bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can the results of anorectal (abdominoperineal) resection be improved: are circumferential resection margins too often positive?
Authors: Radcliffe A. 
Published: February 2006

AbstractCarefully 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

AbstractIntroduction  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

AbstractObjective  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.
Knowledge in the Palm of your hands: PDAs in the clinical setting
Authors: Honeybourne Claire , Sutton Sarah , Ward Linda 
Published: February 2006

AbstractObjective:  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

AbstractObjective:  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

AbstractObjective:  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

AbstractObjectives:  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

AbstractObjective:  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

AbstractRats 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

AbstractThe 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

AbstractThe 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

AbstractThere 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

AbstractCyclic 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

AbstractMicroglial 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.