tbuckley/cabot-search huggingface dataset:
Randomized, Placebo-controlled Clinical Trial of an Aerosolized β<sub>2</sub>-Agonist for Treatment of Acute Lung Injury
Authors: Lung
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

β₂-Adrenergic receptor agonists accelerate resolution of pulmonary edema in experimental and clinical studies.This clinical trial was designed to test the hypothesis that an aerosolized β₂-agonist, albuterol, would improve clinical outcomes in patients with acute lung injury (ALI).We conducted a multicenter, randomized, placebo-controlled clinical trial in which 282 patients with ALI receiving mechanical ventilation were randomized to receive aerosolized albuterol (5 mg) or saline placebo every 4 hours for up to 10 days. The primary outcome variable for the trial was ventilator-free days.Ventilator-free days were not significantly different between the albuterol and placebo groups (means of 14.4 and 16.6 d, respectively; 95% confidence interval for the difference, -4.7 to 0.3 d; P = 0.087). Rates of death before hospital discharge were not significantly different between the albuterol and placebo groups (23.0 and 17.7%, respectively; 95%confidence interval for the difference,-4.0 to 14.7%;P = 0.30). In the subset of patients with shock before randomization, the number of ventilator-free days was lower with albuterol, although mortality was not different. Overall, heart rates were significantly higher in the albuterol group by approximately 4 beats/minute in the first 2 days after randomization, but rates of new atrial fibrillation (10% in both groups) and other cardiac dysrhythmias were not significantly different.These results suggest that aerosolized albuterol does not improve clinical outcomes in patients with ALI. Routine use of β₂-agonist therapy in mechanically ventilated patients with ALI cannot be recommended. Clinical trial registered with www.clinicaltrials.gov (NCT 00434993).
The Double Burden of Obesity and Malnutrition in a Protracted Emergency Setting: A Cross-Sectional Study of Western Sahara Refugees
Authors: Carlos S. Grijalva-Eternod, Jonathan C. K. Wells, Mario Cortina-Borja, Nuria Salse-Ubach, Mélody C. Tondeur, Carmen Dolan, Chafik Meziani, Caroline Wilkinson, Paul Spiegel, Andrew J. Seal
Journal: PLoS Medicine (2012)

Background Households from vulnerable groups experiencing epidemiological transitions are known to be affected concomitantly by under-nutrition and obesity. Yet, it is unknown to what extent this double burden affects refugee populations dependent on food assistance. We assessed the double burden of malnutrition among Western Sahara refugees living in a protracted emergency. Methods and Findings We implemented a stratified nutrition survey in October–November 2010 in the four Western Sahara refugee camps in Algeria. We sampled 2,005 households, collecting anthropometric measurements (weight, height, and waist circumference) in 1,608 children (6–59 mo) and 1,781 women (15–49 y). We estimated the prevalence of global acute malnutrition (GAM), stunting, underweight, and overweight in children; and stunting, underweight, overweight, and central obesity in women. To assess the burden of malnutrition within households, households were first classified according to the presence of each type of malnutrition. Households were then classified as undernourished, overweight, or affected by the double burden if they presented members with under-nutrition, overweight, or both, respectively. The prevalence of GAM in children was 9.1%, 29.1% were stunted, 18.6% were underweight, and 2.4% were overweight; among the women, 14.8% were stunted, 53.7% were overweight or obese, and 71.4% had central obesity. Central obesity (47.2%) and overweight (38.8%) in women affected a higher proportion of households than did GAM (7.0%), stunting (19.5%), or underweight (13.3%) in children. Overall, households classified as overweight (31.5%) were most common, followed by undernourished (25.8%), and then double burden–affected (24.7%). Conclusions The double burden of obesity and under-nutrition is highly prevalent in households among Western Sahara refugees. The results highlight the need to focus more attention on non-communicable diseases in this population and balance obesity prevention and management with interventions to tackle under-nutrition. Please see later in the article for the Editors' Summary
Invasive exercise testing in the evaluation of patients at high-risk for lung resection
Authors: J Ribas, O Diaz, JA Barbera, M Mateu, E Canalis, L Jover, J Roca, R Rodriguez-Roisin
Journal: European Respiratory Journal (1998)

The aim of this study was to investigate whether invasive exercise testing with gas exchange and pulmonary haemodynamic measurements could contribute to the preoperative assessment of patients with lung cancer at a high-risk for lung resection. Sixty-five patients scheduled for thoracotomy (aged 66+/-8 yrs (mean+/-SD), 64 males, forced expiratory volume in one second (FEV1) 54+/-13% predicted) were studied prospectively. High risk was defined on the basis of predicted postpneumonectomy (PPN) FEV1 and/or carbon monoxide diffusing capacity of the lung (DL,CO) &lt;40% pred. Arterial blood gas measurements were performed in all patients at rest and during exercise. In 46 patients, pulmonary haemodynamic measurements were also performed at rest and during exercise. Predicted postoperative (PPO) values for FEV1 and DL,CO were calculated according to quantitative lung scanning and the amount of resected parenchyma. There were four postoperative deaths (6.2% mortality rate) and postoperative cardiorespiratory complications developed in 31 (47.7%) patients. Patients with respiratory complications only differed from patients without or with minimal (arrhythmia) complications in FEV1,PPO. Peak O2 uptake and haemodynamic variables were similar in both groups. The four patients who died had a lower FEV1,PPO, a lower DL,CO,PPO and a greater decrease in arterial oxygen tension during exercise, compared with the remaining patients. In conclusion, the forced expiratory volume in one second, together with the extent of parenchymal resection and perfusion of the affected lung, are useful parameters to identify patients at greatest risk of postoperative complications among those at a high-risk for lung resection. In these patients, pulmonary haemodynamic measurements appear to have no discriminatory value, whereas gas exchange measurements during exercise may help to identify patients with higher mortality risk.
Reversible neural inactivation reveals hippocampal participation in several memory processes
Authors: G. Riedel, J. Micheau, A.G.M. Lam, E.v.L. Roloff, S.J. Martin, H. Bridge, L. de Hoz, B. Poeschel, J. McCulloch, R.G.M. Morris
Journal: Nature Neuroscience (1999)
Appropriateness and Right Price: An Inseparable Binomial to Improve Care and Reduce Cost
Authors: Sergio Crispino, Roberto Labianca
Journal: Journal of Clinical Oncology (2013)

TO THEEDITOR:TherecentarticlepublishedinJournalofClinical OncologybySchnipperetal 1 reportedthattherisingcostofcancercare isincreasingtoalevelthatisnowcausingseriousfinancialburdensfor patients, families, and society at large. The authors reported ASCO’s five key recommendations to improve care and reduce costs: the Top Five list for oncology. The US Congressional Budget Office has estimated that more than 30% of care delivered in the United States goes toward unnecessary tests, procedures, physician visits, hospital stays, and other services that do not improve the patient’s health. 2 In summary, ASCO’s Top Five list for oncology can be considered an innovative effort to increase the appropriateness of prescribing and to reduce the unnecessary use of health care resources. As reported by the authors 1 and in other articles, 3-6 the basis for the rising cost of care is complex and is onlyinpartaresultoftheunnecessaryuseofhealthcareresources.In
Differential response of sebaceous glands to exogenous testosterone
Authors: None Holland, None Cunliffe, None Norris
Journal: British Journal of Dermatology (1998)

To test the hypothesis that the seborrhoea of acne is an end-organ hyper-response to androgens, a standardized dose of 2% testosterone cream was applied to the forehead of eight prepubertal boys for 6 weeks and the effect determined by measurements of sebum excretion rate (SER). Three boys showed a 15-fold increase in SER and three boys were non-responders, whereas two boys had SER values between those of the responders and non-responders. These data show that sebaceous glands are stimulated by androgens to varying degrees and support the theory of an end-organ response in acne.
Ciprofloxacin for 7 days versus 14 days in women with acute pyelonephritis: a randomised, open-label and double-blind, placebo-controlled, non-inferiority trial
Authors: Torsten Sandberg, Gunilla Skoog, Anna Bornefalk Hermansson, Gunnar Kahlmeter, Nils Kuylenstierna, Anders Lannergård, Gisela Otto, Bo Settergren, Gunilla Stridh Ekman
Journal: The Lancet (2012)
Factors influencing airway inflammation in chronic obstructive pulmonary disease
Authors: A. Hill
Journal: Thorax (2000)

Airway inflammation in chronic obstructive pulmonary disease (COPD) is currently the subject of rapidly increasing research interest, investigating both the nature of the inflammatory cells and the cytokines present. The data are being used to define and assess the severity, cause, prognosis, and response to treatment of this disease. The collection of spontaneous sputum or the induction of sputum has been used to study inflammation in the larger airways. It remains unclear, however, how these data relate to the pathological processes at the site of airflow obstruction (the small airways and alveolar region). Nevertheless, even the interpretation of the results from the large airways depends on the many factors that will influence the inflammation.

The initial process of sputum collection, sample processing, and the performance of assays in the biological fluids being tested may all influence the results. In addition, airways inflammation may be altered by the patient's clinical state, current treatment, and the nature of the disease (asthma, COPD, or bronchiectasis). Other factors including smoking, α1-antitrypsin (AAT) deficiency, and bacterial colonisation may also affect airways inflammation. Despite these many factors that may influence airways inflammation, many papers currently in the literature do not address them. The purpose of this review is to indicate the influence of these factors on airways inflammation to assist interpretation of the data currently in the literature.

### EOSINOPHIL

Airway inflammation in asthma is classically related to the eosinophil. Eosinophil granules contain a variety of mediators capable of causing inflammatory damage to the airway epithelium including eosinophil peroxidase (EPO), major basic protein (MBP), eosinophil cationic protein (ECP), metalloproteinases, platelet activating factor, and cysteinyl leukotrienes.1 In addition, the immunological basis of asthma is distinct and reflected in the nature of the cytokines released into the airway.

However, there is some overlap with COPD which may …
How Bacterial Carbohydrates Influence the Adaptive Immune System
Authors: Fikri Y. Avci, Dennis L. Kasper
Journal: Annual Review of Immunology (2009)

The capsular polysaccharides (CPSs) of most pathogenic bacteria are T cell-independent antigens whose conjugation to carrier proteins evokes a carbohydrate-specific response eliciting T cell help. However, certain bacterial CPSs, known as zwitterionic polysaccharides (ZPSs), activate the adaptive immune system through processing by antigen-presenting cells and presentation by the major histocompatibility complex class II pathway to CD4(+) T cells. This discovery was the first mechanistic insight into how carbohydrates-a class of biological molecules previously thought to be T cell independent-can in fact activate T cells. Through their ability to activate CD4(+) T cells, ZPSs direct the cellular and physical maturation of the developing immune system. In this review, we explore the still-enigmatic relations between CPSs and the adaptive immune machinery at the cellular and molecular levels, and we discuss how new insights into the biological impact of ZPSs expand our concepts of the role of carbohydrates in microbial interactions with the adaptive immune system.
Arachidonic acid metabolism by polymorphonuclear leukocytes in psoriasis
Authors: P.D.L. MAURICE, P.C. BATHER, B.R. ALLEN
Journal: British Journal of Dermatology (1986)

The metabolism of endogenous arachidonic acid by human polymorphonuclear leukocytes (PMNL) isolated from peripheral blood has been studied in 19 patients with chronic plaque psoriasis and 19 healthy controls. Using calcium ionophore A23187 as a stimulus, the PMNL synthesized leukotriene B4 (LTB4), 6-trans-leukotriene B4, 12-epi-6-trans-LTB4, and 5-hydroxy-6,8,11,14-eicosatetraenoic acid. There was no significant difference in the amounts of the products formed between the psoriatic and control groups. The elevated levels of LTB4 that have been described in psoriatic skin may therefore be due to the PMNL infiltrate or to enhanced synthesis by another cell type. The reported increase in activity of the circulating PMNL in psoriasis does not appear to be due to increased 5-lipoxygenase activity in these cells.
Delirium: A key challenge for perioperative care
Authors: N.A. O'Regan, J. Fitzgerald, S. Timmons, H. O'Connell, D. Meagher
Journal: International Journal of Surgery (2012)

Delirium is highly prevalent, occurring in 20% of acute hospital inpatients and up to 62% of surgical patients. It is a significant predictor of poor outcomes including mortality and institutionalisation, however it is often viewed as simply a marker of underlying illness and is frequently overlooked in older adults. Although delirium is commonly comorbid with dementia, it represents a more urgent diagnosis, requiring prompt intervention. Delirium presents most commonly with hypoactive features (e.g. withdrawal and reduced spontaneous movement and speech). The common stereotype of hyperactive delirium tremens (e.g. agitation, hallucinations), although more visible, is less common. All presentations share acute disimprovement of cognitive function. Delirium is a highly predictable and preventable occurrence, however a major barrier to improving delirium care and impacting upon outcomes is that it remains poorly detected, particularly in surgical populations and especially in patients with hypoactive presentations. Routine ward-based screening for delirium, particularly in high-risk populations, and improved staff awareness of the significance of the problem can improve detection rates. Preventative strategies, particularly multicomponent approaches, have been most efficacious in improving patient outcomes. Optimising perioperative risk factors can lead to reduced incidence. Appropriate treatment of delirium requires thorough investigation, management of the underlying illness, avoidance of complications and simplification of the care environment. Studies suggest a role for pharmacological prophylaxis, particularly in relation to anaesthetic and sedative agents used intra- and post-operatively. Furthermore, gathering evidence suggests that judicious use of antipsychotic medications may be helpful in delirium prevention and treatment.
Measurement of CT lung density in patients with chronic asthma
Authors: W Biernacki, AT Redpath, JJ Best, W MacNee
Journal: European Respiratory Journal (1997)

Evidence for the presence of emphysema in patients with asthma is controversial. We have previously shown that decreased lung density, measured by computed tomographic (CT) scanning, preoperatively, correlates with morphometric measurements of microscopic emphysema in subsequently resected lungs. The aim of this study was to compare CT lung density, in 17 patients with chronic asthma (forced expiratory volume in one second (FEV1) 1.98 (SD 0.77) L), 17 patients with chronic bronchitis and emphysema (FEV1 0.97 (0.56) L) and seven normal subjects (FEV1 3.5 (034) L). All subjects underwent CT scanning of the lungs and respiratory function testing within 2 days of each other. In five of the asthmatic patients a CT scan was performed on two occasions before and after treatment with nebulized bronchodilator. In a different group of five asthmatics these measurements were performed at the end of and 6 weeks after an exacerbation. The mean value of the lowest fifth percentile of the CT lung density in the patients with chronic obstructive pulmonary disease (COPD) was -942 (SD 36) Hounsfield units (HU), in the 17 asthmatic patients was -912 (34) HU, and in normal subjects was -880 (13). Despite a significant increase in peak expiratory flow rate from 266 (SD 102) to 406 (83) L x s(-1) (p<0.02) following nebulized beta2-agonist in five patients with chronic asthma, there was no significant change in CT lung density (p>0.05) Our study indicates that at least some patients with chronic, stable asthma develop a reduction in computed tomography lung density, similar to that in patients with emphysema.
Th17 cells in immunity and autoimmunity
Authors: M Oukka
Journal: Annals of the Rheumatic Diseases (2008)

The primary function of Th17 cells appears to be the clearance of extracellular pathogens during infections. However, Th17 cells also promote inflammation and have been implicated in the pathogenesis of many experimental autoimmune diseases and human inflammatory conditions. Transforming growth factor β (TGFβ) is a critical differentiation factor for the generation of regulatory T (T-reg) cells, whereas the combination of interleukin 6 (IL6) and TGFβ induces the differentiation of pathogenic Th17 cells. Therefore, it is proposed that at the steady state (in the absence of any inflammatory stimuli), TGFβ, which is produced by various cells types including naturally occurring T-reg (nT-reg) cells, encourages the generation of induced T-reg (iT-reg) cells, which together with nT-reg cells keep autoreactive T cells under check. IL6, an acute phase protein produced by the activated immune system, inhibits the function of T-reg cells and instead promotes the differentiation of Th17 cells. Thus, IL6 plays a pivotal role in dictating the balance between the generation of T-reg and Th17 cells. This reciprocal relationship between T-reg and Th17 cells is further supported by the results obtained in IL6<sup>−/−</sup> mice, which show a severe defect in the generation of Th17 cells and increased numbers of T-reg cells in the peripheral repertoire.
Blood concentrations of alemtuzumab and antiglobulin responses in patients with chronic lymphocytic leukemia following intravenous or subcutaneous routes of administration
Authors: Geoff Hale, Peppy Rebello, Lee R. Brettman, Chris Fegan, Ben Kennedy, Eva Kimby, Mike Leach, Jeanette Lundin, Håkan Mellstedt, Paul Moreton, Andy C. Rawstron, Herman Waldmann, Anders Osterborg, Peter Hillmen
Journal: Blood (2004)
Tumorigenicity of Intraspecific Somatic Cell Hybrids in Nude Mice2
Authors: David P. Aden, Barbara B. Knowles
Journal: JNCI Journal of the National Cancer Institute (1977)

Intraspecific somatic cell hybrids between normal mouse peripheral blood lymphocytes and a highly tumorigenic L-cell line (CI-1 D) produced tumors in nude mice. While the hybrid cells were tumorigenic, the length of time necessary for tumor appearance and the size of the tumor varied. Correlation between the growth rate of the parental and hybrid cells in vitro or their plating efficiency in methyl cellulose with the rapidity of tumor growth in vivo was not found.
Effects of indomethacin and PEEP on oleic acid induced pulmonary oedema in rabbits
Authors: KS Panaretto, C Phillips, N Berend
Journal: European Respiratory Journal (1991)

This study was designed to determine whether indomethacin, a suggested treatment for adult respiratory distress syndrome (ARDS), would inhibit the efficacy of positive end-expiratory pressure (PEEP) in an animal model of ARDS. Functional residual capacity (FRC), alveolar-to-arterial oxygen difference (A-aPo2) and total lung water were measured in rabbits: 30 controls and 30 with oleic acid induced pulmonary oedema. Within each group, four treatments were administered: diluent (n = 12), PEEP (n = 6), indomethacin (n = 6), or PEEP + indomethacin (n = 6). Lung injury was induced at 30 mins and treatment commenced at 45 min. Oleic acid caused a significant increase at 3 h in % increase in A-aPo2 from baseline (105 +/- 12%) attenuated by PEEP (59 +/- 17%) and indomethacin (57 +/- 7%), with the combination of PEEP + indomethacin preventing a significant increase (26 +/- 9%). PEEP increase FRC in both saline and oleic acid animals; this was not reversed by indomethacin. Oleic acid caused an increase in total lung water (5.16 to 6.58 +/- 0.16 g), not influenced by any treatment. These findings suggest that indomethacin did not inhibit the efficacy of PEEP in this model of ARDS.
Decision Analysis of Antibiotic and Diagnostic Strategies in Ventilator-associated Pneumonia
Authors: David E. Ost, Charles S. Hall, Gnanaraj Joseph, Christine Ginocchio, Susan Condon, Emily Kao, Michele LaRusso, Richard Itzla, Alan M. Fein
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

The optimal strategy for ventilator-associated pneumonia remains controversial. To clarify the tradeoffs involved, we performed a decision analysis. Strategies evaluated included antibiotic therapy with and without diagnostic testing. Tests that were explored included endotracheal aspirates, bronchoscopy with protected brush or bronchoalveolar lavage, and nonbronchoscopic mini-bronchoalveolar lavage (mini-BAL). Outcomes included dollar cost, antibiotic use, survival, cost-effectiveness, antibiotic use per survivor, and the outcome perspective of financial cost-antibiotic use per survivor. Initial coverage with three antibiotics was better than expectant management or one or two antibiotic approaches, leading to both improved survival (54% vs. 66%) and decreased cost (US dollars 55447 vs. US dollars 41483 per survivor). Testing with mini-BAL did not improve survival but did decrease costs (US dollars 41483 vs. US dollars 39967) and antibiotic use (63 vs. 39 antibiotic days per survivor). From the perspective of minimizing cost, minimizing antibiotic use, and maximizing survival, the best strategy was three antibiotics with mini-BAL.
Putative IKDCs are functionally and developmentally similar to natural killer cells, but not to dendritic cells
Authors: Irina Caminschi, Fatma Ahmet, Klaus Heger, Jason Brady, Stephen L. Nutt, David Vremec, Suzanne Pietersz, Mireille H. Lahoud, Louis Schofield, Diana S. Hansen, Meredith O'Keeffe, Mark J. Smyth, Sammy Bedoui, Gayle M. Davey, Jose A. Villadangos, William R. Heath, Ken Shortman
Journal: The Journal of Experimental Medicine (2007)

Interferon-producing killer dendritic cells (IKDCs) have been described as possessing the lytic potential of NK cells and the antigen-presenting capacity of dendritic cells (DCs). In this study, we examine the lytic function and antigen-presenting capacity of mouse spleen IKDCs, including those found in DC preparations. IKDCs efficiently killed NK cell targets, without requiring additional activation stimuli. However, in our hands, when exposed to protein antigen or to MHC class II peptide, IKDCs induced little or no T cell proliferation relative to conventional DCs or plasmacytoid DCs, either before or after activation with CpG, or in several disease models. Certain developmental features indicated that IKDCs resembled NK cells more than DCs. IKDCs, like NK cells, did not express the transcription factor PU.1 and were absent from recombinase activating gene-2–null, common γ-chain–null (Rag2−/−Il2rg−/−) mice. When cultured with IL-15 and -18, IKDCs proliferated extensively, like NK cells. Under these conditions, a proportion of expanded IKDCs and NK cells expressed high levels of surface MHC class II. However, even such MHC class II+ IKDCs and NK cells induced poor T cell proliferative responses compared with DCs. Thus, IKDCs resemble NK cells functionally, and neither cell type could be induced to be effective antigen-presenting cells.