The renin–angiotensin system plays a major role in voiding dysfunction of ovariectomized rats

Aims: The renin–angiotensin system (RAS) plays a major role in cardiovascular diseases in postmenopausal women, but little is known about its importance to lower urinary tract symptoms. In this study we have used the model of ovariectomized (OVX) estrogen-deficient rats to investigate the role of RAS in functional and molecular alterations in the urethra and bladder. Main methods: Responses to contractile and relaxant agents in isolated urethra and bladder, as well as cystometry were evaluated in 4-month OVX Sprague–Dawley rats. Angiotensin-converting enzyme activity and Western blotting for AT1/AT2 receptors were examined. Key findings: Cystometric evaluations in OVX rats showed increases in basal pressure, capacity and micturition frequency, as well as decreased voiding pressure. Angiotensin II and phenylephrine produced greater urethral contractions in OVX compared with Sham group. Carbachol-induced bladder contractions were significantly reduced in OVX group. Relaxations of urethra and bladder to sodium nitroprusside and BAY 41-2272 were unaffected by OVX. Angiotensin-converting enzyme activity was 2.6-fold greater (p < 0.05) in urethral tissue of OVX group,whereas enzyme activity in plasma and bladder remained unchanged. Expressions of AT1 and AT2 receptors in the urethra were markedly higher in OVX group. In bladder, AT1 receptors were not detected, whereas AT2 receptor expression was unchanged between groups. 17β-Estradiol replacement (0.1 mg/kg, weekly) or losartan (30 mg/kg/day) largely attenuated most of the alterations seen in OVX group. Significance: Prolonged estrogen deprivation leads to voiding dysfunction and urethral hypercontractility that are associated with increased ACE activity and up-regulation of angiotensin AT1/AT2 receptor in the urethral tissue.

Early and late urodynamic assessment of ileal orthotopic bladder substitutes combined with an afferent tubular segment

PURPOSE: Limited information is available concerning changes in the urodynamic characteristics of orthotopic bladder substitutes with time. Therefore, we compared early and late urodynamic results in patients with an ileal orthotopic bladder substitute combined with an afferent tubular segment. MATERIALS AND METHODS: Of 139 patients surviving at least 5 years after cystoprostatectomy and ileal orthotopic bladder substitution with an afferent tubular segment 119 underwent urodynamic assessment, including 66 at a median of 9 months (early) and 77 at a median of 62 months (late). Of these patients 24 were assessed at each time point. Simultaneously all patients were asked to complete a bladder diary and questionnaire regarding continence for at least 3 days in the week preceding the urodynamic study. RESULTS: Urodynamic parameters were comparable in patients who were evaluated early and late postoperatively. In addition, median values at early and late urodynamic evaluation in the 24 patients with the 2 examinations showed no statistically significant differences for volume at first desire to void (300 vs 333 ml, p = 0.85), pressure at first desire to void (12 vs 13 cm H2O, p = 0.57), maximum cystometric capacity (450 vs 453 ml, p = 0.84), end filling pressure (19 vs 20 cm H2O, p = 0.17), reservoir compliance (25 vs 28 ml/cm H2O, p = 0.58) or post-void residual urine volume (5 vs 15 ml, p = 0.27). CONCLUSIONS: Urodynamic results after 5 years of living with an ileal orthotopic bladder substitute with an afferent tubular segment show grossly unchanged urodynamic characteristics. Patients maintain a reservoir capacity and micturition pattern consistent with a normal life-style. Reservoir pressure remained low, thereby protecting and preserving upper tract function. To achieve these results patients must be regularly followed, and the causes of bacteriuria, increased post-void residual urine and bladder outlet obstruction must be recognized and dealt with accordingly.

A safe and simple solution for intravesical tension-free vaginal tape erosion: removal by standard transurethral resection

OBJECTIVE: To report our experience with the successful removal of visible tension-free vaginal tape (TVT) by standard transurethral electroresection, as intravesical tape erosion after TVT is a rare complication, and removal can be challenging, with few cases reported. PATIENTS AND METHODS: Five patients presenting with TVT erosion into the bladder were treated at our institutions from December 2004 to July 2007; all had standard transurethral electroresection. Their records were reviewed retrospectively to retrieve data on presenting symptoms, diagnostic tests, surgical procedures and outcomes. RESULTS: The median (range) interval between the TVT procedure and the onset of symptoms was 17 (1-32) months. The predominant symptoms were painful micturition, recurrent urinary tract infection (UTI), urgency and urge incontinence. There were no complications during surgery. The storage symptoms and UTI resolved completely after removing the eroded mesh in all but one patient. Cystoscopy at 1 month after surgery showed complete healing of the bladder mucosa. CONCLUSION: Although TVT erosion into the bladder is rare, persistent symptoms, particularly recurrent UTIs, must raise some suspicion for this condition. Standard transurethral electroresection seems to be a safe, simple, minimally invasive and successful treatment option for TVT removal.

Can urethrolysis resolve outlet obstruction related symptoms after Burch colposuspension for stress urinary incontinence?

OBJECTIVE Bladder outlet obstruction may occur after any incontinence surgery and may present as OAB, hesitancy and or the feeling of incomplete emptying. Aim of this study was to analyze the clinical and urodynamical outcome after urethrolysis in patients presenting with various clinical symptoms after Burch colposuspension for stress urinary incontinence. STUDY DESIGN Between January 2005 and December 2014, all patients who presented with symptoms and with bladder outlet obstruction were included. All patients had undergone Burch or Cowan colposuspension for stress urinary incontinence previously. Primary endpoint was the visual analogue scale (VAS) as measurement of patient perceived disease impact. Secondary endpoints were the various domains of the King's Health Questionnaire, urodynamic parameters as detrusor pressure at maximum flow, residual urine and sonographic bladder wall thickness before and six months after intervention. RESULTS Seventy-two female patients were included in this study whereof 42 suffered from urgency and urge incontinence, 20 from hesitancy and/or slow stream, seven from residual urine of more than 100ml and three from a combination of urgency and residual urine. VAS improved significantly (p<0.0001). Quality of life as determined by the King's Health Questionnaire improved for the domains general health, role limitations, emotions, physical limitations, personal limitations and incontinence impact significantly. Micturition pressure dropped significantly from 43cmH2O (95% CI 19-59cmH2O) to 18cmH2O (95% CI 16-23.5 H2O). Residual urine changed from 110ml (range 20-380ml) to 32ml (20-115ml). Bladder wall thickness decreased from 7mm (95% CI 6.235-7.152) to 5mm (95% CI 5.037-5.607; p<0.01). CONCLUSION Urethrolysis may resolve patients' symptoms and lower micturition pressure but irritative symptoms may persist.

Brain responses associated with consciousness of breathlessness (air hunger)

Little is known about the physiological mechanisms subserving the experience of air hunger and the affective control of breathing in humans. Acute hunger for air after inhalation of CO2 was studied in nine healthy volunteers with positron emission tomography. Subjective breathlessness was manipulated while end-tidal CO2- was held constant. Subjects experienced a significantly greater sense of air hunger breathing through a face mask than through a mouthpiece. The statistical contrast between the two conditions delineated a distributed network of primarily limbic/paralimbic brain regions, including multiple foci in dorsal anterior and middle cingulate gyrus, insula/claustrum, amygdala/periamygdala, lingual and middle temporal gyrus, hypothalamus, pulvinar, and midbrain. This pattern of activations was confirmed by a correlational analysis with breathlessness ratings. The commonality of regions of mesencephalon, diencephalon and limbic/paralimbic areas involved in primal emotions engendered by the basic vegetative systems including hunger for air, thirst, hunger, pain, micturition, and sleep, is discussed with particular reference to the cingulate gyrus. A theory that the phylogenetic origin of consciousness came from primal emotions engendered by immediate threat to the existence of the organism is discussed along with an alternative hypothesis by Edelman that primary awareness emerged with processes of ongoing perceptual categorization giving rise to a scene [Edelman, G. M. (1992) Bright Air, Brilliant Fire (Penguin, London)].