bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for Mas-Mediated Bradykinin Potentiation by the Angiotensin-(1-7) Nonpeptide Mimic AVE 0991 in Normotensive Rats
Authors: Carvalho Mariana B.L. , Duarte Fernanda V. , Faria-Silva Raphael , Fauler Beatrix , da Mata Machado Leonor T. , de Paula Renata D. , Campagnole-Santos Maria J. , Santos Robson A.S.
Published: July 2007

We evaluated the effect of the nonpeptide mimic of angiotensin (Ang)-(1-7), AVE 0991, on the hypotensive effect of bradykinin (BK). Increasing doses of intra-arterial or intravenous BK were administered before and 30 minutes after the beginning of AVE 0991 infusion. The effect of AVE 0991 on plasma Ang-converting enzyme activity was tested using Hip-His-Leu as the substrate. The interaction of AVE 0991 with Ang-converting enzyme in vivo was tested by determining its effect on the pressor action of Ang I or Ang II. AVE 0991 produced a significant and similar potentiation of intra-arterial or intravenous bradykinin. AVE 0991 did not inhibit plasma Ang-converting enzyme activity in vitro or the pressor effect of Ang I in vivo.
N
W
-nitro-
l
-arginine methyl ester or D-Ala
7
-Ang-(1-7) administration abolished the BK potentiating effect of AVE 0991. We further examined the BK-potentiating effect of AVE 0991, evaluating its effect on NO production in rabbit endothelial cells. The NO release was measured using the 4-amino-5-methylamino-2′-7′-difluorofluorescein diacetate. A synergistic effect of AVE 0991 and BK on NO release was observed. These results suggest that AVE 0991 potentiates bradykinin through an Ang-converting enzyme–independent, NO-dependent receptor Mas-mediated mechanism. This effect may contribute to the improvement of endothelial function by AVE 0991 in vivo.
Lidocaine Exhibits Dose- and Time-Dependent Cytotoxic Effects on Bovine Articular Chondrocytes in Vitro
Authors: Karpie John C. , Chu Constance R.
Published: July 2007

Background

Intra-articular lidocaine is commonly used.

Purpose

This study was conducted to determine whether short-term exposures to 1% and 2% lidocaine are toxic to articular chondrocytes, whether this is due to pH, and whether an intact articular surface is protective.

Study Design

Controlled laboratory study.

Methods

Fresh bovine articular chondrocytes in alginate bead cultures were treated with 1% or 2% lidocaine or buffered saline (pH 7.4, 7.0, and 5.0) for 15, 30, or 60 minutes. Chondrocytes were then analyzed for viability by flow cytometry 1 hour, 1 day, and 1 week later. Bovine osteochondral cores with and without the superficial 1 mm of cartilage removed were submerged in either 0.9% saline (pH 7.4) or in 1% or 2% lidocaine for 30 minutes and assessed for viability using fluorescent microscopy.

Results

Chondrocyte viability decreased after just 15-minute exposures to 1% lidocaine. Longer exposures to 1% and 2% lidocaine further reduced chondrocyte viability. Chondrotoxicity of 2% lidocaine was greater than 1% lidocaine. There was no difference in chondrocyte viability after exposures to saline solutions of pH 7.4, 7.0, or 5.0. An intact articular surface did not affect lidocaine's chondrotoxic effects.

Conclusion

Results show dose- and time-dependent cytotoxic effects of lidocaine on bovine articular chondrocytes. Reduction of pH alone did not decrease chondrocyte viability, and the intact articular surface was not protective.

Clinical Relevance

Although lidocaine chondrotoxicity was less than previously reported with bupivacaine, these observations suggest that local anesthetics as a class of drugs may negatively affect articular cartilage.
Biomechanical Analysis of Distal Biceps Tendon Repair Methods
Authors: Henry Jon , Feinblatt Jeff , Kaeding Christopher C. , Latshaw James , Litsky Alan , Sibel Roman , Stephens Julie A. , Jones Grant L.
Published: July 2007

Background

The 1-incision and 2-incision techniques are commonly used methods to repair a distal biceps rupture, and they differ in the location of reinsertion of tendon into bone.

Hypothesis

The native distal biceps brachii tendon inserts on the posterior-ulnar aspect of the bicipital tuberosity, which functions as a cam, increasing the tendon's moment arm during its principal action of forearm supination. Repair of the distal biceps tendon to the anterior aspect of the tuberosity compromises forearm supination due to absence of the bicipital tuberosity's cam effect.

Study Design

Controlled laboratory study.

Methods

Eleven matched pairs of fresh-frozen cadaveric upper extremities were prepared for repair of the distal biceps tendon using either anterior or posterior reattachment with transosseous suture fixation. Specimens were tested on a materials testing machine with intact distal biceps insertion and after repair. A load cell at the distal radial-ulnar joint measured resultant elbow flexion and forearm supination torque produced by 100-N force applied to the proximal aspect of the tendon.

Results

Although there was a trend (P = .104) toward loss of supination torque with the anterior reconstruction method, no significant differences in torque (0.80 vs 0.89 N·m) or flexion force (11.87 vs 12.07 N) were found between the anterior and posterior reconstruction techniques.

Conclusion

There is no statistically significant difference in flexion force or supination torque between the anterior and posterior reconstruction techniques.

Clinical Relevance

This study supports existing limited clinical data suggesting no functional differences exist between 2 common repair methods. Further biomechanical and clinical investigations directly comparing the results of distal biceps tendon repairs made to the anterior aspect versus the posterior aspect of the tuberosity are necessary to definitely determine if differences exist in resultant elbow flexion and forearm supination functions.
A Qualitative Evaluation of a Breastfeeding Peer Counselor Program
Authors: Meier Emily R. , Olson Beth H. , Benton Patricia , Eghtedary Kobra , Song Won O.
Published: July 2007

The Breastfeeding Initiative program is a collaboration between the Michigan Department of Community Health (Women, Infants, and Children Division) and Michigan State University Extension. It aims to increase breastfeeding rates among low-income women through the use of peer counselors. The study's purpose was to identify the program's strengths, operation procedures, and improvement areas from participants' and peer counselors' perspectives. Six focus groups were conducted: 3 of peer counselors and 3 of program participants. Findings revealed that peer counselors and participants were satisfied with the quality of services due to emotional and practical assistance and breast pumps provided by peer counselors. Peer counselors' job satisfaction was explained positively by the intrinsic rewards of helping others and negatively by perceived inadequate resources and recognition. Operating procedures varied greatly. Possible improvements include expanding services, providing peer counselors with additional support, and standardizing peer counselor operating procedures. The peer counselor model can effectively support low-income breastfeeding women. J Hum Lact. 23(3):262-268.
Electronic Communication With Patients for Breastfeeding Support
Authors: Thomas Jennifer R. , Shaikh Ulfat
Published: July 2007

The Internet has become an important tool for patients seeking to expand their knowledge of health conditions and medications. Breastfeeding initiation and duration increase because of physician encouragement. Therefore, electronic communication potentially provides additional opportunities for physicians to inform, reassure, encourage, and support breastfeeding families. An e-mail from a breastfeeding mother may deal with a topic well-suited to e-mail communication, such as information on the safety of specific medications during breastfeeding, or may deal with a concern that would make observation of breastfeeding necessary. Physicians have expressed qualms about electronic communication with patients due to privacy, malpractice liability, time, and reimbursement issues. Strategies to optimize e-mail communication include establishing a turnaround time for responses, informing patients of privacy issues, establishing what types of messages are appropriate over e-mail, and setting limits for when an e-mailed concern escalates to a need for an office visit. J Hum Lact. 23(3):275-279.
Feeding Patterns of Brazilian Preterm Infants During the First 6 Months of Life, Londrina, Paraná, Brazil
Authors: Benevenuto de Oliveira Márcia María , Thomson Zuleika , Vannuchi Marli Terezinha Oliveira , Matsuo Tiemi
Published: July 2007

The present study evaluated the breastfeeding practice of 278 preterm infants born at the University Hospital of Londrina, Paraná, Brazil, during hospitalization and in the first 6 months of life. Data were obtained from the hospital records, and the mothers were interviewed by home visit (75.5%) or by telephone (24.5%) when the children were 6 months old. Data were analyzed statistically using the Kaplan-Meier survival method and Cox's multivariate regression model. During hospitalization, 100% of the preterm infants received human milk and 31% received exclusive breastfeeding. The median duration of exclusive breastfeeding and breastfeeding was 63.5 and > 180 days, respectively. The prevalence of breastfeeding in the sixth month was 54.7%, and 6.8% of the infants were still exclusively breastfed. Pacifiers were used (currently using or ever used) by 127 (45.7%) preterm infants and were associated with a 1.67 times higher risk of interruption of exclusive breastfeeding. J Hum Lact. 23(3):269-274.
Issues of Fairness in International Trade Agreements
Authors: Brown Andrew G. , Stern Robert M.
Published: July 2007

In this article, we first describe the characteristics of the World Trade Organization (WTO) that are the basis of the framework of the multilateral trading system. We then provide an overview of concepts of fairness in trade agreements. Thereafter, we offer a critique of the efficiency criterion in assessing multilateral trade agreements, taking issue with T.N. Srinivasan's (2006) analysis and then elaborate on our conception of fairness as reflected in agreements covering market access. We also address considerations of distributive justice, in contrast with Srinivasan's contention that distributive justice has no role to play in the design and negotiation of multilateral trade agreements. Finally, we question bilateral trade agreements from the standpoint of fairness, drawing on the example of the U.S. bilateral FTA negotiated in 2005 with Central America and the Dominican Republic.
Financial Liberalisation and Monetary Policy
Authors: Nachane D.M. , Raje Nishita
Published: July 2007

It is generally believed that financial liberalisation erodes the potency of monetary policy by rendering tenuous the link between monetary aggregates and important macro-economic magnitudes (such as income, prices and exchange rates). This could be accounted for by several factors such as the blurring of the distinction between money and near-money, the breakdown of the money demand function and the easing of credit and liquidity constraints. This hypothesis has been tested in the context of developed economies, where it has derived a measure of support. However, the empirical evidence to test this proposition is somewhat scanty, in the context of less developed countries (LDCs) and emerging market economies (EMEs). This article uses a Structural Vector Auto Regressive (SVAR) model to address this problem in the Indian context over the period January 1980 to August 2004. Using monthly data separate SVAR models are estimated for the pre-liberalisation (1980:03 to 1991:12) and post-liberalisation phases (1992:01 to 2004:08), with a view to recording differential responses (if any) of industrial output, exchange rates and prices to changes in monetary impulses. The analysis brings out that some, though not substantial, differences are evident in this regard over the two periods. The article concludes by spelling out certain reorientations necessary in the conduct of monetary policy in a financially liberalised environment.
India's Growth from China's Perspective
Authors: Bottelier Pieter
Published: July 2007

Bilateral India-China ties, including trade and investment, are increasing rapidly to the benefit of both countries. Looking at India's impressive economic performance of the last 10 years from the perspective of China's experience suggests that sustaining high growth will require a significant further opening of its economy—both externally and internally—a higher national investment rate and stronger labour absorption in the modern sectors. The base of India's current economic growth model—IT-related services and high-end manufacturing—is too narrow. India's poor performance in agriculture is the most important source of massive rural poverty in many parts of the country. Its greatest source of economic strength, a dynamic and relatively highly developed private corporate sector—an area where China lags—can be leveraged more effectively for national development. A partial convergence of the Indian and Chinese growth models is indicated and appears likely. The notion that India-China relations are, or are bound to become, fundamentally antagonistic—held by many in the United States—is mistaken and potentially dangerous.
Loop Shaping Control of a Model-Story Building Using Smart Materials
Authors: Sethi Vineet , Gangbing Song  , Franchek Matthew A.
Published: July 2007

This research concerns active vibration control of a two-story model structural frame by using the method of loop shaping. Piezoceramic smart materials, in particular the PZT (Lead Zirconate Titanate) in the form of patches, are surface-bonded on the structure and function as actuators and sensors. Sensitivity charts are introduced to assist the control system design. A nonparametric system identification is performed to obtain the frequency response function of the model building. A loop-shaped controller is designed using sensitivity charts. The effectiveness of the designed controller is demonstrated by shaker table tests where data from four earthquakes is used for excitation of the structure. The experimental results clearly show that the loop shaping based controller reduces the vibrations experienced by the structure during seismic activities.
The Rationale for SEA to Overcome the Inadequacy of Environmental Assessment in Bangladesh
Authors: Alshuwaikhat Habib M. , Syed Masiur Rahman  , Yusuf Adedoyin Aina
Published: July 2007

The first remarkable environmental initiatives in Bangladesh were taken because of the Stockholm Conference on Human Environment in 1972. The provision that requires Environmental Impact Assessment (EIA) for any new public and private project was first incorporated in the National Environmental Policy, 1992. Still environmental degradation is one of the major concerns in Bangladesh. Like some other developing countries, it initiates and conducts EIA in order to satisfy international donor agencies. Now, EIA is becoming matured through the positive steps of government, non-governmental organizations (NGOs) and international agencies. However, EIA cannot adequately address all the prevailing environmental issues in Bangladesh because of its inherent and contextual limitations. This article explores the evolution of environmental assessment in Bangladesh, mostly at the strategic level. It investigates some of the policy failures, which resulted due to the absence of environmental assessment at the strategic level. Through a questionnaire survey (e-mail) and extensive literature review, this research concludes that Strategic Environmental Assessment (SEA) as a process can effectively address the limitations of EIA and contribute to policy development in order to ensure sustainable development.
A Microsite Analysis of Resource Use Around Kaziranga National Park, India
Authors: Shrivastava Rahul J. , Heinen Joel
Published: July 2007

We used a semistructured social survey of 590 households in 37 villages along the southern boundary of Kaziranga National Park and World Heritage Site, Assam, India in late 2000 and early 2001 to assess resource use and demographic and socioeconomic conditions. Kaziranga, recently expanded in size in a region with a large and diverse human population, is globally important for the conservation of several critically endangered species. This was the first in-depth study of its kind in Kaziranga. The results showed highly variable resource use patterns as a function of caste/ethnic group, educational level, socioeconomic and immigration status of households, and location with respect to the park and wildlife corridors. We highlight the importance of and present a basis for electing a microsite planning approach for conservation and development in areas characterized by (1) high ethnic diversity, (2) high human population densities, and (3) endangered, land-dependent large mammal populations that pose economic risks. Individualized development schemes and participatory approaches to management at the local level are critical to achieve conservation and development goals in these cases.
Testing for Home Team and Favorite Biases in the Australian Rules Football Fixed-Odds and Point Spread Betting Markets
Authors: Schnytzer Adi , Weinberg Guy
Published: July 2007

In this article, the authors test two different kinds of bias—the favorite-long shot/favorite-underdog bias and the home team bias—and distinguish between the two, using a distinctive feature of the Australian Football League (AFL): the fact that many games are played on neutral grounds. The authors conduct their tests by subjecting 2001-2004 data for the AFL to detailed scrutiny, using standard econometric weak-form efficiency models of point spread and fixed-odds betting markets. They reject the existence of any significant pure favorite-long shot/favorite-underdog bias in either market and demonstrate the existence of a significant bias in favor of teams with an apparent home ground advantage in games played outside Victoria in the point spread market and in the fixed-odds market during 2002, 2004, and the period as a whole. Games in Melbourne and in Geelong are free of such a bias (except for 2003 in the point spread market in Geelong). Betting simulations that attempt to exploit these inefficiencies yield modest profits.
The Constraint of Law
Authors: Benesh Sara C. , Spaeth Harold J.
Published: July 2007

To study the behavior of judges, one must first consider whether judges are just like any other political actor (e.g., legislators) or whether, because of their affiliation with the judiciary, law constrains their behavior to some extent. Research aimed at considering the extent to which judges are constrained by the law is sparse, and conclusions resulting from such research are mixed. In this article, the authors explore the extent to which law constrains judges by focusing on the decision to dissent rather than concur when Supreme Court justices write separately. The authors find that, although law matters, it does not constrain.
Strategic Selection of Legal Instruments on the U.S. Supreme Court
Authors: King Chad M.
Published: July 2007

I examine and empirically test a central assumption of strategic models of Supreme Court behavior. Specifically, I consider whether the Court selects legal instruments used in the majority opinions of federal statutory cases to reduce the likelihood that Congress will overturn that opinion, in particular whether the Court invokes constitutional interpretation over statutory interpretation to avoid congressional “overrides” in cases involving federal statutes. Using decisions from the 1953 to 2000 Court terms, I find evidence that when the Court anticipates that Congress may overturn its opinion, the Court is more likely to employ constitutional interpretation in its opinion. These findings confirm that opportunities for the Court to behave strategically are not limited to voting behavior but instead extend to other areas such as choice of legal instruments.
The Effects of Ideology on Federal Trial Judges' Decisions to Admit Scientific Expert Testimony
Authors: Buchman Jeremy
Published: July 2007

This article examines trial court rulings concerning the admissibility of scientific expert testimony. In Daubert v. Merrell Dow Pharmaceuticals (1993), the Supreme Court reaffirmed the trial judge's role as a “gatekeeper” and gave trial judges substantial discretion over their scrutiny of expert testimony. Because the external constraints on admissibility rulings are minimal, one might expect that if trial judges' ideology were to play some role in their decision making, it might do so here. To test this expectation, I perform a binomial logit analysis of federal district court Daubert rulings in tort cases from 1983 to 2003. I find substantial support for the claim that trial judges' ideology can predict decisions on admissibility. I find less support, however, for the claim that Daubert affected trial judges' willingness to admit such testimony, and no evidence that such decisions are affected by the prospect of reversal on appeal.
Premature cardiovascular disease after allogeneic hematopoietic stem-cell transplantation
Authors: Tichelli André , Bucher Christoph , Rovó Alicia , Stussi Georg , Stern Martin , Paulussen Michael , Halter Jörg , Meyer-Monard Sandrine , Heim Dominik , Tsakiris Dimitrios A. , Biedermann Barbara , Passweg Jakob R. , Gratwohl Alois
Published: July 2007

We assessed incidence and risk factors of cardiovascular events in 265 patients undergoing allogeneic hematopoietic stem-cell transplantation (HSCT) between 1980 and 2000 and who survived at least 2 years. Results were compared with a cohort of 145 patients treated during the same period with autologous HSCT. The median age of patients with allogeneic HSCT at last follow-up was 39 years, and median follow-up was 9 years. Eighteen (6.8%) patients after allogeneic and 3 (2.1%) patients after autologous HSCT experienced an arterial event. The cumulative incidence of first arterial event after allogeneic HSCT was 22.1% (95% CI, 12.0-40.9) at 25 years. The cumulative incidence 15 years after allogeneic HSCT was 7.5% as compared with 2.3% after autologous HSCT. Adjusting for age, risk of an arterial event was significantly higher after allogeneic HSCT (RR 6.92; P =.009). In multivariate analysis, allogeneic HSCT (RR: 14.5; P =.003), and at least 2 of 4 cardiovascular risk factors (hypertension, dyslipidemia, diabetes, obesity) (RR: 12.4; P =.02) were associated with a higher incidence of arterial events after HSCT. Thus, long-term survivors after allogeneic HSCT are at high risk for premature arterial vascular disease. HSCT might favor the emergence of established risk factors, such as hypertension, diabetes, and dyslipidemia.
Immunomodulatory properties of mesenchymal stromal cells
Authors: Nauta Alma J. , Fibbe Willem E.
Published: July 2007

Mesenchymal stem cells (MSCs) are multipotential nonhematopoietic progenitor cells capable of differentiating into multiple lineages of the mesenchyme. MSCs have emerged as a promising therapeutic modality for tissue regeneration and repair. Further clinical interest has been raised by the observation that MSCs are immunoprivileged and, more importantly, display immunomodulatory capacities. Although the mechanisms underlying the immunosuppressive effects of MSCs have not been clearly defined, their immunosuppressive properties have already been exploited in the clinical setting. The aim of this review is to critically discuss the immunogenicity and immunomodulatory properties of MSCs, both in vitro and in vivo, the possible underlying mechanisms, the potential clinical use of MSCs as modulators of immune responses in vivo, and to indicate clinical safety concerns and recommendations for future research.
Megakaryocyte-restricted MYH9 inactivation dramatically affects hemostasis while preserving platelet aggregation and secretion
Authors: Léon Catherine , Eckly Anita , Hechler Béatrice , Aleil Boris , Freund Monique , Ravanat Catherine , Jourdain Marie , Nonne Christelle , Weber Josiane , Tiedt Ralph , Gratacap Marie-Pierre , Severin Sonia , Cazenave Jean-Pierre , Lanza François , Skoda Radek , Gachet Christian
Published: July 2007

Mutations in the MYH9 gene encoding the nonmuscle myosin heavy chain IIA result in bleeding disorders characterized by a macrothrombocytopenia. To understand the role of myosin in normal platelet functions and in pathology, we generated mice with disruption of MYH9 in megakaryocytes. MYH9Δ mice displayed macrothrombocytopenia with a strong increase in bleeding time and absence of clot retraction. However, platelet aggregation and secretion in response to any agonist were near normal despite absence of initial platelet contraction. By contrast, integrin outside-in signaling was impaired, as observed by a decrease in integrin β3 phosphorylation and PtdIns(3,4)P2 accumulation following stimulation. Upon adhesion on a fibrinogen-coated surface, MYH9Δ platelets were still able to extend lamellipodia but without stress fiber–like formation. As a consequence, thrombus growth and organization, investigated under flow by perfusing whole blood over collagen, were strongly impaired. Thrombus stability was also decreased in vivo in a model of FeCl3-induced injury of carotid arteries. Overall, these results demonstrate that while myosin seems dispensable for aggregation and secretion in suspension, it plays a key role in platelet contractile phenomena and outside-in signaling. These roles of myosin in platelet functions, in addition to thrombocytopenia, account for the strong hemostatic defects observed in MYH9Δ mice.
The WAVE2/Abi1 complex differentially regulates megakaryocyte development and spreading: implications for platelet biogenesis and spreading machinery
Authors: Eto Koji , Nishikii Hidekazu , Ogaeri Takunori , Suetsugu Shiro , Kamiya Akihide , Kobayashi Toshihiro , Yamazaki Daisuke , Oda Atsushi , Takenawa Tadaomi , Nakauchi Hiromitsu
Published: July 2007

Actin polymerization is crucial in throm-bopoiesis, platelet adhesion, and mega-karyocyte (MK) and platelet spreading. The Wiskott-Aldrich syndrome protein (WASp) homolog WAVE functions downstream of Rac and plays a pivotal role in lamellipodia formation. While MKs and platelets principally express WAVE1 and WAVE2, which are associated with Abi1, the physiologic significance of WAVE isoforms remains undefined. We generated WAVE2−/− embryonic stem (ES) cells because WAVE2-null mice die by embryonic day (E) 12.5. We found that while WAVE2−/− ES cells differentiated into immature MKs on OP9 stroma, they were severely impaired in terminal differentiation and in platelet production. WAVE2−/− MKs exhibited a defect in peripheral lamellipodia on fibrinogen even with phorbol 12-myristate 13-acetate (PMA) costimulation, indicating a requirement of WAVE2 for integrin αIIbβ3-mediated full spreading. MKs in which expression of Abi1 was reduced by small interfering RNA (siRNA) exhibited striking similarity to WAVE2−/− MKs in maturation and spreading. Interestingly, the knockdown of IRSp53, a Rac effector that preferentially binds to WAVE2, impaired the development of lamellipodia without affecting proplatelet production. In contrast, thrombopoiesis in vivo and platelet spreading on fibrinogen in vitro were intact in WAVE1-null mice. These observations clarify indispensable roles for the WAVE2/Abi1 complex in αIIbβ3-mediated lamellipodia by MKs and platelets through Rac and IRSp53, and additionally in thrombopoiesis independent of Rac and IRSp53.
PPARγ regulates the function of human dendritic cells primarily by altering lipid metabolism
Authors: Szatmari Istvan , Töröcsik Daniel , Agostini Maura , Nagy Tibor , Gurnell Mark , Barta Endre , Chatterjee Krishna , Nagy Laszlo
Published: July 2007

Activation of the lipid-regulated nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) modifies the immunophenotype of monocyte-derived dendritic cells (DCs). However it has not been analyzed in a systematic manner how lipid metabolism and immune regulation are connected at the transcriptional level via this receptor. Here we present the genome-wide expression analyses of PPARγ-instructed human DCs. Receptor activation was achieved by exogenous, synthetic as well as endogenous, natural means. More than 1000 transcripts are regulated during DC development by activation of PPARγ; half of the changes are positive effects. These changes appear to enhance and modulate the robust gene expression alterations associated with monocyte to DC transition. Strikingly, only genes related to lipid metabolism are overrepresented among early induced genes. As a net consequence, lipid accumulation appears to be diminished in these cells. In contrast, genes related to immune response are regulated after 24 hours, implying the existence of indirect mechanisms of modulation. Receptor dependence was established by using DCs of patients harboring a dominant-negative mutation of PPARγ. Our data show that PPARγ acts as a mostly positive transcriptional regulator in human developing DCs, acting primarily through controlling genes involved in lipid metabolism and via this, indirectly modifying the immune phenotype.
Premature ventricular complex-induced chronic cough and cough syncope
Authors: Stec S. , Da̧browska M. , Zaborska B. , Bielicki P. , Maskey-Warzęchowska M. , Tarnowski W. , Chazan R. , Kulakowski P.
Published: July 2007

The present case study reports a case of chronic cough and cough syncope associated with frequent premature ventricular complexes (PVCs).

Careful analysis of cough-related symptoms and ECG monitoring led to the suspicion of PVC-induced cough. A coincidence between PVCs and episodes of cough was also documented by a portable multichannel recorder. Moreover, Doppler echocardiography revealed a PVC-induced transient increase in the pulmonary artery blood flow.

After exclusion of other possible aetiologies, complete relief of chronic cough and cough syncope was achieved by radiofrequency ablation of the arrhythmogenic focus located in the right ventricular outflow tract.

Premature ventricular complexes should be considered as a cause of chronic cough and cough syncope and an interdisciplinary cooperation can lead to successful diagnosis and treatment of this condition.
T-cell co-stimulatory molecules: novel targets for the treatment of allergic airway disease
Authors: Beier K. C. , Kallinich T. , Hamelmann E.
Published: July 2007

The first two articles in this series discussed the fundamental concept of T-cell co-stimulation as a key event in the induction of any immune response, in addition to reviewing the current data on the role of co-stimulatory molecules for the induction and progression of allergic airway diseases. Based on these considerations, this final edition will delineate and discuss novel strategies for the prevention and/or therapy of allergic diseases based upon the modulation of co-stimulation.
The effects of hypoxia on the cells of the pulmonary vasculature
Authors: Pak O. , Aldashev A. , Welsh D. , Peacock A.
Published: July 2007

Pulmonary hypertension is associated with remodelling of pulmonary vessels. Chronic hypoxia is a common cause of pulmonary hypertension and pulmonary vascular remodelling. Vascular remodelling is characterised largely by fibroblast, smooth muscle and endothelial cell proliferation, which results in lumen obliteration. Chronic hypoxia elicits expression of mitogens, growth factors and cytokines by fibroblasts and endothelial cells, and also the suppression of endothelial nitric oxide synthase. Although hypoxic pulmonary vascular remodelling is associated with medial hypertrophy, manyin vitrostudies have found that hypoxia does not lead to a direct increase in smooth muscle cell proliferation. This paradox is not well understood and this review aims to examine the various reasons why this might be so. The present authors reviewed data fromin vitrostudies and also considered whether hypoxia could act on adjacent cells such as fibroblasts and endothelial cells to trigger smooth muscle cell proliferation. It is possible that hypoxia is sensed by fibroblasts, endothelial cells, or both, and relayed to adjacent pulmonary artery smooth muscle cells by intercellular signalling, causing proliferation.

The present article reviews the data fromin vitrostudies of hypoxia on the three cellular components of the pulmonary vascular wall, namely endothelial cells, smooth muscle cells and fibroblasts.
The pattern recognition receptor Nod1 activates CCAAT/enhancer binding protein β signalling in lung epithelial cells
Authors: Barton J. L. , Berg T. , Didon L. , Nord M.
Published: July 2007

The innate immune receptor nucleotide-binding oligomerisation domain protein 1 (Nod1) recognises peptidoglycan containingmeso-diaminopimelic acid found in all Gram-negative and some Gram-positive bacteria. Nod1 has been shown to activate nuclear factor (NF)-κB. The aim of the present study was to examine the expression of Nod1 in the lung, particularly in lung epithelial cells, and to investigate the activation of CCAAT/enhancer binding protein (C/EBP) transcription factors downstream of the Nod1 receptor in these cells.

The expression of Nod1 in mouse lung was examined using immunohistochemistry. A tissue array was used to determine the expression pattern in the human lung. Signalling downstream of Nod1 was examined in the human lung epithelial cell type, BEAS-2B, by electrophoretic mobility shift assay and reporter gene activation.

Nod1 expression was seen in various cell types in the lung, including epithelial cells. Activation of Nod1 in these cells resulted in modest activation of NF-κB, together with strong activation of the C/EBP transcription factors, particularly C/EBPβ. This activation appears to be independent ofde novoprotein synthesis.

The present study showed that nucleotide-binding oligomerisation domain protein 1 is expressed in lung epithelial cells. The results demonstrate a novel pathway downstream of the nucleotide-binding oligomerisation domain protein 1 receptor in these cells and suggest that C/EBPβ may play a role in immune responses tomeso-diaminopimelic acid-containing bacteria in the lung.
Trends in ethical and legal frameworks for the use of human biobanks
Authors: Cambon-Thomsen A. , Rial-Sebbag E. , Knoppers B. M.
Published: July 2007

Numerous studies of genetic epidemiology and post-genomics in respiratory diseases rely on the use of biobanks, defined as organised biological sample collections with associated personal and clinical data. The use of biobanks is increasing and raises several ethical issues. What are the ethical trends and legal frameworks in the post-genomic era? Are there new issues in relation to the developments of techniques and new study designs? How does this affect the clinician’s attitudes and relationship with the patients?

The main ethical issues encountered are: informed consent; confidentiality; secondary use of samples and data over time; return of results; and data sharing. Different levels and modalities of dealing with such issues are identified and vary from legally binding measures to “soft” regulations, such as ethical recommendations by various committees or professional organisations.

A further level of complexity appears with the increasing international dimension of such activities in a context in which national positions vary on those topics. There is a tension between a necessary level of diversity in ethical positions and an indispensable common pedestal of principles and procedures to manage these issues in order to foster research.

Current legal and ethical trends favour the facilitation of secondary use of samples, more biobank openness, balanced with a growing attention to dialogue and public/stakeholder consultation, an increased role for research ethics committees and more sophisticated data protection and governance structures.
Evolution of outcome measures in schizophrenia
Authors: Burns Tom
Published: July 2007

Outcome has been a key concern in schizophrenia since Kraepelin first identified the disorder. The outcomes that researchers and clinicians use and value in their work with it have changed to reflect evolving theories about it and the available interventions. This supplement tracks those changes and examines the merits and use of structured approaches to understand this most complex disorder
Social outcomes in schizophrenia
Authors: Priebe Stefan
Published: July 2007

Background

Outcomes reflecting the social situation are widely considered as important in the treatment of people with schizophrenia

Aims

To review concepts of social outcomes in schizophrenia and the corresponding assessment instruments

Method

Non-systematic literature review and reflection on conceptual and methodological issues

Results

Concepts of social outcomes in schizophrenia lack agreed definitions and theoretical models. A fundamental issue is the distinction between objective and subjective indicators. More research has focused on subjective indicators, which are only weaklly correllated with objective life situation and show consistent correlations with mood. Various assessment instruments have been developed pragmatically, particularly to measure quality of life and social functioning, and the literature provides extensive data for comparison

Conclusions

Established instruments exist to measure social outcomes in schizophrenia. Their use requires an awareness of the specific strengths and limitations
Outcomes of public concern in schizophrenia
Authors: Kooyman Iain , Dean Kimberlie , Harvey Samuel , Walsh Elizabeth
Published: July 2007

Background

Schizophrenia is known to be associated with a range of adverse outcomes, which have an impact at the societal level and are therefore of public concern

Aims

To examine the epidemiology and methods for measuring six adverse outcomes in schizophrenia: violence, victimisation, suicide/self-harm, substance use, homelessness and unemployment

Method

Areview of the literature was carried out for each adverse outcome, with attention to critical appraisal of existing measurement tools

Results

Schizophrenia is associated strongly with all six outcomes, although research has mainly focused on violence. Each outcome acts as a risk factor for at least some of the other outcomes. There are few standardised or validated measures for these'hard' outcomes. Each measure has inherent biases but a growing trend is for these to be minimised by using multiple measures

Conclusions

Asingle instrument which systematically measures multiple societal outcomes of schizophrenia would be extremely useful for both clinical and research purposes
Cognition as an outcome measure in schizophrenia
Authors: Kraus Michael S. , Keefe Richard S. E.
Published: July 2007

Background

Cognitive deficits are a core feature of schizophrenia. These deficits are not caused by medication or symptoms, and have a dramatic negative effecton real-world functioning

Aims

To critically examine a selection of the most common batteries used to assess cognition in schizophrenia

Method

Literature review of cognitive assessment batteries for use in schizophrenia

Results

A wide variety of neuro-cognitive test batteries have been developed or adapted to assess cognition in schizophrenia. These differ in time requirements, repeatability, ease of administration, degree of face validity, availability of co-normative data and degree to which results can be parsed into separate domains of cognitive functioning. The most appropriate depends on the setting and the question being addressed

Conclusions

Cognitive outcome measures have reshaped our understanding of schizophrenia and will be essential tools for unravelling the aetiology of the disease and designing more effective interventions
Neuroimaging and other neurobiological indices in schizophrenia: relationship to measurement of functional outcome
Authors: Waddington John L.
Published: July 2007

Background

As understanding of the pathobiology of schizophrenia increases, the challenge is to relate such measures to outcome at a functional level

Aims

To consider our current understanding of how neurobiological variables relate to functional outcome and might constitute outcome measures in their own right

Method

Critical appraisal of recent evidence on structural and functional imaging, neurological evaluation, early neurodevelopmental indices, genomics, proteomics, metabolomics and apoptotic mechanisms in relation to outcome

Results

Studies conducted prospectively from the first episode of schizophrenia are generating more reliable findings but currently lack predictive power. Prediction of transition from ‘high-risk’ status to first episode has proved somewhat more fruitful, but the gain has been modest and circumscribed

Conclusions

Our current level of understanding does not yet allow the generation of predictive models on an individual patient basis. Genomic and metabolomic studies hold particular potential for generating clinically meaningful ‘biomarkers’ but considerable further work is necessary
Schizophrenia outcome measures in the wider international community
Authors: Isaac Mohan , Chand Prabhat , Murthy Pratima
Published: July 2007

Background

Outcome of schizophrenia has been described as favourable in low-and middle-income countries. Recently, researchers have questioned these findings

Aims

To examine the outcome studies carried out in different countries specifically looking atthose from low-and middle-income countries

Methods

Long-term course and outcome studies in schizophrenia were reviewed

Results

A wide variety of outcome measures are used. The most frequent are clinical symptoms, hospitalisation and mortality (direct indicators), and social/ occupational functioning, marriage, social support and burden of care (indirect indicators). Areas such as cognitive function, duration of untreated psychosis, quality of life and effect of medication have not been widely studied in low-and middle-income countries

Conclusions

The outcome of schizophrenia appears to be better in low-and middle-income countries. A host of sociocultural factors have been cited as contributing to this but future research should aim to understand this better outcome. There is a need for more culture-specific instruments to measure outcomes
Characteristics and activities of acute psychiatric in-patient facilities: national survey in Italy
Authors: De Girolamo Giovanni , Barbato Angelo , Bracco Renata , Gaddini Andrea , Miglio Rossella , Morosini Pierluigi , Norcio Bruno , Picardi Angelo , Picardi Angelo , Rossi Elisabetta , Rucci Paola , Santone Giovanni , Dell'Acqua Giuseppe
Published: July 2007

Background

Legislation in 1978 led to the gradual replacement of mental hospitals in Italy with a full range of community-based services, including facilities for acute in-patient care.

Aims

To survey the main characteristics of Italian public and private in-patient facilities for acute psychiatric disorders.

Method

Structured interviews were conducted with each facility's head psychiatrist in all Italian regions, with the exception of Sicily.

Results

Overall, Italy (except Sicily) has atotal of 4108 public in-patient beds in 319 facilities, with 0.78 beds for every 10 000 inhabitants, and 4862 beds in 54 private in-patient facilities, with 0.94 beds per 10 000 inhabitants. In 2001 the rates of psychiatric admissions and admitted patients per 10 000 inhabitants were 26.7 and 17.8 respectively. In the same year the percentage of involuntary admissions was 12.9%, for atotal of 114 570 hospital days. Many in-patient facilities showed significant limitations in terms of architectural and logistic characteristics. Staffing showed a great variability among facilities.

Conclusions

The overall number of acute beds per 10 000 inhabitants is one of the lowest in Europe. The survey has provided evidence of two parallel systems of in-patient care, a public one and a private one, which are not fully interchangeable.
Social identification and post-traumatic stress symptoms in post-conflict Northern Ireland
Authors: Muldoon Orla T. , Downes Ciara
Published: July 2007

Background

Understanding of the psychological impact of politically motivated violence is poor.

Aims

To examine the prevalence of post-traumatic symptoms subsequent to the ‘troubles' in Northern Ireland.

Method

A telephone survey of 3000 adults, representative of the population in Northern Ireland and the border counties of the Irish Republic, examined exposure to political violence, post-traumatic stress disorder (PTSD) and national identity.

Results

Ten per cent of respondents had symptoms suggestive of clinical PTSD. These people were most likely to come from low-income groups, rate national identity as relatively unimportant and have higher overall experience of the ‘troubles' than other respondents.

Conclusions

Direct experience of violence and poverty increase the risk of PTSD, whereas strong national identification appears to reduce this risk.
Frontal release signs and cognition in people with schizophrenia, their siblings and healthy controls
Authors: Hyde Thomas M. , Goldberg Terry E. , Egan Michael F. , Lener Marc C. , Weinberger Daniel R.
Published: July 2007

Background

Frontal release signs, a subset of neurological soft signs, are common in schizophrenia.

Aims

To explore the relationship between frontal release signs and neuropsychological tests of frontal lobe function in people with schizophrenia, their siblings and healthy controls.

Method

Neuropsychological tests and frontal release signs were measured in a cohort of index cases (n=302), their siblings (n=240) and healthy controls (n=346).

Results

The mean total score of frontal release signs was 1.5 (s.d. = 1.58) in the schizophrenia group, 0.54 (s.d.=0.92) for siblings and 0.42 (s.d.=0.77) for controls. Schizophrenia group scores were greater than healthy control or sibling cohort scores (P< 0.0001), which did not differ. In all three cohorts, right grasp reflex scores positively correlated with number of perseverative errors on the Wisconsin Card Sort Task (P<0.05). In the schizophrenia group, frontal release signs scores showed an inverse correlation with IQ (R= −0.199,P<0.0005).

Conclusions

Our findings of relationships between frontal release signs and cognitive assays of cortical dysfunction and the increased frequency of these signs in people with schizophrenia implicate a cortical origin for these clinical signs and evidence of frontal lobe dysfunction in this disorder.
Emotion recognition and genetic vulnerability to schizophrenia
Authors: Bediou Benoit , Asri Fatima , Brunelin Jerome , Krolak-Salmon Pierre , D'Amato Thierry , Saoud Mohamed , Tazi Imane
Published: July 2007

Background

Epidemiological studies of schizophrenia suggest that this disorder has a substantial genetic component. Cognitive and social abilities, as well as the volumes of brain regions involved in emotion processing, have been found to be distributed along a continuum when comparing patients, siblings and controls, with siblings showing intermediate scores.

Aims

To establish whether facial expression recognition is impaired in unaffected siblings of patients.

Method

Emotion and gender recognition were evaluated in a three-group pre–post study design in drugnaive patients with first-episode schizophrenia (n=40) and their unaffected siblings (n=30) compared with controls (n=26).

Results

Patients and their healthy siblings showed impaired emotion recognition but normal gender recognition compared with controls. Patients' performance did not improve despite effective clinical stabilisation.

Conclusions

Impaired performance in healthy siblings and time stability in patients provides evidence of impairment of facial emotion recognition as an actual phenotype of schizophrenia.