Biochemical alterations in partial bladder outlet obstruction in mice: up-regulation of the mitogen activated protein kinase pathway.

PURPOSE: We evaluated the effect of partial bladder outlet obstruction on bladder weight, protein synthesis, mitotic markers and the mitogen activated protein kinase pathway in a mouse model. MATERIALS AND METHODS: Mice were divided into 3 groups, including control, sham treated and partially obstructed. Bladders were harvested from the mice in the partially obstructed group 12, 24, 48, 72 and 168 hours after surgical partial outlet obstruction, respectively. Partially obstructed bladders were compared to bladders in the control and sham treated groups by weight, protein content, and expression of proliferating cellular nuclear antigen, cyclin D3, HsP 70, c-jun and phosphorylated c-jun. Bladders were examined histologically for changes occurring with partial obstruction. RESULTS: We tested 3 groups of mice, including control, sham treated and partially obstructed mice, to understand the pathophysiology of the bladder response to partial obstruction. We found no statistical difference in body weight among the groups. Furthermore, there was a significant increase in bladder weight and protein content in partially obstructed mice compared to those in controls and sham operated mice. There was up-regulation of proliferating cellular nuclear antigen, cyclin D3, HsP70, c-jun and phosphorylated c-jun with partial obstruction. Fibrosis was prominent at 168 hours compared to that in controls. CONCLUSIONS: Bladder weight and protein content increase with partial bladder outlet obstruction in mice. Cell cycle proteins and elements of the mitogen activated protein kinase pathway are up-regulated during this process.

Gene therapy for erectile dysfunction.

Erectile dysfunction is a disease that affects half of American men aged over 50 years. Many men respond to oral phosphodiesterase inhibitors but many do not. For this reason, many researchers are focusing their efforts on developing novel gene therapies for the treatment of erectile dysfunction. Aided by the meticulous characterization of the molecular cascades involved in the physiology of erection, several groups around the world are studying gene therapies in animal models, and one in a human clinical trial. Here we provide a review of the pathophysiology of erectile dysfunction and how it relates to the molecular targets of novel gene therapeutics. The field of gene therapy for the treatment of erectile dysfunction is continually growing, and this decade will likely see exciting results as the expansion from animal models to human clinical trials continues.

Teratoid Wilms' tumor, an important variant of nephroblastoma.

PURPOSE: The teratoid histologic variant of Wilms' tumor is rare, with only 15 prior reported cases. We review these and report an additional case in which a cytogenetic abnormality was identified that has not previously been reported in a teratoid Wilms' tumor. MATERIALS AND METHODS: A medline search revealed 15 previously reported cases of the teratoid variant of Wilms' tumor. We summarized the characteristics of these cases with attention to radiologic appearance, stage, laterality, histology, response to chemotherapy and outcomes. RESULTS: Characteristic radiologic features suggesting teratoid Wilms' tumor were calcific densities and stippling, or areas of attenuation indicating adipose tissue. The majority of teratoid Wilms' tumor patients had a high tumor stage at presentation (50% stage III or greater). The incidence of bilateral tumors was 38%. Chemotherapy was administered in nine cases and in only one (11%) was there a cytoreductive response. Four deaths (25%) occurred amongst these patients. CONCLUSIONS: Teratoid Wilms' tumors appear to present with a high stage, increased incidence of bilaterality and have a high mortality rate. Treatment strategies should focus on total surgical extirpation, including metastatic sites when feasible, due to this entity's limited response to chemotherapy.

Penile rehabilitation after radical prostatectomy: important therapy or wishful thinking?

On the basis of data accumulated thus far, it is reasonable to discuss the implementation of a "penile rehabilitation" program with patients undergoing radical prostatectomy. Central to discussions of penile rehabilitation after radical prostatectomy is evidence demonstrating significant fibrotic changes in the corpus cavernosum that occur postoperatively. Several studies have been published evaluating the efficacy of various pro-erectogenic agents. The limited data regarding intracavernous injections and vacuum constriction devices suggest that an increased percentage of treated patients experienced a return of natural erections compared with patients who received no treatment. Longer, prospective, randomized, placebo-controlled studies will be needed to confirm the utility of these treatments. Data from contemporary studies evaluating the chronic use of oral phosphodiesterase type 5 inhibitors suggest a beneficial effect on endothelial cell function among men suffering from erectile dysfunction due to a variety of causes. Limited data suggest that this effect might be seen among post-prostatectomy patients, implying a possible role for these agents in enhancing the return of sexual function in such individuals.

Gender Differences among Hispanics and Caucasians in symptomatic presentation of kidney and ureteral stones.

PURPOSE: We determined gender differences in the symptomatic presentation of kidney and ureteral stones among the Hispanic population and compared it with presentation in the Caucasian population. PATIENTS AND METHODS: A retrospective chart review was performed on 443 patients seen in our Emergency Department or Urgent Care Center for symptomatic kidney or ureteral stones over a 5-year period. Demographic information was obtained, including sex, race, age, location of stone, stone size, and type of urologic intervention. Of the 443 patients, 263 (59%) were Hispanic, and 180 (41%) were Caucasian. RESULTS: The male-to-female ratio of the symptomatic patients with kidney stones was 1.48 for both Hispanic and Caucasian patients. The male-to-female ratio for ureteral stones was 1.06 and 2.48 for the Hispanic and Caucasian patients, respectively (P < 0.05). The rate of urologic intervention was similar among Caucasian males and females and Hispanic females (approximately 33%) but significantly lower among Hispanic males (18%). CONCLUSIONS: The relative symptomatic presentation of ureteral stones of men and women among the Hispanic population is nearly 1:1, whereas the ratio in Caucasian men and women approaches the previously reported 2.5:1. No significant racial or sex differences were noted in the symptomatic presentation of kidney stones. In comparison with Hispanic men, Hispanic women undergo significantly more urologic interventions for symptomatic urolithiasis.

Spinal cord injury in children: long-term urodynamic and urological outcomes.

PURPOSE: Urological complications in adults with spinal cord injuries (SCIs) are well documented. We sought to determine the effect of SCI on the developing bladder and kidneys in the child. MATERIALS AND METHODS: We retrospectively reviewed cases of SCI with 1-year minimum followup. We identified 42 children with an average age at injury of 5.3 years (range 1 day to 14 years). Mean followup was 5.5 years (range 1 to 15.5). Videourodynamics, sonograms, infection, medications and continence were reviewed. Safe bladder capacity was defined as the pressure specific volume at 40 cm water or less. Patients were divided into 3 groups based on level of injury-cervical (10), thoracic (26) and lumbar (6). RESULTS: Bladder management included clean intermittent catheterization in 40 of 42 patients and antispasmodics in 37. No patient had reflux, hydronephrosis or renal scarring. In the cervical group safe bladder capacity was less than the expected capacity in 80% of patients but all patients undergoing multiple urodynamics had increasing capacity with time. In the thoracic group 58% of patients had a safe bladder capacity less than expected and 76% of those undergoing multiple urodynamics had increasing capacity. In the lumbar group 50% of patients had a safe bladder capacity less than expected and 67% of those undergoing multiple urodynamics had increasing capacity. CONCLUSIONS: To our knowledge this is the largest and longest urological study of young children with SCI. Early clean intermittent catheterization and use of anticholinergics appear to prevent upper tract deterioration, improve continence and decrease infections. Serial urodynamics confirm increasing safe capacity with growth in most children. Close followup is necessary as bladder characteristics may change with time.