Lipogenic regulators are elevated with age and chronic overload in rat skeletal muscle.

AIM: Both muscle mass and strength decline with ageing, but the loss of strength far surpasses what is projected based on the decline in mass. Interestingly, the accumulation of fat mass has been shown to be a strong predictor of functional loss and disability. Furthermore, there is a known attenuated hypertrophic response to skeletal muscle overload with ageing. The purpose of this study was to determine the effect of 28 days of overload on the storage of intramuscular triglycerides (IMTG) and metabolic regulators of lipid synthesis in young and old skeletal muscle. METHODS: The phosphorylation and expression of essential lipogenic regulators were determined in the plantaris of young (YNG; 6-month-old) and aged (OLD; 30-month-old) rats subjected to bilateral synergist ablation (SA) of two-thirds of the gastrocnemius muscle or sham surgery. RESULTS: We demonstrate that age-induced increases in IMTG are associated with enhancements in the expression of lipogenic regulators in muscle. We also show that the phosphorylation and concentration of the 5'AMP-activated protein kinase (AMPK) isoforms are altered in OLD. We observed increases in the expression of lipogenic regulators and AMPK signalling after SA in YNG, despite no increase in IMTG. Markers of oxidative capacity were increased in YNG after SA. These overload-induced effects were blunted in OLD. CONCLUSION: These data suggest that lipid metabolism may be altered in ageing skeletal muscle and is unaffected by mechanical overload via SA. By determining the role of increased lipid storage on skeletal muscle mass during ageing, possible gene targets for the treatment of sarcopenia may be identified.

Chronic aerobic exercise enhances components of the classical and novel insulin signalling cascades in Sprague-Dawley rat skeletal muscle.

AIM: The aim of this study was to provide a more extensive evaluation of the effects of chronic aerobic exercise on various components of the insulin signalling cascade in normal rodent skeletal muscle because of the limited body of literature that exists in this area of investigation. METHODS: Male Sprague-Dawley rats were assigned to either control (n = 7) or chronic aerobic exercise (n = 7) groups. Aerobic exercise animals were run 3 day week(1) for 45 min on a motor-driven treadmill (32 m min(1), 15% grade) for a 12 week period. Following the training period, all animals were subjected to hind limb perfusion in the presence of 500 microU mL(1) insulin to determine what effect chronic aerobic training had on various components of the insulin signalling cascade, c-Cbl protein concentration and c-Cbl phosphorylation. RESULTS: Twelve weeks of aerobic training did not alter skeletal muscle Akt 1/2 protein concentration, Akt Ser 473 phosphorylation, Akt Thr 308 phosphorylation, Akt 1 activity, aPKC-zeta protein concentration, aPKC-lambda protein concentration or c-Cbl protein concentration. In contrast, chronic aerobic exercise increased insulin-stimulated phosphatidylinositol 3-kinase, Akt 2 kinase and aPKC-zeta/lambda kinase activities, as well as c-Cbl tyrosine phosphorylation, in a fibre type specific response to aerobic training. In addition, chronic aerobic exercise enhanced insulin-stimulated plasma membrane glucose transporter 4 (GLUT4) protein concentration. CONCLUSION: Collectively, these findings suggest that chronic aerobic exercise enhances components of both the classical and novel insulin signalling cascades in normal rodent skeletal muscle, which may contribute to an increased insulin-stimulated plasma membrane GLUT4 protein concentration.

Long-term effectiveness of sacral nerve stimulation for refractory urge incontinence.

OBJECTIVES: To evaluate the long-term efficacy of sacral nerve stimulation for refractory urinary urge incontinence. STUDY DESIGN AND METHODS: Urge incontinent patients qualified for surgical implantation of a neurostimulator system after trial screening with percutaneous test stimulation. Surgical implantation of the InterStim System (Medtronic Inc., Minneapolis, Minn., USA) was performed in cases where a >50% reduction in incontinence symptoms was documented during the 3- to 7-day test stimulation period. The InterStim System consists of an implantable pulse generator, a transforamenally placed quadripolar lead, and an extension that connects these two devices for unilateral stimulation of the S3 or S4 sacral nerve. Efficacy for 96 implanted patients was based on urinary symptom changes as quantified in voiding diaries collected at baseline and annually after surgical implantation. RESULTS: As compared to baseline, the group of 96 implanted patients demonstrated significant reductions in urge incontinent symptoms at an average of 30.8+/-14.8 (range 12-60) months with respect to the number of urge incontinent episodes per day, severity of leaking, and the number of absorbent pads/diapers replaced per day due to incontinence (all p<0.0001, respectively). Gender, pretreatment variables, and age were not found to be relevant factors that affected these results. 11 of the 96 patients underwent device explant due to lack of efficacy, pain or bowel dysfunction. These data were conservatively included in the efficacy results. No permanent injuries associated with the devices or therapy were reported. CONCLUSION: Sacral nerve stimulation is an effective treatment for refractory urge incontinence with sustained long-term benefit through an average of 30.8 months.

The management of neurogenic bladder and sexual dysfunction after spinal cord injury.

STUDY DESIGN: Review article. OBJECTIVES: To review the medical literature and comprehensively discuss the management of bladder and sexual dysfunction after spinal cord injury. SUMMARY OF BACKGROUND DATA: The physiologic alterations that accompany spinal cord injury can lead to significant bladder and sexual dysfunction. Fertility in men is also diminished. Without appropriate intervention, the above conditions can lead to significant morbidity and mortality. METHODS: Structured review of published reports obtained through a MED-LINE search and texts. RESULTS/CONCLUSION: With appropriate surveillance and management, morbidity and mortality from neurogenic bladder dysfunction can be successfully prevented. Current treatment interventions also facilitate the restoration of sexual function and fertility after spinal cord injury.

Transurethral microwave thermotherapy of the prostate without intravenous sedation: results of a single United States center using both low- and high-energy protocols. TJUH TUMT Study Group.

PURPOSE: Previous studies have indicated that high-energy transurethral microwave thermotherapy (TUMT) requires intravenous (IV) sedation and/or narcotics for patient tolerance. This study was performed to determine tolerability, patient acceptance, and efficacy of TUMT using both low- and high-energy protocols in a single United States university setting. MATERIALS AND METHODS: Between August 11, 1997 and October 28, 1999, 210 men (mean age 64.9 +/- 9.1 years) presenting with symptomatic benign prostatic hyperplasia (BPH) received treatment with a Prostatron TUMT using either the low-energy Prostasoft 2.O or high-energy Prostasoft 2.5 software. Each patient had digital rectal examination and prostate-specific antigen level consistent with BPH, American Urological Association symptom score > or = 15, and Qmax <15 mL/s. Each patient received TUMT with only ibuprofen 400 mg by mouth (PO), lorazepam 1.0 mg PO, and ketorolac 30 mg intramuscularly (IM) prior to TUMT. A few patients who were concerned about limited pain threshold received oxycodone 5 mg/acetaminophen 325 mg PO. Of 210 patients treated, 12-month efficacy data were available for analysis in 80 patients. RESULTS: Forty-eight men (mean age 65 +/- 9.2 years) received low-energy 2.0 software TUMT, and 32 men (mean age 65.1 +/- 9.2 years) were treated with high-energy 2.5 software. Mean prostatic volume was 44.3 +/- 23.9 mL and 60.7 +/- 26.4 mL for the 2.0 and 2.5 groups, respectively. Mean energy delivered was 108.8 +/- 50.4 kJ and 173.1 +/- 41.1 kJ for the 2.0 and 2.5 treatment groups, respectively. International Prostate Symptom Score decreased from 23 pre-TUMT to 8 post-TUMT and 21 pre-TUMT to 10 post-TUMT at 12 months in the 2.0 and 2.5 groups, respectively. Mean peak flow rate improved 31.9% from 9.1 mL/s pre-TUMT to 12.0 mL/s post-TUMT and 45.8% from 9.6 mL/s pre-TUMT to 14.0 mL/s post-TUMT at 12 months in the 2.0 and 2.5 groups, respectively. All but two patients tolerated treatment without IV sedation. One patient experienced intolerable rectal spasm, and treatment was terminated in another patient because of poorly controlled hypertension. CONCLUSIONS: Patients can be treated safely with TUMT using either low or high energy, with almost universal patient tolerance and without the need for IV sedation or narcotics, if they premedicated effectively using a PO/IM regimen. Patients experience significant relief of symptoms whether low- or high-energy TUMT is used; however, high-energy TUMT improves flow rate to a greater extent than does low-energy therapy.

Sacral neuromodulation in the treatment of urgency-frequency symptoms: a multicenter study on efficacy and safety.

PURPOSE: Neuromodulation of sacral nerves has shown promising results in correcting voiding dysfunction. We report the results of a multicenter trial designed to assess the efficacy of sacral nerve neuromodulation in patients presenting with refractory urinary urgency-frequency. MATERIALS AND METHODS: A total of 51 patients from 12 centers underwent baseline assessment, including a detailed voiding diary, urodynamic evaluation and percutaneous test stimulation of the sacral nerves at S3 and/or S4. All patients enrolled in the study had undergone prior conventional treatment, such as pharmacotherapy, hydrodistention and surgical intervention, which failed. All patients demonstrated a satisfactory response to trial stimulation and were randomly divided into a stimulation group (25 patients) and a control group (26). A sacral nerve stimulation device was implanted after 6 months in the control group. Patients were followed at 1, 3 and 6 months, and at 6-month intervals for up to 2 years after implantation of a neuroprosthetic InterStim* system. dagger The study variables included the number of voids daily, volume voided per void and degree of urgency before void. RESULTS: Compared to the control group, 6-month voiding diary results demonstrated statistically significant improvements (p <0.0001) in the stimulation group with respect to the number voids daily (16.9 +/- 9.7 to 9.3 +/- 5.1), volume per void (118 +/- 74 to 226 +/- 124 ml.) and degree of urgency (rank 2.2 +/- 0.6 to 1.6 +/- 0.9). Patients in the control group showed no significant changes in voiding parameters at 6 months. Significant improvements in favor of the stimulation group were noted in various parameters with respect to water cystometry and quality of life (SF-36). At 6 months after implant, neurostimulators were turned off in the stimulation group and urinary symptoms returned to baseline values. After reactivation of stimulation sustained efficacy was documented at 12 and 24 months. CONCLUSIONS: Neuromodulation of the sacral nerves is an effective, safe therapy that successfully treats significant symptoms of refractory urgency-frequency.

Removal of UroLume endoprosthesis: experience of the North American Study Group for detrusor-sphincter dyssynergia application.

PURPOSE: We present the experience of the North American UroLume Multicenter Study Group with removal of the UroLume endoprosthesis. MATERIALS AND METHODS: A total of 160 neurologically impaired patients were enrolled in the North American UroLume Multicenter Study Group for detrusor external sphincter dyssynergia application. Analysis was performed in 2 groups of patients in which the device was removed during insertion and after implantation, respectively. RESULTS: Device retrieval was required during insertion in 21 patients (13%) mainly due to misplacement or migration in 17. Extraction was done with minimal complications and in all but 2 cases subsequent UroLume implantation was successful. Of 158 men with the device in place 31 (19.6%) required removal. In 34 procedures 44 devices were removed, mainly due to migration. Time from implantation to removal ranged from 4 days to 66 months (mean 22 months). The UroLume was removed en bloc in 20 cases and in parts or wire by wire in 19. The majority of patients had no or minimal complications after extraction. Only 2 patients had serious temporary complications, including bleeding and urethral injury, with no lasting consequences. No malignancy developed as a result of UroLume insertion. CONCLUSIONS: While there is a potential for urethral injury and bleeding, UroLume endoprosthesis removal is largely a simple procedure with minimal complications and consequences.

Beneficial effect of intranasal desmopressin for men with benign prostatic hyperplasia and nocturia: preliminary results.

The aim of this study was to determine the efficacy of intranasal desmopressin in the treatment of nocturnal polyuria in men with benign prostatic hyperplasia (BPH). Twelve men with BPH were treated with intranasal desmopressin at bedtime for nocturnal polyuria. All patients underwent video-urodynamic evaluation. The number of nocturia episodes was the dependent variable. Exclusion criteria included nephrolithiasis, active urinary tact infection, and history of myocardial infarction, congestive heart failure, and angina. Ten of 12 patients improved with the intranasal desmopressin therapy. Nocturia episodes decreased from a median of 3.6 +/- 0.5 episodes/night before treatment to 1.8 +/- 1.1 episodes/night 3 months after therapy (p = .01). The American Urological Association symptom index decreased from 19 +/- 6 before treatment to 12 +/- 6 after therapy (p = .02). Hyponatremia did not occur. We conclude that intranasal desmopressin is a promising therapy for nocturnal polyuria in selected BPH patients.

Sphincteric stent versus external sphincterotomy in spinal cord injured men: prospective randomized multicenter trial.

PURPOSE: In a prospective randomized multicenter trial we compared the treatment results of conventional external sphincterotomy with those of UroLume sphincteric stent prosthesis placement in men with spinal cord injury and external detrusor-sphincter dyssynergia. MATERIALS AND METHODS: We randomized 57 men with spinal cord injury in whom urodynamics verified external detrusor-sphincter dyssynergia into 2 groups to undergo either sphincter defeating procedure. We compared the primary urodynamic parameter of maximum detrusor pressure, and secondary urodynamic parameters of bladder capacity and post-void residual urine volume in men who underwent sphincterotomy or sphincteric stent placement. Parameters were measured preoperatively, and 3, 6, 12 and 24 months postoperatively. Patients completed questionnaires regarding voiding sensation and quality of life issues at each followup visit. RESULTS: Demographic data of the 26 patients treated with sphincterotomy and the 31 treated with sphincteric stent placement were statistically similar. Preoperatively mean maximum detrusor pressure plus or minus standard deviation in sphincterotomy and stent cases was 98.3 +/- 27.6 and 95.7 +/- 27.7 cm. water, respectively (p = 0.73). At 12 months mean maximum detrusor pressure decreased to 48.9 +/- 16.4 and 52.6 +/- 31.6 cm. water in the sphincterotomy and stent groups, respectively (p = 0). Preoperatively mean bladder capacity in sphincterotomy and stent cases was 245 +/- 158 and 251 +/- 145 ml., respectively (p = 0.87). Bladder capacity did not change significantly in either treatment group throughout followup. Preoperatively mean post-void residual urine volume in the sphincterotomy and stent groups was 212 +/- 163 and 168 +/- 114 ml., respectively (p = 0.33). Residual urine volume decreased in each group at some but not all followup evaluations. The duration of hospitalization was greater for sphincterotomy than stenting (p = 0.036). Six stents required explantation. CONCLUSIONS: The UroLume stent is as effective as conventional external sphincterotomy for treating external detrusor-sphincter dyssynergia. However, sphincteric stent placement is advantageous because it involves shorter hospitalization and is potentially reversible.

Long-term followup of the North American multicenter UroLume trial for the treatment of external detrusor-sphincter dyssynergia.

PURPOSE: We determine the long-term efficacy and safety of the UroLume stent as minimally invasive treatment for external detrusor-sphincter dyssynergia in spinal cord injured men. MATERIALS AND METHODS: A total of 160 spinal cord injured men with a mean age plus or minus standard deviation of 36.3 +/- 12.1 years (range 16 to 74) were prospectively treated with an endoprosthesis at 15 centers as part of the North American UroLume trial for external detrusor-sphincter dyssynergia. Urodynamic parameters, including voiding pressure, residual urine volume and bladder capacity, were compared before treatment and at 1, 2, 3, 4 and 5 years after treatment. RESULTS: Mean voiding pressure was 75.1 +/- 28.2 cm. water before treatment in the 160 patients, and 37.4 +/- 23.9 at year 1 in 97, 39.5 +/- 22.2 at year 2 in 84, 42.6 +/- 27.3 at year 3 in 61, 46.3 +/- 33.2 at year 4 in 57 and 44.2 +/- 28.9 cm. at year 5 in 41 after stent insertion (p <0.001). Residual urine volume decreased after stent placement and was maintained throughout the 5-year followup (p <0.001). Mean cystometric capacity remained constant from 269 +/- 155 before insertion to 337 +/- 182 ml. 5 years later (p = 0.17). Hydronephrosis and autonomic dysreflexia improved or stabilized in most patients with functioning stents. Stent explant was necessary in 24 patients (15%), of whom 4 (16.7%) had another stent implanted. CONCLUSIONS: The UroLume stent demonstrates long-term safety and efficacy for the treatment of external detrusor-sphincter dyssynergia. The outcome was similar in men with and without previous sphincterotomy.

Spermatogenesis in early and chronic phases of experimental spinal cord injury in the rodent model.

A rodent model was used to study the degree and dynamics of potential spermatogenic alterations during both acute and chronic phases after experimental spinal cord injury (SCI). Sexually mature Sprague-Dawley rats underwent controlled impact SCI by exposure of the thoracic spine, T-10 laminectomy, and intraoperative somatosensory-evoked potential latency and amplitude. A 50 gm-cm SCI was produced in 35 experimental subjects. Sham surgery was performed on 16 control subjects through exposure of the dura without weight drop. SCI was verified by obliteration of the somatosensory-evoked potential following injury and subsequent neurologic assessment (modified hindlimb Tarlov scale) 4 weeks after injury. Flow cytometry with acridine orange as the DNA probe was used to measure potential spermatogenic alterations in testicular cell development and integrity of epididymal sperm chromatin structure between 2 and 20 weeks following SCI. Flow cytometric analysis revealed that nine of the 35 SCI animals demonstrated altered spermatogenesis; it is not clear whether these effects are specific or nonspecific stress related. These responder animals contributed to dramatic differences in relative percent testicular haploid cells (spermatids) and concurrent differences in percent diploid cells at 2, 4, 8, 12, and 16 weeks. Percentages within the three spermatid populations (round, elongating, and elongated) also differed at these time points. The sperm chromatin structure assay (SCSA) revealed significant epididymal sperm nuclear structure differences at 2, 4, and 12 weeks (P < 0.001). These findings are in concordance with our clinical observations of spermatogenesis in spinal cord injured men and suggest that significant spermatogenic deficit may occur, even in the early phase of injury.

The invention of the modern uroflowmeter by Willard M. Drake, Jr at Jefferson Medical College.

The uroflowmeter is perhaps the most important and certainly the most commonly used urodynamic instrument currently employed in urologic practice. The modern uroflowmeter was invented by Willard M. Drake, Jr., in 1946 at the Jefferson Medical College. The original manuscript, entitled "The uroflometer: an aid to the study of the lower urinary tract," appeared in Journal of Urology in 1948. Drake obtained a US patent for the device, entitled "Uroflometer," in 1953. The flowmeter, originally manufactured by van Beek Industries, was more recently manufactured and distributed by Grewe Plastics. Drake is now retired and living in Nacogdoches, Texas.

Early predictors of bladder recovery and urodynamics after spinal cord injury.

Our purpose was to determine if intact perianal (S4-5) pin sensation (PPS) and bulbocavernosus (S2-4) reflex (BCR) shortly after spinal cord injury (SCI) are predictive of bladder function recovery. Twenty-eight SCI patients (aged 18-68 years, Frankel Classification A-D, spinal injury level C4-T12), admitted within 72 hours of injury, underwent evaluation of initial PPS and BCR. The presence of intact PPS and BCR were correlated with the patient's voiding function and urodynamic evaluation results 1 year postinjury. Of the 28 patients within 72 hours of SCI, PPS was intact in 17 (60%) and absent in 11(40%), while 15 patients (54%) demonstrated a positive BCR and 13 (46%) did not. One year after SCI, no patient with absent PPS voided unassisted, while of the 17 patients with preserved PPS, 11 (65%) were voiding spontaneously. Of these 11 patients, urodynamic evaluation revealed detrusor areflexia in 1 (9%), normal detrusor function in 2 (18%), and detrusor hyperreflexia in 8 (73%), with 3 of these 8 patients (38%) also demonstrating detrusor-sphincter dyssynergia. At 1 year postinjury, only 2 of 13 patients (15%) with an absent BCR voided spontaneously, while 9 of 15 patients (60%) with an intact BCR were able to void. Although PPS and BCR are moderately sensitive in predicting the return of spontaneous voiding, they cannot predict detrusor hyperreflexia and sphincter dyssynergia. Therefore, urodynamic study remains an essential component of initial urologic evaluation after SCI.

Inguinal cystoceles: a previously overlooked etiology of prostatism in men without bladder outlet obstruction.

PURPOSE: We determine whether inguinal cystoceles, a type of extraperitoneal herniation of the bladder, are responsible for symptoms consistent with prostatism in men without bladder outlet obstruction. MATERIALS AND METHODS: From January 1996 to February 1997 inguinal cystoceles were treated with surgical repair of the floor of the inguinal canal in 8 men with a relatively long history of symptoms consistent with prostatism. The diagnosis of inguinal cystoceles was based on the filling phase of video urodynamic studies done with the patient standing. The clinical outcome of surgery was assessed using the International Prostate Symptom Score and urodynamic findings. RESULTS: All inguinal cystoceles studied were physically occult but clearly detected as wide-mouthed, mild protrusions of the bladder wall in the inguinal region on cystograms obtained with the patient standing. Although clear cystoceles were present on radiography on the right side in 1 case, the left side in 2 and bilaterally in 5, apparent bilateral weakness in Hesselbach's triangle was noted in all at surgery. High detrusor opening pressure and a relatively long opening time were regarded as urodynamic parameters characteristic of this condition. These parameters and subjective symptoms dramatically improved after bilateral surgical repair of the floor of the inguinal canal. CONCLUSIONS: Inguinal cystoceles negatively affect voiding dynamics by increasing opening pressure and opening time, indicating that they should be considered in the differential diagnosis of men with symptoms consistent with prostatism. Video urodynamics is mandatory to detect this condition, which to our knowledge has been previously overlooked on radiography and urodynamics.

High incidence of occult neurogenic bladder dysfunction in neurologically intact patients with thoracolumbar spinal injuries.

PURPOSE: We determine the relationship between lower urinary tract function and somatic neurological status after thoracolumbar fracture. MATERIALS AND METHODS: Within 72 hours of thoracolumbar vertebral fracture we evaluated 44 consecutive patients, including 30 men and 14 women 17 to 84 years old (mean age 38.7), with occult neurogenic bladder dysfunction following incomplete thoracolumbar spinal injuries (American Spinal Injury Association impairment classifications C to E). The neurological level and degree of injury were established, and testing for perianal pinprick sensation and bulbocavernosus reflex was done. Video urodynamic evaluation was then performed between 3 and 14 days after injury but before spinal surgery. RESULTS: Urodynamics revealed neurogenic lower urinary tract dysfunction in all 10 patients with classification C, 82% with D and 41% with E (otherwise completely intact neurologically) impairment. Although pinprick sensation deficiency and decreased bulbocavernosus reflex correlated with injury classification, lower urinary tract dysfunction was present in 62% of the patients with intact pinprick sensation and in 59% with intact bulbocavernosus reflex. CONCLUSIONS: Neurologically intact patients with thoracolumbar spinal injuries may have neurogenic lower urinary tract dysfunction on urodynamics. Pinprick sensation and bulbocavernosus reflex are specific but not sensitive indicators of lower urinary tract dysfunction after spinal cord injury. Although these indicators, which demonstrate somatic nerve function, were absent in all patients with detrusor areflexia, intact pinprick sensation and bulbocavernosus reflex are not sensitive for predicting lower urinary tract function, which depends on autonomic nerve function. Urodynamic evaluation is mandatory for the complete evaluation of patients with incomplete lumbosacral spinal injuries.

Effect of intravesical capsaicin and vehicle on bladder integrity control and spinal cord injured rats.

PURPOSE: To determine the acute effect of intravesical capsaicin on bladder mucosal integrity in normal and spinal cord injured (SCI) rats. MATERIALS AND METHODS: Intravesical reagents were instilled in 5 groups of age and weight matched female rats: 1) control + normal saline solution (NSS), 2) control + ethanol (EtOH), 3) control + capsaicin/EtOH, 4) SCI + NSS, 5) SCI + capsaicin/EtOH. Intravesical instillations were performed 4 weeks after a standard T10 SCI. Intravesical capsaicin (1 mM.) was dissolved in 30% EtOH/NSS. The animals (n = 3 each group) were sacrificed at 30 minutes, 24 hours, 72 hours, and 7 days after intravesical instillation. Whole bladders were harvested, fixed in 10% buffered formalin, and paraffin embedded. Tissue blocks were blind coded and sectioned (5 microns thickness) for histopathological analysis. All sections were initially stained with hematoxylin and eosin (H & E). Specific staining for mucin carbohydrate moieties included periodic acid-Schiff (PAS) and alcian blue. Also, immunohistochemical staining for GP51 (a urinary glycoprotein) was performed. RESULTS: Control and SCI rats exhibited similar bladder mucosal histology by H & E and mucin specific stains. Instillation of saline demonstrated no effect on bladder histology, whereas instillation of intravesical capsaicin induced a profound acute effect of thinning of the epithelium, submucosal edema, and diminished presence of GP51. EtOH produced similar pathological findings, but to a lesser degree than capsaicin. Intravesical capsaicin demonstrated a similar effect in both control and SCI animals. The peak effect was seen after 30 minutes and continued for 24 hours. Partial recovery was noted after 72 hours and complete recovery was evident by 1 week. CONCLUSIONS: The control and SCI rats demonstrated a histologically similar mucosa and glycosaminoglycan layer. The effect of saline instillation on the mucosa was negligible. Intravesical capsaicin dissolved in 30% ethanol/NSS had a profound effect on the bladder urothelium submucosa that was more pronounced than that seen with the ethanol vehicle alone in normal animals.

Gracilis urethral myoplasty: preliminary experience using an autologous urinary sphincter for post-prostatectomy incontinence.

PURPOSE: We investigated the effect of a neurovascular intact gracilis muscle urethral wrap to restore urinary continence in men with severe stress urinary incontinence after radical retropubic prostatectomy. MATERIALS AND METHODS: Three men with stress incontinence after radical retropubic prostatectomy and external beam radiation therapy for adenocarcinoma of the prostate underwent gracilis urethral myoplasty. Video urodynamic evaluation and cystourethroscopy revealed Valsalva leak point pressure of less than 40 cm. water and a damaged urinary sphincter mechanism in all 3 patients. One man underwent concomitant ileocystoplasty. RESULTS: At 6 to 24-month followup all patients reported improved continence. Mean Valsalva leak point pressure increased from 26.3 +/- 3.2 cm. water before to 83.0 +/- 32.1 cm. water after surgery. The gracilis muscle urethral wrap did not have a deleterious effect on erectile function or ambulation. Complications included 1 wound infection. CONCLUSIONS: An autologous gracilis muscle urinary neosphincter can be constructed in the bulbous urethra in a fashion similar to that of the artificial urinary sphincter with encouraging results in this preliminary series. The gracilis neosphincter may be an alternative to the artificial sphincter, especially in patients at higher risk for complications, such as after radiation and cryotherapy.

Gracilis urethromyoplasty--an autologous urinary sphincter for neurologically impaired patients with stress incontinence.

PURPOSE: To investigate the effect of a neurovascularly intact gracilis muscle urethral wrap, to be used to restore urinary continence as a transposed urinary sphincter graft, in patients with neurogenic lower urinary tract dysfunction. METHODS: Five neurologically impaired men with a denervated and damaged urinary sphincter mechanisms were treated. The etiology of sphincteric insufficiency included sphincter denervation in three patients, external sphincterotomy in one, and urethral trauma due to a chronic indwelling catheter in one. All patients underwent gracilis urethromyoplasty sphincter reconstruction. Two patients also underwent concomitant ileocystoplasty and one patient ileocystostomy because of poor bladder compliance and a bladder capacity of < 200 ml. RESULTS: The gracilis urethromyoplasty functioned as a new autologous sphincter with follow-ups ranging from 6-35 months. The surgery was successful in four patients. Three of the four patients were managed with intermittent catheterization, and one managed by ileocystostomy. The fifth patient continued to require an indwelling urethral catheter. CONCLUSION: Gracilis urethromyoplasty achieves compression of the urethra using a neurovascularly intact muscle graft. The functional urethral closure, obtained from the gracilis muscle wrap, assures dryness, and permits intermittent self-catheterization. It also avoids the risks of infection, erosion, or malfunction associated with the artificial urinary sphincter. The potential exists for electrical stimulation of this muscle graft to allow volitional control of the neo-sphincter mechanism, and voluntary voiding.

Molecular marker for development of interstitial cystitis in rat model: isoactin gene expression.

PURPOSE: To determine whether the differential expression of bladder smooth muscle isoactin can be used as a molecular marker for the development of interstitial cystitis (IC). METHODS: Three groups of five female Sprague-Dawley rats each underwent urethral catheterization and intravesical instillation of 0.5 ml. of 0.4N HCl. One group was sacrificed one, two and four weeks after the application of HCl, and their bladders harvested for histologic examination and evaluation using Northern blot analysis of bladder smooth muscle isoactins. Five control animals were sacrificed and their bladders harvested to establish isoactin gene expression of bladder smooth muscle in the normal state. The bladders of the rats in each group were excised, immediately frozen in liquid nitrogen, pooled, then stored -70 degrees C until needed for RNA isolation. Isoactin cDNA probes have been developed, therefore isoactin specific cDNA insert fragments were isolated and insert DNA was purified by gel electrophoresis. Total cellular RNA was isolated from 1.0 gm. of bladder smooth muscle from each group. After spectrophotometric quantification, Northern Blot analysis was performed using 2% agarose-formaldehyde gels and Biotrans nylon membranes. Two complete Northern Blot series were run on a single gel and blotted to a single membrane to eliminate gel and blotting discrepancies. RESULTS: Microscopic histologic analysis revealed detrusor mastocystosis and eosinophilia as has been noted in humans with chronic interstitial cystitis. Two weeks after the intravesical application of hydrochloric acid, the relative expression of gamma-smooth muscle isoactin was noted to increase by 1.7-fold, while alpha-smooth muscle isoactin expression increased by a factor of 9. These effects were seen to stabilize four weeks after acid application. CONCLUSIONS: The intravesical application of dilute HCl in rats results in a histologic appearance which mimics that seen in humans with interstitial cystitis. The appearance of detrusor mastocytosis and eosinophilia was accompanied by a relative decrease in the expression of gamma- and a relative increase in alpha-smooth muscle isoactin gene expression. This pattern of smooth muscle isoactin expression is consistent with a more immature and possibly synthetic smooth muscle phenotype, which may be responsible for the clinical presentation of those with IC. Northern blot analysis of bladder smooth muscle cells may serve as an effective marker for the development of interstitial cystitis in humans.