bluuebunny/crossref_metadata_2025 huggingface dataset:
Angiotensin II reduces membranous angiotensin-converting enzyme 2 in pressurized human aortic endothelial cells
Authors: Iizuka Kenji , Kusunoki Asami , Machida Takuji , Hirafuji Masahiko
Published: August 2009

Introduction. We applied pressure stress to human aortic endothelial cells (HAEC) and investigated whether mechanical pressure stress and/or angiotensin II (Ang II) affected angiotensin-converting enzyme (ACE) 2. We then tested whether the administration of nifedipine had a demonstrable and possibly beneficial effect.

Methods. A pulsatile atmospheric pressure with or without Ang II was loaded on HAECs. The expression of ACE2 was studied by immunoblots and reverse transcription/real-time polymerase chain reaction.

Results. The pulsatile mechanical pressure increased the expression of ACE2 mRNA by approximately 80%. Supplementation of Ang II (1 μM) with pulsatile mechanical pressure decreased the expression of ACE2 mRNA by approximately 54%. Pulsatile atmospheric pressure increased ACE2 protein, but supplementation of Ang II (1 μM) also increased ACE2 protein, and the latter failed to show significant change compared to pressurized control without Ang II. Ang II administration reduced ACE2 protein in the membranous fraction under pressurized condition. Administration of nifedipine (1 μM) protected cells from this ACE2 protein reduction at the HAEC membrane.

Conclusions. These results indicate that pulsatile mechanical pressure and Ang II affect ACE2 in HAECs. Our findings suggest that blood pressure reduction with a calcium channel blocker is beneficial for the conservation of ACE2, and may provide a potential therapeutic target beyond blood pressure lowering in hypertensive patients.
Differences in the Relationship of Oral Reading Fluency and High-Stakes Measures of Reading Comprehension
Authors: Wanzek Jeanne , Roberts Greg , Linan-Thompson Sylvia , Vaughn Sharon , Woodruff Althea L. , Murray Christy S.
Published: August 2009

The current study examined the predictive validity of oral reading fluency measures across first, second, and third grades for two reading achievement measures at the end of third grade. Oral reading fluency measures were administered to students from first grade to third. The Texas Assessment of Knowledge and Skills and the Stanford Achievement Test were also administered in the third grade. Oral reading fluency was a reliable predictor of student success on both measures. Data suggest that greater student growth in oral reading fluency is needed through the grade levels to ensure high probabilities of success on the nationally normed measure, as compared to what is needed for the state-normed measure. Implications for practice and future research are discussed.
NOTES-Assisted Transvaginal Splenectomy: The Next Step in the Minimally Invasive Approach to the Spleen
Authors: Targarona Eduardo M. , Gomez Cristina , Rovira Ramon , Pernas Juan Carlos , Balague Carmen , Guarner-Argente Carlos , Sainz Sergio , Trias Manuel
Published: August 2009

Hypothesis. Natural orifice transluminal endoscopic surgery (NOTES) has marked yet another step forward in less-invasive surgical procedures. Access to solid organs located deep in the left hypochondrium can be difficult using this technique but the transvaginal approach with the patient positioned in full lateral decubitus may be an option. Material and methods. We present the case of a 60-year-old woman with a symptomatic splenic polycystic tumor. The procedure was carried out by a multidisciplinary team using a standard flexible videogastroscope and endoscopic instruments. Transvaginal visualization of the spleen and standard dissection of attachments were feasible, and splenectomy was completed using transvaginal stapling of the splenic hilum. The organ was extracted transvaginally. Results. The postoperative course was uneventful. The patient had minimal postoperative pain and minimal scars, and was discharged on the second postoperative day. Conclusions. Transvaginal access can be safely used for operative visualization, hilum transection, and spleen removal with conventional instrumentation, reducing parietal wall trauma to a minimum. The clinical, esthetic, and functional advantages require further analysis.
Perspectives — biological pacing, a clinical reality?
Authors: Morris Gwilym M. , Boyett Mark R.
Published: August 2009

Bradyarrhythmias are common and may be caused by sinus node dysfunction or conduction block. Many of these conditions can be treated by the implantation of electronic cardiac pacemakers that reduce mortality and morbidity in carefully selected patient groups. Implantable electronic pacemakers are small, sophisticated and reliable but not without complication and limitation. Efforts have been made to create a de novo sinus node using gene therapy, the so-called biopacemaker. This approach has potential as permanent cure for bradyarrythmias with greater physiological responsiveness than that provided by rate-responsive electronic pacemakers. This article reviews the current approaches to the problem and gives a perspective on the challenges remaining to bring the therapy to clinical practice.
Nanoscale pseudobrookite layer in the surface glaze of a Japanese sekishu roof tile
Authors: Watanabe K. , Ohfuji H. , Kitagawa R. , Matsui Y.
Published: August 2009

The mineralogy of the glazed surfaces of Japanese sekishu roof tiles covered by a crustose lichen – Lecidella asema (Nyl.) Knoph & Hertel – was investigated using transmission electron microscopy (TEM). The study sought to identify the Ti-Fe mineral observed as a low concentration of Ti and Fe in a previous study of the glazed surfaces of the same roof tile. The TEM analysis revealed that: (1) a thin layer of the Ti-Fe mineral pseudobrookite exists on the glaze surface; (2) the pseudobrookite consists of well-ordered single crystals, continuously and widely distributed on the glaze surface.
Comparing the efficiency of ordinary kriging and cokriging to estimate the Atterberg limits spatially using some soil physical properties
Authors: Baskan O. , Erpul G. , Dengiz O.
Published: August 2009

The spatial distribution of the Atterberg limits can be used to distinguish the consistency and behaviour of a soil and its engineering properties, which strongly depends on the water content of the soil and types of silts and clays in the soil. By spatial modeling, and comparing the results of ordinary kriging with the cokriging approach, this study aims to find correlations between the Atterberg limits and the selected physical soil parameters in order to examine how effective they are in generating an understanding of the dynamics of a physical soil system.

In 156 soil samples, the Atterberg limits and soil moisture conditions were determined, and auxiliary functions were selected by application of cokriging using correlation analysis and regression equations obtained by the residual maximum likelihood (REML). These techniques were evaluated by the results of the mean absolute error (MAE) and the mean squared error (MSE). Cokriging analysis was found to be more effective at estimating the liquid limit (WLL) and the plastic limit (WPL) than kriging analysis and with smaller error values. On the other hand, the kriging approach, which had smaller MAE and MSE values, was more effective at estimating the plasticity index (WPI) values than the cokriging method. Unlike the REML regression equations, the field capacity (FC) value was the more suitable parameter for the cokriging estimates. When the necessary labour and time were considered for determining the Atterberg limits, both kriging and cokriging were found to be applicable for estimation of these limits.
Characterization of size, aspect ratio and degree of dispersion of particles in filled polymeric composites using FIB
Authors: Zhu Y. , Allen G. C. , Adams J. M. , Gittins D. , Heard P. J. , Skuse D. R.
Published: August 2009

Two types of mineral fillers, talc and mica, were compounded into polypropylene (PP) via a twin-screw extruder. The morphologies and mechanical properties of the resultant composites were investigated. The dispersion of minerals in PP was observed using Focused Ion Beam (FIB) techniques. The particle size distribution (PSD) and aspect ratio (AR) of particles in the polymer phase were obtained from FIB image analysis. It was found that FIB imaging displays directly the micron to mesoscale level dispersion of particles in polymeric composites. The technique has significant potential for characterizing such materials, having some advantages over ‘traditional’ scanning and transmission electron microscopy in terms of generating representative data in a realistic timescale. The PSD and AR distribution and degree of dispersion in the composites give insights into the modification of mechanical properties of the composites studied.
Interactions of ammonium smectite with low-molecular-weight carboxylic acids
Authors: Gautier M. , Muller F. , Beny J.-M. , Le Forestier L. , Alberic P. , Baillif P.
Published: August 2009

The percolation of water through waste landfill sites produces leachates with large amounts of pollutants. Clay barriers are often used to limit soil and underground water pollution. A better understanding of the interaction between ammonium smectite and carboxylic acids would contribute significantly to our understanding of such systems. The SWy-2 (Wyoming smectite) was exchanged with NH4+ and then batched with carboxylic acids (acetic, formic, chloroacetic and oxalic) in concentrations between 0.01 M and 1 M. The solid phases obtained were analysed chemically and characterized by infrared absorption spectroscopy (IR) and powder X-ray diffraction (XRD). Ionic chromatography was used for the quantitative measurement of ammonium ions in the solution after the interaction. For the four acids, the interaction was characterized by a cationic exchange of NH4+ to H3O+. A partial exchange to Al3+ due to a partial dissolution of the sample in strong acidic medium was observed with chloroacetic and oxalic acids for which adsorption of molecules on the clay sample occurs, mainly through H-bonding with the cation. Moreover, the intercalation of oxalic acid in the interlayer space was highlighted.
Contrasted mineralogical composition of the laterite cover on serpentinites of Nkamouna-Kongo, southeast Cameroon
Authors: Yongue–Fouateu R. , Yemefack M. , Wouatong A. S. L. , Ndjigui P. D. , Bilong P.
Published: August 2009

Four drill cores along a lateritic hill in Nkamouna-Kongo (southeast Cameroon) were studied using microprobe analysis, X-ray diffraction, scanning electron microscopy, transmission electron microscopy and infrared spectroscopy. The main objective of the study was to investigate the occurrence of clay silicates while evaluating the Ni-Co content of the laterite for potential mineral exploitation. The thick lateritic profiles (>40 m deep) developed on serpentinized ultramafic rocks have an Fe-rich clayey fraction, with goethite as the main mineralogical constituent and secondary quartz and relicts of magnetite-maghemite as accessory minerals. Silicate clays are less abundant and occur mainly towards the top of the profiles. At the summit of the interfluve, kaolinite and some gibbsite are associated with goethite. Along the slopes, at the bottom of profiles, the weathered bedrock shows the presence of smectite (Fe-beidellite) and kaolinite, probably due to slower water-flow conditions. Towards the top of the profile in the lower clay, ferruginous and upper clay horizons, only kaolinite remains with gibbsite, after the leaching of silica and soluble cations following repeated remobilization-recrystallization processes. At the summit, where the downward movement of water is rapid, no smectite was identified. As a whole, the mineralogical composition of the material varies in close relationship with the drainage, leading to a contrasted clay mineralogy marked by the presence of Fe-beidellite and kaolinite at the bottom, and that of kaolinite and gibbsite at the summit of the profiles.
Determination of diffusive transport in HDPy-montmorillonite by H2O-D2O exchange using in situ ATR-FTIR spectroscopy
Authors: Schampera B. , Dultz S.
Published: August 2009

The anion adsorption capability of clays can be improved significantly by modification with certain organic cations. However, surface properties and the microstructure of the clay might change and limit the use of organo-clays in barrier systems. In this study an experimental setup is introduced which allows the rapid determination of effective diffusion coefficients (Deff) for H2O in clay samples. H2O→D2O exchange experiments on hexadecyl-pyridinium (HDPy)-montmorillonite samples were performed in a diffusion cell attached to the ATR unit of a Fourier-transform infrared spectrometer. The mean Deff for H2O in a D2O-saturated original montmorillonite is 2.44 × 10–11 m2/s in the bulk density range of 1.1–1.8 g/cm3. Hydrophobic surfaces increase the diffusivity only at high bulk densities in the saturated state. The mean Deff is lower when HDPy is applied in amounts ⩾80% of the cation exchange capacity in comparison with the original sample. At a saturation degree of the pores of 40%, Deff for all samples is one order of magnitude less than in the saturated state. Results on Deff obtained by ATR-FTIR spectroscopy are in good agreement with through-diffusion studies.
Microwave irradiation used for all steps of pre-pillaring Al-montmorillonite
Authors: Yapar S. , Torres Sánchez R. M. , Emreol M. , Weidler P. , Emmerich K.
Published: August 2009

In this study, a new procedure for the synthesis of pillared clays is proposed. Ageing processes and intercalation reactions were carried out using microwave irradiation in order to decrease the consumption of three industrially-important parameters; time, water consumption and energy. The effects of microwave irradiation, the amount of Al and the Al3+/clay ratio on the physicochemical properties of Al-pillared montmorillonites were investigated. The structural changes, depending on the intercalation and microwave irradiation, were characterized using X-ray diffraction (XRD), Fourier-transform infrared (FTIR) and scanning electron microscopy (SEM) analyses and by measuring the specific surface area and pore-size distribution. Additionally, simultaneous thermal analyses (STA) and zeta potential measurements were carried out to determine physicochemical properties. According to the XRD measurements, the d001 value of microwave-irradiated samples is not affected by the amount of Al and the Al3+/clay ratio; microwave irradiation causes a 0.20 nm contraction in the d001 value in comparison to that of a conventionally pillared sample. The results of FTIR analyses reveal that the intensity of peaks assigned to Keggin-OH and Keggin-H2O stretches is diminished in the case of microwave-irradiated samples. The STA analyses indicate that the amount of water released during dehydroxylation is decreased in the case of microwave-irradiated samples. By considering the contraction in d001 values and the decreases in Keggin-stretching bands and also in the amount of dehydroxylation water, it was concluded that microwave irradiation has a calcination effect.
C/EBPβ regulates transcription factors critical for proliferation and survival of multiple myeloma cells
Authors: Pal Rekha , Janz Martin , Galson Deborah L. , Gries Margarete , Li Shirong , Jöhrens Korinna , Anagnostopoulos Ioannis , Dörken Bernd , Mapara Markus Y. , Borghesi Lisa , Kardava Lela , Roodman G. David , Milcarek Christine , Lentzsch Suzanne
Published: August 2009

CCAAT/enhancer-binding protein β (C/EBPβ), also known as nuclear factor–interleukin-6 (NF-IL6), is a transcription factor that plays an important role in the regulation of growth and differentiation of myeloid and lymphoid cells. Mice deficient in C/EBPβ show impaired generation of B lymphocytes. We show that C/EBPβ regulates transcription factors critical for proliferation and survival in multiple myeloma. Multiple myeloma cell lines and primary multiple myeloma cells strongly expressed C/EBPβ, whereas normal B cells and plasma cells had little or no detectable levels of C/EBPβ. Silencing of C/EBPβ led to down-regulation of transcription factors such as IRF4, XBP1, and BLIMP1 accompanied by a strong inhibition of proliferation. Further, silencing of C/EBPβ led to a complete down-regulation of antiapoptotic B-cell lymphoma 2 (BCL2) expression. In chromatin immunoprecipitation assays, C/EBPβ directly bound to the promoter region of IRF4, BLIMP1, and BCL2. Our data indicate that C/EBPβ is involved in the regulatory network of transcription factors that are critical for plasma cell differentiation and survival. Targeting C/EBPβ may provide a novel therapeutic strategy in the treatment of multiple myeloma.
C-reactive protein and procalcitonin as predictors of survival and septic shock in ventilator-associated pneumonia
Authors: Hillas G. , Vassilakopoulos T. , Plantza P. , Rasidakis A. , Bakakos P.
Published: August 2009

We evaluated the performance of procalcitonin (PCT) and C-reactive protein (CRP) threshold values and kinetics as predictors of ventilator-associated pneumonia (VAP) survival and septic shock development.

45 adult patients with VAP were studied. Serum CRP and PCT levels and the Sequential Organ Failure Assessment (SOFA) score were measured on days 1, 4 and 7 (D1, D4, D7) of VAP and their variations between different days (kinetics) were calculated (ΔPCT, ΔCRP). A multivariate logistic regression model was constructed with either VAP 28-day survival or septic shock development as dependent variables, and PCT values, CRP values, kinetics, age, sex, SOFA and Acute Physiology and Chronic Health Evaluation (APACHE) II score as independent variables.

No difference was found in CRP levels between survivors and nonsurvivors. Nonsurvivors had significantly higher PCT levels on D1 and D7. In the multivariate analysis, the only factors predicting VAP survival were ΔPCT7-1(OR 7.23, 95% CI 0.008–0.468) and ΔCRP7-4(OR 4.59, 95% CI 0.013–0.824). VAP patients who developed septic shock had significantly higher CRP levels on D1 and D7 and higher PCT levels on D1 and D4. The only factor predicting the development of septic shock was SOFA on D1 (OR 7.44, 95% CI 1.330–5.715).

Neither PCT and CRP threshold values nor their kinetics can predict VAP survival or septic shock development.
Absorptive clearance of DTPA as an aerosol-based biomarker in the cystic fibrosis airway
Authors: Corcoran T. E. , Thomas K. M. , Myerburg M. M. , Muthukrishnan A. , Weber L. , Frizzell R. , Pilewski J. M.
Published: August 2009

Biomarkers providingin vivoquantification of the basic elements of cystic fibrosis (CF) lung disease are needed. A study was performed to determine whether the absorption of a small radiolabelled hydrophilic molecule (Indium-111 (In-)DTPA) would be increased in CF airways. DTPA clearance has been used previously to assess epithelial permeability and may also be useful for quantifying liquid absorption.

The absorptive clearance rate of DTPA was quantified in 10 CF and 11 control subjects using a novel aerosol technique. Subjects inhaled an aerosol containing nonabsorbable technetium-99m sulfur colloid (Tc-SC) particles and In-DTPA. Tc-SC clearance from the lung is exclusively mucociliary, while In-DTPA is cleared by both absorption and mucociliary clearance. The difference between the In-DTPA and Tc-SC clearance rates estimates In-DTPA absorption.

Tc-SC (mucociliary) clearance was similar in central and peripheral zones in CF and non-CF lungs. Total In-DTPA clearance was increased in both zones in CF lungs. The absorptive component of In-DTPA clearance was increased in the airway-dominated central lung zones in CF (42%·h−1versus32%·h−1, p = 0.03).

The absorption of In-DTPA is increased in the CF airway. Further study is needed to understand the relative roles of fluid absorption, inflammation and other mechanisms potentially affecting epithelial permeability and DTPA absorption.
Comparative gene expression profiling of post-natal and post-pneumonectomy lung growth
Authors: Wolff J-C. , Wilhelm J. , Fink L. , Seeger W. , Voswinckel R.
Published: August 2009

Although increasing numbers of patients suffer from chronic destructive lung diseases, there are no effective therapeutic options apart from transplantation. Understanding the mechanisms of physiological and regenerative alveolar septation is prerequisite for the development of regenerative therapies for the lung. We compared lung gene expression in the phase of induction of post-natal and post-pneumonectomy alveolarisation to identify regulatory genes involved in both processes.

We performed genome-wide microarray screenings of newborn and pneumonectomised mouse lungs 1 and 3 days after birth or surgery. Selected candidates were validated by real-time PCR, Western blot andin situhybridisation.

We found 58 genes to be regulated in both models with 40 candidates being changed likewise. Many of these genes participated in growth and differentiation processes. Additionally, immune system, structural molecules, respiratory chain, signal transduction and metabolism were involved. Some candidates were not yet linked to specific functions. The highest regulatory concordance was observed for various isoforms of (pro-)collagen molecules, elastin and the elastin-associated protein fibrillin1 being corporately upregulated.

Our findings do not definitively support a common regulating mechanism for induction of post-natal and adult alveolarisation, but some candidates in the intersection of both models are promising for further investigations.
Last 3 months of life in home-ventilated patients: the family perception
Authors: Vitacca M. , Grassi M. , Barbano L. , Galavotti G. , Sturani C. , Vianello A. , Zanotti E. , Ballerin L. , Potena A. , Scala R. , Peratoner A. , Ceriana P. , Di Buono L. , Clini E. , Ambrosino N. , Hill N. , Nava S.
Published: August 2009

We studied the family's perception of care in patients under home mechanical ventilation during the last 3 months of life.

In 11 respiratory units, we submitted a 35-item questionnaire to relatives of 168 deceased patients exploring six domains: symptoms, awareness of disease, family burden, dying, medical and technical problems.

Response rate was 98.8%. The majority of patients complained respiratory symptoms and were aware of the severity and prognosis of the disease. Family burden was high especially in relation to money need. During hospitalisation, 74.4% of patients were admitted to the intensive care unit (ICU). 78 patients died at home, 70 patients in a medical ward and 20 in ICU. 27% of patients received resuscitation manoeuvres. Hospitalisations and family economical burden were unrelated to diagnosis and mechanical ventilation. Families of the patients did not report major technical problems on the use of ventilators. In comparison with mechanical invasively ventilated patients, noninvasively ventilated patients were more aware of prognosis, used more respiratory drugs, changed ventilation time more frequently and died less frequently when under mechanical ventilation.

We have presented good points and bad points regarding end-of-life care in home mechanically ventilated patients. Noninvasive ventilation use and diagnosis have impact on this burden.
Guidelines of the European Respiratory Society and the European Society of Thoracic Surgeons for the management of malignant pleural mesothelioma
Authors: Scherpereel A. , Astoul P. , Baas P. , Berghmans T. , Clayson H. , de Vuyst P. , Dienemann H. , Galateau-Salle F. , Hennequin C. , Hillerdal G. , Le Péchoux C. , Mutti L. , Pairon J-C. , Stahel R. , van Houtte P. , van Meerbeeck J. , Waller D. , Weder W.
Published: August 2009

Malignant pleural mesothelioma (MPM) is a rare tumour but with increasing incidence and a poor prognosis. In 2008, the European Respiratory Society/European Society of Thoracic Surgeons Task Force brought together experts to propose practical and up-to-dated guidelines on the management of MPM.

To obtain an earlier and reliable diagnosis of MPM, the experts recommend performing thoracoscopy, except in cases of pre-operative contraindication or pleural symphysis. The standard staining procedures are insufficient in ∼10% of cases. Therefore, we propose using specific immunohistochemistry markers on pleural biopsies. In the absence of a uniform, robust and validated staging system, we advice use of the most recent TNM based classification, and propose a three step pre-treatment assessment. Patient's performance status and histological subtype are currently the only prognostic factors of clinical importance in the management of MPM. Other potential parameters should be recorded at baseline and reported in clinical trials. MPM exhibits a high resistance to chemotherapy and only a few patients are candidates for radical surgery. New therapies and strategies have been reviewed.

Because of limited data on the best combination treatment, we emphasise that patients who are considered candidates for a multimodal approach should be included in a prospective trial at a specialised centre.
Long-term efficacy of tiotropium in relation to smoking status in the UPLIFT trial
Authors: Tashkin D. P. , Celli B. , Kesten S. , Lystig T. , Mehra S. , Decramer M.
Published: August 2009

UPLIFT (Understanding Potential Long-Term Improvements in Function with Tiotropium), a 4-yr trial of tiotropium in chronic obstructive pulmonary disease, allowed for assessment of smoking status on long-term responses to maintenance bronchodilator therapy.

5,993 patients were randomised (tiotropium/placebo). Lung function, St George's Respiratory Questionnaire, exacerbations and adverse events were followed. Patients were characterised as continuing smokers (CS), continuing ex-smokers (CE), or intermittent smokers (IS) based on self-reporting smoking behaviour.

60%, 14% and 26% of patients were CE, CS and IS, respectively. The rate of forced expiratory volume in 1 s (FEV1) decline for placebo patients was most rapid in CS (-51±4, -36±2 and -23±2 mL·yr−1in CS, IS, and CE, respectively). Tiotropium did not alter FEV1decline, but was associated with significant improvements in pre- and post-bronchodilator FEV1over placebo that persisted throughout the 4-yr trial for each smoking status (pre-bronchodilator: 125, 55 and 97 mL at 48 months in CS, IS and CE, respectively; p≤0.0003). Tiotropium reduced exacerbation risk in CS (HR (95%CI) 0.81 (0.68–0.97)), in CE (0.86 (0.79–0.93)) and trended towards significance in IS (0.89 (0.80–1.01)). At 4 yrs, St George’s Respiratory Questionnaire for tiotropium patients improved the most in CS (-4.62 units, p = 0.0006) and the least in IS (-0.54 units, p = 0.55), compared with control.

Tiotropium provided long-term benefits irrespective of smoking status, although differences among categories were observed.
Bedside end-tidal CO2tension as a screening tool to exclude pulmonary embolism
Authors: Hemnes A. R. , Newman A. L. , Rosenbaum B. , Barrett T. W. , Zhou C. , Rice T. W. , Newman J. H.
Published: August 2009

End tidal carbon dioxide tension (PET,CO2) is a surrogate for dead space ventilation which may be useful in the evaluation of pulmonary embolism (PE). We aimed to define the optimalPET,CO2level to exclude PE in patients evaluated for possible thromboembolism.

298 patients were enrolled over 6 months at a single academic centre.PET,CO2was measured within 24 h of contrast-enhanced helical computed tomography, lower extremity duplex or ventilation/perfusion scan. Performance characteristics were measured by comparing test results with clinical diagnosis of PE.

PE was diagnosed in 39 (13%) patients. MeanPET,CO2in healthy volunteers did not differ fromPET,CO2in patients without PE (36.3±2.8versus35.5±6.8 mmHg).PET,CO2in patients with PE was 30.5±5.5 mmHg (p<0.001versuspatients without PE). APET,CO2of ≥36 mmHg had optimal sensitivity and specificity (87.2 and 53.0%, respectively) with a negative predictive value of 96.6% (95% CI 92.3–98.5). This increased to 97.6% (95% CI 93.2–99.) when combined with Wells score <4.

APET,CO2of ≥36 mmHg may reliably exclude PE. Accuracy is augmented by combination with Wells score.PET,CO2should be prospectively compared to D-dimer in accuracy and simplicity to exclude PE.
Oralversusi.v. antibiotics for community-acquired pneumonia in children: a cost-minimisation analysis
Authors: Lorgelly P. K. , Atkinson M. , Lakhanpaul M. , Smyth A. R. , Vyas H. , Weston V. , Stephenson T.
Published: August 2009

Community-acquired pneumonia represents a high financial burden to healthcare providers. This manuscript seeks to estimate and compare the costs of treating children hospitalised with community-acquired pneumonia, with oral and intravenous antibiotics, thus determining which treatment is cost minimising.

A cost-minimisation analysis was undertaken alongside a randomised controlled non-blinded equivalence trial. 232 children (from eight paediatric centres in England) diagnosed with pneumonia, who required admission to hospital, were randomised to receive oral amoxicillin ori.v.benzyl penicillin. The analysis considered the cost to the health service, patients and society, from pre-admission until the child was fully recovered.

Oral amoxicillin andi.v.benzyl penicillin have equivalent efficacy. Children treated withi.v.antibiotics were found to have significantly longer in-patient stays (3.12versus1.93 days; p<0.001).i.v.treatment was found to be more expensive than oral treatment (£1,256versus£769; difference £488; 95% CI: £233–£750), such that treatment of community-acquired pneumonia with oral amoxicillin would result in savings of between £473 and £518 per child (€545 and €596 per child) admitted.

The findings demonstrate that oral amoxicillin is a cost-effective treatment for the majority of children admitted to hospital with pneumonia.
Atrophy and hypertrophy signalling in the diaphragm of patients with COPD
Authors: Testelmans D. , Crul T. , Maes K. , Agten A. , Crombach M. , Decramer M. , Gayan-Ramirez G.
Published: August 2009

We investigated whether atrophy and hypertrophy signalling were altered in the diaphragm of chronic obstructive pulmonary disease (COPD) patients.

We studied diaphragm fibre dimensions and proportion, expression of markers of the ubiquitin-proteasome pathway, nuclear factor (NF)-κB pathways, muscle regulatory factors and myostatin in diaphragm biopsies from 19 patients with severe COPD and 13 patients without COPD.

Type I proportion was significantly increased in the diaphragm of COPD patients while type II proportion was decreased. The cross-sectional area of all fibre types was reduced in the COPD patients. In addition, MAFbx mRNA was higher in the diaphragm of COPD patients while Nedd4 mRNA decreased. Cytoplasmatic levels of inhibitor protein IκBα and IκBβ were decreased in the COPD patients as was NF-κB p50 DNA-binding activity. MyoD mRNA and its nuclear protein content were decreased in the diaphragm of COPD patients and myogenin mRNA and protein levels remained unchanged. Myostatin mRNA was decreased but its protein levels in the nuclear and cytoplasmic fraction were significantly increased in the COPD patients.

These data show that the ubiquitin-proteasome pathway, the NF-κB pathway and myostatin protein were up-regulated in the diaphragm of COPD patients while MyoD expression was reduced. These alterations may contribute to diaphragm remodeling in COPD.
Newer fluoroquinolones for treating respiratory infection: do they mask tuberculosis?
Authors: Chang K. C. , Leung C. C. , Yew W. W. , Lau T. Y. , Leung W. M. , Tam C. M. , Lam H. C. , Tse P. S. , Wong M. Y. , Lee S. N. , Wat K. I. , Ma Y. H.
Published: August 2009

Possible masking of tuberculosis (TB) in treatment of community-acquired respiratory infection by newer fluoroquinolones has not been examined in randomised controlled trials.

We undertook a randomised, open-label controlled trial involving adults with community-acquired pneumonia or infective exacerbation of bronchiectasis encountered in government chest clinics in Hong Kong. 427 participants were assigned by random permutated blocks of 20 to receive either amoxicillin clavulanate (n = 212) or moxifloxacin (n = 215). Participants were followed for 1 yr for active pulmonary TB.

Excluding three participants with positive baseline culture, 13 developed active pulmonary TB: 10 (4.8%) out of 210 were given amoxicillin clavulanate, and three (1.4%) out of 214 were given moxifloxacin. The difference was significant by both proportion and time-to-event analysis.Post hocanalysis showed a significant decrease in the proportion with active pulmonary TB from 4.8% to 2.4% and 0% among participants given amoxicillin clavulanate (n = 210), moxifloxacin for predominantly 5 days (n = 127) and 10 days (n = 87), respectively. The log rank test for trend also showed a significant difference between the three subgroups. Regression models reaffirmed the linear effect; the adjusted odds ratio (95% confidence interval) of active pulmonary TB after moxifloxacin exposure up to predominantly 10 days was 0.3 (0.1–0.9).

Newer fluoroquinolones appear to mask active pulmonary TB.
Is treatment with ICS and LABA cost-effective for COPD? Multinational economic analysis of the TORCH study
Authors: Briggs A. H. , Glick H. A. , Lozano-Ortega G. , Spencer M. , Calverley P. M. A. , Jones P. W. , Vestbo J.
Published: August 2009

The TOwards a Revolution in COPD Health (TORCH) study was a 3-yr multicentre trial of 6,112 patients randomised to salmeterol (Salm), fluticasone propionate (FP), a Salm/FP combination (SFC) or placebo (P). Here the cost-effectiveness of treatments evaluated in the TORCH study is assessed.

For four regions, 3-yr all-cause hospitalisation, medication and outpatient care costs were calculated. The sample was restricted to the 21 countries (n = 4,237) in which European quality of life five-dimension (EQ-5D) data were collected in order to estimate the number of quality-adjusted life years (QALYs). Regression models were fitted to survival, study medication cost, other medication cost and EQ-5D data in order to estimate total cost, number of QALYs and cost per QALY, adjusted for missing data and region.

SFC had a trial-wide estimate of cost per QALY of 43,600 US dollars (USD) compared with P (95% confidence interval 21,400–123,500 USD). Estimates for SalmversusP (197,000 USD) and FPversusP (78,000 USD) were less favourable. The US estimates were greater than those from other regions; for SFCversusP, the cost per QALY was 77,100 (46,200–241,700) USD compared to 24,200 (15,200–56,100) USD in Western Europe.

Compared with P, SFC has a lower incremental cost-effectiveness ratio than either FP or Salm used alone, and is, therefore, preferred to these monotherapies on the grounds of cost-effectiveness.
Effect of manufacturer-inserted mask leaks on ventilator performance
Authors: Louis B. , Leroux K. , Isabey D. , Fauroux B. , Lofaso F.
Published: August 2009

Most pressure-support devices use a single circuit with an exhalation port integrated in the mask. The aim of the current study was to compare the effects of masks having different manufacturer-inserted leaks on ventilator performance.

We simulated chronic obstructive pulmonary disease and restrictive disease. Four ventilators (VENTImotion (Weinmann, Hamburg, Germany), VPAP III STA (ResMed, Saint Priest, France), Synchrony 2 (Respironics, Nantes, France) and Vivo 40 (Breas, Saint Priest)) were tested with the recommended masks and with the masks having the largest and smallest leaks. Tests were performed with pressure support levels of 10, 15 and 20 cmH2O. Thein vivoevaluation compared two ventilators using recommended masks opposed in terms of exhaled port resistance. The ventilators were tested with their recommended mask, and after mask exchange.

The mask with the largest leak induced auto-triggering and/or increased inspiratory-trigger sensitivity was the VENTImotion under both simulated conditions and VPAP III STA under the simulated obstructive-disease condition. The mask with the smallest leak-increased inspiratory-trigger delay was Synchrony 2 in the simulated obstructive-disease condition and increased rebreathing. Thein vivostudy confirmed the bench results.

When switching to a mask that has a different leak, evaluation is needed to adjust trigger sensitivity and pressurisation level and to check the absence of rebreathing.
Macrophage derived chemokine (CCL22), thymus and activation-regulated chemokine (CCL17), and CCR4 in idiopathic pulmonary fibrosis
Authors: Yogo Yurika , Fujishima Seitaro , Inoue Takashi , Saito Fumitake , Shiomi Takayuki , Yamaguchi Kazuhiro , Ishizaka Akitoshi
Published: August 2009

Background

Idiopathic pulmonary fibrosis (IPF) is a chronically progressive interstitial lung disease of unknown etiology. Previously, we have demonstrated the selective upregulation of the macrophage-derived chemokine CCL22 and the thymus activation-regulated chemokine CCL17 among chemokines, in a rat model of radiation pneumonitis/pulmonary fibrosis and preliminarily observed an increase in bronchoalveolar (BAL) fluid CCL22 levels of IPF patients.

Methods

We examined the expression of CCR4, a specific receptor for CCL22 and CCL17, in bronchoalveolar lavage (BAL) fluid cells, as well as the levels of CCL22 and CCL17, to elucidate their pathophysiological roles in pulmonary fibrosis. We also studied their immunohistochemical localization.

Results

BAL fluid CCL22 and CCL17 levels were significantly higher in patients with IPF than those with collagen vascular diseases and healthy volunteers, and there was a significant correlation between the levels of CCL22 and CCL17 in patients with IPF. CCL22 levels in the BAL fluid did not correlate with the total cell numbers, alveolar lymphocytes, or macrophages in BAL fluid. However, the CCL22 levels significantly correlated with the numbers of CCR4-expressing alveolar macrophages. By immunohistochemical and immunofluorescence analysis, localization of CCL22 and CCR4 to CD68-positive alveolar macrophages as well as that of CCL17 to hyperplastic epithelial cells were shown. Clinically, CCL22 BAL fluid levels inversely correlated with DLco/VA values in IPF patients.

Conclusion

We speculated that locally overexpressed CCL22 may induce lung dysfunction through recruitment and activation of CCR4-positive alveolar macrophages.
A reliable measure of similarity based on dependency for short time series: an application to gene expression networks
Authors: Campiteli Mônica G , Soriani Frederico M , Malavazi Iran , Kinouchi Osame , Pereira Carlos AB , Goldman Gustavo H
Published: September 2009

Background

Microarray techniques have become an important tool to the investigation of genetic relationships and the assignment of different phenotypes. Since microarrays are still very expensive, most of the experiments are performed with small samples. This paper introduces a method to quantify dependency between data series composed of few sample points. The method is used to construct gene co-expression subnetworks of highly significant edges.

Results

The results shown here are for an adapted subset of a Saccharomyces cerevisiae gene expression data set with low temporal resolution and poor statistics. The method reveals common transcription factors with a high confidence level and allows the construction of subnetworks with high biological relevance that reveals characteristic features of the processes driving the organism adaptations to specific environmental conditions.

Conclusion

Our method allows a reliable and sophisticated analysis of microarray data even under severe constraints. The utilization of systems biology improves the biologists ability to elucidate the mechanisms underlying celular processes and to formulate new hypotheses.
Endogenous Fms-like Tyrosine Kinase-3 Ligand levels are not altered in mice after a severe burn and infection
Authors: Bohannon Julia K , Cui Weihua , Toliver-Kinsky Tracy
Published: September 2009

Background

Fms-like tyrosine kinase-3 ligand (Flt3L) is a hemopoietic cytokine and dendritic cell (DC) growth factor that promotes the proliferation and differentiation of progenitor cells into DCs. We have previously found that treatment of severely burned mice with recombinant Flt3L significantly enhances DC production and bacterial clearance from infected burn wounds, and increases global immune cell activation and survival in response to a burn wound infection. These significant benefits of Flt3L treatment after burn injury have prompted the question of whether or not severe burn injury induces deficits in endogenous Flt3L levels that could affect DCs and subsequent responses to infection.

Results

To address this, male BALB/c mice received a 30% total body surface area scald burn. Blood, spleens, and wound-draining lymph nodes were harvested at various time-points after injury. Some mice received a wound inoculation withP. aeruginosa. Murine Flt3L and G-CSF levels were measured by ELISA. Burn injury had no significant effect on Flt3L levels at any post-burn time-point examined compared to normal Flt3L levels in the sera, spleen, or lymph nodes. Additionally, Flt3L levels in the sera, spleen, and lymph nodes were not significantly altered when wounds were inoculated on the day of burn injury or at post-burn time points examined. Alternatively, levels of G-CSF were increased in response to burn injury and burn wound infection. Additionally, DC numbers and functions were not altered following burn injury alone. There was no significant difference between the number of DCs in the spleens of sham-injured mice and mice at 5 days after burn injury. When naïve T cells from sham-injured mice were co-cultured with DCs from either sham- or burn-injured mice, IFN-γ production was similar, however, IFN-γ levels produced by T cells harvested from burn-injured mice were significantly lower than those produced by T cells from sham mice, regardless of which DC group, sham or burn, was used in the coculture.

Conclusion

These data suggest that the beneficial effects of Flt3L treatments after burn injury are not due to correction of a burn-associated Flt3L deficiency but rather, are likely due to supplementary stimulation of DC production and immune responses to infection.
Dietary agent, benzyl isothiocyanate inhibits signal transducer and activator of transcription 3 phosphorylation and collaborates with sulforaphane in the growth suppression of PANC-1 cancer cells
Authors: Hutzen Brian , Willis William , Jones Sarah , Cen Ling , Deangelis Stephanie , Fuh Beng , Lin Jiayuh
Published: September 2009

The Signal Transducer and Activator of Transcription (STAT) proteins comprise a family of latent transcription factors with diverse functions. STAT3 has well established roles in cell proliferation, growth and survival, and its persistent activation has been detected with high frequency in many human cancers. As constitutive activation of STAT3 appears to be vital for the continued survival of these cancerous cells, it has emerged as an attractive target for chemotherapeutics. We examined whether the inhibitory activities of bioactive compounds from cruciferous vegetables, such as Benzyl isothiocyanate (BITC) and sulforaphane, extended to STAT3 activation in PANC-1 human pancreatic cancer cells. BITC and sulforaphane were both capable of inhibiting cell viability and inducing apoptosis in PANC-1. Sulforaphane had minimal effect on the direct inhibition of STAT3 tyrosine phosphorylation, however, suggesting its inhibitory activities are most likely STAT3-independent. Conversely, BITC was shown to inhibit the tyrosine phosphorylation of STAT3, but not the phosphorylation of ERK1/2, MAPK and p70S6 kinase. These results suggest that STAT3 may be one of the targets of BITC-mediated inhibition of cell viability in PANC-1 cancer cells. In addition, we show that BITC can prevent the induction of STAT3 activation by Interleukin-6 in MDA-MB-453 breast cancer cells. Furthermore, combinations of BITC and sulforaphane inhibited cell viability and STAT3 phosphorylation more dramatically than either agent alone. These findings suggest that the combination of the dietary agents BITC and sulforaphane has potent inhibitory activity in pancreatic cancer cells and that they may have translational potential as chemopreventative or therapeutic agents.
Docetaxel-induced prostate cancer cell death involves concomitant activation of caspase and lysosomal pathways and is attenuated by LEDGF/p75
Authors: Mediavilla-Varela Melanie , Pacheco Fabio J , Almaguel Frankis , Perez Jossymar , Sahakian Eva , Daniels Tracy R , Leoh Lai Sum , Padilla Amelia , Wall Nathan R , Lilly Michael B , De Leon Marino , Casiano Carlos A
Published: August 2009

Background

Hormone-refractory prostate cancer (HRPC) is characterized by poor response to chemotherapy and high mortality, particularly among African American men when compared to other racial/ethnic groups. It is generally accepted that docetaxel, the standard of care for chemotherapy of HRPC, primarily exerts tumor cell death by inducing mitotic catastrophe and caspase-dependent apoptosis following inhibition of microtubule depolymerization. However, there is a gap in our knowledge of mechanistic events underlying docetaxel-induced caspase-independent cell death, and the genes that antagonize this process. This knowledge is important for circumventing HRPC chemoresistance and reducing disparities in prostate cancer mortality.

Results

We investigated mechanistic events associated with docetaxel-induced death in HRPC cell lines using various approaches that distinguish caspase-dependent from caspase-independent cell death. Docetaxel induced both mitotic catastrophe and caspase-dependent apoptosis at various concentrations. However, caspase activity was not essential for docetaxel-induced cytotoxicity since cell death associated with lysosomal membrane permeabilization still occurred in the presence of caspase inhibitors. Partial inhibition of docetaxel-induced cytotoxicity was observed after inhibition of cathepsin B, but not inhibition of cathepsins D and L, suggesting that docetaxel induces caspase-independent, lysosomal cell death. Simultaneous inhibition of caspases and cathepsin B dramatically reduced docetaxel-induced cell death. Ectopic expression of lens epithelium-derived growth factor p75 (LEDGF/p75), a stress survival autoantigen and transcription co-activator, attenuated docetaxel-induced lysosomal destabilization and cell death. Interestingly, LEDGF/p75 overexpression did not protect cells against DTX-induced mitotic catastrophe, and against apoptosis induced by tumor necrosis factor related apoptosis inducing ligand (TRAIL), suggesting selectivity in its pro-survival activity.

Conclusion

These results underscore the ability of docetaxel to induce concomitantly caspase-dependent and independent death pathways in prostate cancer cells. The results also point to LEDGF/p75 as a potential contributor to cellular resistance to docetaxel-induced lysosomal destabilization and cell death, and an attractive candidate for molecular targeting in HRPC.