Rapidly progressive parkinsonism in a self-reported user of ecstasy and other drugs.

A 38-year-old man developed parkinsonism that progressed to Hoehn and Yahr stage 5 within 4 years of onset. Response to ropinirole deteriorated, levodopa was not tolerated, and subthalamic nucleus stimulation has provided only partial relief of symptoms. He reported heavy use of Ecstasy through most of his twenties and thirties. His neurological problems may be unrelated to his drug use, but it is also possible they represent an idiosyncratic reaction.     

Engaging religious leaders to promote safe burial practices during the 2014–2016 Ebola virus disease outbreak,Sierra Leone

ObjectiveTo quantify the potential impact of engaging religious leaders in promoting safe burial practices during the 2014–2016 Ebola virus disease outbreak in Sierra Leone.MethodsWe analysed population-based household survey data from 3540 respondents collected around the peak of the outbreak in Sierra Leone, December 2014. Respondents were asked if in the past month they had heard an imam or pastor say that people should not touch or wash a dead body. We used multilevel logistic regression modelling to examine if exposure to religious leaders’ messages was associated with protective burial intentions if a family member died at home and other Ebola protective behaviours.FindingsOf the respondents, 3148 (89%) had been exposed to faith-based messages from religious leaders on safe Ebola burials and 369 (10%) were unexposed. Exposure to religious leaders’ messages was associated with a nearly twofold increase in the intention to accept safe alternatives to traditional burials and the intention to wait ≥ 2 days for burial teams (adjusted odds ratio, aOR: 1.69; 95% confidence interval, CI: 1.23–2.31 and aOR: 1.84; 95% CI: 1.38–2.44, respectively). Exposure to messages from religious leaders was also associated with avoidance of traditional burials and of contact with suspected Ebola patients (aOR: 1.46; 95% CI: 1.14–1.89 and aOR: 1.65; 95% CI: 1.27–2.13, respectively).ConclusionPublic health messages promoted by religious leaders may have influenced safe burial behaviours during the Ebola outbreak in Sierra Leone. Engagement of religious leaders in risk communication should be prioritized during health emergencies in similar settings.     

Transitional cell carcinoma of the renal pelvis and ureter: Outcome and patterns of relapse in patients treated with postoperative radiation

We assessed the records of 101 patients with locally advanced transitional cell carcinoma (TCC) of the renal pelvis and ureter treated with postoperative radiation therapy to determine outcome and patterns of failure. Locally advanced disease (i.e., T3–4N0 or N+ disease) was identified in 65 patients. Postoperative radiation was used to treat 86 patients, with a median dose of 35 Gy in 20 fractions over 4 weeks to the tumor bed and regional lymph nodes. There were 15 patients with no residual disease who were offered no further therapy. No patient received postoperative chemotherapy. Prognostic factors were examined using univariate and multivariate analysis, and the patterns of failure were identified after postoperative irradiation. Median follow-up was 9.3 years, during which 76 deaths occurred. The 5-year overall survival was 43% and 10-year survival was 23%. A multivariate analysis identified T3 category, lymph node involvement, and age at diagnosis as significant prognostic factors for survival. Tumor grade was a significant prognostic factor on univariate analysis but not on multivariate analysis. Failure analysis showed that only 36% of patients with locally advanced disease remained relapse free. For this group of patients, distant metastases developed in 53%, and locoregional failured occurred in 35% despite postoperative irradiation. Locoregional failure occurred in 95% of patients with nodal involvement who received postoperative radiation, and 77% of those developed distant relapse. This leads us to conclude that patients with resected locally advanced (T3, T4N0, N+) TCC of the upper urinary tracts have a high risk of relapse and death from disease despite postoperative radiotherapy. Because the main feature of the disease is early distant failure, post-operative chemotherapy is required to improve the outcome for this group of patients.     

Delivery of a lentiviral vector in a Pluronic F127 gel to cells of the central nervous system.

Lentiviral vectors have been demonstrated as efficient tools for gene delivery to the CNS. We describe a novel approach for vector delivery using the thermoresponsive Gel, Pluronic F127 as a carrier. A HIV-1 lentiviral vector expressing GFP was contained in various concentrations of gel (15, 30 and 40%) and applied to cultures of 293T cells. FACS analysis of cells transduced with 8ng of lentiviral vector revealed a similar transduction efficiency for each Gel concentration compared to vector added to cells without PF127. Primary Rat CNS mixed glial cultures were also transduced with lentiviral vector in 15% Pluronic F127 and results demonstrated a similar transduction efficiency of astrocytes compared to virus without gel and no evidence of cell toxicity or death. Stereotaxic delivery of viral vector in 15% PF127 to the rat brain resulted in transduction of cells, predominantly astrocytes close to the injection site. Pluronic F127 gel delivery of viral vectors to the CNS may provide a platform for localised release particularly in areas of brain or spinal cord injury.     

Changes in bone mineral density in men starting androgen deprivation therapy and the protective role of vitamin D

Summary

Androgen deprivation therapy in 80 men was associated with declines in bone mineral density (BMD), which were greatest in the first year, and in the lumbar spine compared to controls. Vitamin D use was associated with improved BMD in the lumbar spine and in the first year.

Introduction

Decreased BMD is a common side effect of androgen deprivation therapy (ADT), leading to increased risk of fractures. Although loss of BMD appears to be greatest within the first year of starting ADT, there are few long-term studies of change in BMD, and risk factors for bone loss are not well-characterized.

Methods

Men aged 50+ with nonmetastatic prostate cancer starting continuous ADT were enrolled in a prospective longitudinal study. BMD was determined by dual-energy x-ray absorptiometry at baseline and yearly for 3 years. Matched controls were men with prostate cancer not receiving ADT. Multivariable regression analysis examined predictors of BMD loss.

Results

Eighty ADT users and 80 controls were enrolled (mean age 69 years); 52.5 % had osteopenia and 8.1 % had osteoporosis at baseline. After 1 year, in adjusted models, ADT was associated with significant losses in lumbar spine BMD compared to controls (?2.57 %, p?=?0.006), with a trend towards greater declines at the total hip (p?=?0.09). BMD changes in years 2 and 3 were much smaller and not statistically different from controls. Use of vitamin D but not calcium was associated with improved BMD in the lumbar spine in year 1 (+6.19 %, p?<?0.001) with smaller nonsignificant increases at other sites (+0.86 % femoral neck, +0.86 % total hip, p?>?0.10) primarily in the first year.

Conclusions

Loss of BMD associated with ADT is greatest at the lumbar spine and in the first year. Vitamin D but not calcium may be protective particularly in the first year of ADT use.     

Methods for Three-Dimensional Geometric Characterization of the Arterial Vasculature

Complex vascular anatomy often affects endovascular procedural outcome. Accurate quantitative assessment of three-dimensional (3D) in-vivo arterial morphology is therefore vital for endovascular device design, and preoperative planning of percutaneous interventions. The aim of this work was to establish geometric parameters describing arterial branch origin, trajectory, and vessel curvature in 3D space that eliminate the errors implicit in planar measurements. 3D branching parameters at visceral and aortic bifurcation sites, as well as arterial tortuosity were determined from vessel centerlines derived from magnetic resonance angiography data for three subjects. Errors in coronal measurements of 3D branching angles for the right and left renal arteries were 3.1 ± 3.4° and 7.5 ± 3.7°, respectively. Distortion of the anterior visceral branching angles from sagittal measurements was less pronounced. Asymmetry in branching and planarity of the common iliac arteries was observed at aortic bifurcations. The renal arteries possessed considerably greater 3D curvature than the abdominal aorta and common iliac vessels with mean average values of 0.114 ± 0.015 and 0.070 ± 0.019 mm⁻¹ for the left and right, respectively. In conclusion, planar projections misrepresented branch trajectory, vessel length, and tortuosity proving the importance of 3D geometric characterization for possible applications in planning of endovascular interventional procedures and providing parameters for endovascular device design.