bluuebunny/crossref_metadata_2025 huggingface dataset:
Review article: future therapies for management of metastatic gastroenteropancreatic neuroendocrine tumours
Authors: SRIRAJASKANTHAN R. , TOUMPANAKIS C. , MEYER T. , CAPLIN M. E.
Published: March 2009

Background  Gastroenteropancreatic neuroendocrine tumours (GEP NETs) are relatively uncommon tumours that occur anywhere within the gastrointestinal tract. The prevalence of GEP NETs is estimated to be 35 per 100 000 population. Patients often present with metastatic disease and consequently, palliative treatments form the mainstay of therapy.

Aim  To review the current and novel therapeutic options for management of GEP NETs.

Methods  Searches for all studies related to GEP NETs, NETs and carcinoid tumours in Medline and abstracts from international meetings.

Results  Somatostatin analogues remain the first line therapy for management of symptoms of GEP NETs and may have anti‐proliferative action. New somatostatin analogues with different somatostatin receptor affinity have been developed. Radionuclide peptide receptor therapy is established in patients with positive somatostatin scintigraphy. A number of new agents and targeted therapies are currently being evaluated in a phase I and II studies and these include angiogenic inhibitors, mammalian target of rapamycin inhibitors and immune therapies.

Conclusions  A number of nonsurgical therapies are available for management of gastroenteropancreatic neuroendocrine tumours. It is hoped, the development of some of these promising novel therapies will expand the therapeutic armamentarium.
Clinical trial: factors associated with freedom from relapse of heartburn in patients with healed reflux oesophagitis ‐ results from the maintenance phase of the EXPO study
Authors: LABENZ J. , ARMSTRONG D. , ZETTERSTRAND S. , EKLUND S. , LEODOLTER A.
Published: March 2009

Background  Ability to predict freedom from heartburn relapse during maintenance therapy for healed reflux oesophagitis may facilitate optimal treatment choices for individual patients.

Aim  To determine factors predicting freedom from heartburn relapse during maintenance proton pump inhibitor therapy in patients with healed reflux oesophagitis.

Methods  This post‐hoc analysis used data from the maintenance phase of the EXPO study (AstraZeneca study code: SH‐NEG‐0008); 2766 patients with healed reflux oesophagitis and resolved heartburn received once‐daily esomeprazole 20 mg or pantoprazole 20 mg for 6 months. Multiple logistic regression analysis determined factors associated with freedom from heartburn relapse.

Results  Heartburn relapse rates were lower with esomeprazole than pantoprazole in all subgroups analysed. Esomeprazole treatment was the factor most strongly associated with freedom from heartburn relapse (odds ratio 2.08; P < 0.0001). Other factors significantly associated with freedom from heartburn relapse were Helicobacter pylori infection, greater age, non‐obesity, absence of epigastric pain at baseline, pre‐treatment nonsevere heartburn and GERD symptom duration ≤5 years.

Conclusions  Several factors predict freedom from heartburn relapse during maintenance proton pump inhibitor therapy for healed reflux oesophagitis, the strongest being choice of proton pump inhibitor. These findings outline the importance of optimizing acid control and identifying predictors of relapse for effective long‐term symptom management in reflux oesophagitis patients.
Tectonic vs. climate forcing in the Cenozoic sedimentary evolution of a foreland basin (Eastern Southalpine system, Italy)
Authors: Mancin N. , Di Giulio A. , Cobianchi M.
Published: March 2009

This paper discusses the Cenozoic interaction of regional tectonics and climate changes. These processes were responsible for mass flux from mountain belts to depositional basins in the eastern Alpine retro‐foreland basin (Venetian–Friulian Basin). Our discussion is based on the depositional architecture and basin‐scale depositional rate curves obtained from the decompacted thicknesses of stratigraphic units. We compare these data with the timing of tectonic deformation in the surrounding mountain ranges and the chronology of both long‐term trends and short‐term high‐magnitude (‘aberrant’) episodes of climate change. Our results confirm that climate forcing (and especially aberrant episodes) impacted the depositional evolution of the basin, but that tectonics was the main factor driving sediment flux in the basin up to the Late Miocene. The depositional rate remained below 0.1 mm year−1 on average from the Eocene to the Miocene, peaking at around 0.36 mm year−1, during periods of maximum tectonic activity in the eastern Southern Alps. This dynamic strongly changed during the Pliocene–Pleistocene, when the basin‐scale depositional rate increased to an average of 0.26 mm year−1 (Pliocene) and 0.73 mm year−1 (Pleistocene). This result fits nicely with the long‐term global cooling trend recorded during this time interval. Nevertheless, we note that the timing of the observed increase may be connected with the presumed onset of major glaciations in the southern flank of the Alps (0.7–0.9 Ma), the acceleration of the global cooling trend (since 3–4 Ma) and climate variability (in terms of magnitude and frequency). All these factors suggest that combined high‐frequency and high‐magnitude cooling–warming cycles are particularly powerful in promoting erosion in mid‐latitude mountain belts and therefore in increasing the sediment flux in foreland basins.
The imbalance between Survivin and Bim mediates tumour growth and correlates with poor survival in patients with multiple myeloma
Authors: Romagnoli Mathilde , Séveno Céline , Wuillème‐Toumi Soraya , Amiot Martine , Bataille Régis , Minvielle Stéphane , Barillé‐Nion Sophie
Published: March 2009

Survivin is selectively expressed in most of common human cancers and is now viewed as a potent modulator of the cell death/proliferation balance in tumour cells. We previously found that myeloma cells expressed high levels of Survivin protein in correlation with disease progression and that Survivin knock‐down by RNA interference decreased myeloma cell growth. We now demonstrate that Survivin overexpression promotes the proliferation and survival of human myeloma cells both in vitro and in vivo in the absence of their major growth factor, interleukin 6. Of particular interest, this effect correlates with the down regulation of Bim, a critical BH3‐only cell death activator during cytokine deprivation, mainly at transcriptional level. The tight link between Survivin and Bim expression, reported for the first time here in myeloma cells and in other cell lines, is further confirmed in a panel of newly diagnosed patients with myeloma, and BIRC5 is validated as a gene significantly associated with short survival in these patients. Altogether, our findings provide evidence that Survivin directly contributes to malignant progression of myeloma and strongly suggest that targeting Survivin may disrupt the delicate balance controlling cell survival and proliferation, opening new avenues for the therapy of this still difficult‐to‐treat cancer.
Methotrexate and aminopterin exhibit similar in vitro and in vivo preclinical activity against acute lymphoblastic leukaemia and lymphoma
Authors: Kang Min H. , Harutyunyan Narine , Hall Connor P. , Papa Rachael A. , Lock Richard B.
Published: March 2009

Due to the development of neurological toxicity and resistance to methotrexate (MTX), other antifolates have been evaluated for its potential replacement in the treatment of childhood acute lymphoblastic leukaemia (ALL). Aminopterin (AMT) has been suggested to provide clinical advantages over MTX and other antifolates. AMT activity, compared with MTX, was evaluated in ALL and lymphoma preclinical models. The minimum survival fraction at the range of concentrations tested was lower with AMT than with MTX in 3 out of 15 cell lines. Both AMT and MTX significantly extended the event‐free survival of mice bearing 3 out of 4 xenografts with equivalent activity.
MicroRNA‐27 enhances differentiation of myeloblasts into granulocytes by post‐transcriptionally downregulating Runx1
Authors: Feng Jue , Iwama Atsushi , Satake Masanobu , Kohu Kazuyoshi
Published: March 2009

We investigated the regulation of the transcription factor Runx1 by microRNA (miR)‐27 and the resulting effects upon the differentiation of myeloblasts into granulocytes. When 32D.cl3 cell differentiation was induced using granulocyte colony‐stimulating factor (CSF3), Runx1 transcription was moderately downregulated, while Runx1 protein levels were completely inhibited, suggesting an involvement of post‐transcriptional regulation. Simultaneously, levels of miR‐27 and its precursor increased substantially. Reporter assays revealed that miR‐27 targets the 3′UTR of the Runx1 transcript. Furthermore, introduction of pre‐miR‐27 alone into 32D.cl3 cells resulted in downregulation of Runx1 protein, thereby allowing the cell differentiation even in the absence of CSF3. Conversely, transduction of anti‐miR‐27 caused upregulation of Runx1 protein, thereby antagonizing the CSF3‐mediated granulocyte differentiation. Finally, the CSF3‐induced transcription factor C/EBPalpha enhanced transcription of a host gene of miR‐27, C9orf3, via activation of its promoter. Thus, miR‐27 enhances differentiation of myeloblasts into granulocytes via post‐transcriptional downregulation of Runx1.
Chronic rhinosinusitis with and without nasal polyps is associated with decreased expression of glucocorticoid‐induced leucine zipper
Authors: Zhang X‐H. , Lu X. , Long X‐B. , You X‐J. , Gao Q‐X. , Cui Y‐H. , Liu Z.
Published: March 2009

Background
Chronic rhinosinusitis without nasal polyps (CRSsNP) and with nasal polyps (CRSwNP) is characterized by persistent inflammation of sinonasal mucosa. Glucocorticoid‐induced leucine zipper (GILZ) is a recently described anti‐inflammatory mediator.

Objective
Here we analysed the expression of GILZ in CRSsNP and CRSwNP, its association with response to surgery, and its cytokine‐driven expression regulation in the upper airways.

Methods
The messenger RNA (mRNA) and protein expression of GILZ in 33 CRSsNP, 32 CRSwNP, and 11 control samples was assessed by means of a quantitative RT‐PCR and immunohistochemistry, respectively. Nasal explant culture was used to investigate the effect of IFN‐γ, IL‐4, IL‐13, IL‐1β, and TNF‐α on GILZ mRNA expression in normal sinonasal mucosa.

Results
The GILZ mRNA and protein expression was significantly suppressed in both CRSsNP and CRSwNP patients compared with controls. No significant difference in GILZ expression was found between CRSsNP and CRSwNP patients. Comparing patients responsive and patients recalcitrant to surgery, a significant further decrease of GILZ expression was found in recalcitrant patients both in the CRSsNP and in the CRSwNP group. IL‐1β, TNF‐α, IL‐4, and IL‐13 reduced, whereas IFN‐γ enhanced GILZ mRNA levels in the sinonasal mucosa.

Conclusion
Down‐regulated expression of GILZ may contribute to the pathogenesis of CRSsNP and CRSwNP and associate with response to surgery. GILZ expression in the upper airways can be regulated differentially by different cytokines.
Interleukin‐6 is essential for Staphylococcal exotoxin B‐induced T regulatory cell insufficiency in nasal polyps
Authors: Xu G. , Xia J. H , Zhou H. , Yu C. Z. , Zhang Y. , Zuo K. J. , Shi J. B. , Li H. B.
Published: March 2009

Background
The pathogenesis of nasal polyps is still unclear. There is increasing evidence indicating that Staphylococcal aureus (S. aureus) is associated with the formation of nasal polyps, but the mechanism has not been well documented to date.

Methods
We stimulated cultured nasal polyps and turbinate tissues with Staphylococcal exotoxin B (SEB), detected the expression of pro‐inflammatory cytokines (IL‐2, IL‐6, and IL‐8) and T cell cytokines (IFN‐γ, IL‐4, IL‐5, IL‐10, and IL‐17) in the supernatants, and evaluated mRNA expression (T‐bet, GATA‐3, Foxp3, and RORγt) and frequencies of CD4+CD25+ T regulatory cells (Tregs) in nasal tissues. We also evaluated the effects of blocking IL‐6 with monoclonal antibodies to T cell profiles in cultured nasal tissues stimulated by SEB.

Results
Levels of IL‐6, IFN‐γ and IL‐4 increased significantly in SEB‐stimulated nasal polyps. Meanwhile, mRNA expressions of T‐bet and GATA‐3 were significantly up‐regulated, while Foxp3 was inhibited and the frequencies of CD4+CD25+ Tregs were decreased after SEB stimulation. After blocking IL‐6, the levels of IL‐10 and Foxp3 mRNA, as well as the frequencies of CD4+CD25+ Tregs, were significantly increased, while IFN‐γ and IL‐4 production and the mRNA expression of T‐bet and GATA‐3 were significantly inhibited.

Conclusions
SEB is able to modulate pro‐inflammatory factors, T‐helper type 1/Th2 profiles and suppress Treg activity in cultured nasal polyps, which were rescued by blocking IL‐6 activity. Therefore, IL‐6 is essential for SEB‐induced Treg insufficiency in nasal polyps.
Responses of an araneophagic assassin bug, Stenolemus bituberus, to spider draglines
Authors: WIGNALL ANNE E. , TAYLOR PHILLIP W.
Published: March 2009

Abstract 1. Animals, as they move through their environment, leave traces of their passage that can be informative to others and convey significant advantages to the animal producing them. However, such traces may also reveal presence, location or identity to enemies.

2. We studied an araneophagic (‘spider‐eating’) assassin bug, Stenolemus bituberus (Heteroptera, Reduviidae), testing whether it associated with areas containing chemotactile traces (e.g. draglines, excreta) left behind by nine sympatric spider species. Stenolemus bituberus were presented with a choice between a substrate containing draglines and a clean substrate. Each hour, for a duration of 12 h, we recorded which substrate was occupied.

3. Stenolemus bituberus tended to associate especially with draglines left by spiders from the genus Achaearanea, their most common prey in nature.

4. These results suggest that S. bituberus exploits draglines from these spiders as cues for indicating prey presence. We also found an increasing tendency to associate with draglines from some spider species through the day, which may be related to circadian patterns or slower response times of some individuals.
Adaptive management of an environmental watering event to enhance native fish spawning and recruitment
Authors: KING A. J. , WARD K. A. , O’CONNOR P. , GREEN D. , TONKIN Z. , MAHONEY J.
Published: March 2009

1. A common goal of many environmental flow regimes is to maintain and/or enhance the river’s native fish community by increasing the occurrence of successful spawning and recruitment events. However, our understanding of the flow requirements of the early life history of fish is often limited, and hence predicting their response to specific managed flow events is difficult. To overcome this uncertainty requires the use of adaptive management principles in the design, implementation, monitoring and adjustment of environmental flow regimes.

2. The Barmah‐Millewa Forest, a large river red gum forest on the Murray River floodplain, south‐east Australia, contains a wide variety of ephemeral and permanent aquatic habitats suitable for fish. Flow regulation of the Murray River has significantly altered the natural flood regime of the Forest. In an attempt to alleviate some of the effects of river regulation, the Forest’s water regime is highly managed using a variety of flow control structures and also receives targeted Environmental Water Allocations (EWA). In 2005, the largest environmental flow allocated to date in Australia was delivered at the Forest.

3. This study describes the adaptive management approach employed during the delivery of the 2005 EWA, which successfully achieved multiple ecological goals including enhanced native fish spawning and recruitment. Intensive monitoring of fish spawning and recruitment provided invaluable real‐time and ongoing management input for optimising the delivery of environmental water to maximise ecological benefits at Barmah‐Millewa Forest and other similar wetlands in the Murray‐Darling Basin.

4. We discuss possible scenarios for the future application of environmental water and the need for environmental flow events and regimes to be conducted as rigorous, large‐scale experiments within an adaptive management framework.
Diversity patterns of stygobiotic crustaceans across multiple spatial scales in Europe
Authors: MALARD FLORIAN , BOUTIN CLAUDE , CAMACHO ANA I. , FERREIRA DAVID , MICHEL GEORGES , SKET BORIS , STOCH FABIO
Published: March 2009

1. Using species distribution data from 111 aquifers distributed in nine European regions, we examined the pairwise relationships between local species richness (LSR), dissimilarity in species composition among localities, and regional species richness (RSR). In addition, we quantified the relative contribution of three nested spatial units – aquifers, catchments and regions – to the overall richness of groundwater crustaceans.

2. The average number of species in karst and porous aquifers (LSR) varied significantly among regions and was dependent upon the richness of the regional species pool (RSR). LSR–RSR relationships differed between habitats: species richness in karstic local communities increased linearly with richness of the surrounding region, whereas that of porous local communities levelled off beyond a certain value of RSR.

3. Dissimilarity in species composition among aquifers of a region increased significantly with increasing regional richness because of stronger habitat specialisation and a decrease in the geographic range of species among karst aquifers. Species turnover among karst aquifers was positively related to RSR, whereas this relationship was not significant for porous aquifers.

4. The contribution of a given spatial unit to total richness increased as size of the spatial unit increased, although 72% of the overall richness was attributed to among‐region diversity. Differences in community composition between similar habitats in different regions were typically more pronounced than between nearby communities from different habitats.

5. We conclude by calling for biodiversity assessment methods and conservation strategies that explicitly integrate the importance of turnover in community composition and habitat dissimilarity at multiple spatial scales.
Restoring lakes by using artificial plant beds: habitat selection of zooplankton in a clear and a turbid shallow lake
Authors: SCHOU MAJBRITT OVERGÅRD , RISHOLT CASPER , LAURIDSEN TORBEN L. , SØNDERGAARD MARTIN , GRØNKJÆR PETER , JACOBSEN LENE , BERG SØREN , SKOV CHRISTIAN , BRUCET SANDRA , JEPPESEN ERIK
Published: March 2009

1. Return of large‐bodied zooplankton populations is of key importance for creating a shift from a turbid to a clear‐water state in shallow lakes after a nutrient loading reduction. In temperate lakes, recovery is promoted by submerged macrophytes which function as a daytime refuge for large zooplankton. However, recovery of macrophytes is often delayed and use of artificial plant beds (APB) has been suggested as a tool to enhance zooplankton refuges, thereby reinforcing the shift to a clear‐water state and, eventually, colonisation of natural plants.

2. To further evaluate the potential of APB in lake restoration, we followed the day–night habitat choices of zooplankton throughout summer in a clear and a turbid lake. Observations were made in the pelagic and littoral zones and in APB in the littoral representing three different plant densities (coverage 0%, 40% and 80%).

3. In the clear lake, the zooplankton (primarily Daphnia) were mainly found in the pelagic area in spring, but from mid‐May they were particularly abundant in the APB and almost exclusively so in mid‐June and July, where they appeared in extremely high densities during day (up to 2600 ind. L−1). During night Daphnia densities were overall more equally distributed between the five habitats. Ceriodaphnia was proportionally more abundant in the APB during most of the season. Cyclopoids were more abundant in the high APB during day but were equally distributed between the five habitats during night.

4. In the turbid lake, however, no clear aggregation was observed in the APB for either of the pelagic genera (Daphnia and Bosmina). This may reflect a higher refuge effect in the open water due to the higher turbidity, reduced ability to orient to plant beds and a significantly higher fish density (mainly of roach, Rutilus rutilus, and perch, Perca fluviatilis) in the plant beds than in the clear lake. Chydorus was found in much higher proportions among the plants, while cyclopoids, particularly the pelagic Cyclops vicinus, dominated in the pelagic during day and in the pelagic and high density plants during night.

5. Our results suggest that water clarity is decisive for the habitat choice of large‐bodied zooplankton and that introduction of APB as a restoration measure to enhance zooplankton survival is only a useful tool when water clarity increases following loading reduction. Our results indicate that dense APB will be the most efficient.
A comparison of bacteria and benthic invertebrates as indicators of ecological health in streams
Authors: LEAR G. , BOOTHROYD I. K. G. , TURNER S. J. , ROBERTS K. , LEWIS G. D.
Published: March 2009

1. We set out to evaluate the reliability of bacterial communities as an indicator of freshwater ecological health.

2. Samples of epilithic biofilm were taken over a 1‐year period from four streams, each impacted by varying degrees of human modification. The bacteria within each sample were characterised using a whole community DNA fingerprinting technique (automated ribosomal intergenic spacer analysis). Spatial and temporal differences in community structure between samples were visualised using multi‐dimensional scaling and quantified using permutational multivariate anova. Macrobenthic invertebrates, which are commonly used as indicators of stream ecological health, were also sampled for comparison.

3. Multivariate analysis revealed a clear gradient in macroinvertebrate community structure between sites exposed to increased human impact. Bacterial communities, however, could only distinguish the most impacted site from the remainder.

4. Additional research is required to increase the sensitivity of bacterial community analyses before endorsing their use as an indicator of freshwater ecological health.
TGF‐β1 dampens the susceptibility of dendritic cells to environmental stimulation, leading to the requirement for danger signals for activation
Authors: Ohtani Tomoyuki , Mizuashi Masato , Nakagawa Satoshi , Sasaki Yoshinori , Fujimura Taku , Okuyama Ryuhei , Aiba Setsuya
Published: March 2009

In contrast to its favourable effects on Langerhans cell (LC) differentiation, transforming growth factor (TGF)‐β1 has been reported to prevent dendritic cells from maturing in response to tumour necrosis factor (TNF)‐α, interleukin (IL)‐1β, or lipopolysaccharide (LPS). We first characterized the effects of TGF‐β1 on dendritic cell function by testing the response of TGF‐β1‐treated monocyte‐derived dendritic cells (MoDCs) to maturation stimuli that LCs receive in the epidermis, namely, haptens, ATP and ultraviolet (UV). TGF‐β1 treatment, which augmented E‐cadherin and down‐regulated dendritic cell‐specific ICAM3‐grabbing non‐integrin on MoDCs, significantly suppressed their CD86 expression and hapten‐induced expression of IL‐1β and TNF‐α mRNA and protein. As TGF‐β1‐treated MoDCs lacked Langerin expression, we demonstrated the suppressive effects of TGF‐β1 on haematopoietic progenitor cell‐derived dendritic cells expressing both CD1a and Langerin. These suppressive effects of TGF‐β1 increased with the duration of treatment. Furthermore, TGF‐β1‐treated MoDCs became resistant to apoptosis/necrosis induced by high hapten, ATP or UV doses. This was mainly attributable to dampened activation of p38 mitogen‐activated protein kinase (MAPK) in TGF‐β1‐treated MoDCs. Notably, although ATP or hapten alone could only induce CD86 expression weakly and could not augment the allogeneic T‐cell stimulatory function of TGF‐β1‐treated MoDCs, ATP and hapten synergized to stimulate these phenotypic and functional changes. Similarly, 2,4‐dinitro, 1‐chlorobenzene (DNCB) augmented the maturation of TGF‐β1‐treated MoDCs upon co‐culture with a keratinocyte cell line, in which ATP released by the hapten‐stimulated keratinocytes synergized with the hapten to induce their maturation. These data may suggest that TGF‐β1 protects LCs from being overactivated by harmless environmental stimulation, while maintaining their ability to become activated in response to danger signals released by keratinocytes.
New dimensions in endodontic imaging: Part 2. Cone beam computed tomography
Authors: Patel S.
Published: March 2009

Cone beam computed tomography (CBCT) has been specifically designed to produce undistorted three‐dimensional information of the maxillofacial skeleton, including the teeth and their surrounding tissues with a significantly lower effective radiation dose compared with conventional computed tomography (CT). Periapical disease may be detected sooner using CBCT compared with periapical views and the true size, extent, nature and position of periapical and resorptive lesions can be assessed. Root fractures, root canal anatomy and the nature of the alveolar bone topography around teeth may be assessed. The aim of this paper is to review current literature on the applications and limitations of CBCT in the management of endodontic problems.
Canal transportation and centring ability of RaCe rotary instruments
Authors: Pasternak‐Júnior B. , Sousa‐Neto M. D. , Silva R. G.
Published: March 2009

Aim  Evaluate, through computerized tomography, canal transportation and centring ability of RaCe rotary instruments after preparation of mesiobuccal root canals in maxillary molar teeth.

Methodology  Twenty‐seven teeth were submitted to three cone beam tomographic analyses, one preoperatively, and two after preparation with file size 35, .02 taper and size 50, .02 taper. Canal transportation and centring ability were measured with reference to the distance between the noninstrumented portion of the root canals and the mesial and distal periphery of the root, compared with images obtained after the preparation with size 35 and 50 instruments.

Results  Canal transportation after preparation with the size 35 file was 0.030 ± 0.253 mm and after the size 50 file was 0.057 ± 0.317 mm. The centring ratio values after preparation with the size 35 file was 0.42 ± 0.32 and after the size 50 file was 0.54 ± 0.29, with no significant statistical difference between the groups.

Conclusions  RaCe instruments allowed the preparation of curved root canals with preparation diameters larger than those normally used with minimal canal transportation and adequate centring ability.
Nurse‐led vs. conventional physician‐led follow‐up for patients with cancer: systematic review
Authors: Lewis Ruth , Neal Richard D. , Williams Nefyn H. , France Barbara , Wilkinson Clare , Hendry Maggie , Russell Daphne , Russell Ian , Hughes Dyfrig A. , Stuart Nicholas S.A. , Weller David
Published: March 2009

Title.  Nurse‐led vs. conventional physician‐led follow‐up for patients with cancer: systematic review.

Aim.  This paper is a report of a systematic review of the effectiveness and cost‐effectiveness of nurse‐led follow‐up for patients with cancer.

Background.  As cancer survivorship increases, conventional follow‐up puts a major burden on outpatient services. Nurse‐led follow‐up is a promising alternative.

Data sources.  Searches were conducted covering a period from inception to February 2007 of 19 electronic databases, seven online trial registries, five conference proceedings reference lists of previous reviews and included studies.

Review methods.  Standard systematic review methodology was used. Comparative studies and economic evaluations of nurse‐led vs. physician‐led follow‐up were eligible. Studies comparing different types of nurse‐led follow‐up were excluded. Any cancer was considered; any outcome measure included.

Results.  Four randomised controlled trials were identified, two including cost analyses. There were no statistically significant differences in survival, recurrence or psychological morbidity. One study showed better HRQL measures for nurse‐led follow‐up, but one showed no difference, two showed a statistically significant difference for patient satisfaction, but two did not. Patients with lung cancer were more satisfied with nurse‐led telephone follow‐up and more were able to die at home. Patients with breast cancer thought patient‐initiated follow‐up convenient, but found conventional follow‐up more reassuring. One study showed the cost of nurse‐led follow‐up to be less than that of physician‐led follow‐up, but no statistical comparison was made.

Conclusion.  Patients appeared satisfied with nurse‐led follow‐up. Patient‐initiated or telephone follow‐up could be practical alternatives to conventional care. However, well‐conducted research is needed before equivalence to physician‐led follow‐up can be assured in terms of survival, recurrence, patient well‐being and cost‐effectiveness.
Support for family carers of children and young people with developmental disabilities and challenging behaviour: what stops it being helpful?
Authors: Wodehouse G. , McGill P.
Published: March 2009

Background  Many family carers find the support they receive in respect of their child's challenging behaviour unhelpful. This study sought to identify carer perceptions of the ways in which support is unhelpful and how it could be more helpful.

Methods  Thirteen mothers, caring for a child with intellectual disability and challenging behaviour, were interviewed. Parental perceptions and concerns regarding support received were investigated. Transcribed interviews were analysed using interpretive phenomenological analysis.

Results  Parents reported problems with generic disability services including accessing good services, obtaining relevant information, working relationships with professionals and issues with respite provision. Concerns were also expressed about challenging behaviour‐specific provision including ineffective strategies being suggested, an apparent lack of expertise, insufficient input and their child's exclusion from services.

Conclusions  More preventative approaches, more widespread adoption of effective behaviour management and improved partnership between professionals and families appear needed. Increasing family support may be ineffective if not accompanied by greater insight into the factors related to effectiveness and recognition of the role of informal support.
The influence of North American Aboriginal ethnicity on pro‐inflammatory and anti‐inflammatory cytokine responses to IFN‐alpha
Authors: Rempel J. D. , Aborsangaya K. B. , Alphonse M. P. , Minuk G. Y.
Published: March 2009

Summary.  North American Aboriginals have an enhanced propensity to clear HCV infection. Interferon (IFN)‐α is a critical agent in the clearance of hepatitis C virus (HCV) and other viruses; therefore the influence of Aboriginal ethnicity on IFN‐α responses was investigated in healthy Caucasian population control and Aboriginal cohorts. Cohort peripheral blood mononuclear cells produced similar levels of IFN‐α upon culture with reovirus, an innocuous virus capable of triggering IFN‐α synthesis. In addition, similar IFN‐γ synthesis was observed in the presence IFN‐α or reovirus. In contrast, Caucasian supernatants exhibited greater IL‐10 levels (P < 0.005), contributing to the overall cytokine balance as assessed by IFN‐γ/IL‐10 ratios being consistently elevated in the Aboriginal cohort. The potential of HCV proteins to alter IFN‐α cytokine induction was also investigated. Although there was some indication that HCV proteins might increase IFN‐α induced IL‐10 synthesis in Caucasians and conversely, IFN‐γ synthesis in Aboriginals, the addition of HCV proteins did not influence IFN‐γ/IL‐10 ratios. Finally, signal transducer and activator of transcription (STAT) 3 nuclear translocation was examined by western blot because it is a required intermediate in IFN‐α induced IL‐10 synthesis. Supporting the differential IL‐10 production, IFN‐α and core synergistically enhanced STAT3 nuclear translocation in Caucasian (P < 0.05); whereas, nuclear translocation of STAT3 remained unchanged in Aboriginal cells. Taken together, these findings suggest that ethnicity may influence certain responses to IFN‐α, possibly even in the presence of viral agents. These differences could impact early immune events allowing for enhanced viral clearance in Aboriginal populations.
Optimizing analysis of stable isotope breath tests to estimate gastric emptying of solids
Authors: Odunsi S. T. , Camilleri M. , Szarka L. A. , Zinsmeister A. R.
Published: March 2009

Abstract  Breath tests (BT) using 13C–substrates have been proposed for the measurement of gastric emptying (GE). The mathematical analysis of the breath 13CO2 excretion that most accurately predicts GE t1/2 from simultaneous scintigraphy is unresolved. To compare five mathematical methods to estimate GE t1/2 by BT with t1/2 from simultaneous scintigraphy. Data acquired from a dual‐labelled solid–liquid meal containing 99mTc sulphur colloid and 13C‐Spirulina platensis from 57 healthy volunteers were used to compare four mathematical methods reported in the literature [Ghoos method; generalized linear regression (Viramontes); linear regression (Szarka); Wagner–Nelson method] and the total cumulative breath 13CO2 excretion with ≥12 breath samples collected over at least 4 h. The concordance correlation coefficient (CCC) for the t1/2 results obtained with each method using BT data was compared with the results obtained with scintigraphy. The linear regression and generalized linear regression methods used five samples at 45, 90, 120, 150 and 180 min. All methods, except for the Wagner–Nelson method, resulted in mean GE t1/2 that approximated t1/2 obtained with scintigraphy. The highest CCC was observed with the linear regression method. Simple cumulative excretion of breath 13CO2 provides a better CCC than the Ghoos method. The linear regression and generalized linear regression methods (which also require relatively few breath samples) provide the most accurate analyses of breath 13CO2 excretion in stable isotope GEBT.
Age‐dependent association of idiopathic achalasia with vasoactive intestinal peptide receptor 1 gene
Authors: Paladini F. , Cocco E. , Cascino I. , Belfiore F. , Badiali D. , Piretta L. , Alghisi F. , Anzini F. , Fiorillo M. T. , Corazziari E. , Sorrentino R.
Published: March 2009

Abstract  Idiopathic achalasia is a rare disorder of the oesophagus of unknown aetio‐pathogenesis characterized by a myenteric inflammation, aperistalsis and insufficient lower oesophageal sphincter relaxation. Vasoactive intestinal peptide (VIP), present in the myenteric plexus, is involved in smooth muscle relaxation and acts as an anti‐inflammatory cytokine. The human VIP receptor 1 gene (VIPR1) is highly polymorphic and may play a role in idiopathic achalasia. One hundred and four consecutive patients and 300 random controls from the same geographic area were typed for five SNPs mapping in the VIPR1 gene. Patients with idiopathic achalasia show a significant difference in allele, genotype and phenotype distribution of SNP rs437876 mapping in intron 4. This association, however, was almost entirely due to the group of patients with late disease onset (P = 0.0005). These results strongly suggest that idiopathic achalasia is a heterogeneous disease with a different aetiology in cases with early or late disease onset.
Evaluation of the Kudoh swab method for the culturing of Mycobacterium tuberculosis in rural areas
Authors: Jaspe Rossana C. , Rojas Yeimy M. , Flores Lalis A. , Sofia Toro E. , Takiff Howard , De Waard Jacobus H.
Published: March 2009

Objective  To compare the simple, swab ‘Kudoh method’ for culturing Myobacterium tuberculosis from sputum samples, to the standard Petroff digestion‐decontamination procedure. The Kudoh method, which requires no centrifugation and takes only 4–5 min per sample, was also evaluated for its performance in a rural setting.

Methods  Two hospital laboratories in Caracas, Venezuela processed 314 sputum samples, in parallel, with both methods. Separately, sputum specimens were cultured with the Kudoh swab method in a field environment with minimal laboratory facilities.

Results  In the hospital laboratories, the sensitivity of the Kudoh swab method was comparable to that of the standard Petroff culture procedure. The swab method also performed satisfactorily in the field, improving the diagnostic sensitivity by 21% over microscopic examination alone.

Conclusion  The Kudoh swab method is an acceptable alternative for culturing mycobacteria that is particularly suitable for rural laboratories lacking adequate infrastructure for the Petroff method.
Serum lipid profile: a predictor of clinical outcome in dengue infection
Authors: Suvarna Jyoti Chandrashekar , Rane Pankaj P
Published: March 2009

Objectives  To correlate serum lipoproteins levels with dengue severity, clinical outcome (patient survival), bleeding severity, capillary leakage, supportive care requirement and hospital stay duration.

Methods  Single centre, prospective study. Setting: Tertiary care hospital. Subjects: 50 (1 month–18 years) dengue fever cases and 50 age and sex matched non‐febrile controls. Methods: patients were classified (WHO criteria) as dengue fever (DF), dengue haemorrhagic fever (DHF), dengue shock syndrome (DSS). Bleeding score; serum triglyceride, cholesterol, HDL, LDL and VLDL was determined. Statistical analysis was done using Chi‐squared test with continuity correction, Unpaired t‐test, anova with post hoc test, Binary logistic and multinomial regression.

Results  18 (36%) patients were DF, 19 (38%) DHF and 13 (26%) DSS. Lowest cholesterol, VLDL levels seen in DSS and highest in DF. Mean cholesterol level is significantly lower in expired patients and patients with third spacing. Severe bleeding significantly correlated with cholesterol level and hepatic dysfunction but not with platelet count or coagulopathy. Duration of intravenous fluid requirement and packed cell requirement negatively correlated with HDL and cholesterol levels. Fresh frozen plasma requirement negatively correlated with TG, HDL, VLDL and cholesterol levels. Platelet transfusion requirement and duration of hospital stay did not correlate with lipid levels. Intensive care and ventilator requirement negatively correlated with cholesterol level; inotrope requirement negatively correlated with HDL level. Ventilator requirement correlated negatively with TG levels also.

Conclusions  Lipid profile changes accompany dengue infection, some of which may indicate severity and guide therapy.
The nature of resistance to Dectes texanus (Col., Cerambycidae) in wild sunflower, Helianthus annuus
Authors: Michaud J. P. , Grant A. K.
Published: March 2009

The longhorned beetle Dectes texanus LeConte is a serious pest of cultivated sunflowers, Helianthus annuus L. and soybeans, Glycine max (L.), throughout much of the American midwest. Significant yield losses arise from the pre‐harvest lodging of plants when mature larvae girdle the base of stalks in preparation for overwintering. We investigated possible reasons why infestation of wild H. annuus by D. texanus is remarkably rare, whereas 80–90% of plants may be infested in fields of cultivated varieties. When caged on wild sunflower plants in the field, laboratory‐reared, gravid females fed less and made significantly fewer ovipositional punctures than they did when subsequently caged on a cultivated plant. Furthermore, only 18.4% of ovipunctures in wild plants resulted in an egg being laid, compared with 44.9% in cultivated plants, suggesting that additional resistance factors reduce the probability of eggs being laid during ovipositor insertion. Female behaviour was not affected by adult diet prior to testing (wild vs. cultivated H. annuus petioles), nor was there any difference in response between females obtained as larvae from cultivated sunflower or from soybean. Petioles of wild H. annuus exuded more than four times the weight of resinous material when severed as did those of cultivated plants, were significantly less succulent as determined by water content, and required significantly more force to penetrate the epidermis in a standardized puncture test. We conclude that a combination of physical and chemical properties of wild H. annuus confers substantial resistance to oviposition by D. texanus and that this natural antixenosis has been inadvertently diminished in the course of breeding cultivated varieties.
Pea weevil, Bruchus pisorum L. (Coleoptera: Bruchidae), resistance in Pisum sativum×Pisum fulvum interspecific crosses
Authors: Clement S. L. , McPhee K. E. , Elberson L. R. , Evans M. A.
Published: March 2009

The pea weevil, Bruchus pisorum (L.), is one of the most intractable pest problems of cultivated pea, Pisum sativum L., in the world. This study investigated the transfer of pea weevil resistance from two accessions (PI 595946, PI 343955) of wild pea, Pisum fulvum Sibth. & Sm., to interspecific populations derived from crossing these accessions with a weevil‐susceptible pea cultivar (‘Alaska 81’). Partial life tables characterized weevil stage‐specific mortality and survivorship on parents and interspecific progeny in two glasshouse trials. Larval mortality rates on pods (F3 plants) of several F2:3 families were between 36.0% and 52.9%. These means were statistically similar to mean mortality rates on pods of resistant parents (45.4% and 46.2%), but significantly greater than mean rates on the susceptible parent (1.2% and 10.6%). Pod surface characteristics contributed to high neonate larval mortality on pods of resistant parents and interspecific progeny. Seed resistance was not broadly transferred to interspecific progeny [revealed by high weevil survivorship in seeds (means mostly >80%) and high seed damage ratings of 3–5 where ratings of 1–2 denote resistance (production of resistant seed averaged 4.2% to 22.8%)]. Estimates of total weevil mortality on pods and seeds of eight F2:3 families were 50–70%. Thus, weevil resistance in the Pisum secondary gene pool can be transferred to interspecific progeny, thereby providing a potential avenue to develop weevil‐resistant pea cultivars.
EFFECTS OF THORACIC EPIDURAL ANAESTHESIA ON CARDIAC REPOLARIZATION
Authors: Owczuk Radoslaw , Steffek Mariusz , Wujtewicz Magdalena A , Szymanowicz Wiktor , Twardowski Pawel , Marjanski Tomasz , Wojciechowski Jacek , Zienciuk Agnieszka , Rzyman Witold , Wujtewicz Maria
Published: March 2009

Prolongation of the QT interval is associated with a risk of life‐threatening cardiac arrhythmias. In the present study, we examined whether reversible blockade of preganglionic sympathetic fibres of the heart, achieved by thoracic epidural anaesthesia, affects cardiac repolarization and thus confers an anti‐arrhythmic effect.

Fifty‐two men, aged between 28 and 65 years, were included in the study: 28 were patients scheduled for thoracic epidural anaesthesia (Group T) and 24 were patients scheduled for lumbar epidural anaesthesia (Group L). Epidural blockade was achieved with 0.5% isobaric bupivacaine solution. Measurements were taken from electrocardiogram fragments obtained before epidural anaesthesia and after detection of blockade (T1 or T8 segment sensory block in Groups T and L, respectively). Correction of the QT interval was calculated using Bazett's formula (QTcb), Fridericia's correction (QTcf) and the Framingham formula (QTcF). Transmural dispersion of repolarization (TDR) was determined using the Tpeak – Tend time, where Tpeak is the peak of the T wave and Tend is the end of the T wave.

Significant shortening of the QTcb interval and TDR was detected after blockade in Group T. However, there were no changes in the ECG parameters in Group L.

In conclusion, reversible blockade of preganglionic sympathetic fibres to the heart, achieved by thoracic epidural anaesthesia, results in a reduction in QTcb, as well as the TDR. These changes may explain the anti‐arrhythmic action seen with central blockade.
CHROMIUM PICOLINATE INHIBITS RESISTIN SECRETION IN INSULIN‐RESISTANT 3T3‐L1 ADIPOCYTES VIA ACTIVATION OF AMP‐ACTIVATED PROTEIN KINASE
Authors: Wang Yi‐Qun , Dong Yi , Yao Ming‐Hui
Published: March 2009

Chromium picolinate (CrPic) has been recommended as an alternative therapeutic regimen for Type 2 diabetes mellitus (T2DM). However, the molecular mechanism underlying the action of CrPic is poorly understood.

Using normal and insulin‐resistant 3T3‐L1 adipocytes, we examined the effects of CrPic on the gene transcription and secretion of adiponectin and resistin. In addition, using immunoblotting, ELISA and real‐time reverse transcription–polymerase chain reaction (RT‐PCR), we investigated the effects of 10 nmol/L CrPic for 24 h on AMP‐activated protein kinase (AMPK) to determine whether this pathway contributed to the regulation of adiponectin and resistin expression and secretion.

Chromium picolinate did not modulate the expression of adiponectin and resistin; however, it did significantly inhibit the secretion of resistin, but not adiponectin, by normal and insulin‐resistant 3T3‐L1 adipocytes in vitro. Furthermore, although CrPic markedly elevated levels of phosphorylated AMPK and acetyl CoA carboxylase in 3T3‐L1 adipocytes, it had no effect on the levels of AMPK α‐1 and α‐2 mRNA transcripts. Importantly, inhibition of AMPK by 2 h pretreatment of cells with 20 µmol/L compound C completely abolished the CrPic‐induced suppression of resistin secretion.

In conclusion, the data suggest that CrPic inhibits resistin secretion via activation of AMPK in normal and insulin‐resistant 3T3‐L1 adipocytes.
HYPOXIA‐INDUCIBLE FACTOR‐1 IMPROVES THE ACTIONS OF POSITIVE INOTROPIC AGENTS IN STUNNED CARDIAC MYOCYTES
Authors: Tan Tao , Luciano Jason A , Scholz Peter M , Weiss Harvey R
Published: March 2009

In the present study, we tested hypothesis that upregulation of hypoxia‐inducible factor‐1 (HIF‐1) would improve the actions of positive inotropic agents in cardiac myocytes after simulated ischaemia–reperfusion (I/R).

Hypoxia‐inducible factor‐1α was upregulated with deferoxamine (150 mg/kg per day for 2 days). Rabbit cardiac myocytes were subjected to simulated ischaemia (15 min, 95% N2–5% CO2) and reperfusion (re‐oxygenation) and compared with control myocytes. Cell contraction and calcium transients were measured at baseline and after forskolin (10−7 and 10−6 mol/L) or ouabain (10−5 and 10−4 mol/L).

Under control conditions, high‐dose forskolin and ouabain increased percentage shortening by 20 and 18%, respectively. Deferoxamine‐treated control myocytes responded similarly. In stunned myocytes, forskolin and ouabain did not significantly increase shortening (increases of 8% and 9%, respectively). Deferoxamine restored the effects of forskolin (+26%) and ouabain (+28%) in stunning. The results for maximum shortening and relaxation rates were similar. The increased calcium transients caused by forskolin and ouabain were also depressed in stunned myocytes, but were maintained by HIF‐1 upregulation.

These results suggest that simulated I/R impaired the functional and calcium transient effects of positive inotropic agents. Upregulation of HIF‐1 protects cardiac myocyte function after I/R by maintaining calcium release.