Targeting bladder outlet obstruction from benign prostatic enlargement via the nitric oxide/cGMP pathway?
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Cyclic GMP↗
Biomedical subjects
Brigitte Schurch
Publications and source records attributed to Brigitte Schurch.
Functional magnetic stimulation of the spinal cord--a urodynamic study in healthy humans.
AIMS: To study the effects of functional magnetic stimulation of the spinal cord in healthy subjects on somatic and autonomic pathways innervating the anal and the external urethral sphincter, bladder, bladder neck, and rectum. METHODS: Eight healthy male volunteers gave their written informed consent and underwent functional magnetic stimulation of the thoracolumbar and sacral spinal cord. A two-channel microtip pressure transducer catheter was placed rectally measuring the abdominal and anal sphincter pressure. A three-channel microtip pressure transducer catheter was inserted into the urethra measuring the bladder, the bladder neck, and the external urethral sphincter pressure. A comprehensive protocol of single and repetitive magnetic stimulations was performed. Frequency, location, and duration of stimulation were varied while the intensity of stimulation was adapted to the maximum the subjects could tolerate. In four subjects, the degree of bladder filling was changed and the protocol was repeated when the subjects reported a full bladder and desire to void. RESULTS: Continuous magnetic stimulation of the thoracolumbar spinal cord and the sacral roots applied with different frequencies (5, 15, 30, 60, 100 Hz) and different duration of stimulation (10, 30, 120 sec) evoked sphincter contraction of both anal and urethral sphincters. The stimulation could not evoke contractions of the bladder, the bladder neck, or the rectum. Also with filled bladder and present desire to void, the magnetic stimulation could not activate autonomic pathways innervating these structures. CONCLUSIONS: Considering our results, we suggest that in individuals with preserved sensibility magnetic stimulation of the spinal cord with intensities below the pain threshold is ineffective in activating autonomic nerve fibres innervating bladder, bladder neck, and rectum.
Electric Stimulation↗
The effect of nitric oxide on the resting tone and the contractile behaviour of the external urethral sphincter: a functional urodynamic study in healthy humans.
AIMS: This functional urodynamic study assessed the effect of the nitric oxide donor isosorbide dinitrate on the external urethral sphincter and hypothesised first that nitric oxide could lower the resting sphincter pressure, second that nitric oxide could influence the sphincter contractility during magnetic stimulation, and third that nitric oxide could induce a faster external urethral sphincter fatigue during continuous magnetic stimulation. METHODS: Eight healthy males gave their written informed consent and were included. A 2-channel microtip pressure transducer catheter was inserted into the urethra measuring the bladder and the external urethral sphincter pressure. Magnetic stimulation of the sacral roots was performed to evoke reproducible contractions of the external urethral sphincter. The baseline protocol included six single pulse stimulations and three stimulations 10sec in duration each for two frequencies 5Hz and 50Hz with intensities at the motor threshold of the pelvic floor. Then the subjects received 10 mg of isosorbide nitrate sublingually and the protocol was repeated 5min, 20min, 40min and 60min after drug administration. RESULTS: The sublingual administration of isosorbide dinitrate could significantly reduce the resting pressure of the external urethral sphincter for at least one hour. The maximal contractile strength measured as the maximal urethral pressure during single pulse and continuous magnetic stimulation of the sacral roots also decreased significantly. Nitric oxide did not induce a significantly faster fatigue of the external urethral sphincter during continuous magnetic stimulation of the sacral roots. CONCLUSIONS: This study shows a functionally relevant effect of nitric oxide on the resting tone and the contractile behaviour of the human external urethral sphincter in vivo while the fatigue properties did not changed significantly. Nitric oxide donors could offer a new pharmacological approach to treat urinary retention due to overactive or non-relaxing external urethral sphincter.
Adult↗
Oral nitric oxide donors: a new pharmacological approach to detrusor-sphincter dyssynergia in spinal cord injured patients?
PURPOSE: Detrusor-sphincter dyssynergia is a common cause of bladder outlet obstruction in spinal cord injured patients and leads to poor bladder emptying and high bladder pressures, which if left untreated might cause renal failure. In this study, we tested the recently published hypothesis that oral administration of a nitric oxide donor could be a new pharmacological approach to treat detrusor-sphincter dyssynergia in humans with spinal cord injury. METHODS: 12 male spinal cord injured patients presenting with neurogenic detrusor overactivity and detrusor-sphincter dyssynergia were studied. 6 performed clean intermittent catheterisation and 6 used suprapubic tapping for bladder emptying. During cystometry the bladder was filled until the first overactive bladder contraction accompanied by detrusor-sphincter dyssynergia occurred while bladder and external urethral sphincter pressures were continuously recorded. Then the bladder was emptied and the patients received 10 mg of isosorbide dinitrate sublingually. Resting pressures were recorded and cystometry was repeated starting 15 min after drug administration. Maximal and mean values for bladder and external urethral sphincter pressures were calculated in both fillings and statistically compared by analysis of variance for repeated measurements (level of significance p < 0.05). RESULTS: Nitric oxide significantly reduced external urethral sphincter pressures at rest (p < 0.05) and during dyssynergic contraction (p < 0.05) while bladder pressures at rest and during contraction as well as the reflex volume remained unchanged. In the patients who used suprapubic tapping for bladder emptying the mean post triggering residual volume was significantly reduced (p < 0.05). CONCLUSIONS: Oral administration of nitric oxide donors significantly reduced bladder outlet obstruction due to detrusor-sphincter dyssynergia suggesting a role for nitric oxide in inhibitory neurotransmission to the urethral sphincter. This new approach could offer a potential pharmacological option to treat detrusor-sphincter dyssynergia in spinal cord injured patients.
Administration, Oral↗
European experience of 200 cases treated with botulinum-A toxin injections into the detrusor muscle for urinary incontinence due to neurogenic detrusor overactivity.
OBJECTIVES: To present a comprehensive experience with botulinum-A toxin (BTA) injected into the detrusor muscle in patients with spinal cord injuries/diseases causing neurogenic incontinence. METHODS: Ten European medical centers provided the results of 231 patients with neurogenic detrusor overactivity who were treated with BTA. 300 units of Botox (Allergan Inc.) were injected cystoscopically into the detrusor muscle at 30 different locations, while sparing the trigonum. Urinary continence status, concomitant anticholinergic medication use and patient satisfaction were recorded. Key urodynamic parameters (reflex volume, maximum detrusor pressure during voiding, detrusor compliance and maximum cystometric bladder capacity) at baseline and at the first and second urodynamic follow-up examinations were analyzed. RESULTS: By the time of the initial (mean 12 weeks after injection) as well as at the second urodynamic follow-up examinations (mean 36 weeks after injection), the mean cystometric bladder capacity (p < 0.0001) and the mean reflex volume (p < 0.01) increased significantly, while the mean voiding pressure (p < 0.0001) decreased significantly. The mean bladder compliance had increased significantly (p < 0.0001) by the first follow-up examination and non-significantly by the time of the second follow-up. No injection related complications or toxin related side effects were reported. The patients considerably reduced or even stopped taking anticholinergic drugs without recurrence of reflex incontinence and were satisfied with the treatment. CONCLUSIONS: This retrospective European multicenter study presents the most extensive experience to date with BTA injections into the detrusor muscle to treat neurogenic incontinence due to detrusor overactivity and confirms that this new treatment is safe and valuable. Significant improvement of bladder function corresponds with continence and the subjective satisfaction indicated by the treated patients.
Botulinum Toxins, Type A↗
The effect of tamsulosin on the resting tone and the contractile behaviour of the female urethra: a functional urodynamic study in healthy women.
AIMS: The aim of this functional urodynamic experiment was to study the effect of the selective alpha1(A)-blocker tamsulosin on the urethral pressure in healthy human females and assessed first the resting urethral pressure and second the urethral contractility in response to magnetic stimulation of the sacral roots. METHODS: 11 healthy female subjects gave their written informed consent and were included. A microtip pressure transducer catheter was inserted into the bladder and three baseline urethral pressure profiles were obtained. Another three urethral pressure profiles were recorded while magnetic single pulse stimulation of the sacral roots was performed above the motor threshold of the pelvic floor to evoke reproducible urethral contractions. Then the subjects received 0.4 mg of tamsulosin and the entire protocol was repeated 6 hours after drug administration. Cardiovascular monitoring was obtained during the baseline and follow-up measurements. Mean and maximal urethral pressure values calculated over the entire urethra, mean pressure values calculated over the proximal, middle and distal third of the urethra and the pressure amplitudes to magnetic stimulation at baseline were statistically compared to the follow-up measurements with tamsulosin. RESULTS: The oral administration of tamsulosin did not change the systemic blood pressure, but did significantly reduce the mean and maximal urethral pressure acquired over the entire urethra. When the proximal, middle and distal third of the urethra were analysed separately, there was a significant pressure reduction in all three segments. Amplitudes of the urethral contractions evoked by sacral magnetic stimulation remained unchanged after tamsulosin. CONCLUSIONS: These data show a significant relaxing effect of tamsulosin on the resting urethral tone in healthy females in vivo. These results may suggest tamsulosin as a new pharmacological approach to treat urinary retention due to overactive or non-relaxing urethra in women.
Adrenergic alpha-Antagonists↗
Intravesical therapy options for neurogenic detrusor overactivity.
STUDY DESIGN: Review article. SETTING: Neuro-Urology, Spinal Cord Injury Center, Balgrist University Hospital, Zurich, Switzerland. OBJECTIVES: This review considers intravesical treatment options of neurogenic detrusor overactivity and discusses the underlying mechanism of action, clinical safety and efficacy, and the future trends. METHODS: The available literature was reviewed using medline services. RESULTS: Oral anticholinergic drugs are widely used to treat detrusor overactivity, but they are ineffective in some patients or cause systemic side effects such as blurred vision or dry mouth. As an alternative, topical therapy strategies have been suggested to achieve a profound inhibition of the overactive detrusor and to avoid high systemic drug levels. Currently available intravesical treatment options either act on the afferent arc of the reflex such as local anaesthetics or vanilloids or on the efferent cholinergic transmission to the detrusor muscle such as intravesical oxybutynin or botulinum toxin. Although an established and effective therapy, intravesical oxybutynin is not widely used. Evidence for clinical significance of intravesical atropine and local anaesthetic is missing. Intravesical capsaicin has been shown to improve clinical and urodynamic parameters, but cause pain in some patients. The intravesical instillation of resiniferatoxin and the injection of botulinum-A toxin into the detrusor muscle are promising new options; however, randomised placebo-controlled studies to prove their safety and efficacy are still missing. CONCLUSION: Intravesical treatment strategies in patients with neurogenic detrusor overactivity may provide alternatives to established therapies such as oral anticholinergics. The selectivity of the intravesical treatment and the reduction or even the absence of side effects are major advantages of this topical approach.
Administration, Intravesical↗
Botulinum toxin type B injection for management of type A resistant neurogenic detrusor overactivity.
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Adult↗
The role of botulinum toxin in neurourology.
Botulinum toxin is a presynaptic neuromuscular blocking agent that induces a selective and reversible muscle weakness of up to several months when injected intramuscularly in minute quantities. Different medical disciplines have applied the toxin to treat mainly muscular hypercontraction. For neurourologically impaired patients, the reported successful treatment of neurogenic detrusor overactivity and detrusor sphincter dyssynergia with botulinum-A toxin is a promising alternative option to conservative medication or surgery. This review of the literature presents current indications, techniques for and results of the use of botulinum toxin in neurourologically impaired patients and aims to give an insight into this new therapeutic option.
Botulinum Toxins, Type A↗
Afferent fibers of the pudendal nerve modulate sympathetic neurons controlling the bladder neck.
AIMS: Pudendal nerve stimulation is known to have a potential modulative effect on bladder function. However, even if its efficiency has been established for various neurogenic and non-neurogenic bladder dysfunctions, the underlying neuronal mechanism, and the involved pathways in humans remain unknown. In this prospective study we focused on the effects of pudendal nerve stimulation in complete spinal cord injured patients to identify neuromodulative processes that occur on spinal level. METHODS: Twenty complete spinal male presenting with upper motor neuron lesion and neurogenic incontinence underwent pudendal nerve stimulation. Bladder, bladder neck (BN), and external urethral sphincter (EUS) pressures were continuously recorded with a three channel microtip pressure transducer catheter. Fifty six pudendal stimulations using biphasic rectangular impulses (0.2 ms, 10 Hz) with intensities up to 100 mA were applied to the dorsal penile nerve. In six patients, 18 stimulations were repeated after intravenous (i.v.) administration of 7 mg phentolamine. RESULTS: Mean BN and EUS pressure increased during stimulation significantly (P < 0.001). The latencies to the EUS responses range between 27 and 41 ms and those to the BN responses between 188 and 412 ms. Phentolamine decreased initial BN pressure and reduced the pressure rise during stimulation significantly (P < 0.05). CONCLUSIONS: Pudendal nerve stimulation evoked somatic responses in the EUS and autonomic responses in the smooth muscle sphincter controlling the BN. Longer latencies of the BN responses and the sensitivity to the alpha-blocking agent phentolamine suggest that sympathetic alpha-adrenergic fibers are involved. Somatic afferent fibers of the pudendal nerve are supposed to project on sympathetic thoracolumbar neurons to the BN and modulate their function. This neuromodulative effect works exclusively at the spinal level and appears to be at least partly responsible for BN competence and at least continence.
Adrenergic Fibers↗
Botulinum toxin as a new therapy option for voiding disorders: current state of the art.
Botulinum toxin is a presynaptic neuromuscular blocking agent inducing selective and reversible muscle weakness up to several months when injected intramuscularly in minute quantities. Different medical disciplines have discovered the toxin to treat mainly muscular hypercontraction. In urology, indications for botulinum-A toxin have been neurogenic detrusor overactivity, detrusor-sphincter dyssynergia, motor and sensory urge and, more recently, chronic prostatic pain. The available literature was reviewed using Medline Services. The keywords "botulinum-A toxin", "detrusor-sphincter dyssynergia", "neurogenic bladder", "spinal cord injury", "denervation", "chronic prostatic pain", "chronic urinary retention" were used to obtain references. A toxin injection is effective to treat detrusor-sphincter dyssynergia when injected either transurethrally or transperineally. After treatment, external urethral sphincter pressure, voiding pressure and post-void residual volume decreased. The effect lasts between 2 to 9 months depending on the number of injections. Best indications seem to be multiple sclerosis and incomplete spinal cord injury patients suffering from neurogenic detrusor overactivity and detrusor-sphincter dyssynergia. According to the previous results, the use of botulinum-A toxin injections into the external urethral sphincter has been extended to a variety of bladder obstructions and to decrease outlet resistance in patients with acontractile detrusor. In cases of successful treatment, spontaneous voiding re-occurs and catheterization can be resumed. Injections of the toxin into the external urethral sphincter also seem to have a beneficial effect on chronic prostatic pain, presumably by reducing hypertonicity and hyperactivity of the external urethral sphincter. Injections of botulinum-A toxin into the detrusor muscle has first been tested to treat neurogenic detrusor activity in spinal cord injured patients and in myelomeningocele children. Long lasting (mean 9 months) detrusor relaxation occurs after injection of usually 300 units of Botox). Continence is restored in about 95% of the patients and anticholinergic drugs can be markedly reduced or even stopped. Excellent results of botulinum-A toxin injections into the detrusor in neurogenic detrusor overactivity have lead to an expansion of this treatment to incontinence due to idiopathic detrusor overactivity. Although preliminary results are promising, adequate dosage of the toxin required for this indication is not yet known. In conclusion, it appears that botulinum toxin injection into either the external urethral sphincter or the detrusor offers new promising treatment options for many different urological dysfunctions. However, large controlled trials are absolutely required to establish the role of botulinum-A toxin injections in the fields of urology and neurourology on evidence based medicine.
Animals↗
Value of sensory examination in predicting bladder function in patients with T12-L1 fractures and spinal cord injury.
OBJECTIVE: To determine whether early sensory examination, voluntary anal sphincter contraction, or bulbocavernosus reflex (BCR) might predict bladder function in patients with a spinal fracture at the thoracolumbar level. DESIGN: Longitudinal study of consecutive patients admitted to a spinal cord injury (SCI) rehabilitation center. SETTING: Primary care center, university facility in Switzerland. PARTICIPANTS: Fifty-five patients with thoracolumbar fractures. INTERVENTIONS: Neurologic (American Spinal Injury Association [ASIA] protocol) and urodynamic examination during the first hospitalization and at follow-up. MAIN OUTCOME MEASURES: Neurologic sensory scores and type of neurogenic bladder. RESULTS: At first examination, there was no correlation between the sensory examination, voluntary anal sphincter contraction, BCR, and neurogenic bladder type. At follow-up (time since first examination: mean, 698+/-47.2d; median, 481d), the sensory examination remained of no value in distinguishing the neurogenic bladder type. However, voluntary anal sphincter contraction distinguished between complete and incomplete neurogenic bladders and BCR differentiated between complete bladder dysfunction of the lower motoneuron and upper motoneuron type. At follow-up, the bladder function (51 patients) remained unchanged in 44 cases and normalized in only 7 cases. Patients who improved their bladder function tended to have higher initial sensory ASIA scores (P<.05, Kruskal-Wallis test). Of the 7 patients who improved their bladder function, all but 1 (85%) had initial perineal pinprick sensation. Nevertheless, preservation of perineal pinprick sensation was of no positive predictive value, because 21 patients (48%) who initially had perineal pinprick sensation did not improve their voiding function, a finding similar to that of the 23 (52%) without initial perineal pinprick sensation whose bladder function also did not improve. CONCLUSIONS: In SCI patients with thoracolumbar fractures, neurogenic voiding dysfunction cannot be predicted by the sensory evaluation. In patients with an SCI at the thoracolumbar level, pinprick sensation in the perineal area is of negative predictive value: absence of pinprick sensation predicts poor bladder recovery. Most patients with a spinal fracture at T12-L1 did not improve in voiding function.
Adult↗
Sympathetic sudomotor skin activity in human after complete spinal cord injury.
Spinal cord injury (SCI) causes serious disturbances in autonomic innervation and malfunction of the sympathetic nervous system that controls the pelvic organs, blood pressure, skin temperature and sweating. We studied sympathetic sudomotor pathways in 6 healthy subjects and 14 patients with sensory and motor complete SCI on cervical, thoracic and lumbar level. Sympathetic skin responses (SSRs) were provoked by auditory bursts and electrical stimulation of median, pudendal and tibial nerve and recorded from the palmar and plantar skin. The SSRs in healthy subjects occurred generally with the same pattern and with similar latencies suggesting a common sudomotor pathway mediating the SSR. Appearance or absence of the SSRs in SCI following stimulation above the lesion depend on the spinal level of lesion and on the location of stimulation. Lesions below T3 show palmar and lesions below T12 palmar and plantar SSR. Pudendal nerve stimulation evoked plantar SSRs in patients with complete cervical and thoracic SCI. No SSRs were obtained in patients with lesions at L1 and more caudal. SSRs following pudendal nerve stimulation in complete SCI above the level L1 are mediated by sacral somatic afferents and a sympathetic pathway originating at the upper lumbar level. The underlying sacro-lumbar reflex circuit is organized on spinal level and requires intact lumbar segments. Tibial nerve stimulation was not found to elicit SSRs below a SCI lesion and we suppose that this type of electrical stimulation cannot activate the spinal sudomotor reflex circuit.
Adrenergic Fibers↗
Magnetic stimulation of sacral roots for assessing the efferent neuronal pathways of lower urinary tract.
The value of sacral magnetic stimulation (SMS) in neurophysiological evaluation of the sacral efferent pathways of the lower urinary tract was assessed during urodynamic examination in 10 men with chronic suprasacral spinal cord injury (SCI) and in 7 healthy volunteers. Investigated parameters included latency and amplitude of the urodynamic pressure response of the external urethral sphincter and detrusor to different stimulation strengths (50-100%) and single or repetitive (20 and 30 Hz) stimuli. Following SMS, reproducible external urethral sphincter pressure responses (mean latency, 13 ms) were recorded in all subjects. In contrast, a detrusor pressure increase was recorded only in SCI patients after repetitive SMS, with a latency of 1-2 s. This implies the appearance of a polysynaptic spinal reflex due to changes in organization of the sacral micturition reflex after SCI. The method of SMS may be helpful for the evaluation of cases in which urodynamic studies remain inconclusive.
Adult↗
Persistent paraplegia after an aqueous 7.5% phenol solution to the anterior motor root for intercostal neurolysis: a case report.
A 55-year-old white man with severe scoliosis and chest deformity was scheduled for an intercostal neurolysis for pain relief with 7.5% aqueous phenol solution. A 20 G needle was inserted 3 to 4cm lateral to the midline of the spine under the 10th right rib. After negative aspiration for blood and alcohol, 6mL of a 7.5% aqueous phenol solution was injected. Within a minute after the injection, the patient felt a warm sensation in his right leg, followed by loss of leg motor and sensory function on both sides. A lumbar puncture done 3.5 hours after the block showed a phenol concentration of 87.5 microg/mL. The most likely explanation is a diffusion of the phenol through the intervertebral foraminae reaching the spinal space and therefore damaging the motor and sensory roots. This case highlights the danger associated with phenol application in the vicinity of the spinal cord.
Humans↗