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PubMed2003

Morphology, phenotype and ultrastructure of fibroblastic cells from normal and neuropathic human detrusor: absence of myofibroblast characteristics.

PURPOSE: Fibroblasts are functionally diverse and fibroblastic cells with smooth muscle-like characteristics (myofibroblasts) regulate smooth muscle activity in certain tissues. The presence of myofibroblasts has been reported in the bladder with important implications for normal function and detrusor overactivity. We assessed fibroblastic cell characteristics to discern features suggesting a myofibroblast phenotype in normal or neuropathic human detrusor. MATERIALS AND METHODS: A total of 25 control samples were obtained from cadaveric organ donors or patients with a mean age of 42.3 years investigated for hematuria and compared with samples from 18 patients with a mean age of 37.4 years with neurogenic detrusor overactivity. Morphology, phenotypic expression of various markers and the ultrastructure of each fibroblastic cell visible in multiple sections from each specimen was evaluated by 2 independent assessors. RESULTS: Fibroblastic cells were observed throughout the smooth muscle and connective tissue. They were located peripherally on muscle fascicles and had a polar stellate appearance with processes ramifying in interfascicular planes and muscle. They possessed vimentin-like immunoreactivity and weak c-kit-like immunoreactivity but not desmin or alpha-smooth muscle actin-like immunoreactivity. Ultrastructurally they showed dilated rough endoplasmic reticulum with a moderately electron dense amorphous content and prominent golgi complexes. Nuclei had clumped peripheral heterochromatin. There were extensive flattened processes that lacked basal laminae. There was no specific contact with nerve fibers or smooth muscle. Neuropathic bladder samples did not differ overtly from those of controls. CONCLUSIONS: The detrusor possesses an extensive network of fibroblastic cells and processes. No evidence of myofibroblast differentiation was discerned in normal or neuropathic detrusor, although a minority subpopulation or regional variability in cellular phenotype could not be excluded.

Adult↗

PubMed1994

Simple bladder filling with a cough stress test compared with subtracted cystometry for the diagnosis of urinary incontinence.

OBJECTIVE: Our purpose was to compare the diagnostic efficacy of observing urine loss during simple bladder filling (without pressure measurement) and a cough stress test, with multichannel subtracted cystometry. STUDY DESIGN: The urodynamic records of 77 women complaining of urinary incontinence were reviewed. All women had undergone a full evaluation that included a standardized history and physical examination, urinalysis and urine culture, uroflowmetry with measurement of postvoid residual urine, a cough stress test performed during and after simple retrograde bladder filling, and multichannel subtracted cystometry. The results of simple bladder filling and the cough stress test were recorded as "urge incontinence," "stress incontinence,"mixed incontinence," or "incontinence not demonstrated." The subtracted cystometrogram was then performed, and the urodynamic diagnoses were recorded as "detrusor instability," "genuine stress incontinence," "mixed incontinence," or "incontinence not demonstrated." The records were reviewed, and the results of simple bladder filling with a cough stress test were compared with those obtained by subtracted multichannel provocative cystometry. RESULTS: With the subtracted multichannel cystometrogram used as the "gold standard" for diagnosis, the demonstration of "urge incontinence" during simple bladder filling had a sensitivity of 64% and a specificity of 86.8% for the demonstration of detrusor instability during cystometry, with a positive predictive value of 83.3% and a negative predictive value of 70.2%. The demonstration of "stress incontinence" during simple bladder filling had a sensitivity of 88.1% and a specificity of 77.1% for the demonstration of "genuine" stress incontinence during cystometry, with a positive predictive value of 82% and a negative predictive value of 84.4%. CONCLUSIONS: The demonstration of urge incontinence during simple bladder filling is a reliable predictor of detrusor instability, but its absence is less reliable in excluding detrusor overactivity as a cause of urinary incontinence. Similarly, the clinical demonstration of stress incontinence during simple bladder filling is predictive of the presence of "genuine" stress incontinence during subtracted multichannel provocative cystometry. The inability to demonstrate stress incontinence during simple bladder filling is highly correlated with the absence of "genuine" stress incontinence during complex urodynamic testing. Simple bladder filling is a reliable method of diagnosing urinary incontinence. In many cases it can replace complex urodynamic testing, particularly if the proposed treatment for the condition carries a low level of risk, and is helpful in selecting patients who need more extensive evaluation.

Cough↗

PubMed2005

Capsaicin receptor TRPV1 in urothelium of neurogenic human bladders and effect of intravesical resiniferatoxin.

OBJECTIVES: To study TRPV1 immunoreactivity in the urothelium of patients with neurogenic detrusor overactivity (NDO) before and after treatment with resiniferatoxin (RTX) and controls. Functional capsaicin TRPV1 receptors have been demonstrated in urothelial cells of rodent urinary bladder, and TRPV1-knockout mice exhibit diminished nitric oxide and stretch-evoked adenosine triphosphate release from urothelial cells. In patients with NDO, TRPV1 suburothelial nerve density is increased, which is reversed by successful treatment with intravesical RTX. However, the role of urothelial TRPV1 in human bladder disorders is unknown. METHODS: Flexible cystoscopic bladder biopsies were obtained from 14 patients with NDO before and after treatment with RTX and from 8 control patients. Using a specific antibody for immunostaining, TRPV1 immunoreactivity in the urothelium was quantified by image analysis. RESULTS: TRPV1 immunoreactivity was observed in basal and apical urothelial cells. Basal cell layer TRPV1 immunoreactivity was significantly increased in NDO compared with control bladders (P = 0.003). In 5 patients who responded clinically to RTX, basal cell layer and total urothelial TRPV1 immunoreactivity decreased significantly after treatment (P = 0.032 and P = 0.016, respectively). The decreases in the basal cell layer TRPV1 immunoreactivity after RTX were comparable to the decreases in suburothelial TRPV1 nerve fibers in the biopsies previously studied from the same patients. CONCLUSIONS: Increased urothelial TRPV1 in patients with NDO may play a role in the pathophysiology, in concert with increased TRPV1 nerve fibers. Although it is not known whether similar pathogenic mechanisms are involved in the increase of urothelial and neuronal TRPV1, both may be targeted by successful RTX therapy.

Administration, Intravesical↗

PubMed1992

The action potential and net membrane currents in isolated human detrusor smooth muscle cells.

The basic electrophysiological properties of the human detrusor have been investigated in vitro using isolated single cells obtained by collagenase digestion of bladder biopsy specimens. Recordings were made using the 'whole-cell patch clamp' technique using either a physiological filling solution or one in which cesium was used to block any outward current. Spontaneous and stimulated action potentials have been recorded and we have performed the first voltage clamp analysis of the currents that underlie the action potential in human detrusor. The depolarising phase of the action potential occurs by an inward current of Ca2+ ions which can be shown to be of sufficient magnitude to support the rate of upstroke. Repolarisation occurs due to an outward K+ current that is partially Ca2+ dependent. The techniques described here permit the investigation of the ionic basis for the control of contractility in the human bladder and may permit the characterisation of any underlying abnormality in the overactive detrusor.

Action Potentials↗

PubMed2006

Central acute D2 stimulation worsens bladder function in patients with mild Parkinson's disease.

PURPOSE: The different roles of D1 and D2 dopamine receptors in LUT behavior have been demonstrated in animal studies. In particular D2 selective agonists and D1 selective antagonists seem to produce a reduction of the bladder capacity in conscious rats. This finding has never been confirmed in human studies. Thus, in this study we investigated the role of D1 and D2 agonists/antagonists on LUT behavior in patients with PD. MATERIALS AND METHODS: A total of 87 patients with mild PD were evaluated. Patients were evaluated with urodynamic studies (cystometry followed by a pressure flow study with perineal floor electromyography) performed in off status and after oral administration of 250 mg of LD. In 70 patients a third urodynamic evaluation was conducted in one of the following conditions: after simultaneous administration of 250 mg oral LD and 60 or 120 mg oral domperidone (D2 peripheral antagonist); after simultaneous administration of 250 mg oral LD and 25, 50 or 150 mg intramuscular L-sulpiride (D2 central and peripheral antagonist). Several urodynamic parameters were evaluated and results obtained in different conditions compared. RESULTS: LD alone worsened detrusor overactivity: in particular, a reduction of first urinary sensation, involuntary detrusor contraction threshold (reflex volume) and bladder capacity was observed. L-sulpiride (central and peripheral D2 antagonist) coadministration counteracted the worsening in a dose dependent manner. Domperidone (peripheral D2 antagonist) coadministration failed to determine the same counteraction. CONCLUSIONS: According to our results, a central acute D2 stimulation seems to be responsible of a reduction of bladder capacity with worsening of detrusor overactivity in patients with mild PD.

Domperidone↗

PubMedDate not supplied

Is aging a real risk factor for urological pathologies in men and women?

OBJECTIVE: With the progressive aging of the population in industrialized countries, urological pathologies are also increasing and creating a socio-sanitary problem for the community. To investigate this problem we retrospectively analyzed a heterogeneous sample of 283 patients, 134 males and 149 females who attended our urodynamics laboratory. METHODS: The female patients were subdivided into 6 categories and the male patients into 7 categories according to their urodynamic diagnoses. Their age distributions were compared with those of the population of the region of Lazio in Italy in order to calculate the "risk tendency". RESULTS AND CONCLUSIONS: The most frequent pathologies in males were bladder outlet obstruction (BOO) associated or not with detrusor overactivity (DO), and in females it was cystocele associated or not with DO or obstruction. There is a significant increase in these urological pathologies in older people. The relative risks for the females increase from age 20-29, stabilize at around 50 to 69 years and decline thereafter. The risk approximately doubles every ten years of age from 20 to 50. At ages 50-69 the risk is about 8 or 9 times higher than the risk at age 20-29 and double that of women aged over 70 years. The risk for the males also approximately double for every ten years of age. Men aged 60-69 have about 25 times the risk of these pathologies than men aged 20-29, and in the oldest men, those over 70 years, the risk is almost 40 times as high.

Adult↗

PubMed2007

Urodynamic findings in children with myelomeningocele after untethering of the spinal cord.

PURPOSE: The effect on bladder function of tethered spinal cord release in individuals with myelomeningocele differs in published studies, and the benefit has been the subject of debate. We studied the urodynamic findings in a consecutively treated population. MATERIALS AND METHODS: Of 120 children born with myelomeningocele between 1986 and 1999, 20 underwent surgery for the tethered cord syndrome at a median age of 8 years (range 2 to 13). Time points for cystometry used for comparison were before symptoms at a median age of 20 months (range 9 to 106), a median of 5 months preoperatively (1 to 33) and at 12 months postoperatively (6 to 19). Severe bladder dysfunction was defined as basal pressure more than 40 and/or overactivity greater than 60 cm H2O, moderate dysfunction as basal pressure 20 to 40 and/or overactivity 20 to 60 cm H2O, and mild dysfunction as basal pressure less than 20 cm H2O. RESULTS: Of the 20 patients who underwent untethering 7 had improvement to a milder dysfunctional level, while 1 deteriorated postoperatively. Six patients experienced deterioration in bladder dysfunction level before untethering, and all returned to a milder level afterward. A total of 10 patients had unchanged bladder dysfunction before symptoms and preoperatively. Of these patients 9 (90%) continued unchanged after untethering, while 1 deteriorated. CONCLUSIONS: After untethering secondary to myelomeningocele 35% of the patients experienced improved bladder function and 5% deteriorated. All of the patients who deteriorated before untethering improved afterward, and 90% of those who were stable preoperatively continued to be stable postoperatively. Therefore, regular evaluation of bladder function in children with myelomeningocele should be performed.

Child↗

PubMed2005

Intraoperative recording of sacral root nerve signals in humans.

Electroneurographic signals were intraoperatively recorded from the S3 sacral nerve root in two SCI patients. The aim of this study was to record afferent nerve signals in response to mechanical stimulation of the urinary bladder, rectum, and dermatome. Such signals could be used in an implantable neuroprosthesis to treat neurogenic detrusor overactivity. In both patients a neural response was recorded from the dermatome and the rectum, but from the bladder only in one patient. The results were consistent with results from animal and other human studies. Further studies are however, needed because the number of subjects investigated remains low.

Adult↗

PubMed1998

Vesicourethral dysfunction associated with multiple sclerosis: clinical and urodynamic perspectives.

PURPOSE: We investigate the association of clinical and urodynamic findings with corresponding clinical grade and possible predictors of clinical grade of multiple sclerosis (MS). MATERIALS AND METHODS: A total of 90 patients, 28 to 62 years old (mean age 45.8 +/- 12.1), with the clinical syndrome of MS were consecutively and prospectively studied. All patients were subjected to detailed video urodynamic evaluation and electromyography of the external urethral sphincter. RESULTS: Urodynamic evaluation revealed detrusor hyperreflexia in 52 patients (57.7%), detrusor external sphincter dyssynergia in 27 (30%) and hypocontractility or areflexia of the detrusor in 15 (16.6%). Residual urine varied widely from 50 to 900 ml. Decreased compliance with areflexia was seen in 5 patients (5.5%) and nonrelaxing sphincter (but not contracting) with bladder hypercontractility was noted in 9 (10%). Statistical analysis followed comparison of 2 proportions. When patients with a less severe form (grades 1 and 2) were differentiated from those with a more severe form of MS (grade 3), we observed a significant difference only in incontinence, high post-void residual, leg spasticity, urinary stones, hydronephrosis, type 3 detrusor external sphincter dyssynergia, no electromyography activity and positive sharp waves. The variables with the highest predictive value between the groups were urinary stones, sepsis, type 3 detrusor external sphincter dyssynergia and no electromyography activity of the external urethral sphincter (100%). CONCLUSIONS: Proper identification of the bladder and external urethral sphincter status, especially exclusion of detrusor overactivity or a dyssynergic response of the external urethral sphincter, will prevent complications that may result in deterioration of quality of life.

Adult↗

PubMed2006

A selective alpha1A-adrenoceptor antagonist inhibits detrusor overactivity in a rat model of benign prostatic hyperplasia.

PURPOSE: Alpha(1)-adrenoceptor antagonists relax the obstructed prostatic urethra and suppress the irritative symptoms frequently observed in patients with benign prostatic hyperplasia. We investigated the effects of 3 alpha(1)-adrenoceptor antagonists on urodynamics in rats with hormone induced benign prostatic hyperplasia to determine which alpha(1)-adrenoceptor subtype selective antagonists would suppress irritative symptoms. MATERIALS AND METHODS: Rats were treated with testosterone and 17beta-estradiol by weekly intramuscular injections. After 4 weeks a pressure flow study was done and the effects of the alpha(1)-adrenoceptor antagonists KMD-3213 silodosin, tamsulosin and prazosin on urodynamics were compared. We especially investigated the involvement of the bladder and prostatic urethra to clarify the mechanism of detrusor overactivity expression. RESULTS: Hormone treatment induced benign prostatic hyperplasia and resulted in detrusor overactivity, as determined by cystometry. Baseline perfusion urethral pressure and the phenylephrine induced increase in it were significantly higher in rats with vs without benign prostatic hyperplasia. Cystometry in hormone treated female rats did not show detrusor overactivity. KMD-3213 decreased detrusor overactivity, similar to other alpha(1)-adrenoceptor antagonists. CONCLUSIONS: These results suggest that an excessive response to sympathetic nerve stimulation, which is mainly mediated via alpha(1A)-adrenoceptor, in the hypertrophied prostate gives rise to detrusor overactivity. Furthermore, the alpha(1A)-adrenoceptor selective antagonist KMD-3213 would be suitable for improving irritative symptoms in patients with benign prostatic hyperplasia.

Adrenergic alpha-1 Receptor Antagonists↗

PubMed1995

Tethered spinal cord: the effect of neurosurgery on the lower urinary tract and male sexual function.

OBJECTIVE: To determine the effect of neurosurgical untethering on the lower urinary tract and male sexual function, in patients with tethered spinal cord. PATIENTS AND METHODS: Thirty-six children with tethered spinal cord due to neurospinal dysraphism were assessed clinically and urodynamically before and after surgical untethering. Sexual function was evaluated in 14 boys before and after neurosurgery. In young boys, the assessment was by parental observation and was considered normal if erections had been observed regularly, or if the child had mentioned having an erection at any time. Older patients were asked if they had achieved voluntary erections and whether or not they were able to ejaculate. RESULTS: The mean follow-up was 91 months and the mean follow-up after neurosurgery was 34 months. A lasting improvement of urinary tract function occurred in only one patient, while another became worse. Seven children had temporary changes of bladder/sphincter function; two developed detrusor overactivity with sphincter dyssynergia and five had signs of bladder denervation. Long-term follow-up showed no permanent changes of lower urinary tract function in 94% of 34 patients. Sexual function was considered normal in 13 boys. One boy apparently gradually lost erectile ability before untethering and regained it after surgery, while another boy had erectile dysfunction post-operatively for almost 6 months. CONCLUSION: Changes in bladder-sphincter function after untethering are usually transient and often the result of partial denervation. Although a small group of children seem to benefit from untethering, others can become worse and the individual outcome cannot be predicted. Erectile dysfunction can occur and parents and patients have to be informed of this possible complication. As pre-operative progression of neurological symptoms and post-operative denervation were observed only in patients with myelomeningocele and lipomyelomeningocele, this group may be distinct from patients with occult forms of spinal dysraphism. The natural history in the latter group of patients is unclear and a beneficial effect of prophylactic untethering remains to be proven by controlled prospective studies.

Adolescent↗

PubMed1996

TENS: a treatment option for bladder dysfunction.

To ascertain the mode of action and benefits of transcutaneous electrical nerve stimulation (TENS) in detrusor overactivity, stress incontinence and interstitial cystitis, an English-language literature search using Medline (1984-1995) was undertaken with detrusor instability, incontinence, interstitial cystitis, neuromodulation, transcutaneous electrical nerve stimulation and urodynamics as keywords and the material so identified was reviewed. The mode of action of TENS and optimal stimulation parameters in bladder dysfunction remain unclear. Lack of strict selection criteria and deficient reporting of subjective and objective outcomes precluded full assessment of therapeutic efficacy. A beneficial effect was evident in some studies of detrusor overactivity and interstitial cystitis. A trial of TENS in detrusor overactivity and interstitial cystitis refractory to conventional therapy would seem justified. Continued experimental research and further clinical studies will lead to refinement of the treatment modality.

Cystitis, Interstitial↗

PubMed2002

Value of increase in bladder capacity in treatment of refractory monosymptomatic nocturnal enuresis in children.

OBJECTIVES: To evaluate children with refractory monosymptomatic nocturnal enuresis to determine whether detrusor overactivity (DOA) plays a role in 4 weeks of unsuccessful treatment with retention control training (RCT); whether an increase in bladder capacity can eventually be obtained by RCT plus oxybutynin; and whether the increase in capacity is the primary key to success. METHODS: Sixty-eight children with refractory monosymptomatic nocturnal enuresis were included. They all had a maximal cystometric capacity less than the age-expected value. RCT was done by water loading and retention to the point of urgency once daily. During training, changes in bladder capacity were evaluated by voiding charts. If after 4 weeks of RCT, less than a 10% increase in bladder capacity was noted, oral oxybutynin was added. RESULTS: The incidence of DOA was 66%. After 4 weeks of RCT, the bladder capacity increased in 20.6%. Combining RCT with oxybutynin led in the end to normalization of the bladder capacity in 79.4%. Older age and high-pressure DOA negatively influenced the ability to increase the bladder capacity. Fifteen children became completely dry, mainly by converting enuresis to nocturia. CONCLUSIONS: Unsuccessful RCT is often caused by DOA, especially if a bladder capacity rise of at least 10% cannot be achieved within 4 weeks. If oxybutynin is added to the treatment, normalization of bladder capacity can be obtained in most. This increased bladder capacity cures enuresis only in a minority by sharpening their arousal and provoking nocturia.

Administration, Oral↗

PubMed2005

Changes in detrusor smooth muscle myosin heavy chain mRNA expression following spinal cord injury in the mouse.

AIMS: Smooth muscle myosin heavy chain (SMMHC) isoform composition has been shown to be developmentally regulated and to be associated with functional changes in smooth muscle activity. In this study, we sought to determine expression patterns of SMMHC isoforms in a murine model of spinal cord injury (SCI) and to compare these expression patterns to neurologic, cytometric, and morphometric findings. MATERIALS AND METHODS: Baseline cystometry was performed on adult, female mice followed by either thoracic spinal cord transection (SCI) or sham operation (Sham). At 1, 3, or 6 weeks postoperatively neurologic evaluation and cystometry were performed, bladders were harvested, and expression patterns of SMMHC isoforms (SM1 vs. SM2 and SMA vs. SMB) were assessed by RT-PCR. Morphometrics utilizing computer-assisted color image analysis was also performed on all bladders. RESULTS: There was a significant increase in bladder weight and capacity 1 week following SCI which normalized over time, however, morphometric analysis did not reveal an alteration in tissue composition amongst the three groups. One week following SCI, SM1 was predominantly expressed over SM2 and began to normalize at 3 weeks. This coincided with the emergence of reflex voiding and detrusor overactivity. SMA was expressed following SCI only, and the number of bladders found to express SMA decreased with increasing duration since SCI. CONCLUSIONS: Smooth muscle myosin heavy chain mRNA expression patterns appear to be affected by SCI. We believe the induction of SMA may be a factor in altered bladder function following injury.

Animals↗

PubMed2004

Long-term bladder function in patients with locally advanced cervical carcinoma treated with neoadjuvant chemotherapy and type 3-4 radical hysterectomy.

BACKGROUND: The objective of the current study was to evaluate the incidence of long-term bladder dysfunction after type 3-4 radical hysterectomy in patients with locally advanced cervical carcinoma treated with neoadjuvant chemotherapy (NACT). METHODS: A case-control study was conducted to evaluate the occurrence of long-term bladder dysfunction in 76 patients with International Federation of Gynecology and Obstetrics Stage IB-IIA (> 4 cm), Stage IIB, and Stage III cervical carcinoma who underwent type 3-4 radical hysterectomy after NACT. Preoperative assessment included acquisition of a standardized urogynecologic history, evaluation of severity of urinary incontinence symptoms, maintenance of a 3-day voiding diary, pelvic examination, urogynecologic physical examination, urodynamic assessment, and estimation of hydronephrosis. Follow-up was carried out at least 12 months after surgery. RESULTS: Urinary symptoms (sensory loss, difficult micturition, severe urinary incontinence) were reported by 20 patients (26%). Eighteen patients (24%) had a normal urodynamic profile, 16 patients (21%) had detrusor overactivity, 22 patients (29%) had urodynamic stress incontinence, 2 patients (2%) had aconctractile detrusor, and 18 patients (24%) had mixed urinary incontinence. The length of vagina removed was significantly greater among patients who had detrusor overactivity and mixed urinary incontinence compared with patients who had a normal diagnosis. CONCLUSIONS: The observed rate of bladder dysfunction was higher than the corresponding rate reported in the literature (76%). Three main disturbances were found: detrusor overactivity (21%), mixed urinary incontinence (24%), and de novo stress incontinence (21%). Detrusor overactivity was related to a prevalence of hypertonic bladder. Among patients who underwent type 4 radical hysterectomy, the extent of caudal resection of rectovaginal ligaments and vaginal tissue was found to be more strongly associated with bladder dysfunction than was the extent of lateral parametrial resection. Despite the fact that 76% of patients had abnormal urodynamic parameters, most patients were satisfied with their voiding condition.

Adenocarcinoma↗

PubMed2004

The open bladder neck: a significant finding?

Women with lower urinary tract symptoms were retrospectively studied. They were all investigated using a urinary symptoms questionnaire, a frequency-volume chart and videocystourethrography. An open bladder neck was recorded at maximum cystometric capacity with the patient standing in the left lateral position, if contrast medium entered the proximal urethra at rest in the absence of a detrusor contraction or an increase in intra-abdominal pressure. Women with neurological disorders were excluded. Of 4500 women, 2,593 (57.6%) had a single urodynamics diagnosis and were included in the study: 1207 (46.5%) had urodynamics diagnosis of urodynamic stress incontinence, 558 (21.5%) had detrusor overactivity, 118 (4.6%) had sensory urgency, and 710 (27.4%) had a normal urodynamic study. Out of the 2,593 women included, 776 women (29.9%) had an open bladder neck at rest while 1817 (70.1%) had a closed bladder neck at rest. Only 45% (542/1207) of women with urodynamic stress incontinence had an open bladder neck at rest. Seventy percent (542/776) of women with an open bladder neck had a diagnosis of urodynamic stress incontinence whilst 73% of women with detrusor overactivity and 93% of those with sensory urgency had a closed bladder neck. An open bladder neck at rest is not diagnostic of urethral sphincter incompetence but is associated with urodynamic stress incontinence. It is not associated with urgency as few women with sensory urgency and detrusor overactivity were found to have an open bladder neck. Imaging the bladder neck at rest has questionable value.

Adult↗

PubMed2003

Relationship of bladder dysfunction to lesion site in multiple sclerosis.

PURPOSE: We investigated the relationship of voiding dysfunction type and the lesion site in patients with multiple sclerosis. MATERIALS AND METHODS: Voiding dysfunction was evaluated in 32 patients with multiple sclerosis using the International Prostate Symptom Score and urodynamic tests. Lesion sites were determined by combined neurological examination and magnetic resonance imaging findings. RESULTS: Compared with reports from Western countries the ratio of emptying-to-filling symptoms was high in Japan. Of urinary symptoms only filling correlated with disability status and disease duration. Urinary symptoms were not related to lesion sites. Urodynamic evaluation revealed detrusor hyperreflexia in 14 of 32 patients, hyporeflexia or areflexia in 12, detrusor hyperreflexia with impaired contractile function in 4, a low compliance bladder in 1 and normal function in 1. Of 14 patients with hyperreflexia 13 had overactive sphincter concurrently. Incompetent sphincter was identified in 2 patients who had detrusor hyperreflexia with impaired contractility and in 1 with a low compliance bladder. A significant correlation was noted for a pontine lesion and detrusor hyporeflexia, and for a cervical cord lesion and detrusor-sphincter dyssynergia. CONCLUSIONS: Detrusor hyporeflexia and detrusor-sphincter dyssynergia are indicative of a pontine and cervical spinal cord lesion, respectively. Thus, the lesion site in the central nervous system may be a major determinant of the type of bladder and urethral sphincter dysfunction. The high prevalence of emptying symptoms in Japanese patients may reflect the prevalence of detrusor hyporeflexia and detrusor-sphincter dyssynergia.

Adolescent↗

PubMed2006

Gap junction channel activity in short-term cultured human detrusor myocyte cell pairs: gating and unitary conductances.

Several independent lines of investigation indicate that intercellular communication through gap junctions modulates bladder physiology and, moreover, that altered junctional communication may contribute to detrusor overactivity. However, as far as we are aware, there are still no direct recordings of gap junction-mediated intercellular currents between human or rat detrusor myocytes. Northern and Western blots were used to identify connexin expression in frozen human bladder tissue and short-term cultured human detrusor myocytes. Double whole cell patch (DWCP) recording revealed that human detrusor myocyte cell pairs were well coupled with an average junctional conductance of 6.5 +/- 4.6 nS (ranging from 0.1 to 15 nS, n = 22 cell pairs). Macroscopic gap junction channel currents in human detrusor myocytes exhibited voltage dependence similar to homotypic connexin43. The normalized transjunctional conductance-voltage (G(j)-V(j)) relationship was symmetrical and well described by a two-state Boltzmann relation (G(min) approximately 0.33, V(0) = 63.6 mV, Z = 0.117 or equal to 2.95 gating charges), suggestive of a bilateral voltage-gated mechanism. In symmetric 165 mM CsCl, the measured single-channel slope conductance was approximately 120 pS for the fully open channel and approximately 26 pS for the major substate. Occasionally, other subconductance states were also observed. The single-channel mean open time declined with increasing V(j), accounting for the V(j)-dependent decline of macroscopic junctional current. Qualitatively similar electrophysiological characteristics were observed in DWCP of freshly isolated rat detrusor myocytes. These data confirm and extend previous observations and are consistent with reports in other smooth muscle cells types in which Cx43-mediated intercellular communication has been identified.

Animals↗