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Find video protocols related to scientific articles indexed in Pubmed.
Treatment of muscle-invasive bladder cancer in Canada: A survey of genitourinary medical oncologists and urologists.
Can Urol Assoc J
PUBLISHED: 11-20-2014
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Uptake of neoadjuvant chemotherapy (NC) for muscle invasive bladder cancer (MIBC) has been low despite evidence of a survival benefit. The primary aim of this study was to better understand why the rates are low and determine what factors specifically influence the decision to recommend NC for MIBC.
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Discovery and validation of novel expression signature for postcystectomy recurrence in high-risk bladder cancer.
J. Natl. Cancer Inst.
PUBLISHED: 11-01-2014
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Nearly half of muscle-invasive bladder cancer patients succumb to their disease following cystectomy. Selecting candidates for adjuvant therapy is currently based on clinical parameters with limited predictive power. This study aimed to develop and validate genomic-based signatures that can better identify patients at risk for recurrence than clinical models alone.
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Radical trimodality therapy for patients with locally advanced bladder cancer: The British Columbia Cancer Agency experience1?>
Urol. Oncol.
PUBLISHED: 08-25-2014
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To assess the outcomes of patients with locally advanced bladder cancer (clinically T3b-T4 or N+and M0) who were referred to the British Columbia Cancer Agency and treated with radical trimodality therapy (RTMT). RTMT consists of transurethral resection of the tumor, followed by both chemotherapy and radiation.
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Intraoperative Registered Transrectal Ultrasound Guidance for Robot-Assisted Laparoscopic Radical Prostatectomy.
J. Urol.
PUBLISHED: 08-20-2014
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To provide unencumbered real-time ultrasound image guidance during robot-assisted laparoscopic radical prostatectomy (RALRP), we have developed a robotic transrectal ultrasound system (TRUS) that tracks the da Vinci instruments. We describe our initial clinical experience with this system.
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Assessing the quality of studies on the diagnostic accuracy of tumor markers.
Urol. Oncol.
PUBLISHED: 08-19-2014
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With rapidly increasing numbers of publications, assessments of study quality, reporting quality, and classification of studies according to their level of evidence or developmental stage have become key issues in weighing the relevance of new information reported. Diagnostic marker studies are often criticized for yielding highly discrepant and even controversial results. Much of this discrepancy has been attributed to differences in study quality. So far, numerous tools for measuring study quality have been developed, but few of them have been used for systematic reviews and meta-analysis. This is owing to the fact that most tools are complicated and time consuming, suffer from poor reproducibility, and do not permit quantitative scoring.
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Conditional Survival After Radical Nephroureterectomy for Upper Tract Carcinoma.
Eur. Urol.
PUBLISHED: 08-18-2014
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Conditional survival (CS) provides better estimates of the survival probability at each follow-up time, and its usefulness has been proven in several solid malignancies.
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Patterns of Relapse in Patients With Clinical Stage I Testicular Cancer Managed With Active Surveillance.
J. Clin. Oncol.
PUBLISHED: 08-18-2014
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To evaluate the performance of active surveillance as a management strategy in broad populations and to inform the development of surveillance schedules by individual patient data regarding timing and type of relapse.
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DHH Is an Independent Prognosticator of Oncologic Outcome in Clear Cell Renal Cell Carcinoma.
J. Urol.
PUBLISHED: 07-10-2014
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Aberrant HH signaling has proved important in the pathogenesis of several solid cancers. Limited in vitro analyses suggested an oncogenic role for HH in renal cell carcinoma. In this explorative study we sought to validate aberrant HH expression in patients with renal cell carcinoma.
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Fluoroquinolone Resistant Rectal Colonization Predicts Risk of Infectious Complications after Transrectal Prostate Biopsy.
J. Urol.
PUBLISHED: 06-03-2014
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Infection after transrectal prostate biopsy has become an increasing concern due to fluoroquinolone resistant bacteria. We determined whether colonization identified by rectal culture can identify men at high risk for post-transrectal prostate biopsy infection.
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Surgery for intractable epilepsy due to unilateral brain disease: a retrospective study comparing hemispherectomy techniques.
Pediatr. Neurol.
PUBLISHED: 05-22-2014
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Hemispherectomy is a surgical procedure used to treat medically intractable epilepsy in children with severe unilateral cortical disease secondary to acquired brain or congenital lesions. The major surgical approaches for hemispherectomy are anatomic hemispherectomy, traditional functional hemispherectomy, and peri-insular hemispherotomy. We describe the epilepsy outcome, including the need for reoperation, after hemispherectomy in patients with brain malformations or acquired brain lesions who underwent hemispherectomy for refractory epilepsy.
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Multicenter Assessment of Neoadjuvant Chemotherapy for Muscle-invasive Bladder Cancer.
Eur. Urol.
PUBLISHED: 04-21-2014
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The efficacy of neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (BCa) was established primarily with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), with complete response rates (pT0) as high as 38%. However, because of the comparable efficacy with better tolerability of gemcitabine and cisplatin (GC) in patients with metastatic disease, GC has become the most commonly used regimen in the neoadjuvant setting.
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The role of adjuvant chemotherapy for lymph node-positive upper tract urothelial carcinoma following radical nephroureterectomy: a retrospective study.
BJU Int.
PUBLISHED: 04-21-2014
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To evaluate the effect of adjuvant chemotherapy (AC) on mortality after RNU for upper tract urothelial carcinoma (UTUC) with positive lymph nodes and to identify patient subgroups that are most likely to benefit from AC.
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Underutilization of local salvage therapy after radiation therapy for prostate cancer.
Urol. Oncol.
PUBLISHED: 03-12-2014
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To evaluate the rates at which patients are offered and receive local salvage therapy (LST) after failure of primary radiotherapy for localized prostate cancer, as it is the only potentially curative treatment for localized recurrence but appears to be underutilized when compared with androgen-deprivation therapy (ADT) or observation.
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Optimizing intravesical mitomycin C therapy in non-muscle-invasive bladder cancer.
Nat Rev Urol
PUBLISHED: 03-11-2014
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Nearly three-quarters of all newly diagnosed urothelial cancers are non-muscle-invasive bladder cancers (NMIBCs). Although bladder-preserving surgery can be used to treat NMIBC, the rate of recurrence remains high. Intravesical chemotherapy has been shown to reduce the rate of NMIBC recurrence, and mitomycin C (MMC) has become the most commonly used intravesical cytotoxic agent. Despite the popularity of this agent in the treatment of NMIBCs, many questions regarding the optimal approach to MMC therapy remain unanswered. Strategies to enhance delivery of MMC have been well studied and multiple measures are recommended for implementation in routine clinical practice. In addition, less widely investigated techniques, such as hyperthermia and electromotive drug administration, have been shown to increase the efficacy of MMC therapy. Nevertheless, even when the current 'optimal' approaches to MMC administration are used, a large proportion of NMIBCs recur. This apparent treatment resistance might be overcome by combination of MMC with other agents that have different mechanisms of action and are unlikely to have cross-resistance. Study of the mechanisms of resistance is, therefore, important to identify key pathways underlying this phenomenon, which could be rationally targeted using specific combinations of drugs. Knowledge of these mechanisms might also reveal markers of responsiveness to therapy that could be used for patient selection.
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Minimally invasive establishment of murine orthotopic bladder xenografts.
J Vis Exp
PUBLISHED: 02-25-2014
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Orthotopic bladder cancer xenografts are the gold standard to study molecular cellular manipulations and new therapeutic agents in vivo. Suitable cell lines are inoculated either by intravesical instillation (model of nonmuscle invasive growth) or intramural injection into the bladder wall (model of invasive growth). Both procedures are complex and highly time-consuming. Additionally, the superficial model has its shortcomings due to the lack of cell lines that are tumorigenic following instillation. Intramural injection, on the other hand, is marred by the invasiveness of the procedure and the associated morbidity for the host mouse. With these shortcomings in mind, we modified previous methods to develop a minimally invasive approach for creating orthotopic bladder cancer xenografts. Using ultrasound guidance we have successfully performed percutaneous inoculation of the bladder cancer cell lines UM-UC1, UM-UC3 and UM-UC13 into 50 athymic nude. We have been able to demonstrate that this approach is time efficient, precise and safe. With this technique, initially a space is created under the bladder mucosa with PBS, and tumor cells are then injected into this space in a second step. Tumor growth is monitored at regular intervals with bioluminescence imaging and ultrasound. The average tumor volumes increased steadily in in all but one of our 50 mice over the study period. In our institution, this novel approach, which allows bladder cancer xenograft inoculation in a minimally-invasive, rapid and highly precise way, has replaced the traditional model.
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Comparative Effectiveness of Frame-based, Frameless and Intraoperative MRI Guided Brain Biopsy Techniques.
World Neurosurg
PUBLISHED: 02-09-2014
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Intraoperative MRI (IoMRI) guided brain biopsy provides a real time visual feedback of the lesion that is sampled during surgery. The objective of the study is to compare the diagnostic yield and safety profiles of ioMRI needle brain biopsy with two traditional brain biopsy methods: frame-based and frameless stereotactic brain biopsies.
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Is prostate cancer screening cost-effective? A microsimulation model of prostate-specific antigen-based screening for British Columbia, Canada.
Int. J. Cancer
PUBLISHED: 02-04-2014
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Prostate-specific antigen (PSA) screening for prostate cancer may reduce mortality, but it incurs considerable risk of over diagnosis and potential harm to quality of life. Our objective was to evaluate the cost-effectiveness of PSA screening, with and without adjustment for quality of life, for the British Columbia (BC) population. We adapted an existing natural history model using BC incidence, treatment, cost and mortality patterns. The modeled mortality benefit of screening derives from a stage-shift mechanism, assuming mortality reduction consistent with the European Study of Randomized Screening for Prostate Cancer. The model projected outcomes for 40-year-old men under 14 combinations of screening ages and frequencies. Cost and utility estimates were explored with deterministic sensitivity analysis. The incremental cost-effectiveness of regular screening ranged from $36,300/LYG, for screening every four years from ages 55 to 69 years, to $588,300/LYG, for screening every two years from ages 40 to 74 years. The marginal benefits of increasing screening frequency to 2 years or starting screening at age 40 years were small and came at significant cost. After utility adjustment, all screening strategies resulted in a loss of quality-adjusted life years (QALYs); however, this result was very sensitive to utility estimates. Plausible outcomes under a range of screening strategies inform discussion of prostate cancer screening policy in BC and similar jurisdictions. Screening may be cost-effective, but the sensitivity of results to utility values suggests individual preferences for quality versus quantity of life should be a key consideration.
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Contemporary cost-effectiveness analysis comparing sequential bacillus Calmette-Guerin and electromotive mitomycin versus bacillus Calmette-Guerin alone for patients with high-risk non-muscle-invasive bladder cancer.
Cancer
PUBLISHED: 01-13-2014
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Sequential bacillus Calmette-Guerin (BCG) and electromotive mitomycin (sequential therapy) have been shown in a randomized prospective trial to be superior to therapy with BCG alone in patients with high-risk non-muscle-invasive bladder cancer. The objective of the current study was to compare the costs and benefits of these 2 treatment strategies by performing a 5-year and 10-year cost-effectiveness study.
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Combination budesonide/formoterol inhaler as maintenance and reliever therapy in M?ori with asthma.
Respirology
PUBLISHED: 01-02-2014
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There are significant health disparities between M?ori and non-M?ori with asthma, a pattern seen between other ethnic populations. This study investigates outcomes for M?ori in a randomized controlled trial (RCT) of combination budesonide/formoterol inhaler therapy in asthma.
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Morphological differences between circulating tumor cells from prostate cancer patients and cultured prostate cancer cells.
PLoS ONE
PUBLISHED: 01-01-2014
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Circulating tumor cell (CTC) enumeration promises to be an important predictor of clinical outcome for a range of cancers. Established CTC enumeration methods primarily rely on affinity capture of cell surface antigens, and have been criticized for underestimation of CTC numbers due to antigenic bias. Emerging CTC capture strategies typically distinguish these cells based on their assumed biomechanical characteristics, which are often validated using cultured cancer cells. In this study, we developed a software tool to investigate the morphological properties of CTCs from patients with castrate resistant prostate cancer and cultured prostate cancer cells in order to establish whether the latter is an appropriate model for the former. We isolated both CTCs and cultured cancer cells from whole blood using the CellSearch® system and examined various cytomorphological characteristics. In contrast with cultured cancer cells, CTCs enriched by CellSearch® system were found to have significantly smaller size, larger nuclear-cytoplasmic ratio, and more elongated shape. These CTCs were also found to exhibit significantly more variability than cultured cancer cells in nuclear-cytoplasmic ratio and shape profile.
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WITHDRAWN: Prophylactic antibiotic therapy for chronic bronchitis.
Cochrane Database Syst Rev
PUBLISHED: 12-03-2013
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The use of prophylactic antibiotics to reduce the frequency and severity of acute exacerbations of chronic bronchitis is controversial.
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Conditional Survival After Radical Cystectomy for Bladder Cancer: Evidence for a Patient Changing Risk Profile over Time.
Eur. Urol.
PUBLISHED: 08-29-2013
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Standard survival statistics do not take into consideration the changes in the weight of individual variables at subsequent times after the diagnosis and initial treatment of bladder cancer.
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Technologies for label-free separation of circulating tumor cells: from historical foundations to recent developments.
Lab Chip
PUBLISHED: 08-20-2013
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Circulating tumor cells (CTCs) are malignant cells shed into the bloodstream from a tumor that have the potential to establish metastases in different anatomical sites. The separation and subsequent characterization of these cells is emerging as an important tool for both biomarker discovery and the elucidation of mechanisms of metastasis. Established methods for separating CTCs rely on biochemical markers of epithelial cells that are known to be unreliable because of epithelial-to-mesenchymal transition, which reduces expression for epithelial markers. Emerging label-free separation methods based on the biophysical and biomechanical properties of CTCs have the potential to address this key shortcoming and present greater flexibility in the subsequent characterization of these cells. In this review we first present what is known about the biophysical and biomechanical properties of CTCs from historical studies and recent research. We then review biophysical label-free technologies that have been developed for CTC separation, including techniques based on filtration, hydrodynamic chromatography, and dielectrophoresis. Finally, we evaluate these separation methods and discuss requirements for subsequent characterization of CTCs.
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Chronic Obstructive Pulmonary Disease in Non-smokers: A Case-Comparison Study.
COPD
PUBLISHED: 07-11-2013
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Abstract Background: COPD is often regarded as a smokers disease. In fact, up to 50% of COPD could be attributable to other causes. Relatively little is known about COPD among nonsmokers, and this group is usually excluded from studies of COPD. Methods: In this cross-sectional case-comparison study, smokers and nonsmokers aged over 45 with COPD (post-bronchodilator FEV1 ? 70% predicted, FEV1/FVC ratio < 0.7) were recruited from specialist outpatient clinics and from primary care. Subjects completed a questionnaire and interview, and underwent spirometry, venesection, exhaled nitric oxide (ENO) measurement, allergen skinprick testing, formal lung function testing and high resolution CT. Results: 48 nonsmokers and 45 smokers participated. Asthma was nearly universal among nonsmokers and was the commonest identifiable cause of COPD in that group. Nonsmokers also exhibited a high prevalence of objective eosinophilic inflammation (raised ENO and eosinophil counts, positive skinprick tests). Smokers had more severe airflow obstruction, but respiratory symptom prevalences were similar between groups. Nonsmokers reported greater lifetime burdens of respiratory disease. Nonsmokers HRCT results showed functional small airways disease, with no significant emphysema in any subject. Previously undiagnosed bronchiectasis was common in both groups (31% and 42%). Conclusions: Asthma is a very common cause of COPD among nonsmokers. Radiological bronchiectasis is common in COPD; the clinical significance of this finding is unclear.
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Reference values for hematology, plasma biochemical analysis, plasma protein electrophoresis, and Aspergillus serology in elegant-crested tinamou (Eudromia elegans).
J. Avian Med. Surg.
PUBLISHED: 06-19-2013
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Elegant-crested tinamou (Eudromia elegans) are members of the family Tinamidae. A review of postmortem records at the Saint Louis Zoo suggests that this species is highly susceptible to aspergillosis. Antemortem detection of Aspergillus infections can be aided by evaluating results of hematologic, plasma biochemical, protein electrophoretic, and Aspergillus antigen and antibody serologic testing. To establish species-specific reference intervals for these parameters in elegant-crested tinamou, blood samples were collected and analyzed from 19 healthy captive adult and subadult elegant-crested tinamou. The predominant circulating leukocyte in elegant-crested tinamou is the lymphocyte. Prealbumin electrophoresis fractions were detected in 4 of 19 birds (21%), and globulin fractions were detected in all birds. All birds had measurable titers for Aspergillus antibody and galactomannan antigen, including 3 birds with antibody levels considered to be positive. Galactomannan levels were all below the positive threshold of 1.0. Results of hematologic and plasma biochemical analyses performed on blood samples obtained from terminally ill elegant-crested tinamou with confirmed aspergillosis were compared with results from healthy individuals. Significant differences were found in the hematocrit, total white blood cell count, heterophil and monocyte counts, and albumin and globulin levels.
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Validation of a genomic classifier that predicts metastasis following radical prostatectomy in an at risk patient population.
J. Urol.
PUBLISHED: 06-05-2013
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Patients with locally advanced prostate cancer after radical prostatectomy are candidates for secondary therapy. However, this higher risk population is heterogeneous. Many cases do not metastasize even when conservatively managed. Given the limited specificity of pathological features to predict metastasis, newer risk prediction models are needed. We report a validation study of a genomic classifier that predicts metastasis after radical prostatectomy in a high risk population.
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Using the delphi technique to improve clinical outcomes through the development of quality indicators in renal cell carcinoma.
J Oncol Pract
PUBLISHED: 06-04-2013
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Optimal quality of care is needed for ideal outcomes. In renal cell carcinoma (RCC), there is a lack of information defining optimal care. This is particularly important in RCC, with increased complexity of care and a need for coordination among providers. The goal of this study was to identify quality indicators (QIs) and measures of quality care across the RCC disease spectrum.
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Fixed airflow obstruction among nonsmokers with asthma:a case-comparison study.
J Asthma
PUBLISHED: 05-13-2013
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Airflow obstruction in asthma is usually reversible, but fixed obstruction develops in some individuals. Little is known about risk factors for development of fixed airflow obstruction in nonsmokers with asthma.
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Fibroblast growth factor receptor 3 is a rational therapeutic target in bladder cancer.
Mol. Cancer Ther.
PUBLISHED: 05-08-2013
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Activating mutations of fibroblast growth factor receptor-3 (FGFR3) have been described in approximately 75% of low-grade papillary bladder tumors. In muscle-invasive disease, FGFR3 mutations are found in 20% of tumors, but overexpression of FGFR3 is observed in about half of cases. Therefore, FGFR3 is a particularly promising target for therapy in bladder cancer. Up to now, most drugs tested for inhibition of FGFR3 have been small molecule, multityrosine kinase inhibitors. More recently, a specific inhibitory monoclonal antibody targeting FGFR3 (R3Mab) has been described and tested preclinically. In this study, we have evaluated mutation and expression status of FGFR3 in 19 urothelial cancer cell lines and a cohort of 170 American patients with bladder cancer. We have shown inhibitory activity of R3Mab on tumor growth and corresponding cell signaling in three different orthotopic xenografts of bladder cancer. Our results provide the preclinical proof of principle necessary to translate FGFR3 inhibition with R3Mab into clinical trials in patients with bladder cancer.
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Ciprofloxacin resistance in the faecal carriage of patients undergoing transrectal ultrasound guided prostate biopsy.
BJU Int.
PUBLISHED: 03-06-2013
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WHATS KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Transrectal ultrasound guided prostate biopsies (TRUSBx) are associated with a spectrum of complications, including most significantly infection, which affects up to 5% of patients. In the most severe cases, infection leads to sepsis, a life-threatening complication. Escherichia coli is the primary responsible pathogen. Although antibiotic prophylaxis with fluoroquinolones is routinely used, there is evidence that the infection rate after TRUSBx is increasing, and this appears to be due to an increasing prevalence of ciprofloxacin-resistant rectal flora. This is the largest prospective clinical trial to date analysing the rectal flora of men undergoing prostate biopsies. We determined the microbial and antibiotic sensitivity profiles from 849 patients. Ciprofloxacin-resistant Gram-negative organisms were identified in the rectal flora of 19.0% of men. Furthermore, fluoroquinolone use within 6 months preceding a TRUSBx and the presence of a prosthetic heart valve were significant predictors of ciprofloxacin resistance on rectal swab. Determining the prevalence of rectal fluoroquinolone resistance has important implications in evaluation of the suitability of prophylactic regimens. Antimicrobial profiles derived from rectal swabs pre-biopsy may prove useful in guiding targeted antibiotic prophylaxis.
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Efficacy and safety of maintenance and reliever combination budesonide-formoterol inhaler in patients with asthma at risk of severe exacerbations: a randomised controlled trial.
Lancet Respir Med
PUBLISHED: 03-04-2013
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The Single combination budesonide-formoterol inhaler Maintenance And Reliever Therapy (SMART) regimen reduces severe asthma exacerbations in patients, but whether the high doses of corticosteroid and ? agonist increase the risk of adverse effects with both short-term and cumulative exposure is not certain. Our aim was to investigate whether the SMART regimen would reduce the risk of overuse of ? agonist, reduce the likelihood of patients to seek medical review when such episodes occurred, and if any reduction in severe asthma exacerbations would be at the cost of a higher burden of systemic corticosteroid.
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Hiding in plain view: genetic profiling reveals decades old cross contamination of bladder cancer cell line KU7 with HeLa.
J. Urol.
PUBLISHED: 03-04-2013
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KU7 is a popular urothelial carcinoma cell line that was isolated from the bladder of a patient at Keio University in 1980. It has subsequently been widely used in laboratories around the world. We describe how routine cell line authentication revealed that KU7 was cross contaminated almost 30 years ago with HeLa, a cervical carcinoma cell line.
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Adjuvant chemotherapy for upper-tract urothelial carcinoma treated with nephroureterectomy: Assessment of adequate renal function and influence on outcome.
Urol. Oncol.
PUBLISHED: 02-18-2013
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Upper-tract urothelial carcinoma (UTUC) is associated with poor outcomes. Our aim was to assess adequacy of renal function and evaluate the role of adjuvant chemotherapy (AC) in patients with UTUC treated by radical nephroureterectomy (RNU) in a universal health care system.
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Multifocality rather than tumor location is a prognostic factor in upper tract urothelial carcinoma.
Urol. Oncol.
PUBLISHED: 02-13-2013
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Whether a patient has urothelial carcinoma located within the renal pelvis or ureter remains a controversial prognostic indicator in clinical urology. We wished to evaluate whether tumor location is associated with recurrence in patients undergoing nephroureterectomy for upper tract urothelial cancer in a large volume patient cohort.
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Fibroblast growth factor receptors-1 and -3 play distinct roles in the regulation of bladder cancer growth and metastasis: implications for therapeutic targeting.
PLoS ONE
PUBLISHED: 01-21-2013
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Fibroblast growth factor receptors (FGFRs) are activated by mutation and overexpressed in bladder cancers (BCs), and FGFR inhibitors are currently being evaluated in clinical trials in BC patients. However, BC cells display marked heterogeneity in their responses to FGFR inhibitors, and the biological mechanisms underlying this heterogeneity are not well defined. Here we used a novel inhibitor of FGFRs 1-3 and RNAi to determine the effects of inhibiting FGFR1 or FGFR3 in a panel of human BC cell lines. We observed that FGFR1 was expressed in BC cells that also expressed the "mesenchymal" markers ZEB1 and vimentin, whereas FGFR3 expression was restricted to the E-cadherin- and p63-positive "epithelial" subset. Sensitivity to the growth-inhibitory effects of BGJ-398 was also restricted to the "epithelial" BC cells and it correlated directly with FGFR3 mRNA levels but not with the presence of activating FGFR3 mutations. In contrast, BGJ-398 did not strongly inhibit proliferation but did block invasion in the "mesenchymal" BC cells in vitro. Similarly, BGJ-398 did not inhibit primary tumor growth but blocked the production of circulating tumor cells (CTCs) and the formation of lymph node and distant metastases in mice bearing orthotopically implanted "mesenchymal" UM-UC3 cells. Together, our data demonstrate that FGFR1 and FGFR3 have largely non-overlapping roles in regulating invasion/metastasis and proliferation in distinct "mesenchymal" and "epithelial" subsets of human BC cells. The results suggest that the tumor EMT phenotype will be an important determinant of the biological effects of FGFR inhibitors in patients.
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Ultrasound-guided intramural inoculation of orthotopic bladder cancer xenografts: a novel high-precision approach.
PLoS ONE
PUBLISHED: 01-07-2013
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Orthotopic bladder cancer xenografts are essential for testing novel therapies and molecular manipulations of cell lines in vivo. Current xenografts rely on tumor cell inoculation by intravesical instillation or direct injection into the bladder wall. Instillation is limited by the lack of cell lines that are tumorigenic when delivered in this manner. The invasive model inflicts morbidity on the mice by the need for laparotomy and mobilization of the bladder. Furthermore this procedure is complex and time-consuming. Three bladder cancer cell lines (UM-UC1, UM-UC3, UM-UC13) were inoculated into 50 athymic nude mice by percutaneous injection under ultrasound guidance. PBS was first injected between the muscle wall and the mucosa to separate these layers, and tumor cells were subsequently injected into this space. Bioluminescence and ultrasound were used to monitor tumor growth. Contrast-enhanced ultrasound was used to study changes in tumor perfusion after systemic gemcitabine/cisplatin treatment. To demonstrate proof of principle that therapeutic agents can be injected into established xenografts under ultrasound guidance, oncolytic virus (VSV) was injected into UM-UC3 tumors. Xenograft tissue was harvested for immunohistochemistry after 23-37 days. Percutaneous injection of tumor cells into the bladder wall was performed efficiently (mean time: 5.7 min) and without complications in all 50 animals. Ultrasound and bioluminescence confirmed presence of tumor in the anterior bladder wall in all animals 3 days later. The average tumor volumes increased steadily over the study period. UM-UC13 tumors showed a marked decrease in volume and perfusion after chemotherapy. Immunohistochemical staining for VSV-G demonstrated virus uptake in all UM-UC3 tumors after intratumoral injection. We have developed a novel method for creating orthotopic bladder cancer xenograft in a minimally invasive fashion. In our hands this has replaced the traditional model requiring laparotomy, because this model is more time efficient, more precise and associated with less morbidity for the mice.
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Discovery and validation of a prostate cancer genomic classifier that predicts early metastasis following radical prostatectomy.
PLoS ONE
PUBLISHED: 01-01-2013
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Clinicopathologic features and biochemical recurrence are sensitive, but not specific, predictors of metastatic disease and lethal prostate cancer. We hypothesize that a genomic expression signature detected in the primary tumor represents true biological potential of aggressive disease and provides improved prediction of early prostate cancer metastasis.
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Fecal steroid analysis for evaluating ovarian function in the greater kudu (Tragelaphus strepsiceros) and lesser kudu (Tragelaphus imberbis).
J. Zoo Wildl. Med.
PUBLISHED: 12-30-2011
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Seasonal reproductive-endocrine norms have not been described for the genus Tragelaphus, which consists of seven species of African antelope. Longitudinal patterns of progesterone metabolite excretion were assessed by radioimmunoassays in fecal samples collected noninvasively (three to seven samples per week) from greater kudu (Tragelaphus strepsiceros, n = 4) and lesser kudu (Tragelaphus imberbis, n = 4). Progesterone metabolite excretion patterns revealed seasonal estrous cycles in both species, and discrimination of pregnant versus nonpregnant females was achieved in lesser kudu. These data reveal the value of fecal progesterone metabolites for establishing reproductive-endocrine norms in both zoo-maintained and free-living antelopes of the genus Tragelaphus.
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Hematologic parameters in raptor species in a rehabilitation setting before release.
J. Avian Med. Surg.
PUBLISHED: 12-08-2011
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To be considered for release, raptors undergoing rehabilitation must have recovered from their initial injury in addition to being clinically healthy. For that purpose, a good understanding of reference hematologic values is important in determining release criteria for raptors in a rehabilitation setting. In this study, retrospective data were tabulated from clinically normal birds within 10 days of release from a rehabilitation facility. Hematologic values were compiled from 71 red-tailed hawks (Buteo jamaicensis), 54 Eastern screech owls (Megascops asio), 31 Coopers hawks (Accipiter cooperii), 30 great-horned owls (Bubo virginianus), 28 barred owls (Strix varia), 16 bald eagles (Haliaeetus leucocephalus), and 12 broad-winged hawks (Buteo platypterus). Parameters collected included a white blood cell count and differential, hematocrit, and total protein concentration. Comparisons were made among species and among previously published reports of reference hematologic values in free-ranging birds or permanently captive birds. This is the first published report of reference values for Eastern screech owls, barred owls, and broad-winged hawks; and the first prerelease reference values for all species undergoing rehabilitation. These data can be used as a reference when developing release criteria for rehabilitated raptors.
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Neurosurgery certification in member societies of the WFNS: global overview.
World Neurosurg
PUBLISHED: 10-12-2011
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To determine the complexity and diversity of the neurosurgery certification and recertification process in member societies of the World Federation of Neurosurgical Societies.
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Neurosurgery certification in member societies of the WFNS: Africa and the Middle East.
World Neurosurg
PUBLISHED: 08-16-2011
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This study sought to compare objectively the complexity and diversity of the certification process in neurological surgery in member societies of the World Federation of Neurosurgical Societies (WFNS) in the African and Middle Eastern regions.
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Prognostic significance of body mass index in Asian patients with localized renal cell carcinoma.
Nutr Cancer
PUBLISHED: 07-29-2011
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We investigated the prognostic value of BMI (body mass index) in Asian patients with RCC (renal cell carcinoma). We evaluated 170 Asian patients who underwent surgery for localized RCC (pathologic T1-4 tumors in the absence of nodal or distant metastases) between 1996 and 2004 at our institution. Patients were stratified by BMI: 22 or less vs. greater than 22. Overall, CSS (cancer-specific survival) and RFS (recurrence-free survival) was estimated using the Kaplan-Meier method. Multivariate analysis was performed with the Cox regression model. The mean age and BMI of all patients was 62.4 ± 11.4 yr and 23.1 ± 3.2 kg/m(2), respectively. Patients population consisted of 114 (67.1%) men and 56 (32.9%) women. The median follow-up was 50 mo. The BMI was less than 22 in 83 (49%) patients and greater than 22 in 87 (51%). There was a trend toward worse Eastern Cooperative Oncology Group (ECOG) performance status, less likely to have an incidentaloma, higher pathological stage, and more frequent microvascular invasion with lower BMI. Only the correlations between BMI and ECOG performance status (P = 0.003) and pathological stage (P = 0.015) were statistically significant. Of other relevant factors including gender, mode of presentation, ECOG performance status, C-reactive protein, histological type, Fuhrman nuclear grade, microvascular invasion, pathological stage, and adjuvant cytokine therapy, smaller BMI remained an independent predictor for worse CSS (44.5 mo vs. 56.0 mo, P = 0.041, HR = 10.99) and RFS (43.0 mo vs. 55.0 mo, P = 0.03, HR = 2.653), but not for OS (overall survival) (46.0 mo vs. 55.5 mo, P = 0.13, HR = 2.217) on multivariate analysis. Our findings identify increasing BMI in the Asian population as an independent predictor for favorable CSS and RFS in patients with RCC treated by surgery. Further studies, including a multiinstitutional, prospective Asian cohort, are required to confirm these findings.
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Clinically significant urethral stricture and/or subclinical urethral stricture after high-intensity focused ultrasound correlates with disease-free survival in patients with localized prostate cancer.
Urol. Int.
PUBLISHED: 06-20-2011
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To assess the association between the development of a urethral stricture (US) and disease-free survival for patients with localized prostate cancer treated with high-intensity focused ultrasound (HIFU).
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Novel p38? mitogen-activated protein kinase inhibitor shows analgesic efficacy in acute postsurgical dental pain.
J Clin Pharmacol
PUBLISHED: 06-09-2011
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SCIO-469 is a selective p38? mitogen-activated protein kinase (MAPK) inhibitor for preclinical models of acute pain. This prospective, double-blind, randomized clinical study compared efficacy and safety of oral SCIO-469, ibuprofen, and placebo in postsurgical dental pain. Subjects (n = 263) undergoing extraction of 1 or more impacted mandibular third molars received preoperative treatment with SCIO-469 (150, 210, or 300 mg), ibuprofen (400 mg), or placebo; the 210-mg group received 90 mg postoperatively. A 4-point categorical scale and a 100-mm visual analogue scale were used to measure pain intensity. The primary end point was median time from first incision to first rescue medication using the Kaplan-Meier product limit estimator. All SCIO-469 groups had significantly longer times to rescue medication compared with placebo; preoperative and postoperative treatment with 210 + 90 mg SCIO-469 resulted in 8.1 hours versus 4.1 hours to rescue for placebo (P = .003). Ibuprofen also increased time to rescue medication (6.6 hours) versus placebo (P = .04). Dizziness, headache, and nausea were the most frequently reported adverse events. This is the first clinical demonstration of antinociceptive effects in acute pain with preoperative administration of a p38? MAPK inhibitor.
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Statement of Ethics in Neurosurgery of the World Federation of Neurosurgical Societies.
World Neurosurg
PUBLISHED: 05-15-2011
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This Statement of Ethics in Neurosurgery was developed by the Committee for Ethics and Medico-Legal Affairs of the World Federation of Neurosurgical Societies to help neurosurgeons resolve problems in the treatment of individual patients and meet obligations to the larger society. This document is intended as a framework rather than a set of rules. It cannot cover every situation and should be used with flexibility. However, it is our intent that the fundamental principles enunciated here should serve as a guide in the day-to-day practice of neurosurgery.
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Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease.
Cochrane Database Syst Rev
PUBLISHED: 05-13-2011
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Chronic obstructive pulmonary disease (COPD) affects symptoms, lung function, quality of life and life expectancy. Apart from smoking cessation, there are no other treatments that slow lung function decline. Roflumilast and cilomilast are oral phosphodiesterase 4 (PDE(4)) inhibitors proposed to reduce the airway inflammation and bronchoconstriction seen in COPD.
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Imaging of human mesenchymal stromal cells: homing to human brain tumors.
J. Neurooncol.
PUBLISHED: 05-06-2011
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Human mesenchymal stromal cells (hMSC) can be used as a drug delivery vehicle for the treatment of GBM. However, tracking the migration and distribution of these transplanted cells is necessary to interpret therapeutic efficacy. We compared three labeling techniques for their ability to track the migration of transplanted hMSC in an orthotopic mouse xenograft model. hMSC were labeled with three different imaging tags (fluorescence, luciferase or ferumoxide) for imaging by fluorescence, bioluminescence or magnetic resonance imaging (MRI), respectively. hMSC were labeled for all imaging modalities without the use of transfection agents. The labeling efficacy of the tags was confirmed, followed by in vitro and in vivo migration assays to track hMSC migration towards U87 glioma cells. Our results confirmed that the labeled hMSC retained their migratory ability in vitro, similar to unlabeled hMSC. In addition, labeled hMSC migrated towards the U87 tumor site, demonstrating their retention of tumor tropism. hMSC tumor tropism was confirmed by all three imaging modalities; however, MRI provides both real time assessment and the high resolution needed for clinical studies. Our findings suggest that ferumoxide labeling of hMSC is feasible, does not alter their migratory ability and allows detection by MRI. Non invasive tracking of transplanted therapeutic hMSC in the brain will allow further development of human cell based therapies.
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Reduced allergy and immunoglobulin E among adults with intracranial meningioma compared to controls.
Int. J. Cancer
PUBLISHED: 04-25-2011
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Meningioma, the most frequent tumor in the central nervous system, has few recognized risk factors. We explored the role of allergies in a population-based case-control consortium study of meningioma in five geographic areas. We also studied serum levels of a marker of atopic allergy (IgE) in a subset of study participants, a first for a study on meningioma. Participants (N = 1,065) with surgically resected, pathologically confirmed meningioma and controls (N = 634) selected via random-digit dialing were recruited and interviewed. Cases were less likely than controls to report history of physician-diagnosed allergy [odds ratio (OR) = 0.64; 95% confidence interval (95% CI): 0.51-0.80]. Also, cases (N = 295) had lower total serum IgE than controls [N = 192; OR = 0.85, 95% CI: 0.75-0.98 for each unit of Ln(IgE)]. Similar to glioma and cancers at several other sites, meningioma appears to have an inverse relationship with history of allergies and a biomarker of atopic allergy. As some common opposing predisposition or developmental processes for allergy and meningioma may exist, further research into immune processes that can affect the incidence and natural history of meningioma is warranted.
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Cardiac assessment of African hedgehogs (Atelerix albiventris).
J. Zoo Wildl. Med.
PUBLISHED: 03-01-2011
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Cardiomyopathy is a common finding in captive African hedgehogs (Atelerix albiventris) at postmortem exam. To date, treatment attempts have been mostly empirical and unrewarding. The objective of this study was to determine reference cardiac values for captive African hedgehogs based on echocardiogram, electrocardiogram (ECG), and radiographs. Adult African hedgehogs with no clinical signs of cardiac disease (n = 13) were selected. Each animal was anesthetized with isoflurane via facemask and an echocardiogram, ECG, and radiographs were performed. Standard measurements were taken and the descriptive statistics performed. Values were comparable to limited data available in other hedgehog species and other similar-sized exotic species. Two animals were removed from consideration of reference values due to valvular defects that were considered significant. These data are the first establishing cardiac parameters in normal African hedgehogs using radiographic cardiac measurement, echocardiogram, and ECG. Evaluating animals with possible cardiomyopathy may allow for earlier diagnosis and more successful treatment.
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From vision to reality: the origins of intraoperative MR imaging.
Acta Neurochir. Suppl.
PUBLISHED: 02-25-2011
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Intraoperative MR imaging has become one of the most important concepts in present day neurosurgery. The brain shift problem with navigation, the need for assessment of the degree of resection and the need for detection of early postoperative complications were the three most important motives that drove the development of this technology. The GE Signa System with the "double doughnut" design was the worlds first intraoperative MRI. From 1995 to 2007 more than 1,000 neurosurgical cases were performed with the system. The system was used by several different specialties and in neurosurgery it was most useful for complete resection of low-grade gliomas, identification and resection of small or deep metastases or cavernomas, recurrent pituitary adenomas, cystic tumors, biopsies in critical areas and surgery in recurrent GBM cases. Main superiorities of the system were the ability to scan without patient movement to get image updates, the ability to do posterior fossa cases and other difficult patient positioning, the easiness of operation using intravenous sedation anesthesia and the flexibility of the system to be used as platform for new diagnostic and therapeutic modalities.
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Pulmonary fibroblasts from COPD patients show an impaired response of elastin synthesis to TGF-?1.
Respir Physiol Neurobiol
PUBLISHED: 02-23-2011
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Insufficiency of tissue repair by pulmonary fibroblasts may contribute to the decrease in elastic fibres in chronic obstructive pulmonary disease (COPD). In this study, the repair function of COPD fibroblasts was assessed by examining the response to transforming growth factor (TGF)-?1. Primary pulmonary fibroblasts were cultured from lung tissue of COPD patients and smoking control subjects. Cellular proliferation was measured with Alamar Blue reduction method. Levels of tropoelastin mRNA and soluble elastin was measured using real-time RT-PCR and Fastin elastin assay respectively. The percentage of increase in proliferation and elastin production after TGF-?1 (1 ng/ml) treatment was calculated for fibroblasts from each subject. COPD fibroblasts showed slower proliferation than control fibroblasts, and a reduced response to TGF-?1 stimulation. The promotive effect of TGF-?1 on elastin synthesis in control fibroblasts was significantly diminished in fibroblasts from COPD patients. Our findings indicate that COPD lung fibroblasts have a significantly decreased response to TGF-?1 in terms of proliferation and elastin production.
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Immediate titanium mesh cranioplasty for treatment of postcraniotomy infections.
World Neurosurg
PUBLISHED: 02-03-2011
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Postcraniotomy infections have generally been treated by debridement of infected tissues, disposal of the bone flap, and delayed cranioplasty several months later to repair the resulting skull defect. Debridement followed by retention of the bone flap has also been advocated. Here we propose an alternative operative strategy for the treatment of postcraniotomy infections.
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Combining magnetic resonance spectroscopy and molecular genomics offers better accuracy in brain tumor typing and prediction of survival than either methodology alone.
Int. J. Oncol.
PUBLISHED: 01-27-2011
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Recent advents in magnetic resonance spectroscopy (MRS) techniques permit subsequent microarray analysis over the entire human transcriptome in the same tissue biopsies. However, extracting information from such immense quantities of data is limited by difficulties in recognizing and evaluating the relevant patterns of apparent gene expression in the context of the existing knowledge of phenotypes by histopathology. Using a quantitative approach derived from a knowledge base of pathology findings, we present a novel methodology used to process genome-wide transcription and MRS data. This methodology was tested to examine metabolite and genome-wide profiles in MRS and RNA in 55 biopsies from human subjects with brain tumors with ~100% certainty. With the guidance of histopathology and clinical outcome, 15 genes with the assistance of 15 MRS metabolites were able to be distinguished by tumor categories and the prediction of survival was better than when either method was used alone. This new method, combining MRS, genomics, statistics and biological content, improves the typing and understanding of the complexity of human brain tumors, and assists in the search for novel tumor biomarkers. It is an important step for novel drug development, it generates testable hypotheses regarding neoplasia and promises to guide human brain tumor therapy provided improved in vivo methods for monitoring response to therapy are developed.
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Neurosurgery certification in member societies of the World Federation of Neurosurgical Societies: Asia.
World Neurosurg
PUBLISHED: 01-06-2011
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To objectively compare the complexity and diversity of the certification process in neurological surgery in member societies of the World Federation of Neurosurgical Societies.
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A new metric for detecting change in slowly evolving brain tumors: validation in meningioma patients.
Neurosurgery
PUBLISHED: 01-06-2011
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Change detection is a critical component in the diagnosis and monitoring of many slowly evolving pathologies.
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Neurosurgery certification in member societies of the WFNS: Europe.
World Neurosurg
PUBLISHED: 10-11-2010
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To objectively compare the complexity and diversity of the certification process in Neurological Surgery in European member societies of the World Federation of Neurosurgical Societies.
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Advanced glycation end products and its receptor (RAGE) are increased in patients with COPD.
Respir Med
PUBLISHED: 09-01-2010
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Advanced Glycation End products (AGEs) are the products of nonenzymatic glycation and oxidation of proteins and lipids. Formation of AGEs is increased in response to hyperglycaemia, reactive oxygen species and ageing. AGEs are proinflammatory and can modify the extracellular matrix. RAGE (Receptor for Advanced Glycation End Products) mediates some of the effects of AGEs.
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Selected human leukocyte antigen class II polymorphisms and risk of adult glioma.
J. Neuroimmunol.
PUBLISHED: 08-06-2010
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Few studies have examined the relationship between human leukocyte antigen (HLA) polymorphisms and adult glioma, particularly at class II loci. We evaluated the association between selected HLA class II polymorphisms and adult glioma in a large, hospital-based case-control study, using unconditional logistic regression. DQB1 06 (OR=1.67, 95% CI=1.17-2.39) and DRB1 13 (OR=1.69, 95% CI=1.08-2.64) alleles were associated with an increased risk of glioma, while the DQB1 05 allele showed an inverse association (OR=0.63, 95% CI=0.43-0.93). These results, which were of borderline significance once controlled for the false discovery rate, suggest a potential role for the DQB1 06, DQB1 05, and DRB1 13 alleles in glioma susceptibility.
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A nonradiographic system for assessing pressure for the Codman-Hakim Programmable Valve.
Neurosurgery
PUBLISHED: 08-04-2010
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The Codman-Hakim Programmable Valve is widely used in shunting hydrocephalus and other conditions.
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Genomic profiling reveals alternative genetic pathways of meningioma malignant progression dependent on the underlying NF2 status.
Clin. Cancer Res.
PUBLISHED: 08-03-2010
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Meningiomas are the most common central nervous system tumors in the population of age 35 and older. WHO defines three grades predictive of the risk of recurrence. Clinical data supporting histologic malignant progression of meningiomas are sparse and underlying molecular mechanisms are not clearly depicted.
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Pharmacokinetics of tramadol hydrochloride and its metabolite O-desmethyltramadol in peafowl (Pavo cristatus).
J. Zoo Wildl. Med.
PUBLISHED: 07-23-2010
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Tramadol is a centrally acting opiate analgesic that has not been well studied in avian species. Tramadol and its metabolites exert their effects at multiple sites, including opiate (mu, kappa, and delta), adrenergic (alpha-2), and serotonin (5HT) receptors. This multi-receptor mode of action is advantageous for avian patients because the mechanisms for analgesia have not been fully elucidated in all species. The objective of this study was to document the pharmacokinetics of tramadol and its active metabolite O-desmethyltramadol (M1) in common peafowl (Pavo cristatus). Based on results from a pilot animal, six adult peafowl (three male, three female) judged to be clinically healthy based on physical exam and routine bloodwork were selected for this study. Each bird was anesthetized for placement of a jugular catheter, and 7.5 mg/kg tramadol was administered orally via gavage tube. Blood samples were collected just prior to drug administration; at 30 min; and at 1, 2, 3, 4, 6, 8, 10, 12, 24, and 34 hr. Plasma levels of tramadol and M1 were measured and the pharmacokinetics for each drug was calculated. Although tramadol was quickly metabolized, plasma levels of M1 remained at or near human analgesic levels for 12-24 hr. Based on these data, tramadol may be a practical option as an orally administered analgesic agent in avian patients. Further studies, including antinociceptive studies, are needed.
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Scale to predict survival after surgery for recurrent glioblastoma multiforme.
J. Clin. Oncol.
PUBLISHED: 07-19-2010
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Despite initial treatment with surgical resection, radiotherapy, and chemotherapy, glioblastoma multiforme (GBM) virtually always recurs. Surgery is sometimes recommended to treat recurrence. In this study, we sought to devise a preoperative scale that predicts survival after surgery for recurrent glioblastoma multiforme.
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Novel local drug delivery system using thermoreversible gel in combination with polymeric microspheres or liposomes.
Anticancer Res.
PUBLISHED: 06-10-2010
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The purpose of our study was to evaluate the application of thermoreversible gelation polymer (TGP) as a local drug delivery system for malignant glioma.
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The cyclooxygenase-2-765C promoter polymorphism protects against the development of chronic obstructive pulmonary disease.
Respir Med
PUBLISHED: 05-31-2010
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Susceptibility to Chronic Obstructive Pulmonary Disease (COPD) has a genetic component. We undertook a study to determine if a genetic variant of the gene encoding the cyclooxygenase-2 gene influences the likelihood of developing COPD.
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Validating bladder cancer xenograft bioluminescence with magnetic resonance imaging: the significance of hypoxia and necrosis.
BJU Int.
PUBLISHED: 05-27-2010
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To assess the correlation in orthotopic bladder xenografts of bioluminescence imaging (BLI) with tumour volume as determined by magnetic resonance imaging (MRI), and to define the potential role of hypoxia and necrosis in the relationship between BLI and tumour volume at autopsy.
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Long-term quality of life after radical prostatectomy in wives of men in the postoperative adjuvant androgen deprivation trial.
Support Care Cancer
PUBLISHED: 05-11-2010
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We examined quality of life in spouses of men in the Post-Adjuvant Androgen Deprivation trial after radical prostatectomy.
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The role of radical cystectomy in patients with clinical T4b bladder cancer.
Urol. Oncol.
PUBLISHED: 04-24-2010
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Patients with clinical T4b bladder cancer (extension to pelvic wall and/or adjacent organs other than prostate, vagina, or uterus) are commonly considered unresectable. We hypothesized that select patients might achieve durable benefit from multiagent chemotherapy and extirpative surgery.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.