bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharicin B stabilizes retinoic acid receptor-α and presents synergistic differentiation induction with ATRA in myeloid leukemic cells
Authors: Gu Zhi-Min , Wu Ying-Li , Zhou Mei-Yi , Liu Chuan-Xu , Xu Han-Zhang , Yan Hua , Zhao Yong , Huang Ying , Sun Han-Dong , Chen Guo-Qiang
Published: August 2010

All-trans retinoic acid (ATRA), a natural ligand for the retinoic acid receptors (RARs), induces clinical remission in most acute promyelocytic leukemia (APL) patients through the induction of differentiation and/or eradication of leukemia-initiating cells. Here, we identify a novel natural ent-kaurene diterpenoid derived from Isodon pharicus leaves, called pharicin B, that can rapidly stabilize RAR-α protein in various acute myeloid leukemic (AML) cell lines and primary leukemic cells from AML patients, even in the presence of ATRA, which is known to induce the loss of RAR-α protein. Pharicin B also enhances ATRA-dependent the transcriptional activity of RAR-α protein in the promyelocytic leukemia–RARα–positive APL cell line NB4 cells. We also showed that pharicin B presents a synergistic or additive differentiation-enhancing effect when used in combination with ATRA in several AML cell lines and, especially, some primary leukemic cells from APL patients. In addition, pharicin B can overcome retinoid resistance in 2 of 3 NB4-derived ATRA-resistant subclones. These findings provide a good example for chemical biology–based investigations of pathophysiological and therapeutic significances of RAR-α and PML-RAR-α proteins. The effectiveness of the ATRA/pharicin B combination warrants further investigation on their use as a therapeutic strategy for AML patients.
Glucocorticoid treatment skews human monocyte differentiation into a hemoglobin-clearance phenotype with enhanced heme-iron recycling and antioxidant capacity
Authors: Vallelian Florence , Schaer Christian A. , Kaempfer Theresa , Gehrig Peter , Duerst Elena , Schoedon Gabriele , Schaer Dominik J.
Published: August 2010

Glucocorticoids are used extensively to treat autoimmune hemolytic anemias. Some beneficial effects of glucocorticoid pulse therapy have also been reported in sickle cell disease and paroxysmal nocturnal hemoglobinuria. Based on established concepts of hemoglobin (Hb) toxicity and physiologic Hb scavenger systems, we evaluated whether glucocorticoids could support an adaptive response to extracellular Hb independently of their immunosuppressive activities. Using global proteome and transcriptome analysis with mass-spectrometry (isobaric tag for relative and absolute quantitation and liquid chromatography-mass spectrometry) and gene-array experiments, we found that glucocorticoid treatment in vitro and in patients on glucocorticoid-pulse therapy polarized monocytes into a M2/alternatively activated phenotype with high Hb-scavenger receptor (CD163) expression and enhanced Hb-clearance and detoxification capability. Monocytes concurrently exposed to the interactive activity of glucocorticoids and extracellular Hb were characterized by high expression of a group of antioxidant enzymes known to be regulated by the conserved oxidative response transcription factor nuclear factor E2-related factor. Further, suppressed transferrin receptor, together with high ferroportin expression, pointed to a shift in iron homeostasis directed toward an increased cellular export of heme-derived iron. Therefore, stimulating Hb-endocytosis by CD163 and enhancing antioxidative homeostasis and iron recycling may be an essential activity of glucocorticoids that helps alleviate the adverse effects of extracellular Hb.
Endothelial-derived PDGF-BB and HB-EGF coordinately regulate pericyte recruitment during vasculogenic tube assembly and stabilization
Authors: Stratman Amber N. , Schwindt Amy E. , Malotte Kristine M. , Davis George E.
Published: August 2010

Recently, we reported a novel system whereby human pericytes are recruited to endothelial cell (EC)–lined tubes in 3-dimensional (3D) extracellular matrices to stimulate vascular maturation including basement membrane matrix assembly. Through the use of this serum-free, defined system, we demonstrate that pericyte motility within 3D collagen matrices is dependent on the copresence of ECs. Using either soluble receptor traps consisting of the extracellular ligand-binding domains of platelet-derived growth factor receptor β, epidermal growth factor receptor (EGFR), and ErbB4 receptors or blocking antibodies directed to platelet-derived growth factor (PDGF)–BB, or heparin-binding EGF-like growth factor (HB-EGF), we show that both of these EC-derived ligands are required to control pericyte motility, proliferation, and recruitment along the EC tube ablumenal surface. Blockade of pericyte recruitment causes a lack of basement membrane matrix deposition and, concomitantly, increased vessel widths. Combined inhibition of PDGF-BB and HB-EGF–induced signaling in quail embryos leads to reduced pericyte recruitment to EC tubes, decreased basement membrane matrix deposition, increased vessel widths, and vascular hemorrhage phenotypes in vivo, in support of our findings in vitro. In conclusion, we report a dual role for EC-derived PDGF-BB and HB-EGF in controlling pericyte recruitment to EC-lined tubes during developmental vascularization events.
Involvement of TIP60 acetyltransferase in intracellular Salmonellareplication
Authors: Wang Xueqin , Li Dongju , Qu Di , Zhou Daoguo
Published: August 2010

Background

Salmonella enterica is a facultative intracellular pathogen that replicates within a membrane-bound compartment termed Salmonella containing vacuole (SCV). The biogenesis of SCV requires Salmonella type III protein secretion/translocation system and their effector proteins which are translocated into host cells to exploit the vesicle trafficking pathways. SseF is one of these effectors required for SCV formation and Intracellular Salmonella replication through unknown mechanisms.

Results

In an attempt to identify host proteins that interact with SseF, we conduct a yeast two-hybrid screening of human cell cDNA library using SseF as the bait. We identified that TIP60, an acetyltransferase, interacts with SseF. We showed that the TIP60 acetylation activity was increased in the presence of SseF, and TIP60 was upregulated upon Salmonella infection. In addition, TIP60 is required for efficient intracellular Salmonella replication in macrophages.

Conclusion

Taken together, our data suggest that Salmonella may use SseF to exploit the host TIP60 acetyltransferase activity to promote efficient Salmonella replication inside host cells.
Domestic water carrying and its implications for health: a review and mixed methods pilot study in Limpopo Province, South Africa
Authors: Geere Jo-Anne L , Hunter Paul R , Jagals Paul
Published: August 2010

Background

Lack of access to safe water remains a significant risk factor for poor health in developing countries. There has been little research into the health effects of frequently carrying containers of water. The aims of this study were to better understand how domestic water carrying is performed, identify potential health risk factors and gain insight into the possible health effects of the task.

Methods

Mixed methods of data collection from six were used to explore water carrying performed by people in six rural villages of Limpopo Province, South Africa. Data was collected through semi-structured interviews and through observation and measurement. Linear regression modelling were used to identify significant correlations between potential risk factors and rating of perceived exertion (RPE) or self reported pain. Independent t-tests were used to compare the mean values of potential risk factors and RPE between sub-groups reporting pain and those not reporting pain.

Results

Water carrying was mainly performed by women or children carrying containers on their head (mean container weight 19.5 kg) over a mean distance of 337 m. The prevalence of spinal (neck or back) pain was 69% and back pain was 38%. Of participants who carried water by head loading, the distance walked by those who reported spinal pain was significantly less than those who did not (173 m 95%CI 2-343; p = 0.048). For head loaders reporting head or neck pain compared to those who did not, the differences in weight of water carried (4.6 kg 95%CI -9.7-0.5; p = 0.069) and RPE (2.5 95%CI -5.1-0.1; p = 0.051) were borderline statistically significant. For head loaders, RPE was significantly correlated with container weight (r = 0.52; p = 0.011) and incline (r = 0.459; p = 0.018)

Conclusions

Typical water carrying methods impose physical loading with potential to produce musculoskeletal disorders and related disability. This exploratory study is limited by a small sample size and future research should aim to better understand the type and strength of association between water carrying and health, particularly musculoskeletal disorders. However, these preliminary findings suggest that efforts should be directed toward eliminating the need for water carrying, or where it must continue, identifying and reducing risk factors for musculoskeletal disorders and physical injury.
Single locus affects embryonic segment polarity and multiple aspects of an adult evolutionary novelty
Authors: Saenko Suzanne V , Brakefield Paul M , Beldade Patrícia
Published: August 2010

Background

The characterization of the molecular changes that underlie the origin and diversification of morphological novelties is a key challenge in evolutionary developmental biology. The evolution of such traits is thought to rely largely on co-option of a toolkit of conserved developmental genes that typically perform multiple functions. Mutations that affect both a universal developmental process and the formation of a novelty might shed light onto the genetics of traits not represented in model systems. Here we describe three pleiotropic mutations with large effects on a novel trait, butterfly eyespots, and on a conserved stage of embryogenesis, segment polarity.

Results

We show that three mutations affecting eyespot size and/or colour composition in Bicyclus anynana butterflies occurred in the same locus, and that two of them are embryonic recessive lethal. Using surgical manipulations and analysis of gene expression patterns in developing wings, we demonstrate that the effects on eyespot morphology are due to changes in the epidermal response component of eyespot induction. Our analysis of morphology and of gene expression in mutant embryos shows that they have a typical segment polarity phenotype, consistent with the mutant locus encoding a negative regulator of Wingless signalling.

Conclusions

This study characterizes the segregation and developmental effects of alleles at a single locus that controls the morphology of a lineage-specific trait (butterfly eyespots) and a conserved process (embryonic segment polarity and, specifically, the regulation of Wingless signalling). Because no gene with such function was found in the orthologous, highly syntenic genomic regions of two other lepidopterans, we hypothesize that our locus is a yet undescribed, possibly lineage-specific, negative regulator of the conserved Wnt/Wg pathway. Moreover, the fact that this locus interferes with multiple aspects of eyespot morphology and maps to a genomic region containing key wing pattern loci in different other butterfly species suggests it might correspond to a 'hotspot' locus in the diversification of this novel trait.
Assessing motor deficits in compressive neuropathy using quantitative electromyography
Authors: Nashed Joseph , Hamilton-Wright Andrew , Stashuk Daniel W , Faris Matthew , McLean Linda
Published: August 2010

Background

Studying the changes that occur in motor unit potential trains (MUPTs) may provide insight into the extent of motor unit loss and neural re-organization resulting from nerve compression injury. The purpose of this study was to determine the feasibility of using decomposition-based quantitative electromyography (DQEMG) to study the pathophysiological changes associated with compression neuropathy.

Methods

The model used to examine compression neuropathy was carpal tunnel syndrome (CTS) due to its high prevalence and ease of diagnosis. Surface and concentric needle electromyography data were acquired simultaneously from the abductor pollicis brevis muscle in six individuals with severe CTS, eight individuals with mild CTS and nine healthy control subjects. DQEMG was used to detect intramuscular MUPTs during constant-intensity contractions and to estimate parameters associated with the surface- and needle-detected motor unit potentials (SMUPs and MUPs, respectively). MUP morphology and stability, SMUP morphology and motor unit number estimates (MUNEs) were compared among the groups using Kruskal-Wallis tests.

Results

The severe CTS group had larger amplitude and longer duration MUPs and smaller MUNEs than the mild CTS and control groups, suggesting that the individuals with severe CTS had motor unit loss with subsequent collateral reinnervation, and that DQEMG using a constant-intensity protocol was sensitive to these changes. SMUP morphology and MUP complexity and stability did not significantly differ among the groups.

Conclusions

These results provide evidence that MUP amplitude parameters and MUNEs obtained using DQEMG, may be a valuable tool to investigate pathophysiological changes in muscles affected by compressive motor neuropathy to augment information obtained from nerve conduction studies. Although there were trends in many of these measures, in this study, MUP complexity and stability and SMUP parameters were, of limited value.
Ethnoveterinary plant remedies used by Nu people in NW Yunnan of China
Authors: Shen Shicai , Qian Jie , Ren Jian
Published: August 2010

Background

Nu people are the least populous ethnic group in Yunnan Province of China and most are distributed in Gongshan County, NW Yunnan. Animal production plays an important role in Nu livelihoods and the Nu people have abundant traditional knowledge of animal management and ethnoveterinary practices. This study documents the animal diseases, ethnoveterinary plant remedies and related traditional knowledge in three Nu villages of Gongshan County.

Methods

This study was carried out in three Nu villages of Gongshan County between July 2009 and February 2010. Data was obtained through the use of semi-structured questionnaires, field observation and PRA tools. A total of 60 Nu respondents (34 men and 26 women) provided information on animal ailments and ethnoveterinary plant medicines used for Nu livestock production. Information on traditional ethnoveterinary medicine knowledge and choice of treatment providers was also obtained.

Results

Thirty-five animal conditions were identified in the surveyed area. The major and most common animal diseases among livestock were skin conditions, diarrhea, heat, fevers, colds, and parasites. Most ailments occurred between June and August. The ethnoveterinary medicinal use of 45 plant species was documented. Most medicinal species (86.7%) were collected from the wild. The most frequently used plant parts were whole plants (35.6%), followed by roots (22.2%). The most important medicinal plant species wereSaussurea costus(Falc.) Lipech. (UV = 0.67),Senecio scandensBuch.-Ham.ex D.Don (UV = 0.67),Plantago depressaWilld. (UV = 0.63),Rubus corchorifoliusL. f. (UV = 0.62),Bupleurum yunnanenseFranch. (UV = 0.60), andPolygonum paleaceumWall. (UV = 0.60). Animal diseases treated with the highest number of ethnoveterinary plant remedies were diarrhea (16 plant species), heat, fever, colds (11 plant species), retained afterbirth (11 plant species), and skin conditions and sores (11 plant species). Many Nu villagers (52%) considered traditional remedies their first choice of animal disease treatment. Traditional ethnoveterinary knowledge was related to the local social-cultural characteristics of Nu people and communities.

Conclusion

Animal production plays an important role in Nu culture and livelihoods, and the Nu ethnic group has abundant traditional knowledge about animal production and ethnoveterinary plant remedies. This traditional knowledge faces the risk of disappearing due to increasing modern veterinary medicine extension, livelihood changes and environment degradation. Animal diseases are a major constraint in livestock production in Nu villages. Thus, some strategies and measures should be adopted in the future, such as further researches on Nu culture and livelihoods, community-based validation of ethnoveterinary medicine and broad network building and knowledge sharing.
Circulating mediators of bone remodeling in psoriatic arthritis: implications for disordered osteoclastogenesis and bone erosion
Authors: Dalbeth Nicola , Pool Bregina , Smith Timothy , Callon Karen E , Lobo Maria , Taylor William J , Jones Peter B , Cornish Jillian , McQueen Fiona M
Published: August 2010

Introduction

Diverse bone pathologies are observed in patients with psoriatic arthritis (PsA). Uncoupling of bone remodeling with disordered osteoclastogenesis has been implicated in the pathogenesis of PsA. The aim of this study was to examine the role of soluble mediators of bone remodeling within the circulation of patients with PsA.

Methods

Patients with PsA (n = 38), with psoriasis (n = 10), and healthy controls (n = 12) were studied. Serum was obtained for testing of Dikkopf-1 (Dkk-1), macrophage-colony stimulating factor (M-CSF), osteoprotegerin (OPG), and receptor activator of nuclear factor-κB ligand (RANKL) with ELISA. Patients with PsA also had bone densitometry, plain radiographs of the hands and feet, and assessment of peripheral blood osteoclast precursors. Radiographs were scored for erosion, joint-space narrowing, osteolysis, and new bone formation.

Results

Compared with those with psoriasis and healthy controls, patients with PsA had higher circulating concentrations of Dkk-1 and M-CSF. In patients with PsA, M-CSF and RANKL, but not Dkk-1, concentrations positively correlated with radiographic erosion, joint-space narrowing, and osteolysis scores. Mediators of bone remodeling did not correlate with the number of joints with new bone formation or with total hip-bone mineral density. Peripheral blood CD14+/CD11b+ cells, and the number of osteoclast-like cells and resorptive pits after culture with RANKL and M-CSF also correlated with radiographic damage scores. Circulating M-CSF concentrations correlated with the percentage of peripheral blood CD14+/CD11b+ cells.

Conclusions

Systemic expression of soluble factors that promote osteoclastogenesis is disordered in patients with PsA and may contribute to periarticular bone loss in this disease.
Strand-specific RNA sequencing reveals extensive regulated long antisense transcripts that are conserved across yeast species
Authors: Yassour Moran , Pfiffner Jenna , Levin Joshua Z , Adiconis Xian , Gnirke Andreas , Nusbaum Chad , Thompson Dawn-Anne , Friedman Nir , Regev Aviv
Published: August 2010

Background

Recent studies in budding yeast have shown that antisense transcription occurs at many loci. However, the functional role of antisense transcripts has been demonstrated only in a few cases and it has been suggested that most antisense transcripts may result from promiscuous bi-directional transcription in a dense genome.

Results

Here, we use strand-specific RNA sequencing to study anti-sense transcription in Saccharomyces cerevisiae. We detect 1,103 putative antisense transcripts expressed in mid-log phase growth, ranging from 39 short transcripts covering only the 3' UTR of sense genes to 145 long transcripts covering the entire sense open reading frame. Many of these antisense transcripts overlap sense genes that are repressed in mid-log phase and are important in stationary phase, stress response, or meiosis. We validate the differential regulation of 67 antisense transcripts and their sense targets in relevant conditions, including nutrient limitation and environmental stresses. Moreover, we show that several antisense transcripts and, in some cases, their differential expression have been conserved across five species of yeast spanning 150 million years of evolution. Divergence in the regulation of antisense transcripts to two respiratory genes coincides with the evolution of respiro-fermentation.

Conclusions

Our work provides support for a global and conserved role for antisense transcription in yeast gene regulation.
A standard variation file format for human genome sequences
Authors: Reese Martin G , Moore Barry , Batchelor Colin , Salas Fidel , Cunningham Fiona , Marth Gabor T , Stein Lincoln , Flicek Paul , Yandell Mark , Eilbeck Karen
Published: August 2010

Here we describe the Genome Variation Format (GVF) and the 10Gen dataset. GVF, an extension of Generic Feature Format version 3 (GFF3), is a simple tab-delimited format for DNA variant files, which uses Sequence Ontology to describe genome variation data. The 10Gen dataset, ten human genomes in GVF format, is freely available for community analysis from the Sequence Ontology website and from an Amazon elastic block storage (EBS) snapshot for use in Amazon's EC2 cloud computing environment.
PD-L1hi retinal pigment epithelium (RPE) cells elicited by inflammatory cytokines induce regulatory activity in uveitogenic T cells
Authors: Ke Yan , Sun Deming , Jiang Guomin , Kaplan Henry J , Shao Hui
Published: August 2010

Inflammatory cytokine triggered up-regulation of PD-L1 on RPE may accelerate local resolution of uveitis by inducing regulatory activity in uveitogenic T cells.

We previously reported that after exposure to inflammatory cytokines, such as IL-17 and IFN-γ, RPE cells express increased amounts of suppressor of cytokine signaling, leading to general suppression of the inflammatory response. Here, we demonstrate that RPE cells expressed increased levels of PD-L1 in response to IL-17, IFN-γ, or Poly I:C. These PD-L1hi RPE cells inhibited the pathogenic activities of IRBP-specific T cells, which usually induced uveitis when injected into naïve mice (EAU). The suppressed pathogenicity of these uveitogenic T cells after exposure to PD-L1hi RPE cells could be partially reversed by anti-PD-L1 antibodies. Nevertheless, IRBP-specific T cells pre-exposed to PD-L1hi RPE cells displayed substantial suppressor activity, which strongly inhibited the activation of fresh IRBP-Teffs in response to subsequent antigenic challenge and when transferred into naïve mice, inhibited the induction of EAU by IRBP-Teff transfer. These findings suggest that inflammatory cytokine-triggered up-regulation of PD-L1 on RPE constitutes a critical factor for inducing infiltrated uveitogenic T cells with regulatory activities, which may accelerate the natural resolution of T cell-mediated intraocular inflammation.
Extended isochron rays in prestack depth (map) migration
Authors: Duchkov Anton A. , de Hoop Maarten V.
Published: August 2010

Many processes in seismic data analysis and seismic imaging can be identified with solution operators of evolution equations. These include data downward continuation and velocity continuation. We have addressed the question of whether isochrons defined by imaging operators can be identified with wavefronts of solutions to an evolution equation. Rays associated with this equation then would provide a natural way of implementing prestack map migration. Assuming absence of caustics, we have developed constructive proof of the existence of a Hamiltonian describing propagation of isochrons in the context of common-offset depth migration. In the presence of caustics, one should recast to a sinking-survey migration framework. By manipulating the double-square-root operator, we obtain an evolution equation that describes sinking-survey migration as a propagation in two-way time with surface data being a source function. This formulation can be viewed as an extension of the exploding reflector concept from zero-offset to sinking-survey migration. The corresponding Hamiltonian describes propagation of extended isochrons (fronts with constant two-way time) connected by extended isochron rays. The term extended reflects the fact that two-way time propagation now takes place in high-dimensional space with the following coordinates: subsurface midpoint, subsurface offset, and depth. Extended isochron rays can be used in a natural manner for implementing sinking-survey migration in a map-migration fashion.
Shapes of History and the Enigmatic Hero in Dostoevsky: The Case ofCrime and Punishment
Authors: KLIGER ILYA
Published: August 2010

This essay studies a crucial feature of Dostoevsky's novelistic poetics, and the poetics of Crime and Punishment (1866) in particular, in light of contemporaneous debates regarding the historical fate of Russia. The novel, I argue, is a thought experiment exploring the emerging condition of multi-historicity—that is, a simultaneity of multiple emplotment possibilities for the Russian state. In order to bring these possibilities to light, I read the novel with an eye on Dostoevsky's journalism from the early- to mid-sixties, a period characterized by an urgent recognition of the openness of Russia's historical future.

Mediating between the novel and its contemporary journalistic discourse with the help of the formal (narratological) categories of character and emplotment, I argue that the novelistic search for the proper emplotment of its enigmatic hero corresponds to the search in contemporary journalism for the proper trajectory of the Russian nation, which, with the emancipation of the serfs in 1861, is perceived as pregnant with multiple historical possibilities. As an enigma soliciting narrative solutions, Dostoevsky's socially underdetermined (raznochinets) hero is best understood as a formal condition of the possibility of exploring Russia's position at the intersection point of multiple historical vectors. As such, the hero enables a series of temporal shapes, laden with historiographic significance, to be considered and then either chosen or dismissed. A re-inscription of Crime and Punishment into the context of journalistic debates from the period of Great Reforms thus allows us to read the novel as a political allegory that stages and imaginatively resolves the socio-temporal contradictions structuring a world torn between conflicting demands for continuity and radical change.
Construction of Cooperative and Responsive Supramolecular Systems for Molecular Functional Modulation
Authors: Nabeshima Tatsuya
Published: August 2010

The transfer and modulation of the molecular information are necessary processes for cooperative and responsive molecular functions. When functional molecules are responsive to external (intermolecular) as well as internal (intramolecular) stimuli, the molecules exhibit cooperative functions in principle. We have developed a variety of cooperative and responsive supramolecular systems created on the basis of new concepts for the molecular design of sophisticated functional systems. The first uses pseudomacrocycles including pseudocrown ether, pseudocryptands, and pseudocyclophanes as novel frameworks for response functions by utilizing a metal ion as an effector. The second utilizes a molecular gate responding to an external signal. The gate is opened and closed by a signal achieving perfect on–off switching for guest recognition. The next exploits metal-accumulated molecular systems bearing oligo C=N moieties as a binding site for metal ions. This strategy is remarkably useful for producing new binding sites by structural fixation of multi-metal complexes and to modulate properties of metal ions. Other cooperative molecular assembling systems for host generation are also demonstrated in this account. Metallo-frameworks and self-assembled metallo-systems recently developed in our laboratories, which have high potential for synergistic molecular functions, are discussed. Future cooperative functional systems will be widely applicable as multi-responsive multi-functional supramolecules, molecular functional cascades for successive molecular functions and function amplification. Study of cooperative and responsive molecular systems may lead to more general fields such as complex systems science, which is at the interface of chemistry, physics, biology, and mathematics.
Remote care nearby
Authors: Vollenbroek-Hutten Miriam MR , Hermens Hermie J
Published: August 2010

A telemedicine application has a better chance of being accepted if the users can easily handle it and if the application fulfils the clinical needs of both patients and professionals. This requires a methodology for development in which three key matters need to be dealt with: (1) clinical content; (2) design; and (3) outcome. Concerning the clinical content, telemedicine services for patients with chronic disorders that aim to increase their level of functioning need to monitor aspects of the patient's functioning and provide adequate feedback about this. Promising parameters of functioning are related to general physical activity and muscle activation patterns. Providing adequate feedback requires choices about the content of the information, the modality of the feedback and its timing. Unfortunately, research into effective feedback strategies is still in its infancy. Concerning the design it appears that the different stakeholders involved speak different languages, that there is a lack of knowledge about aspects related to acceptance and a lack of good methods to define user requirements. Scenario-based requirements analysis is a promising technique to overcome these barriers. Concerning the outcome, evaluation of telemedicine services in everyday clinical practice has been mainly directed at measurement of technical performance and user satisfaction. Large scale clinical evaluation studies with multiple end points are needed. This development methodology with its three aspects was used for a myofeedback-based teletreatment service. This showed that telemedicine applications can be developed that have the potential to make health care more effective, efficient and accessible.
Operative treatment of Linburg-Comstock syndrome
Authors: Badhe S. , Lynch J. , Thorpe S. K. S. , Bainbridge L. C.
Published: August 2010

Linburg-Comstock syndrome is characterised by an anomalous tendon slip from the flexor pollicis longus to the flexor digitorum profundus, usually of the index finger. An incidence as high as 60% to 70% has been reported. Post-traumatic inflammation of inter-tendinous connections between the flexor pollicis longus and flexor digitorum profundus, usually of the index finger, may cause unexplained chronic pain in the distal forearm. A total of 11 patients (eight females, three males), mean age 29.1 years (14 to 47) with a clinical diagnosis of Linburg-Comstock syndrome underwent surgical release of the inter-tendinous connection. The mean follow-up was for 27 months (2 to 48).

Ten patients reported excellent relief of pain in the forearm, with independent flexion of flexor pollicis longus and flexor digitorum profundus to the index finger. Surgical release was an effective treatment for the Linburg-Comstock syndrome in this series.
Translation of science to surgery
Authors: Moran C. J. , Shannon F. J. , Barry F. P. , O’Byrne J. M. , O’Brien T. , Curtin W.
Published: August 2010

Orthopaedic surgery is in an exciting transitional period as modern surgical interventions, implants and scientific developments are providing new therapeutic options. As advances in basic science and technology improve our understanding of the pathology and repair of musculoskeletal tissue, traditional operations may be replaced by newer, less invasive procedures which are more appropriately targeted at the underlying pathophysiology. However, evidence-based practice will remain a basic requirement of care. Orthopaedic surgeons can and should remain at the forefront of the development of novel therapeutic interventions and their application. Progression of the potential of bench research into an improved array of orthopaedic treatments in an effective yet safe manner will require the development of a subgroup of specialists with extended training in research to play an important role in bridging the gap between laboratory science and clinical practice. International regulations regarding the introduction of new biological treatments will place an additional burden on the mechanisms of this translational process, and orthopaedic surgeons who are trained in science, surgery and the regulatory environment will be essential. Training and supporting individuals with these skills requires special consideration and discussion by the orthopaedic community.

In this paper we review some traditional approaches to the integration of orthopaedic science and surgery, the therapeutic potential of current regenerative biomedical science for cartilage repair and ways in which we may develop surgeons with the skills required to translate scientific discovery into effective and properly assessed orthopaedic treatments.
Outcomes of revision total hip replacement for infection after grading according to a standard protocol
Authors: Oussedik S. I. S. , Dodd M. B. , Haddad F. S.
Published: August 2010

Periprosthetic infection following total hip replacement can be a catastrophic complication for the patient. The treatments available include single-stage exchange, and two-stage exchange. We present a series of 50 consecutive patients with a diagnosis of infected total hip replacement who were assessed according to a standardised protocol. Of these, 11 underwent single-stage revision arthroplasty with no recurrence of infection at a mean of 6.8 years follow-up (5.5 to 8.8). The remaining 39 underwent two-stage revision, with two recurrences of infection successfully treated by a second two-stage procedure. At five years, significant differences were found in the mean Harris Hip Scores (single-stage 87.8; two-stage 75.5; p = 0.0003) and in a visual analogue score for satisfaction (8.6; 6.9; p = 0.001) between the single- and two-stage groups. Single-stage exchange is successful in eradicating periprosthetic infection and results in excellent functional and satisfaction scores.

Identification of patients suitable for the single-stage procedure allows individualisation of care and provides as many as possible with the correct strategy in successfully tackling their periprosthetic infection
The effectiveness of interventions in the management of patients with primary frozen shoulder
Authors: Rookmoneea M. , Dennis L. , Brealey S. , Rangan A. , White B. , McDaid C. , Harden M.
Published: August 2010

There are many types of treatment used to manage the frozen shoulder, but there is no consensus on how best to manage patients with this painful and debilitating condition. We conducted a review of the evidence of the effectiveness of interventions used to manage primary frozen shoulder using the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, the Physiotherapy Evidence Database, MEDLINE and EMBASE without language or date restrictions up to April 2009. Two authors independently applied selection criteria and assessed the quality of systematic reviews using the Assessment of Multiple Systematic Reviews (AMSTAR) tool. Data were synthesised narratively, with emphasis placed on assessing the quality of evidence.

In total, 758 titles and abstracts were identified and screened, which resulted in the inclusion of 11 systematic reviews. Although these met most of the AMSTAR quality criteria, there was insufficient evidence to draw firm conclusions about the effectiveness of treatments commonly used to manage a frozen shoulder. This was mostly due to poor methodological quality and small sample size in primary studies included in the reviews. We found no reviews evaluating surgical interventions.

More rigorous randomised trials are needed to evaluate the treatments used for frozen shoulder.
The plain β-angle measured on radiographs in the assessment of femoroacetabular impingement
Authors: Brunner A. , Hamers A. T. , Fitze M. , Herzog R. F.
Published: August 2010

The β-angle is a radiological tool for measuring the distance between the pathological head-neck junction and the acetabular rim with the hip in 90° of flexion in patients with femoroacetabular impingement. Initially it was measured using an open-chamber MRI. We have developed a technique to measure this angle on plain radiographs. Correlation analysis was undertaken to determine the relationship between the range of movement and the β-angle in 50 patients with femoroacetabular impingement and 50 asymptomatic control subjects. Inter- and intra-observer reliability of the β-angle was also evaluated.

Patients with femoroacetabular impingement had a significantly smaller (p < 0.001) mean β-angle (15.6°, 95% confidence interval (CI) 13.3 to 17.7) compared with the asymptomatic group (38.7°, 95% CI 36.5 to 41.0). Correlation between internal rotation and the β-angle was high in the impingement group and moderate in the asymptomatic group. The β-angle had excellent inter- and intra-observer reliability in both groups.

Our findings suggest that the measurement of the β-angle on plain radiography may represent a valid, reproducible and cost-effective alternative to open MRI in the assessment of the pathological bony anatomy in patients with cam, pincer and mixed femoroacetabular impingement.
Customised femoral stems in osteopetrosis and the development of a guiding system for the preparation of an intramedullary cavity
Authors: Benum P. , Aamodt A. , Nordsletten L.
Published: August 2010

Traditional techniques for the insertion of femoral stems in arthroplasty of the hip in osteopetrosis carry a considerable risk of penetration of the femoral cortex and intra-operative fractures, due to obliteration of the intramedullary cavity and greatly increased stiffness and brittleness of the bone. In order to reduce the risk of such complications we manufactured a customised stem and a computer-based guiding device for the preparation of a cavity within the proximal femur. This system was used successfully in three hips in two patients. We describe the system and the operative technique.
Photographic measurement of the inclination of the acetabular component in total hip replacement using the posterior approach
Authors: Hill J. C. , Gibson D. P. , Pagoti R. , Beverland D. E.
Published: August 2010

The angle of inclination of the acetabular component in total hip replacement is a recognised contributing factor in dislocation and early wear. During non-navigated surgery, insertion of the acetabular component has traditionally been performed at an angle of 45° relative to the sagittal plane as judged by the surgeon’s eye, the operative inclination. Typically, the method used to assess inclination is the measurement made on the postoperative anteroposterior radiograph, the radiological inclination.

The aim of this study was to measure the intra-operative angle of inclination of the acetabular component on 60 consecutive patients in the lateral decubitus position when using a posterior approach during total hip replacement. This was achieved by taking intra-operative photographs of the acetabular inserter, representing the acetabular axis, and a horizontal reference. The results were compared with the post-operative radiological inclination.

The mean post-operative radiological inclination was 13° greater than the photographed operative inclination, which was unexpectedly high. It appears that in the lateral decubitus position with a posterior approach, the uppermost hemipelvis adducts, thus reducing the apparent operative inclination. Surgeons using the posterior approach in lateral decubitus need to aim for a lower operative inclination than when operating with the patient supine in order to achieve an acceptable radiological inclination.
An audit of the role of vitamin K in the reversal of International Normalised Ratio (INR) in patients undergoing surgery for hip fracture
Authors: Bhatia Maneesh , Talawadekar Gautam , Parihar Sailendra , Smith Andrew
Published: August 2010

INTRODUCTION

The objective of this prospective audit was to compare two methods of anticoagulation reversal in the pre-oper-ative period for hip fracture patients.

PATIENTS AND METHODS

In the first part of the audit, our current practice was analysed. Data relating to the number of days from admission to surgery and the reasons for delay to surgery were collected. Also, data concerning common reasons for which the patients were started on warfarin and the time required for INR to drop to 1.5 or below were collected. In the second part of the audit, 45 patients with INR above 1.5 were given a single dose of vitamin K (1 mg i.v.) in addition to stopping warfarin.

RESULTS

The mean difference in the time for INR < 1.5 in the two groups was 2 days (52 h; P < 0.05). The mean difference in wait for surgery since admission between the two groups was 4 days (91 h; P < 0.05). There was no significant difference between the two groups as regards the average number of co-morbidities in the patient groups.

CONCLUSIONS

A single 1 mg intravenous dose of vitamin K significantly reduces the time for the reversal of INR and the pre-operative delay to surgery, in patients on long-term warfarin. We conclude that 1 mg of intravenous vitamin K on admission is a safe and effective treatment to avoid delay in the treatment in this group of patients.
A further survey of surgical management of the axilla in UK breast cancer patients
Authors: Glynn Ronan W , Williams Linda , Dixon J Michael
Published: August 2010

INTRODUCTION

The aims of this study were to investigate the practice of axillary lymph node management within different units throughout the UK, and to assess changes in practice since our previous survey in 2004.

SUBJECTS AND METHODS

A structured questionnaire was sent to 350 members of the British Association of Surgical Oncology.

RESULTS

There were 177 replies from respondents who managed more than 100 patients a year with breast cancer. Of these: 12 did not perform axillary ultrasound at all in their centre; 17 (10%) employed axillary node clearance (ANC) on all patients; 122(69%) performed sentinel node biopsy (SNB) with dual localisation; and 111 respondents had attended the New Start Course. Radioisotope was most frequently injected 2 h or more before operation. Just 13 surgeons were convinced of the value of dissecting internal mammary nodes visualised on a scan. Reasons for not using dual localisation included lack of nuclear medicine facilities, no local ARSAC licence holder, no probe, and no funding. Sixty-six surgeons stated that, if they had an ARSAC licence and could inject the radioactivity in theatre, this would be a major improvement. In addition, 83 (47%) did not perform SLNB in patients receiving neo-adjuvant chemotherapy.

CONCLUSIONS

Despite significant changes since 2004, substantial variation remains in management of the axilla. A number of surgeons are practicing outwith current guidelines.
Systematic review of blunt abdominal trauma as a cause of acute appendicitis
Authors: Toumi Zaher , Chan Anthony , Hadfield Matthew B , Hulton Neil R
Published: August 2010

INTRODUCTION

Acute appendicitis commonly presents as an acute abdomen. Cases of acute appendicitis caused by blunt abdominal trauma are rare. We present a systematic review of appendicitis following blunt abdominal trauma. The aim of this review was to collate and report the clinical presentations and experience of such cases.

SUBJECTS AND METHODS

A literature review was performed using PubMed, Embase and Medline and the keywords ‘appendicitis’, ‘abdominal’ and ‘trauma’.

RESULTS

The initial search returned 381 papers, of which 17 articles were included. We found 28 cases of acute appendicitis secondary to blunt abdominal trauma reported in the literature between 1991 and 2009. Mechanisms of injury included road-traffic accidents, falls, assaults and accidents. Presenting symptoms invariably included abdominal pain, but also nausea, vomiting and anorexia. Only 12 patients had computed tomography scans and 10 patients had ultrasonography. All reported treatment was surgical and positive for appendicitis.

CONCLUSIONS

Although rare, the diagnosis of acute appendicitis must be considered following direct abdominal trauma especially if the patient complains of abdominal right lower quadrant pain, nausea and anorexia. Haemodynamically stable patients who present shortly after blunt abdominal trauma with right lower quadrant pain and tenderness should undergo urgent imaging with a plan to proceed to appendicectomy if the imaging suggested an inflammatory process within the right iliac fossa.
Extra-anatomical bypass grafting – a single surgeon's experience
Authors: Appleton ND , Bosanquet D , Morris-Stiff G , Ahmed H , Sanjay P , Lewis MH
Published: August 2010

INTRODUCTION

Extra-anatomical bypass grafting is a recognised method of lower limb re-vascularisation in high-risk patients who cannot tolerate aortic cross clamping, or in those with a hostile abdomen. We present a single surgeon series of such procedures and determine relevant outcomes.

PATIENTS AND METHODS

A retrospective review was performed on a prospectively maintained database of patients undergoing femoro-femoral or axillo-femoral bypass surgery between 1986 and 2004.

RESULTS

Patency rates for femoral (n = 28; 32%) versus axillary (n = 59; 68%) bypass procedures at 1 month, 1, 3 and 5 years were (92% vs 93%), (69% vs 85%), (60% vs 72%) and (55% vs 67%), respectively. Patient survival rates for the corresponding procedures and time intervals were (96% vs 90%), (96% vs 67%), (85% vs 45%) and (73% vs 38%) and revealed a significantly lower survival rate in those undergoing axillary procedures (P = 0.002). Limb salvage rates were calculated at (100% vs 91%), (96% vs 84%), (96% vs 81%) and (92% vs 81%) with no statistically significant difference found between the two groups (P = 0.124). Two-thirds of the patients who required major amputation died within 12 months of surgery.

CONCLUSIONS

Acceptable 30-day morbidity, long-term primary patency and survival rates are obtainable in patients suitable for extra-anatomical bypass surgery despite having significant co-morbidities. We have shown 5-year patency rates in those that survive axillary procedures to be as good as those undergoing femoral procedures. Furthermore, surviving patients who evade amputation within a year have an excellent chance of long-term limb salvage.
Osteonecrosis of jaws related to intravenous bisphosphonates: the experience of a Jordanian teaching hospital
Authors: Baqain Zaid H , Sawair Faleh A , Tamimi Zaid , Bsoul Nazzal , Al Edwan Ghazi , Almasad Jamal K , Abbadi Abdalla A
Published: August 2010

INTRODUCTION

We describe our experience with oncology patients on a frequent dosing schedule of intravenous (i.v.) bisphosphonates at the Jordan University Hospital (JUH).

PATIENTS AND METHODS

Patients treated by i.v. bisphosphonates in the medical oncology unit at the JUH were examined for bisphosphonate-related osteonecrosis of the jaws (BRONJ). Diagnosis was made according to the guidelines of the American Association of Oral and Maxillofacial Surgeons (AAOMS) original position paper.

RESULTS

Of the 41 patients, four developed BRONJ, two in maxilla, one in mandible and one bimaxillary. Patients with BRONJ were older; mean age was 69.3 ±3.1 years compared to 62.8 ± 12.5 years (P = 0.022). Dental co-morbidities were more commonly present in patients with the disease (P = 0.038). Patients who developed BRONJ were on treatment for a longer duration of time; the mean duration of treatment was 23.5 ± 8.4 months compared to 11.9 ± 13.4 months (P = 0.10).

CONCLUSIONS

The results of this case series demonstrated that age and poor oral health status are significant risk factors of BRONJ for oncology patients on long-term frequent dosing schedule of i.v. bisphosphonates.