bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain‐derived neurotrophic factor (BDNF) gene not associated with antidepressant‐induced mania
Authors: Zai Gwyneth , Mundo Emanuela , Strauss John , Wong Gregory WH , Kennedy James L
Published: August 2007

Background:  Brain‐derived neurotrophic factor (BDNF) plays an important role in the regulation of synaptic plasticity and neurotransmitter release across multiple neurotransmitter systems. Recent studies have suggested that BDNF plays a role in the pathogenesis of bipolar disorder (BPD). Moreover, increasing BDNF production might be one of the mechanisms involved in the alleviation of depression and aggravation of mania in antidepressant treatment.

Objectives:  Thus, we hypothesized that a genetic variant within the BDNF gene might influence susceptibility to antidepressant‐induced mania, as has been suggested previously.

Methods:  We performed a case–control study to test for allelic frequency and genotype distribution differences across six BDNF polymorphisms between 27 patients with antidepressant‐induced mania (IM+) and 29 patients without antidepressant‐induced mania (IM−).

Results:  We did not observe any significant difference in either allelic or genotype frequencies between the two groups.

Conclusions:  Our results did not support the BDNF link to mania hypothesis proposed previously. However, a larger sample would allow for greater power to determine smaller effects of the BDNF gene in antidepressant‐induced mania.
Mood and anxiety spectrum as a means to identify clinically relevant subtypes of bipolar I disorder1
Authors: Fagiolini Andrea , Frank Ellen , Rucci Paola , Cassano Giovanni B , Turkin Scott , Kupfer David J
Published: August 2007

Objectives:  Latent class analysis of demographic and clinical variables can help identify subtypes of patients with bipolar disorder type I (BD I). Classification of patients into clinically relevant and homogeneous subtypes may have implications for further research. We examine the structure of mood and anxiety spectrum features in patients with BD I to identify subtypes with similar profiles.

Methods:  Adult patients diagnosed with BD I, who were also participants in the Bipolar Disorder Center for Pennsylvanians (BDCP) Study, were followed for a median time of 448 days. Data from self‐report instruments of BD I patients were used to derive dichotomous indicators of four spectrum conditions. Latent class analysis was applied to these indicators. Demographic and clinical variables were used as external validators of the classes.

Results:  A 3‐class solution provided a satisfactory data fit and outlined three classes of subjects. Members of the three groups differed in terms of demographic and clinical variables, such as gender, age of onset, mean Clinical Global Impression (CGI) depressive ratings and overall CGI ratings at entry, weighted mean CGI ratings for the period between the first and last evaluation in the BDCP Study and mean Global Assessment of Functioning scores at entry and during the BDCP Study.

Conclusions:  We found substantial clinical heterogeneity among individuals with BD I and found that the levels of lifetime depressive, manic, panic‐agoraphobic, and obsessive‐compulsive spectrum symptoms identify three distinct subtypes characterized by differences in demographic and clinical variables. These results may have implications for research on the neurobiology, genetics, and treatment of BD I.
Benefits of cyclosporine absorption profiling in nephrotic syndrome: Preprandial once‐daily administration of cyclosporine microemulsion improves slow absorption and can standardize the absorption profile
Authors: TAKEDA ASAMI , HORIKE KEIJI , ONODA HIROSHI , OHTSUKA YASUHIRO , YOSHIDA ASTUHIRO , UCHIDA KAZUHARU , MOROZUMI KUNIO
Published: August 2007

Aim:  Cyclosporine is known to improve proteinuria in nephrotic syndrome (NS), but is also associated with drug‐related renal impairment. In this case series, therapeutic drug monitoring using the absorption profile was applied to adults with NS to investigate the efficacy and safety of once‐daily administration of cyclosporine microemulsion (CSAME).

Methods:  Twenty patients received CSAME starting at 100–175 mg/day (1.4–3.1 mg/kg per day) once daily after breakfast. The area under the concentration–time curve up to 4 h after administration of cyclosporine (AUC0−4 h) was determined in each patient within 1 week after the start of CSAME treatment. Thereafter, the dose of CSAME was adjusted according to the absorption profile.

Results:  After 6 months, treatment with CSAME improved efficacy test values compared with those prior to treatment, and the severe nephrotic state was eliminated in all patients. No changes in serum creatinine or blood urea nitrogen levels were observed. The dose of CSAME was adjusted so that AUC0−4 h and the peak level fell within the range of target values, resulting in a significant decrease in the mean dose of cyclosporine (P = 0.0001). Time of peak level was variable among patients, but when CSAME was administered before breakfast, good absorption was achieved in all patients.

Conclusion:  By monitoring the absorption profile in patients with NS, a once‐daily administration of CSAME was used to achieve both efficacy and a reduction in total exposure to the drug. Preprandial administration provided a more stable absorption profile of cyclosporine. The authors hope this method will become standard procedure during cyclosporine treatment in these patients.
Making a spectacle of herself: Reading community mental health nursing assessments
Authors: Street Annette
Published: August 2007

The metaphor of mapping is used in this paper to examine the discursive construction of women whose nudity in public places (making a spectacle of herself) provides dilemmas for community mental health nurses required to make assessments of these women's ability to function in die community. Excerpts from stories provided by die nurses are used to demonstrate the complexity of die decision‐making processes and the limits to die choices they perceive they can make.
Confronting ‘reality’: Nursing, science and the micro‐politics of representation
Authors: Walker Kim
Published: August 2007

In an age where previous frames of reference lose their certainty nurses are finding themselves rethinking their relations to the ‘real’. In this paper I interrogate an empirical ‘text’ of a local nursing cultural practice through a poststructural critique of the ways in which language, discourses, representation and experience intersect to construct ‘reality’ for us with specific consequences. I do this in an attempt to disclose the micro‐politics at work in the processes of signifying and thus representing nursing to a world of potential students. The discourses of science and caring find themselves exposed in particular representational technologies and practices that mark nursing's collusion with the ‘truths’ of science at the expense of those we loosely name ‘caring’. This cultural theoretical work constitutes a provisional and historical fragment of analysis designed to trouble the relations we often unwittingly sustain with dominant ‘regimes of truth’.
Humanism in nursing: the emergence of the light
Authors: Nelson Sioban
Published: August 2007

Humanism in nursing: the emergence of the light

This paper examines Western nursing practices by focusing on their spiritual aspect. The transformation of the informal and poorly trained nurse into the trained and uniform persona of the modern nurse is the subject of many nursing histories and part of nursing mythology. Using the work of Michel Foucault and Marcel Mauss, the nursing that preceded the 19th century reformers is re‐examined and continuities between current and quite ancient practices of nursing are explored. The development of practices or technologies for care of the sick originated with the establishment of hospitals in the 4th century as part of pious Christian practice. Current practices of care and the discourse of holistic nursing are argued to have grown from these traditional Christian technologies of care. Humanist or holistic nursing represents the enshrinement of the Christian edios – freed of doctrine; the discourse of caring a redrafted Christian discipline of love.
Reshaping ethnography: contemporary postpositivist possibilities
Authors: Bruni Nina
Published: August 2007

Reshaping ethnography: contemporary postpositivist possibilities

Following Leinginger's introduction of ethnography into the field of nursing research, numerous descriptive and interpretive studies of health care beliefs and practices have been conducted. The resultant data have been translated into recommendations relative to the areas of nursing education, administration and clinical practice in an effort to ensure that the identified cultural needs are recognized and met. In this paper die discourses that inform such work are explored. Its practices and emergent dilemmas are reassessed in die light of an emerging body of work that challenges its foundational assumptions. Linked under die umbrella of ‘postpositivist ethnography’, such work recognizes the research area as a social and political field of which the researcher is an integral part. Hence, as an informed subject, die researcher, like the informants, is seen to be implicated in the generation of data. She, or he, is not charged with occupying die opposing roles of objective researcher and subjective participant, nor with reporting ‘the truth’ as told by informants. This emergent tradition is not without its dilemmas and of particular concern is the issue of authority; that is, whose voice constructs the text? As nursing academics grapple with questions regarding die nature of die knowledge that informs their discipline, it is imperative that they critique potentially fruitful research practices before they appropriate them. Failure to do so may lead diem to unwittingly generate knowledge that is inimical to their particular quest. The lsquo;new edinographyrsquo; discussed in this paper, offers academics and odiers interested in the generation of knowledge, not only a mediodology that invites the possibility of opening up previously hidden areas of practice, but one that actively involves die researcher in challenging her taken‐for‐granted assumptions.
Courting competency: nursing and the politics of performance in practice
Authors: Walker Kim
Published: August 2007

Courting competency: nursing and the politics of performance in practice

Nurses have long anguished over how best to assess performance in clinical practice. The ‘competency’ movement appears to have provided a solution to this problem. In this paper I undertake a ‘radical hermeneutic’ interrogation of the cultural text of clinical practice doubled with a poststructuralist interpretation of the literal text of the Australian competency project. Through this work I attempt to expose some of the deeply embedded assumptions that underwrite the competency movement and amplify the problems posed by an uncritical appropriation of competency based training and assessment in nursing education.
Foucault and modern medicine
Authors: Peerson Anita
Published: August 2007

Foucault and modern medicine

Modernity as a concept or ideal, resulting from the age of Enlightenment and the French Revolution gave hope of a better future and new possibilities. To be modern means an ‘enlightened’ individual and society, welcoming change and development. In this paper, I will discuss Foucault's analysis (1973) of problematics in medicine in eighteenth century France. Three themes prominent in the text are: ‘the birth of the clinic’, ‘the clinical gaze’ and the power‐knowledge relationship. Three problematics identified in modern medicine by Foucault and which are particularly relevant to twentieth century medicine are: (i) the extension of the clinical gaze from the individual body to the wider population; (ii) the increasing medical intervention and use of technology in fundamental life processes; and (iii) the relationship between society and medicine. I will argue that Foucault's analysis is fraught with ambiguities. It is useful, however, for establishing an explanation for medicine today and for presenting a particular interpretation of modernity.
Discipline and passion: meaning, masochism and mythology in popular medical romances
Authors: DeVries Susan , Dunlop Margaret , Goopy Suzanne , Moyle Wendy , Sutherland‐Lockhart Diane
Published: August 2007

Discipline and passion: meaning, masochism and mythology in popular medical romances

This paper is an interpretive analysis of the discourses within popular romance literature, with a particular focus on the genre that includes constructions of the images of nurses and nursing. An historical contrast is made along with examinations of the uses and meanings encompassed within this body of literature, and its messages for women as nurses as it reflectdcreates societal change. Deviations from the formulaic nature of these works are explored. Discipline and passion are the recurring themes evident throughout in juxtapositions of romance and power differentials in the hospital/medical scene. The soft‐core, sado‐masochistic images evident in many titles are explored in a way that raises questions about sexuality, romance, nursing mythology, and the future of this sub‐genre of the popular romance.
The spirit of nursing and its healing art: a Jungian perspective
Authors: Richmond Jennifer
Published: August 2007

The spirit of nursing and its healing art: a Jungian perspective

Timely change is in the air as interest grows in the riches of nursing literature and other creative arts of nursing. Using Jungian and sociological concepts, this article takes a personal look at the literature's contribution to the profession. As the image of contemporary nursing is redefined, the power of the creative is evident, both in its grounding effect on individual practice and its unifying and strengthening potential for a changing profession.
Massage and sexuality in nursing
Authors: van der Riet Pamela
Published: August 2007

Massage and sexuality in nursing

This paper draws upon data from a students' massage workshop, focuses on the students' discourse as they positioned diem‐selves as masseurs and considers relationships between nursing discourses and genderized self‐hood. For some students, there was a conflation of sex and massage. Massage was more heavily laden with implicit sexual meaning for male students than for female students. The latter were able to negotiate the ambiguities of working with people's bodies in a more comfortable way. This research has implications for teaching students of nursing, particularly in relation to massage, and also nursing practice that involves care for the patient's body.
Containing abjection in nursing: the end of shift handover as a site of containment
Authors: Wiltshire John , Parker Judith
Published: August 2007

This theoretical paper has arisen out of a national study of the end of shift nursing handover. It draws upon and offers postmodern reformulation of the psychodynamic concepts of anxiety and defence as articulated by Menzies Lyth in her study of nursing work in the 1950s. It outlines Kristeva's concept of abjection and draws upon Bion's formulation of the concept of containing to offer an account of how, in the current context of hospital nursing, the handover can function to contain abjection.
The issue of critical paths in Australia: where are they taking us?
Authors: Gibb Heather , Banfield Maree
Published: August 2007

This discussion paper sets out some major concerns with the introduction of critical paths into the Australian health care system. It is argued that in their current form as devised in North America, critical paths may not be appropriate to our organisation of health care and may in fact be detrimental to the development of nursing practice. The discussion centres around the socio‐political context of the development of managed care in North America, as well as research findings from the implementation of critical paths in an Australian hospital.
Eco‐wellness nursing: getting serious about innovation and change
Authors: Avery Alan
Published: August 2007

Eco‐wellness nursing represents a creative, challenging and empowering approach for facilitating a sustainable future for people and their environments, focusing beyond positivistic explanations and solutions, towards a more emancipating eco‐centric praxis. Underlying this approach are the principles of ‘wellness’, ‘holism’, and a ‘reflexive and sustainable eco‐culture’. The goal is helping people understand how to sustain their wellness, including their environments. Negotiating or brokering change from a traditional nursing model will require a revision of focus in roles, attitudes, contexts and actions of nurses. Crucial in this transformation is greater nursing independence in the private marketplace, which may involve consultancies, collaborative ventures, utilization of new technologies such as multimedia communications, and targeted nursing oriented research and development.
Nursing research refrained by the inescapable reality of practice: a personal encounter
Authors: Huntington Annette
Published: August 2007

This paper describes how an innocent venture outside the confines of academia to update my nursing skills completely changed the focus of my research. I was deeply involved in the theoretical development of my thesis, which I thought was a feminist exploration of the meaning of health for mid‐life women. I was immersed in feminist theory and was exploring the work of the French Feminists. I had written comprehensive draft chapters about nursing, women's bodies and science. While I was absorbed in my theoretical exploration I decided to venture back into practice to improve my nursing skills. I am still unsure why I chose to do this; however, in hindsight, my theoretical exploration was inexorably pushing me in that direction. While my conscious thinking was focused on my stated topic, my subconscious (my intuition) turned me towards another. Being confronted with the reality of nursing practice through working with staff nurses in a gynaecological ward caused a major disjunction in every aspect of my research: the topic, my methodology and the setting, and the experience challenged my feelings about nurses and nursing. This inevitably led to a dramatic and fundamental change in my research.
All the young men gone: losing men in the gentrification of Australian nursing circa 1860–1899
Authors: Barber Judith
Published: August 2007

Men played an important role in nursing in colonial Austalia. However the number of men undertaking nursing duties declined dramatically in the second half of the nineteenth century. Reasons for this are explored in relation to ramifications of the introduction of the Nightingale pattern of nurse training in Australia, which occurred within the Victorian ethos of gentility and decorum. In this context, nursing came to be seen as a calling that was natural and appropriate for women. The controlled, decorous ambience of nursing, its subservient relationship to medicine and the attractiveness to employers of female pay rates are all associated with the decline in male participation over this period.
Life and the laundromat: reflections on dirty linen and everyday private life
Authors: Lawler Jocalyn
Published: August 2007

Life and the laundromat: reflections on dirty linen and everyday private life

This is a paper in which I reflect on, and draw issues from, an unplanned ethnographic experience in a London laundromat. The concept of ‘everyday life’ has a kind of simple, even benign, quality. However, diere are many events in everyday life that are complex and complicating. Everyday life can be mundane – boring even. But it can also confront and trouble us, even when it concerns such apparendy ordinary matters like doing the laundry. This paper is about how the ordinary matters of everyday life can become problematic and how our involvement in them can confront us with dilemmas that are unwanted yet require our attention and judgement as participants in social life.
Changing conceptions of practical skill and skill acquisition in nursing education
Authors: Bjark Ida T.
Published: August 2007

Changing conceptions of practical skill and skill acquisition in nursing education

The learning of practical skill in nursing is not a priority of nursing education today. This is a result of a narrow and mechanistic concept of practical skill and its acquisition in nursing education. This paper reviews these conceptions as they have been developed in major textbooks for nurse teachers and in research articles on skill teaching, learning and evaluation over the past 50 years. Nursing research must move out of the laboratory and into the clinical setting in order to incorporate the typical aspects of practical skill learning in nursing. Future challenges in this kind of research are discussed.
An ethic of caring: conceptual and practical issues
Authors: Dyson Lyn
Published: August 2007

An ethic of caring: conceptual and practical issues

The purpose of this paper is to explore the concept of an ethic of care. Caring as a concept has long been associated with nursing, but in more recent times there has been a strong move to promote an ethic of care as a fundamental concept of nursing. Literature and a personal perspective are used to explore the concept of an ethic of care. It is a premise of this paper that care should be taken that an ethic of care, as currently described, does not contribute to nurses' powerlessness in ethical decision‐making in the clinical area. Issues that need to be addressed include the inadequate articulation of the concept to inform and guide practice, and also the emotively laden language utilized by some writers. It is concluded that an ethic of care shows promise to advance nursing knowledge and practice and requires increased research and dialogue to clarify the concept.
CONFERENCE REVIEW
Authors: Taylor Peter G.
Published: August 2007

Report on ‘The Virtual University?’ Symposium Melbourne, Australia
Pap smear brochures, misogyny and language: a discourse analysis and feminist critique
Authors: Lane Vivien , Lawler Jocalyn
Published: August 2007

Pap smear brochures, misogyny and language: a discourse analysis and feminist critique

Text from a public health brochure on pap smears was analysed with particular reference to ways in which the language used conveys particular messages about women and their bodies. In the text, 'humans' were found to be excluded as such. Both the pap smear service provider and the women who are the recipients of this service – and at whom such brochures are targeted – are objectified and their characteristics of human existence (i.e. ontological capacities) were restricted. The language of the pamphlet invokes an image for women associated with vaginal (penile penetrative) sex. The discourse also is found to be didactic, biomedical and written in the voice of the service provider. Further, the encounter of pap smear events is contextualized as procedural such that not only is the woman 'done to' in the process of having a cervical smear test but the woman's and provider's experiences of the encounter are silenced. It is concluded that the texts may be viewed as misogynist and that such texts do not take account of the complexity of women's decisions to 'submit to' or comply with cervical cancer screening.
Patients rewarded: a consideration of The English Patient and the representation of nursing
Authors: Welch Mark
Published: August 2007

Patients rewarded: a consideration of The English Patient and the representation of nursing

This paper explores the representation of nursing in the 1997 Academy Award winning film The English Patient (Director Minghella 1996). It examines the way in which the concerns and dilemmas that have become commonplace in nursing literature are represented through the experiences of the character Hana. In particular, it is concerned with the way in which the essence of what it means to be a nurse, and its loss and reclamation, is epitomized through Hana and her encounters with Count Almasy (the English patient) and the bomb‐disposal expert Kip. Finally, it suggests that there is much to be gained from a close examination of the representation of nursing in popular culture.
Big battles for small gains: a cautionary note for teaching reflective processes in nursing and midwifery practice
Authors: Taylor Bev
Published: August 2007

Since 1988, Australian university nursing courses have adopted die processes of educationalists in embracing reflective practitioner concepts and strategies. The assumption underlying reflective practice appears uniformly to be diat if practitioners reflect on and in their practice worlds they can develop ways of changing diem. This paper will oudine some cautionary points in teaching reflective processes for use in nursing practice, given diat diey have been processes intent on mobilizing change in densely impacted hegemonic structures in healtiicare organizations. To demonstrate diat die limits of reflective practice may constitute big batdes for small gains, a research project undertaken with practising midwives will be used as a case in point.
The nurse educator as teacher: exploring the construction of the ‘reluctant instructor’
Authors: Bruni Nina
Published: August 2007

This paper explores the discursive construction of the category of teacher identified as the ‘reluctant instructor’. Data are drawn from my doctoral study, an ethnography of a school of nursing located in the higher education sector in which I was employed. This study explored the question: What shapes nurse educators and what do they, in turn, shape? Participants included nurse educators who taught a pre‐registration programme. Data were gathered through interview and observation of classroom teaching. Analysis focused on the discursive constitution of participants' sense of being a nurse educator and on the implications of their ways of ‘knowing and doing’ for students. The analysis suggests that the dominant subject positions adopted by participants were those of ‘academic’ and ‘victim’. They employed an ideal/real dichotomy to give a sense of coherence to the inconsistencies or contradications that they saw as structuring their daily activities. Being an academic entailed being an educator, specifically a facilitator, as being competent and having some degree of autonomy. However, participants saw the reality of their situation as markedly different from their ideal; as exhibiting traits of the ‘outmoded’, oppressive, hospital system of nurse training. Within this context most participants positioned themselves as a ‘reluctant instructor’. The implications of their practices for the creation of the ‘passive student’ are suggested in the paper. In this analysis the nurse educator is viewed as implicated in the formation and maintenance of the context in which she or he is located. Such a view challenges the neutrality that is implicated in understandings of the nurse educator that inform nursing texts and that helped constitute participants' sense of self.
Primary small cell carcinoma of the ureter
Authors: Martin Sergio Martin , Gonzalez Jose Ramon Cortinas , Lagarto Elena Garcia , Arteaga Carlos Muller , Garcia‐Ripoll Juan Ramon Torrecilla , del Busto Ernesto Fernandez
Published: August 2007

Abstract:  We report a case of primary small cell carcinoma of the ureter. These tumors are very rare, locally aggressive and with poor prognosis. A 77‐year‐old man presented with left flank pain and microhematuria. Following diagnosis of ureteral carcinoma, nephroureterectomy was carried out, and adjuvant chemotherapy and radiotherapy were given. The patient had no evidence of recurrence or metastasis, 13 months postoperatively. We provide a bibliographic review and comment on its clinical and pathologic characteristics, diagnostic methods and latest modifications in therapy.
Chronic administration of valproic acid inhibits PC3 cell growth by suppressing tumor angiogenesis in vivo
Authors: Gao Dexuan , Xia Qinghua , Lv Jiaju , Zhang Hui
Published: August 2007

Aim:  Chromatin remodeling agents such as histone deacetylase inhibitors have been shown to modulate gene expression in tumor cells and inhibit tumor growth and angiogenesis. We investigated the mechanisms of chronic valproic acid (VPA) inhibiting PC3 cell growth in the study.

Methods:  We established tumor xenografts of the PC3 cell line and investigated the effect of VPA chronic administration on tumor growth. Apoptosis in tumor tissue was measured using the TUNEL Detection Kit. We detected the effect of VPA chronic administration on histone acetylation; p21CIP1/WAF1 gene expression; vascular endothelial growth factor (VEGF) expression by reverse‐transcription Polymerase Chain Reaction (PCR) analysis; immunohistochemistry; and Western Blotting.

Result:  In mouse models with established subcutaneous prostate (PC3), VPA treatment induced 70% inhibition of tumor growth without overt toxicity. Our result showed that chronic administration of VPA has an effect on tumor growth arrest and the effect was associated with increased histone acetylation, p21CIP1/WAF1 up‐regulation, and VEGF down‐regulation.

Conclusion:  We conclude that chronic VPA results in profound decreases in the proliferation of PC3 cells, not only by increasing histone H3 acetylation and up‐regulating p21CIP1/WAF1 expression, but also by down‐regulating VEGF.
Impact of improvement in specificity of primary screening test on total cost of prostate cancer mass screening
Authors: Kobayashi Takashi , Goto Rei , Fukui Tsuguya , Ogawa Osamu
Published: August 2007

Objectives:  Improvement in the specificity of primary screening tests, without significant cost elevation of the assay, provides cost savings in prostate cancer screening programs by reducing unnecessary secondary screening procedures. The purpose of this study was to evaluate the economic impact of improvement in the specificity of primary screening tests and to estimate the socially acceptable cost elevation for improved specificity.

Methods:  A decision‐analytic model was designed to evaluate the total costs of prostate cancer mass screening according to the changes in the specificity and the cost of the primary screening test. All assumed factors were tested by three‐way sensitivity analyses incorporating cost and specificity.

Results:  The base case analysis showed that a 1% improvement in the specificity of the primary screening test provides a $1.19 cost reduction per participant. Sensitivity analyses showed that an acceptable cost elevation for a 1% improvement in the specificity ranged from 0.68 to 2.90 $/% with respect to changes in several factors in the screening program.

Conclusions:  The specificity and cost of the primary screening test has a significant economical impact on prostate cancer mass screening. For each screening program, it should be taken into consideration whether the cost of the new test deserves the specificity.
Nortriptyline delays disease onset in models of chronic neurodegeneration
Authors: Wang Hongyan , Guan Yingjun , Wang Xin , Smith Karen , Cormier Kerry , Zhu Shan , Stavrovskaya Irina G. , Huo Chunfeng , Ferrante Robert J. , Kristal Bruce S. , Friedlander Robert M.
Published: August 2007

This study was to characterize the neuroprotective effects of nortriptyline, a tricyclic antidepressant, in mouse models of chronic neurodegeneration [amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD)]. Nortriptyline was originally selected from a library screening of 1040 FDA‐approved drugs by using isolated mitochondria. It emerged as a strong inhibitor of mitochondrial permeability transition (mPT). Our results showed that nortriptyline significantly delayed disease onset and extended the lifespan of ALS mice although its effect on mortality was less than that on onset. We also tested promethazine, another compound which emerged from the same screening, in ALS mice. Promethazine‐treated ALS mice exhibited a significant delay in disease onset but not in mortality. Histochemistry analysis found that nortriptyline treatment indeed protected motor neurons from death and reduced ventral horn atrophy in ALS mice. Furthermore, release of cytochrome c and activation of caspase 3, two molecular phenomena associated with mitochondrial‐pathway‐mediated cell death, were inhibited by nortriptyline. We also demonstrated similar beneficial effects of nortriptyline in HD mice: it extended the presymptomatic portion of the disease but had no effect on mortality. In an established cellular model of HD, nortriptyline inhibited cell death and decreased loss of mitochondrial membrane potential. In summary, this study indicated the potential therapeutic usefulness of nortriptyline in ALS and HD. In addition, our data suggested a role for mPT in chronic neurodegeneration, particularly at the early rather than the advanced disease stages.
Survival, migration and neuronal differentiation of human fetal striatal and cortical neural stem cells grafted in stroke‐damaged rat striatum
Authors: Darsalia Vladimer , Kallur Therése , Kokaia Zaal
Published: August 2007

Stroke is a neurodegenerative disorder and the leading cause of disability in adult humans. Treatments to support efficient recovery in stroke patients are lacking. Several studies have demonstrated the ability of grafted neural stem cells (NSCs) to partly improve impaired neurological functions in stroke‐subjected animals. Recently, we reported that NSCs from human fetal striatum and cortex exhibit region‐specific differentiation in vitro, but survive, migrate and form neurons to a similar extent after intrastriatal transplantation in newborn rats. Here, we have transplanted the same cells into the stroke‐damaged striatum of adult rats. The two types of NSCs exhibited a similar robust survival (30%) at 1 month after transplantation, and migrated throughout the damaged striatum. Striatal NSCs migrated farther and occupied a larger volume of striatum. In the transplantation core, cells were undifferentiated and expressed nestin and, to a lesser extent, also GFAP, βIII‐tubulin, DCX and calretinin, markers of immature neural lineage. Immunocytochemistry using markers of proliferation (p‐H3 and Ki67) revealed a very low content of proliferating cells (< 1%) in the grafts. Human cells outside the transplantation core differentiated, exhibited mature neuronal morphology and expressed mature neuronal markers such as HuD, calbindin and parvalbumin. Interestingly, striatal NSCs generated a greater number of parvalbumin+ and calbindin+ neurons. Virtually none of the grafted cells differentiated into astrocytes or oligodendrocytes. Based on these data, human fetal striatum‐ and cortex‐derived NSCs could be considered potentially safe and viable for transplantation, with strong neurogenic potential, for further exploration in animal models of stroke.
Calpain cleavage of collapsin response mediator proteins in ischemic mouse brain
Authors: Jiang Susan X. , Kappler Joachim , Zurakowski Bogdan , Desbois Angele , Aylsworth Amy , Hou Sheng T.
Published: August 2007

Collapsin response mediator proteins (CRMPs) are important brain‐specific proteins with distinct functions in modulating growth cone collapse and axonal guidance during brain development. Our previous studies have shown that calpain cleaves CRMP3 in the adult mouse brain during cerebral ischemia [S.T. Hou et al. (2006) J. Neurosci., 26, 2241–2249]. Here, the expression of all CRMP family members (1–5) was examined in mouse brains that were subjected to middle cerebral artery occlusion. Among the five CRMPs, the expressions of CRMP1, CRMP3 and CRMP5 were the most abundant in the cerebral cortex and all CRMPs were targeted for cleavage by ischemia‐activated calpain. Sub‐cellular fractionation analysis showed that cleavage of CRMPs by calpain occurred not only in the cytoplasm but also in the synaptosomes isolated from ischemic brains. Moreover, synaptosomal CRMPs appeared to be at least one‐fold more sensitive to cleavage compared with those isolated from the cytosolic fraction in an in‐vitro experiment, suggesting that synaptosomal CRMPs are critical targets during cerebral ischemia‐induced neuronal injury. Finally, the expression of all CRMPs was colocalized with TUNEL‐positive neurons in the ischemic mouse brain, which further supports the notion that CRMPs may play an important role in neuronal death following cerebral ischemia. Collectively, these studies demonstrated that CRMPs are targets of calpains during cerebral ischemia and they also highlighted an important potential role that CRMPs may play in modulating ischemic neuronal death.
Whole‐genome analysis of the ammonia‐oxidizing bacterium, Nitrosomonas eutropha C91: implications for niche adaptation
Authors: Stein Lisa Y. , Arp Daniel J. , Berube Paul M. , Chain Patrick S. G. , Hauser Loren , Jetten Mike S. M. , Klotz Martin G. , Larimer Frank W. , Norton Jeanette M. , Op den Camp Huub J. M. , Shin Maria , Wei Xueming
Published: August 2007

Analysis of the structure and inventory of the genome of Nitrosomonas eutropha C91 revealed distinctive features that may explain the adaptation of N. eutropha‐like bacteria to N‐saturated ecosystems. Multiple gene‐shuffling events are apparent, including mobilized and replicated transposition, as well as plasmid or phage integration events into the 2.66 Mbp chromosome and two plasmids (65 and 56 kbp) of N. eutropha C91. A 117 kbp genomic island encodes multiple genes for heavy metal resistance, including clusters for copper and mercury transport, which are absent from the genomes of other ammonia‐oxidizing bacteria (AOB). Whereas the sequences of the two ammonia monooxygenase and three hydroxylamine oxidoreductase gene clusters in N. eutropha C91 are highly similar to those of Nitrosomonas europaea ATCC 19718, a break of synteny in the regions flanking these clusters in each genome is evident. Nitrosomonas eutropha C91 encodes four gene clusters for distinct classes of haem‐copper oxidases, two of which are not found in other aerobic AOB. This diversity of terminal oxidases may explain the adaptation of N. eutropha to environments with variable O2 concentrations and/or high concentrations of nitrogen oxides. As with N. europaea, the N. eutropha genome lacks genes for urease metabolism, likely disadvantaging nitrosomonads in low‐nitrogen or acidic ecosystems. Taken together, this analysis revealed significant genomic variation between N. eutropha C91 and other AOB, even the closely related N. europaea, and several distinctive properties of the N. eutropha genome that are supportive of niche specialization.
Establishing pragmatic estimated GFR thresholds to guide metformin prescribing
Authors: Shaw J. S. , Wilmot R. L. , Kilpatrick E. S.
Published: August 2007

Aims  Renal impairment is a contraindication to metformin treatment because of the perceived increased risk of lactic acidosis. Current guidelines define renal impairment according to the serum creatinine of the individual, but this measure is being supplanted by the use of estimated glomerular filtration rate (eGFR) as it gives a closer estimate to true GFR. This study aimed to establish pragmatic eGFR limits for use in patients being considered for metformin treatment.

Methods  Estimated GFR measurements corresponding to currently used metformin creatinine limits of 130 and 150 µmol/l were derived and then applied to 12 482 patients with diabetes in Hull and East Yorkshire.

Results  Few patients with a serum creatinine of 130 or 150 µmol/l have an eGFR of < 30 ml/min/1.73 m2[chronic kidney disease (CKD) stage 4 or greater], while most are between 30 and 59 ml/min/1.73 m2 (CKD stage 3). When applied to the 12 482 patients (median age 67 years, interquartile range 56–75), males predominated when using creatinine cut‐offs (13.6% of males and 8.3% of females had creatinine > 130 µmol/l; 8.2% males and 5.2% females > 150 µmol/l), but not using eGFR CKD thresholds (3.3% males and 4.7% females < 30 ml/min/1.73 m2; 20.8% males and 28.1% females eGFR 30–59 ml/min/1.73 m2). Similar proportions of patients as currently would have metformin withheld if using eGFR cut‐offs between 30 and 49 ml/min/1.73 m2.

Conclusions  We have proposed pragmatic eGFR limits to guide metformin prescribing in patients with renal impairment. CKD stage 4 or greater should be an absolute contraindication to metformin, while CKD stage 3 should alert clinicians to consider other risk factors before initiating or continuing treatment.
Post‐challenge glucose predicts coronary atherosclerotic progression in non‐diabetic, post‐menopausal women1
Authors: Mellen P. B. , Bittner V. , Herrington D. M.
Published: August 2007

Aims  We sought to determine whether fasting or post‐challenge glucose were associated with progression of coronary atherosclerosis in non‐diabetic women.

Methods  We performed a post‐hoc analysis of 132 non‐diabetic women who underwent 75‐g oral glucose tolerance testing. The primary outcome of interest was progression of atherosclerosis determined by baseline and follow‐up coronary angiography, a mean of 3.1 ± 0.9 years apart. We analysed the association of change in minimal vessel diameter (ΔMD) by quartile of fasting and post‐challenge glucose using mixed models that included adjustment for age, systolic blood pressure, total : high‐density lipoprotein cholesterol ratio, current smoking, lipid‐lowering and anti‐hypertensive medication use and other covariates.

Results  At baseline, participants had a mean age of 65.7 ± 6.7 years and a mean body mass index of 27.9 ± 8.5 kg/m2. Although there were no significant differences in atherosclerotic progression by fasting glucose category (P for trend across quartiles = 0.99), there was a significant inverse association between post‐challenge glucose and ΔMD (in mm) (Q1 : 0.01 ± 0.03; Q2 : 0.08 ± 0.03; Q3 : 0.13 ± 0.03; Q4 : 0.11 ± 0.03; P for trend = 0.02).

Conclusions  In post‐menopausal women without diabetes, post‐challenge glucose predicts angiographic disease progression. These findings suggest that even modest post‐challenge hyperglycaemia influences the pathogenesis of atherosclerotic progression.
School physical activity interventions: do not forget about obesity bias
Authors: Rukavina P. B. , Li W.
Published: August 2007

Obesity bias is the tendency to negatively judge an overweight or obese individual based on assumed and/or false character traits, such as being physically unattractive, incompetent, lazy and lacking self‐discipline. Obesity biases, such as teasing or weight criticism during physical activity (PA), can be psychologically or emotionally damaging for overweight children and adolescents. Ultimately, the effects students experience over time may create a psychological barrier and students can become resistant to schools' health and PA interventions that promote lifestyle changes. Fortunately, the psychological effects of obesity bias are mediated by social buffers and coping mechanisms. Several PA‐related researchers have proposed strategic intervention components, but no studies have been completed in PA settings. The purpose of this review was to discuss the nature and different types of obesity bias in PA settings. Major theoretical frameworks of the aetiology and change mechanisms of obesity biases from the psychological literature were reviewed and direct applications for strategic component interventions were made for PA settings. Because of the pervasiveness and entrenchment of obesity bias, it is obvious that multiple theoretical frameworks need to be considered and even combined to create safe and caring school PA environments for students.
The Traditionality of Statutes*
Authors: KRYGIER MARTIN
Published: August 2007

Abstract. The author begins by sketching the characteristics or elements of every tradition. Some reasons are then suggested for the propensity of so many authors to contrast statutes with other, allegedly more traditional kinds of law. However, it is argued that statutes are deeply embedded, along with customary and judge‐made law, in the highly traditional practices of law and that this matters much more than is commonly suspected. The thesis being defended here is not merely that law includes traditions along with rules, principles, maxims, and so on, but rather that legal systems should be understood as traditions, albeit highly complex ones. Not only are ancient legal systems (the Talmudic, for example) held to be traditional; modem legal positive orders are viewed as being traditional too. Finally, the concept of “communities of interpretation” is applied to the contemporary posited statutes which are believed by many to be a distinguishing feature of modem legal systems.
Models of Reason, Types of Principles and Reasoning. Historical Comments and Theoretical Outlines
Authors: PATTARO ENRICO
Published: August 2007

Abstract. The author distinguishes between scientific and prudential reason (practical wisdom) in Aristotle with reference to the nature of the principles assumed as premises, and to the method of inference. In the history of thought these two models of reason are elieved not only to be proper to science and, respectively, ethics, but also, at times, to be the scientific model proper to ethics (for example, in natural law doctrines) and the prudential model proper to science. Mixed models are also given in the history of thought: scientific‐prudential (for example, in Thomas Aquinas) and prudential‐scientific. Furthermore, some aspects of the relationship between authority and reason are examined.
Legal Reasoning as a Special Case of Moral Reasoning
Authors: PECZENIK ALEKSANDER
Published: August 2007

Abstract. Moral statements are related to some ought‐ and good‐making facts. If at least one of these facts exists then it is reasonable that an action in question is prima facie good and obligatory. If all of these facts take place, then it is reasonable that the action is definitively good and obligatory. Yet, moral reasoning is relatively uncertain. The law is more “fixed”. Legal interpretatory statements ought to express a compromise between the literal sense of the law and moral considerations. They can be to a high degree both coherent and accepted. One may emotionally reject them but most people have a disposition to endorse a coherent and commonly accepted value system.
The Ideal Socio‐Legal Order. Its “Rule of Law” Dimension
Authors: SUMMERS ROBERT S.
Published: August 2007

Abstract. The author aims at defining the borderlines of the concept “rule of law.” This has been often inflated to encompass several dimensions of an ideal legal order. The author on the contrary believes that the “rule of law” ought to be a “thin” ideal. As a matter of fact, when the “rule of law” signifies almost any dimension of an ideal legal order, it comes to stand for nothing essential in particular. Deflation is then advocated for the rehabilitation of the normative content of the “rule of law.” This means that the “rule of law” should be defined as a concept covering only some well delimited dimensions of an ideal legal order.
Spontaneous Order and the Rule of Law: Some Problems
Authors: MACCORMICK D. NEIL
Published: August 2007

Abstract. Two conservative theorists, F. A. Hayek and Michael Oakeshott, have advanced theories of law with important and plausible central theses focusing on the rule of law. The author argues, however, that in each case the theorist ‐ or at least some of his followers on the contemporary British and American political scene ‐ have wrongly inferred strong conclusions from these theories which are inimical to the welfare state. In conclusion, the author points to possible ways of reconciling rule of law to social justice.