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Purpose: A bladder control system for spinal cord injured (SCI) patients is needed that can be implanted with minimally invasive methods. New Permaloc bipolar electrodes consisting of 6 mm helical, wire, stimulating surfaces separated by 3 mm and a polypropylene securing barb (Synapse Biomedical Inc) were developed for this application. They are implanted on the bladder wall with a 16 gauge needle, a minimally invasive method. Methods: Seven swines were anesthetized, the lower urinary tract exposed and instrumented with pressure transducers. Four Permaloc TM electrodes were implanted following identification of effective bladder wall stimulation sites next to the ureters and dorsal neurovascular bundle. Bladder stimulation to induce high pressures was conducted at 40 Hz, 400 � s pulses, 5 s stimulation periods and a high stimulating current of 40 mA. Results: At the high stimulating current peak bladder pressures were low, ranging from 12±2 to15±3 cm H20, insufficient to induce urination. Urethral sphincter contractions occurred during high bladder pressure. A spinal reflex role for high sphincter pressures during stimulation was shown by similar high pressures recorded during a bladder squeeze test without stimulation. Conclusions: Stimulation with Permaloc TM bipolar electrodes at high currents produced insufficient bladder pressures for urination. Further modifications of the electrode such as greater separation of the bipolar stimulating surfaces or changes in the testing methods such as alternative animal models are needed to induce high bladder pressures without side effects.

Urinary retention is a serious urological problem associated with spinal cord injuries (SCIs) and other pelvic disorders. Effective methods of pelvic nerve stimulation were investigated for this problem. Following anesthesia in five dogs, the bladder was surgically exposed. Bladder and anal sphincter pressures were recorded. Testing was first conducted with probe electrodes. Barb electrodes were then implanted with a needle near the pelvic plexus nerves and the bladder wall. We tested different electrode arrangements and stimulating parameters to induce bladder contractions without skeletal muscle stimulation. The pelvic plexus nerves near the bladder were identified, and the barb electrodes were effectively implanted. Stimulation with bipolar and bilateral electrodes induced pressures over 30 cmH(2)O without skeletal muscle activation. Common stimulation parameters were 40 pps, 400 microseconds pulse duration, and 15 to 25 mA stimulating current applied for 3 s. Effective electrode implantation methods were shown. Also identified were electrode arrangements and stimulating parameters that induced strong bladder contractions without skeletal muscle activation. However, voiding studies were not conducted. Further studies with barb electrodes are warranted, and these methods may have applications for bladder stimulation following SCI.

Mono-hydroxylated polychlorinated biphenyls (OH-PCBs) are found in human biological samples and lack of data on their potential estrogenic activity has been a source of concern. We have extended our previous in silico 2D QSAR study through the application of advance techniques such as docking and 3D QSAR to gain insights into their estrogen receptor (ERα) binding. The results support our earlier findings that the hydroxyl group is the most important feature on the compounds; its position, orientation and surroundings in the structure are influential for the binding of OH-PCBs to ERα. This study has also revealed the following additional interactions that influence estrogenicity of these chemicals (a) the aromatic interactions of the biphenyl moieties with the receptor, (b) hydrogen bonding interactions of the p-hydroxyl group with key amino acids ARG394 and GLU353, (c) low or no electronegative substitution at para-positions of the p-hydroxyl group, (d) enhanced electrostatic interactions at the meta position on the B ring, and (e) co-planarity of the hydroxyl group on the A ring. In combination the 2D and 3D QSAR approaches have led us to the support conclusion that the hydroxyl group is the most important feature on the OH-PCB influencing the binding to estrogen receptors, and have enhanced our understanding of the mechanistic details of estrogenicity of this class of chemicals. Such in silico computational methods could serve as useful tools in risk assessment of chemicals.

The association between the development of bladder cancer and chronic bladder irritation is well established in the literature. Chronic urinary tract irritation can be the result of bacterial infections, foreign bodies, trauma of repeated catheterization, neurogenic bladder, urolithiasis, or chronic bladder outlet obstruction, all which have been implicated in the pathogenesis of non-bilharzial squamous cell carcinoma of the bladder (SCC). With many of the aforementioned factors present in patients with spinal cord injury, several retrospective studies have demonstrated a 16-28 fold increased relative risk of bladder cancer, with SCC accounting for 10 times more cases of bladder cancer compared to the general population. In this report, we present the case of incidentally-discovered SCC of the bladder found within sphincter/prostate chips of a patient with neurogenic bladder due to spinal cord injury n clean intermittent catheterization ho underwent sphincterotomy with negative cystoscopic findings.

BACKGROUND Microstimulators are new devices that should be considered for management of lower urinary tract problems following spinal cord injury (SCI) such as urinary retention. These devices are small (less than 25 mm by 5 mm) with the electrodes located on the ends of the stimulator. However, it is not known whether the small electrodes on these devices would be effective in stimulating the plexus of nerves that innervate the bladder. The aim of the present study was to provide preliminary observations with model microstimulators (M-Micro) for inducing bladder contractions in an SCI animal model. Bladder wall and pelvic plexus stimulation sites were compared. Additional investigations evaluated parameters such as stimulation polarity, frequency, and period as well as bladder filling volume. METHODS In an initial survival surgery, bilateral M-Micros were implanted on the bladder wall and the pelvic plexus along the urethra in 3 female cats. A second survival surgery was conducted 3 to 5 weeks later to produce a T1 0 SCI. Studies are reported following the second survival surgery. These studies included the effects of stimulation and bladder filling. RESULTS The postmortem location of the implanted pelvic plexus M-Micro was previously described as near the bladder neck. Therefore, the pelvic plexus location is described in this report as "pelvic plexus (bladder neck)" stimulation. The observations showed effective stimulation with pelvic plexus (bladder neck) stimulation and voiding in some cases. Stimulation was limited by side effects of increased abdominal pressure and leg movement. Other factors also affected the response to stimulation, including the initial bladder volume and stimulating parameters. Fluoroscopy showed that when stimulation did not induce voiding the striated urethral sphincter was closed. CONCLUSIONS This case series of 3 SCI animals showed that the small electrodes on the M-Micro could be used to stimulate the bladder with contractions and voiding in some cases. The pelvic plexus (bladder neck) location for the M-Micro may be a better location than higher on the bladder wall. Limiting side effects of stimulation included leg movement and increased abdominal pressure. Additional important factors included the stimulation parameters, initial bladder volume, and the function of the skeletal urethral sphincter.

Microstimulators are a new type of neuroprosthetic device that should be considered for applications such as micturition control after spinal cord injury (SCI). These devices are small (less than 25 mm by 5 mm) and the electrodes are located on the ends of the stimulator. The aim of the current study was to develop methods for chronic implantation of model microstimulators (M-Micro) on the bladder wall and pelvic plexus of female cats. A postmortem evaluation of the effects of 3 months of implantation is reported.Techniques to produce the M-Micro are described. Four of these devices were implanted in 4 female cats and maintained after the initial instrumentation surgery and a second survival surgery for SCI (at T10). Using a single suture tied around the M-Micro, these devices were secured to the bladder wall or the fat pads adjacent to the pelvic plexus. Additional instrumentation was implanted, including 2 catheters in the bladder, 1 abdominal balloon, and electromyography electrodes in the urethral and anal sphincters. Postmortem observations of the location of the M-Micro on the bladder wall were conducted after fixation.The animals' conditions were good. One animal was sacrificed early because of a skin infection. A single suture was sufficient to anchor the M-Micro. However, during the surgical implantation the pelvic plexus M-Micro ended up close to the bladder neck. Extensive fibrous connective tissue formed around the M-Micro and implanted catheters on the bladder wall. This appeared to result, in part, from multiple devices implanted on or near the bladder wall.These pilot studies showed that the M-Micro could be easily constructed and secured to the bladder wall or fat pads close to the pelvic plexus. There was a concern that the pelvic plexus location for the M-Micro ended near the bladder neck during the surgical implantation; however, these devices did not appear to migrate over this short, 3-month implantation period. The extensive connective tissue responses of the bladder wall to the tubes, wires, and M-Micro was a major concern. The M-Micro appears to be a good device to assess the potential of commercial microstimulators for use in micturition control.

THE CASE 63-year-old man presented to our clinic with complaints of a right testicular mass. This mass Awas noted 3 weeks earlier while the patient was performing self-examination in the shower. He reported some aching but denied frank pain. He also denied voiding symptoms, gross hematuria, penile discharge, or weight loss; however, he reported rare night sweats. His urologic history was significant only for a right inguinal hydrocele repair, at age 13, and a vasectomy. His medical and surgical history was significant for coronary artery bypass, hypothyroidism, hypertension, and type 2 diabetes. He had a remote 38 pack-year smoking history. On physical examination, the patient had a large fixed right testicular mass. Complete blood cell count and blood biochemistry results were within normal limits. Serum alpha-fetoprotein, b-human chorionic gonadotropin, and lactate dehydrogenase levels were not elevated. Scrotal ultrasound revealed small bilateral epididymal cysts, small bilateral hydroceles, and a normal-appearing left testicle. A heterogeneous. 6-cm well-circumcised solid mass was present on the inferior pole of the right testicle (Fig. 1). The mass appeared to have a capsule, although this finding could not be definitively determined from the ultrasound alone. Chest x-ray imaging did not show any pulmonary nodules. Computed tomography of the abdomen and pelvis with contrast revealed small lymph nodes in the periaortic, internal and external iliac chain, and in the mesentery. The largest node was in the periaortic region, measuring 8 mm, while the other nodes were in a 5to 7-mm range.

Background/objectives High urethral resistance or detrusor-sphincter dyssynergia (DSD) is characterized by obstructed voiding during bladder contractions. DSD is caused by an exaggerated pelvic floor reflex resulting from sensory input from elevated pressure in the bladder that produces reflex constriction of the urethral sphincter. The objective of this study was to determine whether sensory input from the bladder produced synergistic or dyssynergic pelvic floor reflexes following SCI in an animal model. Methods A pelvic floor reflex that shares the same motor pathway with DSD is the bulbocavernosus (BC) reflex. The BC reflex was elicited with electrical stimulation in 4 male cats with T1 spinal injury, and recorded as an anal sphincter contraction. Recordings were obtained during control and elevated bladder pressures. Increased bladder pressure was induced with either manual pressure (Crede procedure) or spontaneous contractions resulting from bladder filling. Results During the control period, the BC reflex indicated by the peak anal pressure response was 23 +/- 6 cmH2O. During elevated bladder pressure of 34 +/- 18 cmH2O, the BC response decreased to 10 +/- 3 cmH2O (not significant), showing a synergistic relationship. Anal sphincter tone between BC reflex tests showed a dyssynergic response. All 4 animals showed increased tone during elevated bladder pressures that averaged 9 +/- 5 cmH2O. Because abdominal pressure was not recorded, the significance is not clear. However, there was further support of a dyssynergic relationship based on increases in the anal and urethral electromyography recordings and some pelvic floor spasms during the elevated bladder pressure. Conclusions Because 2 different pelvic floor activities were observed during increased bladder pressures, this animal model may be described best as a mixed model. This model shows both synergistic and dyssynergic relationships between the bladder and the BC contractions. Although observed changes were not significant, the unique observations of synergistic bladder-sphincter activity shown by the inhibited BC reflex is in marked contrast to the strictly dyssynergic bladder-sphincter relationship seen in SCI patients.

Sodium and potassium are essential for human health. They are important ions in the body and are associated with many physiologic and pathophysiologic processes. The chapter summarizes the basic physiologic actions of sodium and potassium on membranes of the neurologic and muscular systems. It provides information regarding the kinetics, i.e., absorption, distribution, and excretion of these ions and their movement between the intracellular and extracellular compartments. It also explains the physiologic systems that can influence proper homeostasis between sodium and potassium. Concentrations of sodium in the blood that exceed or do not reach the normal value range are called hypernatremia or hyponatremia, respectively. Similarly, the clinicians recognize hyperkalemia and hypokalemia. Pathologies associated with these states are described and examples of some of the diseases are presented here.

Implantable neuroprosthetic systems are an important area of practice and research in urinary care for individuals with spinal cord injury (SCI). These devices need to manage three lower urinary tract conditions: urethral sphincter contractions during bladder contractions, an underactive bladder producing poor voiding responses, and neurogenic detrusor overactivity causing urinary incontinence. Two neuroprosthetic approaches have addressed these conditions: sacral anterior root stimulation (SARS) and direct bladder wall stimulation (DBWS). The SARS approach is commercialized for SCI bladder management as the Brindley-Finetech Bladder Control System and is available in Europe. Limitations of this device include invasive surgery and the need for rhizotomy of sacral dorsal (sensory) nerve roots. The DBWS implants produced daily voiding in many SCI individuals, however, clinical use was discontinued primarily because of technical concerns with stimulators and electrodes as well as some cases of poor voiding responses and side effects. These limitations are reviewed as well as efforts to return DBWS to clinical investigations using Permaloc® Systems (Synapse Biomedical Inc., Oberlin OH). This new neuroprosthetic platform includes mapping and intramuscular electrodes as well as multilead cables and new stimulator devices.

Purpose: We evaluated a method of estimating detrusor pressure at home in patients with myelomeningocele who perform clean intermittent catheterization to empty the bladder.Materials and Methods: Patients with myelomeningocele who perform clean intermittent catheterization underwent cystometry. At home they determined bladder pressure before draining a full bladder and after partial draining with the bladder almost empty. Home estimate of detrusor pressure was calculated using the formula, full bladder pressure - almost empty bladder pressure.Results: A total of 4 boys and 5 girls with a mean age plus or minus standard deviation of 9.6 ± 7.9 years who were enrolled in our study made 16.9 ± 15.2 home bladder pressure and volume recordings weekly each during a mean of 5.8 ± 4.3 months. Mean bladder capacity determined at home was significantly greater than cystometric capacity (354 ± 185 versus 250 ± 146 ml.). At a mean home and cystometric volume of 190 ± 110 ml. full bladder pressure at home was n...

The purpose of this study was to evaluate a "suture" type electrode for direct bladder stimulation in an animal model of a lower motor neuron lesion. During an initial surgery, five male cats were instrumented under anesthesia using multistranded, 316 LVM, stainless-steel, wire electrodes implanted on the bladder wall serosa above the trigone area. Electrodes were constructed with a needle attached to the end that was removed after suturing the electrode in place. Additional instrumentation included urinary bladder catheters (tubes) for pressure recording and filling, and hook type electrodes for leg and pelvic floor electromyography recording. Chronic bladder filling and stimulation studies were conducted in tethered animals three to four weeks following surgery. To test these electrodes in a spinal cord injury model, a lower motor neuron lesion was performed including the sacral cord and complete nerve roots at L6 and below. These animals were evaluated during weeks 3 and 10 after injury. Direct bladder stimulation induced active contractions and voiding both before and after spinal cord injury. Effective stimulation parameters consisted of 40 pulses per s, 300 micros to 1 ms pulse duration, a stimulation period from 3 to 4 s, and a stimulation current from 10 to 40 mA. Fluoroscopy revealed an open membranous urethra during stimulation and following stimulation. A small diameter penile urethra was observed to limit flow. Postmortem evaluation of the suture electrode revealed no abnormalities such as corrosion, migration into the bladder lumen or displacement. These findings indicate that suture electrodes are suitable and effective for short-term implantation in the lower motor neuron animal model.

This study examined subjective continence status and use of subsequent alternative therapeutic procedures at long-term follow-up after collagen injection for stress incontinence (SI) in women. Seventy women who underwent collagen injection for SI were identified by retrospective chart review and surveyed by mail questionnaire for subjective continence status, daily pad usage pre- and post-treatment, and use of anticholinergics and alternative procedures. Questionnaire responders' versus non-responders' mean age, follow-up, and pad usage were compared. Thirty-three women (47%) responded on questionnaires. Of the 33, 50% were dry or subjectively improved at long-term follow-up and 91% had not chosen an alternative invasive treatment after collagen injection. Chart review showed responders were not significantly different from non-responders in mean age (65.9 vs. 69.2 years), pad usage (0.6 vs. 0.8 pads/day), or follow-up (4.5 vs. 4.3 years). Collagen injection, a minimally invasive treatment for SI, appears to benefit a significant number of women.

Purpose: We evaluate a pressure gauge used at home for patients with myelomeningocele on clean intermittent catheterization to provide a system for inexpensive frequent monitoring of bladder pressures.Materials and Methods: Subjects with myelomeningocele using clean intermittent catheterization underwent cystometry in the laboratory. At home they obtained weekly volumes and bladder pressures before and after emptying. Home estimate of detrusor pressure was defined as full bladder pressure minus empty bladder pressure. Medication changes, subject position and urinary tract symptoms were noted.Results: A total of 11 subjects 10.5 +/− 7.3 years old have been enrolled and have made 16.7 +/− 12.6 weekly home bladder pressure and volume recordings in 4.7 +/− 3.1 months. Bladder capacities measured at home were 132 +/− 47% of cystometric capacities. At volumes of data overlap home full pressures (31 +/− 10 cm. water) were not statistically different from cystometric vesical pressures (25 +/− 9 cm. water)...

Individuals with spinal cord injury and multiple sclerosis are at high risk for developing kidney dysfunction due to high bladder pressures. We have developed a device for frequent monitoring of bladder pressures at home in those patients who use intermittent catheterization to empty their bladders. Of eight subjects enrolled in the study, only five conducted home recording of pressure. Vesical and abdominal pressures measured at home were significantly lower than clinical cystometric pressures. However, subtracted detrusor pressures obtained from home records and cystometric records were not significantly different. The home detrusor pressures were consistent over a large time and volume range. Therefore, the home monitoring method could be used to establish a normal range of bladder pressures at home and to rapidly identify high bladder pressures in advance of upper urinary tract deterioration.

Sacral ventral root stimulation in conjunction with sacral dorsal rhizotomy has been effective in promoting voiding in individuals with upper-motor-neuron spinal cord injury. We report on two patients who had variable voiding responses to stimulation during the first six months after electrode implantation. We used videourodynamic records and daily voiding records to characterize their voiding difficulties. Different methods were used to improve voiding, including seating adjustments and changes in stimulation parameters. The first patient was unable to empty his bladder on a regular basis with stimulation using 24 pulses per sec stimulating frequency for the first two months after implantation. Voiding was substantially improved by using 35 pulses per sec. At the end of six months, he is regularly emptying his bladder with stimulation and is on an every-second-day bowel program. However, his bowel program has been irregular. The second patient had very good voiding when stimulation was applied in bed, but he had poor voiding with high residual volumes when sitting in his wheelchair. Voiding was improved when he used a wheelchair cushion that was cut out in the back or lifted his buttocks off the chair. These procedures appeared to reduce perineal pressures. This patient has bowel care on alternate days and his bowel care time has been reduced following implantation of the device. Neither of the patients experienced an erection with the device. Both patients feel positive about their implant experience.

Sodium and potassium are essential for human health. They are important ions in the body and are associated with many physiologic and pathophysiologic processes. The chapter summarizes the basic physiologic actions of sodium and potassium on membranes of the neurologic and muscular systems. It provides information regarding the kinetics, i.e., absorption, distribution, and excretion of these ions and their movement between the intracellular and extracellular compartments. It also explains the physiologic systems that can influence proper homeostasis between sodium and potassium. Concentrations of sodium in the blood that exceed or do not reach the normal value range are called hypernatremia or hyponatremia, respectively. Similarly, the clinicians recognize hyperkalemia and hypokalemia. Pathologies associated with these states are described and examples of some of the diseases are presented here.

The authors report a case of successful pregnancy following augmentation cystoplasty in a patient who had refractory interstitial cystitis. A review of the literature discusses the incidence of pyelonephritis, premature delivery, impaired urinary drainage, renal insufficiency and the need for Cesarean section in pregnant patients who have had ileal conduits and augmentation cystoplasties. Careful urologic monitoring of such patients after urinary diversion or augmentation cystoplasty should result in a successful pregnancy.

Predicting toxicity quantitatively, using Quantitative Structure Activity Relationships (QSAR), has matured over recent years to the point that the predictions can be used to help identify missing comparison values in a substance’s database. In this manuscript we investigate using the lethal dose that kills fifty percent of a test population (the LD50) for determining relative toxicity of a number of substances. In general, the smaller the LD50 value, the more toxic the chemical, and the larger the LD50 value, the lower the toxicity. When systemic toxicity and other specific toxicity data are unavailable for the chemical(s) of interest, during emergency responses, LD50 values may be employed to determine the relative toxicity of a series of chemicals. In the present study, a group of chemical warfare agents and their breakdown products have been evaluated using four available rat oral QSAR LD50 models. The QSAR analysis shows that the breakdown products of Sulfur Mustard (HD) are predicted to be less toxic than the parent compound as well as other known breakdown products that have known toxicities. The QSAR estimated break down products LD50 values ranged from 299 mg/kg to 5,764 mg/kg. This evaluation allows for the ranking and toxicity estimation of compounds for which little toxicity information existed; thus leading to better risk decision making in the field.

High urethral resistance caused by detrusor-sphincter dyssynergia (DSD) occurs following spinal cord injury (SCI) and results in poor voiding. A major pelvic floor reflex that may be involved in DSD is the bulbocavernosus reflex (BC) and evaluation of this reflex during the micturition cycle may provide additional information regarding this role. The periodic BC observed during micturition via cystometry is described as a dynamic bulbocavernosus reflex (DBC). The DBC was induced in upper motor neuron SCI patients using periodic dorsal penile nerve stimulation; the evoked reflex response was recorded with an anal sphincter pressure sensing balloon. Stimulation of 15-50 mA was applied at the base and dorsal side of the penis with surface electrodes, pulsed at a rate of 0.25 Hz. By applying the stimulation during cystometry, the BC reflex could be evaluated throughout the entire micturition cycle. Results showed that the DBC increased during bladder filling and bladder contractions. These findings indicate that an enhanced BC reflex is a major factor causing increased urethral resistance during micturition.

Urodynamic evaluation has been helpful in the diagnosis of stress incontinence in female patients. We evaluated two new parameters using standard urodynamic measures that were recorded during micturition. These two parameters were obtained by fitting a classic fluid dynamic equation for flow through short rigid tubes to published data of voiding, videourodynamics. This formula, an area equivalent factor female (AEFf) indicates urethral cross-sectional opening area based on bladder pressure and flow measures. The first parameter, maximal urethral opening or maximal AEFf, was observed at maximal flow, and this value further divided by the detrusor pressure determined the second parameter, the urethral total compliance. A preliminary retrospective study was conducted using detrusor pressure and urine flow data from stress incontinent (n=14) and continent (n=5) female patients. There was a trend toward greater maximal urethral opening at 14.2±5.9 mm2 in the stress incontinent group compared to the continent group, 9.2±2.9 mm2 (p=0.09). The stress incontinent group also showed a strong trend (p=0.09) toward greater total compliance values of 0.78±0.5 mm2/ cmH2O, compared to 0.35±0.2 mm2/cmH2O in the continent group. These parameters may have potential in the evaluation and understanding of stress incontinence.

Encouraged by recent clinical reports of micturition induced in patients by direct bladder stimulation, we conducted a study of optimum methods of direct bladder stimulation. During surgery six male cats received eight large surface-area woven eye electrodes sutured to the bladder wall serosa, four on the bladder dome and four adjacent to the trigone area. Two additional small surface-area single knot electrodes were sutured in the trigone area. Suprapubic and intraperitoneal tubes were placed for pressure recording and bladder filling. Leg and pelvic floor EMG electrodes were also used for tethered recordings. One to eight weeks after surgery, optimum stimulation methods were evaluated as the animal freely moved about a urodynamic recording cage. Electrodes in the trigone region were more effective than electrodes on the dome and induced bladder contractions and voiding similar to spontaneously induced voiding with bladder filling. Large surface area, woven eye electrodes, composed of multi-stranded 316LVM stainless steel wire, were more effective than smaller surface area single knot electrodes. High stimulating frequencies (40 Hz) were better than lower frequencies (10 to 20 Hz), and a 1 millisecond pulse duration was optimal. Pulsing with stimulating currents from 10 to 25 mA induced effective bladder contractions with voiding when applied for 3 seconds. However, lower currents using longer stimulation periods were also effective. Bipolar electrodes with both electrodes on the bladder wall were superior to monopolar arrangements with the positive ground electrode along the animal’s back. We concluded that in the able-bodied cat model, bladder contractile activity for micturition can be induced with direct bladder stimulation and with little discomfort. An effective stimulation protocol consists of capacitor-coupled monophasic pulses with large surface area bipolar electrodes in the trigone region. Stimulating parameters of 40 Hz, 1 msec., 10 to 25 mA applied for 3 seconds were optimal. In addition, based on corrosion resistance observations, the electrodes are quite suitable for long-term studies.

SUMMARY The early urologic management of the patient with spinal cord injury can be straightforward. Intermittent catheterization is the most acceptable therapy until final urologic decisions have been made based on appropriate urodynamic studies. The intermittent catheterization should be aggressive and periodic to empty the bladder, and the patients should be encouraged to do this independently when they are able to. Should any changes occur during this management, such as fever, infection, or dysreflexia, urodynamic studies should be done to identify high-pressure voiding with a high (40–60 cm H2O) leak-point pressure. Then, appropriate therapy should be instituted to lower the bladder pressure, including, initially, anticholinergic drugs and, ultimately, maybe another method such as a sphincterotomy. We usually reserve aggressive invasive therapy for patients whose spinal cord injury has totally evolved and who are rehabilitating, usually no less than 6 months after spinal cord injury, except in severe cases. There is controversy about the initial and long-term treatment of patients with intermittent catheterization, antibiotics, or both. This controversy will continue. Upper urinary tract complications associated with spinal cord injury have been virtually eliminated with better urologic therapy, and the incidence should continue to be negligible if proper therapy is given. Patients who have maintained good bladder management and who are doing well physically with good nutritional habits and medical care since their spinal cord injury will have a much better outcome than those who have more severe urologic and medical problems.

Urodynamic evaluation of stress incontinence has failed to result in consistent diagnostic parameters. Using retrospective female bladder pressure and urine flow data, we evaluated two parameters based on a conductance formula. This formula was derived from fitting a classical fluid dynamic equation to published data of voiding cystourethography. The Area Equivalent Factor-female at maximal flow represents maximal urethral opening and this value further divided by the pressure is the total urethral compliance. A stress incontinent group had a strong trend toward greater maximal urethral opening and total urethral compliance than a continent group. These parameters may, therefore, have potential in the evaluation and understanding of stress urinary incontinence.

Background: Although asbestos in general is well known to cause a range of neoplastic and non-neoplastic human health effects, not all asbestos fiber types have the same disease-causing potential, and the mode of action (MOA) of specific types of asbestos and related fibers for various health outcomes are not well understood. Objectives: A workshop was held to discuss the state of the science of the MOA for asbestos-related disease. The objective was to review the range of asbestos-induced health effects (including those at sites remote to the respiratory tract). We sought to identify existing knowledge gaps and define what research is needed to address these gaps and advance asbestos research. Discussion: Discussions centered on areas of uncertainty in the field, including the ways asbestos is defined and characterized, the role of different fiber characteristics (e.g., length and mineralogy) in disease, and the impact of low-dose exposures on human health. Studying the dosimetry and mode of action of multiple fiber types would enhance our understanding of asbestos-related disease. To better elucidate the MOA of specific asbestos fibers, the risk assessor requires data as to specific characteristics of asbestos in determining fiber toxicity (e.g., surface area, mineral type), which may inform efforts to assess and control exposures and prevent adverse human health outcomes for the diverse range of fiber types. Specific research aims were defined for these topics and for overarching issues to be addressed, including the use of standardized terminology, test materials, and better experimental models to aid in data extrapolation to humans. Conclusion: To resolve these and other issues, participants agreed that diverse scientific disciplines must coordinate to better understand the MOA leading to the various asbestos-related disease end points.

Detrusor hyperreflexia causing voiding dysfunction in spinal cord injury patients is a difficult problem and is not always treated effectively by anticholinergic agents. We have been investigating electrical stimulation methods to inhibit hyperreflexia and dorsal penile nerve stimulation is the most promising. Six chronic suprasacral spinal cord injury men (average age 36 years) underwent stimulation testing with water cystometry before, during and after stimulation. Dorsal penile stimulation was done with carbon rubber butterfly electrodes (Medtronic) with parameters of 5 pulses per second, 0.35 msec. pulse duration, and current at a level above the threshold for pelvic twitching activity and adjusted for optimal bladder effect (range 25 to 70 mamp.). In all 6 patients the cystometrogram during stimulation showed an increase in bladder volume over the prestimulation cystometrogram (range 27 to 150%). In 2 patients there was no detrusor activity after filling to 500 cc. Stimulation was then stopped and a spontaneous contraction occurred. The cystometrogram conducted after the stimulus also had less volume than that performed during stimulation but it was larger than the prestimulation volume. Penile nerve stimulation was painless with no side effects. Penile nerve electrical stimulation is effective for inhibiting bladder hyperreflexia and should be easily adaptable for chronic home use as an alternative to current therapy.

Clear cell adenocarcinoma in a urethral diverticulum in the female is a very rare and unusual tumor. We recently treated two patients with this tumor. Their presentation, histologic evaluation, and management are reviewed in light of the limited experience in the literature.

Background Better methods are needed for recording urethral function for complex urologic problems involving the bladder, urethra, and pelvic floor. Objective To evaluate a balloon catheter for recording urethral pressure and function using bench-top testing and evaluation in an animal model. Methods Balloon pressure-recording methods included slightly inflating the balloon with water and placing the pressure transducer on the distal end of the catheter. For bench-top testing, manual procedures and a silastic tube with a restriction were used. In 3 anesthetized dogs, pressure recorded from the skeletal urethral sphincter was induced with electrical stimulation of the sphincter. Anal sphincter pressure was also recorded. Results Bench-top testing showed good pressure recordings, including a confined peak at the tube restriction. Animal tests showed urethral pressure records with rapid responses when electrical stimulation was applied. Peak pressure at the urethral skeletal sphincter was 55.7 +/- 15 cmH2O, which was significantly higher than the peak pressure recorded 2 cm distally in the proximal urethra (3.3 +/- 2.3 cmH2O). Peak anal pressures were smaller and unchanged for the 2 stimulations. Conclusions Balloon-pressure recordings showed rapid responses that were adequate for the tests conducted. In the animal model, high-pressure contractions specific to the skeletal urethral sphincter were shown. Balloon-tipped catheters warrant further investigation and may have applications for the evaluation of detrusor-sphincter dyssynergia after spinal cord injury or for stress urinary incontinence.

We report on a sixty-five-year-old man with hematuria secondary to superficial bladder cancer. Because of previous urethral trauma, a complete transurethral resection of his bladder tumor could not be done. He, therefore, underwent cystectomy, at which time we incidentally found a transitional cell carcinoma of the left ureteral stump that had been left from a previous left nephrectomy for a World War II-related injury. This case underscores the importance of a thorough investigation of the complete urinary tract in a patient with hematuria or other urinary tract symptoms even if an obvious cause is found for his symptoms.

In spinalized dogs under Nembutal anesthesia, electrical stimulation of sacral nerves with electrodes inserted into the sacral canal induced maximal urinary bladder contractions. The amplitude of the peak vesical pressure varied with the bladder volume. Active peak pressures were highest when the bladder volume was 25 to 50 ml. Pressure declined to less than 50% of its maximum value at a bladder volume of 400 ml. In order to further describe the contractile properties of the detrusor muscle, wall tension was calculated using Laplace's law, wall stress was determined as tension per unit wall thickness, and the circumference of the vesical volume was calculated as a measure of muscle length. Active detrusor wall tension during stimulation tended to be highest at the midrange of volumes, whereas the wall stress increased linearly with increasing bladder volume. This increase in wall stress was secondary to the wall becoming thin at large volumes.

This feasibility study was conducted to evaluate design features of the novel intraurethral valved catheter, Surinate (Urovalve, Inc; Newark, New Jersey). The device extends from the bladder neck to just beyond the external sphincter and contains a valve that can be activated by an external magnet for bladder emptying. Five patients were recruited from the Edward Hines Jr Department of Veterans Affairs Hospital spinal cord injury population. We conducted cystometry and cystoscopy to evaluate the lower urinary tract. Then, the device was inserted for 24 hours with careful monitoring. The catheter was removed from the first patient because he developed autonomic dysreflexia during implantation. The next four patients used the catheter overnight and tolerated it well: one with independent use and two with increased abdominal pressure. Emptying time was 208 +/- 99 s, residual was 42 +/- 33 mL, and the first-stream flow rate was 1.8 +/- 0.7 mL/s. The safety tether was used in three patients because the extraction device did not work. Results showed effective implantation and stability of the device in the urethra. However, objectives for use and extraction were not met. This feasibility study provided important information that will help guide design improvements for the intraurethral valved catheter.

The urodynamic results in 68 females with urinary retention were reviewed. Therewere two groups: 39 patients with neurologic causes for retention, and 29 patients in whom possible causes for retention included: psychological history (15 patients), gynecologic pathology, and urinary tract infection. Nine patients in the neurogenic group and 13 patients in the non-neurogenic group had undergone urethral dilatation with no improvement. Upper urinary tract evaluation was unremarkable. Detrusor failure was the prominent bladder pattern in both groups. In the neurogenic group, low pressure detrusor activity was also present in 10 patients, 3 of whom had sphincter dyssynergia. Flow rate, surface electromyography, and bethanechol supersensitivity test could not help differentiate neurogenic from non-neurogenic detrusor failure. The notation of abnormal bladder sensation did significantly differ between the groups, but was of limited accuracy as an indicator of neurogenic retention. Self-intermittent catheterization was the most effective treatment for both groups, with some patients voiding adequately in follow-up. Although no one test can accurately differentiate neurogenic from nonneurogenic female urinary retention, careful neurourologic evaluation will help guide us to more appropriate management.

Rectal involvement from prostate cancer occurs in 1.5-11% of cases. A rarer presentation is that of a separate metastasis to the high rectosigmoid colon causing an annular stricture. We present our experience with six such cases who presented with gastrointestinal symptoms. Two of the cases had undergone intestinal resections. All 6 patients had radiographic evidence of an annular stricture in the rectosigmoid area. Retrospective review revealed evidence of metastatic disease in all cases in the form of abnormalities in one or more of the following: intravenous urography, radionuclide bone scan, liver spleen scan, acid phosphatase, or alkaline phosphatase. The mean survival was 9.3 months. This rare presentation of prostate cancer may be difficult to distinguish from primary colorectal cancer and therefore needs to be ruled out to avoid intestinal resections.

Extracorporeal shock wave lithotripsy (ESWL) was used to manage calculi in 49 renal units in 39 patients with spinal cord dysfunction. Of the kidneys, 18 had staghorn calculi, and 6 had multiple calculi greater than 1.5 cm. Twenty-four patients (62%) had undergone prior stone surgery, and 37 patients (95%) had colonized urine at the time of admission for ESWL. Preoperative placement of ureteral catheters, nephrostomy tubes, or both was carried out in 36 renal units (73%). Thirty-three renal units (67%) were rendered stone free with an average of 1.49 treatments with an average of 2340 shocks at 18 to 24 kV. Ten (56%) of the kidneys with staghorn calculi were rendered stone free. Twenty-one patients (54%) were managed successfully with one treatment. There were no serious complications, and minor complications were experienced with only 8 of 73 procedures (11%). Thus, ESWL proved to be safe and relatively effective in patients with spinal cord dysfunction, but the stone free rate was lower than that report...

We developed a conductance formula for flow through rigid tubes that may be considered in the range for urethral opening important for connolling Fl. Tubes were tested by putting them at the bottom of a water column and letring the water run out of the coumn and recording Pr and Fl. Curve fitting of Pr and Fl data resulted in an exponential formula. A Propaionality constant was further determined to relate tubes of differing cross sectional area to an average curve fit formula. The final conductance formula, therefore, can be described as a cross sectional area equivalent factor (AEF) mm2 = 3.5 (FWPr0.58). that relates Fl and Pr to a rigid tube area. hliminary clinical observations suggest that the formula may have diagnostic potential for micturition dysfunction. Both the rate of urethral opening and maximal urethral opening may be useful information. Furthermore, a urethral compliance value, a ratio of opening area divided by the bladder Pr, may be useful in comparing patients with different Pr.

Microstimulators are new devices that should be considered for management of lower urinary tract problems following spinal cord injury (SCI) such as urinary retention. These devices are small (less than 25 mm by 5 mm) with the electrodes located on the ends of the stimulator. However, it is not known whether the small electrodes on these devices would be effective in stimulating the plexus of nerves that innervate the bladder. The aim of the present study was to provide preliminary observations with model microstimulators (M-Micro) for inducing bladder contractions in an SCI animal model. Bladder wall and pelvic plexus stimulation sites were compared. Additional investigations evaluated parameters such as stimulation polarity, frequency, and period as well as bladder filling volume.In an initial survival surgery, bilateral M-Micros were implanted on the bladder wall and the pelvic plexus along the urethra in 3 female cats. A second survival surgery was conducted 3 to 5 weeks later to produce a T1 0 SCI. Studies are reported following the second survival surgery. These studies included the effects of stimulation and bladder filling.The postmortem location of the implanted pelvic plexus M-Micro was previously described as near the bladder neck. Therefore, the pelvic plexus location is described in this report as "pelvic plexus (bladder neck)" stimulation. The observations showed effective stimulation with pelvic plexus (bladder neck) stimulation and voiding in some cases. Stimulation was limited by side effects of increased abdominal pressure and leg movement. Other factors also affected the response to stimulation, including the initial bladder volume and stimulating parameters. Fluoroscopy showed that when stimulation did not induce voiding the striated urethral sphincter was closed.This case series of 3 SCI animals showed that the small electrodes on the M-Micro could be used to stimulate the bladder with contractions and voiding in some cases. The pelvic plexus (bladder neck) location for the M-Micro may be a better location than higher on the bladder wall. Limiting side effects of stimulation included leg movement and increased abdominal pressure. Additional important factors included the stimulation parameters, initial bladder volume, and the function of the skeletal urethral sphincter.

Severe urinary retention is not a common condition, but may occur following some pelvic surgeries or other medical conditions. Electrical stimulation of the bladder has been examined as a means of managing this difficult problem. We conducted preliminary investigations in cats to prove the hypothesis that pelvic-plexus (bladder-neck) stimulation would produce greater micturition response with reduced side effects, such as animal movement or discomfort, than bladder-wall stimulation with electrodes implanted higher on the bladder wall. We used model microstimulators that mimic the look and function of commercial microstimulators, but that we constructed. We instrumented four female cats during a survival surgery. Animals recovered well and studies were conducted over a 1-month period in the conscious animal and under anesthesia. We performed a variety of studies with different stimulation parameters and electrode locations to evaluate our hypothesis. In the active animal, we supplied only low currents, but two animals responded to stimulation with bladder contractions and voiding. Following anesthesia, higher stimulating currents resulted in greater bladder contractions during stimulation in two of the three animals. In two cases, pelvic-plexus (bladder-neck) stimulation induced greater micturition responses than direct bladder-wall stimulation. In conclusion, we learned from these preliminary observations that stimulation at the pelvic plexus (bladder neck) may induce a better micturition response than stimulation higher on the bladder-wall. Newly available commercial microstimulators should be further studied for the treatment of urinary retention.

Aims Mathematical models are useful for developing predictive parameters for characterizing the biomechanics of voiding dysfunction. The goal of this project was to test a one-dimensional steady flow model used to predict the minimum cross-sectional urethral area from urodynamic data. Methods Nine adult female subjects underwent video-urodynamic testing. By using Bernoulli's formula and the Torricelli theorem, the minimum urethral area was predicted from pressure and flow rate at the moment of maximum flow rate during voiding. This prediction was compared with the minimum cross-sectional area of the urethra, which was calculated from minimum urethral diameter as measured from fluoroscopy, assuming a circular cross-section. Results The maximum flow rate during voiding was 14.4 ± 3.0 mL/sec. Mean bladder, abdominal, and detrusor pressures simultaneous with maximum flow rate were 63 ± 7, 29 ± 6, and 33 ± 6 cm H2O, respectively. Mean minimum cross-sectional area of the urethra from fluoroscopy was 8.0 ± 2.0 mm2. Mean minimum cross-sectional area of the urethra predicted by the mathematical model was 5.0 ± 1.0 mm2 using bladder pressure and 7.0 ± 2.0 mm2 using detrusor pressure. There were no significant differences between the three cross-sectional area measures. However, when area predictions were expressed as percentage of fluoroscopic measurements, the estimate from detrusor pressure (97 ± 13%) was significantly larger than the estimate from bladder pressure (69 ± 7%). Conclusions A steady flow model is accurate enough on average to describe urine flow in the urethra. However, it may not be sufficiently accurate to aid in diagnosis of individuals. Neurourol. Urodynam. 22:277–283, 2003. Published 2003 Wiley-Liss, Inc.

Aims We previously have investigated a technique for serial bladder pressure measurements in patients with spinal cord injury (SCI) using intermittent catheterization. In the current study, we compared an FDA-approved digital gauge with the previously studied analog gauge and studied the effects of hydrostatic pressure differences. Methods Either a digital or an analog pressure gauge was attached to each subject's catheter just before bladder catheterization. Both immediate and stable pressures were recorded. The bladder was then drained until nearly empty and pressure was again recorded (almost empty bladder pressure). Detrusor pressure was estimated as full minus almost empty bladder pressure. Bladder pressures greater than 40 cm H2O were presumed to represent bladder contractions. To investigate the effects of hydrostatic pressure, additional measurements, adjusting the level of the air–urine meniscus, were obtained in three subjects. Results Recordings were made from nine SCI subjects using both gauges. Estimates of detrusor pressure, with and without bladder contractions, and associated bladder volumes, were not significantly different between digital and analog gauges. In the absence of bladder contractions, detrusor pressure with the meniscus at the end of the catheter (5 ± 1 cm H2O) was significantly lower than that recorded with no adjustment of the urine meniscus (12 ± 1 cm H2O). Conclusions Standardizing measurement techniques to equalize hydrostatic pressures should facilitate reliable estimates of detrusor pressure. Frequent monitoring of bladder pressure using this technique may assist with the urological care of SCI patients. Neurourol. Urodynam. 22:250–254, 2003. Published 2003 Wiley-Liss, Inc.

Small wireless microstimulators were implanted on the bladder wall serosa in three cats. The microstimulators were secured with a single polypropylene suture. Two to three microstimulators were implanted in each animal. The stimulators were implanted for eight weeks, and gross observation revealed encapsulation of the microstimulators with no perforation into the bladder lumen or migration from the bladder wall. Histological evaluation confirmed that all the microstimulators were encapsulated with a thin connective tissue sheath and a thickened subserosal layer. Only two microstimulators in one cat revealed a moderate to severe inflammatory response confined to a small area around the stimulator. These results indicate that the microstimulator can be further evaluated for implantation and stimulation of the urinary bladder.

An accurate mathematical model predicting urethral cross-sectional area from urodynamic data could be useful for diagnosis of voiding dysfunction. The purpose of this project was to use fluoroscopy images of the female urethra during voiding to verify a shape assumption for the urethra and a model of laminar flow in the urethra. Maximum flow rate and simultaneous bladder and detrusor pressures during voiding were used independently in a formula based on Bernoulli's Law to predict the minimum cross-sectional area of the urethra. Cross-sectional area of the urethra was also calculated from fluoroscopic data assuming a circular cross-section. Nine adult female subjects were tested using videourodynamics. Maximum flow rate during voiding was 14.4/spl plusmn/3.0 ml/sec. Bladder, abdominal, and detrusor pressure simultaneous with maximum flow rate were 63/spl plusmn/7, 29/spl plusmn/6, and 33/spl plusmn/6 cm H/sub 2/O, respectively. The minimum cross-sectional area of the urethra, predicted from pressure and flow was 4.4/spl plusmn/1.0 mm/sup 2/ using bladder pressure and 6.6/spl plusmn/1.6 mm/sup 2/ using detrusor pressure. The minimum and maximum cross-sectional areas of the urethra from fluoroscopy data were 7.9/spl plusmn/1.9 and 93.1/spl plusmn/31.0 mm/sup 2/, respectively. Percentage error of the predictions of area from pressure and flow were 39/spl plusmn/6% using bladder pressure and 33/spl plusmn/7% using detrusor pressure. Detrusor pressure gives a more accurate prediction of minimum cross-sectional area than bladder pressure, although the predictions were not significantly different. Future work will be aimed at improving the accuracy of both measurements and mathematical models.

Minimal risk levels (MRLs) are health-based guidance values derived for individual substances by conducting a thorough review of the literature, identifying appropriate target organs of response, and identifying a dose level where a no adverse effect or the lowest adverse effect level is seen. This level is then evaluated for uncertainty in the data base and for other extenuating factors and subsequently adjusted with uncertainty or modifying factors. The resulting calculation yields the MRL that is defined as an estimate of the daily human exposure to a hazardous substance that is likely to be without appreciable risk of adverse noncancer health effects over a specified duration of exposure. Typically, MRLs are derived for different durations of exposure (acute, intermediate, chronic) and for different routes of exposure (oral, inhalation). The MRLs serve as useful reference values in evaluating human health from exposure to substances found at hazardous waste sites. Because of numerous requests of various programs, recent work has focused on expanding the applicability of MRLs to other situations and routes of exposure (dermal, food supply, intramuscular) beyond the traditional oral and inhalation exposure routes at waste sites. Results of work, in conjunction with the Agency for Toxic Substances and Disease Registry's computational toxicology laboratory, shows that the use of computational methods, such as physiologically based pharmacokinetic modeling, may allow the MRL process to be adapted to unique durations and routes of exposure such as intramuscular injections.

An interactive data management (IDM) system for the Spinal Cord Injury (SCI) Service was developed to collect self-reported patient data related to secondary medical complications and to provide feedback to the SCI rehabilitation team. The long-term objective is to improve clinical care through a process of staff review of current rehabilitation programs in the areas of prevalence, prevention, and management. Based on data from the first 99 SCI patients visiting the clinic and hospital after the installation of the IDM system, SCI patients reported high rates of current problems with spasticity (53 percent), pain (44 percent), and pressure ulcers (38 percent). Respiratory (12 percent) and bowel (14 percent) problems were less common current problems. The SCI staff questioned the reportedly high spasticity rates. They thought that the patients' answers might have indicated simply the occurrence of spasticity, rather than the more important issue of severe spasticity that interferes with daily activities. The staff suggested several additional spasticity questions to add to the study. In other areas, only a small percentage of patients wanted to talk with a therapist about prevention of pressure ulcers. Patients who had urinary problems consistently reported five urinary signs (e.g., cloudy urine). The clinical staff found these data informative and stated that they should continue to be collected.

Botulinum toxin (BT) injections have been used successfully to treat spastic muscle conditions, including detrusor-sphincter dyssynergia (DSD) seen in spinal cord injury (SCI) patients. In our urology clinic, we used BT to treat three SCI patients who had voiding dysfunction, using a transperineal needle with electromyographic (EMG) monitoring. Two of the patients reported excellent results following the treatment. One patient, with whom the staff had difficulty doing intermittent catheterization (IC), improved significantly. The other patient had improved voiding with an external catheter and minimal urinary residual. The third patient had no improvement of leg spasms with his voiding dysfunction and required a sphincterotomy. Although patients may need repeat injections, BT is minimally invasive and easy to administer with no side effects. Overall, BT injection is an excellent method of managing voiding in SCI patients, especially those on continuous external catheters and with IC management who refuse or are not good candidates for surgery.

This study examined the histological response of the bladder wall serosa to the implantation of wireless microstimulators secured with a single polypropylene suture. Two to three microstimulators were implanted in each of three casts for an eight week implantation period to allow sufficient time for a bladder-wall injury-response to develop. Gross observation revealed encapsulation of the microstimulators with no perforation to the bladder lumen or migration from the bladder wall. Histological evaluation confirmed that all the microstimutators were encapsulated with a thin connective tissue sheath and a thickened subserosal layer. There was no remarkable difference in tissue morphology compared with normal bladder wall sections for five of seven stimulators. Two microstimulators in one cat revealed a moderate to severe inflammatory response confined to a small area around the stimulator. In a second cat, a suture extended through the bladder wall. The microstimulators were observed with a scanning electron microscope after explantation. The electrode surfaces, bonding interface between silicon and glass and insulating films that were exposed to biological fluids were carefully inspected. All these observations indicate that the glass capsule reliably protected the sealed cavity of the microstimulators from moisture. These results indicate the microstimulator should be considered for further studies such as effects of stimulation and long-term implantation.

Transurethral injection of collagen (TCI) may be used to treat urinary incontinence following radical prostatectomy for prostate cancer. The transrectal ultrasound (TRUS) findings after TCI are described in this report. TRUS exams of four postprostatectomy patients who had undergone TCI were reviewed. Findings were correlated with pathologic specimens obtained at TRUS-guided core biopsy. These histologic specimens were compared with others from postprostatectomy patients who had not undergone TCI. Well defined bladder apex masses of uniform echogenicity, hypoechoic to adjacent fat and muscle, were identified sonographically in all TCI patients. Masses from which positive biopsies were obtained were similar in appearance to those with no malignant. Hypocellular fibrous tissue and foci of acellular loose connective tissue were identified in the biopsies of those patients who had undergone TCI No acellular areas were identified in specimens from patients who had not had TCI. Sequelae of to should be included in the differential diagnosis of perianastomotic masses in postprostatectomy patients. However, the need for biopsy is not obviated as residual or recurrent prostate carcinoma may coexist. 14 refs., 4 figs.