bluuebunny/crossref_metadata_2025 huggingface dataset:
Extracellular Matrix Remodeling and Organization in Developing and Diseased Aortic Valves
Authors: Hinton Robert B. , Lincoln Joy , Deutsch Gail H. , Osinska Hanna , Manning Peter B. , Benson D. Woodrow , Yutzey Katherine E.
Published: April 2006

Heart valve disease is an important cause of morbidity and mortality worldwide. Little is known about valve disease pathogenesis, but increasing evidence implicates a genetic basis for valve disease, suggesting a developmental origin. Although the cellular and molecular processes involved in early valvulogenesis have been well described, less is known about the regulation of valve extracellular matrix (ECM) organization and valvular interstitial cell (VIC) distribution that characterize the mature valve structure. Histochemistry, immunohistochemistry, and electron microscopy were used to examine ECM organization, VIC distribution, and cell proliferation during late valvulogenesis in chicken and mouse. In mature valves, ECM organization is conserved across species, and developmental studies demonstrate that ECM stratification begins during late embryonic cusp remodeling and continues into postnatal life. Cell proliferation decreases concomitant with ECM stratification and VIC compartmentalization. Explanted, stenotic bicuspid aortic valves (BAVs) from pediatric patients were also examined. The diseased valves exhibited disruption of the highly organized ECM and VIC distribution seen in normal valves. Cusps from diseased valves were thickened with increased and disorganized collagens and proteoglycans, decreased and fragmented elastic fibers, and cellular disarray without calcification or cell proliferation. Taken together, these studies show that normal valve development is characterized by spatiotemporal coordination of ECM organization and VIC compartmentalization and that these developmental processes are disrupted in pediatric patients with diseased BAVs.
The Bank of England's Monetary Policy Committee: A View from a Parlimentary Specialist Advisor
Authors: Wickens Mike
Published: April 2006

This article assesses the new monetary policy regime introduced in the UK in 1997. It discusses the original remit given to the Bank of England, how it has been interpreted by the Bank and the conduct of monetary policy by the Monetary Policy Committee (MPC) subsequently. The article draws heavily on my experience as Specialist Adviser to the House of Lords Select Committee on Economic Affairs over this whole period. I conclude that the MPC has been very successful in fulfilling its remit, but that a puzzle remains at the heart of the policy over whether the way inflation targeting has worked in practice is consistent with how it is said to work in theory.
The Brave new World of Central Banking: Polcy Challenges posed by Asset Price Booms and Busts
Authors: Cecchetti Stephen G.
Published: April 2006

At the dawn of the 21st century, property and equity ownership are spread more broadly across the population than they once were. One consequence of this is that asset price booms and crashes now have a direct impact on general welfare. The fact that bubbles distort nearly all economic decisions gives policymakers a stronger interest in asset price stability. In this article I examine the theoretical and empirical case for the existence of equity and property bubbles, and then summarise the economic distortions that they create. The evidence suggests increasing our attention to property prices. I go on to discuss the possible policy responses, including examining the consequences of changing the way in which housing is included in standard aggregate price measures.
An Independent Bank of England: Is that Enough
Authors: Hall S.G. , Henry S.G.B.
Published: April 2006

This article argues that an independent central bank is not in itself sufficient to ensure the long-term success and stability of the economy. While there are strong academic arguments for making the central bank independent, these arguments are often developed in a closed economy setting. Where trade is important and the economy is open, making the central bank independent can lead to a strategic interaction between the bank and the fiscal authorities which can produce serious imbalances in the economy over time. In particular, the analysis below suggests that there could be excess demand in the non tradable sector combined with a recession in the sectors of the economy open to trade. Our contention is that the UK economy exhibits all the signs that we would expect to see if this argument were relevant.
“Ancient Caesarian Lawyers” in a State of Nature
Authors: Straumann Benjamin
Published: April 2006

This article examines Grotius’s use of a Roman tradition to establish his notion of a natural and international law in his early treatise De iure praedae (1604-1606). It is argued that De iure praedae, on a methodological level, constituted an attempt to introduce a new doctrine of sources of law by making use of the method of classical rhetoric. On a substantive level, the treatise must be seen as growing out of a Ciceronian tradition of natural law arguments in favor of just war, a tradition further enriched by Grotius with concepts taken from the property law of the Digest. These concepts afforded Grotius with the substantive framework to develop his doctrine of subjective natural rights as sketched in the hitherto unpublished early manuscript Theses LVI. An implication of this investigation of the Roman foundations of Grotius’s theory of natural law is that it challenges widespread assumptions about the “positive” character of ancient liberty.
Stereotypes Focus Defensive Projection
Authors: Govorun Olesya , Fuegen Kathleen , Payne B. Keith
Published: April 2006

Defensive projection is the process of perceiving one’s undesirable qualities in others. The present research shows how stereotypes guide and justify the projection of specific traits onto specific group members. In four studies, the authors demonstrated that people who experienced a threat to a specific dimension of their self-concept selectively activated this dimension in a stereotype and derogated stereotyped others on this dimension. They further showed that stereotyped individuals are more likely to serve as targets of projection than are nonstereotyped individuals. These results demonstrate the functional role of stereotypes in guiding and constraining motivated self-enhancement.
The Future Is Now: Prospective Temporal Self-Appraisals Among Defensive Pessimists and Optimists
Authors: Sanna Lawrence J. , Chang Edward C. , Carter Seth E. , Small Eulena M.
Published: April 2006

Three studies found that prospective temporal self-appraisals can be part of defensive pessimists’ strategy; they felt closer to equally distant negative than positive futures. In Study 1, defensive pessimists felt closer to future failures and reported more negative affect than those considering success. In Study 2, when manipulated negative futures were close, defensive pessimists felt bad and performed well; results suggested that viewing negative futures as close may be part of their natural strategy. Study 3 found that prospective self-appraisals influenced performances through felt preparation. Optimists did not use prospective self-appraisals (Study 1) and their performances were unaffected by manipulated temporal distance (Studies 2 and 3). Discussion centers on prospective self-appraisals and multiple strategies of defensive pessimists.
Defenders of a Lost Cause: Terror Management and Violent Resistance to the Disengagement Plan
Authors: Hirschberger Gilad , Ein-Dor Tsachi
Published: April 2006

Two studies, conducted 3 months before the Israeli pullout from the Gaza Strip and the Northern West Bank, examined whether reminders of death would lead right-wing Israelis to endorse violent resistance against the disengagement plan. More specifically, we hypothesized that this reaction would be particularly strong among participants high in denial—those who were unable to come to terms with the Israeli withdrawal. In Study 1 (N = 63), right-wing Israeli undergraduates were primed with death and asked to indicate whether they view violent resistance as legitimate and whether they would be willing to partake in such violence. In Study 2 (N = 42), Israeli settlers in the Gaza Strip completed a similar procedure as in Study 1. In both studies, primes of death led to greater support of violent resistance, but only among participants high in denial. The discussion examines the applicability of terror management theory to understanding real-life political crises.
Facing Rejection: New Relationships, Broken Relationships, Shame, and Stalking
Authors: Dennison Susan M. , Stewart Anna
Published: April 2006

This study provides a preliminary examination of the relationship among shame-proneness, emotions, and persistent, unwanted courting or pursuit behaviour. A total of 222 undergraduates completed a questionnaire measuring responses to the termination of a relationship or the declining of a date. The Test of Self-Conscious Affect was used to measure shame. Although shame was unrelated to types of intrusive behaviour, individuals who engaged more repetitively in covert pursuit tended to ruminate more over their love interest than did those who rarely engaged in such behaviour. Rumination was positively correlated with shame. Self-harm behaviours and harm toward others were associated with feelings of sadness and depression, and those who engaged more often in harm toward others also reported feelings of anger and jealousy. Conclusions are made regarding the function of shame and other emotions in intrusive behaviour and their potential relevance to treatment of stalkers.
Social Support, Spiritual Program, and Addiction Recovery
Authors: Chen Gila
Published: April 2006

This study compared personal and emotional modifications of inmates who were recovering addicts and who participated in one of two year-long therapeutic intervention programs, one including social support and experiential spiritual program components (Narcotics Anonymous, NA, meetings and the 12-step course), the other including primarily social support (NA meetings only, without the 12-step program). The hypothesis was that supplementing social support programs with a concrete spiritual program would result in more positive personal and emotional changes. The results seem to support the hypothesis: Inmates participating in the 12-step program demonstrated a higher sense of coherence and meaning in life and a gradual reduction in the intensity of negative emotions (anxiety, depression, and hostility) than those participating in NA meetings without the 12-step program. The research findings demonstrate the importance of the 12-step program as part of a rehabilitation process for drug addicts.
The Personal Concerns Inventory (Offender Adaptation)
Authors: Sellen Joselyn L. , McMurran Mary , Cox W. Miles , Theodosi Eleni , Klinger Eric
Published: April 2006

Measuring offenders’ motivation for treatment is important for selection and monitoring treatment engagement, yet few psychometrically robust measures of motivation exist. The Personal Concerns Inventory (PCI) was developed to assess motivation to change in people with addictive behaviours. It focuses on identifying goals in a wide variety of life areas, and two profiles have consistently been identified—adaptive and maladaptive. This study aimed to adapt the PCI for use with offenders and assess its suitability. Following amendment, 11 men serving prison sentences were interviewed using the PCI (Offender Adaptation, OA). Personal concerns related to self-change, and partner, family, and relationships were most commonly identified. Scores suggested that offenders show adaptive and maladaptive profiles, similar to those previously identified. The PCI (OA) has promise for use with offenders, although the issue of whether the PCI (OA) is better viewed as a measure of motivation or a motivational enhancer remains for further research.
A Case of Munchausen Syndrome by Proxy With Subsequent Stalking Behavior
Authors: Reisner Andrew D.
Published: April 2006

A case of Munchausen syndrome by proxy (factitious disorder by proxy) wherein the patient presented with symptoms of severe borderline personality disorder and questionable psychotic symptoms is discussed. This patient was also adjudicated for harassing and stalking a child protective services worker assigned to her case. Issues pertaining to possible feigning of psychotic symptoms were addressed in her inpatient treatment. Despite doubts concerning the veracity of some of her psychotic symptoms, the patient responded well to clozapine, and she was subsequently able to stay out of the psychiatric hospital for longer periods and make a reasonably good adjustment to living in a group home. After refusing to continue with clozapine therapy because of weight gain concerns, her adjustment declined.
Are Effective Drug Courts an Urban Phenomenon?
Authors: Galloway Alyson L. , Drapela Laurie A.
Published: April 2006

Drug courts represent a significant development in criminal justice during the past 15 years, and a small but growing literature suggests they are effective in reducing drug use and criminal behavior. Most of these studies evaluate the effects of drug courts in urban areas, however. This study adds to this literature by considering the effects of this intermediate sanction among adult offenders in a small, nonmetropolitan county of northwest Washington. Using a retrospective comparison group of matched control participants, these results show that the prevalence and incidence of rearrest is significantly lower among drug court graduates than probationers. These differences in recidivism persist even when the age, race, gender, and number of days at risk in the community are statistically controlled. Among those who did recidivate, drug court graduates did not significantly differ from controls in duration to first arrest and arrest incidence. Policy implications are discussed.
Exploitation or Fun?
Authors: Besen Yasemin
Published: April 2006

Objectivist scholars characterize typical teenage jobs as “exploitive”: highly routinized service sector jobs with low pay, no benefits, minimum skill requirements, and little time off. This view assumes exploitive characteristics are inherent in the jobs, ignoring the lived experience of the teenage workers. This article focuses on the lived work experience of particularly affluent, suburban teenagers who work in these jobs and explores the meaning they create during their everyday work experience. Based on a large ethnographic study conducted with the teenage workers at a national coffee franchise, this article unravels the ways in which objectivist views of these “bad jobs” differ from the everyday experience of the actors. The findings show that from the perspective of the teenagers, these “exploitive jobs” are often seen as fun, social, and empowering and are free spaces where they can express their creativity and individuality. These findings demonstrate the importance of employing a constructionist view in understanding teenage employment and inequality.
Social Networks and Self-Rated Health
Authors: Litwin Howard
Published: April 2006

Objective: This article examines the relationship of social network and self-rated health among different cultural groups. Methods: This study examined associations between network structure, interaction, support and social engagement and self-rated health, controlling for sociodemographic background and psychobiological pathways among veteran Jewish-Israelis (n = 2,043), Arab-Israelis (n = 609), and new immigrants from the former Soviet Union (n = 751). Hierarchical multiple regression analysis was performed. Results: Three different patterns emerged. The association of social network and self-rated health among the majority veteran Jewish culture in Israel was similar to that found in Western societies. Among Arab-Israelis, self-rated health was explained by more traditional, familial, and communal network dynamics. The characteristic association between social network and self-rated health among the new immigrants was explained by migration-induced factors. Discussion: The findings demonstrate that social networks impact health differently in different cultural groups and under conditions of social change, such as migration in later-life.
Reports of Abusive Experiences During Childhood and Adult Health Ratings
Authors: Irving Shalon M. , Ferraro Kenneth F.
Published: April 2006

Objectives: This study examines the relationship between reports of childhood abuse and self-rated health in adulthood, and the potential of personal control to serve as a mediator. Method: Regression models were estimated using data from the National Survey of Midlife Development in the United States (MIDUS). Results: Reported emotional abuse was associated with lower personal control. In addition, women who reported emotional abuse by mother or both parents were more likely than women who were not abused to report lower self-rated health. The relationship between emotional abuse by both parents and self-rated health was mediated by personal control. Discussion: The findings suggest that there are long-term health consequences of early childhood abuse. The effects of childhood abusive experiences, however, operate differently for men and women and are dependent on the outcome examined. Childhood abuse compromises personal control that, in turn, leads to lower health ratings.
International Student Quality and Japanese Higher Education Reform
Authors: Lassegard James P.
Published: April 2006

The number of international students in Japan has continued to increase at a rapid pace and has featured very prominently in the so-called internationalization of higher education. International students had been expected to become a catalyst for internationalization and university reform. Recently, however, concern has been raised about the reported decline in the “quality” of international students. This article uses a case study approach to examine the student-quality issue and conducts a review of the closely related problematic educational environment for international students at Japanese universities. Whereas educational-quality problems tend to affect all students, they invariably affect international students to a greater extent because of language obstacles and a lack of awareness regarding cultural and educational differences. The article concludes that for Japanese universities to effectively sustain the current number of international students, particular attention must be given to the improvement of classroom instruction and other educational support.
The Changing Self-Perceptions of Japanese University Students of English
Authors: Pritchard Rosalind M. O. , Maki Hiroaki
Published: April 2006

Traditionally, Japanese learners of English (JLEs) were regarded as poor language learners who underachieved in international comparisons, and cultural factors were often blamed for their underperformance. A university group of JLEs (N = 259) was investigated to discover whether their attitudes toward language learning are becoming more flexible and communicatively oriented. A growing trend of self-assertiveness was found, especially among females who are twice as willing as males to rate themselves good at speaking. Many men students value correctness over fluency (which may impede communicative competence), feel quiet and shy in English classrooms, and assess their English competence more negatively than their female counterparts do. Women enjoy the lessons of Anglophone assistant English teachers much more than men. Both genders are moving away from the traditional reticence and passivity, but there is a divergence between males and females in their attitudes toward language learning.
Peer and Parenting Characteristics of Boys and Girls with Subclinical Attention Problems
Authors: Rielly Nicole E. , Craig Wendy M. , Parker Kevin C. H.
Published: April 2006

Objective: This study examines peer and parenting characteristics of 149 boys and girls with and without subclinical attention problems. Method: Multivariate analyses showed that children with attention problems had higher levels of negative peer nominations and conflict and betrayal in friendships, and their parents tended to use higher levels of negative parenting characteristics compared to comparison children. Children with subclinical attention problems also reported lower levels of positive friendship qualities, and their parents tended to use lower levels of positive parenting characteristics than comparison children. Results: Beyond normative gender differences (e.g., girls reported higher rates of parental involvement than boys), no significant group by gender interactions were found. Conclusion: These findings suggest that both girls and boys who were identified using a subclinical cutoff for attention problems have more difficulties relative to comparison peers across social domains of functioning.
Decision Making in Children With ADHD Only, ADHD-Anxious/Depressed, and Control Children Using a Child Version of the Iowa Gambling Task
Authors: Garon Nancy , Moore Chris , Waschbusch Daniel A.
Published: April 2006

Objective: The goal of this study is to investigate decision making in children with ADHD using a child version of the Iowa Gambling Task (IGT). The effect of internalizing symptoms is also of interest. Method: Twenty-one children with ADHD (high anxiety/depression and no anxiety/depression) are compared to an age- and sex-matched control group on the gambling task. Children in the ADHD-alone group demonstrate impaired performance on the IGT. In contrast, children in the control group and the ADHD-anxiety/depression group learn to choose more from the advantageous decks over time. Results: These findings of impaired decision making in children with ADHD parallel findings of real-life decision-making problems in this population. Conclusion: Furthermore, the findings suggest that having a high number of internalizing symptoms leads to better performance for children with ADHD on this variant of the IGT.
Differences in MAP kinase phosphorylation in response to mechanical strain in asthmatic fibroblasts
Authors: Le Bellego Frédérique , Plante Sophie , Chakir Jamila , Hamid Qutayba , Ludwig Mara S
Published: April 2006

Background

Mechanical strain alters protein expression. It results in phosphorylation of MAP kinases and up-regulation of extracellular matrix proteins. We investigated whether phosphorylation of MAP kinase family members was increased in response to mechanical strain in fibroblasts from asthmatic patients (AF) and normal controls (NF), and whether phosphorylation of these signaling molecules would be different in the two cell populations.

Methods

Fibroblasts were obtained from mild, atopic asthmatics and non-atopic volunteers using endobronchial biopsy. Cells were grown on flexible, collagen I-coated membranes, and subjected to mechanical strain (Flexercell). MAP kinase phosphorylation was measured at baseline, and during one hour of strain. We also examined the effect of strain on proteoglycan production.

Results

At baseline, there was increased phosphorylation of ERK1/2 and p38, and decreased phosphorylation of JNK in AF vs NF. During strain in NF, p38 phosphorylation was increased. Conversely in AF, strain resulted in an increase in JNK phosphorylation, had no effect on phosphorylation of p38, and resulted in a decrease in ERK1/2 phosphorylation. There was a significant increase in versican protein production after 24 h strain in both AF and NF. JNK inhibition reversed the strain-induced increase in versican in NF, but had no effect in AF.

Conclusion

These results show that there are phenotypic differences in MAP kinase phosphorylation in AF vs NF, and that different signaling pathways are involved in transducing mechanical stimuli in these two populations of cells.
Scratch lottery tickets are a poor incentive to respond to mailed questionnaires
Authors: Finsen Vilhjalmur , Storeheier Andreas H
Published: April 2006

Background

It has been demonstrated that the enclosure of money with a mailed questionnaire increases the response rate significantly. We evaluated scratch lottery tickets as an alternative to cash.

Methods

1500 randomly selected Norwegians between the ages of 40 and 65 years were sent a short questionnaire. 250 received one lottery scratch ticket worth 20 Norwegian kroner (approximately 3 US$) together with the questionnaire, 250 received two scratch tickets, and 250 were promised two scratch tickets if they replied within one week. A fourth group of 250 persons received a 50 kroner banknote with the questionnaire. The remaining 500 letters served as controls.

Results

The overall response rate after 6 weeks was 77%. Logistic regression analysis showed that only the 50 kroner group had a response rate that was statistically significantly higher than the controls (p < 0.0001). It was also significantly higher than that in any of the other incentive groups (p < 0.0001, p < 0.004 and p < 0.0001 respectively). Female sex (p < 0.001) and age (p < 0.002) increased the response rate significantly.

Conclusion

It is possible that the recipients scratched their cards before completing the questionnaire, and that it was a disincentive for the majority that they did not win anything. Lottery scratch tickets are no substitute for cash as an incentive to respond to a questionnaire.
Eradication of common pathogens at days 2, 3 and 4 of moxifloxacin therapy in patients with acute bacterial sinusitis
Authors: Ariza Horacio , Rojas Ramon , Johnson Peter , Gower Richard , Benson Alice , Herrington Janet , Perroncel Renee , Pertel Peter
Published: April 2006

Background

Acute bacterial sinusitis (ABS) is a common infection in clinical practice. Data on time to bacteriologic eradication after antimicrobial therapy are lacking for most agents, but are necessary in order to optimize therapy. This was a prospective, single-arm, open-label, multicenter study to determine the time to bacteriologic eradication in ABS patients (maxillary sinusitis) treated with moxifloxacin.

Methods

Adult patients with radiologically and clinically confirmed ABS received once-daily moxifloxacin 400 mg for 10 days. Middle meatus secretion sampling was performed using nasal endoscopy pre-therapy, and repeated on 3 consecutive days during treatment. Target enrollment was 30 bacteriologically evaluable patients (pre-therapy culture positive for Streptococcus pneumoniae, Haemophilus influenzae or Moraxella catarrhalis and evaluable cultures for at least Day 2 and Day 3 during therapy visits), including at least 10 each with S. pneumoniae or H. influenzae.

Results

Of 192 patients enrolled, 42 were bacteriologically evaluable, with 48 pathogens isolated. Moxifloxacin was started on Day 1. Baseline bacteria were eradicated in 35/42 (83.3%) patients by day 2, 42/42 (100%) patients by day 3, and 41/42 (97.6%) patients by day 4. In terms of individual pathogens, 12/18 S. pneumoniae, 22/23 H. influenzae and 7/7 M. catarrhalis were eradicated by day 2 (total 41/48; 85.4%), and 18/18 S. pneumoniae and 23/23 H. influenzae were eradicated by day 3. On Day 4, S. pneumoniae was isolated from a patient who had negative cultures on Days 2 and 3. Thus, the Day 4 eradication rate was 47/48 (97.9%). Clinical success was achieved in 36/38 (94.7%) patients at the test of cure visit.

Conclusion

In patients with ABS (maxillary sinusitis), moxifloxacin 400 mg once daily for 10 days resulted in eradication of baseline bacteria in 83.3% of patients by Day 2, 100% by Day 3 and 97.6% by Day 4.
Multiprofessional training for breastfeeding management in primary care in the UK
Authors: Ingram Jennifer
Published: April 2006

Background

Increasing breastfeeding initiation and duration rates is one of the UK Department of Health national targets for improving the health of the population. One reason contributing to the high rates of breastfeeding discontinuation may be that primary care teams may not have sufficient knowledge to help mothers overcome problems experienced in the early days and may also give conflicting advice. Previous studies have shown that general practitioners are happy to participate in practice-based educational sessions and have expressed a need for breastfeeding education. This study was carried out as part of the training to achieve 'UNICEF UK Baby Friendly Initiative in a community health care setting' status. It aimed to improve the breastfeeding expertise and advice about the management of breastfeeding problems within the primary care team using a CD-ROM breastfeeding learning package, and to assess the usefulness and acceptability of this educational intervention.

Methods

Six UK general practitioner (GP) practices were involved in a questionnaire survey of multiprofessional groups before and after an interactive training session. This focussed on managing and solving problems, particularly mastitis and nipple thrush. The questionnaire included 20 questions on attitudes to and knowledge of breastfeeding, and eight multiple-choice questions on breastfeeding management. Non-parametric statistics (Mann-Whitney, Kruskal-Wallis and Wilcoxon tests) were used to compare the groups and to explore changes in knowledge after training.

Results

Fifty primary care health professionals (29 GPs, 18 health visitors, 3 midwives) attended the sessions. There was an increase in scores relating to knowledge about breastfeeding after training, especially for the GPs and for those who did not have their own children. Health visitors improved their scores on recognition of the symptoms of poor attachment at the breast, and GPs showed greatest improvement in resolving sore nipples and recognising nipple thrush.

Changes in practice were reported and positive comments made about involving GPs and health visitors together in practice-based education.

Conclusion

Using an electronic teaching resource is feasible for updating the knowledge of the primary care team. It can help to improve breastfeeding expertise and advice about breastfeeding problem management.
Atherogenic lipid profile is a feature characteristic of patients with early rheumatoid arthritis: effect of early treatment – a prospective, controlled study
Authors: Georgiadis Athanasios N , Papavasiliou Eleni C , Lourida Evangelia S , Alamanos Yannis , Kostara Christina , Tselepis Alexandros D , Drosos Alexandros A
Published: April 2006

We investigated lipid profiles and lipoprotein modification after immuno-intervention in patients with early rheumatoid arthritis (ERA). Fifty-eight patients with ERA who met the American College of Rheumatology (ACR) criteria were included in the study. These patients had disease durations of less than one year and had not had prior treatment for it. Smokers or patients suffering from diabetes mellitus, hypothyroidism, liver or kidney disease, Cushing's syndrome, obesity, familiar dyslipidemia and those receiving medications affecting lipid metabolism were excluded from the study. Sixty-three healthy volunteers (controls) were also included. Patients were treated with methotrexate and prednisone. Lipid profiles, disease activity for the 28 joint indices score (DAS-28) as well as ACR 50% response criteria were determined for all patients. The mean DAS-28 at disease onset was 5.8 ± 0.9. After a year of therapy, 53 (91.3%) patients achieved the ACR 20% response criteria, while 45 (77.6%) attained the ACR 50% criteria. In addition, a significant decrease in the DAS-28, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were observed. ERA patients exhibited higher serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides, whereas their serum high-density lipoprotein cholesterol (HDL-C) levels were significantly lower compared to controls. As a consequence, the atherogenic ratio of TC/HDL-C as well as that of LDL-C/HDL-C was significantly higher in ERA patients compared to controls. After treatment, a significant reduction of the atherogenic ratio of TC/HDL-C as well as that of LDL-C/HDL-C was observed, a phenomenon primarily due to the increase of serum HDL-C levels. These changes were inversely correlated with laboratory changes, especially CRP and ESR. In conclusion, ERA patients are characterized by an atherogenic lipid profile, which improves after therapy. Thus, early immuno-intervention to control disease activity may reduce the risk of the atherosclerotic process and cardiovascular events in ERA patients.
Dense breast stromal tissue shows greatly increased concentration of breast epithelium but no increase in its proliferative activity
Authors: Hawes Debra , Downey Susan , Pearce Celeste Leigh , Bartow Sue , Wan Peggy , Pike Malcolm C , Wu Anna H
Published: April 2006

Introduction

Increased mammographic density is a strong risk factor for breast cancer. The reasons for this are not clear; two obvious possibilities are increased epithelial cell proliferation in mammographically dense areas and increased breast epithelium in women with mammographically dense breasts. We addressed this question by studying the number of epithelial cells in terminal duct lobular units (TDLUs) and in ducts, and their proliferation rates, as they related to local breast densities defined histologically within individual women.

Method

We studied deep breast tissue away from subcutaneous fat obtained from 12 healthy women undergoing reduction mammoplasty. A slide from each specimen was stained with the cell-proliferation marker MIB1. Each slide was divided into (sets of) areas of low, medium and high density of connective tissue (CT; highly correlated with mammographic densities). Within each of the areas, the numbers of epithelial cells in TDLUs and ducts, and the numbers MIB1 positive, were counted.

Results

The relative concentration (RC) of epithelial cells in high compared with low CT density areas was 12.3 (95% confidence interval (CI) 10.9 to 13.8) in TDLUs and 34.1 (95% CI 26.9 to 43.2) in ducts. There was a much smaller difference between medium and low CT density areas: RC = 1.4 (95% CI 1.2 to 1.6) in TDLUs and 1.9 (95% CI 1.5 to 2.3) in ducts. The relative mitotic rate (RMR; MIB1 positive) of epithelial cells in high compared with low CT density areas was 0.59 (95% CI 0.53 to 0.66) in TDLUs and 0.65 (95% CI 0.53 to 0.79) in ducts; the figures for the comparison of medium with low CT density areas were 0.58 (95% CI 0.48 to 0.70) in TDLUs and 0.66 (95% CI 0.44 to 0.97) in ducts.

Conclusion

Breast epithelial cells are overwhelmingly concentrated in high CT density areas. Their proliferation rate in areas of high and medium CT density is lower than that in low CT density areas. The increased breast cancer risk associated with increased mammographic densities may simply be a reflection of increased epithelial cell numbers. Why epithelium is concentrated in high CT density areas remains to be explained.
Novel gene and gene model detection using a whole genome open reading frame analysis in proteomics
Authors: Fermin Damian , Allen Baxter B , Blackwell Thomas W , Menon Rajasree , Adamski Marcin , Xu Yin , Ulintz Peter , Omenn Gilbert S , States David J
Published: April 2006

Background

Defining the location of genes and the precise nature of gene products remains a fundamental challenge in genome annotation. Interrogating tandem mass spectrometry data using genomic sequence provides an unbiased method to identify novel translation products. A six-frame translation of the entire human genome was used as the query database to search for novel blood proteins in the data from the Human Proteome Organization Plasma Proteome Project. Because this target database is orders of magnitude larger than the databases traditionally employed in tandem mass spectra analysis, careful attention to significance testing is required. Confidence of identification is assessed using our previously described Poisson statistic, which estimates the significance of multi-peptide identifications incorporating the length of the matching sequence, number of spectra searched and size of the target sequence database.

Results

Applying a false discovery rate threshold of 0.05, we identified 282 significant open reading frames, each containing two or more peptide matches. There were 627 novel peptides associated with these open reading frames that mapped to a unique genomic coordinate placed within the start/stop points of previously annotated genes. These peptides matched 1,110 distinct tandem MS spectra. Peptides fell into four categories based upon where their genomic coordinates placed them relative to annotated exons within the parent gene.

Conclusion

This work provides evidence for novel alternative splice variants in many previously annotated genes. These findings suggest that annotation of the genome is not yet complete and that proteomics has the potential to further add to our understanding of gene structures.
Myelin basic protein and myelin oligodendrocyte glycoprotein T-cell repertoire in childhood and juvenile multiple sclerosis
Authors: Correale Jorge , Tenembaum Silvia N
Published: April 2006

Multiple sclerosis (MS) is usually a disease of young adulthood, its clinical onset occurring between 20 and 40 years of age; however, today there is general consensus that MS can also occur in children, adolescents and even in infants. In order to gain further insight into the T-cell repertoire present in this particular group of patients myelin basic protein (MBP)-, MBP exon-2- and myelin oligodendrocyte glycoprotein (MOG)Igd-specific T-cell lines (TCLs) were isolated from 18 patients whose symptoms had started before the age of 16. Epitope specificity was established by measuring proliferative responses, and interferon-g (IFN-g) secretion by using a panel of overlapping synthetic peptides. For MOGIgd, the T-cell response was focused on three main immunodominant epitopes comprising residues 1-26, 36-60 and 63-87. For MBP the predominant immune responses were directed against peptides 83-102, 139-153 and 146-162. When compared to those observed in adult-onset MS patients, anti-MOGIgd specificity and anti-MBP responses showed similar results. Moreover, the number of MBP exon-2 TCLs isolated, and the magnitude of the specific IFN-g secretion induced were similar, both in childhood/juvenile-onset and adult-onset MS patients. Thus, despite differences in the clinical and neuroimaging manifestations of MS, these results would seem to indicate that both the spectrum of MBP found, as well as the MOGIgd epitopes recognized by peripheral blood T cells in MS, appear to be similar for childhood/juvenile-onset and adult-onset patients.
Cognitive-behavioural therapy for substance use disorders in people with psychotic disorders
Authors: Baker Amanda , Bucci Sandra , Lewin Terry J. , Kay-Lambkin Frances , Constable Paul M. , Carr Vaughan J.
Published: April 2006

Background

Few randomised controlled trials have been aimed specifically at substance use reduction among people with psychotic disorders.

Aims

To investigate whether a 10-session intervention consisting of motivational interviewing and cognitive-behavioural therapy (CBT) was more efficacious than routine treatment in reducing substance use and improving symptomatology and general functioning.

Method

A community sample of people with a psychotic disorder and who reported hazardous alcohol, cannabis and/or amphetamine use during the preceding month was recruited. Participants were randomly allocated to motivational interviewing/CBT (n=65) or treatment as usual (n=65), and were assessed on multiple outcomes at baseline, 15 weeks, 6 months and 12 months.

Results

There was a short-term improvement in depression and a similar trend with regard to cannabis use among participants who received the motivational interviewing/CBT intervention, together with effects on general functioning at 12 months. There was no differential benefit of the intervention on substance use at 12 months, except for a potentially clinically important effect on amphetamine use.

Conclusions

The motivational interviewing/CBT intervention was associated with modest improvements.
Grey-matter abnormalities in boys with Tourette syndrome: magnetic resonance imaging study using optimised voxel-based morphometry
Authors: Ludolph Andrea G. , Juengling Freimut D. , Libal Gerhard , Ludolph Albert C. , Fegert Jörg M. , Kassubek Jan
Published: April 2006

The genesis of Tourette syndrome is still unknown, but a core role for the pathways of cortico-striatal-thalamic-cortical circuitry (CSTC) is supposed. Volume-rendering magnetic resonance imaging data-sets were analysed in 14 boys with Tourette syndrome and 15 age-matched controls using optimised voxel-based morphometry. Locally increased grey-matter volumes (corrected P < 0.001) were found bilaterally in the ventral putamen. Regional decreases in grey matter were observed in the left hippocampal gyrus. This unbiased analysis confirmed an association between striatal abnormalities and Tourette syndrome, and the hippocampal volume alterations indicate an involvement of temporolimbic pathways of the CSTC in the syndrome.
Delivering medical care for patients with serious mental illness or promoting a collaborative model of recovery?
Authors: Lester Helen , Gask Linda
Published: April 2006

There is a tension between models of ‘recovery’, which are increasingly important in mental health policy and practice, and systematic models of care delivery based on the notion of ‘chronic illness'. A collaborative approach is central to the development of high-quality recovery-oriented mental healthcare.
The placebo effect
Authors: Rajagopal Sundararajan
Published: April 2006

The placebo effect is a fascinating phenomenon in clinical practice. Studies have shown that there is a significant placebo effect in a wide range of medical conditions including psychiatric disorders. This article looks at the background of the placebo effect, defines the common terms used, describes the various hypotheses that have been put forward to explain this seemingly inexplicable phenomenon and also covers the issue of using placebos in research trials, highlighting the important ethical dilemmas involved. Throughout, specific emphasis is given to psychiatry.
Oral Uracil and Tegafur Plus Leucovorin Compared With Intravenous Fluorouracil and Leucovorin in Stage II and III Carcinoma of the Colon: Results From National Surgical Adjuvant Breast and Bowel Project Protocol C-06
Authors: Lembersky Barry C. , Wieand H. Samuel , Petrelli Nicholas J. , O'Connell Michael J. , Colangelo Linda H. , Smith Roy E. , Seay Thomas E. , Giguere Jeffrey K. , Marshall M. Ernest , Jacobs Andrew D. , Colman Lauren K. , Soran Atilla , Yothers Greg , Wolmark Norman
Published: April 2006

Purpose

The primary aim of this study was to compare the relative efficacy of oral uracil and tegafur (UFT) plus leucovorin (LV) with the efficacy of weekly intravenous fluorouracil (FU) plus LV in prolonging disease-free survival (DFS) and overall survival (OS) after primary surgery for colon carcinoma.

Patients and Methods

Between February 1997 and March 1999, 1,608 patients with stage II and III carcinoma of the colon were randomly assigned to receive either oral UFT+LV or intravenous FU+LV.

Results

Of the total patients, 47% had stage II colon cancer, and 53% had stage III colon cancer. Median follow-up time was 62.3 months. The estimated hazard ratio (HR) for OS of patients who received UFT+LV versus that of patients who received FU+LV was 1.014 (95% CI, 0.825 to 1.246). The estimated HR for DFS was 1.004 (95% CI, 0.847 to 1.190). Cox proportional hazards model analyses with regard to age (< 60 v ≥ 60 years), stage, or number of involved nodes (none v one to three v ≥ four nodes) revealed no interaction with OS or DFS. Toxicity was similar in the two groups. In the UFT+LV arm, 38.2% of patients experienced any grade 3 or 4 toxic event compared with 37.8% of patients in the FU+LV arm. Primary quality-of-life end points did not differ between the two regimens, although convenience of care analysis favored UFT+LV.

Conclusion

UFT+LV achieved similar DFS and OS when compared with an intravenous, weekly, bolus FU+LV regimen. The two regimens were equitoxic and generally well tolerated.
Phase III Trial of an Emulsion Containing Trolamine for the Prevention of Radiation Dermatitis in Patients With Advanced Squamous Cell Carcinoma of the Head and Neck: Results of Radiation Therapy Oncology Group Trial 99-13
Authors: Elliott Elizabeth A. , Wright James R. , Swann R. Suzanne , Nguyen-Tân Felix , Takita Cristiane , Bucci M. Kara , Garden Adam S. , Kim Harold , Hug Eugen B. , Ryu Janice , Greenberg Michael , Saxton Jerrold P. , Ang Kian , Berk Lawrence
Published: April 2006

Purpose

This multicentered phase III trial was designed to compare an emulsion containing trolamine against the usual supportive care within each participating institution for patients with head and neck cancer undergoing radiation therapy.

Patients and Methods

Patients with biopsy-proven squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx were randomly assigned to one of the following treatments: prophylactic trolamine emulsion, interventional trolamine emulsion, or declared institutional preference. The primary outcome was the reduction in grade 2 or higher skin toxicity, as per National Cancer Institute Common Toxicity Criteria version 2.0. Secondary outcomes included patient-reported quality of life (QOL).

Results

From October 2000 to April 2002, 547 patients from 51 institutions were entered onto the trial. The average age was 59 years. Patients were predominately male (79%) and most continued to use tobacco products (52%). The rates of grade 2 or higher radiation dermatitis were 79%, 77%, and 79% in the prophylactic, interventional, and institutional preference arms of the study, respectively. No significant differences in QOL were found.

Conclusion

The results of this trial demonstrate no advantage for the use of trolamine in reducing the incidence of grade 2 or higher radiation dermatitis or improving patient-reported QOL. The use of 15 different local standards of care highlights the need to continue research that will result in evidence-based recommendations to reduce the burden of radiation dermatitis.