bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Fetal Echocardiography on Trends in Disease Patterns and Outcomes of Congenital Heart Disease in a Neonatal Intensive Care Unit
Authors: Chung Mi Lim , Lee Byong Sop , Kim Ellen Ai-Rhan , Kim Ki-Soo , Pi Soo-Young , Oh Yeon Mi , Park In Sook , Seo Dong Man , Won Hye Sung
Published: December 2009

Background: Congenital heart disease (CHD) is the most common developmental malformation and the leading cause of neonatal mortality and morbidity. The introduction of fetal echocardiography has made prenatal diagnosis of CHD possible. Objective: This study was conducted to investigate the impact of fetal echocardiography on the changing disease patterns and outcomes of CHD. Methods: A retrospective analysis of data from infants with CHD admitted to the neonatal intensive care unit (NICU) of the Asan Medical Center during the time periods was performed. Period I (1994–1996) was considered representative of a period before the introduction of fetal echocardiography, while period II (2004–2006) represented a period of more extensive application of fetal echocardiography. Results: A total of 164 patients were admitted to the NICU during period I and 320 during period II. The number of infants prenatally diagnosed with CHD was 5 of 164 (3.0%) in period I and 219 of 320 (68.4%) in period II (p < 0.05). The overall accuracy of fetal diagnosis was approximately 92%. Of the 3 CHD categories, there was a greater proportion of infants with ‘significant’ heart disease in period II than I (47 vs. 32%; p < 0.05). In contrast, there was a smaller proportion of infants with ‘simple’ heart defects in period II than I (22 vs. 40%; p < 0.05). The proportion of infants with ‘complex’ heart disease was similar in both periods (28% in period I and 31% in period II). The 1-year survival rate of patients with CHD has improved remarkably with time (70.1% in period I to 88.8% in period II). Multivariate analysis showed prenatal diagnosis and planned delivery in a tertiary NICU are factors affecting CHD outcomes, especially when defects are ‘complex’ (p < 0.01). Conclusion: Fetal echocardiography has resulted in an increased frequency of prenatal CHD diagnosis, has altered the disease patterns observed in the NICU, and has resulted in better 1-year outcomes.
Inhibition of Adrenocortical Carcinoma by Diphtheria Toxin Mutant CRM197
Authors: Martarelli Daniele , Pompei Pierluigi , Mazzoni Giovanni
Published: December 2009

Background: In this study, we investigated the effect of CRM197 treatment in human adrenocortical carcinoma (AC) implanted in nude mice. CRM197 is a non-toxic mutant of diphtheria toxin that binds heparin-binding epidermal growth factor-like growth factor (HB-EGF) which is implicated in the proliferative activity of several tumor cells. Methods: HB-EGF expression in AC cells was evaluated by reverse transcription PCR and Western blot. AC tumors were implanted in nude mice and then treated with CRM197. Effects of treatment on angiogenesis and apoptosis were investigated by immunohistochemistry and Western blot. The effects on cell invasion and migration were investigated with a matrigel invasion assay. Results: We demonstrated that human AC cells express HB-EGF. A treatment with CRM197 blocked growth, reduced angiogenesis and induced apoptosis in AC tumors implanted in nude mice. CRM197 also inhibited invasion and migration of these tumor cells. Conclusions: These data support the evidence for anticancer properties of CRM197 in AC tumors.
Association of Oxidative Stress with Realgar-Induced Differentiation in Human Leukemia HL-60 Cells
Authors: Wang Li-Wen , Shi Yan-Ling , Wang Nan , Gou Bao-Di , Zhang Tian-Lan , Wang Kui
Published: December 2009

Background: Realgar (arsenic sulfide, As4S4) has been shown to have clinical efficacy in patients with newly diagnosed and relapsed acute promyelocytic leukemia. Mechanistic studies have demonstrated that realgar is able to induce cell differentiation. Methods: The oxidative stress in the realgar-induced differentiation was examined with human leukemia HL-60 cells. Cell differentiation was evaluated by the expression of cell surface antigen CD11b and nitroblue tetrazolium assay. The activities of catalase and superoxide dismutase were measured spectrophotometrically. Flow cytometry was used to assess cell cycle distribution and apoptosis, the cellular level of reactive oxygen species (ROS) and glutathione, as well as mitochondrial transmembrane potential (MTP). Results: The realgar-induced differentiation was enhanced by hydrogen peroxide, and preceded with drastic changes in ROS and catalase, as well as small changes in superoxide dismutase and the reduced form of glutathione. MTP values at 24 h were in linear proportion to the CD11b expression at 48 h when no apoptosis was observed. Conclusion: Oxidative stress and stress-related MTP decrease are associated with realgar-induced differentiation in HL-60 cells.
Antitumor Efficacy of Two Novel Non-Thiazolidinedione Compounds as Peroxisome Proliferator-Activated Receptor-γ Agonists in Human Osteosarcoma Cells in vitro
Authors: Fu Lili , Xiong Xishan , Wang Li , Gao Xiang , Ye Yangliang , Jia Jieshuang , Hu Huimin , Li Lin , Shen Jianhua , Mei Changlin
Published: December 2009

Background: Due to chemotherapy resistance in osteosarcoma subgroups, the prognosis of these patients is still poor, and the development of new agents is of utmost importance. The aim of our study was to test the antitumor effects of two novel α-aryloxy-α-methylhydrocinnamic acid derivatives as peroxisome proliferator-activated receptor (PPAR) γ agonists, together with rosiglitazone, a well-known thiazolidinedione (TZD) acting on several osteosarcoma cell lines. Methods/Results: The MTT assay revealed that cell viability was inhibited in a dose-dependent manner with IC50 6.2–15.8 μM for the two novel compounds and rosiglitazone (48.4–83.5 μM). Exposure to DG8 and DH9 at low micromolar concentrations induced a dose-dependent block of DNA synthesis and colony formation. In these antitumor assays, DG8 and DH9 were more effective than rosiglitazone, although the PPARγ agonistic activity of rosiglitazone is much higher. The SiRNA approach to downregulate specifically PPARγ in U-2OS cells did not affect the cytotoxic efficiency of either the two novel compounds or rosiglitazone. Conclusion: These observations suggest that non-TZDs with less PPARγ agonistic activity might show more potent antitumor efficacy independent of PPARγ in human osteosarcoma cells, which supports the possibility that they could be beneficial in the treatment of osteosarcoma patients.
Anal Mucosal Melanoma with KIT-Activating Mutation and Response to Imatinib Therapy – Case Report and Review of the Literature
Authors: Satzger Imke , Küttler Uta , Völker Bernward , Schenck Florian , Kapp Alexander , Gutzmer Ralf
Published: December 2009

Previously an increased frequency of KIT aberrations in mucosal melanomas was reported, whereas c-KIT in most types of cutaneous melanomas does not appear to be of pathogenetic importance. Imatinib has become the standard of care in other cancers with KIT mutations such as gastrointestinal stromal tumors. Recently 12 cases of metastatic melanoma and KIT-activating mutations have been published to be successfully treated with c-KIT blockers such as imatinib, sunitinib, dasatinib or sorafenib. We report here on one of our patients with KIT-activating mutation in metastatic anal mucosal melanoma, who showed a response to imatinib therapy and summarize the available literature regarding this new therapeutic option.
Immune Reactivity and Attractiveness
Authors: Oberzaucher Elisabeth , Grammer Karl
Published: December 2009

Over the past decades, information about the characteristics of attractiveness has accumulated. We know about eight pillars of beauty, among them youthfulness, symmetry, hormone markers and body odor. But what is the biological function of these attractive signals? Is there one common function to be found in all eight beauty markers? In this paper, we argue that attractiveness signals immune resistance. Being attractive would thus be an honest signal for an immune system that coped well with the environmental challenges it was exposed to during ontogeny. This is a prerequisite for developmental stability, which again affects the differentiation of beauty characteristics. We argue that human preferences and mate choice criteria have evolved in coevolution with parasites, and that the current parasite load modulates our decision making.
Multiple Arrhythmogenic Foci Associated With the Development of Perpetuation of Atrial Fibrillation
Authors: Kurotobi Toshiya , Iwakura Katsuomi , Inoue Koichi , Kimura Ryusuke , Okamura Atsunori , Koyama Yasushi , Tosyoshima Yuko , Ito Norihisa , Fujii Kenshi
Published: December 2009

Background—

The presence of multiple arrhythmogenic sources may be associated with the perpetuation of atrial fibrillation (AF). In this study, we investigated the hypothesis that multiple foci might be involved in the development of AF persistency.

Methods and Results—

Two hundred fourteen consecutive patients with AF undergoing catheter ablation were enrolled in this study. The location of the arrhythmogenic foci was determined using simultaneous recordings from multipolar catheters before and after pulmonary vein isolation during an isoproterenol administration. We detected 500 arrhythmogenic foci (263 foci as AF initiators, and 237 foci as non-AF initiators). High-dose isoproterenol infusions (ranging from 2 to 20 μg/min) revealed potential arrhythmogenic foci, especially non–pulmonary vein foci (55%). Persistent AF was more highly associated with an incidence of multiple (>2) foci than paroxysmal AF (88% versus 65%,
P
=0.002), and a multivariate analysis demonstrated that multiple foci (>2) were an independent contributing factor for persistent AF (odds ratio; 95% confidence interval, 4.69; 1.82 to 12.09,
P
<0.001). In paroxysmal AF, the number of foci was higher in patients with long-term AF (>24 hours) than in those with short-lasting AF (2.64�0.14 versus 1.77�0.16,
P
=0.001). In the persistent AF group, the patients with short-lasting AF (<12 months) had a greater number of foci than did those with long-term AF (>12 months) (3.62�0.15 versus 1.92�0.16,
P
=0.04).

Conclusions—

Multiple foci were likely to be involved in the development of persistent AF. However, if AF persisted for >12 months, they may not have had a significant effect on the AF perpetuation.
Clinical Outcome 2 Years After Intracoronary Administration of Bone Marrow–Derived Progenitor Cells in Acute Myocardial Infarction
Authors: Assmus Birgit , Rolf Andreas , Erbs Sandra , Elsässer Albrecht , Haberbosch Werner , Hambrecht Rainer , Tillmanns Harald , Yu Jiangtao , Corti Roberto , Mathey Detlef G. , Hamm Christian W. , Süselbeck Tim , Tonn Torsten , Dimmeler Stefanie , Dill Thorsten , Zeiher Andreas M. , Schächinger Volker
Published: December 2009

Background—

The aim of this study was to investigate the clinical outcome 2 years after intracoronary administration of autologous progenitor cells in patients with acute myocardial infarction (AMI).

Methods and Results—

Using a double-blind, placebo-controlled, multicenter trial design, we randomized 204 patients with successfully reperfused AMI to receive intracoronary infusion of bone marrow–derived progenitor cells (BMC) or placebo medium into the infarct artery 3 to 7 days after successful infarct reperfusion therapy. At 2 years, the cumulative end point of death, myocardial infarction, or necessity for revascularization was significantly reduced in the BMC group compared with placebo (hazard ratio, 0.58; 95% CI, 0.36 to 0.94;
P
=0.025). Likewise, the combined end point death and recurrence of myocardial infarction and rehospitalization for heart failure, reflecting progression toward heart failure, was significantly reduced in the BMC group (hazard ratio, 0.26; 95% CI, 0.085 to 0.77;
P
=0.015). Intracoronary administration of BMC remained a significant predictor of a favorable clinical outcome by Cox regression analysis when adjusted for classical predictors of poor outcome after AMI. There was no evidence of increased restenosis or atherosclerotic disease progression after BMC therapy nor any evidence of increased ventricular arrhythmias or neoplasms. In addition, regional left ventricular contractility of infarcted segments, as assessed by MRI in a subgroup of patients at 2-year follow-up, was significantly higher in the BMC group compared with the placebo group (
P
<0.001).

Conclusions—

Intracoronary administration of BMC is associated with a significant reduction of the occurrence of major adverse cardiovascular events maintained for 2 years after AMI. Moreover, functional improvements after BMC therapy may persist for at least 2 years. Larger studies focusing on clinical event rates are warranted to confirm the effects of BMC administration on mortality and progression of heart failure in patients with AMIs.

Clinical Trial Registration—

clinicaltrials.gov. Identifier: NCT00279175.
A Validated Risk Score for In-Hospital Mortality in Patients With Heart Failure From the American Heart Association Get With the Guidelines Program
Authors: Peterson Pamela N. , Rumsfeld John S. , Liang Li , Albert Nancy M. , Hernandez Adrian F. , Peterson Eric D. , Fonarow Gregg C. , Masoudi Frederick A.
Published: December 2009

Background—

Effective risk stratification can inform clinical decision-making. Our objective was to derive and validate a risk score for in-hospital mortality in patients hospitalized with heart failure using American Heart Association Get With the Guidelines–Heart Failure (GWTG-HF) program data.

Methods and Results—

A cohort of 39 783 patients admitted January 1, 2005, to June 26, 2007, to 198 hospitals participating in GWTG-HF was divided into derivation (70%, n=27 850) and validation (30%, n=11 933) samples. Multivariable logistic regression identified predictors of in-hospital mortality in the derivation sample from candidate demographic, medical history, and laboratory variables collected at admission. In-hospital mortality rate was 2.86% (n=1139). Age, systolic blood pressure, blood urea nitrogen, heart rate, sodium, chronic obstructive pulmonary disease, and nonblack race were predictive of in-hospital mortality. The model had good discrimination in the derivation and validation datasets (c-index, 0.75 in each). Effect estimates from the entire sample were used to generate a mortality risk score. The predicted probability of in-hospital mortality varied more than 24-fold across deciles (range, 0.4% to 9.7%) and corresponded with observed mortality rates. The model had the same operating characteristics among those with preserved and impaired left ventricular systolic function. The morality risk score can be calculated on the Web-based calculator available with the GWTG-HF data entry tool.

Conclusions—

The GWTG-HF risk score uses commonly available clinical variables to predict in-hospital mortality and provides clinicians with a validated tool for risk stratification that is applicable to a broad spectrum of patients with heart failure, including those with preserved left ventricular systolic function.
Regional Variation in Carotid Artery Stenting and Endarterectomy in the Medicare Population
Authors: Goodney Philip P. , Travis Lori L. , Malenka David , Bronner Kristen K. , Lucas F. Lee , Cronenwett Jack L. , Goodman David C. , Fisher Elliott S.
Published: December 2009

Background—

To describe geographic variation in population-based rates of carotid artery stenting (CAS) and carotid endarterectomy (CEA) performed in Medicare beneficiaries.

Methods and Results—

Medicare claims and enrollment data were used to calculate age, sex, and race-adjusted rates of CAS and CEA for Medicare beneficiaries in each of 306 hospital referral regions between 1998 and 2007. Procedures were identified using a combination of Current Procedural Terminology codes as well as diagnostic and procedural ICD-9 codes. Overall, the rate of carotid revascularization has fallen slightly over the last decade (3.8 procedures per 1000 in 1998, 3.1 procedures per 1000 in 2007;
P
<0.0001). Although the use of CEA decreased, from 3.6 to 2.5 procedures per 1000 beneficiaries in 2007 (
P
<0.0001), the use of CAS has increased >4-fold between 1998 and 2007, growing from 0.1 to 0.6 CAS procedures per 1000 beneficiaries (
P
<0.0001). Further, CAS rapidly disseminated across the country over the last decade. In 1998, 66% of hospital referral regions had a hospital that performed CAS; however, by 2007, nearly all (95%) hospital referral regions performed CAS (
P
<0.0001). Last, in regions with the highest utilization rates of CAS, it appeared that CAS was performed as a substitute for CEA. There was little evidence that CAS was being performed in addition to CEA, as no correlation existed between regional rates of CAS and CEA (
r
=0.06).

Conclusions—

Even though CEA was used less frequently in 2007 than 1998, the use of CAS has grown significantly. Although regional variation in the use of CEA has remained fairly constant, regional variation has increased in the use of CAS. Given these changes in practice patterns, careful examination of the efficacy and cost-effectiveness of CAS is necessary.
The Community That Never Was: The European Defense Community and Its Image in Polish Visual Propaganda of the 1950s
Authors: Kaźmierczak Janusz
Published: December 2009

Communist propaganda was sharply critical of all integration attempts made in Western Europe. In numerous political posters and cartoons published in Poland, the brunt of the criticism was borne by the European Defense Community (EDC) from October 1950, when the idea of military integration was first proposed by French Prime Minister René Pleven, until August 1954, when a vote in the French National Assembly effectively killed the project. Through a contextualized discussion of selected posters and cartoons, which are reproduced in the text, this article relates Polish visual anti-EDC propaganda to aspects of Communist ideology, Soviet geostrategic interests, and Polish domestic politics and shows how the propaganda was intended to help the Communist authorities achieve specific goals.
The Psychological Meaning of Words: LIWC and Computerized Text Analysis Methods
Authors: Tausczik Yla R. , Pennebaker James W.
Published: December 2009

We are in the midst of a technological revolution whereby, for the first time, researchers can link daily word use to a broad array of real-world behaviors. This article reviews several computerized text analysis methods and describes how Linguistic Inquiry and Word Count (LIWC) was created and validated. LIWC is a transparent text analysis program that counts words in psychologically meaningful categories. Empirical results using LIWC demonstrate its ability to detect meaning in a wide variety of experimental settings, including to show attentional focus, emotionality, social relationships, thinking styles, and individual differences.
Science Exchange in an Era of Diminished Capacity: Recreation Management in the U.S. Forest Service
Authors: Ryan Clare M. , Cerveny Lee K.
Published: December 2009

Promotion of effective science exchange between government scientists and managers requires thoughtful arrangement and operation of research and management functions. The U.S. Forest Service was established at the peak of the Progressive Era, when science exchange was designed to occur between researchers and resource managers who worked in distinct arms of the agency, but shared similar goals of effective forest management. In this article, the authors explore the implications of diminished agency capacity for science exchange interactions between researchers and managers in recreation management. Managers and researchers identified their current interactions, their perceptions of ideal interactions, and barriers to achieving those ideals. Reductions in agency capacity for recreation management have resulted in the erosion of interactions between managers and researchers. However, effective science exchange does occur, but requires innovative and adaptive approaches.
Making Decisions About Assessment Practices for Students Who Are Deaf or Hard of Hearing
Authors: Cawthon Stephanie W.
Published: December 2009

Students who are deaf or hard of hearing are a low-incidence population with diverse linguistic characteristics and levels of academic achievement. This article presents findings on teacher recommendations of assessment practices for students who are deaf or hard of hearing. A total of 372 educational professionals responded to a set of three study vignettes that asked for recommendations for accommodations or alternate assessments appropriate for the scenarios. Participants also provided open-ended responses that justified their recommendations. Four randomly assigned conditions controlled for test subject (math or reading), student skill level (two or five grades below grade level in math and/or reading), and communication mode used in instruction (American Sign Language or a combination of sign and speech). Participant recommendations for accommodations or alternate assessments varied by test subject (math or reading) and student skill level but not by communication mode. Justifications for recommendations painted a complex picture of reasons behind proposed assessment practices. This article discusses the implications of these findings for accommodations policy as well as possible evidence toward a theory of decision making in assessment practices for students who are deaf or hard of hearing.
‘‘N the Network?’’
Authors: Buskirk Trent D. , Callegaro Mario , Rao Kumar
Published: December 2009

Despite higher hit rates for cell phone samples, inefficiencies in processing calls to these numbers relative to landline numbers continue to be documented in the U.S. literature. In this study, we propose one method for using cell phone provider information and Internet resources for validating number status. Specifically, we describe how we used ‘‘in network’’ options available from three major providers’ web sites to determine the validity of cell phone numbers. We tested differences in working number rates (WNRs) among valid and nonvalid numbers against a normal processing control group and determined that the WNR among valid numbers was approximately 14 percentage points higher than the WNR of the comparison group. This process also shows promise in reducing the effort required to determine working status and may provide a basis for developing screening tools for cell phones that capitalize on resources that are unique to this technology.
Understanding the Willingness to Participate in Mobile Surveys: Exploring the Role of Utilitarian, Affective, Hedonic, Social, Self-Expressive, and Trust-Related Factors
Authors: Bosnjak Michael , Metzger Gottfried , Gräf Lorenz
Published: December 2009

Mobile technology offers a promising means to collect survey data, though the factors that influence people's willingness to participate in mobile surveys and their actual participation remain unknown. To identify these factors, this study considers six conceptually distinct influences that may relate to the propensity to participate in mobile surveys. Some of them affect technology acceptance and usage of (mobile) technology in general; another set comes from studies of participation in computer-assisted surveys. The proposed unified framework encompasses utilitarian, affective, hedonic, social, self-expressive, and trust-related factors. An empirical study suggests that this framework explains the intention to participate and actual participation well, though of the six factors, hedonic, affective, self-expressive, and trust-related ones are most influential. Utilitarian aspects and beliefs about perceived social pressure to participate do not play significant roles. The authors discuss the practical implications of these results and outline some further research avenues.
Using Gaming Literacies to Cultivate New Literacies
Authors: Hsu Hui-Yin , Wang Shiang-Kwei
Published: December 2009

The use of games in educational contexts has recently received growing attention; however, many teachers struggle with finding a right context to adopt games in the classroom. To strengthen teachers’ beliefs about the educational value of games, this article explains the similarities and differences between new literacies and gaming literacy and defines gaming literacy from the “play” and “design” perspectives. This article presents examples of game use that will help teachers cultivate learners’ new literacies through gaming, understand how the game debriefing process can help scaffold students’ learning, and identify factors affecting the adoption of games in educational contexts. The audience for this article includes teachers and teacher educators who would like greater clarification regarding gaming literacy and its positive effects on the learning and development of new literacies.
Searching for a Frame
Authors: Weaver David A. , Lively Erica , Bimber Bruce
Published: December 2009

How are the news media framing nanoscale science and technology? Primary concerns in the literature have been how news media weigh risks and benefits and how they classify nano with respect to news categories such as business, culture, discovery, or medicine. The authors contribute a new perspective by focusing on issue frames involving how stories imply responsibility for societal outcomes from technology. The authors develop four issue frames for stories about nanoscale science and technology: progress, regulation, conflict, and generic risk. These cut across the frame classifications and story tone assessments employed previously in the literature. Using data from the 10 largest U.S. newspapers for 1999-2008, the frequency of each frame over time is assessed. This study found that progress and generic risk frames, which deemphasize actors and responsibilities, dominated early coverage of nano but that frames involving regulation and the interplay of market incentives and regulatory responsibility mainly supplanted progress frames by 2007.
Gendered and Social Hierarchies in Problem Representation and Policy Processes: “Domestic Violence” in Finland and Scotland
Authors: Hearn Jeff , McKie Linda
Published: December 2009

This article identifies and critiques presumptions about gender and violence that continue to frame and inform the processes of policy formation and implementation on domestic violence. It also deconstructs the agendered nature of policy as gendered, multilevel individual and collective action. Drawing on comparative illustrative material from Finland and Scotland, we discuss how national policies and discourses emphasize physical forms of violence, place the onus on the agency of women, and encourage a narrow conceptualization of violence in relationships. The two countries do this in somewhat comparable, though different ways operating within distinct national gender contexts.The complex interweaving of masculinities, violence, and cultures, although recognized in many debates, is seemingly marginalized from dominant discourses, policy, and legal processes. Despite growth in critical studies on men, there is little attempt made to problematize the gendered nature of violence. Rather, policy and service outcomes reflect processes through which individualized and masculine discourses frame ideas, discourses, and policy work. Women experiencing violence are constructed as victims and potential survivors of violence, although the social and gendered hierarchies evident in policies and services result in longer-term inequities and suffering for women and their dependents.
Redefining hormone resistance in prostate cancer
Authors: Hoimes Christopher J. , Kelly W. Kevin
Published: December 2009

Prostate cancer relies on signaling through the androgen receptor (AR) for maintenance and progression; and androgen-deprivation therapy remains a cornerstone of treatment for advanced prostate cancer. An effective clinical classification of prostate cancer should account for the extent of the disease as well as the mechanisms that are driving the growth of the tumor. The previous terms hormone-sensitive and hormone-refractory described response to treatment. It has become clear that these terms do not reflect the mechanism of disease relapse; however over the last decade there has been a better understanding of androgen-receptor mediated signaling effects and incomplete suppression of androgens in prostate cancer. The Prostate Cancer Clinical Trials Working Group 2 (PCWG2) now recommends addressing the spectrum of clinical states based on castration status as this ligand-centered terminology can more accurately describe the patients’ disease, and ultimately provides a useful framework for patient management and drug development. Optimized use of androgen-deprivation therapy, low molecular weight inhibitors of adrenal androgen biosynthesis, and new AR antagonists are promising new therapeutics that can further define the meaning of castrate state. As hormone resistance is redefined to include patients that are refractory to treatments that ablate adrenal and in situ tumoral androgens, a meaningful new clinical state in patients will be forged. We propose a model for incorporating these patients into the current PCWG2 conceptualization of the disease.
Topographic Patterns of Cartilage Lesions in Knee Osteoarthritis
Authors: Bae Won C. , Payanal Melanie M. , Chen Albert C. , Hsieh-Bonassera Nancy D. , Ballard Brooke L. , Lotz Martin K. , Coutts Richard D. , Bugbee William D. , Sah Robert L.
Published: December 2009

Objective:

Treatments for articular cartilage lesions could benefit from characterization of lesion patterns and their progression to end-stage osteoarthritis. The objective of this study was to identify, quantitatively, topographic patterns of cartilage lesions in the human knee.

Design:

Photographs were taken of 127 unilateral distal femora (from 109 cadavers and 18 arthroplasty remnants) with full-thickness cartilage lesions. Using digital image analysis, the lesions were localized, and normalized lesion size was determined for the patellofemoral groove (PFG) and the lateral and medial femoral condyles (LFC and MFC, respectively). Samples were classified into patterns using cluster analysis of the lesion size at each compartment. For each pattern, maps showing the extent and frequency of lesions were created.

Results:

Four main patterns (a-d) were identified (each P < 0.001), with the lesion size varying from small (a) to large in distinct regions (b-d). Pattern b had a predominant lesion (23% area) in the MFC and smaller (<3%) lesions elsewhere. Pattern c had predominant lesions in the LFC (19%) and MFC (10%). Pattern d had a predominant lesion in the PFG (15%) and smaller lesions in the MFC (6%) and LFC (2%). The subpatterns of a (a1-a3) had relatively small lesions, with similarity between a2 and b and between a3 and d.

Conclusion:

The present methods facilitated quantitative identification of distinct topographic patterns of full-thickness cartilage lesions, based on lesion size and location. These results have implications for stratifying osteoarthritis patients using precise quantitative methods and, with additional longitudinal data, targeting cartilage treatments.
Induction of myeloproliferative disorder and myelofibrosis by thrombopoietin receptor W515 mutants is mediated by cytosolic tyrosine 112 of the receptor
Authors: Pecquet Christian , Staerk Judith , Chaligné Ronan , Goss Valerie , Lee Kimberly A. , Zhang Xiaowu , Rush John , Van Hees Joanne , Poirel Hélène A. , Scheiff Jean-Marie , Vainchenker William , Giraudier Stéphane , Polakiewicz Roberto D. , Constantinescu Stefan N.
Published: December 2009

Constitutively active JAK2V617F and thrombopoietin receptor (TpoR) W515L/K mutants are major determinants of human myeloproliferative neoplasms (MPNs). We show that a TpoRW515 mutation (W515A), which we detected in 2 myelofibrosis patients, and the Δ5TpoR active mutant, where the juxtamembrane R/KW515QFP motif is deleted, induce a myeloproliferative phenotype in mouse bone marrow reconstitution experiments. This phenotype required cytosolic Y112 of the TpoR. Phosphotyrosine immunoprofiling detected phosphorylated cytosolic TpoR Y78 and Y112 in cells expressing TpoRW515A. Mutation of cytosolic Y112 to phenylalanine prevented establishment of the in vivo phenotype and decreased constitutive active signaling by Δ5TpoR and TpoRW515A, especially via the mitogen-activated protein (MAP)–kinase pathway, without decreasing Janus kinase 2 (JAK2) activation. In contrast, mutation of cytosolic Y78 to phenylalanine enhanced the myeloproliferative syndrome induced by the TpoRW515 mutants, by enhancing receptor-induced JAK2 activation. We propose that TpoR cytosolic phosphorylated Y112 and flanking sequences could become targets for pharmacologic inhibition in MPNs.
Survival impact of lung transplantation for COPD
Authors: Lahzami S. , Bridevaux P.O. , Soccal P.M. , Wellinger J. , Robert J.H. , Ris H.B. , Aubert J.D.
Published: December 2009

Chronic obstructive pulmonary disease (COPD) is the primary indication for lung transplantation (LTx), but survival benefit is still under debate. We analysed the survival impact of LTx in COPD with a new approach, using the BODE (body mass index, airway obstruction, dyspnoea, exercise capacity) index.

We retrospectively reviewed 54 consecutive lung transplants performed for COPD. The pre-transplant BODE score was calculated for each patient and a predicted survival was derived from the survival functions of the original BODE index validation cohort. Predicted and observed post-transplant survival was then compared.

In the subgroups with a BODE score ≥7 and <7, a majority of patients (66% and 69%, respectively) lived for longer after LTx than predicted by their individual BODE index. The median survival was significantly improved in the entire cohort and in the subgroup with a BODE score ≥7. 4 yrs after LTx a survival benefit was only apparent in patients with a pre-transplant BODE score of ≥7.

In conclusion, while a majority of COPD patients had an individual survival benefit from LTx regardless of their pre-transplant BODE score, a global survival benefit was seen only in patients with more severe disease. This supports the use of the BODE index as a selection criteria for LTx candidates.
Usual interstitial pneumonia in rheumatoid arthritis-associated interstitial lung disease
Authors: Kim E. J. , Elicker B. M. , Maldonado F. , Webb W. R. , Ryu J. H. , Van Uden J. H. , Lee J. S. , King T. E. , Collard H. R.
Published: December 2009

Interstitial lung disease is a common manifestation of rheumatoid arthritis; however, little is known about factors that influence its prognosis. The aim of the present study was to determine whether or not the usual interstitial pneumonia pattern found on high-resolution computed tomography (HRCT) is of prognostic significance in rheumatoid arthritis-associated interstitial lung disease (RA-ILD).

Patients with RA-ILD were identified retrospectively (n = 82). The relationship of a definite usual interstitial pneumonia pattern on HRCT to survival was determined and compared to that in a cohort of patients with radiologically diagnosed idiopathic pulmonary fibrosis (n = 51).

A definite usual interstitial pneumonia pattern was seen in 20 (24%) out of 82 patients with RA-ILD. These patients showed worse survival than those without this pattern (median survival 3.2versus6.6 yrs), and a similar survival to those with idiopathic pulmonary fibrosis. On multivariate analysis, a definite usual interstitial pneumonia pattern on HRCT was associated with worse survival (hazard ratio of 2.3). Analysis of specific HRCT features demonstrated that traction bronchiectasis and honeycomb fibrosis were associated with worse survival (hazard ratio of 2.6 and 2.1, respectively). Female sex (hazard ratio of 0.30) and a higher baseline diffusing capacity of the lung for carbon monoxide (hazard ratio of 0.96) were associated with better survival.

A definite usual interstitial pneumonia pattern on HRCT has important prognostic implications in RA-ILD.
Graded contrast echocardiography in pulmonary arteriovenous malformations
Authors: Parra J. A. , Bueno J. , Zarauza J. , Fariñas-Alvarez C. , Cuesta J. M. , Ortiz P. , Zarrabeitia R. , Pérez del Molino A. , Bustamante M. , Botella L. M. , Delgado M. T.
Published: December 2009

To compare the results of transthoracic contrast echocardiography (TTCE) adding a grading scale with the results of thoracic computed tomography (CT) in order to optimise the use of both techniques.

95 patients with hereditary haemorrhagic telangiectasia (HHT) were examined with TTCE and thoracic CT to detect pulmonary arteriovenous malformations (PAVMs). According to previous studies, TTCE was divided into a four grade scale depending on the degree of opacification of the left ventricle after the administration of a contrast agent.

Of the 95 patients (50.5% female; mean age 46 yrs), none with normal or grade 1 TTCE had detectable PAVMs on thoracic CT. Shunts of grades 2, 3 and 4 were associated with PAVMs according to thoracic CT in 25, 80, and 100% of the cases. There was a statistically significant association between the TTCE grade and the detection of a PAVM by thoracic CT. There were also statistically significant associations between TTCE grade and the cardiac cycle when the contrast was first visible in the left atrium, and size of the feeding artery.

Graded TTCE and timing of left atrium opacification may be useful techniques in selecting HHT patients for PAVM screening with thoracic CT scans.
Exhaled nitric oxide predicts control in patients with difficult-to-treat asthma
Authors: Pérez-de-Llano L. A. , Carballada F. , Castro Añón O. , Pizarro M. , Golpe R. , Baloira A. , Vázquez Caruncho M. , Boquete M.
Published: December 2009

We aimed to evaluate the accuracy of baseline exhaled nitric oxide fraction (FeNO) to recognise individuals with difficult-to-treat asthma who have the potential to achieve control with a guideline-based stepwise strategy.

102 consecutive patients with suboptimal asthma control underwent stepwise increase in the treatment with maximal fluticasone/salmeterol combination dose for 1 month. Then, those who remained uncontrolled received oral corticosteroids for an additional month.

With this approach, 53 patients (52%) gained control. Those who achieved control were more likely to have positive skin results (60.4%versus34%; p = 0.01), positive bronchodilator test (57.1%versus35.8%; p = 0.02) and peak expiratory flow variability ≥20% (71.1%versus49.1%; p = 0.04). Conversely, depression was more frequent in those who remained uncontrolled (18.4 %versus43.4 %; p = 0.01). AnFeNOvalue ≥30 ppb demonstrated a sensitivity of 87.5% (95% CI 73.9–94.5%) and a specificity of 90.6% (95% CI 79.7–95.9%) for the identification of responsive asthmatics.

The current results suggest thatFeNOcan identify patients with difficult-to-treat asthma and the potential to respond to high doses of inhaled corticosteroids or systemic steroids.
Hedgehog-interacting protein is a COPD susceptibility gene: the Rotterdam Study
Authors: Van Durme Y.M.T.A. , Eijgelsheim M. , Joos G.F. , Hofman A. , Uitterlinden A.G. , Brusselle G.G. , Stricker B.H.Ch.
Published: December 2009

The Hedgehog signalling pathway plays an important role in lung morphogenesis and cellular responses to lung injury. A genome-wide association study has demonstrated that two single nucleotide polymorphisms (SNPs) near the Hedgehog-interacting protein (Hip) gene, SNP identifiers rs1828591 and rs13118928, are associated with risk of chronic obstructive pulmonary disease (COPD). The aim of the present study was to validate the observed association between genetic variation near theHipgene and COPD, and to investigate whether risk estimates were modified by smoking behaviour.

The association between theHipgene SNPs and COPD was investigated in the Rotterdam Study by logistic regression analyses, adjusted for several covariates. In addition, an association meta-analysis was performed that included data from the genome-wide association study on COPD.

Both SNPs were significantly associated with risk of COPD (OR 0.80; 95% CI 0.72–0.91). Homozygosity for the minor G allele resulted in a decreased risk of COPD of ∼40% (95% CI 0.47–0.78). There was a significant interaction with the number of pack-years of smoking (p = 0.004). The meta-analysis yielded an odds ratio for COPD of 0.80 per additional G allele (p = 3.4×10−9).

Genetic variation near theHipgene was significantly associated with risk of COPD, depending on the number of pack-years of smoking.
Recent trends in COPD prevalence in Spain: a repeated cross-sectional survey 1997–2007
Authors: Soriano J.B. , Ancochea J. , Miravitlles M. , García-Río F. , Duran-Tauleria E. , Muñoz L. , Jiménez-Ruiz C.A. , Masa J.F. , Viejo J.L. , Villasante C. , Fernández-Fau L. , Sánchez G. , Sobradillo-Peña V.
Published: December 2009

We aimed to describe changes in the prevalence of chronic obstructive pulmonary disease (COPD) in Spain by means of a repeated cross-sectional design comparing two population-based studies conducted 10 yrs apart.

We compared participants from IBERPOC (Estudio epidemiológico de EPOC en España) (n = 4,030), conducted in 1997, with those of EPI-SCAN (Epidemiologic Study of COPD in Spain) (n = 3,802), conducted in 2007. Poorly reversible airflow obstruction compatible with COPD was defined according to the old European Respiratory Society definitions.

COPD prevalence in the population between 40 to 69 yrs of age dropped from 9.1% (95% CI 8.1–10.2%) in 1997 to 4.5% (95% CI 2.4–6.6%), a 50.4% decline. The distribution of COPD prevalence by severity also changed from 38.3% mild, 39.7% moderate and 22.0% severe in 1997, to 85.6% mild, 13.0% moderate and 1.4% severe in 2007, and in the 40–69 yr EPI-SCAN sub-sample to 84.3% mild, 15.0% moderate and 0.7% severe. Overall, underdiagnosis was reduced from 78% to 73% (not a significant difference) and undertreatment from 81% to 54% (p<0.05) within this 10-yr frame.

The finding of a substantial reduction in the prevalence of COPD in Spain is unexpected, as were the observed changes in the severity distribution, and highlights the difficulties in comparisons between repeated cross-sectional surveys of spirometry in the population.
Lung perfusion and chest wall configuration is altered by glossopharyngeal breathing
Authors: Seccombe L.M. , Chung S.C.S. , Jenkins C.R. , Frater C.J. , Mackey D.W.J. , Pearson M.A. , Emmett L. , Peters M.J.
Published: December 2009

Glossopharyngeal insufflation is used by competitive breath-hold divers to increase lung gas content above baseline total lung capacity (TLC) in order improve performance. Whilst glossopharyngeal insufflation is known to induce hypotension and tachycardia, little is known about the effects on the pulmonary circulation and structural integrity of the thorax.

Six male breath-hold divers were studied. Exhaled lung volumes were measured before and after glossopharyngeal insufflation. On two study days, subjects were studied in the supine position at baseline TLC and after maximal glossopharyngeal insufflation above TLC. Tc 99mlabelled macro-aggregated albumin was injected and a computed tomography (CT) scan of the thorax was performed during breath-hold. Single photon emission CT images determined flow and regional deposition. Registered CT images determined change in the volume of the thorax.

CT and perfusion comparisons were possible in four subjects. Lung perfusion was markedly diminished in areas of expanded lung. 69% of the increase in expired lung volume wasviathoracic expansion with a caudal displacement of the diaphragm. One subject who was not proficient at glossopharyngeal insufflation had no change in CT appearance or lung perfusion.

We have demonstrated areas of hyperexpanded, under perfused lung created by glossopharyngeal insufflation above TLC.
Identification of expressed genes during compatible interaction between stripe rust (Puccinia striiformis) and wheat using a cDNA library
Authors: Ma Jinbiao , Huang Xueling , Wang Xiaojie , Chen Xianming , Qu Zhipeng , Huang Lili , Kang Zhensheng
Published: December 2009

Background

Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is one of the most destructive diseases of wheat worldwide. To establish compatibility with the host, Pst forms special infection structures to invade the plant with minimal damage to host cells. Although compatible interaction between wheat and Pst has been studied using various approaches, research on molecular mechanisms of the interaction is limited. The aim of this study was to develop an EST database of wheat infected by Pst in order to determine transcription profiles of genes involved in compatible wheat-Pst interaction.

Results

Total RNA, extracted from susceptible infected wheat leaves harvested at 3, 5 and 8 days post inoculation (dpi), was used to create a cDNA library, from which 5,793 ESTs with high quality were obtained and clustered into 583 contigs and 2,160 singletons to give a set of 2,743 unisequences (GenBank accessions: GR302385 to GR305127). The BLASTx program was used to search for homologous genes of the unisequences in the GenBank non-redundant protein database. Of the 2,743 unisequences, 52.8% (the largest category) were highly homologous to plant genes; 16.3% to fungal genes and 30% of no-hit. The functional classification of all ESTs was established based on the database entry giving the best E-value using the Bevan's classification categories. About 50% of the ESTs were significantly homologous to genes encoding proteins with known functions; 20% were similar to genes encoding proteins with unknown functions and 30% did not have significant homology to any sequence in the database. The quantitative real-time PCR (qRT-PCR) analysis determined the transcription profiles and their involvement in the wheat-Pst interaction for seven of the gene.

Conclusion

The cDNA library is useful for identifying the functional genes involved in the wheat-Pst compatible interaction, and established a new database for studying Pst pathogenesis genes and wheat defense genes. The transcription patterns of seven genes were confirmed by the qRT-PCR assay to be differentially expressed in wheat-Pst compatible and incompatible interaction.
Cardiovascular risk factor assessment after pre-eclampsia in primary care
Authors: Nijdam Marie-Elise , Timmerman Monique R , Franx Arie , Bruinse Hein W , Numans Mattijs E , Grobbee Diederick E , Bots Michiel L
Published: December 2009

Background

Pre-eclampsia is associated with an increased risk of development of cardiovascular disease later in life. It is not known how general practitioners in the Netherlands care for these women after delivery with respect to cardiovascular risk factor management.

Methods

Review of medical records of 1196 women in four primary health care centres, who were registered from January 2000 until July 2007 with an International Classification of Primary Care (ICPC) code indicating pregnancy. Records were searched for indicators of pre-eclampsia. Of those who experienced pre-eclampsia and of a random sample of 150 women who did not, the following information on cardiovascular risk factor management after pregnancy was extracted from the records: frequency and timing of blood pressure, cholesterol and glucose measurements - and vascular diagnoses. Additionally the sensitivity and specificity of ICPC coding for pre-eclampsia were determined.

Results

35 women experienced pre-eclampsia. Blood pressure was more often checked after pregnancy in these women than in controls (57.1% vs. 12.0%, p < 0.001). In 50% of the cases blood pressure was measured within 3 months after delivery with no further follow-up visit. A check for glucose and cholesterol levels was rare, and equally frequent in PE and control women. 20% of the previously normotensive women in the PE group had hypertension at one or more occasions after three months post partum versus none in the control group. The ICPC coding for pre-eclampsia showed a sensitivity of 51.4% and a specificity of 100.0%.

Conclusion

Despite the evidence of increased risk of future cardiovascular disease in women with a history of pre-eclampsia, follow-up of these women is insufficient and undeveloped in primary care in the Netherlands.