bluuebunny/crossref_metadata_2025 huggingface dataset:
Dogs, detectives and the famous Sherlock Holmes
Authors: Mason Emma
Published: September 2008

A B S T R A C T • The celebrity of Sherlock Holmes is almost universally signified through the iconic silhouetted image of a deerstalker hat and smoking pipe, one that secures his fame as a popular detective from the Victorian period to our own. Despite his aloof and sometimes prickly behaviour on the page, Holmes remains a favourite with a diverse group of audiences, instantly likeable to his contemporary readers. This article will connect the fond regard in which Holmes' character was held in the nineteenth century to the detective's relationship with dogs. Using Donna Haraway's recent theorization of dogs as 'companion species' in her manifesto on otherness, the article will suggest that the Victorians regarded Holmes' sleuthing fame as inseparable from his respect for animal otherness, one with which he is identified throughout Conan Doyle's stories. In this respect, I argue, Holmes is a hudographical detective, his crime-solving powers rooted in his relationship with and to dogs. •
From people power to mass hysteria
Authors: Thomas James
Published: September 2008

with revisions by Elizabeth Barry

A B S T R A C T • This article looks at the phenomenon of mass mourning, its manipulation in the media, and its significance in terms of consensus-building and national politics. Did deaths such as Princess Diana's and the unprecedented outpouring of public grief that followed it signal a national 'togetherness' and communal spirit? Or was this apparent national spirit a product of the press, at the cost of a disturbing suppression of dissent? This article asks what recent, highly publicized celebrity deaths and the press reaction to them tell us about the state of our media, their preoccupations and the celebrity culture that they help to create. •
Dynamics of the `field': multiple standpoints, narrative and shifting positionality in multisited research
Authors: Soni-Sinha Urvashi
Published: September 2008

The article contributes to the epistemological debates in feminism through the analysis of multisited research on jewellery production in India. The multisited research focuses on different localities — Noida Export Processing Zone (NEPZ), Delhi and villages of Medinipur having direct and indirect links to the global market. It analyses how the multiple sites structured by gender, class and age hierarchies reveal the multiple and fluid standpoints of different actors. The multiple standpoints of different actors feed into discursive practices of a complete exclusion of women from the production process of handmade jewellery in NEPZ, their marginal presence in Delhi, and their invisibility despite preponderance in the villages of Medinipur. These narratives constitute the subjectivity of men as `breadwinners' and of women as `housewives'. However, some women contest the discourses around marginalization of their work and present points of break in the configuration of power, questioning their subject position as `housewives'. Weaving these complex webs of narratives, I am reflexive of my multiple positionality as Indian, non-Bengali, elite, woman and the fluidity of my position as an insider/outsider in the `field'.
Hand hygiene: “Simple, inexpensive and an effective tool”
Authors: Bhojani S. , D'Costa S. , Gupta A.
Published: September 2008

Hospital acquired infection severely affects patients, prolongs hospital stays and presents a major challenge for quality of patients' care (Emmerson et al, 1996; Hand washing Liaison Group, 1999). Improvement in hand hygiene can help in reduction of hospital acquired infection (Hand washing Liaison Group, 1999; Kilpatrick et al, 2007; Whitby et al, 2007; Duerink et al, 2006; Sohn et al, 2005; Jumaa 2005; Randle et al, 2006). Three observational audits were carried out to ascertain existing hand hygiene practice. In the first audit, prescribed standards were achieved in only 29% of cases. After appropriate educational interventions, a repeat study after three months showed significant improvement in up to 84% of cases. The final audit, eight months after the second study, showed that although consultants and registrars had maintained high standards (90%), senior house officers' (SHOs) practice deteriorated (46%). Although both SHOs and registrars changed during this period, only SHO performance deteriorated. Possible reasons may be either that SHOs need more education, or that because they have a busier workload, omission is more common among them, but, this requires more exploration.

Conclusion: Hand hygiene is a simple but important practice. Repeat audits plus education appears to drive up standards.

Recommendations: To achieve desirable and sustained behaviour change, there is a need to present information on hand hygiene to all doctors at regular intervals. Regular but random covert surveillance observation of practice with a professionals' prior consent appeared to assist in improving practice in this study.
Environmental reservoirs of meticillin resistant Staphylococcus aureus in patients' rooms: Potential impact on care practices
Authors: Talon D. , Excoffon L. , Tiv M. , Pinçon AL , Gbaguidi-Haoré H. , Bertrand X.
Published: September 2008

To investigate the environmental contamination of rooms of patients colonised with meticillin resistant Staphylococcus aureus (MRSA), we conducted a prospective study during a five month period in a French university hospital. Environmental samples were taken once per week for each MRSA included patient, until the patient was discharged. The surfaces swabbed were the covers, the lifting pole, the bed bars, the table and the trolley. A 500-litre air sample was collected with an impactor air sampler, and a Petri dish was left open in the room for two hours. The aims of the study were to assess the impact of nasal decolonisation and dressing changes on the day of sampling on environmental contamination of the room. Thirty patients were included in this study. In total, 37.5% of the rooms tested positive: surface samples were positive in 11.8% of cases (39/320), and air samples were positive in 17.9% of cases (23/128). Much higher levels of contamination were observed on days on which dressings were changed, in the absence of nasal decolonisation with mupirocin. This study shows that the environment is often contaminated in the rooms of patients with MRSA. Our results are consistent with the findings of other studies suggesting that the environment may play an important role in the persistence of hospital epidemics, and that this contamination should be taken into account in the organisation and delivery of care and in evaluations of preventive measures.
Bridging the Gap — the Co-creation of a Therapeutic Process
Authors: Neander Kerstin , Skott Carola
Published: September 2008

The aim of this study was to explore parents' and therapists' experiences of treatment processes in early childhood interventions. The parents and their therapists reflected on their experiences in joint interviews. The interpretation led to the crystallization of five central themes. The starting point was marked by 'parents' fear versus professional(s') confidence'. This formed the background against which both parties aimed at 'making sense of the situation'. The subsequent therapeutic process was characterized by the parents' and the professionals' 'striving for reciprocal responsiveness' and it led to the 'alteration of inner images'. Finally the two parties made a 'retrospective reflection on the nature of the relation'. Together these themes constitute the co-creation of a therapeutic process by bridging a gap that is created by fear, by power differentials and by differences in familiarity with the context. The parents shoulder responsibility for creating a cooperative relationship, and this is facilitated if they meet a 'normal, friendly and knowledgeable therapist who is capable of admitting that he/she may be wrong'.
Promoting and Managing Innovation
Authors: Baldwin Mark
Published: September 2008

This article describes and analyses a piece of participative action research in which the author, working with three projects in a UK children's voluntary organization, inquired into the nature and management of innovation. The research enabled those involved to reflect upon innovation as an incremental process of service and practice development. We learnt that, for it to be effective, such a process requires opportunities for critical reflection by practitioners, working collaboratively within an organizational framework where individual and organizational learning is valued and facilitated. The concept of the learning organization has proved a useful tool in evaluating and critically analysing this research work.
Evidence of Increased Motoneuron Excitability in Stroke Patients Without Clinical Spasticity
Authors: Udby Blicher Jakob , Nielsen Jørgen Feldbæk
Published: September 2008

Introduction. The contribution of hyperreflexia to impairment after stroke is debated. Spinal motoneuron excitability in healthy subjects and stroke patients with and without spasticity was compared. Methods. Twenty-four patients with single stroke more than 6 months ago and 18 gender-matched healthy volunteers were included. Spasticity was assessed according to the Modified Ashworth Scale. Mmax amplitude and F wave frequency in the abductor pollicis brevis muscle were measured by electrical stimulation of the median nerve. Results . Mmax values were comparable between the groups. However, patients with (n = 7) and without (n = 17) clinically evident spasticity had a significant increase in F wave frequency when compared with healthy subjects. F wave frequency did not differ between spastic and nonspastic patients. Discussion. Increase in spinal motoneuron excitability after stroke is present in stroke patients with minor or no motor deficiencies and does not necessarily lead to spasticity.
A Prescription to Advance Men's Health
Authors: Beals Amber
Published: September 2008

Pharmacists are in a unique position to have a positive effect on men's health in areas such as health care use, smoking cessation, and appropriate use of over-the-counter medications and nutraceuticals. Perhaps pharmacists' greatest opportunity to affect men's health is in the area of medication adherence. This article discusses specific ways that pharmacists can find a niche to help improve the overall health of American men as part of the interdisciplinary health care team.
Low oxidation potential shielding gas instability in GMA welding
Authors: Costa M. C. M. S. , Starling C. M. D. , Modenesi P. J.
Published: September 2008

Gas metal arc (GMA) welding is one of the most important processes for joining metals. However, this process is characterised by a relatively large number of variables and high sensitivity to changes in operational conditions. Furthermore, GMA welding stability can be degraded by several factors. Although some of these instability problems have been studied extensively a few of them, particularly those linked to the arc transition regions, are still poorly known and studied. The present paper studies a strong process instability characterised by repulsive metal transfer, large variations in welding current and voltage, and the formation of large quantity of spatter. It was observed previously in the welding of low carbon steel with gas shielding of low oxidation potential, and was linked to alterations in electron emission mechanisms on the cathode surface. Welding current and voltage oscillograms, arc light intensity measurements, and high speed filming were used in this study. It was shown that this instability can also occur in the welding of austenitic stainless steels. Indications of its occurrence were also observed in Al. Changes in metal transfer, arc light intensity and welding current and voltage occur simultaneously during the instability. Unstable operation was also characterised by alterations in arc position and shape and by the lack of removal of the oxide layer on the base metal surface. The onset of instability was linked to the occurrence of a rapid short circuit between the electrode and the weld pool.
Crystallography of Widmanstätten austenite in duplex stainless steel weld metal
Authors: Menezes Abtibol J. W. , Abreu H. , Kundu S. , Bhadeshia H. K. D. H. , Kelly P. M.
Published: September 2008

Two kinds of austenite grow from δ-ferrite during the cooling of the duplex stainless steel weld deposits studied here, Widmanstätten plates and allotriomorphs which precipitate at δ– δ grain boundaries. It is found using microtexture measurements that the preferred crystallographic orientation of the Widmanstätten austenite can be estimated using established theory if it is assumed that there is an interaction between external stress and the growing plates. It is also demonstrated that the Widmanstätten and allotriomorphic forms of austenite may not be identically oriented even when the former appears to originate from the latter; this may be a consequence of differences in the transformation mechanisms of these two forms of austenite.
Hydrothermal preparation of nanocarbonated hydroxyapatite crystallites
Authors: Xiao X.-F. , Liu R.-F. , Gao Y.-J.
Published: September 2008

Needle-like nanocarbonated hydroxyapatite (CHA) powders were prepared by hydrothermal method using Ca(NO3)2, (NH4)3PO4 and urea as reagents. Element analyse (EMA), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM) and thermogravimetry differential thermogravimetry (TG-DTA) were used to characterise the crystalline phase, microstructure, chemical composition, morphology and thermal stability of CHA. The results show that AB type CHA can be obtained through this method. The carbonate content and the ratio of length to diameter of CHA can be adjusted by controlling the concentration of urea. The results show that CO32−incorporated into the apatite structure has an influence on the properties of CHA, such as the morphology and the size of crystal grain, the lattice parameters and the unit cell volume and the crystallisation degree and the stability.
Bonding of single crystal silicon to Cu and AlN: Trial results
Authors: Connolley T. , Hanks S. , Drakopoulos M. , Hill T.
Published: September 2008

Tests were performed to assess the feasibility of bonding single crystal silicon to copper and aluminium nitride. The application of the bonded component is in a cryocooled monochromator for synchrotron X-ray optics. Aluminium, gold and indium–silver interlayers were tried. Some bonded components were tested by immersion in liquid nitrogen to simulate cooling of the component in service. Although bonds could be formed, they were of insufficient integrity for use in a challenging cryogenic application.
Novel method for quantitative assessment of slag detachability in austenitic stainless steels welds made by SMAW
Authors: Nagaraju S. , Rajadurai A. , Vasudevan M. , Menaka M. , Subbaratnam R.
Published: September 2008

It is essential and important that slag which protects the molten metal from atmospheric contamination during shielded metal arc welding (SMAW) process gets removed as the weld metal gets solidified. During multipass welding in particular it is desirable that slag gets removed easily and totally before the next pass of welding. Otherwise it would lead to slag inclusions in the weld. Hence, the ease with which the slag gets detached from the weld termed as slag detachability is a vital parameter in deciding the weld quality. Till date, slag detachability has been assessed on qualitative terms only. Hence, it is necessary to develop test procedures and methodology for assessing the slag detachability in quantitative terms. In this work, the authors propose a novel slag detachability testing technique called slag detachability tester and a methodology for quantitative assessment of slag detachability. The test procedure and the methodology have been tested first on austenitic stainless steels. The slag on the weldment was removed by dropping varieties of hammers with different end shapes from a standard height with a custom designed drop weight tester. After the test, the adherent slag on the weldment was inspected and measured using infrared (IR) thermography. The acquired IR images were suitably processed using image processing software to identify the area of slag particles sticking on the weld. Testing parameters were standardised and using these data, an expression is proposed for assessing the slag detachability in quantitative terms.
CD47 on experimentally senescent murine RBCs inhibits phagocytosis following Fcγ receptor–mediated but not scavenger receptor–mediated recognition by macrophages
Authors: Olsson Mattias , Oldenborg Per-Arne
Published: September 2008

CD47 functions as a marker of self on red blood cells (RBCs) by binding to signal regulatory protein alpha on macrophages, preventing phagocytosis of autologous RBCs by splenic red pulp macrophages, and Fcγ receptor (FcγR)– or complement receptor–mediated phagocytosis by macrophages in general. RBC senescence involves a series of biochemical changes to plasma membrane proteins or lipids, which may regulate phagocytosis by macrophages. Here, we investigated whether CD47 on experimentally senescent murine RBCs affects their phagocytosis by macrophages in vitro. Clustering of CD47 with antibodies was more pronounced in the plasma membrane of untreated RBCs, compared with that in in vitro oxidized RBCs (Ox-RBCs). Phagocytosis of Ox-RBCs was mediated by scavenger receptors (SRs) distinct from SR-A or CD36 and required serum factors. We found that wild-type (WT) and CD47−/− Ox-RBCs were phagocytosed equally well by macrophages in the presence of serum, suggesting that phagocytosis via SRs is not inhibited by CD47. Despite this, FcγR-mediated phagocytosis of IgG-opsonized Ox-RBCs was strongly inhibited by CD47. These data suggest that based on the specific prophagocytic receptors mediating uptake of senescent RBCs, the phagocytosis-inhibitory role of CD47 may be more or less involved.
Wnt-inducible protein (WISP-1) is a key regulator of alveolar epithelial cell hyperplasia in pulmonary fibrosis
Authors: Königshoff Melanie , Wilhelm Jochen , Jahn Andreas , Amarie Oana , Kitowska Kamila , Wilhelm Anke , Bohle RainerM. , Seeger Werner , Rose Frank , Fink Ludger , Guenther Andreas , Eickelberg Oliver
Published: September 2008

Fibrotic lung disease is characterized by distorted lung architecture and severe loss of respiratory function secondary to alveolar epithelial cell (AEC) hyperplasia, enhanced extracellular matrix (ECM) deposition and fibroblast proliferation. Repetitive epithelial injuries with impaired alveolar wound healing and altered AEC gene expression represent a trigger mechanism for development of fibrosis. To reveal gene regulatory networks in lung fibrosis, we compared gene expression profiles of freshly isolated AEC obtained from mice 14 days after saline or bleomycin (BM) instillation using whole genome microarray analysis. Several genes of the Wnt signaling pathway, in particular WISP-1, a member of the CCN family, were highly regulated. WISP-1 protein expression was demonstrated in proliferating AEC in BM-treated lungs by immunofluorescence. When analyzing all six CCN family members, WISP-1 was upregulated the most 14 days after BM challenge, as analyzed by qRT-PCR. To elucidate WISP-1 function, cultured primary mouse AEC were stimulated with WISP-1 and demonstrated a 230% increase in proliferation, analyzed by 3H-thymidine incorporation. This was mediated through enhanced phosphorylation, but not expression of protein kinase B (PKB/Akt), as detected by immunoblot. Finally, increased expression of WISP-1 was detected in lung homogenates and isolated AEC from IPF patients, using qRT-PCR. Immunohistochemical analysis of WISP-1 and Ki67 verified the existence of hyperplastic and proliferative AEC expressing WISP-1in vivo. Our study thus identifies WISP-1 as a novel regulator of AEC injury and repair, and suggests that WISP-1 is a key mediator in pulmonary fibrosis.
The adult incidence of asthma and respiratory symptoms by passive smokingin uteroor in childhood
Authors: Duelien T. , Eagan T. M. L. , Eide G. E. , Gulsvik A. , Bakke P. S.
Published: September 2008

The effects of pre- or postnatal passive smoking on the adult incidence of asthma have not been reported previously.

Between 1985 and 1996/1997, we conducted an 11-year community cohort study on the incidence of asthma and respiratory symptoms in Western Norway. The cohort included 3,786 subjects aged 15 to 70 years, of which 2,819 were responders at both baseline and follow-up. The incidence of asthma and five respiratory symptoms by self-reported exposure to maternal smoking in utero and in childhood, as well as smoking by other household members in childhood, was examined.

After adjustment for sex, age, education, hay fever, personal smoking, and occupational exposure, maternal smoking was associated with asthma, phlegm cough, chronic cough, dyspnoea grade 2, attacks of dyspnoea, and wheezing, with odds ratios (95% confidence intervals [CI]) of 3.0 (1.6, 5.6), 1.7 (1.1, 2.6), 1.9 (1.2, 3.0), 1.9 (1.2, 3.0), 2.0 (1.3, 3.0), and 1.4 (0.9, 2.2), respectively. The adjusted attributable fractions (95% CI) of the adult incidence of asthma were 17.3% (5.2, 27.9) caused by maternal smoking and 9.3% (23.2, 33.2) caused by smoking by other household members.

Exposure to pre- and postnatal smoking carries a substantial risk for developing adult asthma and respiratory symptoms.
Does creatine supplementation enhance the effects of physical training during pulmonary rehabilitation in COPD?
Authors: Deacon SarahJ. , Vincent EmmaE. , Singh SallyJ. , Steiner MichaelC. , Greenhaff Paul , Morgan MichaelD.
Published: September 2008

We conducted a randomised, placebo-controlled trial to examine whether creatine supplementation augments the benefits of pulmonary rehabilitation (PR), containing aerobic exercise and resistance training (RT).

80 subjects with COPD (GOLD stages I–IV) [mean (SD) age 68 (7.8) yrs, FEV144.1 (20.3) % predicted] completed 21 sessions of PR, with enhanced RT, following baseline measurements and randomisation to take creatine (Cr) or placebo (Pl) supplement. A subgroup had muscle biopsies.

Groups were well matched at baseline except for gender (M:F Cr 19:19, Pl 31:11, Chi2p = 0.03). Mean change in functional performance & muscle strength after PR are shown. Health status (CRQ-SR) improved significantly after PR but did not differ between groups. Muscle biopsies showed evidence of creatine uptake.

This adequately powered study showed significant improvements in all outcomes following PR. Creatine supplementation did not enhance these benefits.
The promoter polymorphism -1562C/T in matrix metalloproteinase-9 and COPD severity
Authors: Yanbaeva D. G. , Korytina G. F. , Akhmadishina L. Z. , Zagidullin S. Z. , Victorova T. V.
Published: September 2008

Chronic obstructive pulmonary disease (COPD) is a complex heterogeneous respiratory disease. COPD is characterized by a progressive irreversible airflow limitation that is due to a loss of lung elasticity resulting from peripheral airflow obstruction (chronic bronchitis) and parenchymal destruction (emphysema). Matrix metalloproteinases (MMP) are a major group of proteases known to regulate extracellular matrix turnover. They have been suggested to be important in the process of lung diseases associated with tissue remodeling. Polymorphisms in MMPs which known to upregulate their activity may result in the degradation of a lung matrix.

A case-control study was performed to investigate the association of polymorphisms ofMMPtype1(-1607G/GG), 9(-1562C/T) and12(-82A/G) genes with COPD and disease severity. A total of 309 COPD patients admitted to departments of respiratory medicine have been recruited in Ufa city hospitals (## 13, 21, and 22). COPD patients have been undergone a spirometry and a physical examination by a chest physician to refer the GOLD II-IV stages. The control group comprised of 305 healthy subjects without evidence of chronic diseases (Table Basic characteristic of study groups).
Endothelin: setting the scene in PAH
Authors: Dupuis J.
Published: September 2008

Endothelin (ET), a 21-amino acid peptide secreted by the vascular endothelial cells, is frequently reported to be one of the most potent vasoconstrictors. ET induces endothelial cell, smooth muscle cell and fibroblast dysfunction and is now well recognised as a contributor to the complex pathogenesis of pulmonary arterial hypertension, a devastating chronic disease characterised by progressive vascular remodelling and occlusion of the pulmonary arterioles.

ET produces its effects through the stimulation of two receptor subtypes, ETAand ETB, both of which are expressed on smooth muscle cells of pulmonary arterioles. Only the ETBreceptor is expressed on vascular endothelial cells. In pre-clinical studies, dual blockade of both receptor subtypes was shown to produce greater inhibition of ET-induced contraction compared with blockade of either of the two receptor subtypes alone. There is also evidence that both the ETAand ETBreceptors contribute to pulmonary artery smooth muscle cell proliferation. Pre-clinical research in various models of pulmonary arterial hypertension suggests that simultaneous blockade of the two receptor subtypes would be an effective therapeutic approach in the management of patients with pulmonary arterial hypertension. This has been shown to be the case in a number of randomised controlled clinical trials in pulmonary arterial hypertension due to a number of aetiologies.
Optimising the duration of antibiotic therapy for ventilator-associated pneumonia
Authors: Chastre J. , Luyt C. E.
Published: September 2008

Ventilator-associated pneumonia (VAP) has traditionally been treated with a 14–21-day course of antibiotics. However, prolonged antibiotic therapy is associated with the emergence of multidrug-resistant strains, as well as higher toxicity and costs.

In a large, randomised, controlled trial in patients with microbiologically confirmed VAP who received appropriate empirical antibiotic therapy, an 8-day antibiotic regimen was not associated with excess mortality or more episodes of recurrent pulmonary infection compared with a 15-day regimen.

Amongst patients who developed recurrent infection, multidrug-resistant pathogens emerged less frequently in the group receiving 8 days of antibiotic therapy. The 8-day regimen was also not associated with excess mortality in the subgroup with VAP caused by nonfermentative Gram-negative bacilli, mostlyPseudomonas aeruginosa, although recurrent infections occurred more often.

Pending confirmatory studies, an 8-day course of antibiotic therapy may be appropriate for many patients with ventilator-associated pneumonia, providing that initial antibiotic therapy is appropriate, the clinical course is favourable and extreme vigilance is maintained after stopping antibiotics. Patients whose initial treatment regimen was inappropriate, those infected with difficult-to-treat pathogens such asPseudomonas aeruginosa, and immunocompromised patients and others at high risk for relapse are likely to require a longer duration of antibiotic therapy.
Combinationversusmonotherapy for nosocomial pneumonia
Authors: Lode H.
Published: September 2008

Combination antibiotic therapy of nosocomial pneumonia is sometimes appropriate and desirable; however, it should be used judiciously. When pneumonia appears in the first 5 days following hospital admission and in the absence of other risk factors for infection by multidrug-resistant pathogens, the infection is likely to be due to a pathogen acquired in the community and is likely to be sensitive to most antibiotics.

These infections should generally be treated with monotherapy. However, pathogens resistant to multiple drugs are increasingly common in the hospital and intensive care unit setting. In the presence of risk factors for such pathogens, any single drug may prove ineffective; treatment with two or more drugs theoretically increases the likelihood that the pathogen will be sensitive to at least one of them. However, combination therapy also increases the cost and the likelihood of adverse effects, as well as the possibility of drug interactions, if the two are not chosen wisely.

The crucial question is whether combination antibiotic therapy actually improves clinical outcome. Most clinical trials suggest that monotherapy and combination therapy provide equivalent efficacy. However, these studies have uniformly excluded the most seriously ill patients: those with Acute Physiology and Chronic Evaluation-II scores >20.

It is concluded that available studies provide no concrete evidence to support the use of combination therapy in moderately ill patients and provide no data for the treatment of seriously ill patients who might be most likely to benefit.
Future options for disease intervention: important advances in phosphodiesterase 4 inhibitors
Authors: McIvor R. A.
Published: September 2008

Current drug treatments for chronic obstructive pulmonary disease (COPD) focus on managing symptoms of the disease and include short- and long-acting β2-agonists, anticholinergic agents (ipratroprium, tiotropium), methylxanthines (theophylline) and inhaled corticosteroids (ICS).

Cyclic nucleotide phosphodiesterases (PDEs) play a key role in cell signalling by degrading cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate. PDE4 is expressed in inflammatory cells and inhibition of this enzyme enhances the anti-inflammatory effects of cAMP in all key cells involved in COPD. Two PDE4 inhibitors, roflumilast and cilomilast, have been extensively evaluated in patients with COPD. Results from patients with moderate-to-severe and severe-to-very severe COPD have shown that roflumilast significantly improves forced expiratory volume in one second (FEV1) and significantly decreases exacerbations, particularly in patients with severe disease. Roflumilast is well tolerated with a low incidence of gastrointestinal adverse events that declines with continued treatment. Clinical trials with cilomilast have produced more varied results. Significant improvements in FEV1and reductions in exacerbation ratesversusplacebo were observed in two of four trials. Cilomilast also has a high risk for gastrointestinal adverse events that does not appear to dissipate over 24 weeks of treatment.

While further research is needed to fully determine the place in chronic obstructive pulmonary disease therapy for phosphodiesterase 4 inhibitors, they have several important potential benefits in the treatment of this disease, including convenient once-daily oral administration and freedom from adverse effects associated with corticosteroids. The fact that phosphodiesterase 4 inhibitors have potent anti-inflammatory effects and are administered orally, thereby reaching the systemic circulation, may decrease the severity of systemic comorbidities in chronic obstructive pulmonary disease patients.
Treatment of obstructive sleep-disordered breathing with positive airway pressure systems
Authors: Pevernagie D. , Masa J. F. , Meurice J. C. , Farré R. , Marrone O. , Rodenstein D.
Published: September 2008

Positive airway pressure systems are widely used to treat patients with moderate-to-severe obstructive sleep-disordered breathing. The application of stable continuous positive airway pressure (CPAP)viathe nose (nasal CPAP) has been the mainstay of treatment since the early 1980s. For treatment to be effective, the pressure level must be fine-tuned to restore patency of the individual patient's upper airway.

Currently, there is ongoing controversy concerning which outcomes to observe when adapting the pressure level, and which methods to use for pressure adaptation. Adjusting the pressure level to control apnoeas and hypopnoeas is one major objective, but may not be sufficient to restore normal sleep. Evidence is available that elimination of inspiratory flow limitation leads to better results.

In recent years, it has become evident that the use of empirically set CPAP or automatic CPAP devices parallel the clinical results obtained with the classical approach of manual CPAP titration. A striking and still unexplained paradox lies in the fact that automatic CPAP devices perform very differently on the bench, but still yield satisfactory results on several clinical outcomes,e.g.control of sleep-related respiratory disturbances, restoration of good sleep quality and daytime alertness. Understanding the functioning of automatic CPAP devices can prove difficult, as the mode of operation is usually not disclosed by the manufacturers.

At present, it is impossible to make any scientifically sound statement on the appropriateness of using automatic continuous positive airway pressure devices for the routine treatment of patients with obstructive sleep-disordered breathing. For this purpose, convincing results of phase I–III clinical trials are needed.
Omalizumab: an anti-immunoglobulin E antibody for the treatment of allergic respiratory diseases
Authors: Bousquet J. , Wahn U. , Meltzer E. O. , Fox H. , Hedgecock S. , Thomas K. , Fowler-Taylor A.
Published: September 2008

Immunoglobulin E (IgE) is central to the development of allergic diseases. Cross-linking of cell-bound IgE by the allergen leads to the initiation of the inflammatory cascade. Omalizumab, an anti-IgE antibody, forms complexes with free IgE, thereby inhibiting the allergic reaction before its commencement.

A survey of the clinical trials performed on omalizumab indicated that this anti-IgE antibody is efficacious and well tolerated in the treatment of separate and concomitant asthma and rhinitis. In patients with poorly controlled asthma, omalizumab reduced the asthma exacerbation and emergency visit rate, along with improving the quality of life. The improvement in asthma control was associated with a reduction of inhaled and oral corticosteroids. Improved nasal symptom scores and a reduced need for antihistamines were observed in patients with allergic rhinitis. Omalizumab was also proven to be effective as an add-on therapy for concomitant asthma and rhinitis.

In conclusion, omalizumab provides an integrated approach for the treatment and management of allergic respiratory diseases.
Viral infection drives tissue fibrosisin vitro
Authors: Malizia Andrea P. , Walls Dermot , Egan Jim J. , Doran Peter P.
Published: September 2008

Idiopathic Pulmonary Fibrosis (IPF) is a refractory and lethal interstitial lung disease characterized by loss of alveolar epithelial cells, fibroblast proliferation and extra-cellular matrix protein deposition. EBV, localised to alveolar epithelial cells of pulmonary fibrosis patients is associated with a poor prognosis.

In this study we utilised a microarray-based differential gene expression analysis strategy to identify molecular drivers of EBV associated with lung fibrosis. A549 cells and an alveolar epithelial cell line infected with EBV (VAAK) were used to identify genes whose expression was altered by EBV reactivation.

EBV reactivation by TGFbeta1 drives alterations in expression of non-canonical Wnt pathway mediators, implicating it in epithelial mesenchymal transition (EMT), the molecular event underpinning scar production in tissue fibrosis. Cell invasion, EMT correlated transcripts expression, GSK-3b and c-Jun activation were altered in response to non-canonical Wnt pathway regulation. The role of EBV in promoting fibrosis can be attenuated by antiviral strategies and inhibition of Wnt signalling.

Activation of non-canonical Wnt signalling pathway by EBV in epithelial cells suggests a novel mechanism of tissue fibrosis. These data present a framework for further description of the link between infectious agents and fibrosis, a significant disease burden.
Infants with recurrent lower respiratory tract symptoms – who benefits of extensive investigations?
Authors: Kotaniemi-Syrjänen Anne , Pelkonen Anna , Malmström Kristiina , Malmberg Pekka , Mäkelä Mika
Published: September 2008

There is limited information on lung function and exhaled nitric oxide fraction (FeNO) in infants with recurrent lower respiratory tract symptoms. In 2000–2003, 201 recurrently symptomatic infants were referred to a tertiary center for further investigation. As part of the clinical investigation, whole-body plethysmography, tidal FeNOmeasurements, and skin prick tests were performed. In addition, 77 (38%) of the children underwent bronchoscopy. Increased work of breathing in clinical examination (in 22%), and abnormal chest radiograph (in 30%), were associated with decreased airway conductance (sGaw z-score ≤−1.65) (p<0.001 and p = 0.048, respectively) and hyperinflation of the lungs (FRC z-score ≥1.65)(p = 0.004 and p = 0.038, respectively). Exposure to environmental tobacco smoke (ETS) was associated with FeNO≥40 ppb (p = 0.009). Increased work of breathing, sGaw z-score ≤−1.65, and FRC z-score ≥1.65, were associated with low FeNO(p = 0.002, p = 0.005, p = 0.026, respectively). A definitive diagnosis was made in 184 (92%) children; asthma was diagnosed in 149 (74%), infection in 23 (11%), and a structural abnormality in 12 (6%). Abnormal findings in clinical examination predicted the diagnosis of asthma or a structural abnormality in 96% of cases, whereas in children with underlying respiratory infection or no definitive diagnosis, clinical examination was normal in 92% (p<0.001). In conclusion, clinical findings of bronchial obstruction predict well lung function and the diagnosis of asthma in recurrently symptomatic infants. FeNOis affected by ETS exposure, clinical state of the child, and the used methods, and the information obtained should be interpreted with care.
Dendritic cells commit T-cells to a tolerant phenotype in tolerant lung transplant recipients
Authors: Botturi K. , Lacoeuille Y. , Thomas P. , Reynaud-Gaubert M. , Magnan A.
Published: September 2008

Immune characteristics distinguishing tolerant lung transplant recipients (LTR) from patients with Bronchiolitis obliterans syndrome (BOS) are largely unknown. We compared the effect of dendritic cells (DC) on T-cell activation in healthy LTR (non BOS) and in BOS patients.

30 Non BOS and 14 BOS recipients were studied. Mature dendritic cells were derived from blood monocytes and co-cultured with autologous T cells at various ratios. T cell CD69, CD25, CD28, ICOS and CTLA-4 expression and IL-4, IL-13, IFN-γ, and IL-10 production were assessed by flow cytometry. Dendritic cell expression of surface markers and indoleamine 2,3 dioxygenase was also studied. Experiments were repeated in presence ofP. aeruginosaor anti-CTLA-4 antibodies.

In dendritic cell/LT co-cultures, T cell CD69, CD28 and ICOS decreased in non BOS (p<0.03). By contrast, CD4+CD25+highT regulatory cells (Treg), CTLA4 expression and IL-10 production increased (p<0.05). Il-13 and IL-4 decreased in non BOS only (p<0.03), whereas IFN-γ did not vary. The increase in dendritic cell/LT ratio induced a decrease in T-cell activation in non BOS, with inverse result in BOS. Compared to BOS, dendritic cells from non BOS displayed a down-modulation of CD83, CD80 and higher levels of IDO (p<0.05). Stimulation byP. aeruginosadid not remove tolerogenic effect of dendritic cells on non BOS T-cells. Finally, decreased Treg and expression of IL-10 were detected when adding anti-CTLA-4 in non BOS (p<0.05) but not in BOS.

In contrast with BOS recipients, dendritic cells from non BOS induce a tolerant T cell phenotype, by using CD80/CD86-CTLA4 axis.
The role of the acute phase protein PTX3 in the ventilator-induced lung injury
Authors: Real JM , Marques MM , Spilborghs GMGT , Negri EM , Matzuk MM , Moura RP , Camargo AA , Deheinzelin D , Dias AAM
Published: September 2008

The pentraxin 3 (PTX3) is an acute phase proinflammatory protein produced by fibroblasts and alveolar epithelial cells. We have previously demonstrated that PTX3 is a key modulator of inflammation. Mechanical ventilation (MV) is a life saving therapeutic approach for patients with acute lung injury that, nevertheless could lead to an inflammatory response and tissue injury (ventilator-induced lung injury: VILI), representing a major cause of iatrogenic lung damage in intensive units. Our objective was to investigate the role of PTX3 in VILI. PTX3 transgenic, knockout and Wt control mice (n = 12/group) were ventilated (45ml·kg−1) until respiratory system Elastance increased 50% (Ers150%), an indicator of VILI. Histological analysis demonstrated that using a Ers150% was appropriate for our analysis since identical degrees of inflammation were observed in Tg, KO and Wt mice as assessed by leukocyte infiltration, oedema, alveolar collapse and number of breaks in alveolar septa. However, Tg mice reached Ers150% faster than Wt controls (p = 0.0225). We also showed that the lack of PTX3 does not abolish the occurrence of VILI in KOs. Gene expression profile of PTX3, IL-1beta, IL-6, KC, IFNgamma, TGFbeta and PCIII were investigated by QPCR. MV drastically up modulated PTX3 as well as IL-1beta, IL-6, IFNgamma and KC. Alternatively, mice were ventilated for 20, 40 and 60 min. The faster kinetics of Tg mice to reach Ers150% was accompanied by an earlier augmentation of IL-1b and PTX3 expression. The kinetics of local PTX3 expression in the lungs of ventilated mice strongly suggests the involvement of this pentraxin in the pathogenesis of VILI.
The bell tolls for the relationship between house dust mite exposure and asthma in childhood
Authors: Almqvist Catarina , Marks Guy , Li Qiang , Crisafulli Daniel , Tovey Euan
Published: September 2008

Prior evidence has suggested a direct relationship between the level of house dust mite (HDM) allergen exposure, sensitisation and asthma. A recent cross-sectional study indicated a bell-shaped relationship between HDM exposure and sensitisation [1]. We examined the effects of cumulative HDM allergen exposure during the first 5 years of life on outcomes at age 5 years in Sydney, a high HDM environment.

In the Childhood Asthma Prevention Study, bed dust samples collected at 3, 6, 9 and 12 months and then 6-monthly (total 6615 samples) until age 5 years were analysed for HDM allergen by ELISA. At five years, 516 children were assessed for wheeze and asthma by questionnaires and spirometry, and 488 for sensitisation by skin test. Time-weighted average HDM allergen concentration was estimated for each individual. The range was divided into quintiles with cut-points being 3,5; 7,8; 13,5 and 23,4 ug Der p 1/g. The association between HDM levels and outcomes was analysed with chi-square test, adjusting for confounders.

The figure shows the prevalence of outcomes by quintile of time-weighted average of HDM allergen.

In this birth cohort, there is a bell-shaped dose response between HDM levels and sensitisation and asthma. This may reflect tolerance to HDM allergen or be attributable to protection from associated exposures, and prompts further research on the mechanisms.
Effectiveness of group counselling for smoking cessation in hospital staff
Authors: Schoonis A. , Celis G. , Wuyts W. , Lemaigre V. , Nackaerts K.
Published: September 2008

Smoking prevalence among hospital staff is still considerable. It is well known that smoking cessation is difficult to establish without any help. Group counselling is effective for smoking cessation. In 2004, therefore, we decided to offer group counselling for smoking cessation to our hospital staff.

(1) To assess the efficacy of group counselling given by a multidisciplinary team of healthcare professionals.

(2) To determine the quit rate after group counselling in hospital staff.

The program is based on 10 group sessions of 90 min each. Each group contains a maximum of 16 participants. The group sessions were led by a nurse specialized in smoking cessation and consisted of education and behavioural interventions provided by health care professionals (respiratory physician, psychologist and a dietician). To improve smoking cessation motivation, spirometry (FEV1 and FVC) and exhaled CO were measured both at the start and at the end of the group counselling.

In total, 38 participants of 3 different groups entered group counselling. The mean age was 48 years, and 71% was female. They smoked an average of 20 cigarettes per day. Based on exhaled CO measurements and self-reports, smoking cessation, the quit rates after 6 months, 1 year and 2 years were, 27/35 (77%), 25/35 (72%) and 23/35 (66%), respectively.

Group counselling program on smoking cessation in hospital staff based on 10 group sessions was able to induce a remarkably high amount of quitters. The hospital setting offered the opportunity to meet the group participants frequently afterwards, what might have helped in keeping the quitting results at about the same level, even after 2 years’ follow-up.
Impact of environmental factors on lung defences
Authors: Olivieri D. , Scoditti E.
Published: September 2008

The lungs are one of the most important organs exposed to environmental agents. The lungs have the ability to protect themselves by both immunological and nonimmunological mechanisms. An individual's susceptibility to the impact of environmental agents will determine their adverse effects.

This article focuses on air pollution, in particular ozone (O3), nitrogen dioxide (NO2), particulate matter (PM) and sulphur dioxide (SO2). O3inhalation first modifies the ciliary cells. O3is an extremely strong oxidant, since it increases the permeability of epithelial cells and decreases mucociliary clearance. NO2is a less potent and less reactive oxidant pollutant and impairs the function of epithelial cells and alveolar macrophages. PM induces oxidative stress in macrophages and epithelial cells, and increases tumour necrosis factor-β, interleukin (IL)-6, interferon-γ, transforming growth factor-β and nuclear factor-▒B. Diesel exhaust particulate, contained in PM, increases IL-8 production. High concentrations of SO2increase the production of reactive oxygen species in the lungs.

In conclusion, air pollution certainly interferes with aspecific and specific lung defences, thus facilitating the development of pulmonary diseases, such as exacerbation of chronic obstructive pulmonary disease, allergies and asthma.
Impact of bacterial infections on airway diseases: FIGURE 1.
Authors: Toews G. B.
Published: September 2008

Bacterial infections play an important role as aetiologic agents in acute exacerbations of chronic obstructive pulmonary disease (COPD). Modern investigational tools, including bronchoscopy, microbial molecular epidemiology and measurement of specific immunity have established that bacteria cause up to 50% of acute exacerbations in COPD.

Acute exacerbations have enormous economic costs and contribute to morbidity, mortality and impairment in health related quality of life. Chronic bacterial persistence in the lower airways and lower respiratory tract in patients with COPD is not innocuous. It is likely to contribute to persistent airway inflammation and might contribute to acute airway exacerbations or progression of airway obstruction. Further investigation is required in these fertile areas of investigation.

Bacteria also play a role in asthma exacerbations, but their role is less well defined than with patients with COPD.Mycoplasma pneumoniaemay be associated with asthma chronicity. Chronic airway infection models document thatM. pneumoniaeplays a role in airway remodelling, including angiogenesis, vascular remodelling and airway wall thickening.

Recent studies have identified patients with asthma as an at-risk group for invasive pneumococcal disease. The feasibility and cost effectiveness of a pneumococcal vaccination strategy among persons with asthma deserves careful, immediate attention.
Developmental factors as determinants of risk for infections and atopy in childhood: FIGURE 1.
Authors: Holt P. G.
Published: September 2008

The nature of the relationship between infections and allergy in children continues to be the subject of vigorous debate, in particular the issue of whether the increased frequency of wheezing respiratory infections in children is a cause or a consequence of atopy.

Recent evidence suggests a subtle twist to this argument, notably that the genetic risk for susceptibility to both atopy and respiratory infections may involve a common set of genetic variations related to the efficiency of maturation of immune function in early post-natal life.