a robust automated analysis of plasma phospholipid fatty acids for metabolic phenotyping of large epidemiological studies
Authors: Laura Yun Wang, Keith Summerhill, Carmen Rodriguez-Canas, Ian Mather, Pinal Patel, Michael Eiden, Stephen Young, Nita G Forouhi, Albert Koulman
Journal: Genome Medicine (2013)

Abstract A fully automated, high-throughput method was developed to profile the fatty acids of phospholipids from human plasma samples for application to a large epidemiological sample set ( n &gt; 25,000). We report here on the data obtained for the quality-control materials used with the first 860 batches, and the validation process used. The method consists of two robotic systems combined with gas chromatography, performing lipid extraction, phospholipid isolation, hydrolysis and derivatization to fatty-acid methyl esters, and on-line analysis. This is the first report showing that fatty-acid profiling is an achievable strategy for metabolic phenotyping in very large epidemiological and genetic studies.
Is heart rate variability the simple solution to diagnose sleep apnoea?
Authors: T. Penzel
Journal: European Respiratory Journal (2003)

Early in the investigation of obstructive sleep apnoea it was recognised that the events of apnoea and hypopnoea are accompanied by concomitant cyclic variations in heart rate 1. The pattern of brady/tachycardia is closely linked to the time course of apnoeic events. As a consequence, this pattern had been used successfully to detect sleep apnoea in patients with clinical symptoms for sleep apnoea. Dedicated devices were developed over the past 15 yrs to detect sleep apnoea at an early stage of the disease using recordings of heart rate, snoring, oxygen saturation and body position 2. These devices were used successfully to stratify the individual risk of patients suffering from sleep-disordered breathing before they were referred to cardiorespiratory polysomnography. Sleep laboratories have limited capacity for cardiorespiratory polysomnography and are expensive in terms of personal costs due to continuous attendance during the night. The sensitivity and specifity of these simplified four channel-based recording systems had been evaluated in many studies giving results for specific systems. A recent systematic review compiled the results of these studies in a comparative overview 3. The review revealed the value and the limitations of systems with respect to the accepted criteria for the diagnosis of sleep apnoea 4. In conclusion, a satisfactory standardisation of terms and of diagnostic criteria regarding the portable diagnosis of sleep apnoea could not be achieved.

In parallel with efforts to define evidence-based criteria for the simplified diagnosis of …
Thymoma-Associated Paraneoplastic Polymyositis
Authors: Ronan J. Kelly, Sarah K. Browne, Arun Rajan, Giuseppe Giaccone
Journal: Journal of Clinical Oncology (2010)

We read with interest the recent commentary by Inoue et al describing the first reported case of thymic carcinoma–associated paraneoplastic polymyositis. We agree with Inoue et al that this is an extremely difficult complication to manage in this rare histological subtype of thymic malignanices. The authors report that only 23 cases of polymyositis associated with thymoma have previously been described. We have recently encountered a similar constellation of symptoms in a 24-year-old white woman, and wish to summarize her case briefly. She was originally diagnosed with a grade B2 stage IVA malignant thymoma in 2003 with coexistent autoimmune myasthenia gravis and diabetes mellitus. Before attending our clinic in November 2008, she had received extensive prior therapy including three separate debulking surgeries followed by adjuvant radiation on two occasions. Previous chemotherapeutic regimens included six cycles of cisplatin, adriamycin, vincristine, and cyclophoshamide, and three cycles of carboplatin/paclitaxel. In November 2008, she was enrolled on a phase I clinical trial of the histone deacetylase inhibitor belinostat 1,000 mg/m days 1 to 5 every 3 weeks. She attained stable disease on belinostat for 10 months until September 2009, when she presented with an urticarial rash, recurrence of myasthenia gravis, and generalized myalgias predominantly in her shoulder and bilateral thigh muscles. Computed tomography scan at that time revealed stable disease; however, her creatinine kinase was markedly elevated at 2,020 U/L (range, 38 to 252 U/L). Magnetic resonance imaging of her thighs revealed an unusual pattern of edema for an inflammatory myopathy with a fascial distribution in the right vastus lateralis. A muscle biopsy of her anterior thigh confirmed myositis. Despite aggressive therapy, which included intravenous immunoglobulin (IVIG), plasmapharesis, pulsed steroids, and rituximab, she continued to deteriorate and developed progressive bulbar symptoms, finally requiring ventilator support for respiratory failure and a prolonged intensive care unit admission. While myasthenia gravis and other autoimmune phenomena tend to be more closely associated with thymomas, our patient demonstrated a range of autoimmune phenomena including myasthenia gravis, type I diabetes mellitus, and autoantibodies to interferon and interferon . Interestingly, patients with autoimmune polyendocrinopathy, candidiasis, and ectodermal dystrophy caused by autosomal recessive mutations in the autoimmune regulator (AIRE) gene also have endocrinopathies and autoantibodies against type I interferons. AIRE is known to promote negative selection of autoreactive T cells and apoptosis of thymic medullary epithelial cells. The suggestion that AIRE expression may be altered in thymic tumors provides a fascinating link between autoimmunity and malignancy as demonstrated by our patient.
Three-year findings of an early lung cancer detection feasibility study with low-dose spiral computed tomography in heavy smokers
Authors: S. Novello, C. Fava, P. Borasio, L. Dogliotti, G. Cortese, B. Crida, G. Selvaggi, P. Lausi, M.P. Brizzi, P. Sperone, L. Cardinale, F. Ferraris, F. Perotto, A. Priola, G.V. Scagliotti
Journal: Annals of Oncology (2005)
Cardiopulmonary exercise testing (CPET) in patients with unexplained dyspnoea
Authors: Owain Griffiths, Banerjee Anindo
Journal: European Respiratory Journal (2014)

Introduction   CPET patients exercise using an incremental workload until limiting symptoms or exhaustion. Variables measured during the test may reveal the cause of dyspnoea. This study was performed to determine whether CPET produces results of clinical value and identify variables with the greatest diagnostic yield.   Methods   Patients referred for CPET for unexplained dyspnoea were identified. Detailed clinical evaluation, lung function testing and echocardiography had not revealed a cause. Incremental workload CPETs were performed using an integrated cycle ergometer system with a ramp chosen to provide a test of 8-12 minutes duration. Tests were reported by a trained physician and reviewed to determine whether a diagnosis was made and analyse the variables of the exercise response.   Results   48 patients were analysed, 23 males, mean age 52.4yrs. Test termination was exhaustion (36 patients), leg ache (4) and dyspnoea (3). 46 patients had clinically relevant results. 5 patients had normal studies with no cause of dyspnoea, 14 deconditioning and 7 dysfunctional breathing. 10 patients had multiple causes, specifically thoracic cage restriction, hyperventilation, cardiac disease, obesity, blunted ventilatory response to acidosis, airflow obstruction, drug effects, upper airway disease, metabolic myopathy and pulmonary vascular disease. Variables most frequently used were Anaerobic Threshold (15 tests), Maximum Oxygen Uptake (10), Maximum Minute Ventilation (14), Flow-volume curves (10), Oxygen Pulse (9) and Respiratory Rate (8).   Conclusion   in patients with dyspnoea but no diagnosis from standard investigations CPET provides important additional information. A limited number of variables provide diagnostic data.
Platelet Factor-4 Variant Chemokine CXCL4L1 Inhibits Melanoma and Lung Carcinoma Growth and Metastasis by Preventing Angiogenesis
Authors: Sofie Struyf, Marie D. Burdick, Elke Peeters, Karolien Van den Broeck, Chris Dillen, Paul Proost, Jo Van Damme, Robert M. Strieter
Journal: Cancer Research (2007)

Abstract The platelet factor-4 variant, designated PF-4var/CXCL4L1, is a recently described natural non-allelic gene variant of the CXC chemokine platelet factor-4/CXCL4. PF-4var/CXCL4L1 was cloned, and the purified recombinant protein strongly inhibited angiogenesis. Recombinant PF-4var/CXCL4L1 was angiostatically more active (at nanomolar concentration) than PF-4/CXCL4 in various test systems, including wound-healing and migration assays for microvascular endothelial cells and the rat cornea micropocket assay for angiogenesis. Furthermore, PF-4var/CXCL4L1 more efficiently inhibited tumor growth in animal models of melanoma and lung carcinoma than PF-4/CXCL4 at an equimolar concentration. For B16 melanoma in nude mice, a significant reduction in tumor size and the number of small i.t. blood vessels was obtained with i.t. applied PF-4var/CXCL4L1. For A549 adenocarcinoma in severe combined immunodeficient mice, i.t. PF-4var/CXCL4L1 reduced tumor growth and microvasculature more efficiently than PF-4/CXCL4 and prevented metastasis to various organs better than the angiostatic IFN-inducible protein 10/CXCL10. Finally, in the syngeneic model of Lewis lung carcinoma, PF-4var/CXCL4L1 inhibited tumor growth equally well as monokine induced by IFN-γ (Mig)/CXCL9, also known to attract effector T lymphocytes. Taken together, PF-4var/CXCL4L1 is a highly potent antitumoral chemokine preventing development and metastasis of various tumors by inhibition of angiogenesis. These data confirm the clinical potential of locally released chemokines in cancer therapy. [Cancer Res 2007;67(12):5940–8]
Bioassay of Pesticides and Industrial Chemicals for Tumorigenicity in Mice: A Preliminary Note&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: J R Innes, B M Ulland, M G Valerio, L Petrucelli, L Fishbein, E R Hart, A J Pallotta, R R Bates, H L Falk, J J Gart, M Klein, I Mitchell, J Peters
Journal: JNCI Journal of the National Cancer Institute (1969)
Physical inactivity and idiopathic pulmonary embolism in women: prospective study
Authors: C. Kabrhel, R. Varraso, S. Z. Goldhaber, E. Rimm, C. A. Camargo
Journal: BMJ (2011)

<b>Objectives</b> To determine the association between physical inactivity (that is, a sedentary lifestyle) and incident idiopathic pulmonary embolism. <b>Design</b> Prospective cohort study. <b>Setting</b> Nurses' Health Study. <b>Participants</b> 69 950 female nurses who completed biennial questionnaires from 1990 to 2008. <b>Main outcome measures </b>The primary outcome was idiopathic pulmonary embolism confirmed in medical records. Multivariable Cox proportional hazards models controlled for age, body mass index (BMI), energy intake, smoking, pack years, race, spouse's educational attainment, parity, menopause, non-aspirin non-steroidal anti-inflammatory drugs, warfarin, multivitamin supplements, hypertension, coronary heart disease, rheumatological disease, and dietary patterns. The primary exposure was physical inactivity, measured in hours of sitting each day. The secondary exposure was physical activity, measured in metabolic equivalents a day. <b>Results</b> Over the 18 year study period, there were 268 cases of incident idiopathic pulmonary embolism. There was an association between time of sitting and risk of idiopathic pulmonary embolism (41/104 720 <i>v</i> 16/14 565 cases in most inactive <i>v</i> least inactive in combined data; P&lt;0.001 for trend). The risk of pulmonary embolism was more than twofold in women who spent the most time sitting compared with those who spent the least time sitting (multivariable hazard ratio 2.34, 95% confidence interval 1.30 to 4.20). There was no association between physical activity and pulmonary embolism (P=0.53 for trend). <b>Conclusions</b> Physical inactivity is associated with incident pulmonary embolism in women. Interventions that decrease time sitting could lower the risk of pulmonary embolism.
Novel Designs and End Points for Phase II Clinical Trials
Authors: Alex A. Adjei, Michaele Christian, Percy Ivy
Journal: Clinical Cancer Research (2009)

The large number of negative phase III trials in oncology over the last several years has renewed interest in refining phase II oncology clinical trials to maximize the chances of success in phase III testing. More efficient phase II study designs will improve our ability to identify promising agents for testing while accurately identifying nonefficacious agents. Recognizing that new paradigms of phase II trial designs need to be developed, the Clinical Trial Design Task Force of the National Cancer Institute (NCI) Investigational Drug Steering Committee has tackled the question of improving efficiency of phase II clinical trials. In this issue of CCR Focus, four of the major topics discussed are presented. First, the task force recommended that alternate phase II end points should be studied. Second, depending on the characteristics of the specific trial and study population, historical controls or a randomized design may be more appropriate. Third, rational incorporation of biomarkers into phase II trials should be encouraged. Last, novel imaging modalities will be critical in evaluating the clinical benefit of new cytostatic agents.
Compulsory helmets for cyclists
Authors: S. Gandevia
Journal: Journal of the Royal Society of Medicine (2004)

Professor Sheikh and colleagues (June 2004 JRSM1) favoured legislation that would compel cyclists to wear helmets. They conceded that the ethical argument was somewhat stronger for children than for adults. Subsequent correspondents questioned the evidence on helmet efficacy and argued that legislation would have negative effects by discouraging the healthful activity of bicycling. When analysing the cost–benefit ratio of legislation we should factor in the full effects which flow from traumatic brain injury, not only to the patient but also to the patient's family and carers.2,3 These involve many levels ranging from the formally quantifiable health costs, through changes in quality and quantity of life, to the less measurable personal, family and social losses. Wearing seat belts in motor vehicles now seems common sense and has reduced the neurological burden imposed by accidents. Wearing helmets by all cyclists should also seem common sense. Combined with public health campaigns on the long-term benefits of exercise, any potential negative impact of mandatory helmet-wearing should disappear. We have already accepted the impositions on our freedom of movement (e.g. airports and elsewhere) brought about by the global terrorist threat. In many countries the risk of traumatic brain injury following a cycle accident may be much greater than a terrorist threat.
Little league shoulder syndrome in an adolescent cricket player: Figure 1
Authors: W R Drescher, A Falliner, T Zantop, K Oehlert, W Petersen, J Hassenpflug
Journal: British Journal of Sports Medicine (2004)

The first case of little league shoulder syndrome in a cricket player is reported. The condition has been reported in baseball pitchers and is characterised by a proximal humeral epiphyseolysis.
Stranded statistical paradigms: The last crusade
Authors: Judith Glück, Oliver Vitouch
Journal: Behavioral and Brain Sciences (1998)

Chow tries to show that for the case of hard-core experimentation, the criticisms of NHST are not valid. Even if one is willing to adopt his epistemological ideology, several shortcomings of NHST remain. We argue for a flexible and thoughtful application of statistical tools (including significance tests) instead of a ritualized statistical catechism that relies on the magic of α.
The Detection of Epstein-Barr Virus DNA in Lung Tissue from Patients with Idiopathic Pulmonary Fibrosis
Authors: JAMES P. STEWART, JIM J. EGAN, ALAN J. ROSS, BRIAN G. KELLY, SHE S. LOK, PHILIP S. HASLETON, ASHLEY A. WOODCOCK
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Idiopathic pulmonary fibrosis (IPF) is a clinical syndrome in which the precipitating factors are unclear. An association between Epstein-Barr Virus (EBV) and IPF had previously been suggested using serology and immunohistochemistry. This study sought confirmation of the presence of EBV DNA in the lung tissue of patients with IPF. Lung tissue obtained surgically from 27 patients with IPF and 28 control subjects was investigated for the presence of EBV by immunohistochemistry and polymerase chain reaction (PCR) analysis. Immunohistochemistry used antibodies specific for EBV lytic cycle antigens (gp340/220 and VCA). Nested PCR analysis used oligonucleotide primers specific for EBV and was sensitive to one copy of EBV DNA. Twelve of the 27 patients with IPF (44%) and three of the 28 control subjects (10%) were EBV positive by immunohistochemistry (p = 0.005). Thirteen of the patients with IPF (48%) and four of the control subjects (14%) were EBV positive by PCR (p = 0.007). Eleven of the patients with IPF (41%) and none of the control subjects were EBV positive by both immunohistochemistry and PCR (p = < 0.001). These data further suggest an association between EBV and IPF. In addition it defines a novel method for detecting EBV in lung tissue. EBV may be involved in the pathogenesis of the disease; however, further studies are required to establish a causal relationship.