Lysanne Campeau

Bone marrow mesenchymal stromal cell therapy for external urethral sphincter restoration in a rat model of stress urinary incontinence

To assess the effect of intra‐sphincteric injections of bone marrow mesenchymal stromal cells (MSCs) on Valsalva leak point pressure (VLPP) changes in an animal model of stress urinary incontinence (SUI).

Normal urodynamic parameters in women

Introduction and hypothesisThis literature review, providing reference ranges of normal variability in urodynamic parameters, is the second part of a two-part article. The first part addresses non-invasive urodynamics (UDS), while the second part addresses invasive techniques.MethodsData were obtained through MEDLINE from articles published between January 1956 and February 2011, International Continence Society meeting abstracts, and standardization reports. Search terms included cystometry, urethral pressure profilometry, leak point pressure, video UDS, normal volunteer, pressure flow studies, and electromyography.ResultsNormal values varied widely in the literature. However, with the help of clinical data, it was possible to define “normality” ranges for most of the different parameters.ConclusionsUrodynamic evaluation of lower urinary tract (LUT) function is not a physiological test. However, it is still the best available tool for LUT function assessment. Even if normality in UDS can be defined, tests must always be interpreted against patient characteristics, complaints, and symptoms.

Normal lower urinary tract assessment in women: I. Uroflowmetry and post-void residual, pad tests, and bladder diaries.

This study aims to provide reference ranges of normal variability in urodynamic parameters through literature review of normal urodynamic values in the literature. Data were obtained through MEDLINE from articles published between January 1956 and February 2011, International Continence Society meeting abstracts and standardization reports. Search terms included urodynamics, bladder diary, uroflowmetry, frequency volume charts, pad tests, normal control, and normal volunteer. Normal values varied widely in the literature. However, with the help of clinical data, it was possible to define “normality” ranges for most of the different parameters. Urodynamic evaluation of lower urinary tract (LUT) function is not a physiological test. However, it is still the best available tool to assess LUT function. Even if normality in urodynamics can be defined, tests must always be interpreted against patient characteristics, complaints, and symptoms.

Effect of the anticonvulsant medications Pregabalin and Lamotrigine on urodynamic parameters in an animal model of neurogenic detrusor overactivity

To assess the effects of different doses and treatment durations of Pregabalin and Lamotrigine on the urodynamic parameters of an animal model of neurogenic detrusor overactivity (NDO).

Effect of Antiepileptic Agent, Levetiracetam, on Urodynamic Parameters and Neurogenic Bladder Overactivity in Chronically Paraplegic Rats

OBJECTIVESnTo investigate the effects of different levetiracetam (LEV) doses on urodynamic parameters in an animal model of neurogenic detrusor overactivity (NDO).nnnMETHODSnA total of 54 female rats were studied. Of the 54 rats, 6 served as normal controls, and 48 underwent T10 spinal cord transection (SCT). Of the latter 48 rats, 12 were paraplegic controls, and the remaining 36 rats were divided into 3 equal subgroups that received LEV by way of a subcutaneous osmotic minipump at a dose of 17, 54, and 108 mg/kg daily, respectively. The paraplegic control and treatment groups were further subdivided (n = 6), and cystometry was performed at 3 and 4 weeks after SCT, respectively.nnnRESULTSnAll paraplegic controls developed NDO, with spontaneous contractions. At 3 and 4 weeks after SCT, the mean frequency of the contractions was 1.6 +/- 0.3/min and 1.7 +/- 0.2/min. The contraction amplitude and bladder capacity were not significantly different. After 1 week of LEV treatment, these urodynamic parameters improved significantly in a dose-dependent manner, and the changes were more striking at 2 weeks. At a LEV dosage of 17, 54, and 108 mg/kg, respectively, the NDO frequency increased from 1.7 +/- 0.3 to 0.7 +/- 0.2 contractions/min (P = .01), 0.48 +/- 0.16 contractions/min (P = .009), and 0.5 +/- 0.17 contractions/min (P = .01). The bladder capacity increased from 0.51 +/- 0.1 mL to 1.5 +/- 0.2 mL (P = .0001), 2.5 +/- 1.7 mL (P = .006), and 2.6 +/- 0.3 mL (P = .0003), and the micturition pressure improved from 105.8 +/- 6.9 to 73.8 +/- 6.8 cm H(2)O (P = .01), 58.6 +/- 8.9 cm H(2)O (P = .006), and 49.7 +/- 8.9 cm H(2)O (P = .002).nnnCONCLUSIONSnThe results of our study have shown that LEV is an effective treatment of NDO after SCT in rats. It might prove to be a novel, alternative therapeutic approach to NDO. The follow-up of these experimental results with a clinical trial is warranted.

Androgen Deprivation Therapy and the Risk of Anemia in Men with Prostate Cancer.

Background: The use of androgen deprivation therapy in prostate cancer may be associated with an increased risk of anemia, but the evidence remains limited. This study aimed to determine if androgen deprivation is associated with increased risk of anemia in patients newly diagnosed with prostate cancer. Methods: This was a population-based cohort study using the United Kingdom Clinical Practice Research Datalink linked to the Hospital Episode Statistics repository. The cohort consisted of 10,364 men newly diagnosed with nonmetastatic prostate cancer between 1 April 1998 and 30 September 2015. We used time-dependent Cox proportional hazards models to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for anemia (hemoglobin <130u2009g/L) associated with current and past use of androgen deprivation therapy, compared with nonuse. Results: There were 3,651 incident anemia events during 31,574 person-years of follow-up (rate: 11.6/100 person-years). Current androgen deprivation therapy use was associated with a nearly three-fold increased hazard of anemia, compared with nonuse (23.5 vs. 5.9 per 100 person-years, respectively; HR: 2.90, 95% CI: 2.67, 3.16). The HR was elevated in the first 6 months of use (HR: 2.20, 95% CI: 1.95, 2.48) and continued to be elevated with longer durations of use. Past androgen deprivation therapy use was associated with a lower estimate (HR: 1.27, 95% CI: 1.12, 1.43), which returned closer to the null ≥25 months after treatment discontinuation (HR: 0.95, 95% CI: 0.79, 1.15). Conclusions: The use of androgen deprivation therapy is associated with increased risk of anemia, which reverses upon treatment discontinuation.

Succinate, increased in metabolic syndrome, activates GPR91 receptor signaling in urothelial cells

Metabolic syndrome is associated with overactive bladder syndrome (OAB) and increased circulating levels of succinate, an intermediate of the Krebs cycle. The urothelium is an essential regulator of bladder muscle contraction. This study aimed to determine if GPR91, the succinate receptor, is expressed and functional in the bladder. Urothelial and smooth muscle cells (SMCs) were cultured and characterized. PCR revealed that urothelial cells express GPR91, twice as much as SMCs. Incubation of cells with succinate stimulated phosphorylation of ERK and JNK in urothelial cells. Succinate also potently inhibited forskolin-stimulated cyclic AMP production in urothelial cells, an effect prevented by a protein Gi inhibitor. ERK phosphorylation stimulated by succinate was abolished by inhibitors of protein Gq, phospholipase C, MAPK pathway and PKC. Incubation of urothelial cells with succinate potently increased iNOS synthesis and secretion of nitric oxide (NO), and decreased secretion of prostaglandin E2 (PGE2). Finally, succinate triggered entry of calcium in urothelial cells. GPR91 knockdown by shRNA abolished most of these signaling effects. We conclude that in the bladder, urothelial cells are a primary target of succinate through its receptor GPR91. Its activation leads to signaling via phospholipase C, MAPK, PKC pathway and protein Gq and Gi. Succinate binding to GPR91 triggers a rise in intracellular calcium, an increase in secretion of NO and a decrease in the release of PGE2. Succinate might be essential in the understanding of OAB that occurs in metabolic syndrome.

A cost-utility analysis of artificial urinary sphincter versus AdVance male sling in post prostatectomy stress urinary incontinence: A publicly funded health care perspective

To investigate the long‐term cost‐utility of the artificial urinary sphincter (AUS) compared with Transobturator Retroluminal Sling (AdVance) in the treatment of patients with severe post prostatectomy stress urinary incontinence (PPSUI) from a Canadian provincial health perspective.

Succinate decreases bladder function in a rat model associated with metabolic syndrome

Succinate and its receptor, GPR91, have been implicated in different aspects of metabolic syndrome. As GPR91 is expressed in the urinary bladder, the aim of this study is to show the effect of chronically increased succinate levels on bladder function.

Bladder overdistension with polyuria in a hypertensive rat model

Polyuria can lead to progressive chronic bladder overdistension. The impact of polyuria on the bladder has been extensively studied in settings of either diabetes or sucrose diuresis in animals. The goal of this study was to investigate the outcomes of polyuria in a hypertension setting.