bluuebunny/crossref_metadata_2025_split huggingface dataset:
Remifentanil discontinuation and subsequent intensive care unit-acquired infection: a cohort study
Authors: Nseir Saad , Hoel Jérémy , Grailles Guillaume , Soury-Lavergne Aude , Di Pompeo Christophe , Mathieu Daniel , Durocher Alain 
Published: April 2009

AbstractIntroductionRecent animal studies demonstrated immunosuppressive effects of opioid withdrawal resulting in a higher risk of infection. The aim of this study was to determine the impact of remifentanil discontinuation on intensive care unit (ICU)-acquired infection.MethodsThis was a prospective observational cohort study performed in a 30-bed medical and surgical university ICU, during a one-year period. All patients hospitalised in the ICU for more than 48 hours were eligible. Sedation was based on a written protocol including remifentanil with or without midazolam. Ramsay score was used to evaluate consciousness. The bedside nurse adjusted sedative infusion to obtain the target Ramsay score. Univariate and multivariate analyses were performed to determine risk factors for ICU-acquired infection.ResultsFive hundred and eighty-seven consecutive patients were included in the study. A microbiologically confirmed ICU-acquired infection was diagnosed in 233 (39%) patients. Incidence rate of ICU-acquired infection was 38 per 1000 ICU-days. Ventilator-associated pneumonia was the most frequently diagnosed ICU-acquired infection (23% of study patients).Pseudomonas aeruginosawas the most frequently isolated microorganism (30%). Multivariate analysis identified remifentanil discontinuation (odds ratio (OR) = 2.53, 95% confidence interval (CI) = 1.28 to 4.99,P= 0.007), simplified acute physiology score II at ICU admission (1.01 per point, 95% CI = 1 to 1.03,P= 0.011), mechanical ventilation (4.49, 95% CI = 1.52 to 13.2,P= 0.006), tracheostomy (2.25, 95% CI = 1.13 to 4.48,P= 0.021), central venous catheter (2.9, 95% CI = 1.08 to 7.74,P= 0.033) and length of hospital stay (1.05 per day, 95% CI = 1.03 to 1.08,P< 0.001) as independent risk factors for ICU-acquired infection.ConclusionsRemifentanil discontinuation is independently associated with ICU-acquired infection.
Coregulation in human leukocytes of the long pentraxin PTX3 and TSG-6
Authors: Maina Virginia , Cotena Alessia , Doni Andrea , Nebuloni Manuela , Pasqualini Fabio , Milner Caroline M , Day Anthony J , Mantovani Alberto , Garlanda Cecilia 
Published: April 2009

Abstract
Coordinated expression of TSG-6 and PTX3 in myelomonocytic cells and MDDC support the hypothesis that these two proteins may have a role in extracellular matrix remodeling at sites of inflammation.
The prototypic long PTX3 is a multifunctional protein involved in innate resistance to pathogens and in controlling inflammation. TSG-6 is a hyaluronan-binding protein that is involved in ECM remodeling and has anti-inflammatory and chondroprotective functions. PTX3 and TSG-6 are coregulated by growth differentiation factor-9 in granulosa cells, where they are produced during the periovulatory period and play essential roles in the incorporation of hyaluronan into the ECM during cumulus expansion. The present study was designed to assess whether PTX3 and TSG-6 are coregulated in leukocytes, in particular, in phagocytes and DC. Monocytes, macrophages, and myeloid DC were found to produce high levels of TSG-6 and PTX3 in response to proinflammatory mediators (LPS or cytokines). Unstimulated neutrophil polymorphonuclear granulocytes expressed high levels of TSG-6 mRNA, but not PTX3 transcript, and stored both proteins in granules. In contrast, endothelial cells expressed substantial amounts of PTX3 mRNA and low levels of TSG-6 transcript under the conditions tested. Anti-inflammatory cytokines, such as IL-4, dampened LPS-induced TSG-6 and PTX3 expression. Divergent effects were observed with IL-10, which synergizes with TLR-mediated PTX3 induction but inhibits LPS-induced TSG-6 transcription. Immunohistochemical analysis confirms the colocalization of the two proteins in inflammatory infiltrates and in endothelial cells of inflamed tissues. Thus, here we show that myelomonocytic cells and MoDC are a major source of TSG-6 and that PTX3 and TSG-6 are coregulated under most of the conditions tested. The coordinated expression of PTX3 and TSG-6 may play a role in ECM remodeling at sites of inflammation.
Impaired M. tuberculosis-mediated apoptosis in alveolar macrophages from HIV+ persons: potential role of IL-10 and BCL-3
Authors: Patel Naimish R , Swan Katharine , Li Xin , Tachado Souvenir D , Koziel Henry 
Published: April 2009

Abstract
HIV alters the lung environment through increased IL-10, leading to an impaired macrophage apoptotic response to Mycobacterium tuberculosis via upregulation of macrophage BCL-3.
The mechanism of increased MTb disease susceptibility in HIV+ persons remains poorly understood. Apoptosis of macrophages in response to MTb represents a critical host defense response, and decreased apoptosis may represent a mechanism of increased susceptibility to MTb in HIV. In the current study, MTb-mediated apoptosis of human AM was reduced in HIV+ subjects compared with healthy subjects in a TNF-α-dependent manner. IL-10 levels in BALF from HIV+ persons were significantly elevated compared with HIV– persons, and exogenous IL-10 reduced MTb-mediated apoptosis in healthy AM, suggesting that IL-10 could mediate decreased apoptosis observed in HIV. Further study showed that IL-10 reduced TNF release in response to MTb in AM through a reduction in TNF mRNA levels, and exogenous TNF could partially reverse IL-10-associated effects on AM apoptosis. IL-10 did not influence p-IRAK, IκB degradation, or NF-κB p65 nuclear translocation in response to MTb, but IL-10 did increase levels of AM BCL-3, an inhibitor of NF-κB nuclear activity. BCL-3 knockdown in human macrophages increased MTb-mediated TNF release. Importantly, BCL-3 levels in AM from HIV+ subjects were higher compared with healthy subjects. Taken together, these data suggest that elevated lung levels of IL-10 may impair MTb-mediated AM apoptosis in HIV through a BCL-3-dependent mechanism. BCL-3 may represent a potential therapeutic target to treat or prevent MTb disease in HIV+ persons.
The Relationship between Central Adrenal Insufficiency and Sleep-Related Breathing Disorders in Children with Prader-Willi Syndrome
Authors: de Lind van Wijngaarden Roderick F. A. , Joosten Koen F. M. , van den Berg Sandra , Otten Barto J. , de Jong Frank H. , Sweep C. G. J. (Fred) , de Weerd Al W. , Hokken-Koelega Anita C. S. 
Published: April 2009

Background: The annual death rate of patients with Prader-Willi syndrome (PWS) is high (3%). Many deaths of children are sudden and unexplained. Sleep apneas have been suggested to play a role in sudden deaths. Recently, we discovered that 60% of patients with PWS suffer from central adrenal insufficiency (CAI) during stress.Objective: The aim was to study the relationship between CAI and sleep-related breathing disorders.Design: In 20 children with PWS who underwent a metyrapone test (30 mg/kg at 2330 h), sleep-related breathing was evaluated by polysomnography before the metyrapone test. In addition, we recorded sleep-related breathing in 10 children with PWS during their metyrapone test. CAI was diagnosed when ACTH levels during the metyrapone test were below 33 pmol/liter at 0730 h. All tests were performed during healthy condition.Setting: The study was conducted in a pediatric intensive care unit and specialized sleep center.Results: Median (interquartile range) age was 8.4 yr (6.5–10.2). After metyrapone administration, median (interquartile range) central apnea index (number/hour) increased significantly from 2.2 (0.4–4.7) to 5.2 (1.5–7.9) (P = 0.007). The increase tended to be higher in children with CAI [2.8 (2.0–3.9) vs. 1.0 (−0.2 to 2.6); P = 0.09]. During polysomnography before the metyrapone test, sleep-related breathing was worse in children with CAI, who had a significantly higher central apnea index and tended to have a lower minimum oxygen saturation compared to those without CAI (P = 0.03 and P = 0.07).Conclusions: In children with PWS, the central apnea index increased significantly after metyrapone administration, particularly in those with CAI during stress. In addition, children with CAI had a higher central apnea index compared to those without several months before the metyrapone test.
Hypoglycemia from IGF2 Overexpression Associated with Activation of Fetal Promoters and Loss of Imprinting in a Metastatic Hemangiopericytoma
Authors: Lawson Elizabeth A. , Zhang Xun , Crocker Jonathan T. , Wang Wei-Lien , Klibanski Anne 
Published: April 2009

Context: The mechanism of IGF2 overexpression in non-islet-cell tumor hypoglycemia is not understood.
Objective: We investigated the imprinting control and promoter usage for IGF2 expression to identify a mechanism for increased IGF-II production in non-islet-cell tumor hypoglycemia.
Patient and Methods: A patient with metastatic hemangiopericytoma was studied. Tissue from the original hemangiopericytoma, metastatic tumor, and uninvolved liver was analyzed for IGF-II immunohistochemistry. IGF2, a paternally imprinted gene, shares a control region with maternally imprinted H19, a putative tumor suppressor. IGF-II and H19 mRNA expression was compared in metastatic tumor and uninvolved liver by quantitative RT-PCR. Imprinting of IGF2/H19 genes and IGF2 promoter usage in metastatic tumor was investigated by RT-PCR and sequence analysis, and the methylation pattern in the IGF2/H19 imprinting control region was analyzed.
Results: IGF-II protein expression was increased in metastatic tumor vs. uninvolved liver and original tumor. In the metastatic tumor, IGF-II mRNA was increased 60-fold, but H19 mRNA was comparable to uninvolved liver; loss of imprinting of IGF2, but not H19, was identified; no major change in methylation of the IGF2/H19 imprinting control regions was observed; and transcripts from four different IGF2 promoters were detected, compared to two in uninvolved liver.
Conclusions: IGF-2 overexpression, newly acquired in the metastatic tumor, was associated with loss of IGF2 gene imprinting and different promoter usage. The imprinting control mechanism governing the IGF2/H19 locus was intact, as evidenced by normal levels of H19, maintenance of H19 imprinting, and no major change in methylation of the imprinting control regions.
Political Conflict and Power Sharing in the Origins of Modern Colombia
Authors: Mazzuca Sebastián , Robinson James A. 
Published: April 2009

Abstract
After a long period of chaos, political order in Colombia emerged in the mid-1900s. This transition was driven by a change in the institutional allocation of political power. After the Thousand Days’ War, Colombia’s two parties agreed to share power by means of a new set of electoral rules. The incomplete vote, the cornerstone of the new electoral rules, was a strategic concession by the Conservative government to the Liberal opposition. In exchange for permanent representation in the legislatures, Liberals abandoned military insurrection as a political strategy. Transition to proportional representation was completed in 1929 with the introduction of the quotient rule. The quotient rule was also a concession from the government. However, it was not driven by Liberalism’s potential military power but by the institutional power that Liberalism had accumulated since the first concession.
The mood stabiliser lithium suppresses PIP3 signalling in Dictyostelium and human cells
Authors: King Jason S. , Teo Regina , Ryves Jonathan , Reddy Jonathan V. , Peters Owen , Orabi Ben , Hoeller Oliver , Williams Robin S. B. , Harwood Adrian J. 
Published: April 2009

SUMMARY
Bipolar mood disorder (manic depression) is a major psychiatric disorder whose molecular origins are unknown. Mood stabilisers offer patients both acute and prophylactic treatment, and experimentally, they provide a means to probe the underlying biology of the disorder. Lithium and other mood stabilisers deplete intracellular inositol and it has been proposed that bipolar mood disorder arises from aberrant inositol (1,4,5)-trisphosphate [IP3, also known as Ins(1,4,5)P3] signalling. However, there is no definitive evidence to support this or any other proposed target; a problem exacerbated by a lack of good cellular models. Phosphatidylinositol (3,4,5)-trisphosphate [PIP3, also known as PtdIns(3,4,5)P3] is a prominent intracellular signal molecule within the central nervous system (CNS) that regulates neuronal survival, connectivity and synaptic function. By using the genetically tractable organism Dictyostelium, we show that lithium suppresses PIP3-mediated signalling. These effects extend to the human neutrophil cell line HL60. Mechanistically, we show that lithium attenuates phosphoinositide synthesis and that its effects can be reversed by overexpression of inositol monophosphatase (IMPase), consistent with the inositol-depletion hypothesis. These results demonstrate a lithium target that is compatible with our current knowledge of the genetic predisposition for bipolar disorder. They also suggest that lithium therapy might be beneficial for other diseases caused by elevated PIP3 signalling.
Potential Impacts of Integrated Oil and Gas Plant on Ambient Air Quality
Authors: Sonibare Jacob Ademola , Ede Precious Nwobidi 
Published: April 2009

The ISCST-3 model has been used to study the ground level concentrations of carbon monoxide (CO), oxides of nitrogen (NOX), particulate matter less than 10.0 microns in diameter (PM10) and sulphur dioxide (SO2). The purpose was to predict air quality effects from an integrated oil and gas project (IOGP) proposed for the Niger Delta, Nigeria. The emissions of 12 elevated point sources for criteria air pollutants were considered with eight different scenarios. Both natural gas-fired and diesel (AGO) fired equipment were considered for the identified emission sources. Five years of hourly meteorological observations were used in the prediction of the ground level concentration of the pollutants. The model outputs show a general maximum ground level concentration between 0.5 – 3.5 km, with easterly and north-easterly receptors having the greatest concentration. The pollutants emitted in the greatest concentration in their order of magnitude were CO, NOx and PM10. Maximum ground level concentration for 1, 8 and 24 – hr periods for CO were below regulatory standards (less than 10 %) for scenarios 1 – 4 when the fuel is natural gas. The 8 – hr ground level concentrations were about 1.3 folds of the World Bank Standard in scenarios 5 – 8 when the fuel sources are switched to AGO. However in these scenarios, the Nigerian environment and petroleum ministries' emission limits were not breached for all the averaging periods. Modelled NOX concentrations were significant in all the scenarios except 3 and 4. Though NOX concentrations were within the standards for all the averaging periods in scenarios 1 – 4, except the 1 – hr limit that was breached in scenarios 1 and 2, these concentrations were about 1.1 – 2.8 folds in all the averaging periods of all the standards in scenarios 5 – 8. The predicted PM10 and SO2 concentrations are all below the guideline limits. If the use of AGO is completely avoided in the entire life of the proposed IOGP, the air quality of its immediate vicinity can be protected. Furthermore, the declaration of a radius 1.75 km natural forest buffer around the plant and continuous monitoring of ground level concentrations of CO, NOX, PM10, and SO2 may further assist in guaranteeing the safety of people in terms of air quality. The study shows the need for policy formulation that will integrate comprehensive cumulative impacts assessment of air quality in the environmental laws regulating the gas development projects in Nigeria.
Irreproducible Results in Thompson Et Al., “Abrupt Tropical Climate Change: Past and Present” (PNAS 2006)
Authors: McCulloch J. Huston 
Published: April 2009

In a prestigious and influential article in the Proceedings of the National Academy of Sciences ( PNAS), Thompson et al. [1] put forward a Tropical Composite Z-score series ( TCZ), purportedly computed from ice core d18O ratios, as evidence of tropical warming over the past 2000 years. This note demonstrates that it bears no replicable linear relationship to the seven series on which they claim it is based, as archived by the authors themselves on the PNAS website. Although TCZ does equal the average of the two Himalayan and Andean component series ( HCZ and ACZ) to within rounding error, HCZ cannot be constructed linearly from the four Himalayan isotope ratio series with an error less than 100 times the expected rounding error, and ACZ cannot be constructed from the three Andean isotope ratio series with an error less than 30 times the expected rounding error. The authors should provide PNAS with corrected and internally consistent data sets and figures for these series.
Long-Term Efficacy and Safety of TDM-Assisted Combination of Voriconazole plus Efavirenz in an AIDS Patient with Cryptococcosis and Liver Cirrhosis
Authors: Carbonara Sergio , Regazzi Mario , Ciracì Emanuela , Villani Paola , Stano Francesca , Cusato Maria , Heichen Manuela , Monno Laura 
Published: April 2009

Objective To report the efficacy, tolerability, and pharmacokinetic effects of combined voriconazole and efavirenz treatment administered at therapeutic drug monitoring (TDM)–based adjusted doses to a patient with AIDS, cryptococcosis, and mild liver cirrhosis. Case Summary A 40-year-old man with AIDS (hemophiliac, antiretroviral-naïve, plasma HIV-RNA = 290,000 copies/mL, CD4+ lymphocytes = 0), hepatitis C virus–related liver cirrhosis (Child-Pugh class A), and cryptococcal meningitis was failing standard antifungal therapies. He received an antifungal–antiretroviral combination treatment based on the association of voriconazole plus efavirenz. Doses of both drugs were serially adjusted based on their plasma concentrations, which were evaluated at steady-state of each dose combination at least once (week 3.1 or later) as full concentration–time profile (samples collected at 0, 1, 2, 3, 4, 6, 8, 12 h postdose). Adequate concentrations of voriconazole in both plasma and cerebrospinal fluid were obtained and target plasma concentrations of efavirenz were achieved at the final dose adjustment (voriconazole 200 mg twice daily plus efavirenz 300 mg once daily, both administered orally). The patient showed prompt and stable suppression of cryptococcosis and plasma viremia of HIV at long-term follow-up (66 wk), with no significant adverse events. Discussion Standard therapies for cryptococcosis in patients with AIDS are often not effective. Voriconazole, despite its promising anticryptococcal efficacy, is currently not approved for cryptococcosis therapy in the US and Europe, nor is it recommended for combination with efavirenz due to the significant pharmacokinetic interactions between the 2 compounds. Thus far, published studies regarding the effects of voriconazole in human cryptococcosis are scarce and none has described the clinical and pharmacokinetic outcomes of a voriconazole/efavirenz combination in patients with AIDS, either with or without liver cirrhosis. Conlusions The combination of voriconazole and efavirenz at TDM-assisted doses may represent a valuable therapeutic option in AIDS patients with cryptococcosis and mild liver cirrhosis.
Safety and Effectiveness of Varenicline in a Veteran Population with a High Prevalence of Mental Illness
Authors: Purvis Tara L , Mambourg Scott E , Balvanz Tracie M , Magallon Heather E , Pham Richard H 
Published: April 2009

Background Varenicline is a selective nicotinic receptor partial agonist used to aid in the process of smoking cessation. Research on varenicline's approval for marketing demonstrated that after 12 weeks of treatment, at least 44% of patients successfully quit smoking and, on average, 13% of individuals discontinued therapy due to an adverse drug event (ADE). Growing postmarketing data linked varenicline to an increase in neuropsychiatric symptoms. Objective To evaluate the safety profile, specifically psychiatric symptoms, and effectiveness of varenicline in a veteran population and to determine whether there is an association among specific baseline demographics and success rate. Methods The study was a retrospective review of a prospective performance measure involving veterans initiated on varenicline. Patients were contacted via telephone throughout treatment and at week 12 for effectiveness follow-up. Smoking history was obtained and medication counseling was provided. The primary endpoint was tobacco cessation between weeks 9 and 12 of therapy. Varenicline's safety profile and discontinuation rates due to ADEs were also analyzed. Results Of the 50 patients included in the study, 30% (n = 15) successfully quit smoking and 70% (n = 35) failed therapy (lack of effectiveness, n = 22; intolerability, n = 13). Prevalence of underlying mental illness in the success group (4/15; 27%) versus failure group (20/35; 57%) was statistically significant (p< 0.001). All patients who discontinued therapy due to an increase in mood and behavioral changes (n = 4) had an underlying psychiatric illness. The study results demonstrate a lower success rate and a higher incidence of discontinuation due to an ADE in our veteran population compared with premarketing data. An inverse association was shown between psychiatric disorders and success. Conclusions Cautious treatment initiation and close monitoring of veterans initiated on varenicline are warranted. Furthermore, the results from this study demonstrate the need for prospective effectiveness trials to determine the clinical significance of the results.
Structure-activity relationships of antitubercular scalaranes: Heteronemin revisited
Authors: Jaisamut Sunan , Thengyai Suriyan , Yuenyongsawad Supreeya , Karalai Chatchanok , Plubrukarn Anuchit , Suwanborirux Khanit 
Published: April 2009

Abstract
A series of heteronemin-related antitubercular scalaranes, both from natural products and from chemical derivatization, were subjected to structure-activity investigations. Based on the activity profile, three main regions; i.e., the substituted groups hovering over C-19/C-18 and furan moiety, the functionalities in the vicinity of C-16 and the right-hand side of ring D, and the substituted groups on C-12, were speculated as the areas influencing the antitubercular activity of the scalaranes. The results suggested the promising possibility for the further investigation towards the modes of actions and/or target sites of the compounds.