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Biomedical subjects

Clare J Fowler

Publications and source records attributed to Clare J Fowler.

33 records · Page 2Linked to original sources
PubMed2004

Sphincter electromyography in diagnosis of multiple system atrophy: technical issues.

Possible technical reasons for the controversy over the role of sphincter electromyography (EMG) in the diagnosis of multiple system atrophy (MSA) were analyzed. In a review of the literature, a high sensitivity (>60%) was found reported in 11 studies that included late components, and no value of the test was found in 4 studies that excluded them. This was also corroborated in a pilot study of 5 patients with probable MSA. With late components included, the mean motor unit potential (MUP) duration was prolonged in all 4 patients with an adequate single-MUP analysis sample and, with late components excluded, in 2 of 5 patients on multi-MUP analysis. At least in diagnostic EMG of MSA patients, late components should be included in the measurement of MUP duration.

Action Potentials↗
PubMed2004

P2X3-immunoreactive nerve fibres in neurogenic detrusor overactivity and the effect of intravesical resiniferatoxin.

OBJECTIVES: The ATP-gated purinergic receptor P2X3 is expressed by small diameter sensory neurons and has been identified in normal and neurogenic human bladder suburothelial fibres. Animal models have shown that ATP is released by the urothelium during bladder distension, suggesting a mechanosensory role for P2X3 receptors in normal bladder function. Successful treatment of spinal neurogenic detrusor overactivity (NDO) with intravesical resiniferatoxin (RTX), which partly acts on suburothelial C fibres, provides evidence for the emergence of a C fibre-mediated spinal reflex. The aim of this study was to investigate the possible role of P2X3-positive innervation in this pathological voiding reflex by comparing suburothelial P2X3 immunoreactivity of controls and in patients with NDO before and after intravesical RTX. METHODS: Bladder biopsies were obtained from 8 controls and 20 patients with refractory NDO enrolled in a trial of intravesical RTX. P2X3 nerve fibre density and intensity were studied in the specimens by immunohistochemistry. RESULTS: P2X3-IR nerve fibres were significantly increased in patients with NDO compared to controls (p=0.014). Thirteen patients had pre- and post-RTX biopsies available for immunohistochemistry; 5 of them responded clinically and 8 were non-responders. In the 5 patients who responded to RTX, there was a significant decrease in P2X3-positive fibres (p=0.032), whereas in non-responders, P2X3-IR nerve fibre density did not change significantly. CONCLUSIONS: In patients with NDO, the numbers of P2X3-IR nerve fibres were increased in the suburothelium. There was a significant decrease in P2X3 immunoreactivity in responders to RTX, indicating a potential pathophysiological role for the P2X3 expressing fibres.

Diterpenes↗
PubMed2004

The perspective of a neurologist on treatment-related research in fecal and urinary incontinence.

Afferent innervation is important in sensing the degree of bladder fullness and in forming the input limb to involuntary detrusor contractions in neurogenic and probably also non-neurogenic detrusor overactivity. It is likely that homologous mechanisms are involved in control of the bowel. Accumulating evidence now suggests that in conditions of bladder hypersensitivity as well as non-neurogenic detrusor overactivity, there is up-regulation of unmyelinated nerve fibers expressing both the vanilloid receptor and purinergic receptors. The development of a selective neurotoxin that could successfully "deafferent" the bladder would have major therapeutic consequences. Women who respond best to neuromodulation through sacral nerve stimulation are those with a primary disorder of sphincter relaxation and a very large capacity without sensations of urgency or a hyperactive sphincter. For these women, neuromodulation may counteract the inhibitory effects of overactive sphincter afferents on the detrusor, and determination of the central nervous system level at which this response occurs may provide an explanation for the paradoxical finding that both urge incontinence and urinary retention are responsive to this intervention. Experimental evidence suggests that the "procontinence" reaction consists of an inhibitory effect on the detrusor and presumably the lower rectum resulting from contraction of the pelvic floor and the anal or urethral sphincter. Development of methods of enhancing the inhibitory reflex effect could lead to improved voluntary control of micturition and defecation for patients with neurogenic bladder overactivity or spinal cord lesions.

Fecal Incontinence↗
PubMed2004

Efficacy of sildenafil in the treatment of female sexual dysfunction due to multiple sclerosis.

PURPOSE: We assessed the tolerability, safety and efficacy of sildenafil for the treatment of women with sexual dysfunction secondary to multiple sclerosis, as well as the role of somatosensory evoked potential neurophysiological testing. MATERIALS AND METHODS: We performed a double-blind, randomized, placebo controlled, crossover study investigating the effects of sildenafil in women with multiple sclerosis and sexual dysfunction. Assessments were done by validated questionnaires. Pudendal and tibial evoked potentials were also recorded. RESULTS: A total of 19 women completed the 2 arms of the double-blind phase and 12 completed the optional open label extension phase. Statistically significant improvement following sildenafil was only reported in the lubrication domain of sexual function during the double-blind phase. There was no overall change in quality of life after sildenafil. There was a significant correlation between the latency of tibial and pudendal evoked potentials. CONCLUSIONS: Sildenafil only appeared to produce limited benefit in certain individuals with female sexual dysfunction. Some measure of the extent of neurological deficit in these patients could be ascertained from the latency of tibial evoked potentials, which correlated with pudendal evoked potentials. However, it could not predict the extent of sexual dysfunction. Sildenafil is unlikely to help all patients with neurogenic female sexual dysfunction.

Algorithms↗
PubMed2004

Urodynamic study of women in urinary retention treated with sacral neuromodulation.

PURPOSE: We investigated the action of sacral neuromodulation in restoring voiding function in women with urinary retention attributable to sphincter overactivity (Fowler's syndrome). MATERIALS AND METHODS: We recruited women within retention who were able to void following neuromodulation by temporary test stimulation or a permanent implant. Urethral pressure profiles, cystometry and sphincter electromyography were performed before and after neuromodulation. RESULTS: A total of 30 women 19 to 52 years old were recruited, including 21 with a permanent implant and 9 undergoing temporary stimulation. Mean maximum urethral closure pressure was elevated compared to expected pressure and it did not change significantly after neuromodulation. The electromyographic abnormality persisted during neuromodulation and voiding was often done with an interrupted flow. There was a slight increase in detrusor contractility. CONCLUSIONS: This evidence suggests that neuromodulation does not restore voiding in these patients by a direct relaxant effect on the sphincter. The modest increase in detrusor pressure appears to be sufficient to overcome the resistance of the overactive sphincter.

Adult↗
PubMed2004

Long-term results of sacral neuromodulation for women with urinary retention.

UNLABELLED: OBJECTIVE ; To review the long-term results of sacral nerve stimulation in the treatment of women with Fowler's syndrome, over a 6-year period at one tertiary referral centre. PATIENTS AND METHODS: Between 1996 and 2002, 26 women with urinary retention were treated by implanting a sacral nerve stimulator. Their case records were reviewed for follow-up, complications and revision procedures, and the most recent uroflowmetry results. RESULTS: There were 20 patients (77%) still voiding spontaneously at the time of review (with two having deactivated their stimulator because of pregnancy). Fourteen patients (54%) required revision surgery, and the most common complications included loss of efficacy, implant-related discomfort and leg pain. The mean postvoid residual volume was 75 mL and mean maximum flow rate 20.8 mL/s. CONCLUSION: In young women with retention, for whom there is still no alternative to lifelong self-catheterization, sacral neuromodulation is effective for up to 5 years after implantation. However, there was a significant complication rate, in line with other reports, which may be improved by new technical developments.

Adult↗
PubMed2003

The management of female voiding dysfunction: Fowler's syndrome -- a contemporary update.

PURPOSE OF REVIEW: Several aspects of voiding dysfunction in women remain under investigation, including standardization of the diagnosis and management of bladder outflow obstruction. This article describes a specific cause of urinary retention in young women, associated with a failure of urethral sphincter relaxation, and a treatment option that can restore voiding in this group of patients - sacral nerve electrical stimulation therapy. Recently there have been advances in the stimulator implantation technique, as well as in our appreciation of its mechanism of action. RECENT FINDINGS: Advances include the use of ancillary investigations such as urethral function tests as well as better understanding of the clinical profile of these patients. Improvements in the surgical technique include better methods of lead fixation and a less invasive surgical approach. Research suggests the action of neuromodulation is on the afferent pathway, though it remains to be shown whether this is at a spinal or supraspinal level. It is likely that sacral nerve stimulation has an indirect modulatory effect on detrusor contractility rather than a direct effect on the sphincter. SUMMARY: Experience of sacral nerve stimulation has increased over the past few years, and its application is expanding to other clinical domains. This knowledge has helped improve the therapy, which is particularly effective in the treatment of women with urinary retention. Although how it works is still not fully understood, this is something that is being addressed by ongoing research.

Adrenergic alpha-Agonists↗
PubMed2003

Bladder, bowel and sexual dysfunction in multiple sclerosis: management strategies.

Although patients with multiple sclerosis (MS) are likely to have problems with bladder, bowel and sexual function, these problems have often been neglected in the past. Bladder dysfunction produces symptoms of urgency, frequency and urge incontinence (due to bladder overactivity and incomplete emptying), and is found in up to 75% of patients with MS. The mainstay of drug treatment for neurogenic bladder overactivity is anticholinergic medication, although intravesical treatments have also been proposed, such as the vanilloids and botulinum toxin, as well as sublingual cannibanoids. There has been much progress with pro-erectile agents in recent years, notably the use of sildenafil citrate, which has been shown to be particularly efficacious in these patients. Other agents include apomorphine hydrochloride and newer phosphodiesterase 5 inhibitors; however, the efficacy of these drugs in patients with MS remains to be proven. Research in female sexual dysfunction is also progressing, although this aspect of patient well being has only recently been addressed; the reported development of a classification system for the condition is likely to help categorise future treatments. Unlike bladder and sexual dysfunction, there have been rather limited advances in the treatment of faecal incontinence and constipation specifically for patients with MS, despite a prevalence of up to 50%. This review highlights the strategies for these types dysfunction commonly seen in patients with MS, with report of recent pharmacological developments.

Constipation↗
PubMed2002

The ultrastructure of bladder lamina propria nerves in healthy subjects and patients with detrusor hyperreflexia.

PURPOSE: Detrusor hyperreflexia is a common finding in patients with neurological disease involving the spinal cord. In animal models it has been attributed to an emergent reflex mediated mostly by unmyelinated C-fibers. We describe and measure ultrastructural features of these nerves in the lamina propria in healthy subjects and patients with detrusor hyperreflexia. MATERIALS AND METHODS: Flexible cystoscopic bladder biopsies were obtained from 51 patients (8 controls, 8 with tropical spastic paraparesis, 23 with multiple sclerosis and 12 with spinal cord disease). Electron micrographs were obtained of every nerve profile seen in the midpoint of the biopsy specimen, and in each nerve profile a number of variables were measured and recorded. RESULTS: The mean nerve profile diameter was greater in patients with tropical spastic paraparesis (mean 2.19 microm.) compared to controls (1.59 microm.) and patients with multiple sclerosis (1.55 microm.) (p <0.001). We observed a sparse urothelial innervation by naked axonal varicosities but similar bare varicosities were more frequent in the superficial layer of the lamina propria. In deeper layers close membrane contacts between axonal varicosities and cells with cytological characteristics of myofibroblasts were seen. CONCLUSIONS: We described and measured ultrastructural characteristics of human bladder lamina propria nerves. The mean profile diameter is larger in patients with tropical spastic paraparesis compared to controls and patients with multiple sclerosis. This study provides a baseline to which other bladder disorders can be compared and may allow the effect of intravesical treatments on these nerves to be assessed. Some possible functional aspects of observed structural interrelationships are presented.

Adult↗
PubMed2002

Maximum urethral closure pressure and sphincter volume in women with urinary retention.

PURPOSE: In 1988 a syndrome of isolated urinary retention in young women that is associated with electromyographic abnormality of the striated urethral sphincter was described. It was hypothesised that urinary retention resulted from a failure of sphincter relaxation. The electromyographic abnormality causes overactivity of the muscle and may induce changes of work hypertrophy. If the hypothesis that the electromyographic abnormality is the cause of urinary retention is correct, we would expect the urethral sphincter to be enlarged and the urethral pressure profile to be increased in these women. We evaluated the role of static urethral pressure profilometry and transvaginal ultrasound in women in urinary retention. MATERIALS AND METHODS: A total of 66 women in complete or partial urinary retention underwent electromyography of the striated urethral sphincter using a concentric needle electrode, followed by urethral pressure profile and/or urethral sphincter volume measurement by transvaginal ultrasound. RESULTS: Maximum urethral closure pressure plus or minus standard deviation was significantly increased in patients with versus without the electromyographic abnormality (103 +/- 26.4 versus 76.7 +/- 18.4 cm. water, p <0.001). Maximum urethral sphincter volume was also increased in women with versus without the abnormality (2.29 +/- 0.64 versus 1.62 +/- 0.32 cm.3, p <0.001). CONCLUSIONS: The results of this study are consistent with the hypothesis that a local sphincter abnormality is the cause of urinary retention in a subgroup of women. Urethral pressure profilometry and sphincter volume measurement are useful for assessing these cases, especially when sphincter electromyography is not readily available.

Adolescent↗
PubMed2002

Bladder afferents and their role in the overactive bladder.

The role of afferent innervation of the bladder in the pathophysiology of urinary incontinence has become the focus of intense interest. In normal health, the afferent pathway is mediated largely by Adelta-fibers, which ultimately send information about the state of bladder fullness to the pontine micturition center via the periaqueductal gray matter. However, after spinal disruption, a different type of afferent pathway emerges, mediated by capsaicin-sensitive C-fibers that drive a spinal segmental reflex pathway, causing neurogenic detrusor overactivity. The common sources of afferent information for either pathway are likely to be afferents from the urothelium, lamina propria, and afferents that originate in the bladder wall. Ultrastructural investigations of the constituent neural elements of these structures contribute to our knowledge of their role in both health and disease and help provide a rational approach to treatment strategies. Evidence of the involvement of capsaicin-sensitive C-fibers in the spinal reflex pathway has been supported by the successful treatment of patients with neurogenic incontinence with intravesical capsaicin or its ultrapotent nonpungent analog, resiniferatoxin. On the other hand, capsaicin has not been shown to be clearly effective in treatment of overactive bladder caused by detrusor overactivity or suprapontine pathology without the emergent C-fiber-mediated reflex. It is hoped that continued investigation of neurotoxins that have the potential to act on afferent innervation will lead to other treatment strategies for bladder disorders and other disorders involving afferent dysfunction.

Afferent Pathways↗
PubMed2002

After a decade of intravesical vanilloid therapy: still more questions than answers.

Vanilloid sensitivity is a functional signature of a subset of unmyelinated fibres innervating the urinary bladder. The role that these nerves have in the physiological control of storage and voiding is unclear. However, after the bladder has been disconnected by spinal injury from the pontine micturition centre, vanilloid-sensitive fibres assume a central role in the reflex emptying of the bladder that occurs at low volumes. Intravesical vanilloid (capsaicin or resiniferatoxin) administration is beneficial in this disorder by "desensitising" these nerves. Resiniferatoxin is superior to capsaicin in terms of its tolerability profile. Investigators are moving rapidly to identify the mechanisms by which desensitisation to vanilloids occurs. Vanilloids induce lasting, but fully reversible, changes in gene expression, including downregulation of the vanilloid receptor subtype 1. It is hoped that application of gene chip technologies will address the global profile of vanilloid-induced changes in gene expression and their relative contribution to desensitisation. Drugs that target signalling mechanisms that bring about these changes in gene expression have obvious therapeutic potential.

Administration, Intravesical↗
PubMed2002

Sexual and urological dysfunction in multiple sclerosis: better understanding and improved therapies.

The fundamental strategy in treating multiple sclerosis patients with unstable bladders involves a combination of suppressing urgency and ensuring effective urinary drainage. Anti-cholinergics remain the first-line treatment, but alternative therapies are undergoing clinical trials. With a range of new pro-erectile oral medications available, interest has grown in treatment of multiple sclerosis-related erectile failure. Female sexual dysfunction is also now gaining some attention, with new classification criteria and methods for assessing and treating these patients.

Copulation↗
PubMed2002

The cause and natural history of isolated urinary retention in young women.

PURPOSE: Using a questionnaire mailed to patients we evaluated the course and natural history of urinary retention in women, of which the cause is attributed to electromyography abnormality of the striated urethral sphincter. Previously urinary retention in young women has often been considered to be due to multiple sclerosis or a manifestation of a psychogenic disorder. MATERIALS AND METHODS: A questionnaire was mailed to 216 women with abnormal sphincter electromyography and urinary retention. Of the 112 responses we analyzed the 91 from those who had been in complete urinary retention. RESULTS: Mean patient age at the onset of complete retention was 27.7 years (range 10 to 50). No patients had neurological features indicating a cauda equina lesion or central demyelination and none had progressed to features of a general neurological disorder. Mean maximum bladder capacity at the initial episode of complete retention was 1,208 ml. Of the women 65% reported an event that had apparently precipitated urinary retention, most commonly a gynecologic surgical procedure using general anesthesia. Sacral neuromodulation was the only therapeutic intervention that restored voiding. CONCLUSIONS: The concept of an organic cause of urinary retention in otherwise healthy young women has considerable importance in terms of correct management. Neurological investigation in these women does not reveal underlying neurological disease. It is thought that this disorder is due to a primary failure of relaxation of the striated urethral sphincter.

Adolescent↗