bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methylene blue reduces pulmonary oedema and cyclo-oxygenase products in endotoxaemic sheep
Authors: Evgenov O.V. , Evgenov N.V. , Mollnes T.E. , Bjertnaes L.J. 
Published: September 2002

The authors recently demonstrated that methylene blue (MB), an inhibitor of the nitric oxide (NO) pathway, reduces the increments in pulmonary capillary pressure, lung lymph flow and protein clearance in endotoxaemic sheep. In the present study, the authors examined whether MB influences pulmonary haemodynamics and accumulation of extravascular lung water (EVLW) by mechanisms other than the NO pathway.Sixteen awake, chronically-instrumented sheep randomly received either an intravenous injection of MB 10 mg·kg−1or isotonic saline. Thirty minutes later, all sheep received an intravenous infusion ofEscherichia coliendotoxin 1 µg·kg−1for 20 min and either an intravenous infusion of MB 2.5 mg·kg−1·h−1or isotonic saline for 6 h.MB markedly attenuated the endotoxin-induced pulmonary hypertension and right ventricular failure, and reduced the accumulation of EVLW. Moreover, MB reduced the increments in plasma thromboxane B2and 6-keto-prostaglandin F1α, and abolished the febrile response. However, MB had no effect on the changes in circulating neutrophils, serum hyaluronan, and total haemolytic activity of the alternative complement pathway.The authors conclude that in sheep, methylene blue attenuates the endotoxin-induced pulmonary hypertension and oedema, at least in part, by inhibiting the cyclo-oxygenase products of arachidonic acid. This is a novel effect of methylene bluein vivo.
Measurements of interrupter resistance: reference values for children 3–13 yrs of age
Authors: Merkus P.J.F.M. , Arets H.G.M. , Joosten T. , Siero A. , Brouha M. , Mijnsbergen J.Y. , de Jongste J.C. , van der Ent C.K. 
Published: September 2002

The interrupter technique is a convenient and sensitive technique for studying airway function in subjects who cannot actively participate in (forced) ventilatory function tests.Reference values for preschool children exist but are lacking for children >7 yrs. Reference values were obtained for expiratory interrupter resistance (Rint,e) in 208 healthy Dutch Caucasian children 3–13 yrs of age.A curvilinear relationship betweenRint,eand height was observed, similar to published airways resistance data measured by plethysmography. No significant differences in cross-sectional trend or level ofRint,ewere observed according to sex. It was found that Z-scores could be used to express individualRint,evalues and to describe intra- and interindividual differences based on the reference equation:10logRint,e=0.645–0.00668×standing height (cm) kPa·L−1·s−1and residual SD (0.093 kPa·L−1·s−1).Expiratory interrupter resistance provides a tool for clinical and epidemiological assessment of airway function in a large age range.
Exhaled nitric oxide measurements with dynamic flow restriction in children aged 4–8 yrs
Authors: Pijnenburg M.W.H. , Lissenberg E.T. , Hofhuis W. , Ghiro L. , Hop W.C.J. , Holland W.P. , de Jongste J.C. 
Published: September 2002

Fractional exhaled nitric oxide concentration (FEno) depends on exhalation flow; however, children often are unable to perform controlled flow procedures. Therefore, a device was developed for off-line FEno sampling, with dynamic flow restriction (DFR).The authors compared off-line with on-line FEno, assessed feasibility, and obtained normal values for FEno in children aged 4–8 yrs. Subjects inhaled nitric oxide (NO)-free air and exhaled into the device, where DFR kept exhalation flow constant at 50 mL·s−1. Dead space air was discarded. Exhaled air was collected in a 150 mL mylar balloon. On-line measurements were performed and values compared with off-line FEno in 19 adult volunteers. Seventy-nine children performed off-line sampling. All samples were analysed with a chemiluminescence NO-analyser. Normal values were obtained in 34 healthy children.There was an excellent correlation between on- and off-line values. Bland and Altman plots showed good agreement between on- and off-line FEno. Seventy-four out of 79 children were able to perform a correct off-line procedure. Geometric mean±sem FEno in healthy children was 4.9±1.2 parts per billion (ppb) for male children and 7.6±1.1 ppb for female children.It can be concluded that off-line fraction of exhaled nitric oxide measurements with dynamic flow restriction are feasible in young children and correspond to on-line values.
Meta-analysis of diagnostic procedures forPneumocystis cariniipneumonia in HIV-1-infected patients
Authors: Cruciani M. , Marcati P. , Malena M. , Bosco O. , Serpelloni G. , Mengoli C. 
Published: September 2002

Sputum induction is a simple and noninvasive procedure forPneumocystis cariniipneumonia (PCP) diagnosis in human immunodeficiency virus-1-positive patients, although less sensitive than bronchoalveolar lavage (BAL). In order to obtain an overview of the diagnostic accuracy of sputum induction, a systematic review and meta-analysis of studies reporting the comparative sensitivity and specificity of BAL (the “gold standard”) and sputum induction was performed.The odds ratio and related 95% confidence interval were calculated using summary receiving operating characteristic curves as well as fixed-effect and random-effect models. Based on pooled data, the negative and positive predictive values were calculated for a range of PCP prevalence using a Bayesian approach.Seven prospective studies assessed the comparative accuracy of BAL and sputum induction. On the whole, sputum induction demonstrated 55.5% sensitivity and 98.6% specificity. The sensitivity of sputum induction was significantly higher with immunofluorescence than with cytochemical staining (67.1versus43.1%). In settings of 25–60% prevalence of PCP, the positive and negative predictive values ranged 86–96.7 and 66.2–89.8, respectively, with immunofluorescence, and 79–94.4 and 53–83.5% with cytochemical staining.In conclusion, in a setting of low prevalence ofPneumocystis cariniipneumonia, sputum induction, particularly with immunostaining, appears to be adequate for clinical decision-making.
Different modes of assisted ventilation in patients with acute respiratory failure
Authors: Chiumello D. , Pelosi P. , Calvi E. , Bigatello L.M. , Gattinoni L. 
Published: September 2002

The aim of the present study was to verify that the patient/ventilator interaction is similar, regardless of the mode of assisted mechanical ventilation (i.e.pressure- or volume-limited) used, if tidal volume (VT) and peak inspiratory flow (PIF) are matched. Therefore, the authors compared the effects of three different modes of assisted ventilation on the work of breathing (WOB) and gas exchange in patients with acute respiratory failure.For Protocol 1, in seven patients, the authors compared pressure support, assist pressure control and assist control (with square and decelerating wave inspiratory flow pattern) set to deliver the sameVTand PIF. For Protocol 2, in another 10 patients, the authors compared pressure support and assist control with high (0.8 L·s−1) and low (0.6 L·s−1) PIFs set to deliver the sameVT.In Protocol 1, there was no difference in WOB and gas exchange between the three modes of assisted ventilation tested. In Protocol 2, the decrease of PIFs during assist control significantly increased WOB.In conclusion, different modes of assisted ventilation similarly reduce work of breathing and provide adequate gas exchange at fixed tidal volume and peak inspiratory flow only. During assist control, tidal volume and peak inspiratory flow (set by the physician) are the main determinants of the patient/ventilator interaction.
Ventilation-induced activation of the mitogen-activated protein kinase pathway
Authors: Uhlig U. , Haitsma J.J. , Goldmann T. , Poelma D.L. , Lachmann B. , Uhlig S. 
Published: September 2002

Mechanical ventilation of patients can be a life-saving treatment, but also imposes additional stress on the lung. Mitogen-activated protein kinases (MAPK) represent a family of protein kinases that become phosphorylated and activated by many different forms of stress.Using Western blot analysis, the present study analysed the effects of high distending pressure ventilation on the activation of the MAPK extracellular signal-related kinases (ERK)-1/2, c-Jun amino-terminal kinases (JNK) and p38 kinase, and on the MAPK-activated transcription factors c-Jun, ETS-like protein (Elk)-1 and activating transcription factor (ATF)-2.In adult rats, ventilation with high pressure (45/10 peak inspiratory pressure/positive end-expiratory pressure in cmH2O) for 30 or 60 min did not affect arterial oxygenation, but resulted in enhanced phosphorylation of ERK-1/2, JNK, c-Jun, Elk-1 and ATF-2 compared to normally ventilated (13/3) rats. The activation of ERK-1/2 and JNK was located to cells resembling alveolar type II cells. In addition, high pressure ventilation enhanced phosphorylation of the inhibitor of nuclear factor (NF)-κB and nuclear translocation of the transcription factor NF-κB. In isolated perfused mouse lungs, the MAPK/ERK kinase inhibitor U0126 prevented ventilation-induced activation of ERK-1/2 and Elk-1, but had no effect on ventilation-induced cytokine release.The present authors conclude that mechanical ventilation triggers specific signalling pathways, such as the mitogen-activated protein kinase and the nuclear factor-κB pathways, which may contribute to pulmonary inflammation and proliferation.
Dose-related effect of inhaled fluticasone on allergen-induced airway changes in rats
Authors: Vanacker N.J. , Palmans E. , Pauwels R.A. , Kips J.C. 
Published: September 2002

To examine whether fluticasone propionate (FP) dose-dependently inhibits inflammatory as well as structural changes, Brown Norway rats were sensitised to ovalbumin (OA) on day 0 and 7. From day 14–28, rats were exposed to aerosolised OA (1%) or phosphate buffered saline every 2 days. Thirty minutes before each allergen exposure, animals were pre-treated with aerosolised placebo or FP (0.1, 1 or 10 mg) or prednisolone 3 mg·kg−1i.p.At day 29, 0.1 mg FP had no measurable effect, either on inflammatory or structural changes, such as goblet cell hyperplasia and airway wall thickening. The allergen-induced increase in eosinophilic inflammation in bronchoalveolar lavage fluid and in the airway mucosa, as well as increased fibronectin deposition, were inhibited by treatment with FP from a dose of 1 mg onwards. Inhibition of goblet cell hyperplasia and thickening of the airway wall required 10 mg inhaled FP. At this dose, systemic effects were observed. However, for a comparable degree of systemic activity, prednisolone was far less effective at preventing airway changes.The dose of inhaled fluticasone propionate required to inhibit allergen-induced structural alterations was higher than to prevent eosinophil influx, and caused systemic side-effects. However, for a similar systemic activity, prednisolone was ineffective in preventing airway remodelling.
Automatic regulation of the cuff pressure in endotracheally-intubated patients
Authors: Farré R. , Rotger M. , Ferrer M. , Torres A. , Navajas D. 
Published: September 2002

To avoid tracheal wall damage or inadvertent falls of the endotracheal tube cuff pressure (Pcuff) in intubated and mechanically-ventilated patients, the authors devised a simple procedure for automatic and continuous regulation ofPcuff.The procedure, only requiring a simple aquarium air pump and conventional tubing, was first tested at the bench when applied to an intubated and ventilated lung model, including an artificial trachea with an externally-variable section. The clinical performance of the procedure was tested in eight intubated patients, in whom the endotracheal tube cuff was connected to the designedPcuffregulator during 24 h.The bench test showed that the procedure was able to maintainPcuffconstant, regardless of the changes imposed in the tracheal section. It was also effective in maintainingPcuffduring routine mechanical ventilation. ActualPcuffrecorded over the 24-h period always coincided with the target value within ±2 cmH2O in all the patients.The procedure devised to maintain endotracheal tube cuff pressure is readily implemented, cheap, easy to operate and can be used regardless of the specific ventilator or tube used. Routine implementation of this procedure may be useful for protecting the trachea from tissue damage and for reducing the risk of ventilator-associated pneumonia.
Impact of COPD in North America and Europe in 2000: subjects' perspective of Confronting COPD International Survey
Authors: Rennard S. , Decramer M. , Calverley P.M.A. , Pride N.B. , Soriano J.B. , Vermeire P.A. , Vestbo J. 
Published: September 2002

To date, no international surveys estimating the burden of chronic obstructive pulmonary disease (COPD) in the general population have been published. The Confronting COPD International Survey aimed to quantify morbidity and burden in COPD subjects in 2000.From a total of 201,921 households screened by random-digit dialling in the USA, Canada, France, Italy, Germany, the Netherlands, Spain and the UK, 3,265 subjects with a diagnosis of COPD, chronic bronchitis or emphysema, or with symptoms of chronic bronchitis, were identified.The mean age of the subjects was 63.3 yrs and 44.2% were female. Subjects with COPD in North America and Europe appear to underestimate their morbidity, as shown by the high proportion of subjects with limitations to their basic daily life activities, frequent work loss (45.3% of COPD subjects of <65 yrs reported work loss in the past year) and frequent use of health services (13.8% of subjects required emergency care in the last year), and may be undertreated. There was a significant disparity between subjects' perception of disease severity and the degree of severity indicated by an objective breathlessness scale. Of those with the most severe breathlessness (too breathless to leave the house), 35.8% described their condition as mild or moderate, as did 60.3% of those with the next most severe degree of breathlessness (breathless after walking a few minutes on level ground).This international survey confirmed the great burden to society and high individual morbidity associated with chronic obstructive pulmonary disease in subjects in North America and Europe.
The new clinical trials on pharmacological treatment in pulmonary arterial hypertension
Authors: Galiè N. , Manes A. , Branzi A. 
Published: September 2002

Past medical therapy for pulmonary arterial hypertension included the use of calcium-channel antagonists in acute vasoreactive subjects and oral anticoagulants and continuous intravenous administration of epoprostenol in the more severe cases. Recently, the thromboxane inhibitor terbogrel, the prostacyclin analogues treprostinil, beraprost and iloprost, and the endothelin receptor antagonist bosentan have been tested in clinical trials in >1,100 patients.Except for terbogrel, all compounds improved the mean exercise capacity by different degrees, as assessed by the 6-min walk test. In the evaluation of the clinical relevance of exercise capacity improvements, additional elements need to be considered, such as baseline functional class and concomitant favourable effects on combined clinical events (including hospitalisations, mortality and rescue therapies), quality of life and haemodynamics. No trials have shown effects on mortality, as the study protocols were not designed for assessing this end-point. Each new compound presents side-effects that are unpredictable in the individual patient and require appropriate attention upon treatment initiation and maintenance.These new therapeutic options will be available in the near future and will allow tailoring of the most appropriate treatment to the single patient, according to an individualised benefit-to-risk ratio.
T-cell activation without proliferation in juvenile idiopathic arthritis
Authors: Black Antony PB , Bhayani Hansha , Ryder Clive AJ , Gardner-Medwin Janet MM , Southwood Taunton R 
Published: September 2002

AbstractA study was done to determine if the differentiation and activation phenotype of T cells in synovial fluid (SF) from patients with juvenile idiopathic arthritis (JIA) is associated with T-cell proliferationin situ.Mononuclear cells were isolated from 44 paired samples of peripheral blood and SF. Differentiation and activation markers were determined on CD4 and CD8 T cells by flow cytometry. Cell-cycle analysis was performed by propidium iodide staining, and surface-marker expression was also assessed after culture of the T cells under conditions similar to those found in the synovial compartment. The majority of the T cells in the SF were CD45RO+CD45RBdull. There was greater expression of the activation markers CD69, HLA-DR, CD25 and CD71 on T cells from SF than on those from peripheral blood. Actively dividing cells accounted for less than 1% of the total T-cell population in SF. The presence or absence of IL-16 in T-cell cultures with SF or in a hypoxic environment did not affect the expression of markers of T-cell activation. T cells from the SF of patients with JIA were highly differentiated and expressed early and late markers of activation with little evidence ofin situproliferation. This observation refines and extends previous reports of the SF T-cell phenotype in JIA and may have important implications for our understanding of chronic inflammation.
Differential clinical efficacy of anti-CD4 monoclonal antibodies in rat adjuvant arthritis is paralleled by differential influence on NF-κB binding activity and TNF-α secretion of T cells
Authors: Pohlers Dirk , Schmidt-Weber Carsten B , Franch Angels , Kuhlmann Jürgen , Bräuer Rolf , Emmrich Frank , Kinne Raimund W 
Published: September 2002

AbstractThe aim of this study was to analyze the differential effects of three anti-CD4 monoclonal antibodies (mAbs) (with distinct epitope specifities) in the treatment of rat adjuvant arthritis (AA) and on T-cell function and signal transduction. Rat AA was preventively treated by intraperitoneal injection of the anti-CD4 mAbs W3/25, OX35, and RIB5/2 (on days -1, 0, 3, and 6, i.e. 1 day before AA induction, on the day of induction [day 0], and thereafter). The effects on T-cell reactivityin vivo(delayed-type hypersensitivity),ex vivo(ConA-induced proliferation), andin vitro(mixed lymphocyte culture) were assessed. Thein vitroeffects of anti-CD4 preincubation on T-cell receptor (TCR)/CD3-induced cytokine production and signal transduction were also analyzed. While preventive treatment with OX35 and W3/25 significantly ameliorated AA from the onset, treatment with RIB5/2 even accelerated the onset of AA by approximately 2 days (day 10), and ameliorated the arthritis only in the late phase (day 27). Differential clinical effects at the onset of AA were paralleled by a differential influence of the mAbs on T-cell functions, i.e. in comparison with OX35 and W3/25, the 'accelerating' mAb RIB5/2 failed to increase the delayed-type hypersentivity (DTH) toMycobacterium tuberculosis,increased thein vitrotumor necrosis factor (TNF)-α secretion, and more strongly induced NF-κB binding activity after anti-CD4 preincubation and subsequent TCR/CD3-stimulation. Depending on their epitope specificity, different anti-CD4 mAbs differentially influence individual proinflammatory functions of T cells. This fine regulation may explain the differential efficacy in the treatment of AA and may contribute to the understanding of such treatments in other immunopathologies.
Tissue factor as a proinflammatory agent
Authors: Bokarewa Maria I , Morrissey James H , Tarkowski Andrej 
Published: September 2002

AbstractTissue factor (TF) is a transmembrane glycoprotein and the main triggering element of blood coagulation. TF expression on monocytes and endothelial cells is induced by exposure to endotoxin, tumor necrosis factor, and IL-1 and is considered to appear in consequence of inflammation. In order to assess the proinflammatory capacity of TF itself, the recombinant extracellular domain of TF was injected intra-articularly into healthy mice. To characterize the role of immune cells in the TF-induced arthritis, mice deprived of lymphocytes, neutrophils and monocytes were used. Histomorphological analysis of the joints with respect to inflammatory cell infiltration, pannus formation and erosion formation revealed development of arthritis in 80% of animals injected with TF. In most of the cases synovial proliferation was accompanied by pannus formation and cartilage destruction. Inflammatory cell infiltrate consisted of CD4-Mac1+ macrophages. Depletion of monocytes was, however, not enough to abolish inflammation. Indeed, combined deficiency of monocytes and lymphocytes was required to prevent inflammation following the injection of TF. We observed that TF induced chemokine production (MIP-1α and RANTES), but did not induce a proliferative response nor cytokine release by mouse spleen cells. TF has strong inflammatogenic properties mediated predominantly by monocytes and their release of chemokines. Our study shows that TF can simultaneously trigger the immune and coagulation systems.
Combined antibiotic and free radical trap treatment is effective at combating Staphylococcus-aureus-induced septic arthritis
Authors: Sakiniene Egidija , Collins L Vincent 
Published: September 2002

AbstractAlthough early antibiotic treatment of patients with septic arthritis eradicates bacteria, joint destruction commonly results from the unregulated host inflammatory responses to infection. The spin trap compound phenyl-N-tert-butyl nitrone (PBN) has been shown to have both anti-inflammatory and antioxidant effects. The aim of this study was to assess the effect of combined systemic administration of PBN and cloxacillin on the development ofStaphylococcus aureusarthritis.Three days after Naval Medical Research Institute (NMRI) mice were infected intravenously withS. aureusLS-1, daily treatment was started with cloxacillin alone, PBN alone, or cloxacillin and PBN. Arthritis, weight loss and general condition were evaluated for each mouse, and joints were analyzed histopathologically. Systemic administration of PBN in conjunction with cloxacillin ameliorated the course of experimentalS. aureusarthritis, as evidenced by an increased cure rate. Thus, combinatorial antioxidant plus antibiotic anti-inflammatory therapies represent a potentially efficacious approach to the management of septic arthritis.