bluuebunny/crossref_metadata_2025 huggingface dataset:
Working conditions and health status of child workers: Cross‐sectional study of the students at an apprenticeship school in Kocaeli
Authors: Caglayan Cigdem , Hamzaoglu Onur , Yavuz Cavit I. , Yüksel Selim
Published: April 2009

Background:  Child labor remains a widespread phenomenon in today's world. The purpose of the present study was to describe the working conditions and health status of child workers in Kocaeli.

Methods:  A cross‐sectional research study has been carried out on 365 working children at the Kocaeli Occupational Training Center. Data were collected on working conditions, smoking habits, work accidents, perceived health status and psychological status using General Health Questionnaire‐12. In order to evaluate the physical growth of children, their height and weight were measured.

Results:  Most working children usually have a low level of education, low income and extended families. The mean age for children to start working was 14.8 ± 1.5 years and their daily working periods were 11.3 ± 1.3 h on average.

Girls were found to have more psychopathology compared to boys on the GHQ‐12 and the results were statistically significant. The height z score was less than −2 SD at 6.9% while the weight z score was less than −2 SD at 1.9%. According to body mass index (BMI) percentiles range, 3% of children were found to be underweight. A statistically significant and negative directional correlation was detected between body mass index z scores with age and daily working periods. Statistically significant but weak correlations were detected between height for age z scores and the starting age of work and also between weight for age z scores and chronological age.

Conclusions:  Both the mental and the physical health of children were found to be negatively affected, by having to work at an early age, and by long working hours. For this reason, immediate and direct intervention should be taken to eradicate child labor, and protect children from unsafe and exploitative working conditions.
Alternative approach in the treatment of adrenal metastasis with a real‐time tracking radiotherapy in patients with hormone refractory prostate cancer
Authors: Sazawa Ataru , Shinohara Nobuo , Harabayashi Toru , Abe Takashige , Shirato Hiroki , Nonomura Katsuya
Published: April 2009

Abstract:  Patients with an adrenal tumor usually undergo laparoscopic adrenalectomy. However, an alternative treatment approach might be needed in some patients with adrenal metastasis from malignancy or with severe complications. Real‐time tracking radiotherapy (RTRT) with a gold marker is considered one of the feasible treatment options because this system can reduce the adverse effects of organ movement such as that in the adrenal gland or kidney. A 64‐year‐old patient with hormone refractory prostate cancer presented with clinically isolated adrenal metastasis. The patient underwent RTRT treatment with an implanted gold marker in the right adrenal metastasis. There were no adverse events. Although disease progression with elevated prostate‐specific antigen occurred 8 months later, there was no further growth of the right adrenal metastasis before he died. From our experience, RTRT with an implanted gold marker might be feasible for the treatment of isolated adrenal metastasis from malignancies including prostate cancer.
Evidence‐based clinical practice guidelines for renal cell carcinoma (Summary – JUA 2007 Edition)
Authors: Fujioka Tomoaki , Obara Wataru ,   The Committee for establishment of the clinical practice guidelines for the management of renal cell carcinoma and the Japanese Urological Association
Published: April 2009

Abstract:  The text of these guidelines was published for general clinicians, general urologists, and patients, with the aim of providing a system of effective and efficient clinical practices for managing renal cell carcinoma based on evidence‐based medicine–intended techniques. The guidelines contain the answers to a total of 21 clinical questions (CQ) that were formulated under the headings of ‘risk factors and prophylaxis,’‘diagnosis,’‘surgical treatment and local treatment,’ and ‘systemic treatment,’ along with the recommendation grades and systems/algorithms for clinical practice based on structured abstracts prepared through critical reviews of the relevant published reports; the literature search was conducted using the key words for each CQ. An abridged edition of these guidelines can be found on the web pages of the Japan Society of Clinical Oncology and the Medical Information Network Distribution Service.
Evaluation of the impact of breast cancer screening in South Australia
Authors: Tallis G. M. , O’Neill T. J.
Published: April 2009

Background:  In 1989 BreastScreen SA started screening for breast cancer in South Australia.

Methods:  The programme concentrated on women between the ages of 50 and 69, using a 24‐month screening interval and a joint method of mammography, clinical examination and self‐detection.

Results:  This paper is a summary of our efforts to provide an assessment of the impact of the screening programme in terms of additional survival time past the age of first detection of the disease.

Discussion:  The concept of benchmarks is introduced, and the survival advantages for screened women is measured from these benchmarks.

Conclusion:  The women in the BreastScreen SA service, who had primary breast tumours, had an estimated additional survival advantage of 2.6 years. Some statistical modelling allowed us to extrapolate to other screening designs.
Patient awareness and concern regarding pharmaceutical manufacturer interactions with doctors
Authors: Edwards D. , Ballantyne A.
Published: April 2009

Background:  The objective of the study was to determine the general public’s level of awareness of and degree of concern about the interactions between pharmaceutical manufacturers and doctors in Melbourne. This Internet was survey administered using Survey Monkey.

Methods:  The participants in the study were employees of The Age Newspaper in Melbourne (n = 1524). Participants’ self‐reported levels of awareness and concern regarding pharmaceutical representatives’ interactions with doctors and the resulting effect on the quality of care they receive were observed.

Results:  One hundred and thirty‐four participants completed the questionnaire between 18 January and 8 February 2007. This was a response rate of 8.8%, and 40% reported a ‘high level’ of awareness of pharmaceutical marketing, whereas 59% reported believing that marketing influenced the prescribing behaviour of their doctors. Participants who reported that information provided by the pharmaceutical industry is inaccurate were significantly more likely to prefer a doctor who did not engage with pharmaceutical marketing (H(2) = 0.19, P < 0.05). There was a significant difference in perceived trustworthiness between academic sources of information and marketing based sources of information (T = 0.000, P < 0.05). The level of perceived trustworthiness of pharmaceutical marketing was significantly related to whether people wanted to be kept informed about pharmaceutical marketing activities (H(2) = 0.004, P < 0.05). Forty‐eight per cent of respondents wanted to be informed about pharmaceutical marketing; 46.2% of these people would like this to be through disclosure in the form of an accredited identification system. If given a choice, 38.8% of respondents would choose a doctor who did not see pharmaceutical representatives over one that did.

Conclusion:  A significant proportion of the sample surveyed was aware of pharmaceutical marketing, believed that it influenced prescribing practices and it was less trustworthy than academic sources of information, would like to be kept informed about industry interactions with their doctor and would prefer to see a doctor who did not receive visits from pharmaceutical marketing representatives.
Rare cause of dyspnoea
Authors: Ghiculescu R. A. , Pillans P.
Published: April 2009

Although primary amyloidosis is the most common systemic form of amyloidosis, its diagnosis remains notoriously difficult. Unless included in the differential diagnosis, the condition may be missed as a cause of severe and ultimately fatal clinical syndromes. We describe two patients with primary amyloidosis who presented with dyspnoea/orthopnoea and oedema due to cardiac and renal involvement. Both had a fatal outcome.
Family history? The forgotten question in high‐risk colorectal cancer patients
Authors: Foo W. , Young J. M. , Solomon M. J. , Wright C. M.
Published: April 2009

Aim  The aim of the study was to investigate the frequency and detail of family history recorded for patients diagnosed with potentially high‐risk colorectal cancer, and to determine the proportion of these patients referred to a high‐risk assessment clinic.

Method  Medical records of patients diagnosed with colorectal cancer under the age of 50 admitted to a major Sydney teaching hospital were reviewed. The proportion of records containing information about family history was calculated. Associations between recording of family history and demographic and clinical characteristics of patients were investigated. Logistic regression modelling was performed to identify significant, independent predictors of study outcomes.

Results  Of 113 patients with colorectal cancer diagnosed under the age of 50 years, 61 (54%, 95% CI: 44–63%) had an entry in their hospital medical record about family history. Family history was significantly less likely to be recorded for females, for those admitted via the Emergency Department, and for those with shorter lengths of stay. A significant family history was found in 51% of the 61 patients who had a family history recorded. Records of patients attending specialist colorectal surgeons were significantly more likely to contain information about family history than those who attended other specialists (P = 0.04). Only 14 patients (12%, 95% CI: 7–20%) were formally referred for further genetic assessment.

Conclusion  These results suggest that family history is still being neglected in routine clinical practice, and high‐risk assessment services are underutilized, implying the need for further dissemination of guidelines with regard to the recognition and management of hereditary colorectal cancer.
Derivative benefits: exploring the body through complementary and alternative medicine
Authors: Baarts Charlotte , Pedersen Inge Kryger
Published: April 2009

Since the 1960s, in Western societies, there has been a striking growth of consumer interest in complementary or alternative medicine (CAM). In order to make this increased popularity intelligible this paper challenges stereotypical images of users’ motives and the results of clinical studies of CAM by exploring bodily experiences of acupuncture, reflexology treatments, and mindfulness training. The study draws on 138 in‐depth interviews with 46 clients, client diaries and observations of 92 clinical treatments in order to identify bodily experiences of health and care: experiences that are contested between forces of mastery, control and resistance. We discuss why clients continue to use CAM even when the treatments do not help or even after they have been relieved of their physiological or mental problems. The encounter between the client and CAM produces derivative benefits such as a fresh and sustained sense of bodily responsibility that induces new health practices.
Market reforms in English primary medical care: medicine, habitus and the public sphere
Authors: McDonald Ruth
Published: April 2009

Drawing on interviews with English primary care doctors (GPs), this paper examines GP responses to reforms intended to introduce a market in primary health care. GPs’ reactions are conceptualised in terms of a GP habitus, which takes for granted the superiority of ‘public’ providers (i.e. GP partnerships) in the provision of care. GPs are actively involved in the defence of the public sphere, which is neither a neo‐liberal minimalist market state, nor a wholly altruistic state, responding to consumers’ wants. The public sphere they defend is one in which boundaries are drawn about entitlements and GPs are actively engaged in defining and policing these boundaries. The GP habitus can be seen as shaping responses in ways which serve GP interests. In the context of struggles involving various social actors (e.g. private providers, third‐party payers, patients) with different stakes in the field of general medical practice; this public service orientation may enable GPs to reap cultural capital. At the same time, the habitus constrains action in a way which limits resistance to reforms threatening GPs’ interests, with GPs responding by coping, rather than downing tools or engaging in active confrontation.
Being good in Ramadan: ambivalence, fragmentation, and the moral self in the lives of young Egyptians
Authors: Schielke Samuli
Published: April 2009

So much has been written in recent years on Muslims who consciously and consistently aim to be pious, moral, and disciplined that the vast majority of Muslims who – like most of humankind – are sometimes but not always pious, at times immoral, and often undisciplined have remained in the shadow of an image of Islam as a perfectionist project of self‐discipline. Taking the month of Ramadan, as a time of exceptional piety, as a starting‐point, this paper tries to account for the different views and experiences that young people of Muslim faith in a northern Egyptian village articulate, the models of action and subjectivity they have access to, and the contradictory outcomes that the Islamic revivalist ideal of perfection has for some of them.

Il a tellement été question, ces dernières années, de musulmans consciemment et constamment soucieux d’être pieux, moraux et disciplinés que la grande majorité des musulmans, qui sont parfois pieux mais pas toujours, parfois immoraux et souvent indisciplinés, comme le reste de l’humanité, est restée dans l’ombre de cette image de l’islam comme projet d’autodiscipline perfectionniste. En prenant pour point de départ le Ramadan, période de piété particulière, l’auteur tente de rendre compte de différents points de vue exprimés par les jeunes musulmans d’un village du Nord de l’Égypte, des modèle d’action et de subjectivité qui leur sont ouverts et des résultats contradictoires que donne pour certains d’entre eux l’idéal de perfection portée par l’idée d’un renouveau islamique.
Doubt, faith, and knowledge: the reconfiguration of the intellectual field in post‐Nasserist Cairo
Authors: Aishima Hatsuki , Salvatore Armando
Published: April 2009

The study of the Islamic Resurgence has underestimated the intellectual trials that some key personalities underwent at a crucial stage of the crisis of post‐colonial societies. The intellectual leaders of the Resurgence faced the task to redefine the social value of faith and of its converse, doubt, as the insidious flip‐side of processes of modernization. Their response to the challenge contributed to a reconfiguration of the intellectual field: in order to reach larger audiences they reinterpreted their cultural credentials and even life narratives in terms of the communicative standards suitable to new media. This paper analyses how the motives of doubt and faith in the trajectories of two personalities aspiring to the status of ‘Islamic intellectual’ (the Sufi scholar and Shaykh al‐Azhar ‘Abd al‐Halim Mahmud and the media‐savvy lay thinker Mustafa Mahmud) contributed to a reconfiguration of the intellectual field. We investigate how their legacy is presently discussed among educated audiences. Finally, we show how the ambivalence of the reception of their public teaching reflects the troubled search for a new ideological balance by the Egyptian middle classes.

L’étude de la Résurgence islamique a sous‐estimé les épreuves intellectuelles par laquelle sont passés certains de ses grands noms à un stade crucial de la crise des sociétés postcoloniales. Les meneurs intellectuels de la Résurgence se sont trouvés confrontés à la tâche de redéfinir la valeur sociale de la foi et de son opposé, le doute, comme le revers insidieux des processus de modernisation. En relevant ce défi, ils ont contribuéà reconfigurer le champ intellectuel : pour atteindre un public plus large, ils ont réinterprété leurs références culturelles et même leurs récits de vies selon les standards de communication adaptés aux nouveaux médias. Les auteurs analysent ici la façon dont les motifs du doute et de la foi dans la trajectoire de deux personnalités aspirant au statut « d’intellectuel islamique », l’érudit soufi Shaykh al‐Azhar ‘Abd al‐Halim Mahmud et le penseur laïque Mustafa Mahmud, fin connaisseur des média, ont contribuéà la reconfiguration du champ intellectuel. Les auteurs étudient le débat dont leur héritage fait aujourd'hui l’objet dans les cercles éduqués. Pour finir, ils montrent comment l’ambivalence de l’accueil fait à leur enseignement public reflète la difficile recherche d’un équilibre idéologique dans les classes moyennes égyptiennes.
Muslim politics in postcolonial Kenya: negotiating knowledge on the double‐periphery
Authors: Kresse Kai
Published: April 2009

This paper investigates Muslim politics in its wider social context in postcolonial Kenya, with a historical focus mainly on the Moi era (1978‐2002). Hereby, I look at the introduction, integration, and internal constestation of Islamic reformist ideologies in Swahili discourse and in social practice. Central to my argument about the interconnections between Muslim politics, national politics, and coastal sociality is the notion of a ‘knowledge economy’, within the postcolonial setting of a ‘double‐periphery’ in which Kenyan coastal Muslims are situated, vis‐à‐vis the state and the Muslim umma (community of believers). I discuss the dynamics between aspects of knowledge and rhetorics, reasoning and power, and ideology and social practice at work in this particular Muslim context. All of this is situated within national Kenyan politics, and discussed against the background of a postcolonial state governed by upcountry Christians with whom coastal Muslims have historically had a tense and antagonistic relationship.

L’auteur étudie l’islam politique dans le contexte social général du Kenya postcolonial, principalement durant l’ère Moi (1978‐2002). Il s’intéresse ainsi à l’introduction, à l’intégration et à la contestation interne des idéologies réformistes islamiques dans le discours et la pratique sociale des Swahilis. Son argumentation est que le lien entre islam politique, politique nationale et socialité dans les régions côtières est constitué par la notion « d’économie du savoir », dans le cadre postcolonial d’une « double périphérie » dans laquelle se situent les musulmans des côtes du Kenya : périphérie vis‐à‐vis de l’État, mais aussi de l’umma, la communauté des croyants musulmans. L’auteur commente la dynamique entre aspects du savoir et rhétorique, raisonnement et pouvoir, idéologie et pratique sociale à l’œuvre dans ce contexte musulman particulier. L’ensemble s’inscrit dans la politique nationale du Kenya et est discuté avec pour toile de fond un État postcolonial, gouverné par les chrétiens de l’arrière‐pays avec lesquels les musulmans de la côte ont toujours eu des relations chargées de tensions et d’antagonismes.
Talkingjihadand piety: reformist exertions among Islamist women in Bangladesh
Authors: Huq Maimuna
Published: April 2009

This paper analyses the discursive regime of Islamic study circles within an organization of female students (BICSa) informally affiliated with the leading Islamic political party in South Asia, the Jamaat‐e‐Islami. I investigate this textual modality of Islamic socialization as a site where members partly discipline their sensibilities in accordance with BICSa's project of Islamization, which is grounded in thejihad(exertion)‐orientated model for Islamic reform in South Asia of the Islamist Abul Ala Maududi. I also explore group discussion dynamics arising from activists' daily experiences that not only critique conventional distinctions between the political, social, and religious, in accord with the Islamist worldview, but also facilitate argumentation interrogative of Islamist ideological‐textual boundaries. The simultaneously centripetal and centrifugal ethos of the study circle as a contemporary Bangladeshi Islamist pedagogical technique is analysed in relation to shifting discussions ofjihadamong Islamist women.

L’auteur analyse le régime discursif des cercles d’études islamiques au sein d’une organisation d’étudiantes (la BICSa) affiliée de loin au principal parti politique islamique d’Asie du sud, le Jamaat‐e‐Islami. Elle explore la modalité textuelle de la socialisation islamique comme lieu où l’on discipline partiellement sa sensibilité, selon le projet d’islamisation de la BICSa, calqué sur le modèle de réforme islamique de l’Asie du sud formulé par l’islamiste Abu Sala Maududi et fondé sur lejihad, au sens d’effort. L’auteur explore également la dynamique des discussions de groupe qui naît de l’expérience quotidienne des activistes. Celle‐ci permet une critique des distinctions classiques entre politique, social et religieux, conformément à la vision du monde islamiste, mais facilite aussi une argumentation qui questionne les limites idéologiques et textuelles de l’islamisme. L’éthos à la fois centripète et centrifuge de ce cercle d’études, qui représente une technique de la pédagogie islamiste contemporaine au Bangladesh, est analysé en relation avec les discussions mouvantes dujihadparmi les femmes islamistes.
SOSA ON SKEPTICISM
Authors: BUENO OTÁVIO
Published: April 2009

Abstract: Ernest Sosa has recently articulated an insightful response to skepticism and, in particular, to the dream argument. The response relies on two independent moves. First, Sosa offers the imagination model of dreaming according to which no assertions are ever made in dreams and no beliefs are involved there. As a result, it is possible to distinguish dreaming from being awake, and the dream argument is blocked. Second, Sosa develops a virtue epistemology according to which in appropriately normal conditions our perceptual beliefs will be apt. Hence, in these conditions, we will have at least animal knowledge, and the conclusion of the dream argument is undermined. In this article, I examine various moves that the skeptic can make to resist Sosa's challenge, and I contrast the proposal to a neo‐Pyrrhonian stance. In the end, there is surprisingly little disagreement about the status of ordinary perceptual beliefs in the two stances.
RESPONSES TO NUCCETELLI, LEMOS, AND BUENO
Authors: SOSA ERNEST
Published: April 2009

Abstract: Susana Nuccetelli discusses critically my account of Moore's Proof of the External World. Noah Lemos takes up my views on skepticism and my distinction between animal knowledge and reflective knowledge. Otávio Bueno focuses on my treatment of dream skepticism. In this article I offer replies to my three critics.
MOTIVES FOR PHILOSOPHIZING DEBUNKING AND WITTGENSTEIN'S PHILOSOPHICAL INVESTIGATIONS
Authors: JOLLEY KELLY DEAN
Published: April 2009

Abstract: In this article I contest a reading of Wittgenstein's Philosophical Investigations—a reading of it as debunking philosophy. I concede that such a reading is not groundless, but I show why it is nonetheless mistaken. To do so, I distinguish two different ways of viewing Philosophical Investigations and its concern with philosophical problems, an External View and an Internal View. On the External View, readers of the book are taken to know ahead of time what philosophical problems are. On the Internal View, readers are not taken to know this ahead of time: the task of the book is to disclose what philosophical problems are, to show them coming into being. One thing disclosed is our participatory role in philosophical problems coming to be. Learning about the nature of philosophical problems is thus learning about our own nature; metaphilosophical knowledge is in part self‐knowledge. If the Internal View is correct (as I believe it is), then Philosophical Investigations does not debunk philosophy but provides a different conception of philosophy and the philosopher's task.
Can Economics be Founded on ‘Indisputable Facts of Experience’? Lionel Robbins and the Pioneers of Neoclassical Economics
Authors: SUGDEN ROBERT
Published: April 2009

Robbins argues that the fundamental propositions of microeconomic theory are deductions from the assumption that individuals act on consistent preferences; this ‘indisputable fact of experience’ does not need to be validated in controlled experiments. While recognising that some neoclassical pioneers based the theory on psychological hedonism, Robbins claims that his own approach of ‘pure theory’ belongs to a parallel and sounder tradition exemplified by Menger and Wicksteed. This paper argues that Robbins' methodological defence of pure theory is incoherent, and that his claim to find an intellectual lineage in the works of Menger and Wicksteed overlooks important discontinuities.
Gender Differences in Time Availability: Evidence from France
Authors: Devetter François‐Xavier
Published: April 2009

The aim of the article is to examine differences in work time from a gender perspective. To this end, a concept broader than mere duration of work time is constructed. This concept, which we call time availability, encompasses not only the volume of hours worked but also the scheduling and predictability of those hours. It is measured by a synthetic indicator showing the extent to which a given group of workers exceeds the societal time norm. After a presentation of the French context, we show that women seem to have less time availability, particularly at the ages that are most decisive in career terms. But these differences do not concern the same aspects of time availability. Thus the time constraints experienced mainly by women are less socially visible and hence undervalued by employers. This lower visibility comes, for a large part, from the social perception of women professionals.
Determining factors leading affiliates to transfer from an individual accounts pension scheme to a pay‐as‐you‐go pension scheme: Evidence from Argentina
Authors: D'Elia Vanesa Valeria
Published: April 2009

Prior to the recent implementation of the Argentine Integrated Social Security System (SIPA —Sistema Integrado Previsional Argentino), the 2007 reform represented the first major change in Argentina's old‐age social security system since 1994. For the first time, workers contributing to the private defined‐contribution individual accounts scheme were able to choose freely to move over to the public pay‐as‐you‐go (PAYG) scheme. This study is an attempt to analyse the special characteristics of those who opted for transfer to the public PAYG scheme and to discover whether the behaviour of these individuals is in line with that of a “simulated worker” attempting to optimize income. The analysis includes an estimate of the probability that individuals with certain characteristics will transfer.
The gender impact of National Pension reforms in the Republic of Korea
Authors: An Mi‐young
Published: April 2009

This article examines the gender impact of National Pension reforms in the Republic of Korea. In 2007, the Korean government introduced an income‐tested basic old‐age pension scheme paying flat‐rate benefits. It also introduced credited pension coverage periods for child rearing and changed entitlement conditions for divorcees and widows and widowers. This paper examines the impact of these policy changes for individuals with shorter working lives and lower wages, for survivors and for the traditional social protection role played by the family in Korea. Findings indicate that the reforms have some positive features. However, the reforms still offer better value for those with higher earnings and an uninterrupted employment history, both of which are more characteristic of male workers. Moreover, the important income security role played by the family is still strongly embedded in the provisions and the protection available to survivors remains weak.
Sphenoid Fungus Balls: Clinical Presentation and Long-Term Follow-Up in 24 Patients
Authors: Leroux E , Valade D , Guichard J-P , Herman P
Published: April 2009

Fungus balls are a non-invasive form of fungal infection involving the maxillary sinus in most cases. Sphenoid sinus fungus balls (SSFB) are rare and their clinical presentation is not well described. We intended to define the clinical presentation of sphenoid fungus balls, and retrospectively reviewed 24 cases of SSFB seen at our institution over a 10-year period, identified through pathological reports. Presenting symptoms were separated into three groups: headache, rhinological and asymptomatic. Headaches were subdivided into acute and chronic, unilateral and diffuse. Radiological clues leading to diagnosis were reviewed. Prognosis was determined from medical files or by phone calls. Sixty-seven per cent of patients were female. The mean age at presentation was 65 years. Sixty-two per cent presented with headache, 36% unilateral, mainly in the first trigeminal branch territory. Rhinological symptoms were seen in 21%. In 16% of patients the SSFB was asymptomatic and found during routine tests. SSFB, even if noninvasive, did lead to recurrent bacterial infections and central nervous system complications in three patients. Of 15 patients presenting with headache, 10 were significantly improved post surgery. The prognosis is good, with no recurrence of fungal infection after a main follow-up of 2.3 years. Our study underlines that SSFB present with headaches, often unilateral and in the fronto-orbital region. Proper imaging of the sphenoid sinus is useful in patients with unexplained headache. The neurologist has to be aware of radiological clues suggesting fungal sinus infection, since surgery is the main treatment, with good prognosis and frequent resolution of headaches.
The Prevalence of Premonitory Symptoms in Paediatric Migraine: A Questionnaire Study in 103 Children and Adolescents
Authors: Cuvellier J-C , Mars A , Vallée L
Published: April 2009

The prevalence and characterization of premonitory symptoms have not been rigorously studied in children and adolescents. Using a questionnaire, we retrospectively studied the prevalence of 15 predefined premonitory symptoms in a clinic-based population. In 103 children and adolescents fulfilling the International Classification of Headache Disorders, 2nd edn criteria for paediatric migraine, at least one premonitory symptom was reported by 69 (67%). The most frequently reported premonitory symptoms were face changes, fatigue and irritability. The mean number of premonitory symptoms reported per subject was 1.8 (median 2.2). Age, migraine subtype (with or without aura) and mean attack frequency per month had no effect on the mean number of premonitory symptoms reported per subject. In conclusion, premonitory symptoms are frequently reported by children and adolescents with migraine. Face changes seem to be a premonitory symptom peculiar to paediatric migraine.
The Tolosa-Hunt Syndrome in Children: A Case Report
Authors: Zanus C , Furlan C , Costa P , Cosentini D , Carrozzi M
Published: April 2009

Tolosa-Hunt syndrome (THS) is characterized by unilateral painful ophthalmoplegia with oculomotor paresis, associated with an idiopathic granulomatous inflammation involving the cavernous sinus, with a typical relapsing-remitting course. We report a case of an 8-year-old girl who was admitted because of an ophthalmoplegia with exotropia and ptosis of the left eyelid, accompanied by diplopia and left sovraorbital pain. The clinical data, neuroradiological findings and response to steroid treatment suggested THS, as defined by the 2004 International Classification of Headache Disorders (ICHD)-II criteria. THS must be considered a possible cause of painful ophthalmoplegia in childhood, as well as in adults, and confirmed with a focused neuroradiological investigation. The few paediatric cases described in the literature that meet the 2004 ICHD-II criteria are not sufficient to identify possible differences between the paediatric and the adult forms. Every new paediatric case should therefore be reported in order to gather and compare further information.
Intracisternal Injection of Inflammatory Soup Activates the Trigeminal Nerve System
Authors: Hoffmann J , Neeb L , Israel H , Dannenberg F , Triebe F , Dirnagl U , Reuter U
Published: April 2009

The release of calcitonin gene-related peptide (CGRP) and sensitization of the trigeminal nerve system are important elements in migraine pathophysiology. Sensitization can be induced by topical meningeal administration of inflammatory soup (IS). CGRP release is a marker of trigeminal nerve activation. We examined the effect of intracisternal IS administration on CGRP release in rat jugular vein blood at baseline, 2 and 15 min after the beginning of IS infusion. IS administration caused a significant increase of CGRP levels after 2 and 15 min compared with baseline. Daily oral treatment with topiramate for 4 and 8 weeks led to a dose- and time-dependent reduction of IS-induced CGRP release. Sumatriptan also attenuated stimulated neuropeptide release. These results indicate that intracisternal IS administration leads to activation of the trigeminal system. The inhibition of CGRP release by topiramate offers a possible mechanism that may in part account for the preventative antimigraine activity of this drug.
Exchange‐mediated dilution of brain lactate specific activity: implications for the origin of glutamate dilution and the contributions of glutamine dilution and other pathways
Authors: Dienel Gerald A. , Cruz Nancy F.
Published: April 2009

The magnitude of metabolic activation is greatly underestimated in autoradiographic studies using [1‐ or 6‐14C]glucose compared to parallel assays with [14C]deoxyglucose indicating that most of the label corresponding to the additional [14C]glucose consumed during activation compared to rest is quickly released from activated structures. Label could be lost by net release of [14C]lactate from brain or via lactate exchange between blood and brain. These possibilities were distinguished by comparison of glucose and lactate specific activities in arterial blood and brain before, during, and after generalized sensory stimulation and during spreading cortical depression. Over a wide range of brain lactate concentrations, lactate specific activity was close to the theoretical maximum, i.e. half that of [6‐14C]glucose, indicating that exchange‐mediated dilution of lactate is negligible and that efflux of [14C]lactate probably accounts for most of the label loss. Low lactate dilution also indicates that dilution of glutamate C4 fractional enrichment in [13C]glucose studies, currently ascribed predominantly to lactate exchange, arises from other unidentified pathways or factors. Alternative explanations for glutamate dilution (presented in Supporting Information) include poorly labeled amino acid pools and oxidative metabolism of minor substrates in astrocytes to first dilute the astrocytic glutamine pool, followed by dilution of glutamate via glutamate–glutamine cycling.
Mutations in human GLUD2 glutamate dehydrogenase affecting basal activity and regulation
Authors: Kanavouras Konstantinos , Borompokas Nikolas , Latsoudis Helen , Stagourakis Argiris , Zaganas Ioannis , Plaitakis Andreas
Published: April 2009

Glutamate dehydrogenase (GDH) in human exists in GLUD1 and GLUD2 gene‐encoded isoforms (hGDH1 and hGDH2, respectively), differing in their regulation and tissue expression pattern. Whereas hGDH1 is subject to GTP control, hGDH2 uses for its regulation, a novel molecular mechanism not requiring GTP. This is based on the ability of hGDH2 to maintain a baseline activity of <10% of its capacity subject to full activation by rising ADP/l‐leucine levels. Here we studied further the molecular mechanisms regulating hGDH2 function by creating and analyzing hGDH2 mutants harboring single amino acid substitutions in the regulatory domain (antenna, pivot helix) of the protein. Five hGDH2 mutants were obtained: two with an amino acid change (Gln441Arg, Ser445Leu) in the antenna, two (Lys450Glu, His454Tyr) in the pivot helix, and one (Ser448Pro) in the junction between the two structures. Functional analyses revealed that, while the antenna mutations increased basal enzyme activity without affecting its allosteric properties, the pivot helix mutations drastically reduced basal activity and impaired enzyme regulation. On the other hand, the Ser448Pro mutation reduced basal activity but did not alter allosteric regulation. Also, compared with wild‐type hGDH2, the antenna mutants were relatively thermostable, whereas the pivot helix mutants were extremely heat labile. Hence, the present data further our understanding of the molecular mechanisms involved in the function and stability of hGDH2, an enzyme thought to be of importance for nerve tissue biology.
Direct measurement of oxidative metabolism in the living brain by microdialysis: a review
Authors: Ronald Zielke H. , Zielke Carol L. , Baab Peter J.
Published: April 2009

This review summarizes microdialysis studies that address the question of which compounds serve as energy sources in the brain. Microdialysis was used to introduce 14C‐labeled glucose, lactate, pyruvate, glutamate, glutamine, and acetate into the interstitial fluid of the brain to observe their metabolism to 14CO2. Although glucose uptake from the systemic system supplies the carbon source for these compounds, compounds synthesized from glucose by the brain are subject to recycling including complete metabolism to CO2. Therefore, the brain utilizes multiple compounds in its domain to provide the energy needed to fulfill its function. The physiological conditions controlling metabolism and the contribution of compartmentation into different brain regions, cell types, and subcellular spaces are still unresolved. The aconitase inhibitor fluorocitrate, with a lower inhibition threshold in glial cells, was used to identify the proportion of lactate and glucose that was oxidized in glial cells versus neurons. The fluorocitrate data suggest that glial and neuronal cells are capable of utilizing both lactate and glucose for energy metabolism.
DNA damage response and cellular senescence in tissues of aging mice
Authors: Wang Chunfang , Jurk Diana , Maddick Mandy , Nelson Glyn , Martin‐Ruiz Carmen , Von Zglinicki Thomas
Published: April 2009

The impact of cellular senescence onto aging of organisms is not fully clear, not at least because of the scarcity of reliable data on the mere frequency of senescent cells in aging tissues. Activation of a DNA damage response including formation of DNA damage foci containing activated H2A.X (γ‐H2A.X) at either uncapped telomeres or persistent DNA strand breaks is the major trigger of cell senescence. Therefore, γ‐H2A.X immunohistochemistry (IHC) was established by us as a reliable quantitative indicator of senescence in fibroblasts in vitro and in hepatocytes in vivo and the age dependency of DNA damage foci accumulation in ten organs of C57Bl6 mice was analysed over an age range from 12 to 42 months. There were significant increases with age in the frequency of foci‐containing cells in lung, spleen, dermis, liver and gut epithelium. In liver, foci‐positive cells were preferentially found in the centrilobular area, which is exposed to higher levels of oxidative stress. Foci formation in the intestine was restricted to the crypts. It was not associated with either apoptosis or hyperproliferation. That telomeres shortened with age in both crypt and villus enterocytes, but telomeres in the crypt epithelium were longer than those in villi at all ages were confirmed by us. Still, there was no more than random co‐localization between γ‐H2A.X foci and telomeres even in crypts from very old mice, indicating that senescence in the crypt enterocytes is telomere independent. The results suggest that stress‐dependent cell senescence could play a causal role for aging of mice.
Acute effects of sustained isometric knee extension on cerebral and muscle oxygenation responses
Authors: Pereira Marta Inez R. , Gomes Paulo Sergio C. , Bhambhani Yagesh N.
Published: April 2009

Cerebral contra‐lateral frontal lobe and the dominant vastus lateralis muscle oxygenation (Cox, Mox) and blood volume (Cbv, Mbv) were recorded simultaneously using near infrared spectroscopy (NIRS) in 12 healthy volunteers (37·4 ± 9·9 years; 72·3 ± 16·1 kg; 171·0 ± 9·6 cm) during 2 min resting baseline, an isometric knee extension with the 1 RM load sustained to the point of fatigue, and 3 min recovery. The mean exercise duration was 19·1 ± 2·6 s. During the contraction, Cox and Cbv increased systematically with no sign of levelling off until the point of fatigue. In contrast, Mox and Mbv declined continuously until the termination of exercise. Qualitative analysis of these NIRS profiles suggested that maximal isometric performance under normoxic conditions was most likely not limited by central neuronal activation, but rather, was due to factors within the exercising muscle. It is likely that depletion of intramuscular stores of high energy phosphates and oxymyoglobin, as well as the accumulation of metabolites from anaerobic pathways, were implicated in fatigue during this sustained high intensity isometric contraction.
Inhibition of colonic motility and defecation by RS‐127445 suggests an involvement of the 5‐HT2B receptor in rodent large bowel physiology
Authors: Bassil AK , Taylor CM , Bolton VJN , Gray KM , Brown JD , Cutler L , Summerfield SG , Bruton G , Winchester WJ , Lee K , Sanger GJ
Published: April 2009

Background:  5‐HT2B receptors are localized within the myenteric nervous system, but their functions on motor/sensory neurons are unclear. To explore the role of these receptors, we further characterized the 5‐HT2B receptor antagonist RS‐127445 and studied its effects on peristalsis and defecation.

Experimental approach:  Although reported as a selective 5‐HT2B receptor antagonist, any interactions of RS‐127445 with 5‐HT4 receptors are unknown; this was examined using the recombinant receptor and Biomolecular Interaction Detection technology. Mouse isolated colon was mounted in tissue baths for isometric recording of neuronal contractions evoked by electrical field stimulation (EFS), or under an intraluminal pressure gradient to induce peristalsis; the effects of RS‐127445 on EFS‐induced and on peristaltic contractions were measured. Faecal output of rats in grid‐bottom cages was measured over 3 h following i.p. RS‐127445 and separately, validation of the effective doses was achieved by determining the free, unbound fraction of RS‐127445 in blood and brain.

Key results:  RS‐127445 (up to 1 µmol·L−1) did not interact with the 5‐HT4 receptor. RS‐127445 (0.001–1 µmol·L−1) did not affect EFS‐induced contractions of the colon, although at 10 µmol·L−1 the contractions were reduced (to 36 ± 8% of control, n= 4). RS‐127445 (0.1–10 µmol·L−1) concentration‐dependently reduced peristaltic frequency (n= 4). RS‐127445 (1–30 mg·kg−1), dose‐dependently reduced faecal output, reaching significance at 10 and 30 mg·kg−1 (n= 6–11). In blood and brain, >98% of RS‐127445 was protein‐bound.

Conclusions and implications:  High‐protein binding of RS‐127445 indicates that relatively high doses are required for efficacy. The results suggest that 5‐HT2B receptors tonically regulate colonic motility.
Potential for vitamin D receptor agonists in the treatment of cardiovascular disease
Authors: Wu‐Wong JR
Published: April 2009

Vitamin D3 is made in the skin and modified in the liver and kidney to form the active metabolite, 1,25‐dihydroxyvitamin D3 (calcitriol). Calcitriol binds to a nuclear receptor, the vitamin D receptor (VDR), and activates VDR to recruit cofactors to form a transcriptional complex that binds to vitamin D response elements in the promoter region of target genes. During the past three decades the field has focused mainly on the role of VDR in the regulation of parathyroid hormone, intestinal calcium/phosphate absorption and bone metabolism; several VDR agonists (VDRAs) have been developed for the treatment of osteoporosis, psoriasis and hyperparathyroidism secondary to chronic kidney disease (CKD). Emerging evidence suggests that VDR plays important roles in modulating cardiovascular, immunological, metabolic and other functions. For example, data from epidemiological, preclinical and clinical studies have shown that vitamin D and/or 25(OH)D deficiency is associated with increased risk for cardiovascular disease (CVD). However, VDRA therapy seems more effective than native vitamin D supplementation in modulating CVD risk factors. In CKD, where decreasing VDR activation persists over the course of the disease and a majority of the patients die of CVD, VDRA therapy was found to provide a survival benefit in both pre‐dialysis and dialysis CKD patients. Although VDR plays an important role in regulating cardiovascular function and VDRAs may be potentially useful for treating CVD, at present no VDRA is approved for CVD, and also no serum markers, beside parathyroid hormone in CKD, exist to indicate the efficacy of VDRA in CVD.
Bepridil up‐regulates cardiac Na+channels as a long‐term effect by blunting proteasome signals through inhibition of calmodulin activity
Authors: Kang L , Zheng MQ , Morishima M , Wang Y , Kaku T , Ono K
Published: April 2009

Background and purpose: Bepridil is an anti‐arrhythmic agent with anti‐electrical remodelling effects that target many cardiac ion channels, including the voltage‐gated Na+channel. However, long‐term effects of bepridil on the Na+channel remain unclear. We explored the long‐term effect of bepridil on the Na+channel in isolated neonatal rat cardiomyocytes and in a heterologous expression system of human Nav1.5 channel.

Experimental approach: Na+currents were recorded by whole‐cell voltage‐clamp technique. Na+channel message and protein were evaluated by real‐time RT‐PCR and Western blot analysis.

Key results: Treatment of cardiomyocytes with 10 µmol·L−1bepridil for 24 h augmented Na+channel current (INa) in a dose‐ and time‐dependent manner. This long‐term effect of bepridil was mimicked or masked by application of W‐7, a calmodulin inhibitor, but not KN93 [2‐[N‐(2‐hydroxyethyl)‐N‐(4‐methoxy benzenesulphonyl)]‐amino‐N‐(4‐chlorocinnamyl)‐N‐methylbenzylamine], a Ca2+/calmodulin‐dependent kinase inhibitor. During inhibition of protein synthesis by cycloheximide, theINaincrease due to bepridil was larger than the increase without cycloheximide. Bepridil and W‐7 significantly slowed the time course of Nav1.5 protein degradation in neonatal cardiomyocytes, although the mRNA levels of Nav1.5 were not modified. Bepridil and W‐7 did not increaseINaany further in the presence of the proteasome inhibitor MG132 [N‐[(phenylmethoxy)carbonyl]‐L‐leucyl‐N‐[(1S)‐1‐formyl‐3‐methylbutyl]‐L‐leucinamide]. Bepridil, W‐7 and MG132 but not KN93 significantly decreased 20S proteasome activity in a concentration‐dependent manner.

Conclusions and implications: We conclude that long‐term exposure of cardiomyocytes to bepridil at therapeutic concentrations inhibits calmodulin action, which decreased degradation of the Nav1.5 α‐subunit, which in turn increased Na+current.