bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Assessing Tumor Vascularity and Vascular Effects of Targeted Therapies in Renal Cell Carcinoma
Authors: Rosen Mark A. , Schnall Mitchell D.
Published: January 2007

Traditional cross-sectional tumor imaging focuses solely on tumor morphology. With the introduction of targeted biological therapies in human trials, morphologic change may lag behind other physiologic measures of response on clinical images. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a new imaging method for assessing the physiologic state of tumor vascularity in vivo. DCE-MRI, which uses available imaging techniques and contrast agents, assays the kinetics of tumor enhancement during bolus i.v. contrast administration. Modeling of the temporal enhancement pattern yields physiologic variables related to tumor blood flow and microvessel permeability. Changes in these variables after vascular-targeted therapy can then be quantified to evaluate the tumor vascular response. As these responses may precede morphologic tumor shrinkage, DCE-MRI might serve as a noninvasive means of monitoring early tumor response to vascular-targeted therapy. Renal cell carcinoma provides an excellent model for assessing the effect on DCE-MRI in clinical trials. The vascular richness of renal tumors provides a large dynamic scale of DCE-MRI measures. Patients with disseminated renal cell carcinoma frequently present with one or several large tumors, creating an easy imaging target for DCE-MRI evaluation. Finally, renal cell carcinoma is clearly susceptible to therapies that target tumor angiogenesis. DCE-MRI can be used to monitor the vascular changes induced by such therapies. Future efforts must be directed to standardizing image acquisition and analysis techniques to quantify tumor vascular responses.
The Role of Mammalian Target of Rapamycin Inhibitors in the Treatment of Advanced Renal Cancer
Authors: Cho Daniel , Signoretti Sabina , Regan Meredith , Mier James W. , Atkins Michael B.
Published: January 2007

Inhibitors of the mammalian target of rapamycin (mTOR) have shown promising efficacy in early-stage trials in patients with advanced renal cell carcinoma (RCC). Most RCCs have been shown to possess biallelic alterations in the von Hippel-Lindau (VHL) gene, resulting in accumulation of hypoxia-inducible factors 1α and 2α, as well as their downstream targets including vascular endothelial growth factor (VEGF). The observed clinical efficacy of mTOR inhibitors in patients with RCC may be mediated in part by the dependence of efficient hypoxia-inducible factor translation on the mTOR pathway. mTOR inhibitors have entered more advanced phase clinical trials either as single agents or in combination with other targeted agents or IFN, which might ultimately result in regulatory approval of one or more agents. Given the likely nonoverlapping mechanism of action of mTOR inhibitors and VEGF pathway–targeted agents, mTOR inhibitors may prove useful if administered in combination or after resistance to VEGF inhibitors. With an increasing number of active agents for treatment of patients with RCC, efforts must continue to develop patient selection models based on predictive biomarkers to direct therapy to appropriate patients.
A Phase I Study of Immunization Using Particle-Mediated Epidermal Delivery of Genes for gp100 and GM-CSF into Uninvolved Skin of Melanoma Patients
Authors: Cassaday Ryan D. , Sondel Paul M. , King David M. , Macklin Michael D. , Gan Jacek , Warner Tom F. , Zuleger Cindy L. , Bridges Alan J. , Schalch Heidi G. , Kim Kyung Mann , Hank Jacquelyn A. , Mahvi David M. , Albertini Mark R.
Published: January 2007

Purpose: We examined in vivo particle-mediated epidermal delivery (PMED) of cDNAs for gp100 and granulocyte macrophage colony-stimulating factor (GM-CSF) into uninvolved skin of melanoma patients. The aims of this phase I study were to assess the safety and immunologic effects of PMED of these genes in melanoma patients.

Experimental Design: Two treatment groups of six patients each were evaluated. Group I received PMED with cDNA for gp100, and group II received PMED with cDNA for GM-CSF followed by PMED for gp100 at the same site. One vaccine site per treatment cycle was biopsied and divided for protein extraction and sectioning to assess transgene expression, gold-bead penetration, and dendritic cell infiltration. Exploratory immunologic monitoring of HLA-A2+ patients included flow cytometric analyses of peripheral blood lymphocytes and evaluation of delayed-type hypersensitivity to gp100 peptide.

Results: Local toxicity in both groups was mild and resolved within 2 weeks. No systemic toxicity could be attributed to the vaccines. Monitoring for autoimmunity showed no induction of pathologic autoantibodies. GM-CSF transgene expression in vaccinated skin sites was detected. GM-CSF and gp100 PMED yielded a greater infiltration of dendritic cells into vaccine sites than did gp100 PMED only. Exploratory immunologic monitoring suggested modest activation of an antimelanoma response.

Conclusions: PMED with cDNAs for gp100 alone or in combination with GM-CSF is well tolerated by patients with melanoma. Moreover, pathologic autoimmunity was not shown. This technique yields biologically active transgene expression in normal human skin. Although modest immune responses were observed, additional investigation is needed to determine how to best utilize PMED to induce antimelanoma immune responses.
Phase 2 Studies of Sunitinib and AG013736 in Patients with Cytokine-Refractory Renal Cell Carcinoma
Authors: George Daniel J.
Published: January 2007

Frequent loss of the von Hippel-Lindau (VHL) gene product in conventional-type renal cell carcinoma results in constitutive expression of proangiogenic growth factors, including vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). VEGF and PDGF function in a paracrine manner to stimulate tumor angiogenesis that results in a hypervascular phenotype. Dependency on this hypervascularity is underscored by the recent clinical efficacy shown by inhibition of the VEGF pathway. Most strategies that primarily target the VEGF pathway (neutralizing antibodies or receptor tyrosine kinase inhibitors) result in objective tumor responses in ≤10% of cases but show a significant delay in time to disease progression. In contrast, two multitargeted receptor tyrosine kinase inhibitors that target both VEGF and PDGF receptors (sunitinib and AG013736) have shown ≥40% objective responses with clinically important duration. Several hypotheses may explain the discrepancy of these response rates from other strategies in the class, including the synergistic effects of dual inhibition of VEGF and PDGF receptors, supported by preclinical studies. Ultimately, further clinical investigations with pharmacodynamic and correlative science end points are needed to clarify the mechanisms of action and resistance to build on the biological and clinical effects of these multitargeted agents.
Developing a Rational Tumor Vaccine Therapy for Renal Cell Carcinoma: Immune Yin and Yang
Authors: Ernstoff Marc S. , Crocenzi Todd S. , Seigne John D. , Crosby Nancy A. , Cole Bernard F. , Fisher Jan L. , Uhlenhake Jill C. , Mellinger Diane , Foster Cathy , Farnham Conrad J. , Mackay Kathleen , Szczepiorkowski Zbigniew M. , Webber Susan M. , Schned Alan R. , Harris Robert D. , Barth Richard J. , Heaney John A. , Noelle Randolph J.
Published: January 2007

In patients with progressive malignancy, the natural balance between proinflammatory (Yang) and inhibitory (regulatory or Yin) immune pathways is disrupted and favors cancer-specific immune suppression. Therapy with interleukin 2 (IL-2) can mobilize immune effector cells that recognize and destroy cancer. High-dose IL-2 is the only therapy that has consistently induced complete durable remissions in patients with metastatic renal cell carcinoma (RCC) but only in a few of them. The lack of benefit in most metastatic RCC patients is likely due to the ineffective manipulation of other immune circuits critical in regulating tumor cytotoxic pathways. The limited clinical activity of IL-2, RCC vaccines, and other immune therapies to date leads us to postulate that effective clinical treatment strategies will need to simultaneously enhance proinflammatory pathways and disrupt regulatory pathways. We present preliminary studies in RCC patients to highlight the complexity of the regulatory pathways and our approach to shifting the balance of proinflammatory and regulatory immune pathways using dendritic cell–tumor lysate vaccine followed by cytokine therapy.
Multimodal Approaches in the Management of Locally Advanced and Metastatic Renal Cell Carcinoma: Combining Surgery and Systemic Therapies to Improve Patient Outcome
Authors: Wood Christopher G.
Published: January 2007

Patients with locally advanced renal cell carcinoma are at high risk of metastatic relapse following surgery. Patients with metastatic disease have a poor prognosis and few systemic therapy options. Radiation, chemotherapy, hormonal therapy, vaccines, and immunotherapy have all been tested as adjuvant therapy without benefit. Neoadjuvant therapy in the metastatic setting holds promise as a new treatment paradigm. It can serve as a litmus test to allow proper patient selection for aggressive surgical intervention and may provide limited downstaging of primary tumors in selected cases. It can also provide a histologic assessment of the effect of targeted therapy. Application of this paradigm may have merit in the locally advanced setting as well. Effective adjuvant therapy for renal cell carcinoma remains elusive. The benefit of new targeted therapies has yet to be tested in this setting. Neoadjuvant strategies that integrate aggressive surgical intervention with systemic therapy may hold promise as a treatment paradigm.
Intercomparison of Water Vapor Data Measured with Lidar during IHOP_2002. Part I: Airborne to Ground-Based Lidar Systems and Comparisons with Chilled-Mirror Hygrometer Radiosondes
Authors: Behrendt Andreas , Wulfmeyer Volker , Bauer Hans-Stefan , Schaberl Thorsten , Di Girolamo Paolo , Summa Donato , Kiemle Christoph , Ehret Gerhard , Whiteman David N. , Demoz Belay B. , Browell Edward V. , Ismail Syed , Ferrare Richard , Kooi Susan , Wang Junhong
Published: January 2007

The water vapor data measured with airborne and ground-based lidar systems during the International H2O Project (IHOP_2002), which took place in the Southern Great Plains during 13 May–25 June 2002 were investigated. So far, the data collected during IHOP_2002 provide the largest set of state-of-the-art water vapor lidar data measured in a field campaign. In this first of two companion papers, intercomparisons between the scanning Raman lidar (SRL) of the National Aeronautics and Space Administration (NASA) Goddard Space Flight Center (GSFC) and two airborne systems are discussed. There are 9 intercomparisons possible between SRL and the differential absorption lidar (DIAL) of Deutsches Zentrum für Luft- und Raumfahrt (DLR), while there are 10 intercomparisons between SRL and the Lidar Atmospheric Sensing Experiment (LASE) of the NASA Langley Research Center. Mean biases of (−0.30 ± 0.25) g kg−1 or −4.3% ± 3.2% for SRL compared to DLR DIAL (DLR DIAL drier) and (0.16 ± 0.31) g kg−1 or 5.3% ± 5.1% for SRL compared to LASE (LASE wetter) in the height range of 1.3–3.8 km above sea level (450–2950 m above ground level at the SRL site) were found. Putting equal weight on the data reliability of the three instruments, these results yield relative bias values of −4.6%, −0.4%, and +5.0% for DLR DIAL, SRL, and LASE, respectively. Furthermore, measurements of the Snow White (SW) chilled-mirror hygrometer radiosonde were compared with lidar data. For the four comparisons possible between SW radiosondes and SRL, an overall bias of (−0.27 ± 0.30) g kg−1 or −3.2% ± 4.5% of SW compared to SRL (SW drier) again for 1.3–3.8 km above sea level was found. Because it is a challenging effort to reach an accuracy of humidity measurements down to the ∼5% level, the overall results are very satisfactory and confirm the high and stable performance of the instruments and the low noise errors of each profile.
Effects of Tides on Maximum Tsunami Wave Heights: Probability Distributions*
Authors: Mofjeld Harold O. , González Frank I. , Titov Vasily V. , Venturato Angie J. , Newman Jean C.
Published: January 2007

A theoretical study was carried out to understand how the probability distribution for maximum wave heights (ηm) during tsunamis depends on the initial tsunami amplitude (A) and the tides. It was assumed that the total wave height is the linear sum of the tides and tsunami time series in which the latter is decaying exponentially in amplitude with an e-folding time of 2.0 days, based on the behavior of observed Pacific-wide tsunamis. Direct computations were made to determine the statistics of maximum height for a suite of different arrival times and initial tsunami amplitudes. Using predicted tides for 1992 when the lunar nodal f factors were near unity during the present National Tidal Datum Epoch 1983–2001, the results show that when A is small compared with the tidal range the probability density function (PDF) of the difference ηm − A is closely confined in height near mean higher high water (MHHW). The ηm − A PDF spreads in height and its mean height ηo − A decreases, approaching the PDF of the tides and MSL, respectively, when A becomes large compared with the tidal range. A Gaussian form is found to be a close approximation to the ηm − A PDF over much of the amplitude range; associated parameters for 30 coastal stations along the U.S. West Coast, Alaska, and Hawaii are given in the paper. The formula should prove useful in probabilistic mapping of coastal tsunami flooding.
A Blended Satellite Total Precipitable Water Product for Operational Forecasting
Authors: Kidder Stanley Q. , Jones Andrew S.
Published: January 2007

Total precipitable water (TPW), the amount of water vapor in a column from the surface of the earth to space, is used by forecasters to predict heavy precipitation. In this paper, a process for blending TPW values retrieved from two satellite sources is detailed: the Advanced Microwave Sounding Unit (AMSU) instruments on three NOAA satellites, and the Special Sensor Microwave Imager (SSM/I) instruments on three Defense Meteorological Satellite Program (DMSP) satellites. The process starts with a blending algorithm, which matches the cumulative probability distribution functions of TPW retrievals from the two instruments to lessen their differences. The data are then mapped to a map projection useful to forecasters and composited for 12 h to make a global map. These maps are produced hourly using Data Processing and Error Analysis System (DPEAS) software and made available to forecasters online.
Trend Identification in Twentieth-Century U.S. Snowfall: The Challenges
Authors: Kunkel Kenneth E. , Palecki Michael A. , Hubbard Kenneth G. , Robinson David A. , Redmond Kelly T. , Easterling David R.
Published: January 2007

There is an increasing interest in examining long-term trends in measures of snow climatology. An examination of the U.S. daily snowfall records for 1900–2004 revealed numerous apparent inconsistencies. For example, long-term snowfall trends among neighboring lake-effect stations differ greatly from insignificant to +100% century−1. Internal inconsistencies in the snow records, such as a lack of upward trends in maximum seasonal snow depth at stations with large upward trends in snowfall, point to inhomogeneities. Nationwide, the frequency of daily observations with a 10:1 snowfall-to-liquid-equivalent ratio declined from 30% in the 1930s to a current value of around 10%, a change that is clearly due to observational practice. There then must be biases in cold-season liquid-equivalent precipitation, or snowfall, or both. An empirical adjustment of snow-event, liquid-equivalent precipitation indicates that the potential biases can be statistically significant.

Examples from this study show that there are nonclimatic issues that complicate the identification of and significantly change the trends in snow variables. Thus, great care should be taken in interpretation of time series of snow-related variables from the Cooperative Observer Program (COOP) network. Furthermore, full documentation of optional practices should be required of network observers so that future users of these data can properly account for such practices.
Tackling the Investment Decision as a “Newsvendor Problem”
Authors: Thompson Gary M.
Published: January 2007

The newsvendor model is a classic approach to determining how to set appropriate inventory levels for products whose value is perishable. While the newsvendor analysis does not yield the richness of data found in a simulation-based model, newsvendor analysis provides a relatively simple way to determine inventory levels.
Sexual health knowledge, attitudes and behaviours among an ethnically diverse sample of young people in the UK
Authors: Coleman Lester , Testa Adrienne
Published: January 2007

Objective To provide evidence about the sexual health knowledge, attitudes and behaviours of an ethnically diverse sample of young people from Secondary/High schools in London.

Design Cross-sectional questionnaire-based survey. The sample consisted of students in school Years 11 to 13 (aged 15–18 years), present in school on the day of questionnaire administration.

Setting Sixteen Secondary/High schools in London where the Black and Minority Ethnic (BME) population exceeded two-thirds of the intake. Questionnaires were completed by 2602 students aged 15 to 18, who self-defined their ethnicity as follows: White British ( n= 559), White Other ( n = 256), Black ( n = 710) and Asian ( n = 1077).

Method Self-administered 30-minute questionnaire completed under ‘exam’ conditions, distributed and collected by a team of ethnically diverse fieldworkers. This questionnaire recorded socio-demographic information, sexual health knowledge, sexual health attitudes, experience of sexual intercourse, and sexual risk behaviour and outcomes.

Results BME groups, relative to White British, generally reported poorer sexual health knowledge. Low level knowledge regarding STIs was particularly evident. The White British students were generally the most liberal in their attitudes to sex. With 65 per cent of Black Caribbean males reporting experience of sexual intercourse, and 48 per cent reporting first intercourse under the age of 16, this group is possibly the most at risk of poor sexual health. Although less likely to report sexual inter-course than Black Caribbeans, Black African females and Asian males and females also reported risk behaviour.

Conclusion The findings demonstrate diverse sexual health knowledge, sexual attitudes and sexual behaviours among ethnic groups. This diversity demonstrates the importance of tailoring health education and promotion to meet the specific needs of ethnic groups.
Decision Making in Acquisitions: The Effect of Outside Directors’ Compensation on Acquisition Patterns
Authors: Deutsch Yuval , Keil Thomas , Laamanen Tomi
Published: January 2007

This article examines how the compensation paid for outside directors affects firms’ acquisition behavior. Using panel data of Standard & Poor’s 1500 firms between 1996 and 2002, the authors find that stock and stock option pay for outside directors are related in an inverted U-shaped manner to a firm’s acquisition rate and that for stock options, this relationship is moderated by board composition. Their findings suggest a dual agency model of corporate governance, according to which not only executives’ incentives but also outside directors’ incentives should be aligned with the shareholder value creation.
White lie-telling in children for politeness purposes
Authors: Talwar Victoria , Murphy Susan M. , Lee Kang
Published: January 2007

Prosocial lie-telling behavior in children between 3 and 11 years of age was examined using an undesirable gift paradigm. In the first condition, children received an undesirable gift and were questioned by the gift-giver about whether they liked the gift. In the second condition, children were also given an undesirable gift but received parental encouragement to tell a white lie prior to being questioned by the gift-giver. In the third condition, the child's parent received an undesirable gift and the child was encouraged to lie on behalf of their parent. In all conditions, the majority of children told a white lie and this tendency increased with age. Coding of children's facial expressions using Ekman and Friesen's (1978) Facial Action Coding System revealed significant but small differences between lie-tellers and control children in terms of both positive and negative facial expressions. Detailed parental instruction facilitated children's display of appropriate verbal and nonverbal expressive behaviors when they received an undesirable gift.
Children's depressive symptoms and their regulation of negative affect in response to vignette depicted emotion-eliciting events
Authors: Reijntjes Albert , Stegge Hedy , Terwogt Mark Meerum , Hurkens Edith
Published: January 2007

The present study examined the relationship between sub-clinical depressive symptoms and children's anticipated cognitive and behavioral reactions to two written vignettes depicting emotion-eliciting stressors (i.e., fight with one's best friend and failure at a roller blade contest). Participants ( N = 244) ranging in age between 10 and 13 were presented each vignette and then asked to rate their anticipated utilization of each of seven emotion-regulation strategies (ERs), along with the anticipated mood enhancement effects of each strategy. In addition, ratings of participants' perceived coping efficacy to manage the stressful situation were collected. Results indicated that participants were more likely to endorse ERs for which they have greater confidence in their mood enhancement effects. Moreover, marked differences were observed between ratings for conceptually distinct cognitive ERs. Consistent with expectations, results revealed that participants displaying higher levels of depressive symptoms were more likely to endorse cognitive and behavioral ERs that are negative, passive, and/or avoidant in nature. Children's ratings of the anticipated mood enhancement effects of several ERs were inversely related to their level of depressive symptoms, as was their perceived self-efficacy to manage the stressor.
Finnish and English children's color use to depict affectively characterized figures
Authors: Burkitt Esther , Tala Katri , Low Jason
Published: January 2007

Recent research has shown that children use colors systematically in relation to how they feel about certain colors and the figures that they draw. This study explored cultural differences between Finnish and English children's use of color to represent figures with contrasting emotional characters. One hundred and eight children (54 Finnish, 54 English) were divided into two age groups (5–7 years and 7–9 years). All children colored three emotionally characterized drawings and rated their affect towards the 10 colors provided and the three differentially characterized figures. It was found that Finnish and English children differed in their use of color for drawings of neutral and nasty figures. The findings are discussed in terms of the need to explore the role of culture in mediating children's use of color when drawing figures they feel negatively and positively towards.
Cardiovascular and affective responses to social stress in adolescents with internalizing and externalizing problems
Authors: Hastings Paul D. , Zahn-Waxler Carolyn , Usher Barbara A.
Published: January 2007

Behavioral responses to stress and challenge are based in emotional and physiological arousal reactions. Adolescents with maladaptive or problematic behavior patterns, such as internalizing or externalizing problems, are likely to show atypical emotional and physiological reactions to stress. Relations between problems and reactions to stress were examined in a sample of 55 young adolescents with normal to clinical levels of internalizing and externalizing problems. Youth had their self-reported emotional states, heart rate, and blood pressure levels measured before and after engaging in two socially challenging, evaluative manipulations. Internalizing problems were associated with less positive affect but greater anxiety and cardiovascular arousal, whereas externalizing problems predicted greater hostility and positive affect but less cardiovascular arousal. The necessity of recognizing and incorporating comorbid characteristics and multiple response systems into studies of the links between problems and reactivity is emphasized in the discussion.
Evaluation and Treatment of Acromioclavicular Joint Injuries
Authors: Mazzocca Augustus D. , Arciero Robert A. , Bicos James
Published: January 2007

Acromioclavicular joint injuries and, more specifically, separations are commonplace both in general practice and during athletic participation. This article reviews the traditional classification as well as the clinical evaluation of patients with acute and chronic acromioclavicular joint separations. It also highlights many recent advances, principally in the anatomy and biomechanics of the acromioclavicular joint ligamentous complex. The concept of increases in superior translation as well as disturbances in horizontal translation with injuries to this joint and ligaments are discussed. This information, coupled with the unpredictable longterm results with the Weaver-Dunn procedure and its modifications, have prompted many recent biomechanical studies evaluating potential improvements in the surgical management of acute and chronic injuries. The authors present these recent works investigating cyclic loading and ultimate failure of traditional reconstructions, augmentations, use of free graft, and the more recent anatomic reconstruction of the conoid and trapezoid ligaments. The clinical results (largely retrospective), including acromioclavicular joint repair, reconstruction and augmentation with the coracoclavicular ligament, supplemental sutures, and the use of free autogenous grafts, are summarized. Finally, complications and the concept of the failed distal clavicle resection and reconstruction are addressed. The intent is to provide a current, in-depth treatise on all aspects of acromioclavicular joint complex injuries to include anatomy, biomechanics, benchmark studies on instability and reconstruction, clinical and radiographic evaluation, and to present the most recent clinical research on surgical outcomes.
Drop Downs and Scroll Mice: The Effect of Response Option Format and Input Mechanism Employed on Data Quality in Web Surveys
Authors: Healey Benjamin
Published: January 2007

Online researchers face whether to use radio buttons or drop downs when presenting respondents with “select one answer from many” questions. However, empirical evidence regarding response effects does not provide direction for favoring one. Using data collected in a New Zealand general population Web survey of 2,400 people, this study contributes to the decision process by investigating format response effects at multiple levels and exploring the potential for input mechanisms to interfere with drop-down answer selection. Format choice did not significantly affect survey completions, number of nonsubstantial answers, or time to completion. However, drop downs led to higher item nonresponse and longer response times. Furthermore, the 76% of respondents using scroll mice to complete the survey were prone to accidentally changing an answer if presented with drop-down questions. This increased average response times and skewed distribution of responses to the drop-down treatment questions toward the bottom of the response list. Implications of these findings for Web-based data collection are discussed.
Poisons admissions in Edinburgh 1981-2001: agent trends and predictors of hospital readmissions
Authors: Rafnsson S B , Oliver J J , Elton R A , Bateman D N
Published: January 2007

Self-poisoning is a major public health problem. This study describes patterns of admissions and readmissions from self-poisoning to the Royal Infirmary of Edinburgh from 1981 to 2001. A database on hospital discharges with a diagnosis (ICD-9/10) of poisoning between 1981 and 2001 was used. Annual admissions were described for seven main drug categories, and proportions of patients readmitted within 1-5 years from first admission, were computed for each category. Cox proportional hazards regression was used to evaluate prognostic factors for readmission risk over 1981-2001. For both sexes, admissions increased from the early to mid 1990s, and declined thereafter. The proportion readmitted varied with the drug taken at first admission, from 11.9% (95% CI: 10.8-13%) for non-opiate analgesics, to 17.6% (16.5-18.7%) for benzodiazepines. Deprivation was positively related to readmission risk after first admissions with paracetamol (P<0.001) and benzodiazepines (P<0.001). Timing of first admissions involving paracetamol (P<0.01), benzodiazepines (P<0.001), antidepressants (P<0.001), non-opiate analgesics (P<0.001), and opiates (P<0.05), was inversely associated with readmission risk. In patients admitted for drug overdose, readmission risk is influenced by type of drug taken at first admission. Information on drug type used in self-poisoning may assist in identifying patients at risk for future events, and in reducing hospital read-missions.
Does unintentional ingestion of ethylene glycol represent a serious risk?
Authors: Křenová M , Pelclová D
Published: January 2007

The objective of this study was to evaluate data retrospectively on accidental ingestion of ethylene glycol (EG), based on calls to the Czech Toxicological Information Centre and from toxicological laboratories, in the years 2000-2004. All patients who ingested a known amount of EG and/or subjects with measured serum EG levels were included. A variety of clinical and laboratory parameters was collected. The medical records of 86 subjects, who had ingested from one to three swallows of EG, were analysed. The following findings emerged-metabolic acidosis (41%), vomiting (36%), nephrotoxicity (10%), and CNS depression (9%). In 15 children, the time interval between ingestion and hospitalisation was 1 hour or less. Ethanol was given to 12 children (four as first aid), and none developed hypoglycaemia. Of the 71 adults, 93% were treated with ethanol (19 as first aid). No side effects were documented. Seventeen patients received haemodialysis (HD). Two patients recovered without HD; their EG levels were higher than in the HD-treated patients. Unintentional EG ingestion usually involves ingestion of a small amount of EG, and was connected with mild signs of intoxication. Early therapy with ethanol alone appears sufficient in such cases, and represents no risk of adverse effects.
Latinos’ Perspectives and Experiences With Intimate Partner Violence
Authors: Klevens Joanne , Shelley Gene , Clavel-Arcas Carmen , Barney David D. , Tobar Cynthia , Duran Elizabeth S. , Barajas-Mazaheri Ruth , Esparza Janys
Published: January 2007

This qualitative study, utilizing focus group interviews with community members and in-depth interviews with victims and perpetrators, explored Latinos’ beliefs and perceptions of IPV in Oklahoma City, Oklahoma, as a basis for developing culturally appropriate intimate partner violence (IPV) services for this population. The findings from these interviews suggest that this community recognizes IPV as a problem and is aware of the multiple dimensions, potential causes, and negative consequences of IPV. In general, participants perceived family and neighbors as preferring to not get involved in situations of IPV. However, family was also expected to, and often did, provide tangible support to victims. Directions for developing prevention programs for this population and future research are suggested.
Occupational and Environmental Risk Factors for the Sick Building Syndrome in Modern Offices in Istanbul: A Cross Sectional Study
Authors: Gül Hülya , Işsever Halim , Ayraz Özkan , Güngör Günay
Published: January 2007

In this study we aimed to research the frequency of and possible risk factors for sick building syndrome (SBS) in indoor workplaces in Istanbul. The investigation was carried out in 50 non-governmental bank offices: 25 had a central ventilation system (the study group) and 25 a local ventilation system (the control group). Clinical outcomes were estimated by a standardised questionnaire completed by employees. In addition, the level of indoor gaseous pollutants and bio-aerosols (micro-fungi and bacteria) were measured. The most prevalent bio-aerosols found in the study offices were high densities of Penicillium and Aspergillus spores in contrast to the control offices where the predominant species were Cladasporium and Alternia spores. Findings of SBS were relatively increased in those working in buildings with a central air conditioning system (OR=1.68; 95% CI: 1.04-2.70); in those working for less than 3 years in the building (OR=1.91; 95% CI: 1.18-3.09); in those operating a photocopier frequently (OR=1.70; 95% CI: 1.15-2.53); in women (OR=1.78; 95% CI: 1.21-2.63) and in those with workplace dissatisfaction (OR=2.06; 95% CI: 1.40-3.05).
Indoor-Outdoor Atmospheric Particulate Matter Relationships in Naturally Ventilated Offices
Authors: Loupa G. , Kioutsioukis I. , Rapsomanikis S.
Published: January 2007

Atmospheric particle size distribution and number concentrations were investigated in three naturally ventilated offices and outdoors. The offices were located in a University suburban campus in newly constructed, one-storey buildings. Measurements were conducted with a laser optical particle counter. Synoptic meteorological data, for the duration of the experiment, were obtained from the NOAA satellite data archive. The indoor to outdoor averaged number concentration ratios in the offices during working hours were in the range of 0.35-14.68. Construction activities in the vicinity of one office had a pronounced effect on the indoor number concentrations of particulate matter (PM). Indoor sources were traced to the movement of people, computer operation and environmental tobacco smoke. Re-suspension, appears to contribute to the number concentrations of PM, over all size ranges. Meteorological conditions with respect to office orientation also had a significant impact on indoor PM number concentrations.
Cardiovascular and metabolic effects of CPAP in obese males with OSA
Authors: Coughlin S. R. , Mawdsley L. , Mugarza J. A. , Wilding J. P. H. , Calverley P. M. A.
Published: January 2007

Obstructive sleep apnoea is associated with increased blood pressure and other features of the metabolic syndrome. The aim of the present study was to determine the relative effectiveness of continuous positive airway pressure (CPAP) in modifying these outcomes.

A randomised placebo-controlled blinded crossover trial comparing cardiovascular and metabolic outcomes after 6 weeks of therapeutic and sham CPAP was performed in 34 CPAP-naïve patients (mean±sdbody mass and respiratory disturbance indices were 36.1±7.6 and 39.7±13.8, respectively).

Mean waking systolic and diastolic blood pressure fell by 6.7 and 4.9 mmHg, respectively, when compared with sham CPAP. No change was observed in glucose, lipids, insulin resistance or the proportion of patients with metabolic syndrome. In CPAP-compliant patients the fall in blood pressure was greater and the baroreceptor sensitivity improved significantly but no metabolic variable changed.

In obese Caucasians with untreated obstructive sleep apnoea, continuous positive airways pressure can improve baroreceptor responsiveness and reduce waking blood pressure within 6 weeks, but this treatment period was insufficient to modify insulin resistance or change the metabolic profile. The mechanisms underlying this difference in the time course of blood pressure and metabolic response to continuous positive airway pressure in obstructive sleep apnoea requires further exploration.
Indacaterol, a novel inhaled β2-agonist, provides sustained 24-h bronchodilation in asthma
Authors: Beeh K. M. , Derom E. , Kanniess F. , Cameron R. , Higgins M. , van As A.
Published: January 2007

The present study examined the bronchodilator and safety profiles of single-dose indacaterol in intermittent or persistent asthma.

In the present double-blind crossover study, 42 patients were randomised to receive single doses of indacaterol (50, 100, 200 and 400 µg) or placeboviaa hydrofluoroalkane pressurised metered-dose inhaler. The primary efficacy comparisons were the per cent changes in forced expiratory volume in one second (FEV1) between indacaterol and placebo 30 min and 21 h post-dose.

All doses resulted in prolonged bronchodilation, with indacaterol 200 and 400 µg meeting pre-specified efficacy criteria. The mean percentage increases in FEV1from placebo with indacaterol 200 and 400 µg were 7.6 and 14.9%, respectively, at 30 min, and 7.5 and 10.4%, respectively, at 21 h post-dose. At these doses, changes in mean FEV1relative to placebo were statistically significant from 5 min to 25 h, inclusive. At 5 min, the geometric least squares mean values for FEV1were 3.08 and 3.22 L for the 200 and 400 µg doses, respectively, compared with 2.99 L for placebo. At 24 h after dosing, the baseline-adjusted geometric least square mean FEV1was 3.13, 3.11, 3.24 and 3.30 L for indacaterol 50, 100, 200 and 400 µg, respectively, and 2.98 L for placebo. All treatments were well tolerated.

Once-daily indacaterol at doses of 200 and 400 µg provided sustained 24-h bronchodilation, with a rapid onset and a good tolerability and safety profile.
Serological test and chest computed tomography findings in patients withMycobacterium aviumcomplex lung disease
Authors: Kitada S. , Nishiuchi Y. , Hiraga T. , Naka N. , Hashimoto H. , Yoshimura K. , Miki K. , Miki M. , Motone M. , Fujikawa T. , Kobayashi K. , Yano I. , Maekura R.
Published: January 2007

The present authors have previously reported the usefulness of a serodiagnostic test to detect serum glycopeptidolipid (GPL) core antibody in diagnosingMycobacterium aviumcomplex (MAC) lung disease in immunocompetent patients. The aim of the present study was to investigate correlations between the levels of antibody against GPL core and chest computed tomography (CCT) findings in patients with MAC lung disease.

A total of 47 patients with MAC-positive culture from their sputum and who had radiographic abnormalities were investigated. Thirty-three patients met the American Thoracic Society criteria for MAC disease; 14 did not. All patients underwent both CCT examination and the serodiagnostic test for MAC at the same time.

Small nodular shadows were seen on CCT in all 47 patients and bronchiectasis shadows were seen in 39 (83%) of them. There was a significant positive correlation between the extent of the disease and the level of GPL core immunoglobulin (Ig)A antibody. The levels of GPL core IgA antibody were significantly elevated in patients who had nodular shadows (10–30 mm) compared with patients who had small nodular shadows (<10 mm).

The present results document that the levels of immunoglobulin A antibody against glycopeptidolipid core correlate with the chest computed tomography findings ofMycobacterium aviumcomplex lung disease.
Identification of rat lung-specific microRNAs by microRNA microarray: valuable discoveries for the facilitation of lung research
Authors: Wang Yang , Weng Tingting , Gou Deming , Chen Zhongming , Chintagari Narendranath Reddy , Liu Lin
Published: January 2007

Background

An important mechanism for gene regulation utilizes small non-coding RNAs called microRNAs (miRNAs). These small RNAs play important roles in tissue development, cell differentiation and proliferation, lipid and fat metabolism, stem cells, exocytosis, diseases and cancers. To date, relatively little is known about functions of miRNAs in the lung except lung cancer.

Results

In this study, we utilized a rat miRNA microarray containing 216 miRNA probes, printed in-house, to detect the expression of miRNAs in the rat lung compared to the rat heart, brain, liver, kidney and spleen. Statistical analysis using Significant Analysis of Microarray (SAM) and Tukey Honestly Significant Difference (HSD) revealed 2 miRNAs (miR-195 and miR-200c) expressed specifically in the lung and 9 miRNAs co-expressed in the lung and another organ. 12 selected miRNAs were verified by Northern blot analysis.

Conclusion

The identified lung-specific miRNAs from this work will facilitate functional studies of miRNAs during normal physiological and pathophysiological processes of the lung.
A proteomic study of Corynebacterium glutamicumAAA+ protease FtsH
Authors: Lüdke Alja , Krämer Reinhard , Burkovski Andreas , Schluesener Daniela , Poetsch Ansgar
Published: January 2007

Background

The influence of the membrane-bound AAA+ protease FtsH on membrane and cytoplasmic proteins of Corynebacterium glutamicum was investigated in this study. For the analysis of the membrane fraction, anion exchange chromatography was combined with SDS-PAGE, while the cytoplasmic protein fraction was studied by conventional two-dimensional gel electrophoresis.

Results

In contrast to the situation in other bacteria, deletion of C. glutamicum ftsH has no significant effect on growth in standard minimal medium or response to heat or osmotic stress. On the proteome level, deletion of the ftsH gene resulted in a strong increase of ten cytoplasmic and membrane proteins, namely biotin carboxylase/biotin carboxyl carrier protein (accBC), glyceraldehyde-3-phosphate dehydrogenase (gap), homocysteine methyltransferase (metE), malate synthase (aceB), isocitrate lyase (aceA), a conserved hypothetical protein (NCgl1985), succinate dehydrogenase A (sdhA), succinate dehydrogenase B (sdhB), succinate dehydrogenase CD (sdhCD), and glutamate binding protein (gluB), while 38 cytoplasmic and membrane-associated proteins showed a decreased abundance. The decreasing amount of succinate dehydrogenase A (sdhA) in the cytoplasmic fraction of the ftsH mutant compared to the wild type and its increasing abundance in the membrane fraction indicates that FtsH might be involved in the cleavage of a membrane anchor of this membrane-associated protein and by this changes its localization.

Conclusion

The data obtained hint to an involvement of C. glutamicum FtsH protease mainly in regulation of energy and carbon metabolism, while the protease is not involved in stress response, as found in other bacteria.
Therapeutic effect of all-trans-retinoic acid (at-RA) on an autoimmune nephritis experimental model: role of the VLA-4 integrin
Authors: Escribese María M , Conde Elisa , Martín Ana , Sáenz-Morales David , Sancho David , de Lema Guillermo Pérez , Lucio-Cazaña Javier , Sánchez-Madrid Francisco , García-Bermejo María L , Mampaso Francisco M
Published: January 2007

Background

Mercuric chloride (HgCl2) induces an autoimmune nephritis in the Brown Norway (BN) rats characterized by anti-glomerular basement membrane antibodies (anti-GBM Ab) deposition, proteinuria and a severe interstitial nephritis, all evident at day 13 of the disease. We assessed the effects of all-trans retinoic acid (at-RA) in this experimental model. At-RA is a vitamin A metabolite which has shown beneficial effects on several nephropathies, even though no clear targets for at-RA were provided.

Methods

We separated animals in four different experimental groups (HgCl2, HgCl2+at-RA, at-RA and vehicle). From each animal we collected, at days 0 and 13, numerous biological samples: urine, to measure proteinuria by colorimetry; blood to determine VLA-4 expression by flow citometry; renal tissue to study the expression of VCAM-1 by Western blot, the presence of cellular infiltrates by immunohistochemistry, the IgG deposition by immunofluorescence, and the cytokines expression by RT-PCR. Additionally, adhesion assays to VCAM-1 were performed using K562 α4 transfectant cells. ANOVA tests were used for statistical significance estimation.

Results

We found that at-RA significantly decreased the serum levels of anti-GBM and consequently its deposition along the glomerular membrane. At-RA markedly reduced proteinuria as well as the number of cellular infiltrates in the renal interstitium, the levels of TNF-α and IL-1β cytokines and VCAM-1 expression in renal tissue. Moreover, we reported here for the first time in anin vivomodel that at-RA reduced, to basal levels, the expression of VLA-4 (α4β1) integrin induced by mercury on peripheral blood leukocytes (PBLs). In addition, using K562 α4 stable transfectant cells, we found that at-RA inhibited VLA-4 dependent cell adhesion to VCAM-1.

Conclusion

Here we demonstrate a therapeutic effect of at-RA on an autoimmune experimental nephritis model in rats. We report a significant reduction of the VLA-4 integrin expression on PBLs as well as the inhibition of the VLA4/VCAM1-dependent leukocyte adhesion by at-RA treatment. Thereby we point out the VLA-4 integrin as a target for at-RAin vivo.
Primary sclerosing cholangitis – The arteriosclerosis of the bile duct?
Authors: Fickert Peter , Moustafa Tarek , Trauner Michael
Published: January 2007

Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of unknown aetiology affecting the large bile ducts and characterized by periductal fibrosis and stricture formation, which ultimately result in biliary cirrhosis and liver failure. Arteriosclerosis involves the accumulation of altered lipids and lipoproteins in large arteries; this drives inflammation and fibrosis and ultimately leads to narrowing of the arteries and hypoperfusion of dependent organs and tissues.

Knowledge of the causative factors is crucial to the understanding of disease mechanisms and the development of specific treatment. Based on pathogenetic similarities between PSC and arteriosclerosis, we hypothesize that PSC represents
"arteriosclerosis of the bile duct"
initiated by toxic biliary lipids. This hypothesis is based on common molecular, cellular, and morphological features providing the conceptual framework for a deeper understanding of their pathogenesis. This hypothesis should stimulate translational research to facilitate the search for novel treatment strategies for both diseases.