bluuebunny/crossref_metadata_2025 huggingface dataset:
Paraganglioma of the mediastinum: challenges in diagnosis and surgical management
Authors: Wald Ori , Shapira Oz M , Murar Aiman , Izhar Uzi
Published: March 2010

Mediastinal paraganglioms are rare, highly vascularized tumors arising from chromaffin tissue located in the para-aortic ganglia. Tumors tend to invade bordering structures and may also form metastasis. Up to 50% of patients are asymptomatic and diagnosis is incidental. Presenting symptoms are related to catecholamine hypersecretion or to a mass effect. Complete surgical resection remains the standard of care due to malignant potential of the tumor and poor response to chemotherapy or radiation. Strategic location of the tumor in proximity to great vessels, trachea, and recurrent laryngeal nerve poses challenge for the surgeon. We report a case of a 59-year old asymptomatic female who was incidentally diagnosed with a middle mediastinal mass on a positron-emission tomography (PET-CT) scan performed as part of breast cancer surveillance. Complete resection of the tumor was achieved using cardiopulmonary bypass. The patient recovered uneventfully and in a ten-month follow up there is no evidence of recurrence.
Identification and characterization of a spontaneous ovarian carcinoma in Lewis rats
Authors: Sharrow Allison C , Ronnett Brigitte M , Thoburn Christopher J , Barber James P , Giuntoli Robert L , Armstrong Deborah K , Jones Richard J , Hess Allan D
Published: March 2010

Background

Ovarian carcinoma is the fourth most common cause of death from cancer in women. Limited progress has been made toward improving the survival rate of patients with this disease in part because of the lack of a good animal model. We present here a model of spontaneous ovarian carcinoma arising in a normal Lewis rat.

Methods

A spontaneously occurring tumor of the left ovary was found in a normal Lewis rat during necropsy, which was sectioned for histological examination and placed into single cell suspension. Tumor cells were passagedin vivoby intraperitoneal injection into immunocompetent Lewis rats, andin vitroculture resulted in generation of a cell line. Tumor cells were examined by flow cytometry for expression of estrogen receptor α, progesterone receptor, androgen receptor, her-2/neu, epithelial cell adhesion molecule, and CA125. β-catenin expression and cellular localization was assessed by immunocytochemistry. RNA was harvested for gene expression profiling and studying the expression of cytokines.

Results

The tumor, designated FNAR, could be serially transplanted into Lewis rats and propagated as a cell linein vitro, maintaining the properties of the original tumor. The FNAR cells displayed striking morphologic similarities to human ovarian carcinoma, resembling the endometrioid carcinoma subtype of surface epithelial neoplasms. The cells expressed estrogen receptor α, progesterone receptor, androgen receptor, her-2/neu, epithelial cell adhesion molecule, CA125, and nuclear β-catenin. A gene expression profile showed upregulation of a number of genes that are also upregulated in human ovarian carcinoma.

Conclusion

This reliable model of ovarian carcinoma should be helpful in better understanding the biology of the disease as well as the development of novel treatment strategies.
Impaired cerebrovascular reactivity in sepsis-associated encephalopathy studied by acetazolamide test
Authors: Szatmári Szilárd , Végh Tamás , Csomós Ákos , Hallay Judit , Takács István , Molnár Csilla , Fülesdi Béla
Published: March 2010

Introduction

The pathophysiology of sepsis-associated encephalopathy (SAE) is not entirely clear. One of the possible underlying mechanisms is the alteration of the cerebral microvascular function induced by the systemic inflammation. The aim of the present work was to test whether cerebral vasomotor-reactivity is impaired in patients with SAE.

Methods

Patients fulfilling the criteria of clinical sepsis and showing disturbance of consciousness of any severity were included (n = 14). Non-septic persons whithout previous diseases affecting cerebral vasoreactivity served as controls (n = 20). Transcranial Doppler blood flow velocities were measured at rest and at 5, 10, 15 and 20 minutes after intravenous administration of 15 mg/kgBW acetazolamide. The time course of the acetazolamide effect on cerebral blood flow velocity (cerebrovascular reactivity, CVR) and the maximal vasodilatory effect of acetazolemide (cerebrovascular reserve capacity, CRC) were compared among the groups.

Results

Absolute blood flow velocities after adminsitration of the vasodilator drug were higher among control subjects than in SAE. Assessment of the time-course of the vasomotor reaction showed that patients with SAE reacted slower to the vasodilatory stimulus than control persons. When assessing the maximal vasodilatory ability of the cerebral arterioles to acetazolamide during vasomotor testing, we found that patients with SAE reacted to a lesser extent to the drug than did control subjects (CRC controls:46.2 ± 15.9%, CRC SAE: 31,5 ± 15.8%, P < 0.01).

Conclusions

We conclude that cerebrovascular reactivity is impaired in patients with SAE. The clinical significance of this pathophysiological finding has to be assessed in further studies.
Editorial: When charge is in charge—“Millikan” for leukocyte biologists
Authors: Pick Edgar
Published: March 2010

Subcellular localization of signaling proteins in leukocytes is regulated by electrostatic interactions between negatively charged membrane phospholipids and polybasic motifs in the proteins.
Differential mechanisms of memory CD8 T cell maintenance by individual myeloid cell types
Authors: Frasca Loredana , Stonier Spencer W , Overwijk Willem W , Schluns Kimberly S
Published: March 2010

DC subsets and macrophages differentially mediate memory CD8 T cell maintenance via IL-15 transpresentation and CD70/CD27 interactions.

This study tested the hypothesis that individual myeloid subsets have a differential ability to maintain memory CD8 T cells via IL-15. Although DCs support IL-15-mediated homeostasis of memory CD8 T cells in vivo, whether various DC subsets and other myeloid cells similarly mediate homeostasis is unknown. Therefore, we studied the ability of different myeloid cells to maintain memory CD8 T cells in vitro. Using an in vitro cocoulture system that recapitulated known roles of DCs and IL-15 on memory CD8 T cells, all in vitro-derived or ex vivo-isolated DCs maintained CD8 T cells better than rIL-15 alone, and FLT-3L-DCs are the most efficient compared with GM-DCs, BM-derived macrophages, or freshly isolated DCs. Although FLT-3L-DCs were the least effective at inducing CD8 T cell proliferation, FLT-3L-DCs promoted better CD8 T cell survival and increased Bcl-2 and MCL-2 expression in CD8 T cells. T cell maintenance correlated only partially with DC expression of IL-15Rα and IL-15, suggesting that DCs provided additional support signals. Indeed, in the absence of IL-15 signals, CD70/CD27 further supported CD8 T cell maintenance. IFN-α enhanced CD70 expression by DCs, resulting in increased proliferation of CD8 T cells. Overall, this study supports our hypothesis by demonstrating that specific DC subtypes had a greater capacity to support memory CD8 T cell maintenance and did so through different mechanisms. Furthermore, this study shows that IL-15 trans-presentation can work in conjunction with other signals, such as CD70/CD27 interactions, to mediate CD8 T cell homeostasis efficiently.
Economic evaluation of online computerised cognitive–behavioural therapy without support for depression in primary care: randomised trial
Authors: Gerhards S. A. H. , de Graaf L. E. , Jacobs L. E. , Severens J. L. , Huibers M. J. H. , Arntz A. , Riper H. , Widdershoven G. , Metsemakers J. F. M. , Evers S. M. A. A.
Published: March 2010

Background

Evidence about the cost-effectiveness and cost utility of computerised cognitive–behavioural therapy (CCBT) is still limited. Recently, we compared the clinical effectiveness of unsupported, online CCBT with treatment as usual (TAU) and a combination of CCBT and TAU (CCBT plus TAU) for depression. The study is registered at the Netherlands Trial Register, part of the Dutch Cochrane Centre (ISRCTN47481236).

Aims

To assess the cost-effectiveness of CCBT compared with TAU and CCBT plus TAU.

Method

Costs, depression severity and quality of life were measured for 12 months. Cost-effectiveness and cost-utility analyses were performed from a societal perspective. Uncertainty was dealt with by bootstrap replications and sensitivity analyses.

Results

Costs were lowest for the CCBT group. There are no significant group differences in effectiveness or quality of life. Cost-utility and cost-effectiveness analyses tend to be in favour of CCBT.

Conclusions

On balance, CCBT constitutes the most efficient treatment strategy, although all treatments showed low adherence rates and modest improvements in depression and quality of life.
Cognitive model of caregiving in psychosis
Authors: Kuipers Elizabeth , Onwumere Juliana , Bebbington Paul
Published: March 2010

Background

There is a long history of research into the attributes of carers of people with psychosis, but few interventions target their distress or their difficulties.

Aims

To describe an empirically based model of the relationships of those caring for people with psychosis to inform clinical and theoretical advances.

Method

We developed a model of informal carer relationships in psychosis, based on an integration of the literature elaborating the concept of expressed emotion. The model accounts for divergent outcomes of three relationship types: positive, overinvolved and critical/hostile relationships.

Results

Good evidence supports a number of hypotheses concerning the origin and maintenance of these relationship outcomes, which relate to specific differences in carer attributions, illness perceptions, coping behaviour, social support, distress, depression and low self-esteem predicted by our model. We propose that interventions aimed at modifying the specific maintenance factors involved in the different styles of relationships will optimise therapeutic change both for service users with psychosis and for their carers.

Conclusions

Family work in psychosis, which improves relationships through problem-solving, reduces service user relapse. It is now time to consider theory-based interventions focused on improving carer outcomes.
Burden of chronic physical conditions and mental disorders in
primary care
Authors: Fernández Anna , Saameño Juan Ángel Bellón , Pinto-Meza Alejandra , Luciano Juan Vicente , Autonell Jaume , Palao Diego , Salvador-Carulla Luis , Campayo Javier García , Haro Josep Maria , Serrano Antoni ,   the Dasmap investigators
Published: March 2010

Background

The World Health Organization (WHO) has stated that the three leading
causes of burden of disease in 2030 are projected to include HIV/AIDS,
unipolar depression and ischaemic heart disease.

Aims

To estimate health-related quality of life (HRQoL) and quality-adjusted
life-year (QALY) losses associated with mental disorders and chronic
physical conditions in primary healthcare using data from the diagnosis
and treatment of mental disorders in primary care (DASMAP) study, an
epidemiological survey carried out with primary care patients in
Catalonia (Spain).

Method

A cross-sectional survey of a representative sample of 3815 primary care
patients. A preference-based measure of health was derived from the
12-item Short Form Health Survey (SF–12): the Short Form–6D (SF–6D)
multi-attribute health-status classification. Each profile generated by
this questionnaire has a utility (or weight) assigned. We used
non-parametric quantile regressions to model the association between both
mental disorders and chronic physical condition and SF–6D scores.

Results

Conditions associated with SF–6D were: mood disorders, β =−0.20 (95% CI
−0.18 to −0.21); pain, β = −0.08 (95%CI −0.06 to −0.09) and anxiety, β
=−0.04 (95% CI −0.03 to −0.06). The top three causes of QALY losses
annually per 100 000 participants were pain (5064), mood disorders (2634)
and anxiety (805).

Conclusions

Estimation of QALY losses showed that mood disorders ranked second behind
pain-related chronic medical conditions.
FREDA: a human rights-based approach to healthcare
Authors: Curtice Martin J. , Exworthy Tim
Published: March 2010

The introduction of the Human Rights Act 1998 in the UK has not led to widespread knowledge and understanding in patient and carer groups, healthcare professionals or at an organisational level. This knowledge deficit has been recognised by government bodies and other agencies, which has led to the introduction of a bottom-up human rights-based approach that can be used by individuals and organisations alike in everyday practice. It avoids the need to have technical knowledge of the Human Rights Act and associated case law and is based upon concepts that underpin all the articles of the Act. The human rights-based approach is the process by which human rights can be protected by adherence to underlying core values of fairness, respect, equality, dignity and autonomy, or FREDA.
Impact of patient suicide on consultant psychiatrists in Ireland
Authors: Landers Anne , O'Brien Sinead , Phelan Darra
Published: March 2010

Aims and method

To study the effects of patient suicide on both personal and professional life of consultant psychiatrists in Ireland. A questionnaire was sent to all practising consultants.

Results

Most respondents (80%) had experienced patient suicide in their careers; in up to 97% it had an impact on either their professional or personal life. The most common effects were preoccupation with the suicide and guilt. Unpredicted suicides and perceived effect on patients' families worsened the distress. Informal support was of most help, with a large proportion of study participants suggesting independent case review would be helpful.

Clinical implications

Patient suicide is an almost universally distressing event for psychiatrists. Although consultants receive psychological support from family and friends, many would also welcome an objective professional review.
Mystery shopping in psychiatric service evaluation – ethical issues
Authors: Walker Tom , George Sanju
Published: March 2010

Mystery shopping is being increasingly used in psychiatric service evaluation but because it involves an element of deception, akin to research involving pseudo-patients, questions have been raised about its ethical acceptability. Here we discuss these ethical issues and argue that mystery shopping should only take place subject to certain conditions. First, it ought to be clear that the evaluation cannot be done by using non-deceptive methods. Second, independent scrutiny should conclude that the importance of the aims of the evaluation is sufficient to justify the deception used.
Phase I Combination Trial of Lenalidomide and Azacitidine in Patients With Higher-Risk Myelodysplastic Syndromes
Authors: Sekeres Mikkael A. , List Alan F. , Cuthbertson David , Paquette Ronald , Ganetsky Rebecca , Latham Deborah , Paulic Katarina , Afable Manuel , Saba Hussain I. , Loughran Thomas P. , Maciejewski Jaroslaw P.
Published: March 2010

Purpose

Lenalidomide and azacitidine are active in patients with lower- and higher-risk myelodysplastic syndromes (MDS). These agents may complement each other by targeting both the bone marrow microenvironment and hypomethylating action on the malignant clone.

Patients and Methods

This phase I trial explored the safety of combination therapy in patients with higher-risk MDS. Response and characterization of molecular and methylation status of responders were secondary objectives. Patients were enrolled using a 3 + 3 dose escalation. Cycles lasted 28 days, and patients received a maximum of seven cycles.

Results

Of 18 patients enrolled, median age was 68 years (range, 52 to 78 years), interval from diagnosis was 5 weeks (range, 2 to 106 weeks), and follow-up was 7 months (range, 1 to 26 months). International Prognostic Scoring System categories were intermediate 1 (n = 2), intermediate 2 (n = 10), and high (n = 6). No dose-limiting toxicities occurred, and a maximum-tolerated dose was not reached. Grades 3 to 4 nonhematologic toxicities (> 1) included febrile neutropenia (n = 5), cardiac (n = 2), and CNS hemorrhage (n = 2). Median absolute neutrophil count decrease was 26%, and platelet decrease was 1% (mean, 24%). The overall response rate was 67%: eight patients (44%) had a complete response (CR); three patients (17%) had hematologic improvement; one patient (6%) had marrow CR. Patients achieving CR were more likely to have normal cytogenetics and lower methylation levels.

Conclusion

The combination of lenalidomide and azacitidine is well tolerated with encouraging clinical activity. The go-forward dose is azacitidine 75 mg/m2 on days 1 through 5 and lenalidomide 10 mg on days 1 through 21.
Design method of self-expanding stents suitable for the patient's condition
Authors: Yoshino D , Inoue K
Published: March 2010

A medical device of mesh-shaped tubular structure, called a stent, is frequently used to expand the stenosis of a blood vessel. The stent normally has the structure of longitudinally repeated wavy wire parts and strut parts, and its mechanical properties, such as bending flexibility and rigidity in the radial direction, mainly depend on the shape of the wavy wire and the construction of the strut. This paper presents, a design support system for self-expanding stents that can design stent shape and evaluate stent performance as routine flow. A two-stage method for designing suitable stent shapes is built into this system. The mechanical properties of self-expandable stents are evaluated using a non-linear finite element method. The wire length of the stent and the wire width are adopted as design parameters, and the sensitivity of the mechanical properties to these parameters is obtained. When the patient's conditions, such as blood vessel type and the diameter of the blood vessel with stenosis, are given by medical examination, the performance of the stent in restoring blood flow has to be determined. Finally, a method is proposed for designing suitable stents with the desired performance on the basis of mechanical properties.
Simulation procedure for the co-optimization of photovoltaic water pumping systems
Authors: Odeh I , Yohanis Y G , Norton B
Published: March 2010

Photovoltaic (PV)-powered centrifugal water pumping systems have been modelled based on field experience and analysis of long-term measured performance of several installed PV-powered water pumping systems. This paper presents detailed modelling of a PV array, an inverter, a three-phase induction motor, a centrifugal pump, a well, a storage tank, an overflow controller, and an integrated reverse osmosis desalination unit. The component models were validated using both laboratory measurements and long-term monitored data. All system components have been modelled separately, and the system was modelled in TRNSYS. The models are capable of simulating grid-connected, diesel-powered, and PV-powered water pumping systems, and can consider the following design and operational variables: constant voltage tracking, voltage frequency modulation, and maximum power point tracking algorithms; variable inverter frequency with variable motor efficiency, variable inverter frequency with constant motor efficiency, and constant inverter frequency with variable motor efficiency algorithms; and variation in PV temperature.
A study of partial admission characteristics on a small-scale radial-inflow turbine
Authors: Cho C-H , Cho S-Y , Ahn K-Y
Published: March 2010

When a turbine is operated at a low partial admission rate, its performance can show wide deviation from the predicted results depending on the operating conditions and geometric parameters. In order to investigate the performance characteristics on a partially admitted turbine based on the geometric parameters, a turbine was tested with various tip clearances and nozzle flow angles. In addition, the effects of the partial admission rates were studied, and the turbine output power on each stage was measured to investigate the effects of the mainstream diffusion along the turbine stage by partial admission. The outer diameter of the turbine rotor was 108 mm, and its partial admission rate was 1.4–4.1 per cent. The tested turbine was designed as a radial-type turbine that had a circular plate disc for rotor rows. The rotor and the stator were designed as a typical axial-type blade, and the turbine consisted of three stages. The turbine performance was obtained in a wide rotational speed range in order to compare its performance according to various operating conditions. The net specific output torque was also measured to compare its overall performance. Computational analysis was conducted for predicting turbine performance. The computed results were in good agreement with the experimental results.
Luminescent Organoboron Conjugated Polymers
Authors: Nagai Atsushi , Chujo Yoshiki
Published: March 2010

The incorporation of luminescent organoboron dyes into π-conjugated polymer backbones is attractive for potential applications as electroluminescent devices, organic field-effect transistors, and photovoltaics. Recent advances in the field of organoboron polymers are reviewed here.
Oligothiophene Bearing 1-Hydroxy-1-oxodithieno[2,3-b:3′,2′-d]phosphole as a Novel Anchoring Group for Dye-sensitized Solar Cells
Authors: Kira Aiko , Shibano Yuki , Kang Soonchul , Hayashi Hironobu , Umeyama Tomokazu , Matano Yoshihiro , Imahori Hiroshi
Published: March 2010

An oligothiophene bearing 1-hydroxy-1-oxodithieno[2,3-b:3′,2′-d]phosphole (TP) as a novel anchoring group has been synthesized for dye-sensitized solar cells (DSSC). Attenuated total reflectance-Fourier transform infrared and X-ray photoelectron spectroscopy measurements disclosed the bidentate binding of the phosphinic acid unit to a TiO2 surface. A TP-sensitized TiO2 cell yielded a maximum incident photon-to-current efficiency of 66% and a power conversion efficiency of 1.8%, indicating that 1-hydroxy-1-oxodithienophosphole is a potential unit as a new type of anchoring groups for DSSC.
Direct Decomposition of NO on C-type Cubic Rare Earth Oxides Based on Y2O3
Authors: Tsujimoto Soichiro , Mima Koji , Masui Toshiyuki , Imanaka Nobuhito
Published: March 2010

C-type cubic (Y0.99−xTbxBa0.01)2O2.99+δ (0 ≤ x ≤ 0.4) catalysts were prepared by coprecipitation. The NO decomposition activities at 1173 K were higher than that of (Gd0.7Y0.26Ba0.04)2O2.96 reported previously. The highest catalytic activity was obtained for (Y0.69Tb0.3Ba0.01)2O2.99+δ, and 100% NO conversion into N2 and O2 was realized at 1173 K on this catalyst. Furthermore, the conversion ratio was maintained as high as 70.8% even in the presence of 5 vol % oxygen.
Modelling the Impact of Changes in Sensitivity on the Outcomes of the Uk Breast Screening Programme
Authors: Taylor Paul
Published: March 2010

Objectives

To assess the impact on breast cancer mortality of improving the sensitivity of breast screening programmes.

Methods

A Markov model was populated with data obtained from published statistics describing the UK National Health Service Breast Screening Programme and the incidence and mortality of breast cancer in the UK. The model was used to study the impact of changes to the sensitivity of screening. The effects on cancer detection rates and breast cancers and total mortality was studied for a cohort of women followed from age 45 to age 89.

Results

Running the model from age 45 to 89, with sensitivity set at the baseline value of 75%, predicts the detection at screening of 44 cancers per thousand of population and the detection outside screening of 82 cancers per thousand of population. Running the model with values of sensitivity from 75% to 95% shows the proportion of cancers detected at screening increasing as screening improves, and deaths from breast cancer falling. The drop in breast cancer deaths is however modest. Increasing sensitivity from 75% to 85% reduces the number of breast cancer deaths from 28 to 27 per thousand.

Conclusions

Likely achievable improvements in the sensitivity of screening do not have a marked effect on breast cancer mortality.
Absolute Numbers of Lives Saved and Overdiagnosis in Breast Cancer Screeninq, from a Randomized Trial and from the Breast Screening Programme in England
Authors: Duffy Stephen W , Tabar Laszlo , Olsen Anne Helene , Vitak Bedrich , Allgood Prue C , Chen Tony H H , Yen Amy M F , Smith Robert A
Published: March 2010

Objectives

To estimate the absolute numbers of breast cancer deaths prevented and the absolute numbers of tumours overdiagnosed in mammographic screening for breast cancer at ages 50–69 years.

Setting

The Swedish Two-County randomized trial of mammographic screening for breast cancer, and the UK Breast Screening Programme in England, ages 50–69 years.

Methods

We estimated the absolute numbers of deaths avoided and additional cases diagnosed in the study group (active study population) of the Swedish Two-County Trial, by comparison with the control group (passive study population). We estimated the same quantities for the mortality and incidence rates in England (1974–2004 and 1974–2003, respectively). We used Poisson regression for statistical inference.

Results

A substantial and significant reduction in breast cancer mortality was associated with screening in both the Two-County Trial ( P < 0.001) and the screening programme in England ( P < 0.001). The absolute benefits were estimated as 8.8 and 5.7 breast cancer deaths prevented per 1000 women screened for 20 years starting at age 50 from the Two-County Trial and screening programme in England, respectively. The corresponding estimated numbers of cases overdiagnosed per 1000 women screened for 20 years were, respectively, 4.3 and 2.3 per 1000.

Conclusions

The benefit of mammographic screening in terms of lives saved is greater in absolute terms than the harm in terms of overdiagnosis. Between 2 and 2.5 lives are saved for every overdiagnosed case.
Randomized Controlled Trial of Mammographic Screening from Age 40 (‘age’ Trial): Patterns of Screening Attendance
Authors: Johns L E , Moss S M ,   Trial Management Group, Bobrow L , Cuckle H , Evans A , Kutt E , Record C , Thomas B A
Published: March 2010

Background

The Age trial was a randomized controlled trial to study the effect on breast cancer mortality of invitation to annual mammography from age 40 to 41. Uptake of invitation to screening mammography in UK women aged below 50 is of interest, particularly in the light of the recent announcement that the national breast screening programme will begin inviting women from age 47.

Methods

The trial took place in 23 National Health Service breast screening units in England, Wales and Scotland between 1991 and 2004. Data on invitation and attendance during 13 years of trial fieldwork were analysed. The participants were 53,884 women in the intervention arm of the Age trial who were randomized to receive annual invitation to mammography from age 40 or 41 up to age 48. The trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN24647151.

Results

Uptake of invitation to routine screening was 68% at first round and 69% at subsequent rounds. A total of 43,709 women in the intervention arm (81%) attended at least one routine screen and 23,262 (43%) attended at least seven screens; 31,392 women attended 75% or more of all routine invitations they were offered. Previous trial attendance was a predictor of subsequent uptake; attendance was inversely related to Townsend deprivation score.

Conclusion

Uptake in this trial was comparable with that in the UK screening programme for women aged over 50. There was an inverse relationship between deprivation level and the number of screens attended.
Endorsement by the Primary Care Practitioner Consistently Improves Participation in Screening for Colorectal Cancer: A Longitudinal Analysis
Authors: Zajac I T , Whibley A H , Cole S R , Byrne D , Guy J , Morcom J , Young G P
Published: March 2010

Objectives

To investigate the effect of general practice (GP) and general practitioner (GPR) endorsement for faecal occult blood test (FOBT)-based screening on maintenance of participation in screening over four successive screening rounds.

Setting

South Australian residents aged ≥50 years.

Methods

Random selection of four groups ( n = 600 per group): one from the Commonwealth electoral roll (ER) and three from the combined patient lists of two collaborating GPs (GP1, GP2, GP3). Subjects were mailed offers to screen using a faecal immunochemical test over four successive rounds, spaced approximately 18 months apart. The GP1 and ER groups were invited to screen without any endorsement from a GPR or medical practice; GP2 invitees received an invitation indicating support for screening from their medical practice; and GP3 invitations were printed on practice letterhead and were signed by a GPR.

Results

Multivariate analyses indicated that initial participation as well as re-participation over four successive rounds was significantly enhanced in the GP2 (39%, 42%, 45% and 44%) and GP3 groups (42%, 47%, 48% and 49%) relative to the ER group (33%, 37%, 40% and 36%). The analyses also indicated that 60–69 year olds were most likely to participate in all rounds (relative risk [RR] 1.49, 1.39, 1.43 and 1.25), and men were generally less likely to participate than women in all screening rounds (RR 0.86, 0.84, 0.80 and 0.83).

Conclusions

Associating a GPR or medical practice of recent contact with an invitation to screen achieves better participation and re-participation than does an invitation from a centralized screening unit. Furthermore, enhanced participation can be achieved by practice endorsement alone without requiring actual GPR involvement.
Distribution of Nuchal Translucency in Antenatal Screening for Down's Syndrome
Authors: Bestwick J P , Huttly W J , Wald N J
Published: March 2010

Objective

To determine whether the standard deviation of nuchal translucency (NT) measurements has decreased over time and if so to revise the estimate and assess the effect of revising the estimate of the standard deviation on the performance of antenatal screening for Down's syndrome.

Setting

Data from a routine antenatal screening programme for Down's syndrome comprising 106 affected and 22,640 unaffected pregnancies.

Methods

NT measurements were converted into multiple of the median (MoM) values and standard deviations of log10 MoM values were calculated in affected and unaffected pregnancies. The screening performance of the Combined and Integrated tests (that include NT measurement) were compared using previous and revised estimates of the standard deviation.

Results

The standard deviation of NT in unaffected pregnancies has reduced over time (from 1998 to 2008) (e.g. from 0.1329 to 0.1105 [log10 MoM] at 12–13 completed weeks of pregnancy, reducing the variance by about 30%). This was not observed in affected pregnancies. Compared with results from the serum, urine and ultrasound screening study (SURUSS), use of the revised NT standard deviations in unaffected pregnancies resulted in an approximate 20% decrease in the false-positive rate for a given detection rate; for example, from 2.1% to 1.7% (a 19% reduction) at a 90% detection rate using the Integrated test with first trimester markers measured at 1 1 completed weeks’ gestation and from 4.4% to 3.5% (a 20% reduction) at an 85% detection rate using the Combined test at 11 completed weeks.

Conclusions

The standard deviation of NT has declined over time and using the revised estimates improves the screening performance of tests that incorporate an NT measurement.
Characterization of the human tRNA-guanine transglycosylase: Confirmation of the heterodimeric subunit structure
Authors: Chen Yi-Chen , Kelly Vincent P. , Stachura Stefanie V. , Garcia George A.
Published: March 2010

The eukaryotic tRNA-guanine transglycosylase (TGT) has been reported to exist as a heterodimer, in contrast to the homodimeric eubacterial TGT. While ubiquitin-specific protease 14 (USP14) has been proposed to act as a regulatory subunit of the eukaryotic TGT, the mouse TGT has recently been shown to be a queuine tRNA-ribosyltransferase 1 (QTRT1, eubacterial TGT homolog)·queuine tRNA-ribosyltransferase domain-containing 1 (QTRTD1) heterodimer. We find that human QTRTD1 (hQTRTD1) co-purifies with polyhistidine-tagged human QTRT1 (ht-hQTRT1) via Ni2+ affinity chromatography. Cross-linking experiments, mass spectrometry, and size exclusion chromatography results are consistent with the two proteins existing as a heterodimer. We have not been able to observe co-purification and/or association between hQTRT1 and USP14 when co-expressed in Escherichia coli. More importantly, under our experimental conditions, the transglycosylase activity of hQTRT1 is only observed when hQTRT1 and hQTRTD1 have been co-expressed and co-purified. Kinetic characterization of the human TGT (hQTRT1·hQTRTD1) using human tRNATyr and guanine shows catalytic efficiency (kcat/KM) similar to that of the E. coli TGT. Furthermore, site-directed mutagenesis confirms that the hQTRT1 subunit is responsible for the transglycosylase activity. Taken together, these results indicate that the human TGT is composed of a catalytic subunit, hQTRT1, and hQTRTD1, not USP14. hQTRTD1 has been implicated as the salvage enzyme that generates free queuine from QMP. Work is ongoing in our laboratory to confirm this activity.
Binding and release of the 6S transcriptional control RNA
Authors: Shephard Lindsay , Dobson Neil , Unrau Peter J.
Published: March 2010

6S RNA is an important noncoding RNA that regulates eubacterial transcription. In Escherichia coli this RNA binds to the σ70 RNA polymerase holoenzyme and is released by the synthesis of a short product RNA. In order to determine how binding and release are controlled by the 6S RNA sequence, we used in vitro selection to screen a high diversity library containing ∼4 × 1012 sequences for functional 6S RNA variants. Residues critical for binding were found to be located in a “-35” region upstream of the 6S RNA transcription bubble mimic structure. Mutating these phylogenetically conserved residues invariably led to decreases in binding and removing them abolished binding, implicating these nucleotides in a biologically important interaction with the Eσ70 complex. Interestingly, mutation of phylogenetically conserved “-10” residues that were also upstream of the site of pRNA synthesis was found to influence 6S RNA release rates in addition to modulating -35 binding. These results indicate how 6S RNA -35 binding to σ70 RNA polymerase holoenzyme can regulate expression from “strong” and “weak” -35 DNA promoters and suggest that 6S RNA release rates have been fine tuned over evolutionary time so as to correctly regulate cellular levels of transcription.
Dicer's helicase domain is required for accumulation of some, but not all, C. elegans endogenous siRNAs
Authors: Welker Noah C. , Pavelec Derek M. , Nix David A. , Duchaine Thomas F. , Kennedy Scott , Bass Brenda L.
Published: March 2010

Years after the discovery that Dicer is a key enzyme in gene silencing, the role of its helicase domain remains enigmatic. Here we show that this domain is critical for accumulation of certain endogenous small interfering RNAs (endo-siRNAs) in Caenorhabditis elegans. The domain is required for the production of the direct products of Dicer, or primary endo-siRNAs, and consequently affects levels of downstream intermediates, the secondary endo-siRNAs. Consistent with the role of endo-siRNAs in silencing, their loss correlates with an increase in cognate mRNA levels. We find that the helicase domain of Dicer is not necessary for microRNA (miRNA) processing, or RNA interference following exposure to exogenous double-stranded RNA. Comparisons of wild-type and helicase-defective strains using deep-sequencing analyses show that the helicase domain is required by a subset of annotated endo-siRNAs, in particular, those associated with the slightly longer 26-nucleotide small RNA species containing a 5′ guanosine.
Vitamin D deficiency in patients with osteoarthritis undergoing total hip replacement
Authors: Nawabi D. H. , Chin K. F. , Keen R. W. , Haddad F. S.
Published: March 2010

We measured the plasma 25-hydroxyvitamin D3 (25(OH)D3) levels in 62 consecutive Caucasian patients undergoing total hip replacement for osteoarthritis. The patients were divided into two groups based on whether they were vitamin D sufficient or deficient. The groups were matched for age, gender and the American Society of Anaesthesiologists (ASA) grade. The prevalence of vitamin D deficiency in our patients was comparable with recent population-based studies performed in the United Kingdom. Patients with vitamin D deficiency had lower pre-operative Harris hip scores (Mann-Whitney test, p = 0.018) and were significantly less likely to attain an excellent outcome from total hip replacement (chi-squared test, p = 0.038). Vitamin D levels were found to positively correlate with both pre- and post-operative Harris hip scores.

These results warrant further study of vitamin D deficiency in patients undergoing joint replacement as it is a risk factor for a suboptimal outcome which is relatively simple and cheap to correct.
Micro-decompression for lumbar spinal stenosis
Authors: Orpen N. M. , Corner J. A. , Shetty R. R. , Marshall R.
Published: March 2010

We describe a modified technique of micro-decompression of the lumbar spine involving the use of an operating microscope, a malleable retractor and a high-speed burr, which allows decompression to be performed on both sides of the spine through a unilateral, hemi-laminectomy approach. The first 100 patients to be treated with this technique have been evaluated prospectively using a visual analogue score for sciatica and back pain, the MacNab criteria for patient satisfaction, and functional assessment with the Oswestry Disability Index.

After a period of follow-up from 12 months to six years and four months, sciatica had improved in 90 patients and back pain in 84 patients. Their result was graded as good or excellent by 82 patients according to the MacNab criteria, and 75 patients had subjective improvement in their walking distance. Late instability developed in four patients.

Lumbar micro-decompression has proved to be safe, with few complications. Postoperative instability requiring fusion was uncommon, and less than using traditional approaches in published series.
The reverse shoulder prosthesis in the treatment of fractures of the proximal humerus in the elderly
Authors: Cazeneuve J. F. , Cristofari D.-J.
Published: March 2010

We have previously described the short-term outcome of the use of reverse shoulder arthroplasty in the treatment of acute complex proximal humeral fractures in the elderly. We now report the clinical and radiological outcome of 36 fractures at a mean of 6.6 years (1 to 16). Previously, at a mean follow-up of 6 years (1 to 12) the mean Constant score was 58.5; this was reduced to 53 points with the further follow-up. A total of 23 patients (63%) had radiological evidence of loosening of the glenoid component. Nevertheless, only one patient had aseptic loosening of the baseplate at 12 years’ follow-up.

The reduction in the mean Constant score with longer follow-up and the further development of scapular notching is worrying.

New developments in design, bearing surfaces and surgical technique, and further follow-up, will determine whether reverse shoulder arthroplasty has a place in the management of complex proximal humeral fractures in the elderly.
The influence of the size of the component on the outcome of resurfacing arthroplasty of the hip
Authors: Shimmin A. J. , Walter W. L. , Esposito C.
Published: March 2010

The survivorship of contemporary resurfacing arthroplasty of the hip using metal-on-metal bearings is better than that of first generation designs, but short-term failures still occur. The most common reasons for failure are fracture of the femoral neck, loosening of the component, osteonecrosis of the femoral head, reaction to metal debris and malpositioning of the component. In 2008 the Australian National Joint Registry reported an inverse relationship between the size of the head component and the risk of revision in resurfacing hip arthroplasty. Hips with a femoral component size of ≤ 44 mm have a fivefold increased risk of revision than those with femoral components of ≥ 55 mm irrespective of gender. We have reviewed the literature to explore this observation and to identify possible reasons including the design of the implant, loading of the femoral neck, the orientation of the component, the production of wear debris and the effects of metal ions, penetration of cement and vascularity of the femoral head. Our conclusion is that although multifactorial, the most important contributors to failure in resurfacing arthroplasty of the hip are likely to be the design and geometry of the component and the orientation of the acetabular component.
The Freeman femoral component with hydroxyapatite coating and retention of the neck
Authors: Mannan K. , Freeman M. A. R. , Scott G.
Published: March 2010

The outcome at ten years of 100 Freeman hip stems (Finsbury Orthopaedics, Leatherhead, United Kingdom) retaining the neck with a proximal hydroxyapatite coating in a series of 52 men (six bilateral) and 40 women (two bilateral), has been described previously. None required revision for aseptic loosening. We have extended the follow-up to 20 years with a minimum of 17 years. The mean age of the patients at total hip replacement was 58.9 years (19 to 84).

Six patients were lost to follow-up, but were included up to their last clinical review. A total of 22 patients (22 hips) had died, all from causes unrelated to their surgery. There have been 43 re-operations for failure of the acetabular component. However, in 38 of these the stem was not revised since it remained stable and there was no associated osteolysis. Two of the revisions were for damage to the trunnion after fracture of a modular ceramic head, and in another two, removal of the femoral component was because of the preference of the surgeon. In all cases the femoral component was well fixed, but could be extracted at the time of acetabular revision. In one case both components were revised for deep infection. There has been one case of aseptic loosening of the stem which occurred at 14 years. This stem had migrated distally by 7.6 mm in ten years and 8.4 mm at the time of revision at which stage it was found to be rotationally loose. With hindsight this component had been undersized at implantation.

The survivorship for the stem at 17 years with aseptic loosening as the endpoint was 98.6% (95% confidence interval 95.9 to 100) when 62 hips were at risk. All remaining stems had a satisfactory clinical and radiological outcome. The Freeman proximally hydroxyapatite-coated femoral component is therefore a dependable implant and its continued use can be recommended.
The impact of pre-operative obesity on weight change and outcome in total knee replacement
Authors: Dowsey M. M. , Liew D. , Stoney J. D. , Choong P. F.
Published: March 2010

We carried out a prospective, continuous study on 529 patients who underwent primary total knee replacement between January 2006 and December 2007 at a major teaching hospital. The aim was to investigate weight change and the functional and clinical outcome in non-obese and obese groups at 12 months post-operatively. The patients were grouped according to their pre-operative body mass index (BMI) as follows: non-obese (BMI < 30 kg/m2), obese (BMI 3 30 to 39 kg/m2) and morbidly obese (BMI > 40 kg/m2). The clinical outcome data were available for all patients and functional outcome data for 521 (98.5%). Overall, 318 (60.1%) of the patients were obese or morbidly obese.

At 12 months, a clinically significant weight loss of ≥ 5% had occurred in 40 (12.6%) of the obese patients, but 107 (21%) gained weight. The change in the International Knee Society score was less in obese and morbidly obese compared with non-obese patients (p = 0.016). Adverse events occurred in 30 (14.2%) of the non-obese, 59 (22.6%) of the obese and 20 (35.1%) of the morbidly obese patients (p = 0.001).
The radiological evaluation of acetabular fractures in the elderly
Authors: Miller A. N. , Prasarn M. L. , Lorich D. G. , Helfet D. L.
Published: March 2010

We have examined the accuracy of reduction and the functional outcomes in elderly patients with surgically treated acetabular fractures, based on assessment of plain radiographs and CT scans. There were 45 patients with such a fracture with a mean age of 67 years (59 to 82) at the time of surgery. All patients completed SF-36 questionnaires to determine the functional outcome at a mean follow-up of 72.4 months (24 to 188). All had radiographs and a CT scan within one week of surgery. The reduction was categorised as ‘anatomical’, ‘imperfect’, or ‘poor’.

Radiographs classified 26 patients (58%) as anatomical,13 (29%) as imperfect and six (13%) as poor. The maximum displacement on CT showed none as anatomical, 23 (51%) as imperfect and 22 (49%) as poor, but this was not always at the weight-bearing dome. SF-36 scores showed functional outcomes comparable with those of the general elderly population, with no correlation with the radiological reduction.

Perfect anatomical reduction is not necessary to attain a good functional outcome in acetabular fractures in the elderly.
Orthopaedic training
Authors: Banaszkiewicz P. A.
Published: March 2010

The Postgraduate Medical Education and Training Board wants either ‘run through’ or ‘uncoupled’ orthopaedic training to be adopted throughout the United Kingdom but it is not willing to let both continue together as is the current situation. This annotation explores the argument for and against ‘run through’ training.
The Relationship between Inpatient Fluoroquinolone Use and Clostridium difficile-Associated Diarrhea
Authors: Novell Marilyn J , Morreale Carol A
Published: March 2010

BACKGROUND:

Limited evidence suggests there may be a link between fluoroquinolone use and Clostridium difficile-associated diarrhea (CDAD), but such an association remains unclear due to conflicting data.

OBJECTIVE:

To determine the relationship between inpatient fluoroquinolone use and CDAD; secondary objectives included the relationship between CDAD and fluoroquinolone selection, duration of therapy, and route of administration, as well as the association between fluoroquinolones and CDAD complications.

METHODS:

We conducted a retrospective, case-control study of adult inpatients diagnosed with CDAD during the period of July 2007-July 2008. In total, 174 case patients were matched on a 1:1 basis with controls. A thorough assessment of all inpatient antibiotic use was conducted, including regimens administered at our institution within the previous 8 weeks. Odds ratios were calculated using univariate logistic-regression analysis.

RESULTS:

Use of fluoroquinolones was not significantly different between patients with CDAD and matching controls (OR 1.36; 95% CI 0.09 to 2.10; p = 0.16). No relationship was found between CDAD and the individual fluoroquinolones: ciprofloxacin (OR 1.36; 95% CI 0.87 to 2.12; p = 0.18), levofloxacin (OR 1.17; 95% CI 0.62 to 2.22; p = 0.63), and moxifloxacin (OR 1.34; 95% CI 0.81 to 2.20; p = 0.25). Fluoroquinolone route of administration did not differ significantly between groups for patients receiving intravenous (OR 1.20; 95% CI 0.74 to 1.94; p = 0.46) or oral (OR 0.79; 95% CI 0.44 to 1.44; p = 0.45) therapy. Complications from CDAD were not significantly increased by fluoroquinolone use (OR 1.37; 95% CI 0.72 to 2.61; p = 0.35).

CONCLUSIONS:

Inpatient administration of fluoroquinolones was not associated with CDAD at our institution. Fluoroquinolone use in patients who developed CDAD was not related to higher incidences of CDAD-related complications.