Potential targets in the treatment of urinary incontinence

Urgency and involuntary urine loss are distressing problems for both men and women. Attempts to block the primary cholinergic excitatory input to the bladder have led to a number of anticholinergic agents, but treatment with anticholinergics, the current first-line therapy, is not always effective. Metabolic and growth factor receptor targets are being investigated as a way to control the signal transduction process that leads to bladder contraction as well as the release of calcium that triggers this process. Because of the redundancy in mechanisms that promote bladder contraction, it is necessary to investigate multiple targets. Medical research is also focusing on purinergic receptors, the targeting of normally silent C-fibers that become activated due to neuroplasticity in the bladder, nerve-growth-factor blockade, and the blockade of neurotransmitters that control the bladder. Moreover, a strong correlation appears to exist between depression and the occurrence of incontinence, and there is evidence that points to a genetic link. However, the problem, with attacking this multiplicity of sites lies in establishing therapeutic efficacy and a high degree of specificity.     

Biofeedback in treatment of urinary incontinence in stroke patients

Urinary incontinence can occur poststroke owing to weakness or incoordination of sphincter muscles, impaired bladder sensation, or hyperreflexic, neurogenic bladder. Four male subjects who had urinary incontinence associated with a stroke that had occurred 8 months to 10 years earlier, and who averaged 1.6 to 7.5 accidental voidings per week, participated in an outpatient study with a 4-week scheduled-voiding baseline, 2 to 5 sessions of biofeedback-assisted bladder retraining, and 6- to 12-month follow-up. Training sessions included stepwise filling of the bladder and manometric feedback display of bladder pressure, abdominal pressure, and external anal sphincter pressure. Training procedures were designed to teach subjects to attend to bladder sensations, inhibit bladder contractions, and improve voluntary sphincter muscle control. All four subjects achieved and maintained continence regardless of substantial differences in subject characteristics, including laterality of stroke, degree of sensory impairment, and independence in daily activities.     

Biofeedback in treatment of urinary incontinence in stroke patients

Urinary incontinence can occur poststroke owing to weakness or incoordination of sphincter muscles, impaired bladder sensation, or hyperreflexic, neurogenic bladder. Four male subjects who had urinary incontinence associated with a stroke that had occurred 8 months to 10 years earlier, and who averaged 1.6 to 7.5 accidental voidings per week, participated in an outpatient study with a 4-week scheduled-voiding baseline, 2 to 5 sessions of biofeedback-assisted bladder retraining, and 6- to 12-month follow-up. Training sessions included stepwise filling of the bladder and manometric feedback display of bladder pressure, abdominal pressure, and external anal sphincter pressure. Training procedures were designed to teach subjects to attend to bladder sensations, inhibit bladder contractions, and improve voluntary sphincter muscle control. All four subjects achieved and maintained continence regardless of substantial differences in subject characteristics, including laterality of stroke, degree of sensory impairment, and independence in daily activities.     

Behavioural treatment of urinary incontinence in geriatric patients.

Urinary incontinence and a program to treat it were studied in a geriatric hospital. Of 161 men, 58 (36%) were incontinent. The most common probable causes were cerebrovascular accident and organic brain syndrome. Evaluation by cystometry (after treatment of infections) in 30 patients showed 24 (80%) to have detrusor hyperreflexia. Twenty patients with hyperreflexia completed a timed-voiding routine, which benefited 17 of them (85%).     

Medical and minimally invasive treatment of urinary incontinence

Newer agents and procedures give urologists more options in treating patients who have urinary incontinence related to such etiologies as an ineffective sphincter, detrusor hypersensitivity, obstruction, or a combination of these. Abolition of the involuntary contractions characteristic of detrusor instability can be accomplished pharmacologically or surgically. First-line anticholinergic agents are tolterodine and oxybutynin XL, given orally. Alternatively, intravesical administration provides a high concentration of drug, such as capsaicin or resiniferatoxin, at the detrusor muscle level. However, this commits the patient to intermittent self-catheterization. Surgery is reserved for those who have failed prolonged trials of conservative therapies. For patients with intractable urge incontinence, urologists have the new technique of sacral nerve stimulation.     

Urodynamic biofeedback treatment of urinary incontinence in children with myelomeningocele

Eight children with myelomeningocele and chronic neurogenic urinary incontinence were provided urodynamic biofeedback training. During urodynamic biofeedback, six of the eight children demonstrated improved self-regulation of detrusor and/or sphincter functioning. However, substantial improvements in clinical symptomatology (i.e., urinary incontinence) were clearly shown by only one child. Unexpectedly, chronic neurogenic fecal incontinence was reduced in four children. Several methodological modifications are discussed which may improve clinical symptomatology and which may facilitate further urodynamic biofeedback research for these children with congenital neurogenic urinary incontinence.This work was supported by a grant from The Crippled Children's Guild through the Behavioral Pediatrics Program at Orthopaedic Hospital.     

Urodynamic biofeedback treatment of urinary incontinence in children with myelomeningocele

Eight children with myelomeningocele and chronic neurogenic urinary incontinence were provided urodynamic biofeedback training. During urodynamic biofeedback, six of the eight children demonstrated improved self-regulation of detrusor and/or sphincter functioning. However, substantial improvements in clinical symptomatology (i.e., urinary incontinence) were clearly shown by only one child. Unexpectedly, chronic neurogenic fecal incontinence was reduced in four children. Several methodological modifications are discussed which may improve clinical symptomatology and which may facilitate further urodynamic biofeedback research for these children with congenital neurogenic urinary incontinence.     

Advances toward tissue engineering for the treatment of stress urinary incontinence

Suburethral pubovaginal sling placement is a common surgical procedure for the treatment of stress urinary incontinence. A wide variety of graft materials is available, each associated with inherent desirable and undesirable characteristics and complications. In this article, we discuss the rationale for and application of small intestinal submucosa (SIS) in lower urinary tract tissue engineering, with emphasis on the use of SIS as a suitable and biologically compatible sling material. In addition, we discuss exciting research regarding the engineering of true functional sphincter reconstruction using this biologic scaffold and pre-seeded muscle cells.     

Ethical and practice considerations for biofeedback therapists in the treatment of urinary incontinence

The treatment of incontinence presents many unique issues for biofeedback therapists that are routine for professionals in fields such as nursing or medicine. Although, all professional practice is guided by ethical standards, the unique circumstances encountered during biofeedback treatments for this disorder warrant the development of specific guidelines. This is true whether insertable or surface EMG devices are used. Therefore, the purpose of this article is to propose a set of ethical guidelines for biofeedback therapists. The intended audience includes professionals such as psychologists, clinical psychophysiologists, and other mental health-care providers who use biofeedback techniques. These are not formally endorsed by any professional organizations (e.g., APA, AAPB) at this time. Ethical considerations include proper medical evaluation, informed consent, patient instruction, disrobing, nonerotic physical contact, patient safety, and patient satisfaction.     

Adipose-derived stromal cell transplantation for treatment of stress urinary incontinence

We aimed to investigate the application of adipose-derived stromal cells in the treatment of stress urinary incontinence (SUI). Animal models of stress urinary incontinence were established with Sprague-Dawley female rats by complete cutting of the pudendal nerve. Rat adipose-derived stromal cells were isolated, cultured and successfully transplanted into animal models. Effects of stem cell transplantation were evaluated through urodynamic testing and morphologic changes of the urethra and surrounding tissues before and after transplantation. Main urodynamic outcome measures were measured. Intra-bladder pressure and leak point pressure were measured during filling phase. Morphologic examinations were performed. Transplantation of adipose-derived stem cells significantly strengthened local urethral muscle layers and significantly improved the morphology and function of sphincters. Urodynamic testing showed significant improvements in maximum bladder capacity, abdominal leak point pressure, maximum urethral closure pressure, and functional urethral length. Morphologic changes and significant improvement in urination control were consistent over time. It was concluded that periurethral injection of adipose-derived stromal cells improves function of the striated urethral sphincter, resulting in therapeutic effects on SUI. Reconstruction of the pelvic floor through transplantation of adipose-derived cells is a minimally invasive and effective treatment for SUI.     

Naphthol derivatives as TRPV1 inhibitors for the treatment of urinary incontinence

We have identified naphthol derivatives as inhibitors of the vanilloid receptor TRPV1 by high throughput screening. The initial lead showed high clearance in rats and has been optimized by enhancing the acidity of the phenol group. Compound 6b has reduced clearance, improved potency and is active in rat cystometry models of urinary incontinence after intravenous administration.