bluuebunny/crossref_metadata_2025 huggingface dataset:
Demographics of pediatric-onset multiple sclerosis in an MS center population from the Northeastern United States
Authors: Chitnis T , Glanz B , Jaffin S , Healy B
Published: March 2009

Background

The prevalence of pediatric-onset multiple sclerosis (MS) in the United States is unknown.

Objective

In a large cohort of MS patients, we sought to identify the proportion with first symptom-onset below the age of 18 years, and to compare their demographic and disease characteristics to a typical adult-onset MS population.

Methods

Patients seen at the Partners Multiple Sclerosis Center, Brigham and Women’s Hospital, Boston, Massachusetts, with clinical histories and characteristics of first symptoms recorded in an electronic database, were included in this study.

Results

We found that 3.06% of patients with a recorded MS history experienced a first attack under the age of 18 years of age compared to 30.83% of patients who experienced first symptoms between the ages of 25–35 years. Gender proportions were similar in both groups, with the exception of a lower female preponderance in pre-pubertal-onset patients. There was a higher proportion of non-Caucasians in the younger cohort. Localization of first symptoms was similar in the two groups.

Conclusion

About 3% of MS patients experience their first symptom prior to the age of 18 years. Standardized follow-up is required after a first demyelinating attack in childhood, which may lead to earlier diagnosis and treatment of pediatric-onset MS.
The clinical effect of neutralizing antibodies against interferon-beta is independent of the type of interferon-beta used for patients with relapsing-remitting multiple sclerosis
Authors: Koch-Henriksen N , Sorensen PS , Bendtzen K , Flachs EM
Published: March 2009

Objective

To establish whether the clinical effect of neutralizing antibodies (NAbs) against interferon-beta (IFNβ) depends on the type of IFNβ (1a or 1b) used for treatment of patients with relapsing-remitting multiple sclerosis (MS).

Introduction

NAbs against IFNβ-1b appear faster and may be more evenly distributed on IgG subclasses, whereas NAbs against IFNβ-1a develop more slowly and may be devoid of IgG3. This might cause different clinical responses to NAbs.

Design/patients

All Danish MS-patients who had started first-time treatment with IFNβ-1a 22 μg s.c tiw (Rebif22) or IFNβ-1b 250 μg s.c. qod (Betaferon) before January 1st 2003 were included. Relapses were recorded at bi-annual visit.

Methods

We measured NAbs every 12 months using a clinically validated cytopathic effect assay. A blood sample with a neutralizing capacity of 20% or more was considered as NAb-positive. We used a mixed logistic regression analysis in which NAb-status (three levels), IFNβ-preparation, and time since treatment started were included as explanatory variables, and relapse rate as response variable.

Results

In 1,309 patients, who were observed for 21,958 months, 32.3% were classified as NAb-positive. The odds-ratio (OR) for relapses in NAb-positive months compared with NAb-negative months was 1.25; P = 0.02. The risk of relapses was higher with Betaferon than with Rebif22 (OR 1.26; P < 0.01). The effect of NAb-level on relapses was independent of whether the patients were treated with Betaferon or Rebif22 ( P = 0.89) and of time ( P = 0.80).

Conclusion

NAbs caused by IFNβ-1a s.c. do not differ from NAbs caused by IFNβ-1b in their detrimental clinical effect.
KIR acquisition probabilities are independent of self-HLA class I ligands and increase with cellular KIR expression
Authors: Andersson Sandra , Fauriat Cyril , Malmberg Jenny-Ann , Ljunggren Hans-Gustaf , Malmberg Karl-Johan
Published: March 2009

Inhibitory killer cell immunoglobulin-like receptors (KIRs) preserve tolerance to self and shape the functional response of human natural killer (NK) cells. Here, we have evaluated the influence of selection processes in the formation of inhibitory KIR repertoires in a cohort of 44 donors homozygous for the group A KIR haplotype. Coexpression of multiple KIRs was more frequent than expected by the product rule that describes random association of independent events. In line with this observation, the probability of KIR acquisition increased with the cellular expression of KIRs. Three types of KIR repertoires were distinguished that differed in frequencies of KIR- and NKG2A-positive cells but showed no dependency on the number of self-HLA class I ligands. Furthermore, the distribution of self- and nonself-KIRs at the cell surface reflected a random combination of receptors rather than a selection process conferred by cognate HLA class I molecules. Finally, NKG2A was found to buffer overall functional responses in KIR repertoires characterized by low-KIR expression frequencies. The results provide new insights into the formation of inhibitory KIR repertoires on human NK cells and support a model in which variegated KIR repertoires are generated through sequential and random acquisition of KIRs in the absence of selection.
Interleukin-6: An Autocrine Regulator of the Mouse Cumulus Cell-Oocyte Complex Expansion Process
Authors: Liu Zhilin , de Matos Daniel G. , Fan Heng-Yu , Shimada Masayuki , Palmer Stephen , Richards JoAnne S.
Published: March 2009

Ovulation has long been regarded as a process resembling an inflammatory response. Recent studies indicate that genes associated with innate immune responses were also expressed during the ovulation process. Because the innate immune genes are induced in cumulus cell oocyte complexes (COCs) later than the inflammation-associated genes, we hypothesize that COC expansion is dependent on specific sequential changes in cumulus cells. Because IL-6 is a potent mediator of immune responses, we sought to determine what factors regulate the induction of Il6 mRNA in COCs and what impact IL-6 alone would have on COC expansion. We found that the levels of Il6 mRNA increased dramatically during COC expansion, both in vivo and in vitro. Moreover, IL-6, together with its soluble receptor (IL-6SR), could bypass the need for either amphiregulin and/or prostaglandin E2 to induce the expansion of COCs. This ability of IL-6/IL-6SR to induce COC expansion was blocked by the inhibitors to p38MAPK, MAPK kinase 1/2, and Janus kinase. More importantly, when COCs were in vitro maturated in the presence of IL-6, they had a significantly higher embryo transfer rate than the ones without IL-6 and comparable with in vivo matured oocytes. IL-6/IL-6SR activated multiple signaling pathways (Janus kinase/signal transducer and activator of transcription, ERK1/2, p38MAPK, and AKT) and progressively induced genes known to impact COC expansion, genes related to inflammation and immune responses, and some transcription factors. Collectively, these data indicate that IL-6 alone can act as a potent autocrine regulator of ovarian cumulus cell function, COC expansion, and oocyte competence.
The Corpuscles of Stannius, Calcium-Sensing Receptor, and Stanniocalcin: Responses to Calcimimetics and Physiological Challenges
Authors: Greenwood Michael P. , Flik Gert , Wagner Graham F. , Balment Richard J.
Published: March 2009

This study has examined whether the calcium-sensing receptor (CaSR) plays a role in control of stanniocalcin-1 (STC-1), the dominant calcium regulatory hormone of fish, comparable with that demonstrated for CaSR in the mediation of ionized calcium regulation of PTH secretion in mammals. In a previous study, we have cloned flounder STC-1 from the corpuscles of Stannius (CS). Here, we report the cloning and characterization of the CS CaSR, and the in vivo responses of this system to altered salinity, EGTA induced hypocalcemia, and calcimimetic administration. Quantitative PCR analysis demonstrated, for the first time, that the CS are major sites of CaSR expression in flounder. Immunoblot analysis of CS proteins with CaSR-specific antibodies revealed a broad band of approximately 215–300 kDa under nonreducing conditions, and bands of approximately 215–300 kDa and approximately 120–150 kDa under reducing conditions. There were no differences in CS CaSR mRNA expression or plasma STC-1 levels between seawater and freshwater (FW)-adapted fish, although CS STC-1 mRNA expression was lower in FW animals. Immunoblots showed that glycosylated monomeric forms of the CaSR migrated at a lower molecular mass in CS samples from FW animals. The ip administration of EGTA rapidly induced hypocalcemia, and a concomitant lowering of plasma STC-1. Calcimimetic administration (1 mg/kg R-568) rapidly increased plasma STC-1 levels, and reduced plasma concentrations of calcium, phosphate, and magnesium when compared with S-568-treated controls. Together, these findings support an evolutionary conserved role for the CaSR in the endocrine regulation of calcium before the appearance of parathyroid glands in tetrapods.
LIM homeobox transcription factors integrate signaling events that control three-dimensional limb patterning and growth
Authors: Tzchori Itai , Day Timothy F. , Carolan Peter J. , Zhao Yangu , Wassif Christopher A. , Li LiQi , Lewandoski Mark , Gorivodsky Marat , Love Paul E. , Porter Forbes D. , Westphal Heiner , Yang Yingzi
Published: March 2009

Vertebrate limb development is controlled by three signaling centers that regulate limb patterning and growth along the proximodistal (PD),anteroposterior (AP) and dorsoventral (DV) limb axes. Coordination of limb development along these three axes is achieved by interactions and feedback loops involving the secreted signaling molecules that mediate the activities of these signaling centers. However, it is unknown how these signaling interactions are processed in the responding cells. We have found that distinct LIM homeodomain transcription factors, encoded by the LIM homeobox(LIM-HD) genes Lhx2, Lhx9 and Lmx1b integrate the signaling events that link limb patterning and outgrowth along all three axes. Simultaneous loss of Lhx2 and Lhx9 function resulted in patterning and growth defects along the AP and the PD limb axes. Similar, but more severe, phenotypes were observed when the activities of all three factors, Lmx1b, Lhx2 and Lhx9, were significantly reduced by removing their obligatory co-factor Ldb1. This reveals that the dorsal limb-specific factor Lmx1b can partially compensate for the function of Lhx2 and Lhx9 in regulating AP and PD limb patterning and outgrowth. We further showed that Lhx2and Lhx9 can fully substitute for each other, and that Lmx1bis partially redundant, in controlling the production of output signals in mesenchymal cells in response to Fgf8 and Shh signaling. Our results indicate that several distinct LIM-HD transcription factors in conjunction with their Ldb1 co-factor serve as common central integrators of distinct signaling interactions and feedback loops to coordinate limb patterning and outgrowth along the PD, AP and DV axes after limb bud formation.
Sonic hedgehog signaling regulates reciprocal epithelial-mesenchymal interactions controlling palatal outgrowth
Authors: Lan Yu , Jiang Rulang
Published: March 2009

The mammalian secondary palate arises by outgrowth from the oral side of the paired maxillary processes flanking the primitive oral cavity. Palatal growth depends on reciprocal interactions between the oral ectoderm and the underlying neural-crest-derived mesenchyme. Previous studies have implicated sonic hedgehog (Shh) as an important epithelial signal for regulating palatal growth. However, the cellular and molecular mechanisms through which Shh regulates palatal development in vivo have not been directly analyzed, due in part to early embryonic lethality of mice lacking Shh or other essential components of the Shh signaling pathway. Using Cre/loxP-mediated tissue-specific inactivation of the smoothened (Smo) gene in the developing palatal mesenchyme, we show that the epithelially expressed Shh signals directly to the palatal mesenchyme to regulate palatal mesenchyme cell proliferation through maintenance of cyclin D1 (Ccnd1) and Ccnd2 expression. Moreover, we show that Shh-Smo signaling specifically regulates the expression of the transcription factors Foxf1a,Foxf2 and Osr2 in the developing palatal mesenchyme. Furthermore, we show that Shh signaling regulates Bmp2, Bmp4 and Fgf10 expression in the developing palatal mesenchyme and that specific inactivation of Smo in the palatal mesenchyme indirectly affects palatal epithelial cell proliferation. Together with previous reports that the mesenchymally expressed Fgf10 signals to the palatal epithelium to regulate ShhmRNA expression and cell proliferation, these data demonstrate that Shh signaling plays a central role in coordinating the reciprocal epithelial-mesenchymal interactions controlling palatal outgrowth.
Map2k1andMap2k2genes contribute to the normal development of syncytiotrophoblasts during placentation
Authors: Nadeau Valérie , Guillemette Stéphanie , Bélanger Louis-François , Jacob Olivier , Roy Sophie , Charron Jean
Published: March 2009

The mammalian genome contains two ERK/MAP kinase kinase genes, Map2k1 and Map2k2, which encode dual-specificity kinases responsible for ERK/MAP kinase activation. In the mouse, loss of Map2k1 function causes embryonic lethality, whereas Map2k2mutants survive with a normal lifespan, suggesting that Map2k1 masks the phenotype due to the Map2k2 mutation. To uncover the specific function of MAP2K2 and the threshold requirement of MAP2K proteins during embryo formation, we have successively ablated the Map2k gene functions. We report here that Map2k2 haploinsufficiency affects the normal development of placenta in the absence of one Map2k1 allele. Most Map2k1+/-Map2k2+/- embryos die during gestation because of placenta defects restricted to extra-embryonic tissues. The impaired viability of Map2k1+/-Map2k2+/- embryos can be rescued when the Map2k1 deletion is restricted to the embryonic tissues. The severity of the placenta phenotype is dependent on the number of Map2k mutant alleles, the deletion of the Map2k1 allele being more deleterious. Moreover, the deletion of one or both Map2k2alleles in the context of one null Map2k1 allele leads to the formation of multinucleated trophoblast giant (MTG) cells. Genetic experiments indicate that these structures are derived from Gcm1-expressing syncytiotrophoblasts (SynT), which are affected in their ability to form the uniform SynT layer II lining the maternal sinuses. Thus, even though Map2k1 plays a predominant role, these results enlighten the function of Map2k2 in placenta development.
p300-mediated acetylation of the Rothmund-Thomson-syndrome gene product RECQL4 regulates its subcellular localization
Authors: Dietschy Tobias , Shevelev Igor , Pena-Diaz Javier , Hühn Daniela , Kuenzle Sandra , Mak Raymond , Miah Mohammad Fahad , Hess Daniel , Fey Monika , Hottiger Michael O. , Janscak Pavel , Stagljar Igor
Published: March 2009

RECQL4 belongs to the conserved RecQ family of DNA helicases, members of which play important roles in the maintenance of genome stability in all organisms that have been examined. Although genetic alterations in the RECQL4 gene are reported to be associated with three autosomal recessive disorders (Rothmund-Thomson, RAPADILINO and Baller-Gerold syndromes), the molecular role of RECQL4 still remains poorly understood. Here, we show that RECQL4 specifically interacts with the histone acetyltransferase p300 (also known as p300 HAT), both in vivo and in vitro, and that p300 acetylates one or more of the lysine residues at positions 376, 380, 382, 385 and 386 of RECQL4. Furthermore, we report that these five lysine residues lie within a short motif of 30 amino acids that is essential for the nuclear localization of RECQL4. Remarkably, the acetylation of RECQL4 by p300 in vivo leads to a significant shift of a proportion of RECQL4 protein from the nucleus to the cytoplasm. This accumulation of the acetylated RECQL4 is a result of its inability to be imported into the nucleus. Our results provide the first evidence of a post-translational modification of the RECQL4 protein, and suggest that acetylation of RECQL4 by p300 regulates the trafficking of RECQL4 between the nucleus and the cytoplasm.
S. pombe btn1, the orthologue of the Batten disease geneCLN3, is required for vacuole protein sorting of Cpy1p and Golgi exit of Vps10p
Authors: Codlin Sandra , Mole Sara E.
Published: March 2009

Batten disease is characterised by lysosomal dysfunction. The most common type of the disease is caused by mutations in the membrane protein CLN3, whose function is unknown. We show that the fission yeast orthologue Btn1p, previously implicated in vacuole function, is required for correct sorting of the vacuole hydrolase carboxypeptidase Y (Cpy1p). This is, in part, due to a defect in trafficking of Vps10p, the sorting receptor for Cpy1p, from the Golgi to the trans-Golgi network in btn1Δ cells. Our data also implicate btn1 in other Vps10-independent Cpy1-sorting pathways. Furthermore, btn1 affects the number, intracellular location and structure of Golgi compartments. We show that the prevacuole location of Btn1p is at the Golgi, because Btn1p colocalises predominantly with the Golgi marker Gms1p in compartments that are sensitive to Brefeldin A. Btn1p function might be linked to that of Vps34p, a phosphatidylinositol 3-kinase, because Btn1p acts as a multicopy suppressor of the severe Cpy1p vacuole protein-sorting defect of vps34Δ cells. Together, these results indicate an important role for Btn1p in the Golgi complex, which affects Golgi homeostasis and vacuole protein sorting. We propose a similar role for CLN3 in mammalian cells.
The nuclear pore component Nup358 promotes transportin-dependent nuclear import
Authors: Hutten Saskia , Wälde Sarah , Spillner Christiane , Hauber Joachim , Kehlenbach Ralph H.
Published: March 2009

Nup358 (also known as RanBP2), a component of the cytoplasmic filaments of the nuclear pore complex, has been implicated in various nucleocytoplasmic transport pathways. Here, we identify Nup358 as an important factor for transportin-mediated nuclear import. Depletion of Nup358 resulted in a strong inhibition of nuclear import of the human immunodeficiency virus type 1 (HIV-1) Rev protein. HIV-1 Rev is an RNA-binding protein that is required for CRM1 (also known as exportin 1)-dependent nuclear export of unspliced or partially spliced viral RNA. We show that transportin is the major nuclear import receptor for HIV-1 Rev in HeLa cells. Overexpression of transportin strongly promoted nuclear import of HIV-1 Rev in Nup358-depleted cells, indicating that the import receptor becomes rate-limiting under these conditions. Importantly, the import rate of other transportin-dependent proteins was also significantly reduced in Nup358-depleted cells. Our data therefore suggest a general role for Nup358 in transportin-mediated nuclear import.
Nucleocytoplasmic shuttling of soluble tubulin in mammalian cells
Authors: Akoumianaki Tonia , Kardassis Dimitris , Polioudaki Hara , Georgatos Spyros D. , Theodoropoulos Panayiotis A.
Published: March 2009

We have investigated the subcellular distribution and dynamics of soluble tubulin in unperturbed and transfected HeLa cells. Under normal culture conditions, endogenous α/β tubulin is confined to the cytoplasm. However, when the soluble pool of subunits is elevated by combined cold-nocodazole treatment and when constitutive nuclear export is inhibited by leptomycin B, tubulin accumulates in the cell nucleus. Transfection assays and FRAP experiments reveal that GFP-tagged β-tubulin shuttles between the cytoplasm and the cell nucleus. Nuclear import seems to occur by passive diffusion, whereas exit from the nucleus appears to rely on nuclear export signals (NESs). Several such motifs can be identified by sequence criteria along the β-tubulin molecule and mutations in one of these (NES-1) cause a significant accumulation in the nuclear compartment. Under these conditions, the cells are arrested in the G0-G1 phase and eventually die, suggesting that soluble tubulin interferes with important nuclear functions. Consistent with this interpretation, soluble tubulin exhibits stoichiometric binding to recombinant, normally modified and hyper-phosphorylated/acetylated histone H3. Tubulin-bound H3 no longer interacts with heterochromatin protein 1 and lamin B receptor, which are known to form a ternary complex under in vitro conditions. Based on these observations, we suggest that nuclear accumulation of soluble tubulin is part of an intrinsic defense mechanism, which tends to limit cell proliferation under pathological conditions. This readily explains why nuclear tubulin has been detected so far only in cancer or in transformed cells, and why accumulation of this protein in the nucleus increases after treatment with chemotherapeutic agents.
Production of a 15-membered Ring Orifice in Open-cage Fullerenes by Double Photooxygenation of Azafulleroid
Authors: Hachiya Houjin , Kabe Yoshio
Published: March 2009

Photooxygenation of silyl-modified azafulleroids 1b and 1c gave open-cage fullerenes having keto lactam 2b and 2c or diketo imide 3b and 3c functional groups on 11- or 15-membered ring orifices. The high reactivity of the bridgehead double bonds was estimated by π-orbital axis vector (POAV) analysis comparing the bisfulleroid derivatives 5d, 5e, 6d, and 6e.
Taxing Capital? Not a Bad Idea After All!
Authors: Conesa Juan Carlos , Kitao Sagiri , Krueger Dirk
Published: March 2009

We quantitatively characterize the optimal capital and labor income tax in an overlapping generations model with idiosyncratic, uninsurable income shocks and permanent productivity differences of households. The optimal capital income tax rate is significantly positive at 36 percent. The optimal progressive labor income tax is, roughly, a flat tax of 23 percent with a deduction of $7,200 (relative to average household income of $42,000). The high optimal capital income tax is mainly driven by the life-cycle structure of the model, whereas the optimal progressivity of the labor income tax is attributable to the insurance and redistribution role of the tax system. (JEL E13, H21, H24, H25)
A comprehensive analysis of the La-motif protein superfamily
Authors: Bousquet-Antonelli Cécile , Deragon Jean-Marc
Published: March 2009

The extremely well-conserved La motif (LAM), in synergy with the immediately following RNA recognition motif (RRM), allows direct binding of the (genuine) La autoantigen to RNA polymerase III primary transcripts. This motif is not only found on La homologs, but also on La-related proteins (LARPs) of unrelated function. LARPs are widely found amongst eukaryotes and, although poorly characterized, appear to be RNA-binding proteins fulfilling crucial cellular functions. We searched the fully sequenced genomes of 83 eukaryotic species scattered along the tree of life for the presence of LAM-containing proteins. We observed that these proteins are absent from archaea and present in all eukaryotes (except protists from the Plasmodium genus), strongly suggesting that the LAM is an ancestral motif that emerged early after the archaea-eukarya radiation. A complete evolutionary and structural analysis of these proteins resulted in their classification into five families: the genuine La homologs and four LARP families. Unexpectedly, in each family a conserved domain representing either a classical RRM or an RRM-like motif immediately follows the LAM of most proteins. An evolutionary analysis of the LAM-RRM/RRM-L regions shows that these motifs co-evolved and should be used as a single entity to define the functional region of interaction of LARPs with their substrates. We also found two extremely well conserved motifs, named LSA and DM15, shared by LARP6 and LARP1 family members, respectively. We suggest that members of the same family are functional homologs and/or share a common molecular mode of action on different RNA baits.
Long-Term Outcome of Continuous Ambulatory Peritoneal Dialysis (CAPD) Peritonitis: Surgery can be Avoided
Authors: Al-Allak A , Jones R , Stiff R , Dharmasena D , Morris-Stiff G
Published: March 2009

INTRODUCTION

Continuous ambulatory peritoneal dialysis (CAPD) has become the preferred method of home dialysis for patients with end-stage renal failure. Peritonitis is a common and serious complication and requires prompt diagnosis and treatment. The aim of this study was to assess what proportion of patients with CAPD peritonitis that required surgical intervention for on-going sepsis or for peritonitis-related bowel obstruction.

PATIENTS AND METHODS

All patients presenting with a first episode of CAPD peritonitis during the 5-year period from 1994–1998 were identified from a prospectively maintained database. Data collected included patient demographics, details of peritonitis episodes and their treatment, and details of any surgical intervention undertaken.

RESULTS

A total of 500 episodes were identified in 168 patients of whom 162 had complete follow-up representing 488 peritonitis episodes. Sixty-three patients experienced one episode of peritonitis, 33 two episodes, 20 had three episodes, and 46 had more than three episodes. None of the patients underwent surgery either primarily or for complications of the infective episode. A total of 465 episodes were due to a single organism (95%) and the remainder were due to multiple organisms (5%). The most common causative organisms were Gram-positive cocci (308 episodes; 71%) followed by Gram-negative bacilli (106 episodes; 24%). In 55 patients (34%), the same organism was implicated in consecutive admissions. Patients with autosomal dominant polycystic kidney disease (ADPKD), whilst accounting for 12 of 169 (7%) patients in the cohort, experienced 23 of 125 (18.4%) episodes of peritonitis by Gram-negative cocci. Such infections were seen in 8 of 12 (66.7%) ADPKD patients and accounted for 23 of 40 (57.5%) infections experienced by the ADPKD patients.

CONCLUSIONS

Whilst CAPD peritonitis is a common problem in the renal failure population, with almost 100 episodes per year, it would appear that most episodes can be managed using intraperitoneal antibiotics without the need for surgical intervention.
Undertaking Procedure-Based Assessment is Feasible in Clinical Practice
Authors: James K , Cross K , Lucarotti ME , Fowler AL , Cook TA
Published: March 2009

INTRODUCTION

With the development of a new curriculum, workplace based assessments such as procedure-based assessment (PBA) are becoming increasingly common within surgical training. However, there have been concerns about the impact of these assessments on clinical practice. This study assessed the time taken to complete PBA forms to determine whether it is feasible in clinical practice.

MATERIALS AND METHODS

PBAs for three colorectal procedures (anterior resection, right hemicolectomy and anal fistula) were undertaken by various trainers and trainees. A pilot study was performed to identify potential reasons for incomplete forms and procedural modifications subsequently applied in the main study. Times taken to complete the consenting and operative components of the forms were recorded.

RESULTS

Incomplete forms in the pilot were mainly attributable to time constraints. In the main study, all assessments were completed within 30 min. Assessment times increased with complexity of the procedure. Median times for completing the consenting and operative components in anterior resection were 13 min (range, 8–15 min) and 15 min (range, 10–18 min), respectively.

CONCLUSIONS

PBAs are feasible in clinical practice and are valued by trainees as a means of enabling focused feedback and targeted training. Commitment from trainers and trainees will be required but, with adequate planning, the assessment tool is effective with minimal impact on clinical practice.
A Brief Comparison of Orthopaedic Training in English-Speaking Countries
Authors: Syed Shakir , Mirza Aun H , Ali Ashgar
Published: March 2009

The purpose of this article is to examine current orthopaedic training in the UK and objectively compare this with other English-speaking countries.
Cost Minimisation Using Clinic-Based Treatment for Common Hand Conditions – A Prospective Economic Analysis
Authors: Webb JA , Stothard J
Published: March 2009

INTRODUCTION

The purpose of this study was to compare the cost of treatment of Dupuytren's disease, ganglia and trigger digits in the out-patient department with the operating theatre.

PATIENTS AND METHODS

All patients seen in a new patient hand clinic with a diagnosis of Dupuytren's disease, trigger digit or ganglion of the wrist or hand requiring treatment were prospectively identified over a 6-month period. The numbers undergoing a procedure in the out-patient clinic or theatre were recorded. Costings of theatre time and out-patient time, as well as national tariff income, were obtained from the hospital management.

RESULTS

Over the 6-month period, 80, 26, and 52 patients were treated with regard to Dupuytren's disease, ganglia and trigger digits, respectively. Of these, 37, 23, and 44 were treated by an out-patient procedure, and 43, 3 and 8 underwent a formal operation. The total cost of the out-patient procedures was calculated at £1560 over 6 months. To perform these as formal operations would have cost £64,896. The cost savings were, therefore, £63,336, or £126,672 per annum.

CONCLUSIONS

Out-patient interventions for Dupuytren's disease, ganglia and trigger digits result in significant cost savings over formal surgical treatment.
A Study of Microbial Colonisation of Orthopaedic Tourniquets
Authors: Ahmed SMY , Ahmad R , Case R , Spencer RF
Published: March 2009

INTRODUCTION

Tourniquets are employed widely in orthopaedic surgery. The use of the same tourniquet on a repetitive basis without a standard protocol for cleaning may be a source of cross-infection. This study examines the contamination of the tourniquets in our institution.

MATERIALS AND METHODS

Agar plates were used to take samples from 20 tourniquets employed in orthopaedic procedures. Four sites on each tourniquet were cultured and incubated at 37°C for 48 h.

RESULTS

All sampled tourniquets were contaminated with colony counts varying from 9 to > 385. Coagulase-negative Staphylococcus spp. were the most commonly grown organisms from the tourniquets (96%).Some tourniquets had growths of important pathogens including methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas spp., and S. aureus. On cleaning five tourniquets with Clinell (detergent and disinfectant) wipes (GAMA Healthcare Ltd, London, UK), there was a 99.2% reduction in contamination of the tourniquets 5 min after cleaning.

CONCLUSIONS

In addition to the manufacturers' guidelines, we recommend the cleaning of tourniquets with a disinfectant wipe before every case.
Recurrent Sigmoid Volvulus – Early Resection may Obviate Later Emergency Surgery and Reduce Morbidity and Mortality
Authors: Larkin JO , Thekiso TB , Waldron R , Barry K , Eustace PW
Published: March 2009

INTRODUCTION

Acute sigmoid volvulus is a well recognised cause of acute large bowel obstruction.

PATIENTS AND METHODS

We reviewed our unit's experience with non-operative and operative management of this condition. A total of 27 patients were treated for acute sigmoid volvulus between 1996 and 2006. In total, there were 62 separate hospital admissions.

RESULTS

Eleven patients were managed with colonoscopic decompression alone. The overall mortality rate for non-operative management was 36.4% (4 of 11 patients). Fifteen patients had operative management (five semi-elective following decompression, 10 emergency). There was no mortality in the semi-elective cohort and one in the emergency surgery group. The overall mortality for surgery was 6% (1 of 15). Five of the seven patients managed with colonoscopic decompression alone who survived were subsequently re-admitted with sigmoid volvulus (a 71.4% recurrence rate). The six deaths in our overall series each occurred in patients with established gangrene of the bowel. With early surgical intervention before the onset of gangrene, however, good outcomes may be achieved, even in patients apparently unsuitable for elective surgery. Eight of the 15 operatively managed patients were considered to be ASA (American Society of Anesthesiologists) grade 4. There was no postoperative mortality in this group.

CONCLUSIONS

Given the high rate of recurrence of sigmoid volvulus after initial successful non-operative management and the attendant risks of mortality from gangrenous bowel developing with a subsequent volvulus, it is our contention that all patients should be considered for definitive surgery after initial colonoscopic decompression, irrespective of the ASA score.
Rapid Fracture Healing in a Patient with Inherited Prion Disease
Authors: Khan RM , Gunaratne LA , Kinmont JC
Published: March 2009

There do not appear to be any reports or guidelines in the published literature regarding the outcomes of operative or conservative management of fractures in patients with known prion disease. This case report may be helpful in the clinical management of fractures in such patients.
Audit of Two-Week Rule Referrals for Suspected Testicular Cancer in Cornwall, 2003–2005
Authors: Kumaraswamy Prakash , Cox Robert , O'Rourke John S , Willis Robert G.
Published: March 2009

INTRODUCTION

The objective was to evaluate the two-week wait referral system for suspected testicular cancer and to compare waiting times from referral to treatment before and after the introduction of the two-week wait process.

PATIENTS AND METHODS

We reviewed 241 case notes for patients referred under the two-week wait system with suspected testicular tumour during a complete 3-year period (2003–2005) and recorded information from the referral letter, findings in the urology clinic, results of ultrasound and final outcomes. We also identified 42 cases of testicular tumour treated during a complete 3-year period (1997–1999) just before the two-week wait system was introduced. The journey from referral to treatment for tumour cases was compared during these two periods.

RESULTS

Testicular cancer was only found in 8% of patients referred by the two-week wait system. We judged the referral to be inappropriate in 48% of cases. Of referred cases, 78% required no surgical treatment. There was a significant improvement of 9 days in the average time from general practitioner (GP) referral to urology clinic attendance but all other journey intervals remained the same.

CONCLUSIONS

The performance of GPs in examining scrotal swellings and applying the two-week wait guidelines was very poor, resulting in many unnecessary urgent clinic visits. The referral system speeds up the visit to a urology clinic but the overall effect is probably not of clinical significance. We suggest that it would be much more cost-effective for all these patients to have an ultrasound scan within 2 weeks instead of a urology clinic appointment.
Fast-Track Management of Patients Undergoing Proximal Pancreatic Resection
Authors: French JJ , Mansfield SD , Jaques K , Jaques BC , Manas DM , Charnley RM
Published: March 2009

INTRODUCTION

To avoid the risk of complications of biliary drainage, a feasibility study was carried out to determine whether it might be possible to fast-track surgical treatment, with resection before biliary drainage, in jaundiced patients with proximal pancreatic/peri-ampullary malignancy.

PATIENTS AND METHODS

Over an 18-month period, based on their presenting bilirubin levels and other logistical factors, all jaundiced patients who might be suitable for fast-track management were identified. Data on complications and hospital stay were compared with those patients in whom a conventional pathway (with biliary drainage) was used during the same time period. Data were also compared with a group of patients from the preceding 6 months.

RESULTS

Nine patients were fast-tracked and 49 patients treated in the conventional pathway. Fast-track patients mean (SD) serum bilirubin level was 265 μmol/l (81.6) at the time of the operation compared to 43 μmol/l (51.3; P ≥ 0.0001) in conventional patients. Mean (SD) of time from referral to operation, 14 days (9) versus 59 days (36.9), was significantly shorter in fast-track patients than conventional patients (P ≤ 0.0001). Length of hospital stay mean (SD) at 17 (6) days versus 22 days (19.6; P = 0.2114), surgical complications and mortality in fast-track patients were similar to conventional patients. Prior to surgery, the 49 conventional patients underwent a total of 73 biliary drainage procedures resulting in seven major complications. Comparison with the group of patients from the previous 6 months indicated that the conventional group were not disadvantaged.

CONCLUSIONS

Fast-track management by resection without biliary drainage of selected patients with distal biliary strictures is safe and has the potential to reduce the waiting time to surgery, overall numbers of biliary drainage procedures and the complications thereof.
It ain't Over Till the Liposuctioned Lady Sings
Authors: Kay Simon
Published: March 2009

Rum old thing, opera. If you want to tell a story what does the music add and where does opera become operetta or slide into musical? Most of us ignorami would recognise perhaps a dozen pieces of music from operas and probably mostly the same ones. I have a sneaky suspicion that this is because they are the great ones, the uplifting and moving ones that set moods and attitudes. That is what the music in an opera can do: allow emotive summaries, herald mood changes or enhance and direct feeling. It also prepares us for the surreal and absolves the librettist of some of the pedantic baggage of realism.
The post-CCT subconsultant grade: the case against
Authors: Stephens Michael
Published: March 2009

The concept of a subconsultant grade is not a new one and has existed within the NHS in various guises for a number of years (such as staff grades and senior registrars). In the main, changes in postgraduate education such as the Calman reforms and Modernising Medical Careers have aimed to reduce such roles as they are inevitably heavily weighted to service provision with limited prospects of career progression. However, the increasing discrepancy between the number of trainees completing their Certificate of Completion of Training (CCT) and the number of vacant consultant posts has pushed this contentious topic back to the fore.
Surgery and medicine in Rwanda
Authors: Anderson Paul
Published: March 2009

The desperate need to upgrade medical resources in developing countries is highlighted by Paul Anderson, who shares his experiences of leading a volunteer surgical team into a Rwandan border town.
Fair and Ethical Trade in Health: Lessons from Surgical Instruments
Authors: Bhutta Mahmood , Roberts Olivia
Published: March 2009

The NHS spends £20 billion on procuring a wide range of medical goods every year. Worldwide, the amount traded in products for health care runs into trillions of dollars. With such large sums of money we quite rightly ask about value for money as well as the quality of the goods we buy. But in addition to quality we should, but don't, ask about the conditions under which those goods are made. Unfortunately, recent research has found that some of the products we are using to promote health in the UK may actually be damaging health elsewhere, through unethical labour practices in their manufacture.
Effect of Mycophenolate Acyl-Glucuronide on Human Recombinant Type 2 Inosine Monophosphate Dehydrogenase
Authors: Gensburger Olivier , Picard Nicolas , Marquet Pierre
Published: March 2009

Background: The immunosuppressive effect of mycophenolic acid (MPA) is essentially attributed to IMPDH II inhibition, which leads to a reduction of lymphocyte proliferation. We investigated the action of the MPA metabolites MPA-phenyl-glucuronide (MPAG) and MPA-acyl-glucuronide (AcMPAG) on recombinant human IMPDH II (rhIMPDH II), as well as their passage into lymphocytes in vitro.

Methods: We measured rhIMPDH II activity spectrophotometrically through the initial velocity of NADH formation, leading to the computation of the kinetic parameters Km, IC50, and Ki (Michaelis constant, half-maximal inhibition concentration, and inhibition constant). We measured intracellular and extracellular concentrations of MPA, MPAG, and AcMPAG after incubation of Jurkat lymphoma cells with each compound separately, using liquid chromatography–tandem mass spectrometry.

Results: MPA and AcMPAG showed an inhibition of rhIMPDH II (IC50 25.6 μg/L and 301.7 μg/L, respectively; the Ki of MPA for NAD and IMP was 50.8 and 57.7 nmol/L, respectively; and that of AcMPAG for NAD and IMP was 382.0 and 511.0 nmol/L. MPAG had no significant effect on the enzyme. AcMPAG apparently acts by the same uncompetitive inhibition mechanism as MPA, with a 12-fold higher IC50 and an 8–10 times higher Ki. When coincubated with MPA, AcMPAG activity was negligible at pharmacological concentrations. Furthermore, after 6-h incubation at their respective maximum concentration (Cmax), MPA was 10 times more concentrated in Jurkat cells than AcMPAG.

Conclusions: AcMPAG is a weaker inhibitor of rhIMPDH II than MPA and is less concentrated in lymphocytes in vitro, suggesting that it would not be pharmacologically active in vivo and might not need to be monitored in MPA-treated patients.
Intense media coverage
Authors: Puijk Roel
Published: March 2009

In an increasingly fragmented media environment, some issues stand out and generate huge publicity for a limited period of time. Using Scannell's categories, event and happening, the article analyses two cases – the 1994 Olympic Winter Games and the death of Princess Diana. It is argued that they, in order to account for audience involvement and the complexity of meanings, should be analyzed in relation to the discourses and narrative developments across different media that embed the main, televised, moments. It is also argued that today's proliferation of media channels and the presence of new media can contribute to increasing attention and involvement of the audience. Ceremonial media events that previously dominated have moved in two directions: integrative, entertainment oriented events organized by the media and disaster events.
Gender and interface agents in the on-line news
Authors: Isotalus Pekka
Published: March 2009

Interface agents are increasingly being used to enhance the user-friendliness of computers. In the new mobile technology of handheld computers, interface agents are also being used to present on-line news. The purpose of the study was to explore how the gender of the interface agent and the user affect evaluations of the agent and the news service. The results revealed that attitudes toward the interface agent significantly correlated with evaluations of the entire news service. Moreover, the gender of the participant and of the agent was significant for an evaluation of the credibility and entertainment value of the news service.
Incorporation of Fracture Information in Specifications
Authors: Payne WF
Published: March 2009

Fracture tests for material and process specifications involving high-strength alloys are necessary to insure adequate inspection standards for material and hardware acceptance. Proper specimen design is necessary to produce useful toughness information, especially a specimen size adequate to avoid general yielding prior to fracture. Evidence of significant toughness variation in commercial alloys is presented. The paper illustrates the use of present analytical expressions to determine inspection standards for isolated defects of various geometry and for linear arrays of multiple defects. Specific rejection criteria for multiple defects are suggested.
A Study of the Deformation Characteristics of a Stiff Fissured Clay
Authors: Lo KY , Seychuk JL , Adams JI
Published: March 2009

The estimation of elastic settlement of a foundation requires a realistic knowledge of the modulus of deformation of the soil. It commonly is known that the modulus value of a soil may vary over wide limits, depending on the method of test and many other factors. A comprehensive evaluation of the modulus of deformation of a stiff fissured clay is presented. The effects of sample disturbance, strain rate of compression, anisotropy, sample size, and confining pressure on the modulus value were investigated in the laboratory. These results were compared with modulus values obtained from plate loading tests in deep test pits. The effect of sample size did not show a marked variation in the value of modulus determined. A comparison between the results of borehole and block samples showed the effect of sample disturbance to be by far the most overriding factor. The results from plate loading tests appeared to provide the most consistent and reliable values.
Sampler Trials in Overconsolidated Sensitive Clay
Authors: Eden WJ
Published: March 2009

During the excavation of pump wells for a sewage treatment plant, it was possible to obtain large, undisturbed, block samples of extremely sensitive yet overconsolidated clay from depths ranging from the surface to 70 ft. With these block samples as a reference, sampling was conducted with four types of piston samples, and the test results were compared with those obtained from the block samples. The in situ strength of the clay also was measured with the field vane test. Samplers used in the trials were the Swedish Foil, the Norwegian 54 mm, the Swedish 50 mm, and the 5-in.-diameter Osterberg hydraulic sampler.

The results showed that none of the samplers nor the field vane test were successful in obtaining results that could be compared consistently with results obtained from the block samples. The main conclusion of this study is that present methods of sampling of such soils by boring from the surface do not produce satisfactory undisturbed samples in this material.
Effect of Thickness on the Fracture Toughness of 7075 Aluminum in the T6 and T73 Conditions
Authors: Allen FC
Published: March 2009

The objectives of the investigation described were to find the variation of fracture toughness with thickness for 7075-T6 and 7075-T73 materials and to provide data upon which a theory could be established for the variation of fracture toughness with thickness. A test program was conducted on 60 centrally cracked specimens varying in thickness from 0.05 to 0.75 in.

Analysis of the results showed that the two materials displayed substantially different characteristics. This is attributed to the fact that, owing to the low proportional limit of the T73 material, the net section stress was in the plastic range for most specimens, whereas for the T6 material the net section stress was always in the elastic range.

It was noted that during slow crack growth, the crack grew faster in the center than at the surface of the material. A generally parabolic shaped crack front, therefore, existed at failure. It was hypothesized that the crack shape corresponded to the development of plane stress at its boundaries and that fracture toughness based on final crack length would be constant. This appeared to be true for the T6 material, within the range tested, but could not be proved for the T73 material.

A lumped parameter, redundant force analysis of three plates of varying thickness was made. The results show the development of plane strain conditions with increased thickness. Although correlation with the test results was not established, extension of the work may provide explanation of the phenomena observed in tests.

An appendix provides theoretical load-deflection relationships for centrally cracked plates which include the effects of plasticity.
The Influence of Curvature on Stress Intensity at the Tip of a Circumferential Crack in a Cylindrical Shell
Authors: Adams NJI
Published: March 2009

The validity of a nondimensional curvature parameter, relating discontinuity size to shell radius and thickness, used to express the effect of curvature on stress intensification at a discontinuity in a cylindrical shell, has been substantiated within a limited range. Fatigue crack growth tests were conducted on flat and curved axially loaded specimens to examine the influence of curvature on stress intensity in cylindrical shells. Using crack growth rates, a curvature correction is obtained which can be used to apply a stress intensity analysis in flat sheets to cylinders. The influence of curvature on stress intensity is found to be similar to that of sheet buckling in flat sheets containing cracks.