bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of intrahepatic blood flow by Doppler ultrasonography: Relationship between the hepatic vein, portal vein, hepatic artery and portal pressure measured intraoperatively in patients with portal hypertension
Authors: Zhang Li , Yin Jikai , Duan Yunyou , Yang Yilin , Yuan Lijun , Cao Tiesheng
Published: July 2011

Background

Abnormality of hepatic vein (HV) waveforms evaluated by Doppler ultrasonography has been widely studied in patients with chronic liver disease. We investigated the correlation between changes in HV waveforms and portal vein velocity (PVVel), the hepatic artery pulsatility index (HAPI), and also the extent of abnormal Doppler HV waveforms expressed as damping index (DI), severity of portal hypertension expressed as Child-Pugh scores and portal pressure (PP) measured directly from patients with portal hypertension (PHT) to evaluate the indicative value of abnormal HV waveforms and discuss the cause of abnormal HV waveform.

Methods

Sixty patients who had been diagnosed with PHT and accepted surgical therapy of portosystemic shunts were investigated. PP was measured intraoperatively. Thirty healthy volunteers with no history of chronic liver disease were enrolled as the control group. HV waveforms were categorized as triphasic, biphasic or monophasic. DI was compared as the quantitative indicator of abnormal HV waveforms. Another two Doppler parameters, PVVel and HAPI were also measured. These Doppler features were compared with PP, Child-Pugh scores and histological changes assessed by liver biopsy.

Results

In the patient group, the Doppler flow waveforms in the middle HV were triphasic in 31.6%, biphasic in 46.7%, and monophasic in 21.6% of subjects. These figures were 86.7%, 10.0%, and 3.3%, respectively, in healthy subjects. With the flattening of HV waveforms, the HAPI increased significantly (r= 00.438,p< 0.0001), whereas PVVel decreased significantly (r= -0.44,p <0.0001). Blood flow parameters, HAPI, PVVel and HV-waveform changes showed no significant correlations with Child-Pugh scores. The latter showed a significant correlation with PP (r= 0.589,p= 0.044). Changes of HV waveform and DI significantly correlated with PP (r= 0.579,r= 0.473,p <0.0001), and significant correlation between DI and Child-Pugh scores was observed (r= 0.411,p =0.001). PP was significantly different with respect to nodule size (p< 0.05), but HV-waveform changes were not significantly correlated with pathological changes.

Conclusion

In patients with PHT, a monophasic HV waveform indicates higher portal pressure. Furthermore, quantitative indicator DI can reflect both higher portal pressure and more severe liver dysfunction. Flattening of HV waveforms accompanied by an increase in the HAPI and decrease in PVVel support the hypothesis that histological changes reducing HV compliance be the cause of abnormality of Doppler HV waveforms from the hemodynamic angle.
Molecular markers of resistance to sulphadoxine-pyrimethamine during intermittent preventive treatment of pregnant women in Benin
Authors: Bertin Gwladys , Briand Valérie , Bonaventure Diana , Carrieu Ambre , Massougbodji Achille , Cot Michel , Deloron Philippe
Published: July 2011

Background

The prevention of malaria faces with the repeated emergence of Plasmodium falciparum resistance to drugs, often involving point mutations of the target gene. In the pregnant woman, currently the WHO recommendation is the administration of an intermittent preventive treatment (IPTp) with sulphadoxine-pyrimethamine. Sulphadoxine-pyrimethamine (SP) resistance has increased for several years in Africa, stressing the need for alternative molecules. In this context, the first randomized clinical trial comparing the efficacy of SP and mefloquine for IPTp has been conducted recently in Benin. Using samples from this trial, the current study evaluated and quantified the prevalence of mutations on the pfdhfr and pfdhps genes as well as the copy number of the pfmdr1 gene in parasites from P. falciparum-infected pregnant women before first and second IPTp administration, and at delivery.

Methods

PCR-restriction fragment length polymorphism of polymorphic codons of the pfdhfr gene (51, 59, 108, and 164) was performed. The identification of mutations in three codons of the pfdhps gene (436, 437 and 540) was achieved by PCR and sequencing. Copy number quantification for pfmdr1 gene was performed using real-time PCR.

Results

Results show a high prevalence rate of mutant parasites in women taking IPTp with sulphadoxine-pyrimethamine or mefloquine. The prevalence of triple and quadruple mutants was high before first drug regimen administration (79/93, 85%), and remained similar until delivery. Infection with mutant parasites was not correlated with low birth weight nor placental infection. In all samples, the copy number of pfmdr1 gene was equal to one.

Conclusions

The clinical trial comparing SP and mefloquine efficacy during IPTp showed SP remained efficacious in preventing low birth weight. The present study shows a high prevalence of triple and quadruple mutations implicated in SP resistance. Although the pfdhfr/pfdhps triple and quadruple mutations were frequent, there was no evidence of correlation between these genotypes and the lack of efficacy of SP in the context of IPTp. Nevertheless, it is now obvious that SP will soon be compromised in whole Africa. Molecular markers have been recommended to monitor SP efficacy for IPTp, but given the current prevalence of mutant parasites their usefulness is questionable.
Follow-up study on lead exposure in children living in a smelter community in northern Mexico
Authors: Rubio-Andrade Marisela , Valdés-Pérezgasga Francisco , Alonso J , Rosado Jorge L , Cebrián Mariano E , García-Vargas Gonzalo G
Published: July 2011

Background

To study the changes of children lead exposure in the city of Torreon during the last five years, after environmental and public health interventions, using the timeline of lead in blood concentration as the biomarker of exposure and its relation to lead in soil concentrations.

Methods

This follow-up study started in 2001 and consisted of 232 children living in nine neighborhoods in Torreon. Children were tested at 0, 6, 12 and 60 months. Lead in blood concentrations, Hemoglobin, Zinc-Protoporphyrin, anthropometric measures and socioeconomic status questionnaire was supplied to the parents.

Results

Median and range of lead in blood concentrations obtained at 0, 6, 12, 60 months were: 10.12 μg/dl (1.9 - 43.8), 8.75 μg/dl (1.85 - 41.45), 8.4 μg/dl (1.7 - 35.8) and 4.4 μg/dl (1.3 - 30.3), respectively. The decrease of lead in blood levels was significantly related to ages 0, 6, 12 and 60 months of the follow-up study. The timeline of B-Pb was associated with the timeline of lead in soil concentrations.

Conclusions

B-Pb levels have significantly decreased in the group of children studied. This could be explained by a) environmental interventions by authorities and the smelter companies, b) normal changes in hygienic habits as children age and c) lead redistribution from blood to hard tissues.
Development of a PCR Assay to detect Papillomavirus Infection in the Snow Leopard
Authors: Mitsouras Katherine , Faulhaber Erica A , Hui Gordon , Joslin Janis O , Eng Curtis , Barr Margaret C , Irizarry Kristopher JL
Published: July 2011

Background

Papillomaviruses (PVs) are a group of small, non-encapsulated, species-specific DNA viruses that have been detected in a variety of mammalian and avian species including humans, canines and felines. PVs cause lesions in the skin and mucous membranes of the host and after persistent infection, a subset of PVs can cause tumors such as cervical malignancies and head and neck squamous cell carcinoma in humans. PVs from several species have been isolated and their genomes have been sequenced, thereby increasing our understanding of the mechanism of viral oncogenesis and allowing for the development of molecular assays for the detection of PV infection. In humans, molecular testing for PV DNA is used to identify patients with persistent infections at risk for developing cervical cancer. In felids, PVs have been isolated and sequenced from oral papillomatous lesions of several wild species including bobcats, Asian lions and snow leopards. Since a number of wild felids are endangered, PV associated disease is a concern and there is a need for molecular tools that can be used to further study papillomavirus in these species.

Results

We used the sequence of the snow leopard papillomavirus UuPV1 to develop a PCR strategy to amplify viral DNA from samples obtained from captive animals. We designed primer pairs that flank the E6 and E7 viral oncogenes and amplify two DNA fragments encompassing these genes. We detected viral DNA for E6 and E7 in genomic DNA isolated from saliva, but not in paired blood samples from snow leopards. We verified the identity of these PCR products by restriction digest and DNA sequencing. The sequences of the PCR products were 100% identical to the published UuPV1 genome sequence.

Conclusions

We developed a PCR assay to detect papillomavirus in snow leopards and amplified viral DNA encompassing the E6 and E7 oncogenes specifically in the saliva of animals. This assay could be utilized for the molecular investigation of papillomavirus in snow leopards using saliva, thereby allowing the detection of the virus in the anatomical site where oral papillomatous lesions develop during later stages of infection and disease development.
Histological subtype is the most important determinant of survival in metastatic papillary thyroid cancer
Authors: Chrisoulidou Alexandra , Boudina Maria , Tzemailas Athanasios , Doumala Eleni , Iliadou Pashalia K , Patakiouta Frideriki , Pazaitou-Panayiotou Kalliopi
Published: July 2011

Background

Papillary thyroid cancer (PTC) comprises the commonest type of thyroid cancer and carries the highest rate of survival. However, when metastatic disease occurs, survival is significantly affected.

Methods

We aimed to identify prognostic histopathological and clinical factors that modify survival in metastatic PTC. All cases of metastatic PTC treated at our department in the last 20 years were reviewed and analyzed.

Results

Histological subtype was the most important determinant of survival, as classic PTC demonstrated clearly improved survival compared to follicular subtype of PTC and other less frequently seen histological subtypes. The instant risk of death for the other histological subtypes was 4.56 times higher than the risk for the classic papillary type. Overall, a 10-year survival of 76.6% in our patients was seen.

Conclusions

Patients with aggressive variants of PTC are more at risk for the development of metastatic disease. In these patients, established treatment modalities (surgery, radioiodine therapy) should be offered promptly, as well as close follow-up.
Effects of discontinuing or continuing ongoing statin therapy in severe sepsis and septic shock: a retrospective cohort study
Authors: Mekontso Dessap Armand , Ouanes Islem , Rana Nerlep , Borghi Beatrice , Bazin Christophe , Katsahian Sandrine , Hulin Anne , Brun-Buisson Christian
Published: July 2011

Introduction

Recent publications suggest potential benefits from statins as a preventive or adjuvant therapy in sepsis. Whether ongoing statin therapy should be continued or discontinued in patients admitted in the intensive care unit (ICU) for sepsis is open to question.

Methods

We retrospectively compared patients with severe sepsis and septic shock in whom statin therapy had been discontinued or continued. The primary endpoint was the number of organ failure-free days at day 14. Secondary end-points included hospital mortality and safety. The association of statin continuation with outcome was evaluated for crude analysis and after propensity score matching and adjustment. We also measured plasma atorvastatin concentrations in a separate set of ICU septic patients continuing the drug.

Results

Patients in whom statin therapy had been continued in the ICU (n = 44) had significantly more organ failure-free days (11 [6–14] vs. 6 [0-12], mean difference of 2.34, 95%CI from 0.47 to 5.21, P = 0.03) as compared to others (n = 32). However, there were important imbalances between groups, with more hospital-acquired infections, more need for surgery before ICU admission, and a trend towards more septic shock at ICU admission in the discontinuation group. The significant association of statin continuation with organ failure free days found in the crude analysis did not persist after propensity-matching or multivariable adjustment: beta coefficients [95% CI] of 2.37 [-0.96 to 5.70] (P = 0.20) and 2.24 [-0.43 to 4.91] (P = 0.11) respectively. We found particularly high pre-dose and post-dose atorvastatin concentrations in ICU septic patients continuing the drug.

Conclusions

Continuing statin therapy in ICU septic patients was not associated with reduction in the severity of organ failure after matching and adjustment. In addition, the very high plasma concentrations achieved during continuation of statin treatment advocates some caution.
Dextromethorphan As a Phenotyping Test to Predict Endoxifen Exposure in Patients on Tamoxifen Treatment
Authors: de Graan Anne-Joy M. , Teunissen Sebastiaan F. , de Vos Filip Y.F.L. , Loos Walter J. , van Schaik Ron H.N. , de Jongh Felix E. , de Vos Aad I. , van Alphen Robbert J. , van der Holt Bronno , Verweij Jaap , Seynaeve Caroline , Beijnen Jos H. , Mathijssen Ron H.J.
Published: July 2011

Purpose

Tamoxifen, a widely used agent for the prevention and treatment of breast cancer, is mainly metabolized by CYP2D6 and CYP3A to form its most abundant active metabolite, endoxifen. Interpatient variability in toxicity and efficacy of tamoxifen is substantial. Contradictory results on the value of CYP2D6 genotyping to reduce the variable efficacy have been reported. In this pharmacokinetic study, we investigated the value of dextromethorphan, a known probe drug for both CYP2D6 and CYP3A enzymatic activity, as a potential phenotyping probe for tamoxifen pharmacokinetics.

Methods

In this prospective study, 40 women using tamoxifen for invasive breast cancer received a single dose of dextromethorphan 2 hours after tamoxifen intake. Dextromethorphan, tamoxifen, and their respective metabolites were quantified. Exposure parameters of all compounds were estimated, log transformed, and subsequently correlated.

Results

A strong and highly significant correlation (r = −0.72; P < .001) was found between the exposures of dextromethorphan (0 to 6 hours) and endoxifen (0 to 24 hours). Also, the area under the plasma concentration–time curve of dextromethorphan (0 to 6 hours) and daily trough endoxifen concentration was strongly correlated (r = −0.70; P < .001). In a single patient using the potent CYP2D6 inhibitor paroxetine, the low endoxifen concentration was accurately predicted by dextromethorphan exposure.

Conclusion

Dextromethorphan exposure after a single administration adequately predicted endoxifen exposure in individual patients with breast cancer taking tamoxifen. This test could contribute to the personalization and optimization of tamoxifen treatment, but it needs additional validation and simplification before being applicable in future dosing strategies.
Randomized Phase II Study of Erlotinib Plus Tivantinib Versus Erlotinib Plus Placebo in Previously Treated Non–Small-Cell Lung Cancer
Authors: Sequist Lecia V. , von Pawel Joachim , Garmey Edward G. , Akerley Wallace L. , Brugger Wolfram , Ferrari Dora , Chen Yinpu , Costa Daniel B. , Gerber David E. , Orlov Sergey , Ramlau Rodryg , Arthur Susan , Gorbachevsky Igor , Schwartz Brian , Schiller Joan H.
Published: July 2011

Purpose

c-MET (MET) receptor activation is associated with poor prognosis and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance in non–small-cell lung cancer (NSCLC). This global, randomized phase II trial examined erlotinib plus tivantinib (ARQ 197; ArQule, Woburn, MA), a novel MET inhibitor.

Methods

Previously treated patients with EGFR TKI–naive advanced NSCLC were randomly assigned to receive oral erlotinib (150 mg daily) plus oral tivantinib (360 mg twice daily) or erlotinib plus placebo (EP). The primary end point was progression-free survival (PFS). At the time of progression, cross-over from EP to erlotinib plus tivantinib (ET) was permitted. Archival tumor tissue specimens were required.

Results

One hundred sixty-seven patients were randomly assigned to ET (n = 84) and to EP (n = 83). Median PFS was 3.8 months for ET and 2.3 months for EP (hazard ratio [HR], 0.81; 95% CI, 0.57 to 1.16; P = .24). Exploratory analysis revealed that the small cohort with KRAS mutations achieved a PFS HR of 0.18 (95% CI, 0.05 to 0.70; interaction P = .006). Objective responses were seen in 10% of patients on ET, 7% of patients on EP, and in two patients who crossed over from EP to ET, including one with EGFR mutation and MET gene copy number greater than 5. There were no significant differences in adverse events between study arms.

Conclusion

The combination of the MET inhibitor tivantinib and erlotinib is well-tolerated. Although the study did not meet its primary end point, evidence of activity was demonstrated, especially among patients with KRAS mutations. Additional study of tivantinib and erlotinib in patients with NSCLC is planned.
Clinical and Biologic Features Predictive of Survival After Relapse of Neuroblastoma: A Report From the International Neuroblastoma Risk Group Project
Authors: London Wendy B. , Castel Victoria , Monclair Tom , Ambros Peter F. , Pearson Andrew D.J. , Cohn Susan L. , Berthold Frank , Nakagawara Akira , Ladenstein Ruth L. , Iehara Tomoko , Matthay Katherine K.
Published: July 2011

Purpose

Survival after neuroblastoma relapse is poor. Understanding the relationship between clinical and biologic features and outcome after relapse may help in selection of optimal therapy. Our aim was to determine which factors were significantly predictive of postrelapse overall survival (OS) in patients with recurrent neuroblastoma—particularly whether time from diagnosis to first relapse (TTFR) was a significant predictor of OS.

Patients and Methods

Patients with first relapse/progression were identified in the International Neuroblastoma Risk Group (INRG) database. Time from study enrollment until first event and OS time starting from first event were calculated. Cox regression models were used to calculate the hazard ratio of increased death risk and perform survival tree regression. TTFR was tested in a multivariable Cox model with other factors.

Results

In the INRG database (N = 8,800), 2,266 patients experienced first progression/relapse. Median time to relapse was 13.2 months (range, 1 day to 11.4 years). Five-year OS from time of first event was 20% (SE, ± 1%). TTFR was statistically significantly associated with OS time in a nonlinear relationship; patients with TTFR of 36 months or longer had the lowest risk of death, followed by patients who relapsed in the period of 0 to less than 6 months or 18 to 36 months. Patients who relapsed between 6 and 18 months after diagnosis had the highest risk of death. TTFR, age, International Neuroblastoma Staging System stage, and MYCN copy number status were independently predictive of postrelapse OS in multivariable analysis.

Conclusion

Age, stage, MYCN status, and TTFR are significant prognostic factors for postrelapse survival and may help in the design of clinical trials evaluating novel agents.
Four-Year Follow-Up of Trastuzumab Plus Adjuvant Chemotherapy for Operable Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: Joint Analysis of Data From NCCTG N9831 and NSABP B-31
Authors: Perez Edith A. , Romond Edward H. , Suman Vera J. , Jeong Jong-Hyeon , Davidson Nancy E. , Geyer Charles E. , Martino Silvana , Mamounas Eleftherios P. , Kaufman Peter A. , Wolmark Norman
Published: July 2011

Purpose

Trastuzumab is a humanized monoclonal antibody against the human epidermal growth factor receptor 2 (HER2). The clinical benefits of adjuvant trastuzumab have been demonstrated in interim analyses of four large trials. Initial data of the combined analysis of the North Central Cancer Treatment Group (NCCTG) N9831 Intergroup trial and National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31 trial were reported in 2005. Long-term follow-up results on disease-free survival (DFS) and overall survival (OS) have been awaited.

Patients and Methods

Patients with HER2-positive operable breast cancer were randomly assigned to doxorubicin plus cyclophosphamide followed by paclitaxel with or without trastuzumab in the NCCTG N9831 and NSABP B-31 trials. The similar design of both trials allowed data from the control and trastuzumab-containing arms to be combined in a joint analysis.

Results

At 3.9 years of median follow-up, there continues to be a highly statistically significant reduction in DFS event rate in favor of the trastuzumab-containing arm (P < .001). Similarly, there continues to be a statistically significant 39% reduction in death rate in favor of the trastuzumab-containing arm (P < .001).

Conclusion

These data demonstrate consistent DFS and OS advantages of adjuvant trastuzumab over time, with the longest follow-up reported to date. The clinical benefits continue to outweigh the risks of adverse effects.
From the Beginnings: Debates on the History of Science in Brazil
Authors: Kropf Simone Petraglia , Hochman Gilberto
Published: July 2011

This article analyzes the ways in which the book Beginnings of Brazilian Science: Oswaldo Cruz, Medical Research and Policy, 1890 – 1920, published by Nancy Leys Stepan in 1976, has been received in the debates on science and the history of science in Brazil. Our purpose is to show how the discussions prompted by Stepan’s book have been directly linked to the emergence of a new historiography of science in that country since the early 1980s, as a professionalized and institutionalized scholarly field. This process has been associated, in turn, with a broader policy debate in Brazil and Spanish America on the particular features of science, and of the history of science, in the so-called developing countries. We also seek to show the extent to which some of the questions posed in The Beginnings of Brazilian Science are still richly relevant to academic and political consideration of the complexity and specificity of the historical and social process of institutionalization of science. Rather than attempt an exhaustive analysis of the readings of Stepan’s work, we will focus on the main areas of historiographic debate, based on the more representative works and authors, especially in the 1980s and 1990s.
A Complex Fabric: Intersecting Histories of Race, Gender, and Science in Latin America
Authors: Rodriguez Julia
Published: July 2011

This essay describes historians’ recent and growing awareness of the significance of science in modern Latin America. It focuses first on the work and influence of the historian Nancy Leys Stepan, who in the past 30 years pioneered the joining of methods in the history of science — in particular, the tendency to see science in its specific social context — with some of the most central concerns of Latin Americanists. For example, a key contribution of Stepan’s work is her analysis of scientific representations of human difference that shaped the creation and legitimating of racist and sexist ideas across Latin American societies. Moreover, her work was part of an early wave that brought the application of feminist and critical race theory to the field, with valuable outcomes. Her work has been a springboard for continuing investigations of the interplay between scientific ideas and practices and larger social forces. After an overview of Stepan’s approach and findings, the essay discusses two major trends in the literature that emerge from and build on Stepan’s work: the incorporation of sexuality along with race, gender, and class in studies of science and medicine in Latin American history; and further developments in the history of transatlantic science in the modern period.
“The Hour of Eugenics” in Veracruz, Mexico: Radical Politics, Public Health, and Latin America’s Only Sterilization Law
Authors: Stern Alexandra Minna
Published: July 2011

In 1932, the Mexican state of Veracruz passed Latin America’s only eugenic sterilization law. Building on the foundational scholarship of Nancy Leys Stepan, this article critically examines Veracruz’s eugenics movement, exploring how it intersected with public health, antivice campaigns, and radical agrarian and labor politics. I pay particular attention to Governor Adalberto Tejeda, who, during his second term in office (1928 – 1932) incorporated a zealous version of Latin eugenics into state laws and policies. This article suggests that Veracruz’s experiment with eugenics, especially the state’s sterilization statute, was intimately connected to concerns about prostitution, sexual health, and working-class vigor. This article highlights an unexplored dimension of society and medicine in Latin America and raises questions about the orientation and limits of preventive eugenics in Mexico, and about the homologies among eugenics movements in the Americas and across the globe in the twentieth century.
Dietary folate protects against azoxymethane-induced aberrant crypt foci development and oxidative stress in rat colon
Authors: Al-Numair Khalid S , Waly Mostafa I , Ali Amanat , Essa Mohamed M , Farhat Mohamed F , Alsaif Mohamed A
Published: July 2011

Azoxymethane (AOM) induces cancer and oxidative stress in rat colon. This study tested the hypothesis that dietary folate supplementation protects against AOM-induced oxidative stress and reduces aberrant crypt foci (ACF) development in rat colon. Fifty-four weanling male albino rats, with an average body weight of 50 ± 5 g, were randomly divided into three groups – A, B and C (18 rats per group) – and fed 2, 8 or 40 mg of folic acid per kg of supplemented diets, respectively, throughout the eight weeks' experimental period. The animals were supplied with diet and water ad libitum for four weeks and they reached an average body weight of 100 g. Thereafter each group was then further randomly subdivided into three subgroups (six rats per subgroup): control, vehicle and AOM-injected groups. The control group did not receive any treatment (neither AOM injection nor saline), the rats in the vehicle group were given 1 mL intraperitoneal injection of saline once a week for two weeks and the rats in the AOM-injected group were given two intraperitoneal injections of AOM dissolved in saline once a week for two weeks totaling 30 mg/kg body weight. After the last AOM injection, animals were continuously fed ad libitum their specified diet for two weeks of last AOM injection, all rats were sacrificed, and colon tissues were collected and used for ACF enumeration and measurements of glutathione (GSH) and total antioxidant capacity (TAC). The results revealed that AOM-injected rats showed lower levels of GSH and TAC as compared with control and vehicle groups. Folic acid-supplemented diets suppressed the AOM-induced ACF and GSH depletion in a dose-dependent manner and augmented the TAC. It was concluded that folic acid supplementation protects against the AOM-induced ACF formation by suppressing the AOM-induced GSH depletion in rat colon cells.
Effect of multiple infection of cells on the evolutionary dynamics of HIVin vivo: implications for host adaptation mechanisms
Authors: Wodarz Dominik , Levy David N
Published: July 2011

The dynamics between human immunodeficiency virus type 1 and the immune system have been studied both experimentally and mathematically, exploring aspects of host adaptation and viral mechanisms to escape host control. The majority of this work, however, has been performed assuming that any cell can only be infected by one copy of the virus. In recent years, it has become clear that multiple copies of the virus can infect the same cell, a process we refer to as co-infection. Here, we review this topic and discuss how immune control of the infection and the ability of the virus to escape immune control is affected by co-infection.
Mechanisms maintaining genomic integrity in embryonic stem cells and induced pluripotent stem cells
Authors: Tichy Elisia D
Published: July 2011

Embryonic stem cells (ESCs) are pluripotent, self-renewing cells that are isolated during the blastocyst stage of embryonic development. Whether these cells are derived from humans, mice or other organisms, all ESCs must employ mechanisms that prevent the propagation of mutations, generated as a consequence of DNA damage, to somatic cells produced by normal programmed differentiation. Thus, the prevention of mutations in ESCs is important not only for the health of the individual organism derived from these cells but also, in addition, for the continued survival and genetic viability of the species by preventing the accumulation of mutations in the germline. Induced pluripotent stem cells (IPSCs) are reprogrammed somatic cells that share several characteristics with ESCs, including a similar morphology in culture, the re-expression of pluripotency markers and the ability to differentiate into defined cell lineages. This review focuses on the mechanisms employed by murine ESCs, human ESCs and, where data are available, IPSCs to preserve genetic integrity.
Assessing computational tools for the discovery of small RNA genes in bacteria
Authors: Lu Xiaojun , Goodrich-Blair Heidi , Tjaden Brian
Published: July 2011

Over the past decade, a number of biocomputational tools have been developed to predict small RNA (sRNA) genes in bacterial genomes. In this study, several of the leading biocomputational tools, which use different methodologies, were investigated. The performance of the tools, both individually and in combination, was evaluated on ten sets of benchmark data, including data from a novel RNA-seq experiment conducted in this study. The results of this study offer insight into the utility as well as the limitations of the leading biocomputational tools for sRNA identification and provide practical guidance for users of the tools.
The role of the transverse acetabular ligament for acetabular component orientation in total hip replacement
Authors: Kalteis T. , Sendtner E. , Beverland D. , Archbold P. A. , Hube R. , Schuster T. , Renkawitz T. , Grifka J.
Published: July 2011

Orientation of the native acetabular plane as defined by the transverse acetabular ligament (TAL) and the posterior labrum was measured intra-operatively using computer-assisted navigation in 39 hips. In order to assess the influence of alignment on impingement, the range of movement was calculated for that defined by the TAL and the posterior labrum and compared with a standard acetabular component position (abduction 45°/anteversion 15°).

With respect to the registration of the plane defined by the TAL and the posterior labrum, there was moderate interobserver agreement (r = 0.64, p < 0.001) and intra-observer reproducibility (r = 0.73, p < 0.001). The mean acetabular component orientation achieved was abduction of 41° (32° to 51°) and anteversion of 18° (−1° to 36°). With respect to the Lewinnek safe zone (abduction 40° ±10°, anteversion 15° ±10°), 35 of the 39 acetabular components were within this zone. However, there was no improvement in the range of movement (p = 0.94) and no significant difference in impingement (p = 0.085).

Alignment of the acetabular component with the TAL and the posterior labrum might reduce the variability of acetabular component placement in total hip replacement. However, there is only a moderate interobserver agreement and intra-observer reliability in the alignment of the acetabular component using the TAL and the posterior labrum. No reduction in impingement was found when the acetabular component was aligned with the TAL and the posterior labrum, compared with a standard acetabular component position.
Distal tibial fracture repair in a neurofibromatosis type 1-deficient mouse treated with recombinant bone morphogenetic protein and a bisphosphonate
Authors: Schindeler A. , Birke O. , Yu N. Y. C. , Morse A. , Ruys A. , Baldock P. A. , Little D. G.
Published: July 2011

Congenital pseudarthrosis of the tibia is an uncommon manifestation of neurofibromatosis type 1 (NF1), but one that remains difficult to treat due to anabolic deficiency and catabolic excess. Bone grafting and more recently recombinant human bone morphogenetic proteins (rhBMPs) have been identified as pro-anabolic stimuli with the potential to improve the outcome after surgery. As an additional pharmaceutical intervention, we describe the combined use of rhBMP-2 and the bisphosphonate zoledronic acid in a mouse model of NF1-deficient fracture repair.

Fractures were generated in the distal tibiae of neurofibromatosis type 1-deficient (Nf1+/−) mice and control mice. Fractures were open and featured periosteal stripping. All mice received 10 μg rhBMP-2 delivered in a carboxymethylcellulose carrier around the fracture as an anabolic stimulus. Bisphosphonate-treated mice also received five doses of 0.02 mg/kg zoledronic acid given by intraperitoneal injection.

When only rhBMP but no zoledronic acid was used to promote repair, 75% of fractures in Nf1+/− mice remained ununited at three weeks compared with 7% of controls (p < 0.001). Systemic post-operative administration of zoledronic acid halved the rate of ununited fractures to 37.5% (p < 0.07).

These data support the concept that preventing bone loss in combination with anabolic stimulation may improve the outcome following surgical treatment for children with congenital pseudarthoris of the tibia and NF1.
Chronic haematogenous osteomyelitis in children
Authors: Jones H. Wynn , Beckles V. L. L. , Akinola B. , Stevenson A. J. , Harrison W. J.
Published: July 2011

From a global point of view, chronic haematogenous osteomyelitis in children remains a major cause of musculoskeletal morbidity. We have reviewed the literature with the aim of estimating the scale of the problem and summarising the existing research, including that from our institution. We have highlighted areas where well-conducted research might improve our understanding of this condition and its treatment.
Operativeversusnon-operative treatment of acute rupture of tendo Achillis
Authors: Keating J. F. , Will E. M.
Published: July 2011

A total of 80 patients with an acute rupture of tendo Achillis were randomised to operative repair using an open technique (39 patients) or non-operative treatment in a cast (41 patients). Patients were followed up for one year. Outcome measures included clinical complications, range of movement of the ankle, the Short Musculoskeletal Function Assessment (SMFA), and muscle function dynamometry evaluating dorsiflexion and plantar flexion of the ankle. The primary outcome measure was muscle dynamometry.

Re-rupture occurred in two of 37 patients (5%) in the operative group and four of 39 (10%) in the non-operative group, which was not statistically significant (p = 0.68). There was a slightly greater range of plantar flexion and dorsiflexion of the ankle in the operative group at three months which was not statistically significant, but at four and six months the range of dorsiflexion was better in the non-operative group, although this did not reach statistically significance either. After 12 weeks the peak torque difference of plantar flexion compared with the normal side was less in the operative than the non-operative group (47% vs 61%, respectively, p < 0.005). The difference declined to 26% and 30% at 26 weeks and 20% and 25% at 52 weeks, respectively. The difference in dorsiflexion peak torque from the normal side was less than 10% by 26 weeks in both groups, with no significant differences. The mean SMFA scores were significantly better in the operative group than the non-operative group at three months (15 vs 20, respectively, p < 0.03). No significant differences were observed after this, and at one year the scores were similar in both groups.

We were unable to show a convincing functional benefit from surgery for patients with an acute rupture of the tendo Achillis compared with conservative treatment in plaster.
Arthroscopic treatment of labral tears in femoroacetabular impingement
Authors: Schilders E. , Dimitrakopoulou A. , Bismil Q. , Marchant P. , Cooke C.
Published: July 2011

Labral tears are commonly associated with femoroacetabular impingement. We reviewed 151 patients (156 hips) with femoroacetabular impingement and labral tears who had been treated arthroscopically. These were subdivided into those who had undergone a labral repair (group 1) and those who had undergone resection of the labrum (group 2). In order to ensure the groups were suitably matched for comparison of treatment effects, patients with advanced degenerative changes (Tönnis grade > 2, lateral sourcil height < 2 mm and Outerbridge grade 4 changes in the weight-bearing area of the femoral head) were excluded, leaving 96 patients (101 hips) in the study. At a mean follow-up of 2.44 years (2 to 4), the mean modified Harris hip score in the labral repair group (group 1, 69 hips) improved from 60.2 (24 to 85) pre-operatively to 93.6 (55 to 100), and in the labral resection group (group 2, 32 hips) from 62.8 (29 to 96) pre-operatively to 88.8 (35 to 100). The mean modified Harris hip score in the labral repair group was 7.3 points greater than in the resection group (p = 0.036, 95% confidence interval 0.51 to 14.09). Labral detachments were found more frequently in the labral repair group and labral flap tears in the resection group. No patient in our study group required a subsequent hip replacement during the period of follow-up.

This study shows that patients without advanced degenerative changes in the hip can achieve significant improvement in their symptoms after arthroscopic treatment of femoroacetabular impingement. Where appropriate, labral repair provides a superior result to labral resection.
An unusual high-pressure injection injury involving the cervical spinal cord
Authors: Gao X. , Wu Q.-H. , Chen W.-S. , Chen Q.-X. , Xu K. , Li F.-C. , Yan S.-G.
Published: July 2011

High-pressure injection injuries occur infrequently but are usually work-related and involve the non-dominant hand. The neck is a very rare site for such an injury. We describe the management of a 36-year-old man with a high-pressure grease-gun injection injury to his neck causing a cervical spinal cord injury. He developed severe motor and sensory changes which were relieved by surgical removal of the grease through anterior and posterior approaches.
Clinical outcome and quality of life after surgery for peri-acetabular metastases
Authors: Ji T. , Guo W. , Yang R.-L. , Tang S. , Sun X.
Published: July 2011

We set out to determine the impact of surgery on quality of life and function in patients who had undergone surgery for symptomatic peri-acetabular metastases. From a prospective database we retrospectively reviewed 46 consecutive patients who had been treated operatively between June 2003 and June 2009. The mean age of the patients was 56.4 years (20 to 73) and the mean post-operative follow-up was 19.2 months (4 to 70). Functional evaluation and quality-of-life assessments were performed. At the most recent follow-up, 26 patients (56.5%) were alive. Their median survival time was 25.0 months. Ten major postoperative complications had occurred in eight patients (17.4%). The mean post-operative Musculoskeletal Tumor Society score (MSTS 93) was 56.3% (6.7% to 90.0%). Improvement in the Eastern Cooperative Oncology Group (ECOG) performance status was seen in 32 patients (69.6%). On the European Organisation for Research and Treatment of Cancer core quality-of-life questionnaire (QLQ-C30) measure of global health status there was a statistically significant improvement from the patients’ pre-operative status (42.8 (sd 13.7)) to that found at the latest follow-up (58.0 (sd 12.5)) (p = 0.001). The only statistically significant change in the nine symptom domains of the QLQ-C30 was a reduction in the mean level of pain (from 59.1 to 29.5 (out of 100)) (p < 0.001).

Surgery for patients with peri-acetabular metastases reduces pain and improves their quality of life, and has a low rate of surgical complications.
Fixation of pathological humeral fractures by the cemented plate technique
Authors: Weiss K. R. , Bhumbra R. , Biau D. J. , Griffin A. M. , Deheshi B. , Wunder J. S. , Ferguson P. C.
Published: July 2011

Pathological fractures of the humerus are associated with pain, morbidity, loss of function and a diminished quality of life. We report our experience of stabilising these fractures using polymethylmethacrylate and non-locking plates. We undertook a retrospective review over 20 years of patients treated at a tertiary musculoskeletal oncology centre. Those who had undergone surgery for an impending or completed pathological humeral fracture with a diagnosis of metastatic disease or myeloma were identified from our database. There were 63 patients (43 men, 20 women) in the series with a mean age of 63 years (39 to 87).

All had undergone intralesional curettage of the tumour followed by fixation with intramedullary polymethylmethacrylate and plating. Complications occurred in 14 patients (22.2%) and seven (11.1%) required re-operation. At the latest follow-up, 47 patients (74.6%) were deceased and 16 (25.4%) were living with a mean follow-up of 75 months (1 to 184). A total of 54 (86%) patients had no or mild pain and 50 (80%) required no or minimal assistance with activities of daily living. Of the 16 living patients none had pain and all could perform activities of daily living without assistance.

Intralesional resection of the tumour, filling of the cavity with cement, and plate stabilisation of the pathological fracture gives immediate rigidity and allows an early return of function without the need for bony union. The patient’s local disease burden is reduced, which may alleviate tumour-related pain and slow the progression of the disease. The cemented-plate technique provides a reliable option for the treatment of pathological fractures of the humerus.
A randomised study of peri-prosthetic bone density after cementedversustrabecular fixation of a polyethylene acetabular component
Authors: Periasamy K. , Watson W. S. , Mohammed A. , Murray H. , Walker B. , Patil S. , Meek R. M. D.
Published: July 2011

The ideal acetabular component is characterised by reliable, long-term fixation with physiological loading of bone and a low rate of wear. Trabecular metal is a porous construct of tantalum which promotes bony ingrowth, has a modulus of elasticity similar to that of cancellous bone, and should be an excellent material for fixation.

Between 2004 and 2006, 55 patients were randomised to receive either a cemented polyethylene or a monobloc trabecular metal acetabular component with a polyethylene articular surface. We measured the peri-prosthetic bone density around the acetabular components for up to two years using dual-energy x-ray absorptiometry.

We found evidence that the cemented acetabular component loaded the acetabular bone centromedially whereas the trabecular metal monobloc loaded the lateral rim and behaved like a hemispherical rigid metal component with regard to loading of the acetabular bone. We suspect that this was due to the peripheral titanium rim used for the mechanism of insertion.
Distal metatarsal osteotomy for hallux varus following surgery for hallux valgus
Authors: Choi K. J. , Lee H. S. , Yoon Y. S. , Park S. S. , Kim J. S. , Jeong J. J. , Choi Y. R.
Published: July 2011

We reviewed the outcome of distal chevron metatarsal osteotomy without tendon transfer in 19 consecutive patients (19 feet) with a hallux varus deformity following surgery for hallux valgus. All patients underwent distal chevron metatarsal osteotomy with medial displacement and a medial closing wedge osteotomy along with a medial capsular release.

The mean hallux valgus angle improved from −11.6° pre-operatively to 4.7° postoperatively, the mean first-second intermetatarsal angle improved from −0.3° to 3.3° and the distal metatarsal articular angle from 9.5° to 2.3° and the first metatarsophalangeal joints became congruent post-operatively in all 19 feet. The mean relative length ratio of the metatarsus decreased from 1.01 to 0.99 and the mean American Orthopaedic Foot and Ankle Society score improved from 77 to 95 points.

In two patients the hallux varus recurred. One was symptom-free but the other remained symptomatic after a repeat distal chevron osteotomy. There were no other complications.

We consider that distal chevron metatarsal osteotomy with a medial wedge osteotomy and medial capsular release is a useful procedure for the correction of hallux varus after surgery for hallux valgus.
Long-term results of the surgical treatment of type III acromioclavicular dislocations
Authors: Lizaur A. , Sanz-Reig J. , Gonzalez-Parreño S.
Published: July 2011

The purpose of this study was to review the long-term outcomes of a previously reported prospective series of 46 type III acromioclavicular dislocations. These were treated surgically with temporary fixation of the acromioclavicular joint with wires, repair of the acromioclavicular ligaments, and overlapped suture of the deltoid and trapezius muscles. Of the 46 patients, one had died, four could not be traced, and three declined to return for follow-up, leaving 38 patients in the study. There were 36 men and two women, with a mean age at follow-up of 57.3 years (41 to 71). The mean follow-up was 24.2 years (21 to 26).

Patients were evaluated using the Imatani and University of California, Los Angeles (UCLA) scoring systems. Their subjective status was assessed using the Disabilities of the Arm, Shoulder and Hand and Simple Shoulder Test questionnaires, and a visual analogue scale for patient satisfaction. The examination included radiographs of the shoulder.

At a follow-up of 21 years, the results were satisfactory in 35 (92.1%) patients and unsatisfactory in three (7.9%). In total, 35 patients (92.1%) reported no pain, one slight pain, and two moderate pain. All except two patients had a full range of shoulder movement compared with the opposite side. Unsatisfactory results were the result of early redisplacement in two patients, and osteoarthritis without redisplacement in one. According to the Imatani and UCLA scores, there was no difference between the operated shoulder and the opposite shoulder (p > 0.05). Given the same situation, 35 (92.1%) patients would opt for the same surgical treatment again.

Operative treatment of type III acromioclavicular joint injuries produces satisfactory long-term results.