tbuckley/cabot-search huggingface dataset:
Use of heated humidification during nasal CPAP titration in obstructive sleep apnoea syndrome
Authors: M. Duong, L. Jayaram, D. Camfferman, P. Catcheside, I. Mykytyn, R. D. McEvoy
Journal: European Respiratory Journal (2005)

Nasal symptoms associated with the use of nasal continuous positive airway pressure (nCPAP) in obstructive sleep apnoea (OSA) can adversely impact on patients' tolerance, acceptance and adherence to nCPAP therapy. Regular use of heated humidification is effective in alleviating these symptoms and improve patient comfort. In a randomised, parallel, double-blinded, controlled study, the present authors examined the use of heated humidification during a single night laboratory nCPAP titration in untreated OSA patients and its effect on nasal symptoms, nasal airway resistance (NAR), effective pressure and treatment tolerability and acceptance. Baseline characteristics of subjects (n = 70) receiving placebo and humidification were (mean± sem ): age 51.2±2.2 versus 50.6±1.6 yrs; body mass index 33.6±0.9 versus 35.2±0.9 kg·m −2 ; Epworth Sleepiness Scale 10.8±1.0 versus 11.3±0.7; and apnoea-hypopnoea index 43.5±4.6 versus 44.4±4.1 events·h −1 . Total inspiratory NAR, before (0.36±0.09 (placebo) versus 0.33±0.09 kPa·L −1 ·s −1 ) and after nCPAP (0.47±0.11 versus 0.29±0.04 kPa·L −1 ·s −1 ) were not significantly different between the groups. No difference was found in the frequency and severity of nasopharyngeal symptoms, therapeutic pressure and subjective response to nCPAP. In conclusion, heated humidification during the initial nasal continuous positive airway pressure titration offers no additional benefit in nasal physiology, symptoms or subjective response to nasal continuous positive airway pressure, and, therefore, should not be routinely recommended.
Detection of pseudomonas aeruginosa (Pa) specific peaks by ion mobility spectrometry (IMS) in exhaled breath of bronchiectasis patients
Authors: Thomas Rabis, Olaf Anhenn, Jörg-Ingo Baumbach, Isabella Kurth, Gerhard Weinreich, Helmut Teschler, Lutz Freitag, Kaid Darwiche, Uwe Mellies, Peter-Michael Rath, Urte Sommerwerck
Journal: European Respiratory Journal (2011)

Introduction:  Colonisation or infection of airways from bronchiectasis patients by  Pa  results in chronic inflammation leading to a progressive destruction of the lung and to a decline in lung function. Therefore more inpatient stays for intravenous antibiotic treatment are necessary and the quality of life in these patients is severely limited.   Objectives:  Aim of our study was to detect and compare volatile organic compounds (VOCs) by IMS in exhaled breath of bronchiectasis patients either colonised or infected by  Pa  with healthy non-smoking controls (hc).   Methods:  We have analysed VOCs by IMS coupled to a multi-capillary column (MCC) for pre-separation (MCC-IMS, B&S Analytik) in exhaled breath of bronchiectasis patients either colonised (Pac,n=3) or infected (Pai,n=9) by  Pa  (Pac+Pai=Pa+,n=12) compared to hc (n=39) and compared Pac with Pai. In addition we analysed VOCs from  Pa  cultures growing on agar plates.   Results:  Using IMS for VOC analysis, differences between Pa+ and hc could be found. Different peaks were detected between Pac and hc, Pai and hc as well as Pac and Pai. VOC analysis from  Pa  cultures revealed two peaks which could be found in the Pa+ bronchiectasis patients.   Conclusions:  IMS seems to be a promising method for the non-invasive identification of patients which are colonized or infected with  Pa . A differentiation between patients colonised or infected with  Pa  seems to be possible, as well. However, confirmation of our findings in a larger study population is needed. The comparison of Pa+ with  Pa  cultures will help to identify peaks caused by the presence of  Pa . Furthermore, it is required to identify the molecules representing the peaks.
Prognosis Research Strategy (PROGRESS) 3: Prognostic Model Research
Authors: Ewout W. Steyerberg, Karel G. M. Moons, Danielle A. van der Windt, Jill A. Hayden, Pablo Perel, Sara Schroter, Richard D. Riley, Harry Hemingway, Douglas G. Altman
Journal: PLoS Medicine (2013)

Prognostic models are abundant in the medical literature yet their use in practice seems limited. In this article, the third in the PROGRESS series, the authors review how such models are developed and validated, and then address how prognostic models are assessed for their impact on practice and patient outcomes, illustrating these ideas with examples.
Pre-eclamptic Toxaemia
Authors: O. V. Jones
Journal: BMJ (1957)

During the course of this century maternal mortality has fallen from a peak of 7.6 in 1918 to well below 1 per 1,000 births to-day, but nevertheless a study of the Registrar-General's Review (1956-7) reveals that a third of these deaths are still due to toxaemia of pregnancy.Whilst information of the maternal cause of stillbirths and neonatal deaths is scanty, Baird, Walker, and Thom- son (1954), in analysing 1,008 foetal deaths, found that 20% were due to toxaemia and accidental haemorrhage.A total loss of child life in Great Britain, as shown in a report of the Ministry of Health (1949) for all toxaemias, varies between 25 and 40%, while 15 to 20% of all infant losses are associated with toxaemia.In this paper the theories regarding the aetiology of toxaemia of pregnancy are omitted, as a general treat- ment of the subject, with particular reference to known clinical facts, is of greater import.Gemmell, Logan, and Benjamin (1954), in analysing a large series of pregnancies, found that 8.5% of primigravidae and 4.2% of multigravidae developed toxaemia; this is close to the commonly accepted 10% for all preg- nancies.The incidence increases in primigravidae over the age of 30 and in multigravidae over 40, whilst it recurs in subsequent pregnancies in 30 to 40% of patients.Few to-day consider that chronic renal damage is a sequela of toxaemia, and most workers, including
Renin-Angiotensin System
Authors: W. Stanley Peart
Journal: New England Journal of Medicine (1975)

ALTHOUGH the names of Tigerstedt and Bergman1 are associated with the first description in 1898 of renin extracted from the kidney, it may come as a surprise that when Tigerstedt, who was the senior worker in the partnership and the Professor of Physiology in the Karolinska Institute, Stockholm, died, there was no mention of renin in the various reviews of his life's work. He would probably have been equally surprised to see the vast new field of renal, adrenal and cardiovascular physiology that this discovery opened up.2 , 3 Renin and Renin-like EnzymesRenin should refer purely to the enzyme extracted . . .
Long-term intake of dietary long-chain n-3 polyunsaturated fatty acids and risk of rheumatoid arthritis: a prospective cohort study of women
Authors: Daniela Di Giuseppe, Alice Wallin, Matteo Bottai, Johan Askling, Alicja Wolk
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To analyse the association between dietary long-chain n-3 polyunsaturated fatty acids (PUFAs) and incidence of rheumatoid arthritis (RA) in middle-aged and older women from the Swedish Mammography Cohort, a population-based prospective study. <h3>Methods</h3> Data on diet were collected in 1987 and 1997 via a self-administered food-frequency questionnaire (FFQ). The risk of RA associated with dietary long-chain n-3 PUFAs and fish intake was estimated using Cox proportional hazard regression models, adjusted for age, cigarette smoking, alcohol intake, use of aspirin and energy intake. <h3>Results</h3> Among 32 232 women born 1914–1948, 205 RA cases were identified during a mean follow-up of 7.5 years (1 January 2003 to 31 December 2010; 2 41 120 person-years). An intake of dietary long-chain n-3 PUFAs (FFQ1997) of more than 0.21 g/day (lowest quintile) was associated with a 35% decreased risk of developing RA (multivariable adjusted relative risk (RR) 0.65; 95% CI 0.48 to 0.90) compared with a lower intake. Long-term intake consistently higher than 0.21 g/day (according to both FFQ1987 and FFQ1997) was associated with a 52% (95% CI 29% to 67%) decreased risk. Consistent long-term consumption (FFQ1987 and FFQ1997) of fish ≥1 serving per week compared with&lt;1 was associated with a 29% decrease in risk (RR 0.71; 95% CI 0.48 to 1.04). <h3>Conclusions</h3> This prospective study of women supports the hypothesis that dietary intake of long-chain n-3 PUFAs may play a role in aetiology of RA.
Calcium attenuates epinephrine's beta-adrenergic effects in postoperative heart surgery patients.
Authors: G P Zaloga, R A Strickland, J F Butterworth, L J Mark, S A Mills, C R Lake
Journal: Circulation (1990)

Epinephrine and calcium possess both cardiac inotropic and vasopressor activity. In addition, epinephrine's cardiovascular effects are mediated via increases in intracellular calcium. As a result, many clinicians administer the two agents together in an attempt to augment their effects. Although this approach seems rational, it has never been proven effective. We evaluated the cardiovascular and hyperglycemic actions of epinephrine (10 and 30 ng/kg/min), with and without calcium chloride administration (10 mg/kg bolus followed by 2 mg/kg/hr infusion), in a prospective, randomized, blinded, crossover designed study. Twelve adult patients were studied 1 day after aortocoronary bypass surgery. Calcium chloride raised ionized calcium levels from 1.06 +/- 0.03 (mean +/- SEM) to 1.44 +/- 0.05 mM (p less than 0.05). Calcium raised mean arterial pressure from 85 +/- 1 to 94 +/- 2 mm Hg (p less than 0.05) but had no significant effect on cardiac index. Epinephrine alone at 10 and 30 ng/kg/min significantly raised cardiac index from 2.7 +/- 0.2 to 3.0 +/- 0.2 (p less than 0.05) and 3.6 +/- 0.3 (p less than 0.05) l/min/m2. After calcium, epinephrine failed to significantly increase cardiac index. Epinephrine at 30 ng/kg/min significantly increased mean arterial pressure from 87 +/- 1 to 95 +/- 2 mm Hg (p less than 0.05). After calcium, epinephrine had no significant effect on blood pressure. In addition, epinephrine's hyperglycemic effect was blunted by calcium. Plasma epinephrine levels were similar during control and calcium infusions. We conclude that calcium blunts epinephrine's beta-adrenergic actions in postoperative cardiac surgery patients.
NHS chief executive denies BMA took health department “for a ride” over GP contract
Authors: Adrian O’Dowd
Journal: BMJ (2008)

A new report is calling for changes in the conduct of clinical trials in the United States to reduce disparities of age, sex, race, and comorbidity.The goal is to give a more representative picture of the benefits and risks of a treatment across the entire population but particularly among those who bear the greatest burden of the morbidity.The eliminating disparities in clinical trials (EDICT) initiative was conducted over two years by the Baylor College of Medicine in Houston and the Intercultural Cancer Council.It is part of an ongoing four year project to reduce barriers to participation in trials.The report of the initiative was released on 1 April in Washington, DC.The report describes itself as a "nationwide call to action . . .that removes the barriers to clinical trial participation and advances education and information sharing [as] a critical step to improving the health status of all Americans."Recommendations include harmonising the Food and Drug Administration's regulations on trial design and conduct with those of the National Institutes of Health requiring diversity; increasing collaboration between government and industry in trials; and fostering community involvement in all phases of trial design and implementation.It calls on journals to require researchers to include an analysis of how their trial participants match the population that bears the greatest burden of that condition.It also seeks better education of institutional review boards on their ethical responsibilities and of the general public about the trials process.Calls for better education of review boards and the public are likely to draw little opposition.But other recommendations are likely to require an increase in the size of a trial to provide sufficient numbers for subgroup analysis according to sex, race, age, and comorbidity.This will increase the cost of trials and could delay the introduction of new drugs to the marketplace.Information on EDICT is available at www.bcm.edu/edict. Trial participants need to represent patients betterUK NEWS Wakefield tells GMC he was motivated by concern for autistic children, p 738 World NEWS Australian drug firms give details of sums spent courting doctors, p 742 bmj.com reducing inequalities in health will need a long timeframe, MPs are told
ANCA Disease
Authors: Ronald J. Falk, J. Charles Jennette
Journal: Journal of the American Society of Nephrology (2010)

ANCA disease remains a subject of great experimental and clinical interest. The subcategories of names and descriptions for this collection of vasculitides and necrotizing glomerulonephritides is still a subject of some debate. The various forms of ANCA disease share some characteristics, and similar therapies are often recommended for overlapping categories of disease. The immunopathogenic effects of myeloperoxidase and proteinase 3 antibodies are well established, and good mechanisms for initiation of disease are starting to emerge, particularly the role of autoantigen complementarity. Here we examine these various topics and discuss an approach to treatment.
An unusual case of gastric erosions
Authors: D. K. Jothimani, U. Zanetto, R. J. Owen, A. J. Lawson, P. G. Wilson
Journal: Gut (2009)

A 37-year old Caucasian woman was referred by her general practitioner for a gastroscopy with a 4 week history of dyspepsia and dysphagia to solids and liquid. There was no history of vomiting or weight loss, nor of aspirin, non-steroidal drugs or excess alcohol intake. She lives with her male partner and a child. There was no significant medical history. Gastroscopy showed a normal oesophagus and four small punched-out erosions with raised edges in the gastric antrum (fig 1). The duodenum was …
Quantitative importance of the 25-hydroxylation pathway for bile acid biosynthesis in the rat
Authors: William C. Duane, Ingemar Björkhem, Jan Neal Hamilton, Susan M. Mueller
Journal: Hepatology (1988)

During biosynthesis of bile acid, carbons 25-26-27 are removed from the cholesterol side chain. Side-chain oxidation begins either with hydroxylation at the 26-position, in which case the three-carbon fragment is released as propionic acid, or with hydroxylation at the 25-position, in which case the three-carbon fragment is released as acetone. In the present study, we have quantitated the relative importance of these two pathways in vivo by measuring production of [ 14 C]acetone from [ 14 C] -26-cholesterol. Four days after intraperitoneal injection of 20 to 40 μCi [ 14 C]-26-cholesterol and 1 day after beginning a constant intravenous infusion of unlabeled acetone at 25 μmoles per kg per min, 6 male and 2 female Sprague-Dawley rats underwent breath collections. Expired acetone was trapped and purified as the 2,4-dinitrophenylhydrazine derivative. 14 CO 2 was trapped quantitatively using phenethylamine. Specific activity of breath acetone was multiplied times the acetone infusion rate to calculate production of [ 14 C]acetone. [ 14 C] Acetone production averaged 1.7% of total release of 14 C from [ 14 C]-26-cholesterol, estimated by 14 CO 2 output. The method was validated by showing that [ 14 C] acetone production from [ 14 C]isopropanol averaged 111% of the [ 14 C]isopropanol infusion rate. We conclude that, in the normal rat, the 25-hydroxylation pathway accounts for less than 2% of bile acid synthesis.
Dynamic cortical actin remodeling by ERM proteins controls BCR microcluster organization and integrity
Authors: Bebhinn Treanor, David Depoil, Andreas Bruckbauer, Facundo D. Batista
Journal: The Journal of Experimental Medicine (2011)

Signaling microclusters are a common feature of lymphocyte activation. However, the mechanisms controlling the size and organization of these discrete structures are poorly understood. The Ezrin-Radixin-Moesin (ERM) proteins, which link plasma membrane proteins with the actin cytoskeleton and regulate the steady-state diffusion dynamics of the B cell receptor (BCR), are transiently dephosphorylated upon antigen receptor stimulation. In this study, we show that the ERM proteins ezrin and moesin influence the organization and integrity of BCR microclusters. BCR-driven inactivation of ERM proteins is accompanied by a temporary increase in BCR diffusion, followed by BCR immobilization. Disruption of ERM protein function using dominant-negative or constitutively active ezrin constructs or knockdown of ezrin and moesin expression quantitatively and qualitatively alters BCR microcluster formation, antigen aggregation, and downstream BCR signal transduction. Chemical inhibition of actin polymerization also altered the structure and integrity of BCR microclusters. Together, these findings highlight a crucial role for the cortical actin cytoskeleton during B cell spreading and microcluster formation and function.
Secretory leukocyte protease inhibitor: a human saliva protein exhibiting anti-human immunodeficiency virus 1 activity in vitro.
Authors: T B McNeely, M Dealy, D J Dripps, J M Orenstein, S P Eisenberg, S M Wahl
Journal: Journal of Clinical Investigation (1995)

Infection of adherent primary monocytes with HIV-1Ba-L is significantly suppressed in the presence of human saliva. By reverse transcriptase (RT) levels, saliva, although present for only 1 h during monocyte viral exposure, inhibited HIV-1 infectivity for 3 wk after infection, whereas human plasma and synovial fluid failed to inhibit HIV-1 infectivity. Antiviral activity was identified in the saliva soluble fraction, and to determine the factor(s) responsible, individual saliva proteins were examined. Of those proteins examined, only secretory leukocyte protease inhibitor (SLPI) was found to possess anti-HIV-1 activity at physiological concentrations. SLPI anti-HIV-1 activity was dose dependent, with maximal inhibition at 1-10 micrograms/ml (> 90% inhibition of RT activity). SLPI also partially inhibited HIV-1IIIB infection in proliferating human T cells. SLPI appears to target a host cell-associated molecule, since no interaction with viral proteins could be demonstrated. However, SLPI anti-HIV-1 activity was not due to direct interaction with or downregulation of the CD4 antigen. Partial depletion of SLPI in whole saliva resulted in decreased anti-HIV-1 activity of saliva. These data indicate that SLPI has antiretroviral activity and may contribute to the important antiviral activity of saliva associated with the infrequent oral transmission of HIV-1.
Down-regulation of <i>Epidermal Growth Factor Receptor</i> by Selective Expansion of a 5′-End Regulatory Dinucleotide Repeat in Colon Cancer with Microsatellite Instability
Authors: Svetlana Baranovskaya, Yolanda Martin, Sergio Alonso, Ksenia L. Pisarchuk, Mario Falchetti, Yuichi Dai, Sophia Khaldoyanidi, Stan Krajewski, Inna Novikova, Yuri S. Sidorenko, Manuel Perucho, Sergei R. Malkhosyan
Journal: Clinical Cancer Research (2009)

Abstract Purpose: The epidermal growth factor receptor (EGFR) is overexpressed in several tumor types, and its expression is influenced by the length of a 5′-end microsatellite repeat (CA)n: the longer the repeat, the lower the expression. Dinucleotide repeats accumulate insertion/deletion types of mutations in tumors with microsatellite instability. We designed this study to estimate the occurrence of these mutations in EGFR(CA)n and their relevance in carcinogenesis of microsatellite instability–positive colon and gastric tumors. Experimental Design: We analyzed the frequency of EGFR(CA)n mutations in vivo in 55 colorectal and 14 gastric microsatellite instability–positive cancers, and in vitro in single-cell clone cultures of microsatellite instability–positive colon tumor cell line LS174. Single-cell clone cultures with different repeat lengths were analyzed by fluorescent-activated cell sorter for EGFR cell-surface expression. A correlation analysis was done between EGFR(CA)n mutations and mutations in KRAS, BRAF, and p53. Results: Unlike single-cell clone cultures, which exhibited higher rate of deletions compared with insertions, most of EGFR(CA)n mutations in colon and gastric tumors were insertions. Longer EGFR(CA)n correlated with lower EGFR cell-surface expression in single-cell clone cultures. In colon cancers, the elongation of the repeat was associated negatively with mutations in KRAS and BRAF, but not in p53. Conclusions: The EGFR(CA)n elongation observed in tumors cannot be explained by an intrinsic property of this repeat favoring insertions versus deletions. Instead, a selection for repeat elongation occurs in microsatellite instability–positive tumors, leading to EGFR down-regulation. These findings suggest that in microsatellite instability–positive tumors current therapies targeting EGFR overexpression may have either no effect or an opposite to the expected effect.
Secondary Disease Mortality in Rat-Mouse Radiation Chimeras&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: C. C. Congdon, M.D., T. J. Mitchell, Ph.D., D. A. Gardiner, Ph.D., M. A. Kastenbaum, Ph.D., R. E. Toya, M.S.
Journal: JNCI Journal of the National Cancer Institute (1970)

Two statistical experimental designs were used to investigate factors involved in 90-day mortality from secondary disease in lethally irradiated mice treated with rat bone marrow. Secondary disease is a graft-versus-host syndrome that has a mortality of about 65-95% in this transplant situation. When the factors—age-of-donor-cells, day-of-cell-injection, dose-of-marrow-cells, sex, and environment—were examined for their main effects and interactions, some combinations of these factors were found to give about 25% 90-day mortality. The experiments indicate that the lowest mortality can be achieved with an injection of 40 million or more cells 1 day after irradiation and an ultraclean environment of unlimited filter-top caging.
Lysophosphatidic Acid Acyltransferase-β Is a Prognostic Marker and Therapeutic Target in Gynecologic Malignancies
Authors: Gregory M. Springett, Lynn Bonham, Amanda Hummer, Irina Linkov, Dipika Misra, Chia Ma, Gabriella Pezzoni, Stefano Di Giovine, Jack Singer, Hiroaki Kawasaki, David Spriggs, Robert Soslow, Jakob Dupont
Journal: Cancer Research (2005)

Abstract Lysophosphatidic acid, the substrate for lysophosphatidic acid acyltransferase β (LPAAT-β), is a well-studied autocrine/paracrine signaling molecule that is secreted by ovarian cancer cells and is found at elevated levels in the blood and ascites fluid of women with ovarian cancer. LPAAT-β converts lysophosphatidic acid to phosphatidic acid, which functions as a cofactor in Akt/mTOR and Ras/Raf/Erk pathways. We report that elevated expression of LPAAT-β was associated with reduced survival in ovarian cancer and earlier progression of disease in ovarian and endometrial cancer. Inhibition of LPAAT-β using small interfering RNA or selective inhibitors, CT32521 and CT32228, two small-molecule noncompetitive antagonists representing two different classes of chemical structures, induces apoptosis in human ovarian and endometrial cancer cell lines in vitro at pharmacologically tenable nanomolar concentrations. Inhibition of LPAAT-β also enhanced the survival of mice bearing ovarian tumor xenografts. Cytotoxicity was modulated by diacylglycerol effectors including protein kinase C and CalDAG-GEF1. LPAAT-β was localized to the endoplasmic reticulum and overexpression was associated with redistribution of protein kinase C-α. These findings identify LPAAT-β as a potential prognostic and therapeutic target in ovarian and endometrial cancer.