bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of rapid screening and pre-emptive contact isolation for detecting and controlling methicillin-resistant Staphylococcus aureus in critical care: an interventional cohort study
Authors: Harbarth Stephan , Masuet-Aumatell Cristina , Schrenzel Jacques , Francois Patrice , Akakpo Christophe , Renzi Gesuele , Pugin Jerome , Ricou Bara , Pittet Didier
Published: February 2006

Introduction

Rapid diagnostic tests may allow early identification of previously unknown methicillin-resistant Staphylococcus aureus (MRSA) carriers at intensive care unit (ICU) admission. The aim of this study was twofold: first, to assess whether a new molecular MRSA screening test can substantially decrease the time between ICU admission and identification of MRSA carriers; and, second, to examine the combined effect of rapid testing and pre-emptive contact isolation on MRSA infections.

Method

Since November 2003, patients admitted for longer than 24 hours to two adult ICUs were screened systematically on admission using quick, multiplex immunocapture-coupled PCR (qMRSA). Median time intervals from admission to notification of test results were calculated for a five-month intervention phase (November 2003–March 2004) and compared with a historical control period (April 2003–October 2003) by nonparametric tests. ICU-acquired MRSA infection rates were determined for an extended surveillance period (January 2003 through August 2005) and analyzed by Poisson regression methods.

Results

During the intervention phase, 97% (450/462) of patients admitted to the surgical ICU and 80% (470/591) of patients admitted to the medical ICU were screened. On-admission screening identified the prevalence of MRSA to be 6.7% (71/1053). Without admission screening, 55 previously unknown MRSA carriers would have been missed in both ICUs. Median time from ICU admission to notification of test results decreased from 87 to 21 hours in the surgical ICU (P < 0.001) and from 106 to 23 hours in the medical ICU (P < 0.001). In the surgical ICU, 1,227 pre-emptive isolation days for 245 MRSA-negative patients were saved by using the qMRSA test. After adjusting for colonization pressure, the systematic on-admission screening and pre-emptive isolation policy was associated with a reduction in medical ICU acquired MRSA infections (relative risk 0.3, 95% confidence interval 0.1–0.7) but had no effect in the surgical ICU (relative risk 1.0, 95% confidence interval 0.6–1.7).

Conclusion

The qMRSA test decreased median time to notification from four days to one day and helped to identify previously unknown MRSA carriers rapidly. A strategy linking the rapid screening test to pre-emptive isolation and cohorting of MRSA patients substantially reduced MRSA cross-infections in the medical but not in the surgical ICU.
Atmospheric pollutants study of particles and metallic elements during high wind speed (wind speed >6 m/s) near Taiwan Strait around central Taiwan
Authors: Wu Yuh-Shen , Fang Guor-Cheng , Lin Jum-Bo , Lin Jhih-Guang , Huang Shih-Han , Rau Jui-Yeh
Published: February 2006

The purpose of this study was to characterize metallic elements associated with atmospheric particulate matter in total suspended particulate (TSP), fine particles (particle matter with an aerodynamic diameter of B / 2.5 mm, PM2.5) and coarse particles (particle matter with an aerodynamic diameter of 2.5-10 mm, PM2.5- 10), at high wind speed (wind speed-6 m/s) at Taichung Harbor (TH) and Wuci traffic (WT) in central Taiwan from March to December 2004. The correlation coefficient (R2) between TSP, coarse, fine particulate concentrations versus wind speed at the TH and WT sampling site during high wind speed (-6 m/s) are shown in this study. In addition, the correlation coefficients between TSP, coarse and fine particles of metallic species versus high wind speed were also observed. The results indicated that the correlation coefficient order was TSP-coarse-fine for particles at both sampling sites during high wind speed (-6 m/s) near central Taiwan. In addition, the concentrations of Fe, Zn, Mn, Cu, Pb, Cr, Mg for TSP, coarse and fine particulates were also analysed in this study.
Subacute administration of tributyltin chloride modulates neurotransmitters and their metabolites in discrete brain regions of maternal mice and their F1 offspring
Authors: Tsunoda Masashi , Aizawa Yoshiharu , Konno Nobuhiro , Kimura Kimiko , Sugita-Konishi Yoshiko
Published: February 2006

Tributyltin (TBT) compounds have been used as anti-fouling agents and the central nervous system is one of its target organs. TBT-induced modulations of neurotransmitters in the brains of adult mice have been reported. However, little is known about the developmental neurotoxicity of TBT. In this study, we evaluated the effects of TBT on neurotransmitters and their metabolites in discrete brain regions of female ICR mice and their offspring. Pregnant ICR mice were exposed to TBT chloride at concentrations of 0, 15 or 50 ppm in water or 125 ppm in food. Male offspring were sacrificed at one, two and three weeks after birth. The concentrations of norepinephrine, dopamine (DA), dihydoxyphenylacetic acid, homovanillic acid (HVA), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) were determined in different brain regions by HPLC. All offspring from the 125 ppm group died immediately after birth. A significant decrease in the body weight of the TBT-treated F1 groups compared to the control group was observed in the first week. Significant increases compared to the controls were observed for the DA concentration in the striatum of the 50 ppm F1 group, and for the HVA concentration in the cerebrum and the 5-HT concentration in the medulla oblongata of the 15 and 50 ppm F1 groups in the third week. At three weeks of age, the neurotransmitters and their metabolites may be useful indexes for developmental neurotoxicity. For the dams, a significant decrease in the 5-HT concentration was observed in the cerebellum, medulla, midbrain and striatum of the 125 ppm group compared to the control group. A significant decrease in the 5-HIAA concentration was also observed in the cerebellum, midbrain and striatum of the dams in the 125 ppm group compared to the control. TBT may induce a decrease in the synthesis of 5-HT in the dams. The discrepancy between dams and offspring may be due to several factors such as age, dose, route, sex and pregnancy.
Characteristic study of ionic species in nano, ultrafine, fine and coarse particle size mode at a traffic sampling site
Authors: Fang Guor-Cheng , Wu Yuh-Shen , Chang Shih-Yo , Rau Jui-Yeh , Huang Shih-Han , Lin Chi-Kwong
Published: February 2006

A micro-orifice uniform deposit impactor (MOUDI) and a nano-MOUDI were used to measure the atmospheric coarse (PM2.5-10), fine (PM2.5), ultrafine (PM0.056 - 1) and nano (< 0.056 μm) particle concentrations at a traffic sampling site in central Taiwan during the winter period from November 2004 to January 2005. Meanwhile, concentrations of major ionic species (Cl-, NO3−, SO42−, NH4+, Na+, K+, Ca2+ and Mg2+) were also extracted from various particle size modes (nano, ultrafine, fine and coarse) and analysed by ion chromatography (DIONEX-100). The mass size distribution of ambient suspended particles exhibited two modes. The size ranges of the particles at these two particle size modes were between 1.0 and 1.8 mm and 3.2 and 5.6 mm, respectively. The average mass media aerodynamic diameter (MMAD) of suspended particles was 0.99 mm in this study. In addition, statistical methods, such as correlation coefficient and principal component analysis, were also used to identify the possible pollutant source for various particles size modes (nano, ultrafine, fine and coarse) during the winter months at a traffic sampling site in central Taiwan
Possible peripheral markers for chronic aluminium toxicity in Wistar rats
Authors: Kaur Amarpreet , Gill Kiran Dip
Published: February 2006

This investigation gives detailed analysis of peripheral marker enzymes as well as neurobehavioral tests following chronic aluminium (Al) exposure (10 mg/kg b.w. for 12 weeks intragastrically). We observed a significant decrease in the levels of serum cholinesterase after toxicity. The enzymatic activity of cytochrome oxidase (CO), the terminal enzyme of the electron transport chain, was significantly diminished and that of glucose-6-phosphate dehydrogenase (G-6-PD) was significantly enhanced. Neuromuscular co-ordination was assessed using motor and memory function tests. Deficits were observed suggesting a probable model for chronic Al neurotoxicity.
Effects of Ginkgo biloba on plasma oxidant injury induced by bleomycin in rats
Authors: Erdogan Hasan , Fadillioğlu Ersin , Kotuk Mahir , Iraz Mustafa , Tasdemir Seda , Oztas Yesim , Yildirim Zeki
Published: February 2006

Bleomycin is an anti-neoplastic agent and its clinical usage is limited by its toxicity, which is mostly induced by oxygen radicals. The aim of this study was to investigate the effect of Ginkgo biloba on plasma indices of oxidants induced by bleomycin in rats.

Male Sprague-Dawley rats were divided into five groups: none medicated or 0.9% NaCl injected or only Ginkgo biloba (orally, 100 mg/kg per day for 14 days) or only a single dose of bleomycin (intratracheal, 2.5 U/kg) or Gingko biloba and bleomycin-treated groups. After 14 days, blood was taken before the rats were sacrificed. The plasma was removed and stored at −85°C until the study day. Plasma superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and xanthine oxidase (XO) enzyme activities with malondialdehyde and nitric oxide (NO) levels were studied.

The levels of malondialdehyde and NO with activity of XO were higher in plasma of bleomycin group than the other groups (P B / 0.05). The activities of SOD and GSH-Px were increased in the bleomycin plus Gingko biloba group in comparison with the bleomycin group (P B / 0.05). There was a positive correlation between malondialdehyde and NO levels in the bleomycin group (r-/0.859, P B / 0.05). There were positive correlations between SOD and GSH-Px activities (r-/0.760, P B/0.05) and between XO activity and malondialdehyde level (r-/0.822, P B/0.05) in the bleomycin plus Gingko biloba group.

In conclusion, it was thought that bleomycin induced oxidative stress can be prevented by Gingko biloba treatment via high anti-oxidant enzyme activity together with decreased radical production from XO.
A survey and measurement of residues of lindane (organochlorine pesticides) in four species of the most consumed fish in the Caspian Sea (Iran)
Authors: Ebadi AG , Shokrzadeh M
Published: February 2006

In this study, samples of four species of the most consumed fish (sefid, koli, kilca and kafal fish) were analysed for concentrations of lindane (organochlorine pesticides). Fish were caught using electric fishing at four sites (Chalous and Babolsar cities, Khazar Abad and Miankaleh regions) in the Mazandaran provinces of Iran. Quantitative determination of the lindane was performed by gas chromatography electron-capture detection (GC-ECD). Samples contained detectable concentrations of lindane, but at concentrations below the maximum residue limit (MRL). No differences were found in the lindane concentrations between the types of fish at each site, but there were two groups of sites that were significantly different from one another in terms of lindane concentrations: sites II-IVB/site I (PB/0.05). However, the concentrations of lindane residues in the muscle were found to be less than the FAO/WHO (1993) recommended permissible intake and should not be of public concern in Mazandaran province.
Acute toxicity of polychlorinated naphthalenes and their effect on cytochrome P450
Authors: Galoch A , Sapota A , Skrzypinska-Gawrysiak M , Kilanowicz A
Published: February 2006

Polychlorinated naphthalenes (PCNs) are able to induce cytochrome P-450-dependent microsomal monooxygenase activities in vivo and in vitro. The aim of this study was to investigate the toxicity of a PCN mixture, and its effect on the levels of cytochrome P-450 in rats.

The animals were intragastrically administered a mixture of PCNs in single doses of 250, 500 and 1000 mg/kg b.w. Dissection of animals was performed 24, 72 and 240 hours after administration.

After PCN administration (all doses) the body weight loss (up to 30% in comparison with the control group, 240 hours after administration) and an increase of relative liver mass (about 126 - 153% of controls, 72 hours after administration) were observed.

The exposure to PCN evoked an increase in the level of total cytochrome P-450 as well as the activity of CYP 1A (mediated 7-ethoxyresorufin O-deethylation) at all time points. The maximum activity of CYP 1A (about 12-to 15-fold increase in comparison with the control group) was observed 72 hours after dosing.

Malondialdehyde (MDA), determined in the liver, showed a high increase and 240 hours after administration, the level of MDA was about one order of magnitude greater in comparison with control.
Melatonin can suppress the cytotoxic effects of chlorpyrifos on human HepG2 cell lines
Authors: Gultekin F , Patat S , Akca H , Akdogan M , Altuntas I
Published: February 2006

The cytotoxic effect of chlorpyrifos (CP) on human HepG2 cell lines and the protective role of melatonin were investigated. TD50 of CP for HepG2 cells was also determined. The viability of HepG2 cells decreased with CP treatment in a dose-dependent manner (P <0.05). Preincubation with melatonin prior to CP application caused an increase in cell viability (P <0.05). TD50 of CP for HepG2 was determined as 84.5 μg/mL. A 1-hour melatonin treatment caused a decrease in TD50 from 84.5 to 34.1 μg/mL. The level of thiobarbituric acid reactive substance (TBARS) and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) were determined in cell lines with or without melatonin administration to find out the possible mechanism of melatonin. CP caused a significant decrease in SOD, GSH-Px and CAT activities and an increase in TBARS level (P <0.05). Pre-incubation of cells with melatonin prevented an increase in TBARS. Melatonin also reduced the CP-caused inhibition of the activities of GSH-Px and CAT (P <0.05). It was suggested that CP shows a cytotoxic effect on HepG2 cell lines and melatonin can suppress cytotoxicity caused by CP with its antioxidant properties. Melatonin also reduces TD50 of CP for HepG2 cell lines.
Protective effect of saffron (Crocus sativus L.) aqueous extract against genetic damage induced by anti-tumor agents in mice
Authors: Premkumar K , Thirunavukkarasu C , Abraham S K , Santhiya S T , Ramesh A
Published: February 2006

The genotoxic potential of anti-tumor drugs limits their efficacy in the treatment of cancers. Since ancient times, saffron (dried stigmas of Crocus sativus L.) has been used as a spice and medicinal herb. Saffron is a rich source of carotenoids and is known for its anti-cancer and antitumor properties. The present study was designed to ascertain the chemoprotective potential of saffron against the genotoxicity of three well-known anti-tumor drugs-cisplatin (CIS), cyclophosphamide (CPH) and mitomycin C (MMC)-using comet assay. Three doses of saffron (20, 40 and 80 mg/kg b.w.) were orally administered to mice for five consecutive days prior to the administration of anti-tumor drugs under investigation. Pre-treatment with saffron significantly inhibited anti-tumor drugs induced cellular DNA damage (strand breaks) as revealed by decreased comet tail length, tail moment and percent DNA in the tail. These findings, together with our previous results, suggest a potential role for saffron as an anti-genotoxic, anti-oxidant and chemopreventive agent and could be used as an adjuvant in chemotherapeutic applications.
Molecular mechanisms of cadmium induced mutagenicity
Authors: Filipič M , Fatur T , Vudrag M
Published: February 2006

Cadmium is a human carcinogen of worldwide concern because it accumulates in the environment due to its extremely long half-life. Its compounds are classified as human carcinogens by several regulatory agencies. Cadmium affects cell proliferation, differentiation, apoptosis and other cellular activities and can cause numerous molecular lesions that would be relevant to carcinogenesis. For a long time cadmium has been considered as a non-genotoxic carcinogen, as it is only weakly mutagenic in bacterial and mammalian cell test systems. Recently, we presented evidence that when assayed in a test system, in which both intragenic and multilocus mutations can be detected, cadmium acts as a strong mutagen which induces predominantly multilocus deletions. In this review, we discuss two mechanisms that play an important role in cadmium mutagenicity: (i) induction of reactive oxygen species (ROS); and (ii) inhibition of DNA repair. Experimental evidence suggests that cadmium at low, for environmental exposure relevant concentrations, induces mutations by inducing oxidative DNA damage and that it decreases genetic stability by inhibiting the repair of endogenous and exogenous DNA lesions, which in turn increase the probability of mutations and consequently cancer initiation by this metal.
Altered gene expression in human cells treated with the insecticide diazinon: correlation with decreased DNA excision repair capacity
Authors: Mankame T , Hokanson R , Fudge R , Chowdhary R , Busbee D
Published: February 2006

Many industrial and agricultural chemicals have steroid hormone agonist or antagonist activities and disrupt hormone-regulated gene expression. The widely-used agricultural insecticide, diazinon, was evaluated using MCF-7 cells a breast cancer-derived, estrogen-dependent, human cell line-to examine the capacity of this chemical to alter steroid hormone-regulated gene expression. MCF-7 cells were treated with 30, 50, or 67 ppm of diazinon, and gene expression in treated cells was measured as mRNA levels in the cells compared to mRNA levels in untreated or estrogen-treated cells. DNA microarray analysis showed significant up-or down-regulation of a number of genes in treated cells compared to untreated cells. Of the 600 human genes on the chip utilized, specific genes with related functions were selected for additional consideration. Real time quantitative PCR (qrtPCR) completed to corroborate mRNA levels as a measure of specific gene expression, confirmed results obtained from analysis of the micro-array data. The data show that ERCC5, encoding Xeroderma pigmentosum protein G (XPG), essential for DNA excision repair, and ribonucleotide reductase subunit M1 (RNRM1), encoding a gene necessary for providing the nucleotides needed for DNA repair, were down-regulated in cells treated with diazinon. These studies were designed to provide base-line data on the gene expression-altering capacity of a specific agricultural chemical, diazinon, and allow assessment of some of the potentially deleterious effects associated with exposure of human cells to diazinon.
Does dioxin exert toxic effects in humans at or near current background body levels?: an evidence-based conclusion
Authors: Guzelian P , Quattrochi L , Karch N , Aylward L , Kaley R
Published: February 2006

Evidence-based toxicology like evidence-based medicine, provides scientifically grounded evidence-based conclusions as distinguished from authority-based opinions. As an example, we address a proposition from the US Environmental Protection Agency's (EPA) Draft Dioxin [2,3, 7,8-tetrachlorodibenzo-P-dioxin (TCDD)] reassessment that: ‘dioxin... can produce effects... at or near current background body burdens or intake levels’. Guided by a systematic, objective, and unbiased analysis of the available molecular, physiological, and clinical/epidemiologic data, in accordance with accepted principles of scientific logic, we reach the evidence-based conclusion that the proposition is rejected. When gaps in scientific knowledge necessitate formulation of opinions to meet preventive or precautionary goals, the reversion to authority should be explicitly acknowledged.
Alcohol distribution in different postmortem body fluids
Authors: De Martinis B S , de Paula C MC , Braga A , Moreira H T , Martin C CS
Published: February 2006

Aims: The determination of postmortem ethanol is one of the most frequently requested analyses in forensic toxicology and of extreme importance, especially when the concentration is found to be above the legal level for intoxication at one sampling site and below that level at another sampling site. Because of the unavailability of blood samples for toxicological analysis or even contaminated samples, there is an enormous effort to find alternative sampling sites, such as vitreous humor for ethanol analysis. The main purpose of this study was to establish correlations between urine and blood alcohol concentrations collected from different sites and vitreous humor. Methods: Ethanol concentrations were determined in specimens of heart, subclavian and femoral blood, urine and vitreous humor, collected from 21 cadavers who were victims of different causes of death. Determinations of ethanol were performed in duplicate using capillary gas chromatography/flame ionization detector and headspace techniques. Results: Statistical analysis of the results indicated that there were no significant differences among urine and blood samples collected from different sites compared to vitreous humor. Regarding vitreous humor ethanol concentration, Pearson's correlation coefficient was 0.97 for femoral blood and urine, 0.96 for heart blood and 0.94 for subclavian blood. The results demonstrated that all the fluids tested against vitreous humor significantly correlated with P (associated probability for the used correlation tests) B<0.05. Conclusions: Vitreous humor can be considered as an alternative sample to urine and blood specimens.
Systemic lupus erythematosus arising in a patient with epidermodysplasia verruciformis
Authors: Aghaei S , Aslani F S
Published: February 2006

Few cases have been published relating systemic lupus erythematosus (SLE) and epidermodysplasia verruciformis (EV). We describe a patient with this association. A 22-year-old female with classical skin lesions of EV since childhood together with systemic lupus erythematosus (SLE) which developed 10 years later. According to the knowledge of the authors, this case is the third report of association of EV and SLE and the first report of a patient with EV who developed SLE several years after initiation of EV.
Systemic lupus erythematosus in a multiethnic US cohort (LUMINA) XXVII: factors predictive of a decline to low levels of disease activity
Authors: Bertoli A M , Alarcón G S , McGwin G , Fernández M , Bastian H M , Fessler B J , Vilá L M , Reveille J D ,   LUMINA Study Group
Published: February 2006

The objective of this study was to examine factors predictive of a decline to low levels of disease activity in a cohort of systemic lupus erythematosus (SLE) patients. Patients with SLE of Hispanic (from Texas or Puerto Rico), African-American or Caucasian ethnicity from a multiethnic cohort were included. A decline to low levels of disease activity was defined as a score ≤5 as per the Systemic Lupus Activity Measure-Revised (SLAM-R) at any annual study visit if preceded by a SLAM-R 8. Using Generalized Estimating Equation (GEE), socioeconomic-demographic, behavioral, function, psychological, laboratory and clinical data [disease manifestations, number of ACR criteria accrued at diagnosis and damage accrual as per the Systemic Lupus International Collaborating Clinics (SLICC) Damage Index (SDI)] from the visit preceding that meeting the definition were examined as predictors of decline to low levels of disease activity. Two-hundred and eighty-seven patients (67 Hispanics from Texas, 32 Hispanics form Puerto Rico, 120 African-Americans and 68 Caucasians), accounting for 632 visits were analyzed. In the GEE multivariable analysis, higher degrees of social support (OR = 1.208, 95% CI 1.059-1.379; P = 0.005) were predictive of a decline to low levels of disease activity, while the number of ACR criteria accrued at diagnosis (OR = 0.765, 95% CI 0.631-0.927; P = 0.006) and damage (OR = 0.850, 95% CI 0.743-0.972, P = 0.018) were negatively associated. These data suggest that a decline to low levels of disease activity in lupus patients seems to be multifactorial; this study also underscores the importance of social support for lupus patients.
Systemic lupus erythematosus in a multiethnic US cohort (LUMINA) XXXI: factors associated with patients being lost to follow-up
Authors: Bertoli A M , Fernández M , Calvo-Alén J , Vilá L M , Sanchez M L , Reveille J D , Alarcón G S ,   LUMINA Study Group
Published: February 2006

The objective of this study was to determine the frequency of loss to follow-up and the factors predictive of its occurrence in a systemic lupus erythematosus (SLE) multiethnic cohort. We studied SLE patients from the LUMINA cohort (Hispanics from Texas and from the Island of Puerto Rico, African-Americans and Caucasians). Loss to follow-up was defined as subjects who failed to attend two or more of the latest consecutive yearly study visits. The relationship between baseline features and loss to follow-up was examined by univariable and multivariable Cox regression analyses with loss to follow-up as the dependent variable. The retention rate in the cohort was estimated by the Kaplan-Meier method. Five-hundred and fifty-four patients with a mean (SD) follow-up of 3.4 (2.9) years were studied. One-hundred and fifty-eight (29%) met the definition of lost to follow-up. The cumulative loss to follow-up rate at five years was 36%. The cumulative loss to follow-up rate at five years was higher for the African-Americans. Patients lost to follow-up tended to be younger and more likely to have poor social support and higher levels of helplessness. They also tended to have more renal involvement and more active disease as per the Systemic Lupus Activity Measure-Revised. Disease activity (hazard ratio = 1.04, 95% confidence interval 1.01-1.07, P = 0.02) was the only variable independently contributing to loss to follow-up. Our data suggest that in longitudinal SLE studies, loss to follow-up does not occur at random and it differs between ethnic groups and is also particularly higher among patients with more active disease. Pro-active measures may need to be applied to decrease the probability of patients ‘at risk’ of becoming lost to follow-up and to preserve the integrity of the cohort.
Myocardial perfusion defects in patients with autoimmune diseases: a prospective study. Analysis of two diagnostic tests
Authors: Espinola-Zavaleta N , Alexanderson-Rosas E , Granados N , Soto M Elena , Amigo M-C
Published: February 2006

A significant correlation between autoimmune diseases and premature or accelerated coronary atherosclerosis has been found. The objectives of the study were: (a) to evaluate myocardial perfusion defects in patients with autoimmune diseases by contrast echocardiography and nuclear imaging; and (b) to evaluate the prevalence of alterations in subclinical myocardial perfusion defects in autoimmune diseases. Myocardial perfusion in 37 patients was evaluated by contrast echocardiography at rest and with dobutamine and with nuclear imaging. The agreement between the two diagnostic tests at rest was 0.72 ( P < 0.0001) and with dobutamine was 0.65 ( P < 0.0001). The prevalence of abnormalities in myocardial perfusion in autoimmune diseases by contrast echocardiography and nuclear imaging was 27% and in patients with primary antiphospholipid syndrome was 30%. We concluded that there is a high level of agreement between contrast ecocardiography and nuclear imaging for assessment of myocardial perfusion defects in patients with autoimmune diseases, and their prevalence is similar to that reported in the literature.
Modelling risks in disease mapping
Authors: Ugarte M D , Ibáñez B , Militino A F
Published: February 2006

In this article, we propose a strategy of analysis of mortality data with the aim of providing a guideline for epidemiologists and public health researchers to choose a reasonable model for estimating mortality (or incidence) risks. Maps displaying the crude mortality rates or ratios are usually misleading because of the instability of the estimators in low populated areas. As an alternative, many smoothing methods have been presented in the literature based on Poisson inference. They account for the extra-Poisson variation (overdispersion), frequently present in the homogeneous Poisson model, by incorporating random effects. Here, we recommend to test for the potential sources of extra-Poisson variation because, depending on them, the models which fit better the data may be different. Overdispersion can be mainly due to spatial autocorrelation, unstructured heterogeneity or to a combination of these two, and also, when studying very rare diseases, it can be due to an excess of zeros in the data. In this article, different situations the analyst may encounter are detailed and appropriate procedures for each case are presented. The alternative models are illustrated using mortality data provided by the Statistical Institute of Navarra, Spain.
Indirect Regulation of Human Dehydroepiandrosterone Sulfotransferase Family 1A Member 2 by Thyroid Hormones
Authors: Huang Ya-Hui , Lee Chih-Yi , Tai Pei-Ju , Yen Chun-Che , Liao Chu-Yu , Chen Wei-Jan , Liao Cheng-Jung , Cheng Wan-Li , Chen Ruey-Nan , Wu Sheng-Ming , Wang Chia-Siu , Lin Kwang-Huei
Published: February 2006

Thyroid hormone, T3, regulates cell metabolism, differentiation, and development. cDNA microarrays were performed to study the mechanism of target gene regulation after T3 treatment in a thyroid hormone receptor-α (TRα)-overexpressing hepatoma cell line (HepG2-TRα). The differentially expressed target genes are several metabolic enzymes, including dehydroepiandrosterone-sulfotransferase family 1A member 2 (SULT2A1). Enzyme SULT2A1 was elevated roughly 5-fold at the protein level and 9-fold increase at the mRNA level after 48 h T3 treatment in HepG2-TRα cells. Cycloheximide inhibited T3-induced SULT2A1 expression, suggesting that regulation was indirect. SULT2A1 has been reported to be regulated by the two transcription factors, steroidogenic factor 1 (SF1) and GATA, in the human adrenal gland. T3 induced a 2.5- to 3.5-fold elevation of SF1 at the protein level and a 6.2-fold increase at the RNA level in HepG2-TRα cells. About seven SF1 binding sites exist on the SULT2A1 gene. To identify and localize the critical SF1 binding site, series of deletion mutants of SULT2A1 promoter fragments in pGL2 plasmid were constructed. The promoter activity of the SULT2A1 gene was enhanced about 2.8- to 7.1-fold by T3. The −228 SF1 binding site was identified as the most critical site because deleting this region reduced T3-induced expression. Transcription factor SF1 application enhanced the −228 but not −117 reporter plasmid activities. SULT2A1 and SF1 up-regulation at protein and RNA levels in thyroidectomized rats occurred after T3 application. In summary, this work demonstrated that the SULT2A1 gene was mediated by SF1 and indirectly regulated by T3. Further study is required to elucidate the physiological importance of SULT2A1 induction mediated by T3.
Identification of the Chicken Growth Hormone-Releasing Hormone Receptor (GHRH-R) mRNA and Gene: Regulation of Anterior Pituitary GHRH-R mRNA Levels by Homologous and Heterologous Hormones
Authors: Porter Tom E. , Ellestad Laura E. , Fay Allison , Stewart Joanna L. , Bossis Ioannis
Published: February 2006

GHRH stimulates GH secretion in chickens as in mammals. However, nothing is known about the chicken GHRH receptor (GHRH-R). Here we report the cDNA sequence of chicken GHRH-R. Comparison of the cDNA sequence with the chicken genome localized the GHRH-R gene to chicken chromosome 2 and indicated that the chicken GHRH-R gene consists of 13 exons. Expression of all exons was confirmed by RT-PCR amplification of pituitary mRNA. The amino acid sequence predicted by the GHRH-R cDNA is homologous to that in other vertebrates and contains seven transmembrane domains and a conserved hormone-binding domain. The predicted size of the GHRH-R protein (48.9 kDa) was confirmed by binding of 125I-GHRH to chicken pituitary membranes and SDS-PAGE. GHRH-R mRNA was readily detected by RT-PCR in the pituitary but not in the hypothalamus, total brain, lung, adrenal, ovary, or pineal gland. Effects of corticosterone (CORT), GHRH, ghrelin, pituitary adenylate cyclase-activating peptide, somatostatin (SRIF), and TRH on GHRH-R and GH gene expression were determined in cultures of chicken anterior pituitary cells. GHRH-R and GH mRNA levels were determined by quantitative real-time RT-PCR. Whereas all treatments affected levels of GH mRNA, only CORT, GHRH, and SRIF significantly altered GHRH-R mRNA levels. GHRH-R gene expression was modestly increased by GHRH and suppressed by SRIF at 4 h, and CORT dramatically decreased levels of GHRH-R mRNA at 72 h. We conclude that adrenal glucocorticoids may substantially impact pituitary GH responses to GHRH in the chicken through modulation of GHRH-R gene expression.
Continuous Human Metastin 45–54 Infusion Desensitizes G Protein-Coupled Receptor 54-Induced Gonadotropin-Releasing Hormone Release Monitored Indirectly in the Juvenile Male Rhesus Monkey (Macaca mulatta): A Finding with Therapeutic Implications
Authors: Seminara Stephanie B. , DiPietro Meloni J. , Ramaswamy Suresh , Crowley William F. , Plant Tony M.
Published: February 2006

The effect of continuous administration of the C-terminal fragment of metastin, the ligand for the G protein-coupled receptor, GPR54, on GnRH-induced LH secretion was examined in three agonadal, juvenile male monkeys whose responsiveness to GnRH was heightened by pretreatment with a chronic pulsatile iv infusion of synthetic GnRH. After bolus injection of 10 μg human (hu) metastin 45–54 (equivalent to kisspeptin 112–121), the GPR54 agonist was infused continuously at a dose of 100 μg/h and elicited a brisk LH response for approximately 3 h. This rise was then followed by a precipitous drop in LH despite continuous exposure of GPR54 to metastin 45–54. On d 4, during the final 3 h of the infusion, single boluses of hu metastin 45–54 (10 μg), N-methyl-dl-aspartic acid (NMDA) (10 mg/kg) and GnRH (0.3 μg) were administered to interrogate each element of the metastin-GPR54-GnRH-GnRH receptor cascade. Although the NMDA and GnRH boluses were able to elicit LH pulses, that of hu metastin 45–54 was not, demonstrating functional integrity of GnRH neurons (NMDA) and GnRH receptors (NMDA and GnRH) but desensitization of GPR54. The desensitization of GPR54 by continuous hu metastin 45–54 administration has therapeutic implications for a variety of conditions currently being treated by GnRH and its analogs, including restoration of fertility in patients with abnormal GnRH secretion (i.e. idiopathic hypogonadotropic hypogonadism and hypothalamic amenorrhea) and selective, reversible suppression of the pituitary-gonadal axis to achieve suppression of gonadal steroids (i.e. precocious puberty, endometriosis, uterine fibroids, and prostate cancer).
Fetal Growth and the Adrenocortical Response to Psychological Stress
Authors: Jones Alexander , Godfrey Keith M. , Wood Peter , Osmond Clive , Goulden Peter , Phillips David I. W.
Published: February 2006

Context: Experimental studies in animals show that adverse prenatal environments lead to lifelong alterations in the activity of the hypothalamic-pituitary-adrenal axis, which mediates the stress response through secretion of glucocorticoid hormones. The extent to which such prenatal hypothalamic-pituitary-adrenal axis adaptations occur in humans is unknown.

Objective: The objective of the study was to determine whether smaller but otherwise healthy term babies are more likely to demonstrate increased glucocorticoid responses to psychological stress in childhood.

Design and Participants: This was a cross-sectional study of 68 boys and 72 girls (aged 7–9 yr) who have been followed up since 12 wk gestation when their mothers took part in a study of healthy children born in Southampton, United Kingdom.

Main Outcome Measure: Salivary cortisol responses to psychological stress were measured.

Results: In boys, birth weight was inversely related to salivary cortisol responses to stress (r = −0.56, P < 0.001) but not morning cortisol levels, whereas in girls, morning peak cortisol was inversely related to birth weight (r = −0.36, P < 0.05). These associations were independent of gestational age and potential confounding factors including obesity, social class, and educational achievement.

Conclusions: This study suggests that processes occurring during fetal life, resulting in smaller newborns, have a lasting effect on adrenocortical responses to stress in boys and on basal adrenocortical activity in girls. Given the known associations between small alterations in adrenocortical activity and features of the metabolic syndrome such as raised blood pressure and glucose intolerance, these effects warrant further investigation of their potential impact on the future health of prepubertal children.
A Novel Activating Mutation in the RET Tyrosine Kinase Domain Mediates Neoplastic Transformation
Authors: Cranston Aaron , Carniti Cristiana , Martin Sam , Mondellini Piera , Hooks Yvette , Leyland Jean , Hodgson Shirley , Clarke Sue , Pierotti Marco , Ponder Bruce A. J. , Bongarzone Italia
Published: February 2006

We report the finding of a novel missense mutation at codon 833 in the tyrosine kinase of the RET proto-oncogene in a patient with a carcinoma of the thyroid. In vitro experiments demonstrate that the R833C mutation induces transformed foci only when present in the long 3′ splice isoform and, in keeping with a model in which the receptor has to dimerize to be completely activated, glial cell line-derived neurotrophic factor stimulation leads the RETR833C receptor to a higher level of activation. Tyrosine kinase assays show that the RETR833C long isoform has weak intrinsic kinase activity and phosphorylation of an exogenous substrate is not elevated even in the presence of glial cell line-derived neurotrophic factor. Furthermore, the R833C mutation is capable of sustaining the transformed phenotype in vivo but does not confer upon the transformed cells the ability to degrade the basement membrane in a manner analogous to metastasis. Our functional characterization of the R833C substitution suggests that, like the V804M and S891A mutations, this tyrosine kinase mutation confers a weak activating potential upon RET. This is the first report demonstrating that the introduction of an intracellular cysteine can activate RET. However, this does not occur via dimerization in a manner analogous to the extracellular cysteine mutants.
Socs2 and Elf5 Mediate Prolactin-Induced Mammary Gland Development
Authors: Harris Jessica , Stanford Prudence M. , Sutherland Kate , Oakes Samantha R. , Naylor Matthew J. , Robertson Fiona G. , Blazek Katrina D. , Kazlauskas Michael , Hilton Heidi N. , Wittlin Sergio , Alexander Warren S. , Lindeman Geoffrey J. , Visvader Jane E. , Ormandy Christopher J.
Published: February 2006

The proliferative phase of mammary alveolar morphogenesis is initiated during early pregnancy by rising levels of serum prolactin and progesterone, establishing a program of gene expression that is ultimately responsible for the development of the lobuloalveoli and the onset of lactation. To explore this largely unknown genetic program, we constructed transcript profiles derived from transplanted mammary glands formed by recombination of prolactin receptor (Prlr) knockout or wild-type mammary epithelium with wild-type mammary stroma. Comparison with profiles derived from prolactin-treated Scp2 mammary epithelial cells produced a small set of commonly prolactin-regulated genes that included the negative regulator of cytokine signaling, Socs2 (suppressor of cytokine signaling 2), and the ets transcription factor, E74-like factor 5 (Elf5). Homozygous null mutation of Socs2 rescued the failure of lactation and reduction of mammary signal transducer and activator of transcription 5 phosphorylation that characterizes Prlr heterozygous mice, demonstrating that mammary Socs2 is a key regulator of the prolactin-signaling pathway. Reexpression of Elf5 in Prlr nullizygous mammary epithelium restored lobuloalveolar development and milk production, demonstrating that Elf5 is a transcription factor capable of substituting for prolactin signaling. Thus, Socs2 and Elf5 are key members of the set of prolactin-regulated genes that mediate prolactin-driven mammary development.
Intricate Alliances: Some Spanish Formulations of Language and Empire
Authors: Brownlee Marina
Published: February 2006

Marina Brownlee is Robert Schirmer Professor of Spanish and professor of comparative literature at Princeton University. Her works include, among others, The Severed Word: Ovid's “Heroides” and the Novela Sentimental (1990); the collection Cultural Authority in Golden Age Spain, edited with Hans Ulrich Gumbrecht (1995); and The Cultural Labyrinth of María de Zayas (2000). Her current research explores the nature and impact of sixteenth-century tabloid literature in Spain, cultural interactions between Spain and England, and periodization in medieval and early modern Spain.
New polymorph friction-stir-welded aluminium liquid petroleum gas tank
Authors: Oosterkamp L D , Heurtaux F
Published: February 2006

This paper presents the development of the new flexible polymorph liquid-petrol-gas (LPG) tank. Research has been carried out in close collaboration between Renault (France), Hydro Aluminium (Norway), and Witte van Moort (The Netherlands). The term polymorph is used here to describe a complex shape built from different simple forms. This type of tank is specifically designed to be integrated under a vehicle floor and, owing to its flexibility in design, it enables an increased range compared with conventional steel tanks. The new LPG tank is made from aluminium extruded sections, longitudinally joined by applying the friction-stir-welding process and aluminium end closures made by stamping. This allows good mechanical properties and a significant mass reduction.
Aerodynamics of a wing in ground effect in generic racing car wake flows
Authors: Soso M D , Wilson P A
Published: February 2006

In an effort to provide more detailed insight into the aerodynamic factors that may influence the creation of overtaking opportunities in modern open-wheeled racing series, a set of wind tunnel experiments was initiated in the moving ground facilities at the University of Southampton. To generate data typical of one car following another, a single-element wing in ground effect was tested downstream of a bluff body that incorporated a diffuser and rear wing. The tests included variations in the height and angle of attack of the wing, while data collection was achieved via force and pressure measurements, flow visualization and flowfield surveys. The results were then compared with baseline data that were obtained without the presence of the bluff body. It was found that, while behind the upstream body, the wing experienced a decrease in its downforce values, with the amount of downforce lost depending on its height above the ground. It was also shown that more downforce was lost from sections closer to the mid-span of the wing than was the case from sections closer to the tips of the wing.
A semi-automated parallel parking system for passenger cars
Authors: Pohl J , Sethsson M , Degerman P , Larsson J
Published: February 2006

Car parking has been, and still is, a growing problem, with increasing vehicle sizes in the luxury segment as well as sport-utility vehicles. This is especially true when bearing in mind the confined parking spaces in parking lots and cities. While damage during parking generally does not cause any injury to the passengers, it is costly and annoying. Park assist systems are by no means new on the market, since passive systems which provide longitudinal guidance using ultrasonic distance sensors have been available on the market for a number of years.

The system presented is a semi-automated approach to parallel parking problems, as they frequently occur in European and Asian cities. The challenge during the development of this system was to have as few components as possible added to a standard vehicle, seeking reuse of many of the already built-in functionalities. The result is a system that leaves the longitudinal control of the vehicle to the driver but automates the steering process, and even stops the vehicle when the final parking position is reached.
A comparison of fuel consumption between hybrid and intelligent vehicles during urban driving
Authors: Manzie C , Watson H C , Halgamuge S , Lim K
Published: February 2006

Two major emerging automotive technologies are the continued development of hybrid-electric drivetrains and telematics-enabled (or ‘intelligent’) vehicles capable of garnering and utilizing information about the traffic environment in which the vehicles are operating. The significant costs of each of these technologies are located internal to the vehicle (i.e. the powertrain) in the former case and external to the vehicle (i.e. the road and communication infrastructure) in the latter. In this paper, a simple algorithm is proposed for shaping the velocity profile of an intelligent vehicle subjected to different degrees of traffic information. The fuel consumption of this intelligent vehicle is then compared to a hybrid vehicle with a configuration optimized for an urban drive cycle under the constraint that its performance must match the conventional vehicle it is replacing. This provides some perspective on the extent to which telematics can be used to improve fuel economy relative to the best possible hybrid alternative. Finally, the fuel consumption of an intelligent-hybrid vehicle is investigated; however, the optimal use of information and switching control in the hybrid drivetrain remains an unsolved problem to date.
Effects of porosity on the fatigue performance of polymethyl methacrylate bone cement: An analytical investigation
Authors: Evans S L
Published: February 2006

Porosity has been shown to affect the fatigue life of bone cements, but, although vacuum mixing is widely used to reduce porosity in the clinical setting, results have been mixed and the effects of porosity are not well understood. The aim of this study was to investigate the effects of porosity using stress analysis and fracture mechanics techniques.

The stress concentrations arising at voids in test specimens were found using analytical solutions and boundary element methods. The fatigue life of specimens containing voids of various sizes was predicted using fracture mechanics techniques.

For spherical voids that do not occupy a significant proportion of the cross-section, the resulting stress concentration is independent of void size and too small to account for the observed crack initiation. Cracks must therefore initiate at additional stress raisers such as radiopacifier particles or additional voids. For large voids, the stress increases as the remaining cross-section of the specimen decreases, and this may account for much of the observed reduction in fatigue strength in hand-mixed cement.

Although crack initiation may be largely independent of void size, there is an effect on crack growth rate. Cracks are predicted to grow faster around larger voids, since they remain in the stress concentration around the void for longer. This effect may account for the relationship between porosity and fatigue life that has been observed in samples without large voids.

Since porosity appears to affect crack growth more than initiation, it may be less damaging in high-cycle clinical fatigue, which may be predominantly initiation controlled, than in short laboratory tests.