tbuckley/cabot-search huggingface dataset:
Oral Decontamination with Chlorhexidine Reduces the Incidence of Ventilator-associated Pneumonia
Authors: Mirelle Koeman, Andre J. A. M. van der Ven, Eelko Hak, Hans C. A. Joore, Karin Kaasjager, Annemarie G. A. de Smet, Graham Ramsay, Tom P. J. Dormans, Leon P. H. J. Aarts, Ernst E. de Bel, Willem N. M. Hustinx, Ingeborg van der Tweel, Andy M. Hoepelman, Marc J. M. Bonten
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Rationale: Ventilator-associated pneumonia (VAP) is the most frequently occurring nosocomial infection associated with increased morbidity and mortality. Although oral decontamination with antibiotics reduces incidences of VAP, it is not recommended because of potential selection of antibiotic-resistant pathogens. We hypothesized that oral decontamination with either chlorhexidine (CHX, 2%) or CHX/colistin (CHX/COL, 2%/2%) would reduce and postpone development of VAP, and oral and endotracheal colonization.Objectives: To determine the effect of oral decontamination with CHX or CHX/COL on VAP incidence and time to development of VAP.Methods: Consecutive patients needing mechanical ventilation for 48 h or more were enrolled in a randomized, double-blind, placebo-controlled trial with three arms: CHX, CHX/COL, and placebo (PLAC). Trial medication was applied every 6 h into the buccal cavity. Oropharyngeal swabs were obtained daily and quantitatively analyzed for gram-positive and gram-negative microorganisms. Endotracheal colonization was monitored twice weekly.Results: Of 385 patients included, 130 received PLAC, 127 CHX and 128 CHX/COL. Baseline characteristics were comparable. The daily risk of VAP was reduced in both treatment groups compared with PLAC: 65% (hazard ratio [HR] = 0.352; 95% confidence interval [CI], 0.160, 0. 791; p = 0.012) for CHX and 55% (HR = 0.454; 95% CI, 0.224, 0. 925; p = 0.030) for CHX/COL. CHX/COL provided significant reduction in oropharyngeal colonization with both gram-negative and gram-positive microorganisms, whereas CHX mostly affected gram-positive microorganisms. Endotracheal colonization was reduced for CHX/COL patients and to a lesser extent for CHX patients. No differences in duration of mechanical ventilation, intensive care unit stay, or intensive care unit survival could be demonstrated.Conclusions: Topical oral decontamination with CHX or CHX/COL reduces the incidence of VAP.
Carbon dioxide in the prevention of air embolism during open-heart surgery
Authors: W. S. Ng, M. Rosen
Journal: Thorax (1968)

The factors which are important in the design and use of apparatus for the effective displacement of air by carbon dioxide from chest cavities are examined. High levels of carbon dioxide can be achieved by flowing carbon dioxide at a total flow rate of 51./min. into the chest cavity through two nozzles of 0·5 to 1·0 cm. diameter. The effect of factors which might diminish the carbon dioxide levels is examined.
THE DIFFERENT CENTRAL HEMODYNAMICS IN PATIENTS WITH BICUSPID AORTIC VALVE AND ITS ASSOCIATION WITH ASCENDING AORTA DILATATION
Authors: In Jeong Cho, Chi Young Shim, Jeonggeun Moon, Sungha Park, Jong-Won Ha, Yangsoo Jang, Namsik Chung
Journal: Journal of the American College of Cardiology (2010)
Dietary supplementation with ω-3 PUFA increases adiponectin and attenuates ventricular remodeling and dysfunction with pressure overload
Authors: M DUDA, K OSHEA, B LEI, B BARROWS, A AZIMZADEH, T MCELFRESH, B HOIT, W KOP, W STANLEY
Journal: Cardiovascular Research (2007)

Objective Epidemiological studies suggest that consumption of ω-3 polyunsaturated fatty acids (ω-3 PUFA) decreases the risk of heart failure. We assessed the effects of dietary supplementation with ω-3 PUFA from fish oil on the response of the left ventricle (LV) to arterial pressure overload.
Is cardiac IKs a relevant drug target?
Authors: M Curtis
Journal: Cardiovascular Research (2004)

Journal Article Is cardiac IKs a relevant drug target? Get access Michael J Curtis Michael J Curtis * Cardiovascular Research, The King's Centre for Cardiovascular Biology and Medicine, The Rayne Institute, St Thomas' Hospital, London, SE1 7EH, UK *Tel.: +44-207-928-9292x2330; fax: +44-207-922-8139. [email protected] Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 61, Issue 4, March 2004, Pages 651–652, https://doi.org/10.1016/j.cardiores.2004.01.001 Published: 01 March 2004 Article history Received: 22 December 2003 Accepted: 02 January 2004 Published: 01 March 2004
Moral realism and cross-cultural normative diversity
Authors: Edouard Machery, Daniel Kelly, Stephen P. Stich
Journal: Behavioral and Brain Sciences (2005)

We discuss the implications of the findings reported in the target article for moral theory, and argue that they represent a clear and genuine case of fundamental moral disagreement. As such, the findings support a moderate form of moral anti-realism – the position that, for some moral issues, there is no fact of the matter about what is right and wrong.
Signatures Associated with Rejection or Recurrence in HER-2/<i>neu</i>–Positive Mammary Tumors
Authors: Andrea Worschech, Maciej Kmieciak, Keith L. Knutson, Harry D. Bear, Aladar A. Szalay, Ena Wang, Francesco M. Marincola, Masoud H. Manjili
Journal: Cancer Research (2008)

Abstract We have previously shown T-cell–mediated rejection of the neu-overexpressing mammary carcinoma cells (MMC) in wild-type FVB mice. However, following rejection of primary tumors, a fraction of animals experienced a recurrence of a neu antigen-negative variant (ANV) of MMC (tumor evasion model) after a long latency period. In the present study, we determined that T cells derived from wild-type FVB mice can specifically recognize MMC by secreting IFN-γ and can induce apoptosis of MMC in vitro. Neu transgenic (FVBN202) mice develop spontaneous tumors and cannot reject it (tumor tolerance model). To dissect the mechanisms associated with rejection or tolerance of MMC tumors, we compared transcriptional patterns within the tumor microenvironment of MMC undergoing rejection with those that resisted it either because of tumor evasion/antigen loss recurrence (ANV tumors) or because of intrinsic tolerance mechanisms displayed by the transgenic mice. Gene profiling confirmed that immune rejection is primarily mediated through activation of IFN-stimulated genes and T-cell effector mechanisms. The tumor evasion model showed combined activation of Th1 and Th2 with a deviation toward Th2 and humoral immune responses that failed to achieve rejection likely because of lack of target antigen. Interestingly, the tumor tolerance model instead displayed immune suppression pathways through activation of regulatory mechanisms that included in particular the overexpression of interleukin-10 (IL-10), IL-10 receptor, and suppressor of cytokine signaling (SOCS)-1 and SOCS-3. These data provide a road map for the identification of novel biomarkers of immune responsiveness in clinical trials. [Cancer Res 2008;68(7):2436–46]
More From the Pesky Pasteurella
Authors: B. Eugene Beyt
Journal: JAMA (1983)

<i>Pasteurella multocida</i>was first isolated from birds more than 100 years ago, and only recently has the frequency and full clinical spectrum of human infection with this organism been recognized. In this issue, Kalish and Sands (p 514) along with Stein et al (p 508) further expand and elucidate the current clinical problems caused by this pleomorphic gram-negative organism.<i>Pasteurella multocida</i>is primarily an animal pathogen that causes septicemia in many domestic and wild animals, thus deriving the name<i>many killing</i>. In humans, clinical infections can be grouped into one of three types. A local infection may occur after animal-inflicted wounds, preponderantly cat and dog bites and scratches. Severe swelling, erythema, and pain may develop, and the infection is associated with a gray serous or sanguinopurulent discharge.<sup>1</sup>With sharp animal teeth, penetration and inoculation of the synovium and periosteum may result in osteomyelitis or septic arthritis. Among infections not
Association of Immunohistochemical Staining for p53 With Metastatic Progression and Poor Survival in Patients With Renal Cell Carcinoma
Authors: D. L. Uhlman, P. L. Nguygen, J. C. Manivel, D. Aeppli, J. M. Resnick, E. E. Fraley, G. Zhang, G. A. Niehans
Journal: JNCI Journal of the National Cancer Institute (1994)

Mutations of the p 53 gene have been found in many types of human tumors. In some tumors, p 53 gene mutations are associated with advanced disease and poor prognosis. There is wide variation in the reported incidence of p 53 mutation in renal cell carcinoma, and its prognostic significance for this tumor is unknown. Purpose : This retrospective immunohistochemical study was designed to examine associations between p 53 immunostaining and histologic type, tumor grade, clinical behavior, and survival. Methods : Paraffin-embedded nephrectomy specimens collected from 1978 through 1986 from 175 patients were immunostained for p 53 using the D07 monoclonal antibody. Positive staining for p 53 has been linked to the accumulation of mutant p 53 protein. Thirteen specimens of concurrent metastatic lesions were available from 11 primary cases. Clinical follow-up information was available on 164 patients. Results : Immunostaining for p 53 suggested the presence of p 53 mutation in 49 (28%) of 175 renal tumors studied. Staining was associated with high tumor grade and stage but not with cell type or histologic pattern. Eleven (85%) of 13 metastatic lesions stained positively for p 53 , versus only our (36%) of the 11 paired primary tumors. Immunostaining for p 53 was strongly associated with poor survival among patients without distant metas-tases at presentation. In this group, 10-year disease-specific survival was 78% for patients with nonstaining tumors versus 48% for those with p 53 -positive tumors (P<.003). There was an 87% 10-year disease-specific survival rate for patients with nonstaining Robson stage 1 tumors versus a 62% 10-year survival rate for patients with p 53 -positive Robson stage 1 tumors (P<.01). Multivariate analysis showed p 53 im-munoreactivity to be an independent predictor of survival for patients with nonmetastatic renal cell carcinoma, whereas tumor grade was not. Conclusions : Positive p 53 immunostaining in renal cell carcinoma is associated with metastatic disease and poor survival in patients with early-stage disease. Implications: In renal cell carcinoma, mutations of the p 53 gene may allow or contribute to the acquisition of metastatic potential. [J Natl Cancer Inst 86: 1470–1475, 1994]
Incidence and correlation between serum IgG and IgM antibodies to native type II collagen in patients with chronic inflammatory arthritis.
Authors: R B Clague, M J Shaw, P J Holt
Journal: Annals of the Rheumatic Diseases (1981)

Raised serum IgG and IgM antibody levels to native type II collagen were found in patients with rheumatoid arthritis and in patients with juvenile chronic arthritis. There was a good correlation between the serum IgG and the IgM antibody levels in rheumatoid arthritis and a weaker correlation in juvenile chronic arthritis. Raised serum IgM antibody levels to native type II collagen were found in only 1 patient each with ankylosing spondylitis and psoriatic arthritis, and in these groups here was no correlation between the serum IgG and the IgM antibody levels. The highest serum IgG and IgM antibody levels to native type II collagen were found in rheumatoid arthritis. These results, together with the results on serum antiglobulin levels, indicate that patients with rheumatoid arthritis produce antibodies of both IgG and IgM immunoglobulin class which may have pathogenetic significance in the more severe arthritis found in this condition.
Selective intestinal decontamination in advanced chronic heart failure: a pilot trial
Authors: Viviane M. Conraads, Philippe G. Jorens, Luc S. De Clerck, Hendrik K. Van Saene, Margaretha M. Ieven, Johan M. Bosmans, Annemie Schuerwegh, Chris H. Bridts, Floris Wuyts, Wim J. Stevens, Stefan D. Anker, Mathias Rauchhaus, Christiaan J. Vrints
Journal: European Journal of Heart Failure (2004)
Abnormality of glycophorin-alpha on paroxysmal nocturnal hemoglobinuria erythrocytes.
Authors: C J Parker, C M Soldato, W F Rosse
Journal: Journal of Clinical Investigation (1984)

To investigate the greater enzymatic activity of the alternative pathway convertase (and the subsequent greater fixation of C3b) on paroxysmal nocturnal hemoglobinuria (PNH) erythrocytes, we have examined the topography of binding of C3b to PNH and normal erythrocytes. Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography, the alpha-chain of C3b was found to bind via predominantly ester bonds to free hydroxyl groups on glycophorin-alpha, the major erythrocyte sialoglycoprotein. The pattern of binding of nascent C3b was the same for normal and PNH erythrocytes. Thus, although C3b binding to a different membrane constituent did not appear to account for the greater enzymatic activity of the alternative pathway convertase when affixed to PNH erythrocytes, it seemed possible that the glycoproteins to which C3b bound might be qualitatively abnormal on the PNH cells, and that structural differences in these molecules might impose modifications in the enzyme-substrate interactions of the alternative pathway convertase. Using methods for radiolabeling both protein and carbohydrate residues, we therefore compared the electrophoretic pattern of the cell-surface glycoproteins on PNH and normal erythrocytes. The glycophorin-alpha dimer was found to be qualitatively abnormal on the PNH cells as evidenced by its greater susceptibility to trypsin-mediated proteolysis. In addition, the abnormal erythrocytes from patients with PNH had fewer periodate oxidizable constituents than did normal erythrocytes, indicating a relative deficiency of cell-surface sialic acid. These investigations suggest that abnormalities in membrane glycoproteins may underlie the aberrant interactions of complement with the hematopoietic elements of PNH.
Electrical Activity of Single Fibers of the Atrioventricular Node
Authors: BRIAN F. HOFFMAN, ANTONIO PAES DE CARVALHO, WALMOR CARLOS MELLO, PAUL F. CRANEFIELD
Journal: Circulation Research (1959)

The mechanism of atrioventricular delay has been studied in isolated rabbit hearts. Multiple intracellular microelectrodes have been employed to obtain simultaneous records from single fibers of atrium, A-V node and His bundle. An appreciable delay in the transmission of excitation has been found only in the atrial portion of the A-V node. Action potentials recorded from single fibers in this area show a low resting potential, slow diastolic depolarization, slow upstroke and low amplitude. These action potentials frequently show one or more notches or steps on the rising phase. Action potentials recorded from fibers of the His bundle are similar in shape and amplitude to those of peripheral Purkinje fibers. Records obtained at several sites between the atrial portion of the node and the His bundle show a gradual transition in action potential shape. The mechanism of slow transmission across the A-V node is discussed in relation to the electrical activity of fibers at the atrial end of this structure.
Regular Physical Activity Modifies Smoking-related Lung Function Decline and Reduces Risk of Chronic Obstructive Pulmonary Disease
Authors: Judith Garcia-Aymerich, Peter Lange, Marta Benet, Peter Schnohr, Josep M Antó
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

We have previously reported that regular physical activity reduces risk of chronic obstructive pulmonary disease (COPD) exacerbation. We hypothesized that higher levels of regular physical activity could reduce the risk of COPD by modifying smoking-related lung function decline.To estimate the longitudinal association between regular physical activity and FEV(1) and FVC decline and COPD risk.A population-based sample (n = 6,790) was recruited and assessed with respect to physical activity, smoking, lung function, and other covariates, in Copenhagen in 1981-1983, and followed until 1991-1994. Mean level of physical activity between baseline and follow-up was classified into "low," "moderate," and "high." FEV(1) and FVC decline rates were expressed as milliliters per year. COPD was defined as FEV(1)/FVC < or = 70%. Adjusted associations between physical activity and FEV(1) and FVC decline, and COPD incidence, were obtained using linear and logistic regression, respectively.Active smokers with moderate and high physical activity had a reduced FEV(1) and FVC decline compared with those with low physical activity (relative change of +2.6 and +4.8 ml/yr of FEV(1), P-for-trend = 0.006, and +2.6 and +7.7 ml/yr of FVC, P-for-trend < 0.0001, for the moderate and high physical activity group, respectively), after adjusting for all potential confounders and risk factors of lung function decline. Active smokers with moderate to high physical activity had a reduced risk of developing COPD as compared with the low physical activity group (odds ratio, 0.77; p = 0.027).This prospective study shows that moderate to high levels of regular physical activity are associated with reduced lung function decline and COPD risk among smokers.
Quality of Life with Defibrillator Therapy or Amiodarone in Heart Failure
Authors: Daniel B. Mark, Kevin J. Anstrom, Jie L. Sun, Nancy E. Clapp-Channing, Anastasios A. Tsiatis, Linda Davidson-Ray, Kerry L. Lee, Gust H. Bardy
Journal: New England Journal of Medicine (2008)

Implantable cardioverter-defibrillator (ICD) therapy significantly prolongs life in patients at increased risk for sudden death from depressed left ventricular function. However, whether this increased longevity is accompanied by deterioration in the quality of life is unclear.In a randomized trial, we compared ICD therapy or amiodarone with state-of-the-art medical therapy alone in 2521 patients who had stable heart failure with depressed left ventricular function. We prospectively measured quality of life at baseline and at months 3, 12, and 30; data collection was 93 to 98% complete. The Duke Activity Status Index (which measures cardiac physical functioning) and the Medical Outcomes Study 36-Item Short-Form Mental Health Inventory 5 (which measures psychological well-being) were prespecified primary outcomes. Multiple additional quality-of-life outcomes were also examined.Psychological well-being in the ICD group, as compared with medical therapy alone, was significantly improved at 3 months (P=0.01) and at 12 months (P=0.003) but not at 30 months. No clinically or statistically significant differences in physical functioning among the study groups were observed. Additional quality-of-life measures were improved in the ICD group at 3 months, 12 months, or both, but there was no significant difference at 30 months. ICD shocks in the month preceding a scheduled assessment were associated with a decreased quality of life in multiple domains. The use of amiodarone had no significant effects on the primary quality-of-life outcomes.In a large primary-prevention population with moderately symptomatic heart failure, single-lead ICD therapy was not associated with any detectable adverse quality-of-life effects during 30 months of follow-up.
A High-Affinity, High-Stability Photoacoustic Agent for Imaging Gastrin-Releasing Peptide Receptor in Prostate Cancer
Authors: Jelena Levi, Ataya Sathirachinda, Sanjiv S. Gambhir
Journal: Clinical Cancer Research (2014)

To evaluate the utility of targeted photoacoustic imaging (PAI) in providing molecular information to complement intrinsic functional and anatomical details of the vasculature within prostate lesion.We developed a PAI agent, AA3G-740, that targets gastrin-releasing peptide receptor (GRPR), found to be highly overexpressed in prostate cancer. The binding specificity of the agent was evaluated in human prostate cancer cell lines, PC3 and LNCaP, and antagonist properties determined by cell internalization and intracellular calcium mobilization studies. The imaging sensitivity was assessed for the agent itself and for the PC3 cells labeled with agent. The in vivo stability of the agent was determined in human plasma and in the blood of living mice. The in vivo binding of the agent was evaluated in PC3 prostate tumor models in mice, and was validated ex vivo by optical imaging.AA3G-740 demonstrated strong and specific binding to GRPR. The sensitivity of detection in vitro indicated suitability of the agent to image very small lesions. In mice, the agent was able to bind to GRPR even in poorly vascularized tumors leading to nearly 2-fold difference in photoacoustic signal relative to the control agent.The ability to image both vasculature and molecular profile outside the blood vessels gives molecular PAI a unique advantage over currently used imaging techniques. The imaging method presented here can find application both in diagnosis and in image-guided biopsy.
Single-Nucleotide Polymorphisms of DNA Damage Response Genes Are Associated with Overall Survival in Patients with Pancreatic Cancer
Authors: Taro Okazaki, Li Jiao, Ping Chang, Douglas B. Evans, James L. Abbruzzese, Donghui Li
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The goals of this study were to determine if single-nucleotide polymorphisms in DNA damage repair genes and cell cycle regulating genes affect clinical response to combined gemcitabine radiation therapy and the overall survival (OS) of patients with pancreatic cancer. Experimental Design: We evaluated six single-nucleotide polymorphisms of the ATM, ATM and Rad3-related (ATR), CHEK1, and CHEK2 genes in 119 patients with potentially resectable pancreatic cancer who were enrolled in clinical trials at The University of Texas M. D. Anderson Cancer Center from February 1999 to January 2006, with follow-up until February 2007. Patients received neoadjuvant concurrent gemcitabine and radiation therapy with or without gemcitabine-cisplatin induction therapy. Genotypes were determined and tested for associations with OS by Kaplan-Meier estimation, the log-rank test, and Cox regression analysis. P values of ≤0.05 were considered significant. Results: The ATM G60A and CHEK1 G35A genotypes were significant (P &amp;lt; 0.05), and the ATR C340T genotype borderline significantly (P = 0.079) associated with OS. The hazard ratio of CHEK1 35AA was 2.01 (95% confidence interval, 1.20-3.37; P = 0.007) compared with CHEK1 35GG/GA with adjustments for race, sex, diabetes status, CA19-9 level, and success of tumor resection. A significant combined genotype effect was observed between ATM 60GA/GG, ATR 340CT/CC, and CHEK1 35AA with median OS times of 31.0, 16.2, and 10.5 months for patients carrying ≤1, 2, and 3 deleterious alleles, respectively (P = 0.004). Conclusions: These observations suggest that polymorphic variations of DNA damage response genes affect clinical response to gemcitabine radiation therapy and OS of patients with resectable pancreatic cancer.