Resonance(®) metallic stent in patients with ureterocutaneostomies.

PURPOSE: To evaluate the effectiveness and the safety of Resonance(®) stents in patients with ureterocutaneostomies (UCS). MATERIALS AND METHODS: We retrospectively enrolled all patients with UCS who presented with impaired ureteral drainage with traditional polymeric ureteral prosthesis. Preoperative and follow-up (1, 3, 6, 12 months) workup, after Resonance(®) placement, included: medical history, physical examination, serum laboratory tests, urinalysis, urine culture and urinary tract imaging by ultrasound, administration of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) and an evaluation of patients' satisfaction rate. In addition, the number of emergency department patient admissions and hospitalizations occurred 1 year before and after the stent Resonance(®) placement was noted. RESULTS: Twenty-five renal units in 14 patients with UCS were included. Statistically significant improvements in creatinine serum levels, patients' satisfaction rate, hydronephrosis and number of urinary tract infections (UTI) were found at 1-, 3-, 6-, and 12-month follow-up compared to baseline. Statistically significant differences in EORTC QLQ-C30 were detected only in Emotional, Social and Global QoL domains before and after Resonance(®) placement (p < 0.0001). At inclusion, a total of 39 referrals to ED were recorded; at 1-year follow-up, only five cases of ED presentations have been recorded (p < 0.01). At the same endpoints, the number of hospitalizations was 18 and 2, respectively (p < 0.05). Failure rate was 8.3%. CONCLUSION: At 1-year follow-up, Resonance(®) stents are effective and safe in patients with UCS refractory to polymeric ureteral prosthesis, reporting evidence for significant improvements in hydronephrosis rate, renal function, UTI, and patients' satisfaction rate and QoL.

Cystoman® and calculi: a good alternative to standard therapies in preventing stone recurrence.

To assess the efficacy and tolerability of D-mannose-containing product (Cystoman(®)) in preventing recurrence in patients who underwent surgical treatment for infection related urinary stones. From January 2011 to February 2013 we have enrolled all consecutive patients affected by staghorn calculi and recurrent urinary tract infections (UTIs). All patients recommended for surgery were scheduled for percutaneous nephrolithotomy. The study agent was administered daily for 5 months after surgical procedure. At baseline and 5-month follow-up all patients underwent abdominal Computed Tomography (CT) scan and they also completed Medical Outcomes Study short-form, 36-item questionnaire (SF-36). They performed urine and urine culture monthly. The primary endpoints were the assessment of the efficacy with regard to infection-related urinary stone recurrence and the tolerability of Cystoman(®). The secondary endpoint was the evaluation of quality-of-life symptoms. During the study period, a total of 27 patients were included in the study. The data from 25 patients were analyzable. Seventeen patients (68%) did not report UTIs during follow-up. Eight patients (32%) remained infected and the average number of UTIs was 2.6 ± 1.6 in 5 months. At 5-month follow-up 17 (68%) patients were free from stones recurrence; in 8 (32%) cases CT scan revealed stone recurrence with an average stone diameter of 1.1 ± 0.4 cm. In nonrecurring patients, 2 (11.7%) reported an average of 1.5 ± 0.7 UTIs episodes; in recurring patients, 6 (75%) showed 3 ± 1.67 of UTIs episodes. Statistically significant differences were seen in the occurrence of UTIs episodes were detected between nonrecurring stone patients and recurring patients (p < 0.05). Moreover, statistically significant changes were detected in SF-36 scores from baseline to month 5 in the categories of physical functioning and energy/fatigue (p < 0.05). Cystoman(®) is effective in preventing infection-related urinary stones.

Technical aspects of botulinum toxin type A injection in the bladder to treat urinary incontinence: reviewing the procedure.

AIMS: Standardise the injection technique with botulinum toxin type A (BoNT A) in the bladder of patients with overactive bladder (OAB) [idiopathic overactive bladder (iOAB) or neurogenic overactive bladder (nOAB) with urinary incontinence], using a literature review and a survey of an International expert panel. METHODS: PubMed literature searches of BoNT A in adults with iOAB/nOAB together with a survey of 13 experts from 10 countries. RESULTS: Data from 21 articles and completed questionnaires were collated. The procedure can be carried out in an out-/inpatient setting. Dose used in clinical studies vs. clinical practice was 300 and 200 U for nOAB and 200 and 100 U for iOAB. Recent studies have also demonstrated that there are no clinically relevant benefits between 100 and 150 U in iOAB or between 300 and 200 U in nOAB, though adverse effects are increased with higher doses. Usually, 30 sites for nOAB (range: 6.7-10 U/ml) and 20-30 sites for iOAB (range: 5-10 U/ml) are injected in clinical studies vs. 20-30 sites of 1 ml/injection for 200 U in nOAB and 10-20 sites of 0.5-1 ml/injection for 100 U in iOAB in clinical practice. BoNT A is usually injected directly into the detrusor, sparing the trigone. Flexible or rigid cystoscopes are used. The needle should be typically 22-27 gauge and 4 mm in length and should have a stopper to avoid any leakage or perforation of the bladder wall while ensuring a targeted injection. CONCLUSION: Based on the literature and survey analysis, recommendations are proposed for the standardisation of the injection procedure.

Lower urinary tract symptoms and urodynamic dysfunction in clinically isolated syndromes suggestive of multiple sclerosis.

BACKGROUND AND PURPOSE: Urinary symptoms associated with multiple sclerosis (MS) are common and negatively impact on quality of life, representing a considerable psychosocial and economic burden, often requiring care and hospitalization. Although the importance of identifying and adequately treating urinary symptoms in MS is now well recognized, there is no information, to date, about the real prevalence and impact of bladder symptoms in patients with clinically isolated syndromes (CISs) suggestive of MS. METHODS: The aim of the present study was to investigate, in a cohort of patients with a diagnosis of CIS suggestive of MS, the prevalence of urinary tract symptoms, their impact on quality of life measures and their association with functional urodynamic dysfunctions. Patients underwent a complete neurological and urological visit, urodynamic investigation and the MSQoL-54 questionnaire. RESULTS: Twenty-eight consecutive patients presenting with CISs were enrolled in the study; 53.6% of CIS patients reported urinary symptoms, 46.7% reporting irritative symptoms, 33.3% both irritative and obstructive symptoms and 20% obstructive symptoms alone. Urodynamic abnormalities were observed in 57.1% of the CIS patients. In 17.9% of the CIS patients urodynamic dysfunctions were asymptomatic. The presence of urinary symptoms was associated with lower scores on specific quality of life domains, particularly in women with obstructive symptoms. CONCLUSIONS: A high prevalence of urinary symptoms and urodynamic dysfunctions in patients with CISs and an association of urinary symptoms with quality of life measures were found. These results highlight the importance of identifying and optimally treating urinary symptoms also at the very early stages of MS.

Botulinum toxin A modulates afferent fibers in neurogenic detrusor overactivity.

BACKGROUND: Although botulinum toxin (BoNT/A) injected into the detrusor muscle improves overactive bladder symptoms in patients with neurogenic detrusor overactivity, how it does so remains unclear. In this study, we investigated whether BoNT/A improves detrusor overactivity by modulating bladder afferent activity. METHODS: To do so, during urodynamic assessment, we tested the soleus muscle Hoffmann (H) reflex during bladder filling before and after intradetrusor BoNT/A in patients with Parkinson's disease (PD) and in patients with complete chronic spinal cord lesion (SCI) and detrusor overactivity refractory to conventional therapy. Healthy subjects underwent H reflex studies during urodynamic assessment and acted as controls. RESULTS: Our findings show that BoNT/A injected into the detrusor muscle effectively reduces clinical overactive bladder symptoms in patients with PD and SCI. In healthy subjects and patients with PD, bladder filling [at maximum cystometric capacity, (MCC)] significantly decreased the H reflex size, whereas in patients with SCI, it slightly facilitated the H reflex size. At MCC, in patients with PD, BoNT/A significantly reduced the expected H reflex inhibition, whereas in those with SCI, BoNT/A turned the H reflex facilitation at maximum bladder filling into a slight inhibition. CONCLUSIONS: These findings show that BoNT/A injected into the detrusor muscle in patients with PD and SCI modulates bladder afferent activity. Modulation of bladder afferents possibly explains why BoNT/A improves detrusor overactivity.

Recommendations for the management of urinary disorders in multiple sclerosis: a consensus of the Italian Multiple Sclerosis Study Group.

Urinary disorders are uncommon in the initial phases of multiple sclerosis, but increase in frequency as the disease progresses, with a negative impact on quality of life. The goal of this study was to propose a protocol for the diagnosis and treatment of urinary disorders in multiple sclerosis, based on data from the scientific literature and the experience of Italian clinical centres. In particular, the following clinical aspects were considered: what to do with patients with asymptomatic multiple sclerosis; what to do with symptomatic patients; how and when to perform a second-level diagnostic evaluation; and how to treat urinary disorders. A diagnostic-therapeutic algorithm is proposed, that can be applied in Italian clinical centres.

Effect of botulinum neurotoxin on the urinary bladder: novel insights on mechanism of action.

Botulinum neurotoxins (BoNTs) recently tarted to be used in common urologic practice for the treatment of neurogenic and non neurogenic detrusor overactivity (DO) refractory to all conventional treatments. The rationale was that botulinum toxin, particularly BoNT type A (BoNT/A), was able to block the presynaptic release of acetylcholine (ACh) from the parasympathetic efferent nerves thus paralyzing the detrusor smooth muscle, an action similar to that performed in skeletal muscles. With the present review we aimed at assessing the state of the art on the mechanisms of function of botulinum toxins in the management of urological dysfunctions. We searched PubMed using the medical subject heading (MeSH) term botulinum toxin in conjunction with any of the following terms: mechanism of action, bladder, afferent and efferent nervous transmission, urothelium and suburothelium, detrusor overactivity. Review articles and published abstracts were identified by limiting for review and abstract, respectively. The reference list of review and original papers were reviewed to identify any missed papers. A similar search strategy was applied in EMBASE using identical EMTREE terms. Recent evidences in in vivo and in in vitro studies suggest that in addition to a direct effect on detrusor motor innervation, BoNT/A also modulates intrinsic bladder reflexes through a multimodal effect on sensory pathways. Such mechanisms may contribute to the efficiency of this treatment and partly explain how it affects abnormal detrusor contractions more markedly than voluntary bladder emptying.

Urgency of micturition and detrusor contractility in men with prostatic obstruction and overactive bladders.

AIMS: In men with prostatic obstruction and detrusor overactivity (DO), to ascertain whether urgency of micturition affects bladder contractility. MATERIALS AND METHODS: We urodynamically assessed five groups of 20 men each who had bladder outflow obstruction (BOO) from benign prostatic enlargement-Groups 1 (with no DO and no urgency), 2 (with DO and no urgency), 3A (with DO and moderate urgency), 3B (with DO and severe urgency), and 4 (with DO, severe urgency and chronic ischemic cerebral lesions). Urgency was graded as moderate or severe by the ability to avert an urgent void at cystometry for > or =2 or <2 min, respectively. BOO was assessed by the "Abrams-Griffiths number" (AG) and bladder contractility by the parameters PIP and WF(max). RESULTS: AG did not differ significantly in Groups 2, 3A, and 3B, proved higher in such groups than in Group 1, and was nearly the same in Groups 1 and 4. PIP and WF(max) were significantly higher in Groups 2, 3A, and 3B than in Groups 1 and 4, had the highest levels in Group 3B, and did not differ significantly in Groups 1-4 and 2-3A. CONCLUSIONS: In DO patients with prostatic obstruction there seems to be a DO-related facilitation of bladder contractility. In the same patients, severe urgency of micturition might over-amplify (i.e., enhance a DO-related facilitation of) bladder contractility, provided there are no neurogenic (chronic ischemic cerebral) lesions.

New therapeutic options for refractory neurogenic detrusor overactivity.

AIM: Current pharmacologic treatment of detrusor overactivity relies on anticholinergic drugs. However, they often have untolerable side effects so that they are administered in doses insufficient to restore urinary continence. Recently, intravesical instillations and injections into the detrusor muscle of new pharmacological agents have been developed. The present study report our own experience in the treatment of detrusor overactivity with intravesical administrations of vanilloid agents and with botulinum-A toxin injections into the detrusor muscle in a group of spinal cord injured patients. In particular, we compared the clinical and urodynamic effects of the 2 drugs in an attempt to find a new and valid therapeutic option in those cases unresponsive to conventional treatment. METHODS: Seventy-five patients with spinal cord injury and refractory detrusor overactivity were included in the study: 35 patients received repeated intravesical instillations of resiniferatoxin (RTX) dissolved in normal saline; 40 patients received repeated injections of 300 units botulinum A-toxin diluted in 30 ml normal saline. Clinical assessment and urodynamics were performed at baseline and 6, 12 and 24 months after treatment. RESULTS: With both treatments there was a significant reduction in mean catheterization and episodes of incontinence and a significant increase in mean first involuntary detrusor contraction and in mean maximum bladder capacity at 6, 12 and 24 months after therapy. We did not detect any local side effects with either treatment. Botulinum-A toxin significantly reduced also the maximum pressure of uninhibited detrusor contractions more than RTX at all follow-up time points. CONCLUSION: In patients with spinal cord injury and refractory detrusor overactivity intravesical RTX and botulinum-A toxin injections into the detrusor muscle provided beneficial clinical and urodynamic results with reduction of detrusor overactivity and restoration of urinary continence in most patients. Botulinum-A toxin injection provided better clinical and urodynamic benefits than intravesical RTX.

Transdermal electromotive administration of verapamil and dexamethasone for Peyronie's disease.

OBJECTIVE: To evaluate the effects of the transdermal electromotive administration of verapamil and dexamethasone on plaque size, penile deviation, pain, erectile function and capacity for vaginal penetration in patients with Peyronie's disease. PATIENTS AND METHODS: Forty-nine patients were treated four times weekly for six consecutive weeks. During each session the drug mixture was administered from a receptacle fixed to the skin overlying the plaques, using 2.4 mA pulsed current for 20 min. Plaque size and penile deviation were evaluated by dynamic penile duplex ultrasonography, X-ray and photographs; pain, erectile function and capacity for vaginal penetration were assessed using a questionnaire. Vital signs and side-effects were recorded. Differences before and after treatment were assessed. RESULTS: The plaque disappeared in 8% of patients, with a measurable reduction in volume in 74% and no change in 18% (P < 0.001). Penile deviation resolved in 10% of the men, decreased in 74% and remained unchanged in 16% (P < 0.001). The plaque volume was halved in two-thirds of the men, to a mean (sd) of 515 (301) mm3, and the penile deviation halved in 45% of patients, to 24 (5) degrees; pain was completely eliminated in 88% (P < 0.001). Erectile function was completely restored in 42% of patients with initial erectile dysfunction and improved in 17% (P < 0.001); vaginal penetration improved in 73%. No toxicity was noted, except for a transient skin erythema at the site of the penile and dispersive electrodes. CONCLUSION: The transdermal electromotive administration of verapamil and dexamethasone is clinically safe and appears to be an effective treatment in patients with Peyronie's disease.

Intravesical oxybutynin: mode of action assessed by passive diffusion and electromotive administration with pharmacokinetics of oxybutynin and N-desethyl oxybutynin.

PURPOSE: A proportion of patients with detrusor hyperreflexia who are unresponsive to oral oxybutynin often benefit from intravesical oxybutynin instillation. To our knowledge the precise mode of action of this method is obscure. MATERIALS AND METHODS: In 12 patients with detrusor hyperreflexia who were previously unresponsive to oral and intravesical passive diffusion of 5 mg. oxybutynin we administered 5 mg. oxybutynin orally as well as increased doses of 15 mg. oxybutynin intravesically with passive diffusion and with 15 mA. associated electric current. Each administration mode per patient was associated with an 8-hour urodynamic monitoring session during which oxybutynin and N-desethyl oxybutynin plasma levels, and intravesical oxybutynin uptake were measured. RESULTS: A dose of 5 mg. oxybutynin orally induced no urodynamic improvement with an area under the plasma concentration time curve of combined N-desethyl oxybutynin plus oxybutynin of 16,297 ng./8 hours and an area under the curve ratio of N-desethyl oxybutynin-to-oxybutynin of 11:1. Passive diffusion oxybutynin resulted in 12 mg. oxybutynin intravesical uptake and significant improvement in 3 of 8 urodynamic measurements, although the area under the curve of combined N-desethyl oxybutynin plus oxybutynin was only 2,123 ng./8 hours and the N-desethyl oxybutynin-to-oxybutynin ratio was 1.1:1.0. Electromotive administration of oxybutynin resulted in almost complete intravesical uptake of the 15 mg. dose, significant improvement in all 8 urodynamic measurements and an increased oxybutynin level versus oral and passive diffusion, although the area under the curve of combined N-desethyl oxybutynin plus oxybutynin was 4,574 ng./8 hours and the N-desethyl oxybutynin-to-oxybutynin ratio was inverted at 1.0:1.4. The oral dose of 5 mg. oxybutynin caused anticholinergic side effects in 8 of the 12 patients. Neither intravesical passive diffusion nor electromotive administration caused side effects with an uptake of 12 and 15 mg., respectively. CONCLUSIONS: A large proportion of intravesical oxybutynin is sequestered, probably in the urothelium. Intravesical oxybutynin administration confers therapeutic benefits via localized direct action within the bladder wall.

Intermittent catheterization with a prelubricated catheter in spinal cord injured patients: a prospective randomized crossover study.

PURPOSE: We compared the safety and patient acceptance of a conventional Nélaton and a prelubricated nonhydrophilic catheter in 18 spinal cord injured patients on intermittent catheterization. MATERIALS AND METHODS: In a prospective crossover study each catheter was used for 7 weeks and the initial course was randomized. Urinalysis and urine culture were performed at 2, 4 and 7 weeks. Urethral trauma was evaluated by urethral cell count on the surface of each catheter used on the last day of each study period. Patient satisfaction was assessed at the end of the study by a questionnaire using multiple visual analog scales. RESULTS: Urinary tract infection was identified in 12 and 4 patients on a Nélaton and a prelubricated nonhydrophilic catheter (p = 0.03), while asymptomatic bacteruria was identified in 18 and 8 (p = 0.0244), respectively. The mean urethral cell count plus or minus standard deviation on the catheter surface was 6.7 +/- 2.8 x 10(4) and 15.1 +/- 8.9 x 10(4) for the prelubricated nonhydrophilic and the Néelaton catheter, respectively (p = 0.01). The prelubricated nonhydrophilic catheter resulted in a better mean satisfaction score than the Nélaton catheter (2.33 +/- 1.06 versus 4.72 +/- 2.13, p = 0.022). Urethral bleeding was reported in 2 patients during the study period while using the Nélaton catheter. CONCLUSIONS: The prelubricated nonhydrophilic catheter is a safe, effective and comfortable option in spinal cord injured patients on intermittent self-catheterization.

Intravesical electromotive administration of oxybutynin in patients with detrusor hyperreflexia unresponsive to standard anticholinergic regimens.

PURPOSE: About 15% to 20% of patients with detrusor hyperreflexia do not benefit from oral oxybutynin regimens, frequently because of unpleasant side effects. Several reports indicate that intravesical oxybutynin is effective in many of these patients but there are some who still fail to respond. MATERIALS AND METHODS: A select group of 10 adults with detrusor hyperreflexia unresponsive to standard oral and intravesical oxybutynin regimens were treated at weekly intervals with 5 mg. oxybutynin orally, or 5 mg. oxybutynin in 100 ml. intravesically for 60 minutes of passive diffusion and for 30 minutes with 5 mA. electrical current. Each treatment (plus oral placebo and 2 intravesical controls) was associated with an 8-hour, full urodynamic monitoring session, and periodic blood and bladder content sampling. RESULTS: There was no significant objective improvement with oral or intravesical passive diffusion oxybutynin. Conversely there was significant improvement in 5 of 6 objective urodynamic measurements with intravesical electromotive oxybutynin. Plasma profiles were a single peak and decay following oral oxybutynin and 2 distinct peaks with intravesical passive diffusion and electromotive oxybutynin. Area under the curve for intravesical passive diffusion were 709 ng. per 8 hours versus oral 1,485 (p <0.05) versus intravesical electromotive 2,781 (p <0.001). Bladder content samples confirmed oxybutynin absorption. Oral oxybutynin caused anticholinergic side effects in 7 of 10 patients. There were no side effects with intravesical passive diffusion or electromotive administrations. CONCLUSIONS: Accelerated intravesical administration results in greater bioavailability and increased objective benefits without side effects in previously unresponsive patients compared with oral and intravesical passive diffusion oxybutynin administration.

One year follow up of spinal cord injury patients using a reciprocating gait orthosis: preliminary report.

OBJECTIVE: To examine the influence of social, physical and psychological factors in determining the usage/non usage of reciprocating gait orthosis (RGO) in spinal cord injury (SCI) patients. DESIGN: Prospective clinical trial. SETTING: A large rehabilitation hospital in Rome, Italy. PARTICIPANTS: Twenty four SCI patients of traumatic aetiology (all fulfilling the criteria to prescribe the device). METHODS: Social, physical and neurological examination according to ASIA standards; psychological enquiry by means of the Eysenck Personality Questionnaire (EPQ) and the scale for self rating anxiety and depression of the Cognitive Behavioural Assessment. RESULTS: After 1 year follow up 11 (46%) of our patients no longer used the RGO. There was no statistically significant difference between patients who used the RGO and those who rejected the orthosis with regard to social and physical data. There was a significant difference (P=0.005 at the end of training and P=0.003 at 1 year follow up) with regard to functional ambulation level. With regard to psychological enquiry RGO-non users showed a higher frequency of values over the mean in the E scale (extroversion) of the EPQ than RGO-users (P=0.05). CONCLUSIONS: None of the identified parameters were useful to predict the use/rejection of the orthosis. Although they need to be confirmed, our psychological data suggest that extensive psychological testing could be useful to sharpen the ability to predict.

Urodynamics in spinal cord injured patients walking with reciprocating gait orthosis.

PURPOSE: We evaluated the effects of walking with reciprocating gait orthosis on bladder function and upper urinary tract status in spinal cord injured patients. MATERIALS AND METHODS: Seven patients using reciprocating gait orthosis underwent urodynamics before and during walking. Abdominal ultrasound was performed before and after urodynamics. RESULTS: Baseline urodynamics showed detrusor areflexia in 3 patients and hyperreflexia in 4. During walking urodynamics revealed hyperreflexia in 6 patients with worse uninhibited detrusor contraction amplitude (38.2 +/- 41.2 versus 73.7 +/- 44.4 cm. water, p = 0.006) and duration (2.1 +/- 2.1 versus 6.8 +/- 5.3 minutes, p = 0.023). After walking ultrasound demonstrated bilateral pyelectasia in 2 patients. CONCLUSIONS: Spinal cord injured patients using reciprocating gait orthosis have worse urodynamic measurements and upper urinary tract disorders during walking. They require close urological followup.

[Ultrasonography of the upper urinary tract in patients with spinal cord injury]. / Studio ecografico dell'alto tratto urinario in pazienti con trauma vertebro-midollare.

A lesion of the upper urinary tract (UUT) is a possible outcome of the bladder dysfunction following a spinal cord injury (SCI). The most common findings are hydronephrosis, bladder-ureteral reflux and pyelonephritis. Aim of the study was to evaluate the prevalence of UUT abnormalities, evaluable by ultrasound (US), in a population of SCI patients; furthermore we correlated the presence of such abnormalities to clinical findings. We evaluated 115 consecutive patients who underwent US scan of UUT. Mean time between injury and our evaluation was 81.5 +/- 100.2 months. Lesion level was cervical (38/115), dorsal (59/115) and lumbar (18/115). Eight patients emptied their bladder spontaneously, 105 by means of intermittent catheterization, while 2 were wearing indwelling catheter. Seventy-four patients used anticholinergics drugs. It was evaluated the presence of: hydronephrosis, renal stones and chronic pyelonephritis using US. Afterward the presence of such alterations was correlated to sex and age of patients, time between injury and our evaluation, method of bladder emptying and use of anticholinergics drugs. In 25/115 patients (21.7%) were found abnormalities of UUT. A significative correlation was found between presence of UUT lesions and older age. In our series, prevalence of UUT abnormalities observed by means of US in SCI patients is 21.7%. This finding could be due to correct management and strict follow up of the patients.

Extraction and determination of oxybutynin in human bladder samples by reversed-phase high-performance liquid chromatography.

A reversed-phase high-performance liquid chromatography method is described for the determination of oxybutynin (OXB) in human bladder samples. Following homogenization, tissue samples underwent double extraction with hexane and eventually were concentrated by freeze-drying before analysis. Chromatographic separation was performed with a mobile phase of acetonitrile-water-1 M ammonium acetate, pH 7.0 (85:13:2, v/v/v) at a flow-rate of 0.5 ml/min and double (electrochemical and UV) detection was applied. The retention time of oxybutynin eluting peak was around 18 min. Using a standard curve range of 10 to 500 ng/ml the quantification limit with electrochemical detection was 5 ng/ml with an injection volume of 100 microl. Within-day and day-to-day relative standard deviation values were 4.9 and 9.81%, respectively, while a 94% accuracy and a 72% recovery was attained. We applied this method to compare the OXB levels into bladder wall tissue samples after passive diffusion and after electromotive drug administration (EMDA), using a two-chambered poly(vinyl chloride) diffusion cell designed and developed in our laboratory. The results obtained show that EMDA enhanced OXB penetration into bladder wall and that this novel way of local drug administration can be potentially used in patients with neurogenic bladder dysfunction or urinary incontinence.

Electromotive versus passive diffusion of mitomycin C into human bladder wall: concentration-depth profiles studies.

The objectives of these investigations were: (a) to make a preliminary study to assess concentration-depth profiles of mitomycin C (MMC) in the bladder wall at specified time intervals after passive diffusion (PD); and (b) to conduct a major study to compare concentration-depth profiles after PD and electromotive drug administration (EMDA) of MMC. Full thickness sections of viable human bladder wall were placed in two-chamber cells with urothelium exposed to donor compartments containing 40 mg of MMC in 100 ml of 0.96% NaCl solutions and with serosa-facing receptor compartments containing 0.9% NaCl solutions. In the preliminary study during each of nine experimental sessions, five sections of bladder wall were individually exposed to MMC for either 5, 15, 30, 45, or 60 min. In the major study, an anode and a cathode were sited in the donor and receptor compartments, and 14 paired experiments--current (20 mA)/no current--were conducted over a 30-min period. Bladder wall sections were cut serially into 40-microm slices parallel to the urothelium and analyzed by high-performance liquid chromatography for MMC concentration (microg/g wet tissue weight). Tissue viability and morphology and MMC stability were assessed by trypan-blue exclusion test, histological examination, and mass spectrometry analysis. In the preliminary study (PD only), mean MMC concentrations (microg) at 5, 15, 30, 45, and 60 min were: (a) for urothelium, 15.3, 60.0, 58.2, 60.1, and 57.8, respectively; (b) for lamina propria, 2.2, 18.9, 19.3, 16.1, and 17.3, respectively; and (c) for muscularis, 0.4, 2.0, 1.8, 1.3, and 2.4, respectively. In the comparative study, MMC concentrations and coefficients of variation (CV) were as follows: (a) for urothelium after PD, 46.6 with CV = 69%, and after EMDA, 170.0 with CV = 43% (P < 0.0001); (b) for lamina propria after PD, 16.1, with CV = 60%, and after EMDA, 65.6 with CV = 29% (P < 0.0001); and (c) for muscularis after PD, 1.9 with CV = 82%, and after EMDA, 15.9 with CV = 82% (P < 0.0005). All of the bladder sections remained viable, and the chemical structure of MMC was unchanged. It was concluded that EMDA significantly enhances MMC transport into all of the layers of the bladder wall, and sections of viable human bladder are a reliable tool for assessing different modes of drug delivery.