Pentosan polysulfate decreases prostate smooth muscle proliferation and extracellular matrix turnover.

Benign prostatic hyperplasia (BPH) involves proliferation of smooth muscle cells and increased deposition of extracellular matrix (ECM). We recently found that pentosan polysulfate (PPS) has marked effects on growth and ECM of smooth muscle cells derived from vascular tissues. We examined smooth muscle cells cultured from human prostates and the effects of PPS on their growth and ECM production. Fragments of surgical prostatectomy specimens were diced, digested with collagenase (0.01%), and placed in culture medium supplemented with 20% fetal bovine serum. Outgrowths of elongated cells were characterized by light microscopic examination and immunohistochemical techniques by the presence of F-actin, alpha-smooth muscle actin, and myosin, which is a characteristic of smooth muscle cells. Two independent isolates were propagated, and growth curves and ECM production were assessed in the presence and absence of PPS (10 or 100 microg/ml). PPS decreased cell number beginning at day 1 and throughout the incubation period, up to 4 days. The amount of the ECM degradative enzymes, metallo-proteinases MMP-9 and MMP-2, was examined by zymography. PPS did not alter the amount of MMP-2 in the supernatants but MMP-9 was increased 234.4 +/- 17.23-fold over control cells. Tissue inhibitor of MMP (TIMPS), examined by reverse zymography, increased 200% over control. The amount of alpha I type (IV) and alpha I type (I) collagen released in the supernatant, measured by ELISA, significantly decreased in PPS-treated cultures. In conclusion, we found that the administration of PPS decreased proliferation as well as ECM production in prostate smooth muscle. Since smooth muscle proliferation and ECM are involved in the pathophysiology of BPH, PPS may have therapeutic potential.

Factors associated with clinical assessment of overactive bladder and selection of treatment.

BACKGROUND: Overactive bladder (OAB) affects >17 million individuals in the United States, but the symptoms of OAB are frequently underreported by patients and therefore untreated by physicians. OBJECTIVE: The purpose of this observational study was to investigate the demographic and clinical factors associated with the decision to treat OAB pharmacologically and identify factors associated with physicians' assessment of symptom severity. METHODS: We studied 31 physicians treating 217 patients with OAB and collected data on patient demographic characteristics, OAB symptoms, previous management strategies, physicians' assessments of OAB severity, and treatment prescribed. Stepwise logistic regression was used to identify factors associated with selecting pharmacologic treatment and with physician assessment of severity of OAB symptoms. RESULTS: The mean age of the patients was 61.3 years; approximately 82% were female, and approximately 73% were white. Participants with urinary incontinence were significantly (P < 0.001) more likely to be treated with medication than were those with only symptoms of nocturia or urinary frequency. Other significant factors associated with pharmacologic treatment were being white (odds ratio [OR], 9.5; 95% CI, 2.9-30.8); being black (OR, 5.9; 95% CI, 1.2-29.7); physician's clinical assessment of OAB as moderate (OR, 3.5; 95% CI, 1.5-8.2) or severe (OR, 3.8; 95% CI, 1.1-13.7); previous use of medication (OR, 2.9; 95% CI, 1.1-8.1); and number of incontinence episodes in the last 24 hours (OR, 1.2; 95% CI, 1.0-1.5). Factors associated with physician assessment of OAB severity included distress due to OAB symptoms (OR, 2.1; 95% CI, 1.3-3.2), number of incontinence episodes in the last 24 hours (OR, 1.2; 95% CI, 1.1-1.4), and use of previous treatment(s) (OR, 0.4; 95% CI, 0.2-0.8). CONCLUSIONS: Both demographic and clinical symptoms of OAB were associated with the decision to treat OAB with medication, whereas physicians' assessment of OAB severity was associated only with clinical symptoms. Urinary incontinence was the key symptom associated with the decision to treat patients with medication and with the assessment of OAB symptom severity.

Burch-Cooper's ligament sling procedure: an augmented incontinence operation.

PURPOSE: The Burch procedure is used in conjunction with a modified pubovesical sling to produce a potentially more durable incontinence operation. This augmented incontinence procedure is recommended for use in patients at particularly high risk of recurrence of incontinence or in patients with intrinsic sphincter deficiency who have concomitant cystocoele (paravaginal defect). MATERIALS AND METHODS: A prospective study was initiated to demonstrate the efficacy of this combined operative procedure that incorporates two established operative techniques. RESULTS: Ten of 13 patients in whom this operation was performed are completely continent. They have neither stress nor urgency incontinence. They have all resumed active lifestyles. Three patients experienced postoperative problems. They had complex presentations and/or required multiple operative procedures. Two women continue to have mild urge incontinence postoperatively. One of these women has occasional urinary retention. The third woman who had a large cystocele, intrinsic sphincter deficiency, and rectal prolapse has functional obstruction postoperatively. CONCLUSION: Support and stability are developed at the urethrovesical angle by means of a combined operative procedure.

Randomized trial of safety and efficacy of transurethral resection of the prostate using contact laser versus electrocautery.

The aim of this study was to prospectively evaluate the safety and efficacy of contact laser ablation of the prostate (CLAP) vs. transurethral resection of the prostate (TURP) in symptomatic benign prostatic hypertrophy (BPH). During a 1-year period (1995-1996), 37 males 50 years of age or older were randomized to either CLAP using Nd:YAG laser treatment or TURP. Patients with Qmax <15 mL/s, American Urological Association (AUA) symptom score >12, and postvoid residual (PVR) >125 mL were enrolled. Patients were excluded if they had prior surgical treatment for BPH or known conditions that could affect bladder function. Comparisons of preoperative and postoperative symptom scores, Qmax, PVR, total catheter time, hospital stay, complications, and hematocrit changes were performed. A 2:1 randomization was used, which resulted in 26 CLAP and 12 TURP patients. One-year follow-up data were available for 21 CLAP and 7 TURP patients. The mean prostate volume, age, AUA symptom score, and Qmax were not significantly different between the two arms. Significant differences in favor of CLAP were shorter catheter time (27.2 vs. 40.4 hours; p < .05) and shorter hospital stays (28.5 vs. 60.0 hours; p < .05). The only other significant difference between the two arms was a lower AUA symptom score in favor of TURP at 1 year (4.7 vs. 8.4; p < .05). Qmax, PVR, and postoperative hematocrit were similar between the groups. The only complications included recatheterizations, which occurred more frequently in the TURP patients (25% vs. 14%). CLAP appears to be slightly less effective in AUA symptom score reduction; however, it is equally safe and is superior for shortening catheter time and hospital stay compared to TURP.

Urinary incontinence and depression.

PURPOSE: Serotonergic neuronal systems have been implicated in anxiety and depression. Because descending serotonin pathways from the brain stem inhibit bladder contractions, we postulated that depression associated with altered serotonin function may predispose to urge incontinence. We demonstrate an association between depression and idiopathic urge incontinence. MATERIALS AND METHODS: A total of 115 consecutive incontinent patients presenting to an incontinence clinic were compared to 80 continent controls. Patients were queried for a history of depression and completed a Beck Depression Inventory (BDI). Cases were classified by history and video urodynamics as genuine stress (36), urge (44) or mixed (35) incontinence. RESULTS: A BDI of greater than 12 and/or a history of depression was noted in 30% of incontinent patients and 17% of controls (odds ratio 2.3, 95% confidence interval 1.0 to 5.0, p = 0.044). An abnormal BDI or history of depression was revealed in 60% of patients with idiopathic urge incontinence (p<0.001). Patients with stress or urge incontinence due to neuropathology or obstruction had no greater odds of having depression than continent controls. CONCLUSIONS: These data suggest a strong association between depression and idiopathic urinary incontinence. This link may be due to altered serotonin function and may help explain the efficacy of serotonergic based antidepressants in the treatment of urge incontinence.

Evaluation and treatment of infertility in spinal cord injured men through rectal probe electroejaculation.

A total of 18 men older than 19 years with spinal cord injury was evaluated for fertility potential with testing of semen obtained by rectal probe electroejaculation. After fertility testing, including sperm penetration assay, semen cryopreservation and sperm antibody status, 6 of the 18 men proceeded with their partners to use rectal probe electroejaculation in efforts to conceive. Sperm was obtained in 16 of 18 cases. Average ejaculate total sperm count (306 million) was good but motility (22%) was poor. Adequate sperm retrieval after processing yielded a normal sperm penetration assay in 4 of 16 cases (25%) in which sperm were obtained. Favorable semen cryopreservation (greater than 33% of pre-freeze motility noted after thaw) was present in 5 of 16 cases (31%). Live births were achieved in 2 of 6 couples attempting conception. Despite the typically poor sperm motility noted in electroejaculates, rectal probe electroejaculation can result in pregnancies from couples involving spinal cord injured men. The sperm penetration assay data indicate that pregnancy should be achievable in at least 25% of spinal cord injured couples. Achieving these conceptions requires a team approach involving a urologist/andrologist, gynecologist/reproductive endocrinologist and a sperm-processing laboratory.

Combined pancreas--kidney transplantation in Nebraska.

UNLABELLED: In the last 2 years, we have performed combined pancreas-kidney transplantation in 38 Type I diabetics with nephropathy. The mean age of the recipient group was 35 years (range 24-51) with a mean duration of diabetes of 22 years (range 13-41). All patients received quadruple immunosuppression with OKT3 induction. All patients are normoglycemic and insulin independent with a mean glycosylated hemoglobin level of 5.2 +/- 1.1% and a mean serum creatinine of 1.9 +/- 0.5 mg/dl. Metabolic effects of pancreas transplantation included fasting hyperinsulinemia and hyperglucagonemia with exaggerated insulin and glucagon responses to glucose and arginine, respectively, that improved slightly with time. Patient and kidney graft survival are 100% and pancreas graft survival is 94.7% after a mean follow-up interval of 15 months. CONCLUSION: Combined pancreas-kidney transplantation is the treatment of choice for selected Type I diabetics with nephropathy and results in euglycemia despite immunosuppression.

Combined pancreas-kidney transplantation: preliminary results and metabolic effects.

UNLABELLED: Vascularized pancreas transplantation (PT) results in a self-regulating endogenous source of insulin. In the last 18 months, we have performed combined pancreas-kidney transplantation in 25 type I diabetics with nephropathy. The mean age of the recipient group was 35 yr (range 24-51) with a mean duration of diabetes of 22 yr (range 13-41). All patients received quadruple immunosuppression with OKT3 induction. All patients remained normoglycemic and insulin independent with a mean glycosylated hemoglobin level of 6.0 +/- 1.1% and a mean serum creatinine of 1.7 +/- 0.5 mg/dl. Metabolic control and hormonal profiles were assessed by intravenous glucose challenge followed by arginine stimulation. Metabolic effects of PT included fasting hyperinsulinemia and hyperglucagonemia with exaggerated insulin and glucagon responses to glucose and arginine, respectively. Patient and graft survival is 100% after a mean follow-up interval of 8 months. CONCLUSION: combined pancreas-kidney transplantation is a valid treatment option for diabetic nephropathy, and results in near-complete normalization of glucose metabolism.

Cost-benefit analysis of pharmacologic erection program (PEP) versus penile prosthesis.

We compared the current dollar inclusive costs of the two most commonly implanted penile prostheses with our pharmacologic erection program (PEP). The inclusive cost of implantation for the inflatable penile prosthesis (IPP) is $9,000 and for the malleable penile prosthesis (MPP) $3,150. The inclusive cost of PEP at maximal dose and maximal frequency of use over a five-year period is $3,450. Penile prosthesis was found to be more cost-effective for the long-term treatment of younger impotent men, whereas in the elderly group the use of PEP over a limited time span may be equally or more cost-effective.