bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgery and pre‐operative irradiation for locally advanced or recurrent rectal cancer in patients over 75 years of age
Authors: Larsen S. G. , Wiig J. N. , Tretli S. , Giercksky K.‐E.
Published: February 2006

Objective  Reports of multimodal treatment regimens especially focusing on locally advanced or recurrent rectal cancer in the elderly, aged > 75 years, are unavailable. We have tried to identify and evaluate pre‐ and peri‐operative risk factors for morbidity and mortality and outcome after irradiation/surgery regimens in such patients.

Patients and methods  Prospective registration of 86 consecutive patients aged > 75 years undergoing elective surgery after irradiation 46–50 Gy for either primary locally advanced rectal cancer (n = 51) or recurrent rectal cancer (n = 35) from January 1991 to August 2003, 51 men and 35 women, median age 78 years (range 75–85 years) in a national cancer hospital.

Results  Multivisceral resections were needed in 63% of patients and 70% R0 resections were obtained in locally advanced cases and 46% in recurrent ones. Both in‐hospital‐ and 30‐day‐mortality was 3.5%. Sixty‐two postoperative complications occurred in 38 patients, three of them fatal. Both operation times over 5 h and transfusion of more than 3 SAG were prognostic factors regarding infections. Estimated five‐year survival in R0 patients was 46%. Estimated five‐year survival for patients with nonmetastatic tumours with locally advanced primary cancer was 29% and for locally recurrent rectal cancer 32%. Old males had a higher mortality rate the first year after surgery than females with only 65% relative survival compared to a matched normal population. The estimated five‐year local recurrence rates were 24% for R0 resections and 54% for R1 resections (P = 0.434 ns) and 24% and 45% for locally advanced and recurrent rectal cancer (P = 0.248 ns), respectively.

Conclusion  Thorough pre‐operative evaluation and preparation and judicious surgery are important for achieving potentially curative treatment with acceptable morbidity in locally advanced and recurrent rectal cancer in patients over 75 years of age. We suggest that these patients should be evaluated and considered for treatment by multidisciplinary teams as younger patients.
Can the results of anorectal (abdominoperineal) resection be improved: are circumferential resection margins too often positive?
Authors: Radcliffe A.
Published: February 2006

Carefully executed surgery for rectal cancer has reduced the incidence of local recurrence after restorative resection. Three recent large prospective series have confirmed the perception of a higher positive circumferential resection margin (CRM) rate after abdominoperineal resection. Tumour spread is different for low tumours and the surgical technique of abdominoperineal resection, perhaps better known as anorectal excision, may vary between surgeons. There is a need to redefine the place of anorectal excision and the contribution that can be made by pre‐operative chemoradiation and/or extended surgery to reduce local recurrence and increase survival. Defined surgery, validated by histopathological assessment, as applied to TME surgery, would determine whether the perceived higher rates are due to the differences in routes of tumour spread or to surgically related variables. Unnecessary R1 or R2 resections and operative perforation can be minimized by an understanding of the surgical anatomy, the pattern of spread and difference in operative technique between anorectal excision and a low restorative operation. Surgical technique to maximize R0 resection should be based on a detailed understanding of the pelvic fascia and the levator ani and the use of pre‐operative imaging to define lines of excision. With the adoption of even lower restorative resection (intersphincteric) there is a need to reassess the method of anorectal excision. This may be achieved by histopathological assessment of CRM positivity and MDT audit to improve results. Clinical trials are essential.
The routine use of intra‐operative ultrasound in patients with colorectal cancer improves the detection of hepatic metastases
Authors: Agrawal N. , Fowler A. L. , Thomas M. G.
Published: February 2006

Introduction  Up to one fifth of patients with carcinoma of the colon have occult liver metastases at the time of presentation. Intra‐operative hepatic ultrasonography might improve disease staging. We report the use of intra‐operative ultrasonography (IOUS) in routine clinical practice over a five‐year period.

Method  Seventy‐six patients with colorectal carcinoma (F 21, M 55) of median age 67 years (range 43–89 years) for whom full data were available had IOUS at the time of colonic resection. All patients had had a computerized tomography (CT), magnetic resonance imaging (MRI) or ultrasonography (USS).

Results  Of 76 patients, 10 had a Dukes A, 32 had a Dukes B and 34 a Dukes C carcinoma. In 20 patients IOUS detected lesions not seen on pre‐operative scanning including 11 metastases (one suitable for resection), seven benign hepatic cysts and two were benign hepatic nodules. Forty‐nine patients have remained free of disease and 25 have died with systemic disease (mean survival 10 months, range 2–24months). In the seven patients diagnosed as having hepatic cysts at IOUS two have died of systemic disease. The remaining patients (n = 12) who died with systemic disease had a negative IOUS.

Conclusion  IOUS increases diagnostic yield but a significant proportion of patients with occult hepatic metastases are not detected. IOUS improves disease staging in some patients refining the indications for adjuvant therapy and enhancing the estimate of prognosis and improving decision‐making.
Nationwide quality assurance of rectal cancer treatment
Authors: Wibe A. , Carlsen E. , Dahl O. , Tveit K. M. , Weedon‐Fekjær H. , Hestvik U. E. , Wiig J. N. ,   The Norwegian Rectal Cancer Group
Published: February 2006

Objective  The purpose of this prospective study was to examine the influence of the efforts for nationwide quality assurance of rectal cancer treatment. The study focuses on local recurrence and overall survival.

Methods  This study includes all 3388 Norwegian patients with a rectal cancer within 15 cm from the anal verge treated with curative intent in the period November 1993–December 1999. A comprehensive educational programme was established, and training courses were arranged in different Health Regions demonstrating the TME technique. A specific Rectal Cancer Registry enabled the monitoring of outcome of rectal cancer treatment for single hospitals. Radiotherapy was given to 10% of the patients.

Results  The risk of local recurrence has been significantly reduced, so that in 1999 the level was 50% below that observed in 1994 (Hazard ratio (HR)1999 = 0.5; 95% CI 0.4–0.8, P = 0.002). Similarly, during 1998, the mean national overall survival was significantly improved, compared to the rate in1994 (HR1998 = 0.8; 95% CI 0.6–1.0, P = 0.014).

Conclusion  The prognosis for rectal cancer can be improved by increased organizational focus on rectal cancer treatment and by establishing a rectal cancer registry monitoring treatment standards throughout the country.
RENAISSANCE GOTHIC: PICTURES OF GEOMETRY AND NARRATIVES OF ORNAMENT
Authors: KAVALER ETHAN MATT
Published: February 2006

The profuse Gothic ornament of the early sixteenth century has often been judged typical of Gothic decline, in accordance with the long‐standing dictates of modernism. Yet ornament offered a means of refurbishing this traditional mode, which was then being challenged by alternative Italian practice. In central Europe especially, architects inscribed conspicuous geometrical patterns on the interior of their churches – on elegantly figured vaults and on the balustrades to galleries and ecclesiastical furnishings. Framed and isolated for regard, these were pictures of geometry that could be received as utterances in that ideal mathematical language of divine conception and creation. Furthermore, designers often arranged geometrical shapes in sequences that invited a narrative reading, imbuing the forms with a sense of direction and purpose. Late Gothic ornament thus provided a commentary on religious authority and mediated the experience of sacred structures.
PARIS CIRCUS NEW YORK JUNK: JEAN DUBUFFET AND CLAES OLDENBURG, 1959–1962
Authors: BERREBI SOPHIE
Published: February 2006

This article explores the artistic relation between Jean Dubuffet and Claes Oldenburg, attentive to the shifts in the critical reception of Dubuffet in the United States in the late 1950s and early 1960s. The essay focuses on Oldenburg's two major early environments, The Street and The Store, arguing that Oldenburg anticipated his critical reception by claiming the influence of Dubuffet over his work and turning this into a creative tool. In the process, Oldenburg transposed and ultimately rewrote Dubuffet's postwar vision of the ‘common man’ in the context of early pop art. Dubuffet's Paris Circus paintings from 1961–62 are briefly discussed in order to underscore a concept of influence as productive anachronism.
RE‐VISIONING THE HOPI FOURTH WORLD: DAN NAMINGHA, INDIGENOUS MODERNISM, AND THE HOPIVOTSKWANI
Authors: MARTÍNEZ DAVID
Published: February 2006

This article demonstrates, through an analysis of the work of Hopi‐Tewa artist Dan Namingha, that the discourse on contemporary American Indian art has moved beyond issues of ‘assimilation’. Whereas consideration of modern American Indian art has been limited to the ‘two‐world’ motif, in which indigenous artists had to make a choice between being ‘traditional’ or ‘progressive’, the paradigm today, it is argued, consists in ‘recovering’ and ‘revitalizing’ of indigenous values and beliefs. What results is the appropriation by indigenous artists of a sovereign space within the ‘art world’ for non‐Western sources of culture. Namingha's Hopi‐Tewa images are all drawn from the Hopi villages, Polacca and Hano, on First Mesa, in which he grew up. The essay elucidates that Namingha, through his art, accomplishes the extension of the Hopivotskwani, which is the Hopi ‘way of doing things’, into the world of modern art, thereby making a claim for the continued relevance of an otherwise ancient tradition.
Suggestion Reduces the Stroop Effect
Authors: Raz Amir , Kirsch Irving , Pollard Jessica , Nitkin-Kaner Yael
Published: February 2006

We examined the effects of suggestion on Stroop interference in highly suggestible individuals. Participants completed the Stroop task with and without a suggestion to perceive Stroop words as meaningless symbols. Half the participants were given this suggestion in hypnosis, and half were given the suggestion without the induction of hypnosis. Suggestion produced a significant reduction in Stroop inhibition, accounting for about 45% of the variance in Stroop responding, regardless of whether hypnosis had been induced. These findings indicate that suggestion can at least partially overcome the automaticity associated with the Stroop effect.
New Data Analysis of the Stroop Matching Task Calls for a Reevaluation of Theory
Authors: Goldfarb Liat , Henik Avishai
Published: February 2006

In Stroop matching tasks, participants indicate whether the color of an object matches the meaning of a color word printed in color. Previously in this journal, Luo (1999) concluded that interference between two incongruent representations of the same attribute (ink color) occurs prior to the response stage. However, this conclusion was based on questionable data analysis. We suggest analyzing the data by separating “same” and “different” responses and then analyzing three congruency conditions within the “different” responses: (a) congruence between word color and word meaning, (b) congruence between word color and object color, and (c) incongruence between word color, word meaning, and object color. In an experiment similar to Luo's, such an analysis revealed that responding was slowest in the first condition. This pattern of results does not fit with previous conclusions regarding this task, but rather indicates that task conflict and response competition contribute to interference. This analysis has implications for matching tasks other than the Stroop matching task.
Culture and the Physical Environment
Authors: Miyamoto Yuri , Nisbett Richard E. , Masuda Takahiko
Published: February 2006

Westerners' perceptions tend to focus on salient foreground objects, whereas Asians are more inclined to focus on contexts. We hypothesized that such culturally specific patterns of attention may be afforded by the perceptual environment of each culture. In order to test this hypothesis, we randomly sampled pictures of scenes from small, medium, and large cities in Japan and the United States. Using both subjective and objective measures, Study 1 demonstrated that Japanese scenes were more ambiguous and contained more elements than American scenes. Japanese scenes thus may encourage perception of the context more than American scenes. In Study 2, pictures of locations in cities were presented as primes, and participants' subsequent patterns of attention were measured. Both Japanese and American participants primed with Japanese scenes attended more to contextual information than did those primed with American scenes. These results provide evidence that culturally characteristic environments may afford distinctive patterns of perception.
Expanding the Topography of Social Anxiety
Authors: Kashdan Todd B. , Steger Michael F.
Published: February 2006

The relation between social anxiety and hedonic activity remains poorly understood. From a self-regulatory perspective, we hypothesized that socially anxious individuals experience diminished positive experiences and events on days when they are unable to manage socially anxious feelings adequately. In this 21-day experience-sampling study, we constructed daily measures of social anxiety and emotion regulation. Greater dispositional social anxiety was associated with less positive affect and fewer positive events in everyday life. Among individuals defined as socially anxious from their scores on a global self-report measure of social anxiety, the number of positive events was lowest on days when they both were more socially anxious and tended to suppress emotions and highest on days when they were less socially anxious and more accepting of emotional experiences. Irrespective of dispositional social anxiety, participants reported the most intense positive emotions on the days when they were both least socially anxious and most accepting of emotional experiences. Possible clinical implications are discussed.
Essentializing Differences Between Women and Men
Authors: Prentice Deborah A. , Miller Dale T.
Published: February 2006

People represent many social categories, including gender categories, in essentialist terms: They see category members as sharing deep, nonobvious properties that make them the kinds of things they are. The present research explored the consequences of this mode of representation for social inferences. In two sets of studies, participants learned (a) that they were similar to a member of the other gender on a novel attribute, (b) that they were different from a member of the other gender on a novel attribute, or (c) just their own standing on a novel attribute. Results showed that participants made stronger inductive inferences about the attribute in question when they learned that it distinguished them from a member of the other gender than in the other conditions. We consider the implications of these results for the representation of social categories and for everyday social inference processes.
Turning the Other Cheek
Authors: Meier Brian P. , Robinson Michael D. , Wilkowski Benjamin M.
Published: February 2006

Aggression-related cues (e.g., violent media) can prime both hostile thoughts and the tendency to commit aggression. However, not everyone engages in an aggressive act after being exposed to an aggression-related cue. Some thought pattern, perhaps an automatic one, may prevent the cue-aggression sequence in some individuals. These considerations motivated the present research, which examined the potential for agreeableness to moderate the effect of aggression-related cues on behavior and cognition. In Study 1, we found that priming with aggression-related cues increased aggressive behavior, but only among individuals low in agreeableness. Study 2 showed that aggression-related cues activated prosocial thoughts among individuals high in agreeable affect (a component of agreeableness). These results reveal that agreeable individuals are able to short-circuit the cue-aggression sequence, likely by recruiting prosocial thoughts in response to aggression-related primes.
Doing Better but Feeling Worse
Authors: Iyengar Sheena S. , Wells Rachael E. , Schwartz Barry
Published: February 2006

Expanding upon Simon's (1955) seminal theory, this investigation compared the choice-making strategies of maximizers and satisficers, finding that maximizing tendencies, although positively correlated with objectively better decision outcomes, are also associated with more negative subjective evaluations of these decision outcomes. Specifically, in the fall of their final year in school, students were administered a scale that measured maximizing tendencies and were then followed over the course of the year as they searched for jobs. Students with high maximizing tendencies secured jobs with 20% higher starting salaries than did students with low maximizing tendencies. However, maximizers were less satisfied than satisficers with the jobs they obtained, and experienced more negative affect throughout the job-search process. These effects were mediated by maximizers' greater reliance on external sources of information and their fixation on realized and unrealized options during the search and selection process.
Nature and Nurture in Own-Race Face Processing
Authors: Bar-Haim Yair , Ziv Talee , Lamy Dominique , Hodes Richard M.
Published: February 2006

A standard visual preference task was used to examine 3-month-olds' looking times at own-race versus other-race faces as a function of environmental exposure to faces from the two categories. Participants were Caucasian infants living in a Caucasian environment, African infants living in an African environment, and African infants living in a predominantly Caucasian environment. The results indicate that preference for own-race faces is present as early as 3 months of age, but that this preference results from exposure to the prototypical facial environment.
Not All Executive Functions Are Related to Intelligence
Authors: Friedman Naomi P. , Miyake Akira , Corley Robin P. , Young Susan E. , DeFries John C. , Hewitt John K.
Published: February 2006

Accumulating evidence suggests that executive functions (EFs) are related to intelligence, despite neuropsychological results initially considered evidence of no such relation. However, findings that EFs are not unitary raise the issue of how intelligence relates to different EFs. This study examined the relations of fluid and crystallized intelligence and Wechsler Adult Intelligence Scale IQ to three separable EFs—inhibiting prepotent responses (inhibiting), shifting mental sets (shifting), and updating working memory (updating)—in young adults. Updating was highly correlated with the intelligence measures, but inhibiting and shifting were not. Furthermore, in structural equation models controlling for the inter-EF correlations, updating remained strongly related to intelligence, but the relations of inhibiting and shifting to intelligence were small and not significant. The results indicate that intelligence measures differentially relate to these three EFs, suggesting that current intelligence measures do not equally assess a wide range of executive control abilities likely required for many “intelligent” behaviors.
Knowledge in the Palm of your hands: PDAs in the clinical setting
Authors: Honeybourne Claire , Sutton Sarah , Ward Linda
Published: February 2006

Objective:  To explore the impact of hand‐held computers on patient care by identifying: (i) how often clinical staff accessed resources on hand‐held computers to inform their clinical decision making; (ii) Which hand‐held resources were thought to be most useful in the clinical setting; (iii) the barriers to using hand‐held resources to support patient care.

Design:  A descriptive study comparing aspects of Personal Digital Assistant (PDA) resource use in two phases, between August 2002 and December 2003. There was variability in the way that resources were accessed between the two studies.

Setting:  University Hospitals of Leicester NHS Trust, an acute teaching hospital, and one primary care practice.

Participants:  A purposive sample of 14 clinical and librarian staff participated in phase one and 14 in phase two of the study. Participants consisted of consultants, nurses, pharmacist, junior doctors, clinical librarians, and a general practitioner.

Main outcome measures:  Baseline Data Questionnaire to identify the participants’ level of knowledge and use of hand‐helds on entering the study. End‐of‐phase questionnaire with self‐reported measures of use of the hand‐held and PDA resources during the study.

Results:  All of the participants used hand‐helds in their clinical setting to support evidence‐based practice and education, but with varying frequency. More staff reported using the hand‐held to answer specific patient questions in phase two than phase one of the study. UK resources were preferred to American resources. The ‘plug‐in and go’ method using Secure Digital (SD) cards was preferred to downloading resources from the Internet.

Conclusions:  Hand‐held technology is emerging as an effective clinical tool to aid evidence‐based practice and support the educational needs of clinical staff. The hand‐held can provide a critical mass of information that is relevant, quickly accessible and in a coherent format: delivering clinical information at the point of need with a resulting benefit to patient safety.
Developing efficient search strategies to identify reports of adverse effects in medline and embase
Authors: Golder Su , McIntosh Heather M. , Duffy Steve , Glanville Julie
Published: February 2006

Objective:  This study aimed to assess the performance, in terms of sensitivity and precision, of different approaches to searching medline and embase to identify studies of adverse effects.

Methods:  Five approaches to searching for adverse effects evidence were identified: approach 1, using specified adverse effects; approach 2, using subheadings/qualifiers; approach 3, using text words; approach 4, using indexing terms; approach 5, searching for specific study designs. The sensitivity and precision of these five approaches, and combinations of these approaches, were compared in a case study using a systematic review of the adverse effects of seven anti‐epileptic drugs.

Results:  The most sensitive search strategy in medline (97.0%) required a combination of terms for specified adverse effects, floating subheadings, and text words for ‘adverse effects’. In embase, a combination of terms for specified adverse effects and text words for ‘adverse effects’ provided the most sensitive search strategy (98.6%). Both these search strategies yielded low precision (2.8%).

Conclusions:  A highly sensitive search in either database requires a combination of approaches, and has low precision. This suggests that better reporting and indexing of adverse effects is required and that an effective generic search filter may not yet be feasible.
Clinical effectiveness and allied health professionals: an information needs assessment
Authors: Haigh Valerie
Published: February 2006

Objective:  To determine the information needs and support required by AHPs whilst building services based on clinical effectiveness.

Methods:  A qualitative approach using action research in co‐operation with a Rehabilitation Department Clinical Effectiveness group, leading to interviews with eight therapists. The sampling strategy was purposive.

Results:  Therapists have well‐developed professional networks, but are unsure how to access traditional library areas. Library training can stop AHPs in asking for help or services, whilst the library is thought to be very different to their everyday work, but confidence in using the library service can be acquired by getting to know a librarian. A departmental‐based service was thought to provide better access to, and understanding of, information through mentorship, whilst also providing up‐to‐date evidence so that clinicians can concentrate on their clinical work whilst being more clinically effective.

Conclusions:  When seeking information, AHPs are more likely to use professional networks than libraries. However, when working alongside an AHP, a librarian can upgrade information‐seeking skills through mentorship, whilst named library contacts can make it easier to access the library for help.
Market orientation: a concept for health libraries
Authors: Sen Barbara
Published: February 2006

Objectives:  This paper is the result of exploratory research forming part of ongoing study into the value and relevance of market orientation as a strategic option for library managers. The aim of the study is to gain an understanding of the concept of market orientation relative to the health library sector.

Methodology:  A focus group was used to gather data from health librarians working at different levels in the sector. The data was coded and categorized by an expert panel and analysed using a taxonomic map developed during the study.

Results:  Health library professionals define and understand market orientation in the same way as the concept is defined in the management literature. Their understanding of the concept is developing. A greater emphasis is given to some aspects of market orientation than others.

Conclusions:  There are implications for further research. Methods used to measure market orientation in other domains are likely to be relevant for libraries. Research should be extended to different sectors to explore any cross‐sector differences. Fostering an organizational culture that supports market orientation has implications for service management and development.
A journal club is an effective tool for assisting librarians in the practice of evidence‐based librarianship: a case study
Authors: Pearce‐Smith Nicola
Published: February 2006

Objective:  To establish a journal club for librarians, which aimed to develop appraisal skills and assist in the application of research to practice.

Methods:  Fourteen health librarians were invited to attend a journal club. Each month a librarian was responsible for preparing a scenario, choosing a research paper, and selecting a checklist. The paper was appraised by the club, and a critically appraised topic (CAT) prepared. Six months later, a questionnaire was sent to all librarians.

Results:  Six out of 14 librarians attended the journal club and five out of six returned the questionnaire. All five agreed that attending the journal club helped them develop appraisal skills, write a CAT and be more critical of research. Four agreed they always identified a research paper first, then formulated a question. One librarian agreed that applying results to their own practice was difficult, one disagreed and three were neutral.

Conclusion:  Journal clubs can be effective at developing appraisal skills and writing a CAT, as well as increasing the reading of library research. Librarians still need assistance in identifying and using questions directly from their own practice. The journal club has helped some librarians to apply evidence to practice, but others find the research is not always directly relevant.
Effects of extracellular matrix‐degrading proteases matrix metalloproteinases 3 and 9 on spatial learning and synaptic plasticity
Authors: Meighan Starla E. , Meighan Peter C. , Choudhury Papiya , Davis Christopher J. , Olson Mikel L. , Zornes Peter A. , Wright John W. , Harding Joseph W.
Published: February 2006

Rats learning the Morris water maze exhibit hippocampal changes in synaptic morphology and physiology that manifest as altered synaptic efficacy. Learning requires structural changes in the synapse, and multiple cell adhesion molecules appear to participate. The activity of these cell adhesion molecules is, in large part, dependent on their interaction with the extracellular matrix (ECM). Given that matrix metalloproteinases (MMPs) are responsible for transient alterations in the ECM, we predicted that MMP function is critical for hippocampal‐dependent learning. In support of this, it was observed that hippocampal MMP‐3 and ‐9 increased transiently during water maze acquisition as assessed by western blotting and mRNA analysis. The ability of the NMDA receptor channel blocker MK801 to attenuate these changes indicated that the transient MMP changes were in large part dependent upon NMDA receptor activation. Furthermore, inhibition of MMP activity with MMP‐3 and ‐9 antisense oligonucleotides and/or MMP inhibitor FN‐439 altered long‐term potentiation and prevented acquisition in the Morris water maze. The learning‐dependent MMP alterations were shown to modify the stability of the actin‐binding protein cortactin, which plays an essential role in regulating the dendritic cytoskeleton and synaptic efficiency. Together these results indicate that changes in MMP function are critical to synaptic plasticity and hippocampal‐dependent learning.
Pramipexole protects against MPTP toxicity in non‐human primates
Authors: Iravani Mahmoud M. , Haddon Claire O. , Cooper J. Mark , Jenner Peter , Schapira Anthony H.
Published: February 2006

The neurotoxin MPTP induces nigral dopaminergic cell death in primates and produces a partial model of Parkinson's disease (PD). Pramipexole is a D2/D3 dopamine receptor agonist used in the symptomatic treatment of PD, and which also protects neuronal cells against dopaminergic toxins in vitro. We now demonstrate that pramipexole partially prevents MPTP toxicity in vivo in a primate species. Common marmosets were repeatedly treated with pramipexole either before, coincidentally with, or after low‐dose MPTP treatment designed to induce a partial lesion of the substantia nigra. Animals pretreated with pramipexole had a significantly greater number of surviving tyrosine hydroxylase (TH) positive neurones in the pars compacta of the substantia nigra. Pramipexole pretreatment also prevented degeneration of striatal dopamine terminals. Treatment with pramipexole concurrently with MPTP or following MPTP did not prevent TH‐positive cell loss. Pramipexole pretreatment appears to induce adaptive changes that protect against dopaminergic cell loss in primates.
Enhancement of nitric oxide production by association of nitric oxide synthase with N‐methyl‐d‐aspartate receptors via postsynaptic density 95 in genetically engineered Chinese hamster ovary cells: real‐time fluorescence imaging using nitric oxide sensitive dye
Authors: Ishii Hirotaka , Shibuya Keisuke , Ohta Yoshihiro , Mukai Hideo , Uchino Shigeo , Takata Norio , Rose John A. , Kawato Suguru
Published: February 2006

The current quantitative study demonstrates that the recruitment of neuronal nitric oxide synthase (nNOS) beneath N‐methyl‐d‐aspartate (NMDA) receptors, via postsynaptic density 95 (PSD‐95) proteins significantly enhances nitric oxide (NO) production. Real‐time single‐cell fluorescence imaging was applied to measure both NO production and Ca2+ influx in Chinese hamster ovary (CHO) cells expressing recombinant NMDA receptors (NMDA‐R), nNOS, and PSD‐95. We examined the relationship between the rate of NO production and Ca2+ influx via NMDA receptors using the NO‐reactive fluorescent dye, diaminofluorescein‐FM (DAF‐FM) and the Ca2+‐sensitive yellow cameleon 3.1 (YC3.1), conjugated with PSD‐95 (PSD‐95‐YC3.1). The presence of PSD‐95 enhanced the rate of NO production by 2.3‐fold upon stimulation with 100 µm NMDA in CHO1(+) cells (expressing NMDA‐R, nNOS and PSD‐95) when compared with CHO1(–) cells (expressing NMDA‐R and nNOS lacking PSD‐95). The presence of nNOS inhibitor or NMDA‐R blocker almost completely suppressed this NMDA‐stimulated NO production. The Ca2+ concentration beneath the NMDA‐R, [Ca2+]NR, was determined to be 5.4 µm by stimulating CHO2 cells (expressing NMDA‐R and PSD‐95‐YC3.1) with 100 μm NMDA. By completely permealizing CHO1 cells with ionomycin, a general relationship curve of the rate of NO production versus the Ca2+ concentration around nNOS, [Ca2+]NOS, was obtained over the wide range of [Ca2+]NOS. This sigmoidal curve had an EC50 of approximately 1.2 µm of [Ca2+]NOS, implying that [Ca2+]NR = 5.4 µm can activate nNOS effectively.
Interaction between interferon γ and insulin‐like growth factor‐1 in hippocampus impacts on the ability of rats to sustain long‐term potentiation
Authors: Maher Frank O. , Clarke Rachael M. , Kelly Aine , Nally Rachel E. , Lynch Marina A.
Published: February 2006

There is compelling evidence to suggest that inflammation significantly contributes to neurodegenerative changes. Consistent with this is the observation that several neurodegenerative disorders are accompanied by an increase in the concentration of interleukin (IL)‐1β. IL‐1β has a negative impact on synaptic plasticity and therefore an increased concentration of IL‐1β, such as that in the hippocampus of the aged rat, is associated with a deficit in long‐term potentiation (LTP). IL‐1β is derived mainly from activated microglia but the trigger leading to this activation, specifically in the aged brain, remains to be identified. Here we examined the possiblity that interferon (IFN)γ may stimulate microglial activation and increase IL‐1β concentration, thereby inhibiting LTP. The IFNγ concentration was increased in hippocampus prepared from aged, compared with young, rats and inversely correlated with the ability of rats to sustain LTP. Intracerebroventricular injection of IFNγ inhibited LTP, and increased microglial activation was observed in both IFNγ‐injected and aged rats. The age‐related increase in IFNγ was accompanied by a decrease in the hippocampal concentration of insulin‐like growth factor (IGF)‐1. The evidence presented suggests that IGF‐1 acts to antagonize the IFNγ‐induced microglial activation, the accompanying increase in IL‐1β concentration and the consequent deficit in LTP.
Molecular identification and functional characterization of an adenylyl cyclase from the honeybee
Authors: Wachten Sebastian , Schlenstedt Jana , Gauss Renate , Baumann Arnd
Published: February 2006

Cyclic AMP (cAMP) serves as an important messenger in virtually all organisms. In the honeybee (Apis mellifera), cAMP‐dependent signal transduction has been implicated in behavioural processes as well as in learning and memory. Key components of cAMP‐signalling cascades are adenylyl cyclases. However, the molecular identities and biochemical properties of adenylyl cyclases are completely unknown in the honeybee. We have cloned a cDNA (Amac3) from honeybee brain that encodes a membrane‐bound adenylyl cyclase. The Amac3 gene is an orthologue of the Drosophila ac39E gene. The corresponding proteins share an overall amino acid similarity of approximately 62%. Phylogenetically, AmAC3 belongs to group 1 adenylyl cyclases. Heterologously expressed AmAC3 displays basal enzymatic activity and efficient coupling to endogenous G protein signalling pathways. Stimulation of β‐adrenergic receptors induces AmAC3 activity with an EC50 of about 3.1 µm. Enzymatic activity is also increased by forskolin (EC50 approximately 15 µm), a specific agonist of membrane‐bound adenylyl cyclases. Similar to certain biogenic amine receptor genes of the honeybee, Amac3 transcripts are expressed in many somata of the brain, especially in mushroom body neurones. These results suggest that the enzyme serves in biogenic amine signal transduction cascades and in higher brain functions that contribute to learning and memory of the bee.
Aminoguanidine inhibits caspase‐3 and calpain activation without affecting microglial activation following neonatal transient cerebral ischemia
Authors: Dingman Andra , Lee Sarah Y. , Derugin Nikita , Wendland Michael F. , Vexler Zinaida S.
Published: February 2006

Microglial cells, the resident macrophages of the CNS, can be both beneficial and detrimental to the brain. These cells play a central role as mediators of neuroinflammation associated with many neurodegenerative states, including cerebral ischemia. Because microglial cells are both a major source of inducible nitric oxide synthase (iNOS)/nitric oxide (NO) production locally in the injured brain and are activated by NO‐mediated injury, we tested whether iNOS inhibition reduces microglial activation and ischemic injury in a neonatal focal ischemia‐reperfusion model. Post‐natal day 7 rats were subjected to a 2 h transient middle cerebral artery (MCA) occlusion. Pups with confirmed injury on diffusion‐weighted magnetic resonance imaging (MRI) during occlusion were administered 300 mg/kg/dose aminoguanidine (AG) or vehicle at 0, 4 and 18 h after reperfusion, and animals were killed at 24 or 72 h post‐reperfusion. The effect of AG on microglial activation as judged by the acquisition of ED1 immunoreactivity and proliferation of ED1‐positive cells, on activation of cell death pathways and on injury volume, was determined. The study shows that while AG attenuates caspase 3 and calpain activation in the injured tissue, treatment does not affect the rapidly occurring activation and proliferation of microglia following transient MCA occlusion in the immature rat, or reduce injury size.
Astrocyte control of fetal cortical neuron glutathione homeostasis: up‐regulation by ethanol
Authors: Rathinam Mary Latha , Watts Lora Talley , Stark Avishay A. , Mahimainathan Lenin , Stewart Jennifer , Schenker Steven , Henderson George I.
Published: February 2006

Ethanol increases apoptotic neuron death in the developing brain and at least part of this may be mediated by oxidative stress. In cultured fetal rat cortical neurons, Ethanol increases levels of reactive oxygen species (ROS) within minutes of exposure and reduces total cellular glutathione (GSH) shortly thereafter. This is followed by onset of apoptotic cell death. These responses to Ethanol can be blocked by elevating neuron GSH with N‐acetylcysteine or by co‐culturing neurons with neonatal cortical astrocytes. We describe here mechanisms by which the astrocyte‐neuron γ‐glutamyl cycle is up‐regulated by Ethanol, enhancing control of neuron GSH in response to the pro‐oxidant, Ethanol. Up to 6 days of Ethanol exposure had no consistent effects on activities of γ‐glutamyl cysteine ligase or glutathione synthetase, and GSH content remained unchanged (p < 0.05). However, glutathione reductase was increased with 1 and 2 day Ethanol exposures, 25% and 39% for 2.5 and 4.0 mg/mL Ethanol by 1 day, and 11% and 16% for 2.5 and 4.0 mg/mL at 2 days, respectively (p < 0.05). A 24 h exposure to 4.0 mg/mL Ethanol increased GSH efflux from astrosoyte up to 517% (p < 0.05). Ethanol increased both γ‐glutamyl transpeptidase expression and activity on astrocyte within 24 h of exposure (40%,p = 0.05 with 4.0 mg/mL) and this continued for at least 4 days of Ethanol treatment. Aminopeptidase N activity on neurons increased by 62% and 55% within 1 h of Ethanol for 2.5 and 4.0 mg/mL concentration, respectively (p < 0.05), remaining elevated for 24 h of treatment. Thus, there are at least three key points of the γ‐glutamyl cycle that are up‐regulated by Ethanol, the net effect being to enhance neuron GSH homeostasis, thereby protecting neurons from Ethanol‐mediated oxidative stress and apoptotic death.
Postsynaptic recruitment of Dendrin depends on both dendritic mRNA transport and synaptic anchoring
Authors: Kremerskothen Joachim , Kindler Stefan , Finger Indra , Veltel Stefan , Barnekow Angelika
Published: February 2006

Synaptic plasticity and memory formation involve remodeling of the postsynaptic cytoskeleton, a process that is in part based on both local translation of dendritic mRNAs and synaptic recruitment of newly synthesized proteins. The postsynaptic component Dendrin that is encoded by a dendritically localized mRNA is thought to modulate the structure of the synaptic cytoskeleton. However, molecular mechanisms that control extrasomatic Dendrin mRNA transport and postsynaptic protein recruitment are unknown. The data presented here reveal that Dendrin interacts with the cytoskeletal components α‐actinin and Maguk with inverted orientation (MAGI) or synaptic scaffolding molecule (S‐SCAM). The latter retains Dendrin in the cytoplasm of mammalian cells and prevents its nuclear import. Furthermore in neurons, postsynaptic clustering of Dendrin requires dendritic targeting of its messenger RNA (mRNA), a process that is mediated by a sequence motif within the 3′ untranslated region. In summary our finding suggest that postsynaptic recruitment of Dendrin appears to critically depend on both local protein synthesis and association with the synaptic scaffolding protein MAGI/S‐SCAM. Its nuclear localization capacity further points to a function in retrograde signaling from the synapse to the nucleus.
Syn‐deformational migmatites and magmatic‐arc metamorphism in the Xolapa Complex, southern Mexico
Authors: CORONA‐CHÁVEZ P. , POLI S. , BIGIOGGERO B.
Published: February 2006

The Xolapa Complex (XC) is the largest plutonic and metamorphic mid‐crustal basement unit in Mexico and represents an ancient continental magmatic‐arc. A complete range from metatexite to diatexite migmatitic structures has been produced during a single high‐grade metamorphic event. However, structural relics reveal the existence of early Cpx + Pl + Qtz ± Opx and Grt + Opx + Pl + Qtz ± Cpx pre‐migmatitic metamorphic assemblages. Field relationships and microstructural observations allow us to constrain five pre‐, syn‐ and post‐migmatitic deformational phases. It is argued that migmatitic structures and minor anatectic granites were developed during ductile recumbent folding and shear structures related to the D2–D3 phases. Late post‐migmatitic ductile‐brittle deformation is evidenced by the development of NNE trending transpressional thrusting (D4), and E–W left‐lateral mylonitic shear zones (D5). Biotite‐breakdown melting in felsic rocks and amphibole‐breakdown melting in mafic rocks, as well as geothermobarometric results, indicate that metamorphism took place at temperatures from 830 to 900 °C and pressures ranging from ≥6.3 to 9.5 kbar. Late migmatitic assemblages equilibrated in the highest temperature range along a clockwise P–T path. The relationships between the large diversity of migmatitic structures and the progressive production of melt suggest that feedback relations prevailed as a time‐marker during a contractional regime. Deformation, metamorphism, and plutonism of the XC show that this terrane evolved as a north‐east‐verging thrust system with synkinematic metamorphism and partial melting, during the Late Cretaceous – Palaeogene. The tectonothermal history of XC is analogous to a Cordilleran metamorphic magmatic‐arc formed in an accretionary tectonic framework. This new model provides constraints on the exhumation mechanism and thermal evolution of southern Mexico.
Age‐Dependent Relationships Among Pain, Depressive Symptoms, and Functional Disability in Youth With Recurrent Headaches
Authors: Lewandowski Amy S. , Palermo Tonya M. , Peterson Catherine C.
Published: February 2006

Objective.—To assess age differences associated with depressive symptoms and functional disability in children and adolescents with recurrent headache.

Background.—Research has indicated that psychological factors, especially depression, are related to the extent and nature of functional disability experienced from headaches. There is a lack of research examining how age impacts the relationship between pain, psychological factors, and activity restriction in children and adolescents with recurrent headache.

Methods.—Seventy‐seven participants from a pediatric neurology clinic completed self‐report measures of pain intensity, depressive symptoms, and functional disability.

Results.—Findings demonstrated a significant positive correlation between pain and functional disability, and depressive symptoms and functional disability for children. Correlations for adolescents failed to reach significance. Functional disability emerged as a mediator between headache pain and depressive symptoms for children but not for adolescents.

Conclusions.—Results indicate potentially important age differences when examining the impact of functional disability on depressive symptoms in this sample. Findings suggest that functional disability may contribute to depressive symptoms differently for children versus adolescents with recurrent headache. Age‐specific interventions that differentially focus on the specific roles that pain, depressive symptoms, and disability have for children and adolescents with recurrent headache may be warranted.
Acupuncture for Chronic Headaches—An Epidemiological Study
Authors: Melchart Dieter , Weidenhammer Wolfgang , Streng Andrea , Hoppe Andrea , Pfaffenrath Volker , Linde Klaus
Published: February 2006

Objective.—To investigate the characteristics and outcomes of patients undergoing acupuncture treatment for chronic headaches under conditions of routine care provided within the framework of statutory health insurance in Germany. Furthermore, we investigated correlations between different outcomes.

Patients and Methods.—Patients with migraine, episodic or chronic tension‐type headache (TTH), or several other forms of chronic headache (cluster, vascular, drug‐induced headache; other specific headaches) treated with acupuncture (mean number of sessions 8.6 ± 3.0) were included into an observational study. Detailed questionnaires including questions on headache days and instruments measuring disability (Pain Disability Index) and quality of life (SF‐36) were completed before treatment, after treatment, and at 6 months after inclusion.

Results.—A total of 2022 patients (732 with migraine, 351 with episodic and 440 with chronic TTHs, and 499 with other diagnoses) treated by 1418 physicians were included in the main analysis. Sociodemographic and baseline characteristics differed considerably in the four diagnostic groups. Statistically highly significant and clinically relevant improvements were seen for all clinical outcome measures in all diagnostic groups. In 52.6% of patients headache frequency decreased by at least 50% compared to baseline. The comparison of headache frequency, pain intensity, and generic outcome measures showed that some of these outcomes correlate only weakly.

Conclusions.—In this epidemiological study, headache patients reported clinically relevant improvements after receiving acupuncture. Randomized trials performed in parallel to this study confirm the relevant overall effect, however, the effect may largely be due to potent unspecific needling and placebo effects.