tbuckley/cabot-search huggingface dataset:
Pulmonary fibrosis is associated with an elevated risk of thromboembolic disease
Authors: D.B. Sprunger, A.L. Olson, T.J. Huie, E.R. Fernandez-Perez, A. Fischer, J.J. Solomon, K.K. Brown, J.J. Swigris
Journal: European Respiratory Journal (2011)

Recent epidemiological studies have suggested an increased risk of venous thromboembolism (VTE) in lung fibrosis. Large-scale epidemiological data regarding the risk of VTE in pulmonary fibrosis-associated mortality have not been published. Using data from the National Center for Health Statistics from 1988-2007, we determined the risk of VTE in decedents with pulmonary fibrosis in the USA. We analysed 46,450,489 records, of which 218,991 met our criteria for idiopathic pulmonary fibrosis. Among these, 3,815 (1.74%) records also contained a diagnostic code for VTE. The risk of VTE in pulmonary fibrosis decedents was 34% higher than in the background population, and 44% and 54% greater than among decedents with chronic obstructive pulmonary disease and lung cancer, respectively. Those with VTE and pulmonary fibrosis died at a younger age than those with pulmonary fibrosis alone (females: 74.3 versus 77.4 yrs (p<0.0001); males: 72.0 versus 74.4 yrs (p<0.0001)). Decedents with pulmonary fibrosis had a significantly greater risk of VTE. Those with VTE and pulmonary fibrosis died at a younger age than those with pulmonary fibrosis alone. These data suggest a link between a pro-fibrotic and a pro-coagulant state.
A STUDY OF THE TOTAL PROTEIN OF THE CEREBROSPINAL FLUID IN UNCOMPLICATED AND UNTREATED NEUROSYPHILIS
Authors: Purcell G. Schube
Journal: American Journal of Psychiatry (1934)

A study of the cerebrospinal fluid total protein measured in mg. per 100 c. c. of cerebrospinal fluid of 446 cases of uncomplicated and untreated neurosyphilis is presented. There were 357 cases of general paresis, 48 cases of tabes without psychosis and 44 cases of cerebrospinal syphilis with psychosis. The statistical technic was used throughout in evaluating the results. The average value (M) for cerebrospinal fluid total protein measured in mg. per 100 c. c. of cerebrospinal fluid was 75.4 for all cases of neurosyphilis, 79.0 in general paresis, 57.9 in tubes without psychosis, and 65.68 in cerebrospinal syphilis with psychosis. The middle 50 per cent (" Q ") of the cases had a cerebrospinal fluid total protein falling between 41.01 and 109.79 mg. for all cases of neurosyphilis, between 43.70 and 114.30 mg. in general paresis, 37.06 and 78.74 in tabes without psychosis, and 31.96 and 99.40 mg. in cerebrospinal syphilis with psychosis. There is no true difference between any of the means excepting neurosyphilis and tabes without psychosis, and general paresis and tabes without psychosis. In these two instances the difference is so pronounced that there is no question concerning its existence. If 39.99 mg. per 100 c. c. of cerebrospinal fluid is accepted as the upper limit of normal protein, it was found that 23.09 per cent of all the cases of neurosyphilis possessed normal values. 20.72 per cent of the cases of general paresis, 29.16 per cent of the cases of tabes without psychosis, and 34.09 per cent of the cases of cerebrospinal syphilis with psychosis also possessed normal values.
APOL1 Variants Increase Risk for FSGS and HIVAN but Not IgA Nephropathy
Authors: Natalia Papeta, Krzysztof Kiryluk, Ami Patel, Roel Sterken, Nilgun Kacak, Holly J. Snyder, Phil H. Imus, Anand N. Mhatre, Anil K. Lawani, Bruce A. Julian, Robert J. Wyatt, Jan Novak, Christina M. Wyatt, Michael J. Ross, Jonathan A. Winston, Mary E. Klotman, David J. Cohen, Gerald B. Appel, Vivette D. D'Agati, Paul E. Klotman, Ali G. Gharavi
Journal: Journal of the American Society of Nephrology (2011)

A chromosome 22q13 locus strongly associates with increased risk for idiopathic focal segmental glomerulosclerosis (FSGS), HIV-1-associated nephropathy (HIVAN), and hypertensive ESRD among individuals of African descent. Although initial studies implicated MYH9, more recent analyses localized the strongest association within the neighboring APOL1 gene. In this replication study, we examined the six top-most associated variants in APOL1 and MYH9 in an independent cohort of African Americans with various nephropathies (44 with FSGS, 21 with HIVAN, 32 with IgA nephropathy, and 74 healthy controls). All six variants associated with FSGS and HIVAN (additive ORs, 1.8 to 3.0; P values 3 × 10−2 to 5 × 10−5) but not with IgA nephropathy. In conditional and haplotype analyses, two APOL1 haplotypes accounted for virtually all of the association with FSGS and HIVAN on chromosome 22q13 (haplotype P value = 5.6 × 10−8). To assess the role of MYH9 deficiency in nephropathy, we crossbred Myh9-haploinsufficient mice (Myh9+/−) with HIV-1 transgenic mice. Myh9+/− mice were healthy and did not demonstrate overt proteinuria or nephropathy, irrespective of the presence of the HIV-1 transgene. These data further support the strong association of genetic variants in APOL1 with susceptibility to FSGS and HIVAN among African Americans.
Prostate-specific Antigen–Based Prostate Cancer Screening: Reduction of Prostate Cancer Mortality After Correction for Nonattendance and Contamination in the Rotterdam Section of the European Randomized Study of Screening for Prostate Cancer
Authors: Leonard P. Bokhorst, Chris H. Bangma, Geert J.L.H. van Leenders, Jan J. Lous, Sue M. Moss, Fritz H. Schröder, Monique J. Roobol
Journal: European Urology (2013)
Effects of Testosterone on Coronary Vasomotor Regulation in Men With Coronary Heart Disease
Authors: Carolyn M. Webb, John G. McNeill, Christopher S. Hayward, Dominique de Zeigler, Peter Collins
Journal: Circulation (1999)

Background —The increased incidence of coronary artery disease in men compared with premenopausal women suggests a detrimental role of male hormones on the cardiovascular system. However, testosterone has direct relaxing effects on coronary arteries in animals, as shown both in vitro and in vivo. The effect of testosterone on the human coronary circulation remains unknown. Methods and Results —We studied 13 men (aged 61±11 years) with coronary artery disease. They underwent measurement of coronary artery diameter and blood flow after a 3-minute intracoronary infusion of vehicle control (ethanol) followed by 2-minute intracoronary infusions of acetylcholine (10 −7 to 10 −5 mol/L) until peak velocity response. A dose-response curve to 3-minute infusions of testosterone (10 −10 to 10 −7 mol/L) was then determined, and the acetylcholine infusions were repeated. Finally, an intracoronary bolus of isosorbide dinitrate (1000 μg) was given. Coronary blood flow was calculated from measurements of blood flow velocity using intracoronary Doppler and coronary artery diameter using quantitative coronary angiography. Testosterone significantly increased coronary artery diameter compared with baseline (2.78±0.74 mm versus 2.86±0.72 mm [ P =0.05], 2.87±0.71 mm [ P =0.038], and 2.90±0.75 mm [ P =0.005] for baseline versus testosterone 10 −9 to 10 −7 mol/L, respectively). A significant increase in coronary blood flow occurred at all concentrations of testosterone compared with baseline (geometric mean [95% CI]: 32 [25, 42] versus 36.3 [27, 48] { P =0.006}, 35.3 [26, 47] { P =0.029}, 36.8 [28, 49] { P =0.002}, and 37 [28, 48] { P =0.002} mL/min for baseline versus testosterone 10 −10 to 10 −7 mol/L, respectively). No differences existed in coronary diameter or blood flow responses to acetylcholine before versus after testosterone. Conclusions —Short-term intracoronary administration of testosterone, at physiological concentrations, induces coronary artery dilatation and increases coronary blood flow in men with established coronary artery disease.
P53 The Effect of co-morbidities on response to pulmonary rehabilitation
Authors: K. A. Ingram, R. P. Fowler, A. L. Clark, C. M. Nolan, W. D. Man
Journal: Thorax (2010)

<h3>Introduction</h3> Most patients with COPD are elderly, and the presence of co-morbidities is not uncommon. Co-morbidities are an important determinant of health related quality of life in patients with COPD. Although pulmonary rehabilitation (PR) is well known to improve exercise performance, health-related quality of life and symptoms, a proportion of patients are non-responders. We hypothesised that improvement in exercise capacity and health-related quality of life following PR may be limited in the presence of co-morbidities. <h3>Methods</h3> A structured history was taken from 128 patients referred to an 8-week supervised outpatient PR programme. Individuals9 self-reported co-morbidities were assessed by the Charlson index, which assigns to each disease a score that is proportional to the disease related risk of death. The calculated Charlson index did not include COPD in the individual9s score as suggested in the original description. In 115 patients completing the programme, changes in incremental shuttle walk (ISW) and chronic respiratory disease questionnaire (CRQ) domains following PR were calculated, and compared between those patients with and without co-morbidities (Charlson index 1 or more vs 0) using unpaired t-test or non-parametric equivalent. <h3>Results</h3> 84 patients (73%) had a Charlson index of 1 or more. No difference in age, gender, FEV1, or MRC Dyspnoea score was seen between those with and without co-morbidities. Mean (SD) change in ISW following PR was not significantly different between those with and without co-morbidities (63 (96) vs 33 (88); p=0.13). Similarly there were no significant differences in CRQ-D change (4.1 (6.4) vs 5.7 (7.1); p=0.26), CRQ-F change (2.6 (5.1) vs 4.4 (5.7); p=0.13), CRQ-E change (3.6 (7.8) vs 6.4 (7.7); p=0.09) or CRQ-M change (2.7 (4.8) vs 2.3 (6.9); p=0.75). No association was seen between Charlson index and change in ISW following PR (Spearman rank=0.09; p=0.32). <h3>Discussion</h3> The prevalence of co-morbidities in COPD patients undergoing PR is high. The presence of co-morbidities does not seem to affect patients9 response to pulmonary rehabilitation.
Erythropoietin guides multipotent hematopoietic progenitor cells toward an erythroid fate
Authors: Amit Grover, Elena Mancini, Susan Moore, Adam J. Mead, Deborah Atkinson, Kasper D. Rasmussen, Donal O’Carroll, Sten Eirik W. Jacobsen, Claus Nerlov
Journal: The Journal of Experimental Medicine (2014)

The erythroid stress cytokine erythropoietin (Epo) supports the development of committed erythroid progenitors, but its ability to act on upstream, multipotent cells remains to be established. We observe that high systemic levels of Epo reprogram the transcriptomes of multi- and bipotent hematopoietic stem/progenitor cells in vivo. This induces erythroid lineage bias at all lineage bifurcations known to exist between hematopoietic stem cells (HSCs) and committed erythroid progenitors, leading to increased erythroid and decreased myeloid HSC output. Epo, therefore, has a lineage instructive role in vivo, through suppression of non-erythroid fate options, demonstrating the ability of a cytokine to systematically bias successive lineage choices in favor of the generation of a specific cell type.
Erythema something or other.
Authors: P Copeman
Journal: BMJ (1980)

Manipulation trialsSIR,-Every doctor and most laymen are well aware of patients who have been treated for backache for months, even years, within the NHS and have finally been adjured to "live with it."A proportion of such patients secured rapid relief from a lay manipulator.It was this well-recognised fact that let me teach spinal manipulation (among other techniques) to my physiotherapy students from 1940 to 1970.The intention was that those who needed this treatment should get it immediately, from skilled personnel, and in full view within the hospital rather than wander off in the end on their own to try their luck with some self-styled layman.This policy worked very well, many patients recovering swiftly-in half of all cases, backache recovered in one session of manipulation.It is very noble of Dr H Sims-Williams and others (24 November, p 1318) to have put up the controlled trial that they describe.The result was negative; but, firstly, the patients were not selected as suited or unsuited to manipulation; secondly, they were treated by Maitland's adaptation of Balfour's' (1819) and Recamier's oscillatory techniques2 (methods with scant resemblance to those taught by me3); and, thirdly, they were all assessed at the end of a month.Physiotherapy (that is, heat and exercises) for backache is useless.Their article states, "The management of non-specific back pain is unsatisfactory and physiotherapy is often prescribed empirically."On what grounds?No patient should be treated until the cause of his symptoms becomes clear, and the measure prescribed should be appropriate to the diagnosis.If manipulation were confined to suitable cases, proper methods were employed, and the assessment were made after a few days a very different picture would emerge.Meanwhile, doctors are discouraged by papers like this one from adopting sensible measures and the jubilant lay manipulators cash in again.
Analysis of epigenetic changes in survivors of preterm birth reveals the effect of gestational age and evidence for a long term legacy
Authors: Mark N Cruickshank, Alicia Oshlack, Christiane Theda, Peter G Davis, David Martino, Penelope Sheehan, Yun Dai, Richard Saffery, Lex W Doyle, Jeffrey M Craig
Journal: Genome Medicine (2013)

Preterm birth confers a high risk of adverse long term health outcomes for survivors, yet the underlying molecular mechanisms are unclear. We hypothesized that effects of preterm birth can be mediated through measurable epigenomic changes throughout development. We therefore used a longitudinal birth cohort to measure the epigenetic mark of DNA methylation at birth and 18 years comparing survivors of extremely preterm birth with infants born at term.Using 12 extreme preterm birth cases and 12 matched, term controls, we extracted DNA from archived neonatal blood spots and blood collected in a similar way at 18 years of age. DNA methylation was measured at 347,789 autosomal locations throughout the genome using Infinium HM450 arrays. Representative methylation differences were confirmed by Sequenom MassArray EpiTYPER.At birth we found 1,555 sites with significant differences in methylation between term and preterm babies. At 18 years of age, these differences had largely resolved, suggesting that DNA methylation differences at birth are mainly driven by factors relating to gestational age, such as cell composition and/or maturity. Using matched longitudinal samples, we found evidence for an epigenetic legacy associated with preterm birth, identifying persistent methylation differences at ten genomic loci. Longitudinal comparisons of DNA methylation at birth and 18 years uncovered a significant overlap between sites that were differentially-methylated at birth and those that changed with age. However, we note that overlapping sites may either differ in the same (300/1,555) or opposite (431/1,555) direction during gestation and aging respectively.We present evidence for widespread methylation differences between extreme preterm and term infants at birth that are largely resolved by 18 years of age. These results are consistent with methylation changes associated with blood cell development, cellular composition, immune induction and age at these time points. Finally, we identified ten probes significantly associated with preterm individuals and with greater than 5% methylation discordance at birth and 18 years that may reflect a long term epigenetic legacy of preterm birth.
Breech: vaginal delivery or caesarean section?
Authors: J S. Crawford
Journal: BMJ (1982)

breech presentation at term.Factors affecting the mode of breech delivery were discussed in a recently published textbook,2 as were also the place for induction of labour and that of external cephalic version.Professor Russell mentions too the important consideration of possible litigation if all does not proceed perfectly.Clinical practices in many disciplines have changed because of the worry of possible litigation, and this, sadly, may not always be to the benefit of the public our profession serves.
An Evolutionary Analysis of RAC2 Identifies Haplotypes Associated with Human Autoimmune Diseases
Authors: M. Sironi, F. R. Guerini, C. Agliardi, M. Biasin, R. Cagliani, M. Fumagalli, D. Caputo, A. Cassinotti, S. Ardizzone, M. Zanzottera, E. Bolognesi, S. Riva, Y. Kanari, M. Miyazawa, M. Clerici
Journal: Molecular Biology and Evolution (2011)

The human RAC2 gene encodes a small GTP-binding protein with a pivotal role in immune activation and in the induction of peripheral immune tolerance through restimulation-induced cell death (RICD). Different human pathogens target the protein product of RAC2, suggesting that the gene may be subject to natural selection, and that variants in RAC2 may affect immunological phenotypes in humans. We scanned the genomic region encompassing the entire transcription unit for the presence of putative noncoding regulatory elements conserved across mammals. This information was used to select two RAC2 gene regions and analyze their intraspecific genetic diversity. Results suggest that a region covering the 3′ untranslated region has been a target of multiallelic balancing selection (or diversifying selection), and three major RAC2 haplogroups occur in human populations. Haplotypes belonging to one of these clades are associated with increased susceptibility to multiple sclerosis (P = 0.022) and earlier onset of disease symptoms (P = 0.025). This same haplogroup is significantly more common in patients with Crohn's disease compared with healthy controls (P = 0.048). These data reinforce recent evidences that susceptibility alleles/haplotypes are shared among multiple autoimmune disorders and support a causal “role for RAC2” variants in the pathogenesis of autoimmune diseases. Other genes with a role in RICD have previously been associated with autoimmunity in humans, suggesting that this pathway and RAC2 may represent novel therapeutic targets in autoimmune disorders.
Overexpression of Shp2 tyrosine phosphatase is implicated in leukemogenesis in adult human leukemia
Authors: Rongzhen Xu, Yingzi Yu, Shu Zheng, Xiaoying Zhao, Qinghua Dong, Zhiwen He, Yun Liang, Qinghua Lu, Yongmin Fang, Xiaoxian Gan, Xiaohua Xu, Suzhan Zhang, Qi Dong, Xiaohong Zhang, Gen-Sheng Feng
Journal: Blood (2005)
Exhaled nitric oxide and COPD
Authors: D.R. Taylor, J. Dummer
Journal: European Respiratory Journal (2010)

We were interested to read the paper by LEHTIMA ¨KI et al. [1] recently published in the European Respiratory Journal, in which those authors reported that ''high pre-treatment levels of J9aw,NO [bronchial nitric oxide flux] are related to symptom relief and improvement of airway obstruction'' when inhaled fluticasone is given to patients with chronic obstructive pulmonary disease (COPD).Their data complement those which we ourselves have recently published [2].
The Coping with Asthma Study: a randomised controlled trial of a home based, nurse led psychoeducational intervention for adults at risk of adverse asthma outcomes
Authors: J R Smith
Journal: Thorax (2005)

Morbidity and mortality associated with severe asthma might be reduced by interventions that address psychosocial factors contributing to adverse outcomes. A study was undertaken to assess the effectiveness of a 6 month home based psychoeducational intervention delivered by a respiratory nurse specialist for adults at risk of adverse asthma outcomes.A pragmatic randomised controlled trial was performed in 92 adults registered with hospital or primary care asthma clinics. All had previous hospital admissions and/or were on British Thoracic Society step 4-5 treatment and had failed to attend clinic appointments or were considered to have poor adherence to other aspects of their agreed management. Patients were visited in their homes for assessment and, where appropriate, intervention. The main outcomes measured were symptom control, asthma specific quality of life, and generic health status.At the 6 month primary time point there were no significant differences between usual care and intervention groups in mean symptom control, physical functioning, or mental health scores (differences (with 95% CI) -0.35 (-1.83 to 1.13), 3.10 (-11.42 to 17.63), 0.42 (-10.22 to 11.07), respectively). Small effects on asthma specific quality of life up to 12 months (e.g. adjusted difference at 12 months 0.13 (95% CI 0.02 to 0.25)) and short term effects on generic health status, which mirrored improvements in aspects of self-care observed at the end of the intensive phase of the intervention, were apparent only from fully adjusted analyses.A home based intervention provided by a nurse receiving psychological supervision may have effects on quality of life but is overall of limited long term benefit to adults at risk of adverse asthma outcomes.
Pulmonary Biomarkers in Chronic Obstructive Pulmonary Disease
Authors: Peter J. Barnes, Badrul Chowdhury, Sergei A. Kharitonov, Helgo Magnussen, Clive P. Page, Dirkje Postma, Marina Saetta
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

There has been increasing interest in using pulmonary biomarkers to understand and monitor the inflammation in the respiratory tract of patients with chronic obstructive pulmonary disease (COPD). In this Pulmonary Perspective we discuss the merits of the various approaches by reviewing the current literature on pulmonary biomarkers in COPD and underscore the need for more systematic studies in the future. Bronchial biopsies and bronchoalveolar lavage provide valuable information about inflammatory cells and mediators, but are invasive, so that repeated measurements have to be very limited in assessing any interventions. Induced sputum has provided considerable information about the inflammatory process, including mediators and proteinases in COPD, but selectively samples proximal airways and may not closely reflect distal inflammatory processes. Exhaled gases and breath condensate are noninvasive procedures, so repeated measurements are possible, but for some assays the variability is relatively high. There is relatively little information about how any of these biomarkers relate to other clinical outcomes, such as progression of the disease, severity of disease, clinical subtypes, or response to therapy. More information is also needed about the variability in these measurements. In the future, pulmonary biomarkers may be useful in predicting disease progression, indicating disease instability, and in predicting response to current therapies and novel therapies, many of which are now in development.
BAFF/BLyS can potentiate B-cell selection with the B-cell coreceptor complex
Authors: Hidenori Hase, Yumiko Kanno, Masaru Kojima, Kaoru Hasegawa, Daisuke Sakurai, Hidefumi Kojima, Naoyuki Tsuchiya, Katsushi Tokunaga, Nobuhide Masawa, Miyuki Azuma, Ko Okumura, Tetsuji Kobata
Journal: Blood (2003)
Intravascular large B-cell lymphoma: Remission after rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisolone chemotherapy
Authors: Barbara Horváth, Judit Demeter, Nóra Erős, Judit Hársing, Judit Csomor, András Matolcsy, Gyula Bottlik, Gabriella Győri, Márta Marschalkó, Sarolta Kárpáti
Journal: Journal of the American Academy of Dermatology (2009)