bluuebunny/crossref_metadata_2025 huggingface dataset:
Survey of methadone-drug interactions among patients of methadone maintenance treatment program in Taiwan
Authors: Lee Hsin-Ya , Li Jih-Heng , Wu Li-Tzy , Wu Jin-Song , Yen Cheng-Fang , Tang Hsin-Pei
Published: March 2012

Background

Although methadone has been used for the maintenance treatment of opioid dependence for decades, it was not introduced in China or Taiwan until 2000s. Methadone-drug interactions (MDIs) have been shown to cause many adverse effects. However, such effects have not been scrutinized in the ethnic Chinese community.

Methods

The study was performed in two major hospitals in southern Taiwan. A total of 178 non-HIV patients aged ≥ 20 years who had participated in the Methadone Maintenance Treatment Program (MMTP) ≥ 1 month were recruited. An MDI is defined as concurrent use of drug(s) with methadone that may result in an increase or decrease of effectiveness and/or adverse effect of methadone. To determine the prevalence and clinical characteristics of MDIs, credible data sources, including the National Health Insurance (NHI) database, face-to-face interviews, medical records, and methadone computer databases, were linked for analysis. Socio-demographic and clinical factors associated with MDIs and co-medications were also examined.

Results

128 (72%) MMTP patients took at least one medication. Clinically significant MDIs included withdrawal symptoms, which were found among MMTP patients co-administered with buprenorphine or tramadol; severe QTc prolongation effect, which might be associated with use of haloperidol or droperidol; and additive CNS and respiratory depression, which could result from use of methadone in combination with chlorpromazine or thioridazine. Past amphetamine use, co-infection with hepatitis C, and a longer retention in the MMTP were associated with increased odds of co-medication. Among patients with co-medication use, significant correlates of MDIs included the male gender and length of co-medication in the MMTP.

Conclusions

The results demonstrate clinical evidence of significant MDIs among MMTP patients. Clinicians should check the past medical history of MMTP clients carefully before prescribing medicines. Because combinations of methadone with other psychotropic or opioid medications can affect treatment outcomes or precipitate withdrawal symptoms, clinicians should be cautious when prescribing these medications to MMTP patients and monitor the therapeutic effects and adverse drug reactions. Although it is difficult to interconnect medical data from different sources for the sake of privacy protection, the incumbent agency should develop pharmacovigilant measures to prevent the MDIs from occurring. Physicians are also advised to check more carefully on the medication history of their MMTP patients.
A simple method for construction of pir
+
Enterobacterial hosts for maintenance of R6K replicon plasmids
Authors: Kvitko Brian H , Bruckbauer Steven , Prucha John , McMillan Ian , Breland Erin J , Lehman Stephanie , Mladinich Katie , Choi Kyoung-Hee , Karkhoff-Schweizer RoxAnn , Schweizer Herbert P
Published: March 2012

Background

The R6K replicon is one of the best studied bacterial plasmid replicons. Replication of the R6K plasmid and derivatives harboring its γ origin of replication (ori
R6Kγ) is dependent on the pir gene-encoded π protein. Originally encoded by R6K, this protein is usually provided in trans in hosts engineered to support replication of plasmids harboring ori
R6Kγ. In Escherichia coli this is commonly achieved by chromosomal integration of pir either via lysogenization with a λpir phage or homologous recombination at a pre-determined locus.

Findings

Current methods for construction of host strains for ori
R6Kγ-containing plasmids involve procedures that do not allow selection for presence of the pir gene and require cumbersome and time-consuming screening steps. In this study, we established a mini-Tn7-based method for rapid and reliable construction of pir
+ host strains. Using a curable mini-Tn7 delivery plasmid, pir expressing derivatives of several commonly used E. coli cloning and mobilizer strains were isolated using both the wild-type pir

+
gene as well as the copy-up pir-116 allele. In addition, we isolated pir
+ and pir-116 expressing derivatives of a clinical isolate of Salmonella enterica serovar Typhimurium. In both E. coli and S. enterica serovar Typhimurium, the presence of the pir

+
wild-type or pir-116 alleles allowed the replication of ori
R6Kγ-containing plasmids.

Conclusions

A mini-Tn7 system was employed for rapid and reliable engineering of E. coli and S. enterica serovar Typhimurium host strains for plasmids containing ori
R6Kγ. Since mini-Tn7 elements transpose in most, if not all, Gram negative bacteria, we anticipate that with relatively minor modifications this newly established method will for the first time allow engineering of other bacterial species to enable replication of plasmids with ori
R6Kγ.
The reliability of plantar pressure assessment during barefoot level walking in children aged 7‐11 years
Authors: Cousins Stephen D , Morrison Stewart C , Drechsler Wendy I
Published: March 2012

Background

Plantar pressure assessment can provide information pertaining to the dynamic loading of the foot, as well as information specific to each region in contact with the ground. There have been few studies which have considered the reliability of plantar pressure data and therefore the purpose of this study was to investigate the reliability of assessing plantar pressure variables in a group of typically developing children, during barefoot level walking.

Methods

Forty‐five participants, aged 7 to 11 years, were recruited from local primary and secondary schools in East London. Data from three walking trials were collected at both an initial and re‐test session, taken one week apart, to determine both the within‐ and between‐session reliability of selected plantar pressure variables. The variables of peak pressure, peak force, pressure‐time and force‐time integrals were extracted for analysis in the following seven regions of the foot; lateral heel, medial heel, midfoot, 1st metatarsophalangeal joint, 2nd‐5th metatarsophalangeal joint, hallux and the lesser toes. Reliability of the data were explored using Intra Class Correlation Coefficients (ICC 3,1 and 3,2) and variability with Coefficients of Variation (CoV's).

Results

The measurements demonstrated moderate to good levels of within‐session reliability across all segments of the foot (0.69‐0.93), except the lesser toes, which demonstrated poor reliability (0.17‐0.50). CoV's across the three repeated trials ranged from 10.12‐19.84% for each of the measured variables across all regions of the foot, except the lesser toes which demonstrated the greatest variability within trials (27.15‐56.08%). The between‐session results demonstrated good levels of reliability across all foot segments (0.79‐0.99) except the lesser toes; with moderate levels of reliability reported at this region of the foot (0.58‐0.68). The CoV's between‐sessions demonstrated that the midfoot (16.41‐36.23%) and lesser toe region (29.64‐56.61) demonstrated the greatest levels of variability across all the measured variables.

Conclusions

These findings indicate that using the reported protocols, reliable plantar pressure data can be collected in children, aged 7 to 11 years in all regions of the foot except the lesser toes which consistently reported poor‐to‐moderate levels of reliability and increased variability.
Functional characterization of the 19q12 amplicon in grade III breast cancers
Authors: Natrajan Rachael , Mackay Alan , Wilkerson Paul M , Lambros Maryou B , Wetterskog Daniel , Arnedos Monica , Shiu Kai-Keen , Geyer Felipe C , Langerød Anita , Kreike Bas , Reyal Fabien , Horlings Hugo M , van de Vijver Marc J , Palacios Jose , Weigelt Britta , Reis-Filho Jorge S
Published: March 2012

Introduction

The 19q12 locus is amplified in a subgroup of oestrogen receptor (ER)-negative grade III breast cancers. This amplicon comprises nine genes, including cyclin E1 (CCNE1), which has been proposed as its 'driver'. The aim of this study was to identify the genes within the 19q12 amplicon whose expression is required for the survival of cancer cells harbouring their amplification.

Methods

We investigated the presence of 19q12 amplification in a series of 313 frozen primary breast cancers and 56 breast cancer cell lines using microarray comparative genomic hybridisation (aCGH). The nine genes mapping to the smallest region of amplification on 19q12 were silenced using RNA interference in phenotypically matched breast cancer cell lines with (MDA-MB-157 and HCC1569) and without (Hs578T, MCF7, MDA-MB-231, ZR75.1, JIMT1 and BT474) amplification of this locus. Genes whose silencing was selectively lethal in amplified cells were taken forward for further validation. The effects of cyclin-dependent kinase 2 (CDK2) silencing and chemical inhibition were tested in cancer cells with and without CCNE1 amplification.

Results

19q12 amplification was identified in 7.8% of ER-negative grade III breast cancer. Of the nine genes mapping to this amplicon, UQCRFS1, POP4, PLEKHF1, C19ORF12, CCNE1 and C19ORF2 were significantly over-expressed when amplified in primary breast cancers and/or breast cancer cell lines. Silencing of POP4, PLEKHF1, CCNE1 and TSZH3 selectively reduced cell viability in cancer cells harbouring their amplification. Cancer cells with CCNE1 amplification were shown to be dependent on CDK2 expression and kinase activity for their survival.

Conclusions

The 19q12 amplicon may harbour more than a single 'driver', given that expression of POP4, PLEKHF1, CCNE1 and TSZH3 is required for the survival of cancer cells displaying their amplification. The observation that cancer cells harbouring CCNE1 gene amplification are sensitive to CDK2 inhibitors provides a rationale for the testing of these chemical inhibitors in a subgroup of patients with ER-negative grade III breast cancers.
Depression and Survival in Metastatic Non–Small-Cell Lung Cancer: Effects of Early Palliative Care
Authors: Pirl William F. , Greer Joseph A. , Traeger Lara , Jackson Vicki , Lennes Inga T. , Gallagher Emily R. , Perez-Cruz Pedro , Heist Rebecca S. , Temel Jennifer S.
Published: March 2012

Purpose

In a randomized trial, early palliative care (EPC) in patients with metastatic non–small-cell lung cancer (NSCLC) was observed to improve survival. In a secondary analysis, we explored the hypothesis that the survival benefit resulted from improving depression.

Patients and Methods

In total, 151 patients with newly diagnosed metastatic NSCLC participated in a randomized trial of EPC integrated with standard oncology care versus standard oncology care alone. Depression was assessed at baseline and at 12 weeks with the Patient Health Questionnaire-9 (PHQ-9) and was scored diagnostically by using Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, criteria for major depression syndrome (MDS). Depression response was considered ≥ 50% reduction in PHQ-9 scores at 12 weeks. Survival differences were tested with log-rank and Cox proportional hazards models.

Results

At baseline, 21 patients (14%) met MDS criteria. MDS significantly predicted worse survival (hazard ratio, 1.82; P = .02). Patients assigned to EPC had greater improvements in PHQ-9 scores at 12 weeks (P < .001); among patients with MDS, those receiving EPC had greater rates of depression response at 12 weeks (P = .04). However, improvement in PHQ-9 scores was not associated with improved survival, except in a sensitivity analysis in which patients who died before 12 weeks were modeled to have worse depression. The group randomly assigned to EPC remained independently associated with survival after adding improvement in PHQ-9 scores to the survival model.

Conclusion

Depression predicted worse survival in patients with newly diagnosed metastatic NSCLC. Although EPC was associated with greater improvement in depression at 12 weeks, the data do not support the hypothesis that treatment of depression mediated the observed survival benefit from EPC.
Financial Relationships in Economic Analyses of Targeted Therapies in Oncology
Authors: Valachis Antonis , Polyzos Nikolaos P. , Nearchou Andreas , Lind Pehr , Mauri Davide
Published: March 2012

Purpose

A potential financial relationship between investigators and pharmaceutical manufacturers has been associated with an increased likelihood of reporting favorable conclusions about a sponsor's proprietary agent in pharmacoeconomic studies. The purpose of this study is to investigate whether there is an association between financial relationships and outcome in economic analyses of new targeted therapies in oncology.

Materials and Methods

We searched PubMed (last update June 2011) for economic analyses of targeted therapies (including monoclonal antibodies, tyrosine-kinase inhibitors, and mammalian target of rapamycin inhibitors) in oncology. The trials were qualitatively rated regarding the cost assessment as favorable, neutral, or unfavorable on the basis of prespecified criteria.

Results

Overall, 81 eligible studies were identified. Economic analyses that were funded by pharmaceutical companies were more likely to report favorable qualitative cost estimates (28 [82%] of 34 v 21 [45%] of 47; P = .003). The presence of an author affiliated with manufacturer was not associated with study outcome. Furthermore, if only studies including a conflict of interest statement were included (66 of 81), studies that reported any financial relationship with manufacturers (author affiliation and/or funding and/or other financial relationship) were more likely to report favorable results of targeted therapies compared with studies without financial relationship (32 [71%] of 45 v nine [43%] of 21; P = .025).

Conclusion

Our study reveals a potential threat for industry-related bias in economic analyses of targeted therapies in oncology in favor of analyses with financial relationships between authors and manufacturers. A more balanced funding of economic analyses from other sources may allow greater confidence in the interpretation of their results.
Inducible deletion of epidermal Dicer and Drosha reveals multiple functions for miRNAs in postnatal skin
Authors: Teta Monica , Choi Yeon Sook , Okegbe Tishina , Wong Gabrielle , Tam Oliver H. , Chong Mark M. W. , Seykora John T. , Nagy Andras , Littman Dan R. , Andl Thomas , Millar Sarah E.
Published: March 2012

MicroRNAs (miRNAs) regulate the expression of many mammalian genes and play key roles in embryonic hair follicle development; however, little is known of their functions in postnatal hair growth. We compared the effects of deleting the essential miRNA biogenesis enzymes Drosha and Dicer in mouse skin epithelial cells at successive postnatal time points. Deletion of either Drosha or Dicer during an established growth phase (anagen) caused failure of hair follicles to enter a normal catagen regression phase, eventual follicular degradation and stem cell loss. Deletion of Drosha or Dicer in resting phase follicles did not affect follicular structure or epithelial stem cell maintenance, and stimulation of anagen by hair plucking caused follicular proliferation and formation of a primitive transient amplifying matrix population. However, mutant matrix cells exhibited apoptosis and DNA damage and hair follicles rapidly degraded. Hair follicle defects at early time points post-deletion occurred in the absence of inflammation, but a dermal inflammatory response and hyperproliferation of interfollicular epidermis accompanied subsequent hair follicle degradation. These data reveal multiple functions for Drosha and Dicer in suppressing DNA damage in rapidly proliferating follicular matrix cells, facilitating catagen and maintaining follicular structures and their associated stem cells. Although Drosha and Dicer each possess independent non-miRNA-related functions, the similarity in phenotypes of the inducible epidermal Drosha and Dicer mutants indicates that these defects result primarily from failure of miRNA processing. Consistent with this, Dicer deletion resulted in the upregulation of multiple direct targets of the highly expressed epithelial miRNA miR-205.
Actin branching in the initiation and maintenance of lamellipodia
Authors: Vinzenz Marlene , Nemethova Maria , Schur Florian , Mueller Jan , Narita Akihiro , Urban Edit , Winkler Christoph , Schmeiser Christian , Koestler Stefan A. , Rottner Klemens , Resch Guenter P. , Maeda Yuichiro , Small J. Victor
Published: March 2012

Using correlated live cell imaging and electron tomography we found that actin branch junctions in protruding and treadmilling lamellipodia are not concentrated at the front as previously supposed, but link actin filament subsets in which there is a continuum of distances from a junction to the filament plus ends, up to at least 1 µm. When branch sites were observed closely spaced on the same filament their separation was commonly a multiple of the actin helical repeat of 36 nm. Image averaging of branch junctions in the tomograms yielded a model for the in vivo branch at 2.9 nm resolution, which compared closely to that derived for the in vitro actin - Arp2/3 complex. Lamellipodia initiation was monitored in an intracellular wound-healing model and involved branching from the sides of actin filaments oriented parallel to the plasmalemma. Many filament plus ends, presumably capped, terminated behind the lamellipodium tip and localized on the dorsal and ventral surfaces of the actin network. These findings reveal how branching events initiate and maintain a network of actin filaments of variable length and provide the first structural model of the branch junction in vivo. A possible role of filament capping in generating the lamellipodium leaflet is discussed and a mathematical model of protrusion is also presented.
Changing patterns of infant death over the last 100 years: autopsy experience from a specialist children's hospital
Authors: Pryce JW , Weber MA , Ashworth MT , Roberts SEA , Malone M , Sebire NJ
Published: March 2012

Objectives

Infant mortality has undergone a dramatic reduction in the UK over the past century because of improvements in public health policy and medical advances. Postmortem examinations have been performed at Great Ormond Street Hospital for over 100 years, and analysis of cases across this period has been performed to assess changing patterns of infant deaths undergoing autopsy.

Design

Autopsy reports from 1909 and 2009 were examined. Age, major pathology and cause of death was reviewed from these cases and entered into an anonymized database. A subsequent comparative analysis was performed.

Setting

All postmortems performed and reported at Great Ormond Street Hospital in 1909 and 2009.

Participants

Infant deaths, aged 0–365 days, were identified and subsequently analysed for the two years.

Main outcome measures

Comparative proportional analysis of postmortem findings from the two time periods.

Results

Three-hundred and fifty-seven and 347 autopsy reports were identified from 1909 and 2009 including 178 and 128 infant deaths, respectively. The commonest cause of death in 1909 was infection (74%) compared to 20% of deaths in 2009. The most frequent final ‘diagnosis’ in 2009 was ‘unexplained sudden unexpected infant death (SUDI)’, despite a full postmortem including ancillary investigations. In contrast, there were no such cases recorded in 1909, but there were frequent deaths due to gastroenteritis and malnutrition together accounting for 16% of cases, compared to one case of gastroenteritis in 2009. Fifteen percent of 1909 cases had infections which are almost never fatal with appropriate treatment in 2009, including tuberculosis, diphtheria and syphilis. Congenital anomalies were detected with similar frequencies at both time points, (21% and 19% in 1909 and 2009, respectively).

Conclusion

In the UK, significant changes in patterns of pathology have occurred in paediatric autopsy cases performed at a single specialist centre. Fatal infections and malnutrition (both poverty-related) have reduced yet the incidence of congenital anomalies has remained similar.
Supporting hospital staff to provide compassionate care: Do Schwartz Center Rounds work in English hospitals?
Authors: Goodrich Joanna
Published: March 2012

Objective

To assess (1) whether the Schwartz Center Rounds (“Rounds”), a multidisciplinary forum which brings together hospital staff to discuss the nonclinical, social and emotional aspects of caring for patients, could transfer from the US to a UK setting; and (2) whether UK Rounds would achieve a similar positive impact on individuals and teams, and hospital culture.

Design

The results reported are based on 41 qualitative interviews with context provided by additional quantitative research.

Setting

We introduced Rounds at two pilot sites, both NHS hospitals providing acute care.

Participants

Over the one-year, ten-Rounds pilot period, Rounds were attended by 1250 staff across the two sites. We conducted qualitative research into the experiences of staff involved in implementing Rounds at the outset and the end of the pilot.

Main outcome measures

Interviewees' assessment of the effects of Rounds on participants, their relationships with colleagues, and the wider hospital.

Results

The findings show that in the two pilot trusts, Rounds are perceived by participants as a source of support and that their benefit may translate into benefits for patients and team working; and that Rounds have the potential to effect change in the hospital culture.

Conclusion

Rounds appear to transfer successfully from the US to the UK, and there is some evidence that they are having a similarly positive impact, but more research is needed.
Minimum ten-year results of a prospective randomised study of autologous chondrocyte implantationversusmosaicplasty for symptomatic articular cartilage lesions of the knee
Authors: Bentley G. , Biant L. C. , Vijayan S. , Macmull S. , Skinner J. A. , Carrington R. W. J.
Published: March 2012

Autologous chondrocyte implantation (ACI) and mosaicplasty are methods of treating symptomatic articular cartilage defects in the knee. This study represents the first long-term randomised comparison of the two techniques in 100 patients at a minimum follow-up of ten years. The mean age of the patients at the time of surgery was 31.3 years (16 to 49); the mean duration of symptoms pre-operatively was 7.2 years (9 months to 20 years). The lesions were large with the mean size for the ACI group being 440.9 mm2(100 to 1050) and the mosaicplasty group being 399.6 mm2(100 to 2000). Patients had a mean of 1.5 previous operations (0 to 4) to the articular cartilage defect. Patients were assessed using the modified Cincinnati knee score and the Stanmore-Bentley Functional Rating system. The number of patients whose repair had failed at ten years was ten of 58 (17%) in the ACI group and 23 of 42 (55%) in the mosaicplasty group (p < 0.001).

The functional outcome of those patients with a surviving graft was significantly better in patients who underwent ACI compared with mosaicplasty (p = 0.02).
Loss to follow-up after arthroplasty
Authors: Rowden N. J. , Harrison J. A. , Graves S. E. , Miller L. N. , de Steiger R. N. , Davidson D. C.
Published: March 2012

We assessed the outcome of patients who were lost to follow-up after arthroplasty by a single surgeon. The aim was to validate the surgeon’s data set with the Australian Orthopaedic Association National Joint Replacement Registry and determine the outcome of those patients lost to follow-up.

Prospective data on patient demographics, operative details and outcomes of the surgeon’s 1192 primary unicompartmental knee arthroplasty (UKA) procedures were analysed. There were 69 knees in patients who were lost to follow-up, among whom the Registry identified 31 deaths and eight revisions.

The cumulative percentage revision (CPR) at seven years using the additional Registry data was 8.8% (95% confidence interval (CI) 7 to 11). Using the surgeon’s data, the CPR at seven years was 8% (95% CI 6.3 to 10.1) for the best-case scenario where loss to follow-up was excluded, and 16% (95% CI 13.8 to 19.4) for the worst-case scenario, where all patients lost to follow-up were deemed to have been revised. There was a significantly higher mortality rate in those patients lost to follow-up.

This study demonstrates that a national joint registry can be used by individual surgeons to establish more accurate revision rates in their arthroplasty patients. This is expected to facilitate a more rigorous audit of surgical outcomes by surgeons and lead to more accurate and uniform reporting of the results of arthroplasty in general.
Obesity and symptomatic osteoarthritis of the knee
Authors: Sridhar M. S. , Jarrett C. D. , Xerogeanes J. W. , Labib S. A.
Published: March 2012

Given the growing prevalence of obesity around the world and its association with osteoarthritis of the knee, orthopaedic surgeons need to be familiar with the management of the obese patient with degenerative knee pain. The precise mechanism by which obesity leads to osteoarthritis remains unknown, but is likely to be due to a combination of mechanical, humoral and genetic factors.

Weight loss has clear medical benefits for the obese patient and seems to be a logical way of relieving joint pain associated with degenerative arthritis. There are a variety of ways in which this may be done including diet and exercise, and treatment with drugs and bariatric surgery. Whether substantial weight loss can delay or even reverse the symptoms associated with osteoarthritis remains to be seen.

Surgery for osteoarthritis in the obese patient can be technically more challenging and carries a risk of additional complications. Substantial weight loss before undertaking total knee replacement is advisable. More prospective studies that evaluate the effect of significant weight loss on the evolution of symptomatic osteoarthritis of the knee are needed so that orthopaedic surgeons can treat this patient group appropriately.
A prospective randomised controlled trial comparing three alternative bearing surfaces in primary total hip replacement
Authors: Nikolaou V. S. , Edwards M. R. , Bogoch E. , Schemitsch E. H. , Waddell J. P.
Published: March 2012

The ideal bearing surface for young patients undergoing total hip replacement (THR) remains controversial. We report the five-year results of a randomised controlled trial comparing the clinical and radiological outcomes of 102 THRs in 91 patients who were <  65 years of age. These patients were randomised to receive a cobalt–chrome on ultra-high-molecular-weight polyethylene, cobalt–chrome on highly cross-linked polyethylene, or a ceramic-on-ceramic bearing. In all, 97 hip replacements in 87 patients were available for review at five years. Two hips had been revised, one for infection and one for peri-prosthetic fracture.

At the final follow-up there were no significant differences between the groups for the mean Western Ontario and McMaster Universities osteoarthritis index (pain, p = 0.543; function, p = 0.10; stiffness, p = 0.99), Short Form-12 (physical component, p = 0.878; mental component, p = 0.818) or Harris hip scores (p = 0.22). Radiological outcomes revealed no significant wear in the ceramic group.

Comparison of standard and highly cross-linked polyethylene, however, revealed an almost threefold difference in the mean annual linear wear rates (0.151 mm/year versus 0.059 mm/year, respectively) (p < 0.001).
The early management of patients with multiple injuries
Authors: Moran C. G. , Forward D. P.
Published: March 2012

There have been many advances in the resuscitation and early management of patients with severe injuries during the last decade. These have come about as a result of the reorganisation of civilian trauma services in countries such as Germany, Australia and the United States, where the development of trauma systems has allowed a concentration of expertise and research. The continuing conflicts in the Middle East have also generated a significant increase in expertise in the management of severe injuries, and soldiers now survive injuries that would have been fatal in previous wars. This military experience is being translated into civilian practice.

The aim of this paper is to give orthopaedic surgeons a practical, evidence-based guide to the current management of patients with severe, multiple injuries. It must be emphasised that this depends upon the expertise, experience and facilities available within the local health-care system, and that the proposed guidelines will inevitably have to be adapted to suit the local resources.
Ten-year clinical, radiological and metal ion analysis of the Birmingham Hip Resurfacing
Authors: Holland J. P. , Langton D. J. , Hashmi M.
Published: March 2012

We present the clinical results and survivorship of consecutive 100 Birmingham Hip Resurfacings in 90 patients at a minimum follow-up of ten years. All procedures were carried out by an independent surgeon who commenced a prospective study in 1998. Patients were assessed clinically using the Western Ontario and McMaster Universities osteoarthritis index, Short-Form 36, Harris hip score and University of California, Los Angeles activity score. Radiological analysis was performed by an independent observer and blood metal ion levels concentrations were measured at ten years post-operatively in 62 patients. The median acetabular component inclination was 46.2° (34° to 59°) and anteversion 11.0° (0° to 30°). The median chromium concentration in the unilateral group was 1.74 (0.41 to 15.23) and for the bilateral group was 2.98 (1.57 to 18.01). The equivalent values for cobalt were 1.67 (0.54 to 20.4) and 1.88 (1.38 to 19.32).

In total there were eight failures giving an overall survival at ten years of 92% (95% confidence interval (CI) 86.7 to 97.3). BHR in male patients had an improved survivorship of 94.6% (95% CI 89.4 to 100) compared with females at 84.6% (95% CI 70.7 to 98.5), but this did not reach statistical significance (p = 0.119). Four of the nine BHRs with a bearing diameter of 42 mm failed.

The overall results were consistent with data produced from other centres in that the clinical outcome of large male patients was extremely encouraging, whereas the survival of the smaller joints was less satisfactory.
Validation of a standardised gait score to predict the healing of tibial fractures
Authors: Macri F. , Marques L. F. , Backer R. C. , Santos M. J. , Belangero W. D.
Published: March 2012

There is no absolute method of evaluating healing of a fracture of the tibial shaft. In this study we sought to validate a new clinical method based on the systematic observation of gait, first by assessing the degree of agreement between three independent observers regarding the gait score for a given patient, and secondly by determining how such a score might predict healing of a fracture.

We used a method of evaluating gait to assess 33 patients (29 men and four women, with a mean age of 29 years (15 to 62)) who had sustained an isolated fracture of the tibial shaft and had been treated with a locked intramedullary nail. There were 15 closed and 18 open fractures (three Gustilo and Anderson grade I, seven grade II, seven grade IIIA and one grade IIIB). Assessment was carried out three and six months post-operatively using videos taken with a digital camera. Gait was graded on a scale ranging from 1 (extreme difficulty) to 4 (normal gait). Bivariate analysis included analysis of variance to determine whether the gait score statistically correlated with previously validated and standardised scores of clinical status and radiological evidence of union.

An association was found between the pattern of gait and all the other variables. Improvement in gait was associated with the absence of pain on weight-bearing, reduced tenderness over the fracture, a higher Radiographic Union Scale in Tibial Fractures score, and improved functional status, measured using the Brazilian version of the Short Musculoskeletal Function Assessment questionnaire (all p < 0.001). Although further study is needed, the analysis of gait in this way may prove to be a useful clinical tool.
Reporting and interpretation of the functional outcomes after the surgical treatment of disruptions of the pelvic ring
Authors: Lefaivre K. A. , Slobogean G. P. , Valeriote J. , O’Brien P. J. , Macadam S. A.
Published: March 2012

We performed a systematic review of the literature to evaluate the use and interpretation of generic and disease-specific functional outcome instruments in the reporting of outcome after the surgical treatment of disruptions of the pelvic ring. A total of 28 papers met our inclusion criteria, with eight reporting only generic outcome instruments, 13 reporting only pelvis-specific outcome instruments, and six reporting both. The Short-Form 36 (SF-36) was by far the most commonly used generic outcome instrument, used in 12 papers, with widely variable reporting of scores. The pelvis-specific outcome instruments were used in 19 studies; the Majeed score in ten, Iowa pelvic score in six, Hannover pelvic score in two and the Orlando pelvic score in one. Four sets of authors, all testing construct validity based on correlation with the SF-36, performed psychometric testing of three pelvis-specific instruments (Majeed, IPS and Orlando scores). No testing of responsiveness, content validity, criterion validity, internal consistency or reproducibility was performed.

The existing literature in this area is inadequate to inform surgeons or patients in a meaningful way about the functional outcomes of these fractures after fixation.
Femoral offset is underestimated on anteroposterior radiographs of the pelvis but accurately assessed on anteroposterior radiographs of the hip
Authors: Merle C. , Waldstein W. , Pegg E. , Streit M. R. , Gotterbarm T. , Aldinger P. R. , Murray D. W. , Gill H. S.
Published: March 2012

The aim of this retrospective cohort study was to identify any difference in femoral offset as measured on pre-operative anteroposterior (AP) radiographs of the pelvis, AP radiographs of the hip and corresponding CT scans in a consecutive series of 100 patients with primary end-stage osteoarthritis of the hip (43 men and 57 women with a mean age of 61 years (45 to 74) and a mean body mass index of 28 kg/m2(20 to 45)).

Patients were positioned according to a standardised protocol to achieve reproducible projection and all images were calibrated. Inter- and intra-observer reliability was evaluated and agreement between methods was assessed using Bland-Altman plots.

In the entire cohort, the mean femoral offset was 39.0 mm (95% confidence interval (CI) 37.4 to 40.6) on radiographs of the pelvis, 44.0 mm (95% CI 42.4 to 45.6) on radiographs of the hip and 44.7 mm (95% CI 43.5 to 45.9) on CT scans. AP radiographs of the pelvis underestimated femoral offset by 13% when compared with CT (p < 0.001). No difference in mean femoral offset was seen between AP radiographs of the hip and CT (p = 0.191).

Our results suggest that femoral offset is significantly underestimated on AP radiographs of the pelvis but can be reliably and accurately assessed on AP radiographs of the hip in patients with primary end-stage hip osteoarthritis.

We, therefore, recommend that additional AP radiographs of the hip are obtained routinely for the pre-operative assessment of femoral offset when templating before total hip replacement.
An information revolution in orthopaedics
Authors: Goldberg A. J. , MacGregor A. , Spencer S. A.
Published: March 2012

With the established success of the National Joint Registry and the emergence of a range of new national initiatives for the capture of electronic data in the National Health Service, orthopaedic surgery in the United Kingdom has found itself thrust to the forefront of an information revolution. In this review we consider the benefits and threats that this revolution poses, and how orthopaedic surgeons should marshal their resources to ensure that this is a force for good.
Growth disturbance after lengthening of the lower limb and quantitative assessment of physeal closure in skeletally immature patients with achondroplasia
Authors: Song S. H. , Kim S. E. , Agashe M. V. , Lee H. , Refai M. A. , Park Y. E. , Choi H. J. , Park J. H. , Song H. R.
Published: March 2012

This study evaluated the effect of limb lengthening on longitudinal growth in patients with achondroplasia. Growth of the lower extremity was assessed retrospectively by serial radiographs in 35 skeletally immature patients with achondroplasia who underwent bilateral limb lengthening (Group 1), and in 12 skeletally immature patients with achondroplasia who did not (Group 2). In Group 1, 23 patients underwent only tibial lengthening (Group 1a) and 12 patients underwent tibial and femoral lengthening sequentially (Group 1b).

The mean lengthening in the tibia was 9.2 cm (59.5%) in Group 1a, and 9.0 cm (58.2%) in the tibia and 10.2 cm (54.3%) in the femur in Group 1b. The mean follow-up was 9.3 years (8.6 to 10.3). The final mean total length of lower extremity in Group 1a was 526.6 mm (501.3 to 552.9) at the time of skeletal maturity and 610.1 mm (577.6 to 638.6) in Group 1b, compared with 457.0 mm (411.7 to 502.3) in Group 2. However, the mean actual length, representing the length solely grown from the physis without the length of distraction, showed that there was a significant disturbance of growth after limb lengthening. In Group 1a, a mean decrease of 22.4 mm (21.3 to 23.1) (4.9%) was observed in the actual limb length when compared with Group 2, and a greater mean decrease of 38.9 mm (37.2 to 40.8) (8.5%) was observed in Group 1b when compared with Group 2 at skeletal maturity.

In Group 1, the mean actual limb length was 16.5 mm (15.8 to 17.2) (3.6%) shorter in Group 1b when compared with Group 1a at the time of skeletal maturity. Premature physeal closure was seen mostly in the proximal tibia and the distal femur with relative preservation of proximal femur and distal tibia.

We suggest that significant disturbance of growth can occur after extensive limb lengthening in patients with achondroplasia, and therefore, this should be included in pre-operative counselling of these patients and their parents.
Nerve injuries sustained during warfare
Authors: Birch R. , Misra P. , Stewart M. P. M. , Eardley W. G. P. , Ramasamy A. , Brown K. , Shenoy R. , Anand P. , Clasper J. , Dunn R. , Etherington J.
Published: March 2012

The outcomes of 261 nerve injuries in 100 patients were graded good in 173 cases (66%), fair in 70 (26.8%) and poor in 18 (6.9%) at the final review (median 28.4 months (1.3 to 64.2)). The initial grades for the 42 sutures and graft were 11 good, 14 fair and 17 poor. After subsequent revision repairs in seven, neurolyses in 11 and free vascularised fasciocutaneous flaps in 11, the final grades were 15 good, 18 fair and nine poor. Pain was relieved in 30 of 36 patients by nerve repair, revision of repair or neurolysis, and flaps when indicated. The difference in outcome between penetrating missile wounds and those caused by explosions was not statistically significant; in the latter group the onset of recovery from focal conduction block was delayed (mean 4.7 months (2.5 to 10.2) vs 3.8 months (0.6 to 6); p = 0.0001). A total of 42 patients (47 lower limbs) presented with an insensate foot. By final review (mean 27.4 months (20 to 36)) plantar sensation was good in 26 limbs (55%), fair in 16 (34%) and poor in five (11%). Nine patients returned to full military duties, 18 to restricted duties, 30 to sedentary work, and 43 were discharged from military service. Effective rehabilitation must be early, integrated and vigorous. The responsible surgeons must be firmly embedded in the process, at times exerting leadership.
Rapid Diagnosis of Aneuploidy by High-Resolution Melting Analysis of Segmental Duplications
Authors: Guo Qiwei , Xiao Li , Zhou Yulin
Published: March 2012

BACKGROUND

Several molecular methods, such as quantitative fluorescence PCR and multiplex ligation-dependent probe amplification, currently serve as important adjuncts to traditional karyotyping for the diagnosis of aneuploidy; however, the performance or throughput limitations of these methods hinder their use for routine prenatal diagnosis and population-based postnatal screening. We developed a novel approach, called “high-resolution melting analysis of segmental duplications,” to detect common aneuploidies.

METHODS

In this method, similar sequences located on different chromosomes are amplified simultaneously with a single primer set; the PCR products are then analyzed by high-resolution melting. Aneuploidy-associated dosage abnormalities produce different ratios of similar amplicons, which produce melting curves that are detectably different from those of samples from unaffected individuals. We applied this method to DNA samples isolated from individuals with trisomy 21 (n = 48), trisomy 18 (n = 10), trisomy 13 (n = 3), 45,X (n = 8), and 47,XXY (n = 14), and from unaffected controls (n = 48).

RESULTS

As judged by the karyotyping results, our method attained 100% diagnostic sensitivity and 99.6% diagnostic specificity. Moreover, our method was able to detect a change in chromosome dosage as low as 1.05-fold.

CONCLUSIONS

This novel method clearly differentiates samples of patients with common aneuploidies from those of unaffected controls, while markedly simplifying the assays and reducing time and costs. The assay has sufficient throughput to meet the demands of large-scale testing, such as population-based postnatal screening, and is thus suitable for routine use.
Competitive Sorption of Pb, Cd, and Ni on Chicken Feathers from Binary Aqueous Solutions
Authors: Reynel-Avila Hilda Elizabeth , Bonilla-Petriciolet Adrian , de la Rosa Guadalupe
Published: March 2012

In this paper, we report the competitive removal of Pb, Cd, and Ni ions from binary metal solutions using chicken feathers. These heavy metals are very toxic for human being and are present in wastewaters of several industrial activities. Therefore, multi-component sorption studies are required to identify the capabilities and limitations of chicken feathers as low-cost sorbent for the simultaneous removal of these metal ions from wastewaters. To the best of our knowledge, sorption equilibrium studies involving chicken feathers and Pb, Cd, and Ni in binary aqueous solutions have not been reported. Therefore, the binary sorption data for systems Pb - Cd, Pb â Ni, and Cd - Ni at different pH conditions are reported in this paper. Our experimental data are modeled using multi-component isotherm equations and desorption studies were also performed. In summary, this study provides new experimental data to identify the competitive effects of these metal ions onto the multi-component sorption performance of chicken feathers.
A Positive Theory of Constitutional Judicial Review: Evidence from Singapore and Taiwan
Authors: Ip Eric
Published: March 2012

The consensus over independent constitutional judicial review – that it inevitably stems from electoral and inter-branch competition – has been weakened by recent empirical discoveries; however, empiricists have yet to offer a coherent explanation why non-competitive, authoritarian, governments would tolerate constitutional courts that strike down their legislation. This article proposes a “Constitutional Investment Theory” that solves this puzzle: expressive symbolism is central to these regimes’ calculus for acquiescing in the activation of judicial review; the variable perdurability of judicial review depends on how much trust the regime invest in the judiciary; and activism in judicial review is the likelier to emerge the higher the transaction costs of retaliating against offending courts. Evidence from Singapore and pre-2000 Taiwan lends support to this theory.
Nucleocytoplasmic shuttling of human inositol phosphate multikinase is influenced by CK2 phosphorylation
Authors: Meyer Rüdiger , Nalaskowski Marcus M. , Ehm Patrick , Schröder Constantin , Naj Xenia , Brehm Maria A. , Mayr Georg W.
Published: March 2012

Human inositol phosphate multikinase (IPMK) is a multifunctional protein in cellular signal transduction, namely, a multispecific inositol phosphate kinase, phosphatidylinositol 3-kinase, and a scaffold within the mTOR-raptor complex. To fulfill these nuclear and cytoplasmic functions, intracellular targeting of IPMK needs to be regulated. We show here that IPMK, which has been considered to be a preferentially nuclear protein, is a nucleocytoplasmic shuttling protein, whose nuclear export is mediated by classical nuclear export receptor CRM1. We identified a functional nuclear export signal (NES) additionally to its previously described nuclear import signal (NLS). Furthermore, we describe a mechanism by which the activity of the IPMK-NLS is controlled. Protein kinase CK2 binds endogenous IPMK and phosphorylates it at serine 284. Interestingly, this phosphorylation can decrease nuclear localization of IPMK cell type specifically. A controlled nuclear import of IPMK may direct its actions either toward nuclear inositol phosphate (InsPx) metabolism or cytoplasmic actions on InsPx, phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P2], as well as mTOR-raptor.
Apolipoprotein A5 internalized by human adipocytes modulates cellular triglyceride content
Authors: Zheng Xiao-Yan , Zhao Shui-Ping , Yu Bi-Lian , Wu Chen-Lu , Liu Ling
Published: March 2012

Apolipoprotein A5 (apoA5), an important determinant of plasma triglyceride (TG) levels, has been recently reported to modulate TG metabolism in hepatocytes. In this study, we investigated whether apoA5 can be internalized by adipocytes and regulate cellular TG storage. Human preadipocytes, derived from subcutaneous adipose tissue of patients undergoing abdominal surgery, were differentiated into mature adipocytes. Pulse-chase experiments revealed that apoA5 was internalized into human adipocytes, and ∼70% of the apoA5 internalized during the pulse remained intracellular within a 24-h chase, while 30% was degraded. Preincubation with heparin and the receptor-associated protein, both of which prevented the apoA5 interaction with members of the low-density lipoprotein receptor gene family, markedly reduced the uptake of apoA5 by 61% and 52%, respectively, which were subsequently confirmed by Western blot analysis. Using confocal microscopy, we demonstrated that labeled apoA5 surrounded lipid droplets in human adipocytes and colocalized with the known lipid droplet protein perilipin. Importantly, treatment of adipocytes with apoA5 significantly decreased cellular TG storage. In conclusion, apoA5 can be internalized by human adipocytes and may act as a novel regulator to control TG storage in human adipocytes.
Mammalian carboxylesterase (CES) releases GPI-anchored proteins from the cell surface upon lipid raft fluidization
Authors: Orihashi Kaoru , Tojo Hiromasa , Okawa Katsuya , Tashima Yuko , Morita Takashi , Kondoh Gen
Published: March 2012

Mammalian carboxylesterase (CES) is well known as a biotransformation enzyme for prodrugs and xenobiotics. Here, we purified CES as a GPI-anchored protein (GPI-AP)-releasing factor (GPIase) that releases such protein from the cell surface. All five isoforms of CES showed this activity to various degrees. When the serine residue of the catalytic triad for esterase was replaced by alanine, esterase activity was completely disrupted, while full GPIase activity remained, suggesting that these two activities are exhibited via different mechanisms. CES6, a new class of mammalian CES, exhibited the highest GPIase activity and released specific GPI-APs from the cell surface after lipid raft fluidization. The released product contained a GPI component, indicating that GPI-AP was released by cleavage in GPI. These results revealed for the first time that CES recognizes and catalyzes macromolecule GPI-AP as well as small molecules.