Spatial object recognition memory formation under acute stress

Stress is known to have a critical impact on memory processes. In the present work, we focus on the effects of an acute stress event closely associated to an unrelated learning task. Here, we show that acute stress (elevated platform [EP] session) experienced 1 hr after a weak spatial object recognition (SOR) training, which only induces a short‐term memory (STM), promoted the formation of SOR‐long term memory (SOR‐LTM) in rats. The effect induced by stress was dependent on the activation of glucocorticoid‐ and mineralocorticoid‐receptors, brain‐derived neurotrophic factor (BDNF) and protein synthesis in the dorsal hippocampus. In contrast, EP after a strong SOR impaired SOR‐LTM probably by interfering with the use of necessary resources. Moreover, we show that the EP session before training induced anterograde interference, which it was not reversed by a subsequent exposure to an open field. Our findings provide novel insights into the impact of stress on LTM formation in rodents and they are discussed under the behavioral analogue of the synaptic tagging and capture hypothesis.     

Dutasteride Treatment Over 2 Years Delays Prostate-specific Antigen Progression in Patients with Biochemical Failure After Radical Therapy for Prostate Cancer: Results from the Randomised,Placebo-controlled Avodart After Radical Therapy for Prostate Cancer Study (ARTS)

Background

Rising prostate-specific antigen (PSA) levels after radical therapy are indicative of recurrent or residual prostate cancer (PCa). This biochemical recurrence typically predates clinically detectable metastatic disease by several years. Management of patients with biochemical recurrence is controversial.

Objective

To assess the effect of dutasteride on progression of PCa in patients with biochemical failure after radical therapy.

Design, setting, and participants

Randomised, double-blind, placebo-controlled trial in 294 men from 64 centres across 9 European countries.

Intervention

The 5α-reductase inhibitor, dutasteride.

Outcome measurements and statistical analysis

The primary end point was time to PSA doubling from start of randomised treatment, analysed by log-rank test stratified by previous therapy and investigative-site cluster. Secondary end points included time to disease progression and the proportion of subjects with disease progression.

Results and limitations

Of the 294 subjects randomised (147 in each treatment group), 187 (64%) completed 24 mo of treatment and 107 discontinued treatment prematurely (71 [48%] of the placebo group, 36 [24%] of the dutasteride group). Dutasteride significantly delayed the time to PSA doubling compared with placebo after 24 mo of treatment (p < 0.001); the relative risk (RR) reduction was 66.1% (95% confidence interval [CI], 50.35–76.90) for the overall study period. Dutasteride also significantly delayed disease progression (which included PSA- and non-PSA-related outcomes) compared with placebo (p < 0.001); the overall RR reduction in favour of dutasteride was 59% (95% CI, 32.53–75.09). The incidence of adverse events (AEs), serious AEs, and AEs leading to study withdrawal were similar between the treatment groups. A limitation was that investigators were not blinded to PSA levels during the study.

Conclusions

Dutasteride delayed the biochemical progression of PCa in patients with biochemical failure after radical therapy for clinically localised disease. The safety and tolerability of dutasteride were generally consistent with previous experience.

Clinical trial registry

ClinicalTrials.gov, NCT00558363.     

Brief report: Focused transthoracic echocardiography training in a cohort of Canadian anesthesiology residents: a pilot study

Purpose

Bedside transthoracic echocardiography (TTE) is useful for rapid assessment and treatment of hemodynamic disturbances. Transthoracic echocardiography is not standard in Canadian anesthesia training even though undifferentiated hemodynamic disturbances are common in the perioperative setting. The objectives of this pilot study were to determine 1) whether it is feasible to implement a focused bedside TTE curriculum within core anesthesiology training, 2) whether changes could be detected and quantified following the program of study, and 3) whether curriculum implementation might lead to a significant increase in anesthesiology residents’ TTE knowledge-base.

Methods

In this single-centre cohort pilot investigation, anesthesiology residents at Queen’s University received focused bedside TTE training during the winter of 2011. The curriculum consisted of four three-hour sessions with both didactic and practical components. Pre- and post-curriculum examinations were administered, and examination results were compared using non-parametric tests. The primary outcome was the difference in mean pre- and post-curriculum examination scores.

Results

Ten participants completed pre- and post-curriculum examinations. Four residents were unable to participate in the curriculum but served as controls. Mean pretest scores (out of 50) were similar between the two groups (participants 23.9 vs controls 23.5; P = 0.83, Mann-Whitney U). Mean scores improved by 13.0 points following intervention but improved by only 1.3 points for controls, (P = 0.009, Mann-Whitney U).

Conclusion

This pilot investigation suggests that implementation of a focused bedside TTE curriculum within anesthesia training is feasible, quantifiable, and effective for increasing anesthesia residents’ TTE knowledge-base. This pilot study suggests that further investigation is warranted to determine the impact of this perioperative TTE curriculum.     

New bone formation and osteolysis by a metastatic, highly invasive canine prostate carcinoma xenograft

BACKGROUND: Osteoblastic metastases are commonly induced by prostate cancer. A canine prostate carcinoma xenograft (Ace-1) was developed and used to evaluate neoplastic prostate cell growth, metastasis, and effects on bone formation in nude mice. METHODS: Characteristics of the Ace-1 cells were evaluated with histopathology, radiography, and bioluminescent imaging (BLI). Immunohistochemistry and quantitative RT-PCR were used to evaluate the expression of factors important in the development of osteoblastic metastases. RESULTS: The Ace-1 cells were invasive and induced bone formation and destruction. Radiographs demonstrated a mixed osteoblastic/osteolytic reaction. Lung and lymph node metastases occurred in 30% of mice. The tumor cells expressed parathyroid hormone-related protein (PTHrP-141 isoform), cathepsin K, keratins 8/18, and vimentin, but not keratins 5/14, and were androgen receptor negative. Intracardiac (IC) injections resulted in metastases in vertebrae and long bones. CONCLUSIONS: The Ace-1 xenograft is a useful model for investigating the pathogenesis of prostate cancer invasion and mixed osteoblastic/osteolytic bone metastases.     

Nocturia improvement in the combination of Avodart® and tamsulosin (CombAT) study

Purpose

The purpose of the study was to assess the impact of dutasteride plus tamsulosin combination therapy, compared with dutasteride or tamsulosin monotherapy, on nocturia in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) using data from the 4-year CombAT study.

Methods

Nocturia was assessed using Question 7 of the International Prostate Symptom Score questionnaire. Efficacy measures included as follows: mean change in nocturia at 3-month intervals up to 48 months; proportion of patients with improvement/worsening in nocturia; nocturnal voiding frequency at baseline and study end, overall and by baseline subgroups; and nocturnal voiding frequency <2 at study end in patients with a baseline score ≥2.

Results

In total, 4,722 patients with a mean age of 66 years were included. Mean nocturia improvements were significantly superior (p ≤ 0.01) with combination therapy than with either monotherapy (adjusted mean change from baseline in IPSS Question 7 score at month 48: combination therapy ?0.5, dutasteride ?0.4, tamsulosin ?0.3). Reduction in nocturia score with combination therapy was significantly (p ≤ 0.01) better than tamsulosin monotherapy across all baseline subgroups tested, except for men with previous 5ARI use. Among those with a baseline IPSS Q7 score ≥2, more patients with combination therapy had a score <2 at month 48 (34 %) compared with dutasteride (30 %, p = 0.018) or tamsulosin (26 %, p < 0.0001).

Conclusions

Combination therapy provided greater improvements and less worsening of nocturia compared with both dutasteride and tamsulosin monotherapies. These analyses are the first to show greater improvement with a 5ARI/α-blocker combination versus either agent alone for the management of nocturia in patients with LUTS/BPH.     

Jejuno-ileal diverticulitis with localized perforation: CT and US findings

Purpose

To describe the computed tomography and ultrasound findings of five cases of small bowel diverticulitis with localized perforation.

Material and methods

Our database, from April 2003 to August 2007, was reviewed and five cases of small bowel diverticulitis were identified.

Results

Jejuno-ileal diverticulitis with covered perforation usually presents as wall thickening of a small bowel loop and an adjacent inflammatory mass containing air bubbles.

Conclusion

Small bowel diverticula are rare and mostly asymptomatic. They become clinically relevant when complications arise, such as diverticulitis. The symptoms of jejuno-ileal diverticulitis are non-specific and the diagnosis is performed mainly by imaging studies.