Intraurethral alprostadil for treatment of erectile dysfunction in patients with spinal cord injury.

OBJECTIVES: To assess the efficacy of intraurethral prostaglandin E1 (alprostadil, MUSE) in treating erectile dysfunction in patients with spinal cord injury (SCI). METHODS: Intraurethral alprostadil was tested in 15 patients with SCI to evaluate its effectiveness in treating SCI-associated erectile dysfunction. All patients were at least 1 year after injury, and all had previously used intracavernosal injections successfully (Schramek's grade 5 erection). The intraurethral drug was administered in the office, in the presence of a physician, with monitoring of blood pressure. If effective, the patient was then able to use MUSE at home. The first 3 patients underwent gradual dose escalation starting with 125 microg, without the use of a constriction ring. Because of hypotension, the remaining 12 patients all used a penile constriction ring prior to intraurethral drug administration using 1000 microg. The quality of the erection was compared with that achieved with intracavernosal injections using Schramek's grading. RESULTS: The dose escalation (titration) in the first 3 patients demonstrated that the 1000-microg dose was the most effective in creating an erectile response. Transient hypotension was noted in these first 3 patients in whom the constricting band was not used. The highest dose of MUSE (1000 microg) was, therefore, used in the remaining 12 patients, with the constriction band. The quality of the erection varied and appeared to be less rigid in all patients (12 patients with grade 1 to 3; 3 patients with grade 4) than that noted with intracavernosal injection therapy (1 5 patients with grade 5). There was no incidence of priapism. The 3 patients with grade 4 erections tried the MUSE at home. All 3 patients were dissatisfied with the quality of the erection and did not continue to use the MUSE at home and returned to intracavernosal injection therapy. CONCLUSIONS: MUSE appears to be somewhat effective in creating erections; however, these were less rigid erections than those obtained with intracavernosal therapy and provided less overall satisfaction. It should always be used in the patient with SCI after placement of a constriction ring to prevent hypotension. Its ultimate use depends on the patient's level of satisfaction with the quality of the erection compared with intracavernosal injections.

Hepatotoxicity related to intracavernous pharmacotherapy with papaverine.

OBJECTIVES: To determine the incidence of hepatotoxicity related to self-administration of intracavernous papaverine or papaverine/phentolamine (bimix). METHODS: From October 1994 through June 1996, we retrospectively reviewed the medical records of 71 consecutive patients diagnosed with organic erectile dysfunction (ED) and receiving intracavernous injection therapy. Inclusion criteria were documentation of normal baseline liver function tests (LFTs), a minimum of 6 months of follow-up that included LFTs, at least one self-injection every 2 weeks, and no other prior or concurrent treatment for ED. Thirty evaluable patients satisfied the inclusion criteria and formed group 1. Mean age was 63 years (range 40 to 77), mean follow-up was 18 months (range 6 to 32), and mean number of injections per month was 5.7 (range 3 to 12). An age-matched population of 20 patients (mean age 69 years, range 46 to 90) without ED but with similar comorbid risk factors formed the control group (group 2). All patients in group 2 had routine long-term follow-up of LFTs (mean 52 months, range 10 to 1 14). RESULTS: Two patients (6.67%) from group 1 had elevated LFTs during treatment: one experienced a mild elevation in alanine aminotransferase and the other developed transient elevations of total bilirubin and aspartate aminotransferase 6 months after beginning therapy. Both patients reported a history of alcohol abuse. Both patients remained asymptomatic. Neither patient required discontinuation of therapy. One patient (5%) from group 2 developed an elevation of total bilirubin at a follow-up of 12 months. CONCLUSIONS: Routine monitoring of LFTs is probably unnecessary during intracavernous pharmacotherapy. Patients with a history of alcohol abuse or liver disease, however, should be followed up more closely when papaverine is selected for intracavernous injection. In these patients, LFTs should be obtained before initiating treatment and at 6-month intervals.

Role of finasteride in the treatment of recurrent hematuria secondary to benign prostatic hyperplasia.

OBJECTIVES: We evaluated the efficacy of finasteride for the treatment of gross hematuria secondary to benign prostatic hyperplasia in a prospective fashion. METHODS: Twelve patients with recurrent episodes of gross hematuria secondary to benign prostatic hyperplasia were treated with finasteride 5 mg/day. Before initiating treatment, we excluded other sources of hematuria using intravenous urography, cystoscopy, and urine culture. RESULTS: Bleeding subsided within 2 weeks of treatment in all 12 patients. Minimum follow-up was 6 months. Finasteride was well tolerated by all 12 patients. CONCLUSIONS: Finasteride appears to be effective in treating recurrent gross hematuria secondary to benign prostatic hyperplasia. This therapy should be considered an alternative to transurethral resection of the prostate or hormonal ablation in patients with recurrent hematuria and no significant obstructive uropathy or adenocarcinoma of the prostate.

Trimethoprim-sulfamethoxazole prophylaxis against urinary tract infection in the chronic spinal cord injury patient.

Suppressive therapy with antibiotics has long been thought to decrease the number of complications from the neuropathic bladder in spinal cord injury patients, but it may also induce resistance to antibiotics which subsequently causes difficulties in treating symptomatic urinary tract infections. Forty-three chronic spinal cord injury patients were randomized to continue to receive daily trimethoprim-sulfamethoxazole (TMP-SMX) urinary tract prophylaxis versus discontinuing antibiotic prophylaxis. Patients were all at least 6 months after spinal cord injury. Patients were followed for a minimum of 3 months, with weekly catheter urine cultures. The difference in the colonization rate at onset and after 3 months (percent of cultures with asymptomatic bacteriuria) between the control and prophylaxis group was not statistically significant (P > 0.1). There was a significant decrease in the percentage of TMP-SMX resistant asymptomatic bacteriuria in the control group, 78.8%, compared to 94.1% in the suppressive group (P < 0.05). There was no significant difference in the number of symptomatic urinary tract infections following the withdrawal of suppressive therapy between the control group, 0.035/week, and the prophylaxis group, 0.043/week (P > 0.5). There was a larger percentage of TMP-SMX resistant symptomatic urinary tract infections in the treated group, 42.5% versus 37.5% in the control group, but the difference was not significant (P > 0.5). Irrespective of the method of bladder management, suppressive therapy with TMP-SMX did not reduce the incidence of symptomatic bacteriuria and did increase the percentage of cultures resistant to TMP-SMX in asymptomatic patients.

Evaluation and treatment of bladder rupture.

The presence of urologic injury must be considered in patients who have sustained severe lower abdominal blunt trauma and in all patients with pelvic fracture. Physical findings that suggest the possibility of a bladder rupture include gross hematuria and an inability to urinate. A properly performed cystogram is diagnostic of bladder rupture and will define whether the rupture is intraperitoneal or extraperitoneal. Selected cases of extraperitoneal bladder rupture can be safely managed by catheter drainage, antibiotics, and close clinical observation. Intraperitoneal perforations require surgical exploration and bladder closure. Complications occurring as a result of bladder injury are minimized provided the injury is identified and repaired when indicated, and provided continuous unobstructive bladder drainage is achieved.

CWR22: androgen-dependent xenograft model derived from a primary human prostatic carcinoma.

The long-term propagation of primary human prostate cancer (PCA) in vivo or in vitro has been rare. Most such PCAs are phenotypically different from most PCAs in humans; i.e., they make little prostate specific antigen and respond little, if at all, to androgen deprivation. A serially transplantable, primary human PCA, designated CWR22, exhibits a clonal cytogenetic aberration, causes high elevations of prostate specific antigen in the peripheral blood of nude mice, and is unusually responsive to androgen deprivation as compared with other xenografts. Studies of mRNA from CWR22 have demonstrated the expression of prostate specific antigen and the epidermal growth factor receptor family including erbB1/epidermal growth factor receptor, erbB2/neu, and erbB3, but not erbB4. A ligand for these receptors, the neu differentiation factor, is also expressed.

Review of sacral electrical stimulation in the management of the neurogenic bladder.

In patients with spinal cord injury above the conus medullaris, electrical stimulation of the sacral anterior nerve roots can produce micturition with low residual volumes of urine and reduced urinary tract infection. Vowing pressures appear to be maintained at safe levels by the use of an intermittent pattern of stimulation. The procedure is usually combined with division of the sacral posterior roots, which increases bladder capacity and continence; this also increases bladder compliance, which may be protective for the upper urinary tracts.The procedure has now been applied in about 900 patients with spinal cord injury, some of whom have been followed up for over 15 years. The nerves do not appear to be damaged by long-term stimulation and technical faults with the equipment are now uncommon.

Sexual dysfunction after spinal cord injury.

Treatment of sexual dysfunction is an integral part of the rehabilitation of the patient with spinal cord injury. The degree of sexual dysfunction varies with the level and completeness of injury. A multidisciplinary approach is necessary to evaluate and treat these patients. Intracorporeal injections of vasoactive medications or vacuum devices are effective means of restoring erections in selected patients with spinal cord injury. Penile prostheses are rarely indicated for this purpose.

Xenografts of primary human prostatic carcinoma.

BACKGROUND: Prostatic carcinoma is both the most common invasive cancer and the second most common cause of cancer deaths in men in the United States. Before 1991, attempts to propagate prostatic carcinoma from primary tumors for periods longer than 3 months were unsuccessful in vivo and in vitro with rare exceptions. In 1991, we reported establishment of slowly growing tumors for six of 10 human primary prostatic carcinomas approximately 2-6 months after transplantation. However, none of the tumors were larger than 5 mm or serially transplantable. PURPOSE: Our purpose in this study was to determine whether human primary prostatic carcinoma could be grown as serially transplantable xenografts. METHODS: Cells from primary prostatic carcinomas obtained from transurethral prostatic resections or total prostatectomies in 20 patients were injected subcutaneously into male nude mice on the day of surgery. Sustained-release testosterone pellets were placed subcutaneously in the mice 2-24 days before transplantation of tumors and at intervals of 10-12 weeks. Serial transplantations in subsequent generations of mice were carried out by similar methods. Chromosome analysis was performed on six tumors. RESULTS: Six of 20 primary prostatic carcinomas have grown sufficiently to permit serial transplantation into second mice; four have been documented histopathologically in the second mouse and serially transplanted into three or more successive mice. When a single primary tumor was injected into several mice by the same procedure, tumors failed to grow in some recipients but became serially transplantable in others. Growth of these tumors is slow and irregular, with frequent regressions. Short-term cultures of 10 tumors, eight of which were injected into mice in parallel, were initiated on the day of surgery; CWR31, which was successfully transplanted serially, exhibited only aberrant metaphases and showed clonal, chromosomal changes in culture. Including CWR31, three of the six tumors for which chromosomal analysis was successful contained clonal aberrations. Preliminary studies of SCID (severe combined immunodeficient) mice suggest that they are not superior to nude mice for establishment of serially transplantable prostatic carcinoma xenografts. CONCLUSIONS: A proportion of human primary prostatic carcinomas can be grown as xenografts. Four new serially transplantable xenografts (CWR21, CWR31, CWR91, and CWR22) are currently propagated in our laboratory, a resource that was not previously available. IMPLICATIONS: Our experience suggests that the most important factor in serial transplantation is the collaboration of urologists and pathologists in expediting placement of the tumor in cold saline, examination of the frozen section, and transplantation.

Spinal cord compression secondary to prostate carcinoma: treatment and prognosis.

Of 35 patients with prostate carcinoma and suspected spinal cord compression 26 (74%) had myelograms and/or magnetic resonance imaging studies demonstrating epidural spinal cord compression. In 5 of 26 patients (19%) spinal cord compression was the first indication of prostate cancer. All patients were initially treated with radiation, steroids and androgen deprivation therapy. Three patients underwent laminectomy. Of 12 patients (100%) ambulatory at presentation 12 remained ambulatory. Of 12 patients (83%) who were paraparetic at presentation 10 were ambulatory after treatment. However, 2 of these patients subsequently had recurrent compression and became paraplegic. Overall, 7 of 26 patients (27%) had recurrent compression. Of 5 patients who either presented with paraplegia or in whom paraplegia developed secondary to recurrent spinal cord compression 4 remained paraplegic despite treatment. The average survival of these 5 patients after treatment was 3.9 months versus 18 months for the group as a whole. In ambulatory or paraparetic patients radiation, androgen deprivation therapy and steroids are effective palliative therapy. However, patients who present with paraplegia or in whom paraplegia developed secondary to recurrent compression are often not palliated by this combination therapy. Prophylactic radiation of vertebral metastases discovered concurrently with compressive metastases may be valuable in preventing paraplegia.

The development of urologic complications in relationship to bladder pressure in spinal cord injured patients.

The medical records of 88 patients followed through our spinal cord injury clinic were reviewed to determine if elevated intravesical pressures result in more urologic complications than are seen with low pressure bladders. Fifty-two of the patients were noted to have a high bladder pressure (sustained detrusor pressure greater than 40 cm water) on cystogram while 36 had low pressures. All patients had routine urine cultures, urodynamics, ultrasonography, radioisotope renal scans, and excretory urograms. Bladder management was directed at maintaining a low bladder pressure and included one or more of the following: intermittent catheterization, anticholinergics, alpha blockers, transurethral sphincterotomy, or indwelling catheters. Average follow-up was 6 years. Mild degrees of hydronephrosis were noted in seven (14 percent) of the patients with a high pressure bladder and in one (3 percent) with a low pressure bladder. Pyelonephritis was noted in two (4 percent) with high bladder pressure and two (5 percent) with low bladder pressure. Preservation of renal function occurred as the result of patient compliance with bladder management and bladder pressure. Sustained high detrusor pressure, when not corrected, leads to upper tract deterioration which was reversed by aggressive lower tract management.

Twelve-month comparison of two treatments for erectile dysfunction: self-injection versus external vacuum devices.

This study directly compared two nonsurgical treatments for erectile dysfunction, self-injection of papaverine/phentolamine and external vacuum devices, in terms of usage rates, effectiveness, side effects, dropout rates, and impact on patient sexual and psychologic functioning. Both alternatives were regularly, successfully, and safely used by patients, though dropout rates were higher for self-injection. Both produced erections of improved quality, and effected sustained improvements in frequency of intercourse, orgasm, and sexual satisfaction. Spontaneous erections also improved with both treatments. General psychiatric symptomatology was decreased, and anxiety was improved. There were no differences between the two treatments in sexual or psychologic impact. Relative contraindications and esthetic considerations are presented.

The role of intracavernous injection of vasoactive medications for the restoration of erection in spinal cord injured males: a three year follow up.

Fifty-eight spinal cord injured men entered our self injection program for restoration of erections since the program began in September 1985. Early complications included sustained erection (greater than 8 hours) in 4 patients on 6 occasions requiring aspiration of the corpora cavernosa and injection of a dilute epinephrine solution (1/100,000). Bruising at the site of injection was reported at least once by 10 patients. Blood draining from the urethra was noted in 3 patients when the urethra was inadvertently injected. Rigid erections were obtained in all but 5 patients that injected (90%). Late complications included penile plaque in 3 patients (15%). There were no abnormal liver function tests. Average time on the injection program was 2 years (range of 0.5 to 4.5 years). Thirty-one (53%) of the patients have dropped out of the program, most doing so prior to the first injection or during the titration period. The average frequency of injection was twice a month. Injection therapy remains an effective and relatively safe alternative for selective patients with spinal cord injury.

Tissue concentrations of prostate-specific antigen in prostatic carcinoma and benign prostatic hyperplasia.

Prostate-specific antigen (PSA), as measured in peripheral blood, is currently the most widely used marker for the assessment of tumor burden in the longitudinal study of patients with carcinoma of the prostate (PCA). Studies from other laboratories have led to the conclusion that a given volume of PCA causes a much higher level of PSA in the peripheral circulation of patients than a similar volume of prostate without carcinoma. We have evaluated PSA in the resected tissues immunohistochemically and in extracts of PCA and of prostates resected because of benign prostatic hyperplasia (BPH) with an enzyme-linked immunosorbent assay. Immunohistochemical results were less quantitative than but consistent with the results of the ELISA of tissue extracts. Immunohistochemically, there was considerable heterogeneity in the expression of PSA by both PCA and BPH both within and among prostatic tissues from different patients. While the levels of expression of PSA in these tissues overlap broadly, PSA is expressed at a lower level in PCA than in BPH when PSA is expressed as a function of wet weight of tissue (p = 0.0095), wet weight of tissue/% epithelium (p less than 0.0001), protein extracted from the tissue (p = 0.0039), or protein extracted/% epithelium (p less than 0.0001).

External vacuum devices in the treatment of erectile dysfunction: a one-year study of sexual and psychosocial impact.

This prospective study assessed the sexual and psychosocial effects of 12 months' use of an external vacuum device in the treatment of erectile dysfunction. Results showed that the external vacuum device produced erections sufficient for intercourse in 87% of the men in our sample. The dropout rate was only 20% over the 12-month period. Use of the external vacuum device was associated with improvements in men's and their partners' sexual functioning. These improvements included erections of better quality, increased partner arousal, and increased frequency of orgasm and sexual satisfaction for men and women. The external vacuum device was also associated with decreases in general psychiatric symptomatology for men. Similar improvements in psychological functioning were not found for partners. Side effects and factors in patient and partner acceptance of the external vacuum device are discussed.

Application of office ultrasound in the management of the spinal cord injury patient.

The effectiveness of office ultrasonography of the bladder and kidneys to provide routine urological followup was assessed in the outpatient spinal cord injury clinic. A total of 86 asymptomatic spinal cord injury patients underwent office ultrasonography of the kidneys and bladder as part of the routine urological followup. There were 106 ultrasound scans performed. Of the patients 68 had a blinded excretory urogram for comparison, including 20 who underwent additional studies (computerized tomography scans of the abdomen and pelvis, and/or radiologist-performed ultrasound examinations of the kidneys and bladder). All 18 patients who underwent office ultrasound but not excretory urography each underwent computerized tomography scans of the abdomen and pelvis and/or radiologist-performed ultrasound examinations of the kidneys and bladder. Office ultrasound detected 5 of 6 kidney stones, 6 of 6 hydronephrotic kidneys, 5 of 7 renal masses (4 of 6 cysts and 1 of 1 renal tumor), 3 of 3 bladder stones and 3 of 3 bladder diverticula. Subtle changes of chronic renal infection noted on excretory urography in 4 patients were not detected on corresponding ultrasound scans but voiding cystourethrograms revealed no reflux, and comparison to prior studies confirmed that these renal units were stable. Outpatient ultrasonography performed by the urologist proved to be a cost-effective and sensitive screening examination for urological disorders in the spinal cord injury population. The technique is easily learned, well tolerated and indicated when further urological evaluation is required.

Urologic changes after cauda equina compression in dogs.

Relative degrees (25%, 50% or 75%) of constriction of the entire cauda equina at the seventh lumbar level were performed on eighteen pure bred female beagle hounds by surgically implanting a circular polyethylene loop with an imbedded stainless steel wire. The wire was mechanically constricted by external control and the degree of compression was confirmed by pre- and postoperative magnetic resonance imaging or computed tomography scanning. A control group of two dogs had laminectomy only. Neurologic function was evaluated daily. Cystometrics were performed on each dog after constriction had been present for three months. Cortical evoked potentials (CEPs) were obtained on all dogs preoperatively, immediately following constriction and at monthly intervals for three months. Dogs were sacrificed at three months and the cauda equina and spinal cord were examined histopathologically. Cystometric tracings were noted to become a flat line with 75% compression of the cord. Less compression had minimal effect on the cystometric curves. The mean latency, determined by cortical evoked potentials, was noted to increase by 3.2%, 7.8%, and 17.2% immediately after 25%, 50% and 75% constriction, respectively. Histologic changes ranged from occasional enlargement of the axons on the periphery of the cauda equina with 25% constriction to severe loss of all axons and atrophic roots at the level of the constricting band with 75% constriction.