bluuebunny/crossref_metadata_2025_split huggingface dataset:
A study of the teratogenic and fetotoxic effects of large doses of barbital, hexobarbital and butobarbital used for suicide attempts by pregnant women
Authors: Timmermann G , Czeizel AE , Bánhidy F , Ács N 
Published: September 2008

The teratogenic potential of barbiturates is debated. The objective of this study was to evaluate the effects of very large doses of different barbiturates, except phenobarbital and amobarbital, on fetal development in pregnant women who attempted suicide. These self-poisoned pregnant women were identified among the patients of the Department of Toxicology Internal Medicine, Korányi Hospital, Budapest. The prevalence at birth of congenital abnormalities and intrauterine fetal growth, based on pregnancy age at delivery and birth weight, as well as cognitive-behavioral status in exposed children born to mothers who attempted suicide with barbiturates alone or in combination with other drugs, during pregnancy, were compared with their sibs as controls. Of 1044 women with self-poisoning during pregnancy between 1960 and 1993, 411 delivered live-born babies; of these, 367 (89.3%) exposed children were evaluated. Of the 367 exposed children, 6, 5, 4 and 4 were born to mothers who attempted suicide with very large doses of Barbamid® (butobarbital and aminophenazone), hexobarbital, butobarbital and Belloid® (butobarbital, hyoscyamine and secalis cornuti alkaloida) tablets, respectively. Of 19 exposed children, two children with a congenital inguinal hernia were born to mothers who attempted suicide with 30 tablets of Belloid® (900 mg butobarbital) in the 20th postconceptional week or with 20 tablets of Belloid® in combination with chlordiazepoxide (100 mg) and nitrazepam (100 mg) in 12th postconceptional week. However, the critical period for production of congenital inguinal hernia is in the last months of pregnancy. None of the exposed children born to the other 12 pregnant women who attempted suicide with these barbiturates between the third and 12th postconceptional week, i.e., during the critical period for production of most major congenital abnormalities, had a congenital abnormality. Congenital abnormalities did not occur among 16 sib controls. Intrauterine fetal growth was similar between sibs and exposed children; cognitive status and behavioral scale also did not indicate any neurotoxic effects from large doses of these barbiturates. The very large doses of barbital, hexobarbital and/or butobarbital used for self-poisoning during pregnancy were not teratogenic to the children, although it must be recognized that the number of exposed children was limited.
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. •
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.
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

AbstractCD47 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.
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.
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.