bluuebunny/crossref_metadata_2025 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

A 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

The 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

Tissue 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

Although 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.
Differential expression of the angiogenic Tie receptor family in arthritic and normal synovial tissue
Authors: Shahrara Shiva , Volin Michael V , Connors Matthew A , Haines G Kenneth , Koch Alisa E
Published: September 2002

Angiopoietins (Ang) are vascular endothelial cell-specific growth factors that play important roles principally during the later stages of angiogenesis. We have compared the distribution of the receptor tyrosine kinase (Tie) and the Ang ligands in synovial tissues from normal subjects and those with rheumatoid arthritis (RA) and osteoarthritis (OA).

Immunohistochemical analysis was used to determine the expression of Ang-1, Ang-2, Tie1 and Tie2 in synovial tissue of normal subjects and those with RA and OA. Ang-1, Ang-2, Tie1 and Tie2 mRNA and protein expression were quantified in synovial tissues and RA synovial tissue fibroblasts with real-time reverse transcription polymerase chain reaction and western blot analysis.

In RA, Ang-1 positive immunostaining on lining cells, macrophages and endothelial cells was significantly higher than in OA and normal synovial tissue. The expression pattern of Ang-2 in synovial tissue was similar in RA and OA, whereas the Ang-2 expression was low in normal tissue. Synovial tissue from subjects with RA and OA showed a significant upregulation of Tie1 on lining cells, macrophages and endothelial cells compared to that from normal subjects. Tie2 was significantly upregulated in the RA and OA synovial tissue lining cells, macrophages and smooth muscle cells compared to normal synovial tissue. Generally Ang-1, Ang-2, Tie1 and Tie2 mRNA levels were higher in RA synovial tissue compared to normal and OA synovial tissues, and RA synovial tissue fibroblasts. Western blot analysis also demonstrated greater Tie1 and Tie2 protein expression in RA and OA synovial tissue compared to RA synovial tissue fibroblasts. In conclusion, the dominance of Ang-1 mRNA and protein expression over Ang-2 is in agreement with an active neovascularization in RA synovial tissue.
Differential binding of chemokines to macrophages and neutrophils in the human inflamed synovium
Authors: Patterson Angela M , Schmutz Caroline , Davis Scott , Gardner Lucy , Ashton Brian A , Middleton Jim
Published: September 2002

In chronic inflammatory foci, such as the rheumatoid joint, there is enhanced recruitment of phagocytes from the blood into the tissues. Chemokines are strongly implicated in directing the migration of these cells, although little is known regarding the chemokine receptors that could mediate their chemotaxis into the joint tissue. Therefore the objective of the study was to identify chemokine binding sites on macrophages and neutrophils within the rheumatoid synovium using radiolabeled ligand binding andin situautoradiography. Specific binding sites for CCL3 (macrophage inflammatory protein-1α), CCL5 (RANTES), CCL2 (monocyte chemoattractant protein-1) and CXCL8 (IL-8) were demonstrated on CD68+macrophages in the subintimal and intimal layers. The number and percentage of intimal cells that bound chemokines were greater in inflamed regions compared to noninflamed regions. The intensity of intimal binding varied between chemokines with the rank order, CCL3 > CCL5 > CCL2 > CXCL8. Neutrophils throughout the synovium bound CXCL8 but did not show any signal for binding CCL2, CCL3 or CCL5.

Immunohistochemistry showed that both CXCR1 and CXCR2 are expressed by macrophages and neutrophils in the rheumatoid and nonrheumatoid synovia, suggesting that both of these receptors are responsible for the CXCL8 binding. The chemokine binding sites described on phagocytes may be involved in the migration of these cells into the inflamed joint.
Highly efficient genetic transduction of primary human synoviocytes with concentrated retroviral supernatant
Authors: Yang Jianmin , Friedman Michael S , Bian Huimin , Crofford Leslie J , Roessler Blake , McDonagh Kevin T
Published: September 2002

We are developing retroviral-mediated gene transfer to human fibroblast-like synovial cells (FLS) as one approach to characterizing genetic pathways involved in synoviocyte pathophysiology. Prior work has suggested that FLS are relatively refractory to infection by Moloney murine leukemia virus based vectors. To determine if viral titer influenced the transduction efficiency of FLS, we optimized a rapid, efficient, and inexpensive centrifugation method to concentrate recombinant retroviral supernatant. The technique was evaluated by measurement of the expression of a viral enhanced green fluorescent protein transgene in transduced cells, and by analysis of viral RNA in retroviral supernatant. Concentration (100-fold) was achieved by centrifugation of viral supernatant for four hours, with 100% recovery of viral particles. The transduction of FLS increased from approximately 15% with unconcentrated supernatant, to nearly 50% using concentrated supernatant. This protocol will be useful for investigators with applications that require efficient, stable, high level transgene expression in primary FLS.
Proteinase-3 as the major autoantigen of c-ANCA is strongly expressed in lung tissue of patients with Wegener's granulomatosis
Authors: Brockmann Holger , Schwarting Andreas , Kriegsmann Jörg , Petrow Peter , Gaumann Andreas , Müller Klaus-Michael , Galle Peter Robert , Mayet Werner
Published: September 2002

Proteinase-3 (PR-3) is a neutral serine proteinase present in azurophil granules of human polymorphonuclear leukocytes and serves as the major target antigen of antineutrophil cytoplasmic antibodies with a cytoplasmic staining pattern (c-ANCA) in Wegener's granulomatosis (WG). The WG disease appears as severe vasculitis in different organs (e.g. kidney, nose and lung). Little is known about the expression and distribution of PR-3 in the lung. We found that PR-3 is expressed in normal lung tissue and is upregulated in lung tissue of patients with WG. Interestingly, the parenchymal cells (pneumocytes type I and II) and macrophages, and not the neutrophils, express PR-3 most strongly and may contribute to lung damage in patients with WG via direct interaction with antineutrophil cytoplasmic antobodies (ANCA). These findings suggest that the PR-3 expression in parenchymal cells of lung tissue could be at least one missing link in the etiopathogenesis of pulmonary pathology in ANCA-associated disease.
Production of interleukin-1 receptor antagonist by human articular chondrocytes
Authors: Palmer Gaby , Guerne Pierre-Andre , Mezin Francoise , Maret Michel , Guicheux Jerome , Goldring Mary B , Gabay Cem
Published: September 2002

Interleukin-1 receptor antagonist (IL-1Ra) is a natural IL-1 inhibitor possessing anti-inflammatory properties. IL-1Ra is produced as different isoforms, one secreted (sIL-1Ra) and three intracellular (icIL-1Ra1, icIL-1Ra2 and icIL-1Ra3), derived from the same gene. We examined the production of IL-1Ra species by cultured human articular chondrocytes in response to various cytokines. The levels of IL-1Ra were undetectable in culture supernatants of untreated cells, but were significantly increased by IL-1β. Cell lysates contained very low levels of IL-1Ra, even in response to IL-1β, suggesting that chondrocytes produce predominantly sIL-1Ra. IL-6, which had no effect on its own, enhanced the effect of IL-1β, while dexamethasone prevented the response. We observed by RT-PCR that IL-1β and IL-6 induced primarily the production ofsIL-1RamRNA. Furthermore, IL-1β alone or combined with IL-6 increased the levels of nascent unsplicedsIL-1RamRNA, suggesting that sIL-1Ra expression is regulated at the transcriptional level. Reporter gene assays in immortalized chondrocytes, C-20/A4, consistently showed increasedsIL-1Rapromoter activity in response to IL-1β and IL-6. In conclusion, human articular chondrocytes produce sIL-1Ra in response to IL-1β and IL-6. The production of sIL-1Ra by chondrocytes may have a protective effect against articular inflammatory and catabolic responses.
Systematic review: The relation between nutrition and nosocomial pneumonia: randomized trials in critically ill patients
Authors: Cook Deborah , Jonghe Bernard De , Heyland Daren
Published: September 2002

Objective

To review the effect of enteral nutrition on nosocomial pneumonia in critically ill patients as summarized in randomized clinical trials.

Study identification and selection

Studies were identified through MEDLINE, SCISEARCH, EMBASE, the Cochrane Library, bibliographies of primary and review articles, and personal files. Through duplicate independent review, we selected randomized trials evaluating approaches to nutrition and their relation to nosocomial pneumonia.

Data abstraction

In duplicate, independently, we abstracted key data on the design features, population, intervention and outcomes of the studies.

Results

We identified four trials of enteral vs total parenteral nutrition, one trial of early enteral nutrition vs delayed enteral nutrition, one trial of gastric vs jejunal tube feeding, one trial of intermittent vs continuous enteral feeding, and three trials evaluating different enteral feeding formulae. Sample sizes were small, pneumonia definitions were variable and blinded outcome assessment was infrequent. Randomized trial evidence is insufficient to draw conclusions about the relation between enteral nutrition and nosocomial pneumonia.

Conclusions

Nutritional interventions in critically ill patients appear to have a modest and inconsistent effect on nosocomial pneumonia. This body of evidence neither supports nor refutes the gastropulmonary route of infection.
Geomagnetic field variations in northern Sweden during the Holocene quantified from varved lake sediments and their implications for cosmogenic nuclide production rates
Authors: Snowball Ian , Sandgrena Per
Published: September 2002

Palaeomagnetic analyses were conducted on two varved lake-sediment sequences in northern Sweden. The magnetic properties of the sediment sequences are dominated by stable single-domain magnetite with characteristics typical of bacterial magnetosomes. Alternating field demagnetization measurements indicate that the single-domain magnetite is the dominant carrier of a stable natural remanent magnetization. Temporal variations in inclination and declination were obtained from a total of four cores and the data points were stacked according to their independent calendar-year (varve) ages. Statistically significant patterns in inclination and declination form a regional palaeomagnetic secular variation (PSV) curve, which possesses features that are identical in form to the UK Holocene PSV master curve. However, the calibrated radiocarbon ages of UK features identified prior to 1500 BC are approximately 500 years older than their Swedish varve-dated equiva lents, which points to dating errors and/or drifting of the geomagnetic field. The sediments meet the uniformity criteria proposed for palaeointensity reconstruction and estimates of relative geomagnetic field intensity are calibrated against global dipole-moment compilations. A calculated nuclide production curve is derived from the reconstructed geomagnetic field intensity, which empirically demonstrates the dominant modulation of cosmogenic nuclide production by dipole-moment between 5000 BC and ad 1500.
Interpreting stable-isotope records from freshwater snail-shell carbonate: a Holocene case study from Lake Gölhisar, Turkey
Authors: Jones Matthew D. , Leng Melanie J. , Eastwood Warren J. , Keen David H. , Turney Chris S.M.
Published: September 2002

The oxygen and carbon stable-isotope ratios from fossil snail shells within a small intramontane lake in southwest Turkey are used to highlight the potential, and problems, of using freshwater snail carbonate as a palaeoenvironmental proxy. Two species (Gyraulus piscinarum and Valvata cristata) yielded different isotope ratios at the same sampling intervals, probably due to differences in water-isotope composition between different microhabitats. Isotope ratios from a number of individual shells from the same sampling intervals (representing 7–25 years), show large ranges (up to 8‰ for 18O) for each species. Only by analysis of a significant number of species-specific shells (5) from each sampling interval can a true understanding of environmental change be obtained. Averages of the data provide an insight into longer-term climatic variation while the ranges provide an estimate of short-term (decadal) environmental variability.
The ‘Mediaeval Warm Period’ drought recorded in Lake Huguangyan, tropical South China
Authors: Chu Guoqiang , Liu Jiaqi , Sun Qing , Lu Houyuan , Gu Zhaoyan , Wang Wenyuan , Liu Tungsheng
Published: September 2002

The geochemistry of dated sediment cores from Lake Huguangyan (21°9′N, 110°17′E), tropical South China, reveals distinct stratigraphical patterns in total organic and inorganic carbon (TOC, TIC), biogenic silica (BS) and total nitrogen (TN) over the past 1400 years. In this hydrologically closed lake, TIC variations may re‘ ect changes in the precipitation/evaporation ratio, which controls the evaporative enrichment of carbonate. TOC, BS and TN in the sediment are proxy indicators of lake productivity and nutrient input, which we believe are linked to local precipitation. High TIC content correlates with low concentrations of TOC, BS and TN, and indicates two drought episodes dated to ad 670–760 and ad 880–1260 in the sediments of Lake Huguangyan. Local historical chronicles support these data, suggesting that the climate of tropical South China was dry during the ‘Mediaeval Warm Period’ (MWP) and wet during the ‘Little Ice Age’ (LIA). The detected MWP drought is temporally correlated with evidence for lower precipitation on the Guliya (China) and Quelccaya (Peru) ice caps, and with increased salinity in Moon Lake (US Great Plains).
Vegetation development and introduction of agriculture to Saaremaa Island, Estonia: the human response to shore displacement
Authors: Poska A. , Saarse L.
Published: September 2002

Three pollen profiles from Saaremaa Island (West Estonian Archipelago) record vegetation history from the early Holocene up to the present, and land-use history since the late Mesolithic. A new numerical zonation approach for distinguishing between human and climatic impacts in the pollen record in boreal forest is suggested. Zonation and correlation of the studied profiles suggests four pollen-assemblage zones, regarded as regionally significant. Land uplift, in interaction with a milder climate and easily cultivated soils, facilitated by changing economy, has been the most important factor during the colonization and management of coastal areas. Human impact on Saaremaa Island may be divided into four main phases: (a) Mesolithic and Early Neolithic forest disturbance by hunter-gathering people; (b) forest clearances, pastoral farming and first attempts of cereal cultivation by Neolithic people; (c) more regular cultivation with introduction of slash-and-burn agriculture since the Late Neolithic; (d) permanent field cultivation since the Migration Period/Viking Age.
Palynological evidence for late-Holocene human occupation recorded in two wetlands in SW Turkey
Authors: Vermoere M. , Bottema S. , Vanhecke L. , Waelkens M. , Paulissen E. , Smets E.
Published: September 2002

Pollen diagrams from mountain lakes and marshes in SW Turkey show evidence of intensive anthro pogenic influence in the landscape between 3500 and 1300 BP. Three cores from within the territory of the classical city Sagalassos (Western Taurus, Pisidia) were palynologically analysed to make a reconstruction of the past vegetation in the territory of Sagalassos and to estimate the impact of its inhabitants on the landscape in Pisidia. Two cores originate from an intramontane marsh (Gravgaz; elevation 1215 m) and one from a seasonal intramontane lake (ÇanaklK; elevation 1030 m). Human acitivity is apparent from c. 2530 BP in the pollen diagrams. A deforestation phase/‘disturbance’ phase (from c. 2530 BP/c. 2480 BP till c. 2280 BP/c. 2270 BP), anthropogenically or climatologically driven, precedes a cultivation period (arboricultural phase) (from c. 2280 BP/2270 BP till c. 1480 BP/c. 1270 BP). The results of the pollen analyses of the three cores are compared and show many similarities. There are also similarities with other cores from SW Turkey, although the arboricultural phase (mainly olive cultivation) occurs later in the cores from the Sagalassos territory than in other cores from SW Turkey.
Pinus and Prostomis: a dendrochronological and palaeoentomological study of a mid-Holocene woodland in eastern England
Authors: Boswijk Gretel , Whitehouse Nicki J.
Published: September 2002

Tree-ring analysis of subfossil Pinus sylvestris L. and Quercus sp. and their associated subfossil insect assemblages from tree rot-holes have been used to study a prehistoric forest buried in the basal peats at Tyrham Hall Quarry, Hatfield Moors SSSI, in the Humberhead Levels, eastern England. The site provided a rare opportunity to examine the date, composition, age structure and entomological biodiversity of a mid-Holocene Pinus-dominated forest. The combined approaches of dendrochronology and palaeoentomology have enabled a detailed picture of the forest to be reconstructed, within a precise time-frame. The Pinus chronology has been precisely dated to 2921–2445 bc against the English Quercus master curve and represents the first English Pinus chronology to be dendrochronologically dated. A suite of important xylophilous (wood-loving) beetles that are today very rare and four species that no longer live within the British Isles were also recovered, their disappearance associated with the decline in woodland habitats as well as possible climatic change. The subfossil insects indicate that the characteristic species of the site's modern-day fauna were already in place 4000 years ago. These findings have important implications in terms of maintaining long-term invertebrate biodiversity of forest and mire sites.
A 2100-year trace-element and stable-isotope record at decadal resolution from Rice Lake in the Northern Great Plains, USA
Authors: Yu Zicheng , Ito Emi , Engstrom Daniel R. , Fritz Sherilyn C.
Published: September 2002

A 2100-year multiple proxy record at decadal resolution from a topographically closed (but hydrolog ically open) lake basin was used to reconstruct changes in lake salinity and evaporative intensity and to evaluate the reliability of different proxies for inferring climatic change in the glaciated Northern Great Plains (NGP). At Rice Lake, North Dakota, the ostracode-Mg/Ca ratios show good correlation with other ostracode, diatom and aeolian proxy records from other sites in the NGP. All of these records show significant century-scale periodicities, which have been related to solar variability as inferred from atmospheric radiocarbon records. This coherent and consistent pattern suggests that these sites record climatic variability at regional scales. The interval of the Mediaeval Climatic Anomaly from|900 to 550 cal. yr BP contains two pronounced dry periods. During the following ‘Little Ice Age’, a single period of frequent drought that peaked at|300 cal. yr BP was bracketed by wet periods before and after. In contrast, the ostracode-Sr/Ca ratios and ostracode- and mollusc-180 records from Rice Lake have different patterns and do not correlate well with each other or with the same proxies at other sites. This lack of consistent pattern within a site and among several regional sites suggests seasonal and/or site-specific in‘ uences on these proxies. Variable contributions of groundwater, with low 18O values because of selective recharge from snowmelt, may have played an important role in determin ing the isotopic composition of the lake. The poor correlation of Sr/Ca with other proxies is caused by mediation of inorganic carbonate mineralogy, owing to active uptake of Sr in the formation of inorganic aragonite. Thus, our sediment data along with present-day lakewater chemistry suggest that carbonate-180 records in the NGP cannot be interpreted simply in terms of climate because of significant local groundwater in‘ uences. Ostracode-Mg/Ca ratios tend to be a better indicator of past salinity because of the conservative nature of Mg in oligo-saline waters (10‰ salinity).
Holocene history of the Wilson Piedmont Glacier along the southern Scott Coast, Antarctica
Authors: Hall Brenda L. , Denton George H.
Published: September 2002

Geometric and cross-cutting relationships between the Wilson Piedmont Glacier and raised beach ridges indicate that the glacier margin has undergone Holocene ‘ uctuations. During mid-Holocene time, the Wilson Piedmont Glacier retreated to a position less extensive than at present. A subsequent readvance culmi nated less than 250 years ago. Since ad 1956, the glacier and adjacent large snow ramps have retreated up to 600 m in some locations. Large snowbanks have also disappeared. Although the cross-cutting relationships and chronology indicate a late-Holocene advance at approximately the same time as the ‘Little Ice Age’ event, the magnitude and style of that advance differ from those of the classic ‘Little Ice Age’ glacier ‘ uctuations in the Northern Hemisphere.
Estimating cerebral atrophy in multiple sclerosis patients from various MR pulse sequences
Authors: Leigh R , Ostuni J , Pham D , Goldszal A , Lewis B K , Howard T , Richert N , McFarland H , Frank J A
Published: September 2002

Purpose: The purpose of this study was to determine how measures reflecting cerebral atrophy (CA) are influenced by pulse sequence (PS) and segmentation algorithm (SA) used in multiple sclerosis (MS) patients and healthy control (HC)s. Methods: Magnetic resonance imaging (MRI) scans from 10 relapsing-remitting MS (RRMS) patients and five HCs were used to determine the change in brain fractional volume (BFV) over a two-year period. T1-weighted, fluid-attenuated inversion recovery (FLAIR), and proton density (PD)/T2-weighted sequences were analysed. Image segmentation to determine brain volume was performed using the following: a histogram SA, an adaptive fuzzy c-means algorithm (AFCM), and an adaptive Bayesian segmentation with a K-means clustering. Results: Combinations of the SA and PS in MS patients demonstrated significant differences in the per cent change in BFV from baseline. For the combination of PS and SA the per cent change in BFV for year one and year two varied from +2.05% to −1.6% and +0.79% to −3.11%, respectively. Analysis of the HCs data revealed fluctuations in BFV varying from +0.26% to −0.29%. Conclusions: MRI estimates of CA are dependent on both the type of PS and SA; therefore, the choice of SA technique and PS should be consistent during an MS treatment trial. The progression of CA in MS should only be used as a secondary or tertiary outcome measure in treatment trials until a better understanding of how this measurement is affected by the disease, the image acquisition and analysis techniques.
Technical note: the comparison of hypointense lesions from ‘pseudo-T1’ and T1-weighted images in secondary progressive multiple sclerosis
Authors: Hickman S J , Barker G J , Molyneux P D , Miller D H
Published: September 2002

There is a large historical database of dual-echo conventional spin-echo (CSE) magnetic resonance images in multiple sclerosis (MS). If new analysis techniques can be developed then this database could provide valuable information. We have investigated a technique in which the late echo of a dual-echo data set is subtracted from the corresponding early echoyielding images, which appear qualitatively similar to T1- weighted images. This study investigated whether the hypointense lesions on the ‘pseudo-T1’ images (created as described above) were related to hypointense lesions on conventional T1-weighted images. The hypointense lesion areas were measured by a blinded observer using a computer-assisted contouring technique applied to pseudo-T1 and T1-weighted CSE images obtained from 17 patients with secondary progressive MS (SPMS). The mean hypointense lesion area from T1-weighted images was 2218- 2072 mm2, compared to 1426-1353 mm2 from pseudo-T1 images (p =0.008). There was, however, a strong correlation between the values obtained from the two sets of images (r =0.93, p <0.001). The strong correlation between the values obtained from the two sets of images suggests that pseudo-T1 images may be useful to investigate a subgroup of more destructive lesions in MS from historical databases and in future prospective studies when imaging time is limited.
Predictors of short-term disease activity following a first clinical demyelinating event: analysis of the CHAMPS placebo groupy
Authors:   CHAMPS Study Group
Published: September 2002

We evaluated 190 patients in the placebo group of the CHAMPS trial in order to assess factors associated with short-term clinical and brain magnetic resonance imaging (MRI) outcomes in patients with a first clinical demyelinating event involving the optic nerve, spinal cord, or brainstem/cerebellum, and subclinical demyelination on brain MRI. The two study outcomes were 1) development of clinically definite multiple sclerosis (CDMS) and 2) development of CDMS or two or more new or enlarging brain MRI T2 lesions. The presence of gadolinium (Gd)- enhancing lesions on the baseline scan was the only MRI characteristic associated with a higher risk of both the clinical and combined outcomes (p=0.003 and <0.001, respectively). The only demographic or clinical characteristic associated with an increased risk of these outcomes was younger age (p<0.001 for both outcomes). The lowest risk subgroups we could define had a 30% risk of CDMS and a 65% risk of the combined clinical/MRI outcome. Our results indicate that all patients presenting with a first demyelinating event who also have brain MRI evidence of subclinical demyelination have at least a moderate risk of short-term disease activity. This finding provides support for initiating disease-modifying therapy at the time of the first demyelinating event in patients meeting the CHAMPS enrollment criteria.