Urodynamic pattern changes in multiple sclerosis.

OBJECTIVES: Multiple sclerosis (MS) causes neurologic symptoms to change over time. Voiding dysfunction is common in patients with MS, and few studies have examined the changes in urodynamic patterns in these patients over time. The purpose of this study was to examine the frequency and nature of urodynamic pattern changes in patients with MS who underwent two or more urodynamic studies. METHODS: Twenty-two patients (7 men and 15 women) with well-documented MS were referred to one urologist (T.B.B.) for evaluation of lower urinary tract symptoms. All patients had undergone two or more urodynamic evaluations during a 14-year period for persistent or new symptoms, and a retrospective comparison was made among the urodynamic test results. RESULTS: Overall, 12 (55%) of 22 patients experienced a change in their urodynamic patterns and/or compliance during a mean follow-up interval of 42 +/- 45 months between the urodynamic studies. Most patients initially had urodynamic patterns showing detrusor hyperreflexia, detrusor external sphincter dyssynergia, or detrusor hypocontractility. Fourteen (64%) of the 22 patients studied had the same or worsening of the same symptoms and 8 (36%) of 22 had new urologic symptoms. Six (43%) of 14 patients with no new symptoms and 6 (75%) of 8 with new symptoms had significant changes found with follow-up urodynamic testing. CONCLUSIONS: A significant proportion of patients with MS with and without new urinary symptoms will develop changes in their underlying urodynamic patterns and detrusor compliance. Therefore, urodynamic evaluations should be repeated at regular intervals in symptomatic patients to optimize clinical management, reduce complications, and better enable these patients to manage their neurogenic bladder dysfunction.

The "bends" and neurogenic bladder dysfunction.

Decompression sickness (the "bends") is a well-known risk of scuba diving. The pathophysiology and treatment is well documented. In the urologic data, no reference to the development of a neurogenic bladder as a result of an episode of the bends was found. We present the evaluation and management of a previously asymptomatic man who developed detrusor hyperreflexia after an episode of decompression sickness. Urologists in coastal communities should be aware of the potential risk of the development of neurogenic bladder.

Cooperative therapeutic effects of androgen ablation and adenovirus-mediated herpes simplex virus thymidine kinase gene and ganciclovir therapy in experimental prostate cancer.

Adenovirus-mediated transduction of the herpes simplex thymidine kinase gene (HSV-tk) in conjunction with ganciclovir (GCV) has been shown to result in significant growth suppression and to enhance survival in a model of mouse prostate cancer. However, this therapeutic activity is not sustained, because in most cases tumors eventually regrow and ultimately cause the death of the host. Androgen ablation, an inducer of apoptosis in prostate cells which is used widely as palliative therapy in patients with prostate cancer, was combined with HSV-tk plus GCV using an androgen-sensitive mouse prostate cancer cell line. The combination of castration and HSV-tk plus GCV led to markedly enhanced tumor growth suppression in both subcutaneous and orthotopic models compared with either treatment alone and resulted in an enhanced survival in which combination-treated animals lived twice as long as controls in the subcutaneous model and over 50% longer than controls in the orthotopic model. Further analysis of apoptotic activity demonstrated high levels of apoptosis only in combined androgen ablation and HSV-tk plus GCV-treated tumors after 14 days of growth in an androgen-depleted environment and 8 days after HSV-tk plus GCV therapy. At this time, the apoptotic index, but not the percent of necrotic tissue, was significantly higher for combination therapy-treated tumors relative to control-treated tumors or either treatment alone. These data indicate that the therapeutic effects of androgen ablation and HSV-tk plus GCV are cooperative and that increased apoptosis may, in part, underlie these activities.

Ileovesicostomy as an alternative form of bladder management in tetraplegic patients.

OBJECTIVES: Bladder management in tetraplegic patients traditionally has been intermittent catheterization by a caretaker, placement of indwelling suprapubic or urethral catheters, sphincterotomy and external catheter drainage, or supravesical urinary diversion with an ileal conduit. The aim of this study was to examine the ileovesicostomy as an alternative form of bladder management in such patients. METHODS: We report our experience with ileovesicostomy as an incontinent cutaneous urinary diversion not requiring ureteral reimplantation. Six tetraplegic patients who had experienced significant morbidity with their preoperative form of bladder management were managed with an ileovesicostomy fashioned like a funnel from the bladder dome to the right lower quadrant. All patients underwent preoperative and postoperative fluoroscopic and urodynamic evaluations. Patients were evaluated preoperatively and followed postoperatively with serum chemistries, upper urinary tract imaging, and urine bacteriologic studies. RESULTS: There were no perioperative complications. Postoperative urodynamics demonstrated subjects to have a mean stomal leak-point pressure of 7.7 cm H2O (range 5 to 10). Radiographically, patients carried low urinary residuals (less than 100 cc) and did not exhibit vesicoureteral reflux. In follow-up of 12 to 15 months, no patient has demonstrated calculus formation, hydronephrosis, autonomic dysreflexia, or worsening renal function. CONCLUSIONS: This procedure successfully creates continuous urinary drainage without catheterization, while maintaining the native antireflux mechanism of the ureterovesical junction and avoiding indwelling foreign materials in the urinary tract. Longer follow-up with more cases will be necessary to confirm these findings and to support a recommendation of the incontinent ileovesicostomy as a standard method for managing the neurogenic bladder in tetraplegic patients.

Adenovirus-mediated herpes simplex virus thymidine kinase gene and ganciclovir therapy leads to systemic activity against spontaneous and induced metastasis in an orthotopic mouse model of prostate cancer.

It is critical to develop new therapies, such as gene therapy, which can impact on both local and metastatic prostate cancer progression. We have developed an orthotopic mouse model of metastatic prostate cancer using a cell line (RM-1) derived from the mouse prostate reconstitution (MPR) model system. This mouse model closely simulates the anatomical and biological milieu of the prostate and allows for realistic testing of experimental gene therapy protocols. Adenovirus (ADV)-mediated transduction of the herpes simplex virus thymidine kinase (HSV-tk) gene in conjunction with ganciclovir (GCV) in this model led to significant suppression of growth and of spontaneous metastasis at 14 days post-tumor inoculation. Longer-term studies produced a significant survival advantage and a continued suppression of metastatic activity for treatment animals despite regrowth of the primary tumor. Challenge by injection of tumor cells into the tail vein following excision of treated and control s.c. primary tumors resulted in 40% reduction in lung colonization in the treatment group, indicating the possible production of systemic anti-metastatic activity following a single in situ treatment with ADV/HSV-tk + GCV in this model system.

Immunohistochemical localization of androgen receptors with mono- and polyclonal antibodies to androgen receptor.

Rat, human, and mouse tissues were stained immunohistochemically using mono- and polyclonal androgen receptor antibodies. Monoclonal antibodies were raised in rats and used to stain human and mouse tissues; polyclonal antibodies were raised in rabbits and used to stain rat tissues. Frozen tissue sections were incubated with the appropriate androgen receptor antibody and staining was completed by the indirect avidin-biotin peroxidase method. A comprehensive survey of rat and mouse tissues was performed. Antibody staining was found exclusively in the nucleus of certain specific cell types, suggesting that the androgen receptor is a nuclear protein. All male sexual organs in the rat showed strong positive nuclear staining for androgen receptor. Weaker positive reactions were seen in kidney, liver, adrenal cortex and pituitary gland. Furthermore, positive staining for androgen receptor was exhibited in skeletal, cardiac and smooth muscle cells, and central nervous tissue. Female reproductive organs also contained androgen receptor-positive cells. The spleen was found to be the only organ examined which did not stain for androgen receptor. The monoclonal antibody could also demonstrate androgen receptor-positive cells in a human prostatic cancer and in a prostate with benign hyperplasia. These data demonstrate the use of antibodies in revealing cellular/subcellular distribution of androgen receptor in target tissues.