tbuckley/cabot-search huggingface dataset:
Labile hypertension: a faulty concept? The Framingham study.
Authors: W B Kannel, P Sorlie, T Gordon
Journal: Circulation (1980)

Labile blood pressure elevation is believed to have less clinical significance than "fixed hypertension." This assertion was examined in the Framingham cohort of 5209 men and women followed for 20 years for the development of cardiovascular events in relation to three routinely measured blood pressures at each of 10 biennial examinations. Variability of pressure judged from the standard deviation about the mean of three pressures was not a consistent characteristic of subjects from one examination to the next (r = 0.07). Higher pressures were more labile than low ones, so that "fixed hypertensives" actually had more labile pressures than did so-called labile hypertensives. Lability, also increased with age. Labile hypertension, determined during a 1-hour period of observation, adds nothing to the ability of the mean blood pressure to predict cardiovascular disease. The mean, minimum and maximum of three pressures measured during an examination were equally efficient predictors of cardiovascular disease. In multivariate analysis, for any given average pressure, risk of cardiovascular events was unaffected by the degree of variability of the pressure. It is recommended that the average of a series of pressures be used to determine risk, preferably over more than one examination.
COPD prevalence and its association with occupational exposures in a general population
Authors: A.M. Melville, T. Pless-Mulloli, O.A. Afolabi, S.C. Stenton
Journal: European Respiratory Journal (2010)

The aim of this study was to ascertain the population prevalence of chronic obstructive pulmonary disease (COPD) in an area with past heavy industry and to establish the relative contributions of occupational and other risk factors. We investigated respiratory symptoms and the prevalence of spirometrically-defined COPD in a population-based study in North-East England (UK) between 2002 and 2004. Questionnaires were posted to 6,000 males and 6,000 females, 45-69 yrs of age, who were randomly selected from a primary care database (response rate 64%, n = 7,566). Spirometric measurements were performed on 845 randomly selected responders. We defined COPD by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) II criteria. The prevalence of respiratory symptoms was 55%. Symptoms were strongly associated with smoking, occupational exposures and hay fever. COPD was present in 10% of subjects. Its presence was significantly associated with occupational exposures, smoking and hay fever. COPD is common in North-East England. Respiratory effects of occupational exposures can be detected within the general population: there were clear associations between occupational exposures and respiratory symptoms. The association with COPD was more marked in females.
Pulmonary rehabilitation at home.
Authors: P. J. Wijkstra
Journal: Thorax (1996)

Pulmonary rehabilitation at homePulmonary rehabilitation programmes are now well es- tablished to provide a comprehensive approach to con- trolling and alleviating symptoms and to optimising the functional capacity of patients with chronic obstructive pulmonary disease (COPD).Recently, pulmonary re- habilitation was defined as "a multidimensional continuum of services directed to persons with pulmonary disease and their families, usually by an interdisciplinary team of specialists, with the goal of achieving and maintaining the individual's maximum level of independence and func- tioning in the community."'The benefits of pulmonary
Monocytes and tissue factor promote thrombosis in a murine model of oxygen deprivation.
Authors: C A Lawson, S D Yan, S F Yan, H Liao, Y S Zhou, J Sobel, W Kisiel, D M Stern, D J Pinsky
Journal: Journal of Clinical Investigation (1997)

Clinical conditions associated with local or systemic hypoxemia can lead to prothrombotic diatheses. This study was undertaken to establish a model of whole-animal hypoxia wherein oxygen deprivation by itself would be sufficient to trigger tissue thrombosis. Furthermore, this model was used to test the hypothesis that hypoxia-induced mononuclear phagocyte (MP) recruitment and tissue factor (TF) expression may trigger the local deposition of fibrin which occurs in response to oxygen deprivation. Using an environmental chamber in which inhaled oxygen tension was lowered to 6%, hypoxic induction of thrombosis was demonstrated in murine pulmonary vasculature by 8 h based upon: (a) immunohistologic evidence of fibrin formation in hypoxic lung tissue using an antifibrin antibody, confirmed by 22.5-nm strand periodicity by electron microscopy; (b) immunoblots revealing fibrin gamma-gamma chain dimers in lungs from hypoxic but not normoxic mice or hypoxic mice treated with hirudin; (c) accelerated deposition of 125I-fibrin/fibrinogen and 111In-labeled platelets in the lung tissue of hypoxic compared with normoxic animals; (d) reduction of tissue 125I-fibrin/fibrinogen accumulation in animals which had either been treated with hirudin or depleted of platelets before hypoxic exposure. Because immunohistochemical analysis of hypoxic pulmonary tissue revealed strong MP staining for TF, confirmed by increased TF RNA in hypoxic lungs, and because 111In-labeled murine MPs accumulated in hypoxic pulmonary tissue, we evaluated whether recruited MPs might be responsible for initiation of hypoxia-induced thrombosis. This hypothesis was supported by several lines of evidence: (a) MP depletion before hypoxia reduced thrombosis, as measured by reduced 125I-fibrin/fibrinogen deposition and reduced accumulation of cross-linked fibrin by immunoblot; (b) isolated murine MPs demonstrated increased TF immunostaining when exposed to hypoxia; and (c) administration of an anti-rabbit TF antibody that cross-reacts with murine TF decreased 125I-fibrin/fibrinogen accumulation and cross-linked fibrin accumulation in response to hypoxia in vivo. In summary, these studies using a novel in vivo model suggest that MP accumulation and TF expression may promote hypoxia-induced thrombosis.
Cigarette Smoking Affects Urinary Liver-Type Fatty Acid–Binding Protein Concentration in Patients With Early Diabetic Nephropathy
Authors: Tsukasa Nakamura, Takeshi Sugaya, Hikaru Koide
Journal: Diabetes Care (2006)

Cigarette smoking causes a decrease in the glomerular filtration rate in diabetic patients with normal renal function, independent of confounding factors including severe proteinuria (1). It increases the risk of microalbuminuria and accelerates the progression from microalbuminuria to overt proteinuria as well as the progression of renal failure in patients with type 2 diabetes (2). It is widely accepted that the rate of functional decline correlates with the degree of renal tubulointerstitial fibrosis. Previous studies have shown …
Effect of adults' self-regulation of diabetes on quality-of-life outcomes.
Authors: K W Watkins, C M Connell, J T Fitzgerald, L Klem, T Hickey, B Ingersoll-Dayton
Journal: Diabetes Care (2000)

To examine the relationships among cognitive representations of diabetes, diabetes-specific health behaviors, and quality of life using Leventhal and Diefenbach's self-regulation model of illness (Leventhal H, Diefenbach M: The active side of illness cognition. In Mental Representation in Health and Illness. SkeltonJA, Croyle RT, Eds. New York, Springer-Verlag, 1991, p. 247-272).This research involved secondary analysis of a mailed survey completed by 296 adults (ages 20-90 years). Structural equation modeling was conducted to investigate relationships among cognitive representations, diabetes-specific health behaviors, and quality of life. Model differences by diabetes type were also investigated.Findings indicated that certain cognitive representation constructs were related to increased diabetes-specific health behaviors, decreased sense of burden, and positive quality-of-life outcomes. Individuals levels of understanding of diabetes and their perceptions of control over diabetes were the most significant predictors of outcomes. However, diabetes-specific health behaviors were related to an increased sense of burden that was negatively associated with quality of life. Multigroup analyses indicated that this self-regulatory model provided a good fit for individuals with type 1 diabetes, those with type 2 diabetes who take insulin, and those with type 2 diabetes who do not take insulin.These findings advance what is known about cognitive representations of illness and the self-regulation of diabetes as well as the relationships between cognitive representations of illness, quality of life, and behavioral factors. In particular, results from this study suggest the need for further study to address ways of reducing the burden of diabetes associated with health behaviors and decreased quality of life.
Innate partnership of HLA-B and KIR3DL1 subtypes against HIV-1
Authors: Maureen P Martin, Ying Qi, Xiaojiang Gao, Eriko Yamada, Jeffrey N Martin, Florencia Pereyra, Sara Colombo, Elizabeth E Brown, W Lesley Shupert, John Phair, James J Goedert, Susan Buchbinder, Gregory D Kirk, Amalio Telenti, Mark Connors, Stephen J O'Brien, Bruce D Walker, Peter Parham, Steven G Deeks, Daniel W McVicar, Mary Carrington
Journal: Nature Genetics (2007)
α2 Isoform–specific activation of 5′adenosine monophosphate–activated protein kinase by 5-aminoimidazole-4-carboxamide-1-β-d-ribonucleoside at a physiological level activates glucose transport and increases glucose transporter 4 in mouse skeletal muscle
Authors: Masako Nakano, Taku Hamada, Tatsuya Hayashi, Shin Yonemitsu, Licht Miyamoto, Taro Toyoda, Satsuki Tanaka, Hiroaki Masuzaki, Ken Ebihara, Yoshihiro Ogawa, Kiminori Hosoda, Gen Inoue, Yasunao Yoshimasa, Akira Otaka, Toru Fushiki, Kazuwa Nakao
Journal: Metabolism (2006)
A First Prospective, Randomized, Double-Blind, Placebo-Controlled Clinical Trial Evaluating Extracorporeal Shock Wave Therapy for the Treatment of Peyronie's Disease
Authors: Alessandro Palmieri, Ciro Imbimbo, Nicola Longo, Ferdinando Fusco, Paolo Verze, Francesco Mangiapia, Massimiliano Creta, Vincenzo Mirone
Journal: European Urology (2009)
Colopleural fistula due to strangulated Bochdalek hernia in an adult.
Authors: M Sinha, P Gibbons, S C Kennedy, H R Matthews
Journal: Thorax (1989)

An elderly patient presented with a right sided pneumothorax due to strangulation of part of the colon through a congenital Bochdalek hernia. Congenital posterolateral diaphragmatic hernia of Bochdalek is rare in an adult and strangulation with pneumothorax has not been reported before.
A comprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and co-occurrence among distinct therapeutic targets
Authors: Niantao Deng, Liang Kee Goh, Hannah Wang, Kakoli Das, Jiong Tao, Iain Beehuat Tan, Shenli Zhang, Minghui Lee, Jeanie Wu, Kiat Hon Lim, Zhengdeng Lei, Glenn Goh, Qing-Yan Lim, Angie Lay-Keng Tan, Dianne Yu Sin Poh, Sudep Riahi, Sandra Bell, Michael M Shi, Ronald Linnartz, Feng Zhu, Khay Guan Yeoh, Han Chong Toh, Wei Peng Yong, Hyun Cheol Cheong, Sun Young Rha, Alex Boussioutas, Heike Grabsch, Steve Rozen, Patrick Tan
Journal: Gut (2012)

Gastric cancer is a major gastrointestinal malignancy for which targeted therapies are emerging as treatment options. This study sought to identify the most prevalent molecular targets in gastric cancer and to elucidate systematic patterns of exclusivity and co-occurrence among these targets, through comprehensive genomic analysis of a large panel of gastric cancers.Using high-resolution single nucleotide polymorphism arrays, copy number alterations were profiled in a panel of 233 gastric cancers (193 primary tumours, 40 cell lines) and 98 primary matched gastric non-malignant samples. For selected alterations, their impact on gene expression and clinical outcome were evaluated.22 recurrent focal alterations (13 amplifications and nine deletions) were identified. These included both known targets (FGFR2, ERBB2) and also novel genes in gastric cancer (KLF5, GATA6). Receptor tyrosine kinase (RTK)/RAS alterations were found to be frequent in gastric cancer. This study also demonstrates, for the first time, that these alterations occur in a mutually exclusive fashion, with KRAS gene amplifications highlighting a clinically relevant but previously underappreciated gastric cancer subgroup. FGFR2-amplified gastric cancers were also shown to be sensitive to dovitinib, an orally bioavailable FGFR/VEGFR targeting agent, potentially representing a subtype-specific therapy for FGFR2-amplified gastric cancers.The study demonstrates the existence of five distinct gastric cancer patient subgroups, defined by the signature genomic alterations FGFR2 (9% of tumours), KRAS (9%), EGFR (8%), ERBB2 (7%) and MET (4%). Collectively, these subgroups suggest that at least 37% of gastric cancer patients may be potentially treatable by RTK/RAS directed therapies.
Memorial states of awareness versus volitional control: The role of task differences
Authors: Sachiko Kinoshita
Journal: Behavioral and Brain Sciences (1999)

Dienes &amp; Perner's analysis provides a clear theoretical justification for using a demonstration of volitional control as a criterion for conscious awareness. However, in memory tasks, the converse does not hold: A phenomenological awareness of a memory episode can arise involuntarily, even when the task does not require retrieval of the episode. The varying amounts of volitional retrieval required by different memory tasks need to be recognized.
A novel method for assessing unchallenged levels of mediators in nasal epithelial lining fluid
Authors: Bo L.K. Chawes, Matthew J. Edwards, Betty Shamji, Christoph Walker, Grant C. Nicholson, Andrew J. Tan, Nilofar V. Følsgaard, Klaus Bønnelykke, Hans Bisgaard, Trevor T. Hansel
Journal: Journal of Allergy and Clinical Immunology (2010)
Updating prognostic parameters in COPD: the updated BODE index and ADO
Authors: F. Bazari
Journal: Thorax (2010)

The BODE index was devised to better reflect the multisystem effects of chronic obstructive pulmonary disease (COPD), allowing for better prognostic estimation than that provided by forced expiratory volume in 1 s (FEV1) alone. The grading system, based on four parameters—that is, body mass index, airflow obstruction, Medical Research Council (MRC) dyspnoea score and the 6 min walk distance—was verified by population studies.

This study set out to assess whether the BODE index …
Effect of orthotopic liver transplantation on bone mineral content and serum vitamin D metabolites in infants and children with chronic cholestasis
Authors: Eric A. Argao, William F. Balistreri, Bruce W. Hollis, Frederick C. Ryckman, James E. Heubi
Journal: Hepatology (1994)

Almost all infants and children with chronic cholestasis have osteopenia. We evaluated the effect of orthotopic liver transplantation on bone mineral content and serum 25(OH)-vitamin D-[25(OH)D]-of nine infants and children (five girls; age, 6 to 21 mo at the time of orthotopic liver transplantation) with end-stage liver disease resulting from chronic cholestasis. We hypothesized that after orthotopic liver transplantation, decreased bone mineral content will recover and the serum 25(OH)D level will either normalize or remain normal in those who were previously vitamin D deficient or sufficient, respectively. All had subnormal bone mineral content before transplant. On long-term follow-up (> 4 mo) of seven patients, bone mineral content normalized in all between 6.5 and 19 mo after transplant, with a mean of 11.2 +/- 4.5 mo. In six patients with normal serum 25(OH)D levels before orthotopic liver transplantation, the serum 25(OH)D levels had declined markedly 1 to 2 mo after transplant, followed by return to normal by 3 to 6 mo. Low serum 25(OH)D levels (< 15 ng/ml) in three patients before orthotopic liver transplantation normalized after transplant. Although there was no correlation between bone mineral content and serum 25(OH)D level before transplant, sustained normal serum 25(OH)D and 1,25(OH)2D levels preceded or accompanied normalization of bone mineral content in the seven patients available for long-term follow-up. We conclude that (a) in infants and children younger than 2 yr with chronic cholestasis, bone mineral content normalizes approximately 11 mo after orthotopic liver transplantation. This normalization is preceded by a sustained period of normal serum 25(OH)D levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Assessing the metabolic effects of prednisolone in healthy volunteers using urine metabolic profiling
Authors: Sandrine Ellero-Simatos, Ewa Szymańska, Ton Rullmann, Wim Ha Dokter, Raymond Ramaker, Ruud Berger, Thijs Mp van Iersel, Age K Smilde, Thomas Hankemeier, Wynand Alkema
Journal: Genome Medicine (2012)

Glucocorticoids, such as prednisolone, are widely used anti-inflammatory drugs, but therapy is hampered by a broad range of metabolic side effects including skeletal muscle wasting and insulin resistance. Therefore, development of improved synthetic glucocorticoids that display similar efficacy as prednisolone but reduced side effects is an active research area. For efficient development of such new drugs, in vivo biomarkers, which can predict glucocorticoid metabolic side effects in an early stage, are needed. In this study, we aim to provide the first description of the metabolic perturbations induced by acute and therapeutic treatments with prednisolone in humans using urine metabolomics, and to derive potential biomarkers for prednisolone-induced metabolic effects.A randomized, double blind, placebo-controlled trial consisting of two protocols was conducted in healthy men. In protocol 1, volunteers received placebo (n = 11) or prednisolone (7.5 mg (n = 11), 15 mg (n = 13) or 30 mg (n = 12)) orally once daily for 15 days. In protocol 2, volunteers (n = 6) received placebo at day 0 and 75 mg prednisolone at day 1. We collected 24 h urine and serum samples at baseline (day 0), after a single dose (day 1) and after prolonged treatment (day 15) and obtained mass-spectrometry-based urine and serum metabolic profiles.At day 1, high-dose prednisolone treatment increased levels of 13 and 10 proteinogenic amino acids in urine and serum respectively, as well as levels of 3-methylhistidine, providing evidence for an early manifestation of glucocorticoid-induced muscle wasting. Prednisolone treatment also strongly increased urinary carnitine derivatives at day 1 but not at day 15, which might reflect adaptive mechanisms under prolonged treatment. Finally, urinary levels of proteinogenic amino acids at day 1 and of N-methylnicotinamide at day 15 significantly correlated with the homeostatic model assessment of insulin resistance and might represent biomarkers for prednisolone-induced insulin resistance.This study provides evidence that urinary metabolomics represents a noninvasive way of monitoring the effect of glucocorticoids on muscle protein catabolism after a single dose and can derive new biomarkers of glucocorticoid-induced insulin resistance. It might, therefore, help the development of improved synthetic glucocorticoids.ClinicalTrials.gov NCT00971724.
Clinical Tumor Staging of Adenocarcinoma of the Esophagus and Esophagogastric Junction
Authors: Richard C. Turkington, Eileen Parkes, Richard D. Kennedy, Martin M. Eatock, Claire Harrison, Paula McCloskey, Colin Purcell
Journal: Journal of Clinical Oncology (2015)

TO THEEDITOR: We congratulate Davies et al 1 on the retrospective analysis of 400 patients treated with neoadjuvant chemotherapy followed by surgery at two high-volume London centers over the course of a decade. Rather than examining the prognostic effect of tumor regression, the authors focused on the downstaging effect of neoadjuvant chemotherapy as a predictor of recurrence-free and overall survival. Following adjustment for known clinicopathologic variables, tumor downstaging was associated with a reduction in the risk of recurrence and death, suggesting that major clinical decisions should be based on postchemotherapy staging. As mentioned by the authors, advanced diagnostic staging procedures, such as positron emission tomography-computed tomography (PET-CT),areimportantfordetectingnodaldiseaseanddistantmetastases.Toclassifyatumorasdownstaged,itisessentialtonotonlyaccurately define the pathologic stage following surgical resection but also to define the clinical stage before chemotherapy. Although much work has been carried out to standardize the reporting of pathologic stage, the use of clinical staging methodologies has varied over time and between centers. 2,3 StagingthatusesPET-CTcandetectoccultmetastaticdiseaseinup
Combination Treatment of Prostate Cancer Cell Lines with Bioactive Soy Isoflavones and Perifosine Causes Increased Growth Arrest and/or Apoptosis
Authors: Ruth L. Vinall, Kimberley Hwa, Paramita Ghosh, Chong-Xian Pan, Primo N. Lara, Ralph W. de Vere White
Journal: Clinical Cancer Research (2007)

To determine whether targeting the androgen receptor (AR) and Akt pathways using a combination of genistein combined polysaccharide (GCP) and perifosine is more effective at inducing growth arrest/apoptosis in prostate cancer cells compared with treatment with GCP or perifosine as single agents.The effect of GCP and perifosine treatment was assessed in five prostate cancer cell lines: LNCaP (androgen sensitive), LNCaP-R273H, C4-2, Cds1, and PC3 (androgen insensitive). A clonogenic assay assessed the long-term effects on cell growth and survival. Flow cytometry and Western blot analysis of poly(ADP)ribose polymerase cleavage were used to assess short-term effects. Preliminary studies to investigate mechanism of action included Western blot for P-Akt, Akt, P-p70S6K, p70S6K, p53, and p21; prostate-specific antigen analysis; and the use of myristoylated Akt and AR-specific small interfering RNA.Combination treatment with GCP and perifosine caused a decrease in clonogenic potential in all cell lines. In short-term assays, growth arrest was observed in the majority of cell lines, as well as increased inhibition of Akt activity and induction of p21 expression. Increased apoptosis was only observed in LNCaP. Knockdown of AR caused a further increase in apoptosis.Combination treatment with GCP and perifosine targets the Akt pathway in the majority of the prostate cancer cell lines and causes increased inhibition of cell growth and clonogenicity. In LNCaP, combination treatment targets both the Akt and AR pathways and causes increased apoptosis. These data warrant clinical validation in prostate cancer patients.
The fruits of our efforts: time for a different view of lung cancer and CT screening
Authors: F. Detterbeck
Journal: Thorax (2009)

room for hospitals to undertake practices that will markedly decrease their VAP rates and yet do little or nothing to improve patient outcomes. 12he implications are as follows: (1) VAP as currently defined is not a suitable measure for benchmarking hospitals or for external assessment of quality of care since the diagnosis is too inexact and liable to be gamed; (2) internal quality improvement initiatives to decrease VAP rates need to pay close attention to the diagnostic protocol to ensure consistency over time; and (3) we need a new, more objective and accurate measure for quality of care in ventilated patients that will reliably predict patients' outcomes.Until then, quality improvement initiatives would do well to track directly patient outcomes, such as duration of ventilation, length of stay and mortality, to increase confidence that an observed change in VAP rates translates into improved patient outcomes.This is critical to avoid unintended consequences from well-meaning initiatives to drive our hospital-acquired infection rates to zero.