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Purpose: The computer generated recordings for 2 nights in 40 patients studied with the RigiScan† †Dacomed, Minneapolis, Minnesota. device were reevaluated using the new RigiScan Plus software to test its value in improving the discrimination between psychogenic and organic erectile dysfunction.Materials and Methods: Each man was evaluated for erectile dysfunction with a detailed medical and sexual history, physical examination, biothesiometry, plethysmography, 2 nights of ambulatory RigiScan monitoring and a psychological evaluation that usually included a private interview with the sexual partner. At the conclusion of evaluation each patient was broadly classified as having organic or psychogenic erectile dysfunction. The RigiScan reports were initially independently analyzed without the investigator's knowledge of the final diagnosis by determining the single best erectile event, with a minimal cutoff value of 60 percent erection for 5 minutes as necessary to be considered normal and the sum of...

We identified molecular markers of erectile function, particularly those responding to erectile dysfunction treatment.Sprague-Dawley retired breeder rats were intracorporeally injected with pVAX-hSlo, pSMAA-hSlo or the control plasmid pVAX. One week later the intracorporeal pressure-to-blood pressure ratio and gene expression were determined by microarray analysis and quantitative reverse transcriptase-polymerase chain reaction. Rat corporeal cells were transfected in vitro with pVAX-hSlo, pSMAA-hSlo or pVAX and the change in gene expression was determined. We also determined whether Vcsa1 expression was changed after pharmacotherapy using tadalafil.Animals treated with vectors expressing hSlo had significantly improved erectile function compared to that in controls, accompanied by changed expression of a subset of genes. Vcsa1 was one of the genes that was most changed in expression (the third of approximately 31,000 with greater than 10-fold up-regulation). Changes in gene expression were different than those observed in corporeal cells transfected in vitro, distinguishing gene expression changes that were a direct effect of hSlo over expression. When tadalafil was administered in retired breeder rats, the Vcsa1 transcript increased 4-fold in corporeal tissue compared to that in untreated controls.Our study identifies a set of genes that are changed in response to improved erectile function, rather than as a direct effect of treatment. We noted Vcsa1 may act as marker of the restoration of erectile function after gene transfer and pharmacotherapy.

Laparoscopic radical nephrectomy has been accepted as the preferred management for low stage renal masses not amenable to partial nephrectomy. Early in the mid 1990s several studies suggested that obesity should be a relative contraindication to laparoscopy. We present our surgical outcomes and complications in patients undergoing open and laparoscopic nephrectomy, stratified by body mass index.We retrospectively identified 88 patients, of whom 43 underwent open nephrectomy and 45 were treated laparoscopically. All patients were stratified by body mass index to compare multiple perioperative end points and pathological outcomes of laparoscopy.Overall our data showed that compared to open nephrectomy laparoscopic nephrectomy resulted in statistically significant lower estimated blood loss (147.95 vs 640.48 cc, p0.0002), operative time (156.11 vs 198.95 minutes, p0.003) and hospital stay (3.7 vs 5.9 days, p0.004). When stratified by body mass index less than 25, 25 to 29.9 and 30 kg/m(2) or greater, there was a statistically significant difference in estimated blood loss and hospital stay that was in favor of the laparoscopic approach in each body mass index category. Operative time did not show a statistical difference in the subgroups but all laparoscopic procedure times were shorter than open procedure times in each body mass index category. When patients with a body mass index of greater than 30 kg/m(2) were further subgrouped into 35 kg/m(2) or greater and 40 kg/m(2) or greater, there was a statistically significant difference in estimated blood loss and hospital stay that was again in favor of the laparoscopic method.Laparoscopic radical nephrectomy is technically more challenging as body mass index increases due to many factors but our data show that it is feasible and safe in experienced hands. Laparoscopy appears to result in perioperative outcomes that are superior to those of open nephrectomy in this high risk population with a complication profile that is equivalent to that of the open method for each stratified body mass index category.

Purpose: The involvement of the lower urinary tract in chronic Chagas' disease has received little attention. Therefore, we investigated pathology and functional alterations in the bladder of Trypanosoma cruzi infected mice. Materials and Methods: CD1 mice were infected with 5 × 10 4 T. cruzi trypomastigotes of the Brazil strain of T. cruzi. At day 100 after infection bladder structure and function were examined by pathological evaluation, magnetic resonance imaging and cystometric studies. Results: The bladder in infected mice weighed more and were large, dilated, deformed, friable and thin walled compared with control mice. Magnetic resonance imaging confirmed these observations. Inflammation, fibrosis and ganglionitis was observed. Cystometric studies revealed that baseline, threshold and micturition pressures were increased in infected mice. Bladder overactivity and decreased bladder compliance were also noted in infected mice. There were no detectable differences in bladder capacity, micturition volume or residual volume between infected and uninfected mice. Conclusions: Bladder abnormalities may be a more common clinical sequelae of T. cruzi infection than previously appreciated.

Purpose: Sustained contraction of human corporeal smooth muscle depends on continuous transmembrane calcium flux through voltage gated calcium channels. K channels modulate corporeal smooth muscle membrane potential and, thus, ultimately affect transmembrane calcium flux. Therefore, we characterized relaxation responses elicited by the K channel modulators pinacidil and levcromakalim on isolated human corporeal tissue strips. We also evaluated the possibility that there may be alterations in adenosine triphosphate sensitive K channel pharmacology/function related to the presence of diabetes mellitus. Materials and Methods: A total of 215 isolated human corporeal tissue strips obtained from 57 male patients with organic erectile dysfunction were investigated. Cumulative concentrationresponse curves were constructed at half log increments for steady state relaxation responses elicited by pinacidil and levcromakalim on equivalently phenylephrine pre-contracted (to approximately 75% of maximum) isolated corporeal tissue strips. Potassium currents were measured using the cell attached whole cell patch clamp technique on freshly isolated corporeal smooth muscle cells. Results: A concentration dependent, glibenclamide sensitive relaxation response of phenylephrine pre-contracted corporeal tissue strips was observed for pinacidil and levcromakalim. Consistent with such observations, electrophysiological recordings on freshly isolated myocytes revealed that pinacidil (10 M.) and levcromakalim (10 M.) induced whole cell potassium currents that were blocked by glibenclamide (10 M.). In addition, statistical analysis revealed that phenylephrine pre-contracted corporeal tissue strips from patients without diabetes were more sensitive to relaxation by both compounds than corporeal tissue strips excised from those with diabetes. Furthermore, relaxation responses elicited by pinacidil and levcromakalim were not affected by charybdotoxin or 4-aminopyridine but were completely reversed by KCl or tetraethylammonium chloride. Conclusions: These data indicate that the adenosine triphosphate sensitive K channel subtype is likely to have an important role in the relaxation of isolated corporeal tissue strips and, moreover, they are the molecular target for the K channel modulators/openers levcromakalim and pinacidil. Such observations are consistent with the supposition that alterations in the structure/function/activity of these potassium channels may underlie at least some aspects of observed diabetes related differences in tissue sensitivity to K channel modulators.

Recent evidence indicates that the large conductance, voltage dependent, Ca2+ sensitive K channel or Maxi-K has an important role in the modulation of human corporeal smooth muscle tone and, thus, in erectile capacity. We further clarified the contribution of the Maxi-K channel subtype to the generation of contractile responses in isolated human corporeal tissue strips.We performed pharmacological studies of phenylephrine contracted isolated corporeal tissue strips in the presence and absence of the 2 Maxi-K channel blockers tetraethylammonium chloride (TEA) and charybdotoxin, and the Maxi-K opener NS1619. K channel treatment effects were evaluated using 2 parameters, including 1) the steady state parameter of the empirically determined peak magnitude of the steady state contractile response and 2) the kinetic parameter of time required to achieve half of the peak steady state contractile response or half-time. Electrophysiological studies in freshly isolated and cultured myocytes were performed in parallel to corroborate findings further at the tissue level.Pre-incubating isolated human corporeal tissue strips with 1 mM. TEA and 1 microM. charybdotoxin was associated with an approximate 20% increase in the peak steady state contractile response and a corresponding approximate 20% decrease in the half-time of the phenylephrine induced contractile response. Conversely, pre-incubation with 10 microM. NS1619 produced a significant, approximately 20% decrease in the peak steady state contractile response and an approximate 38% increase in the half-time of the phenylephrine induced contractile response. Adding 30 to 180 microM. NS1619 to phenylephrine pre-contracted smooth muscle strips resulted in a 30% to 50% reduction in steady state contractile tension. No detectable effect of NS1619 was observed in 120 mM. KCl or 100 mM. TEA pre-contracted corporeal tissue strips. Whole cell recordings of freshly isolated and cultured corporeal myocytes confirmed that 30 microM. NS1619 induced a charybdotoxin sensitive hyperpolarizing current mediated by the Maxi-K channel.These in vitro studies confirm and extend previous observations indicating the importance of the Maxi-K channel for regulating human corporeal smooth muscle tone, and by extension, erectile capacity and function.

We evaluated the effects of vitamin A and E supplementation alone or in combination with non-steroidal anti-inflammatory drugs (NSAIDs) on the development of inflammation in an animal model of ascending pyelonephritis.Ascending pyelonephritis was induced in adult rats by surgical bladder inoculation with P-pili-forming Escherichia coli. Treatment of pyelonephritic rats was initiated at 72 hours post-infection. Treatment groups included no treatment, or a five day regimen of antibiotic only, antibiotic plus vitamins A and E, or antibiotic, vitamins and either of two NSAIDs. Kidneys were harvested at six weeks post-infection and assessed for histopathologic inflammation.Antibiotic treatment of pyelonephritic rats with vitamins A and E alone or in combination with NSAIDs resulted in significantly less kidney inflammation, as compared with untreated rats or rats treated with antibiotic alone. There was no significant difference in inflammation between animals treated with vitamins alone or vitamins plus NSAIDs.Antibiotic therapy and diet supplementation with vitamins A and E can significantly reduce the inflammation associated with ascending pyelonephritis, suggesting a potential use in the medical management of reflux nephropathy in children.

The standard care for patients with metastatic disease or inoperable prostate cancer is orchiectomy or the administration of luteinizing hormone releasing hormone agonists with or without an antiandrogen. With the use of leuprolide the reported incidence of gynecomastia and breast pain has ranged from 3 to 12.7%.lS2 Mastodynia in women has been treated with local support, dietary changes (low salt diets, vitamins and so forth) and/or hormonal manipulation. Fentimen et al reported a trial using 20 mg. tamoxifen, an estrogen receptor blocker, and com1 pared it to placebo for the treatment of ma~todynia.~ They obtained a 71% success rate with tamoxifen compared to 29% with placebo. This same group showed that 10 mg. could be as effective as 20 mg. tamoxifen with less side effects. Thus, it seems that 10 or 20 mg. tamoxifen may be used for the treatment of mastodynia. Some of the side effects reported are nausea, malaise, urticaria, alopecia, weight gain, depression, hot flashes, liver enzyme changes and irritability. We decided to try tamoxifen for the treatment of gynecomastia and breast pain in men with prostate cancer during androgen deprivation. A decrease and/or resolution of gynecomastia and/or pain was considered a good response to treatment. CASE REPORTS

We studied the pathological specimens obtained from 24 impotent men who underwent proximal penile vein ligation and 6 potent men who underwent total penectomy as part of male-to-female transsexual surgery to determine if a correlation exists between venous pathology and surgical outcome. Pathology specimens, consisting of cavernosal tissue and penile veins, were independently reviewed by a single uropathologist (V. A.). The degree of vein wall thickness was carefully quantified for each patient. Venous leakage was documented by cavernosometry and cavernosography. Followup ranged from 7 to 19 months (mean 11 months). Within 6 months of the procedure 10 patients (41%) achieved rigid erections while 14 (59%) did not. Although no preoperative index could predict operative success, in the 10 patients with successful outcome histological examination of the excised vein segments revealed normal venous architecture with minimal vein wall thickness (calculated mean per cent vein wall thickness 39.4, range 17.5 to 51.7). In contrast, in the 14 patients in whom ligation failed there was marked vein wall thickness and sclerosis (calculated mean per cent vein wall thickness 68.0, range 55.3 to 85.6). In comparison, the vein segments obtained from the 6 potent patients had a wall thickness of 32.8% (range 8 to 39), which was equivalent to the 10 patients with postoperative erections. These findings suggest that there may be a correlation between vein wall thickness and the prognosis of patients who undergo venous ligation surgery for erectile dysfunction secondary to presumed corporeal venous incompetence.

Electrical stimulation of the S2 nerve root can be used to produce detrusor contraction and voiding in patients with spinal cord injury, but concurrent stimulation of the external urethral sphincter causes detrusor-sphincter dyssynergia. This has been managed with a second surgical procedure, peripheral transection of the pudendal nerve. In this study, performed in dogs after spinal cord transection, laminectomy and ventral foraminotomy permitted tracing of the S2 root into the pelvis, where its branches were identified by electrical stimulation and urodynamic recording. The pudendal (somatic) branch was sectioned; the autonomic branch innervating the detrusor was preserved. Electrical stimulation of the proximal S2 root then produced detrusor contraction without contraction of the external urethral sphincter. This approach, which requires a single operation and spares pudendal nerve functions mediated by nerve roots other than S2, may enable a neurostimulator to provide effective voiding, without detrusor-external sphincter dyssynergia, in man.

Results of pediatric renal transplantation have been variable. We evaluated our experience with renal transplantation in children less than 5 years old to determine its safety and efficacy. Of the 428 renal transplants done at our institution from August 1983 to December 1989, 14 were performed in 13 children 13 to 50 months old (mean age 34 months). All of the patients were small for age with height standard deviation scores ranging from -1.7 to -4.5. Patient survival, allograft survival and statural growth were used as determinants of successful outcome. Followup was complete in all patients, including renal function studies and serial height measurements. Growth velocity standard deviation scores were calculated. Patient survival was 100%. Allograft survival was 100% 2 to 7.3 years after transplantation for living related donor recipients whereas 1-year graft survival was poor (40%) for cadaveric graft recipients. Of 10 patients with good graft function at 1 year 9 demonstrated improvement in the height standard deviation score. Seven of 10 patients demonstrated significant catch-up growth (growth velocity standard deviation score greater than 0, p = 0.04). Our study supports the safety and efficacy of renal transplantation in young children. Early transplantation using living-related donor organs is the optimal therapy to prevent growth retardation and allow the young child with end stage renal disease to have a normal life.

Two cases of the management and pathophysiology of high flow arterial priapism are presented. Both cases were post-traumatic with delayed onset of priapism and both had angiographically diagnosed arteriocorporeal fistulas. Case 1 was managed with selective cavernous artery ligation and case 2 resolved spontaneously, both with excellent return of premorbid levels of erectile function. We propose that the pathophysiological mechanism involves injury to the intracavernous artery, causing ischemic necrosis. After a delay the arterial segment blows out, leading to unregulated blood flow into the corpus cavernosum. Management with surgical ligation is highly selective and nondisruptive to unaffected vessels, offering precise control of the bleeding vessel.

Fertility and potential fertility were evaluated in 9 young men on cyclosporine A therapy following renal transplantation. Semen analysis was normal in most parameters in 8 patients as was testicular hormonal function. Of 4 men who had attempted to impregnate their wives 3 succeeded. Cyclosporine A does not seem to affect adversely fertility in men.

Dynamic cavernosometry and cavernosography can be used to identify patients with corporeal venous incompetence as a cause of erectile dysfunction. We reviewed our series of 16 patients with venous leakage who underwent surgical correction of the specific abnormality identified on cavernosography. Short-term and long-term results were obtained, and while at least temporary improvement was noted in 89.5% of the patients the long-term results tended to show a reversion to the preoperative status in the majority.

We performed an in-depth interview to ascertain the psychosocial and functional status in 10 of 22 male-to-female transsexuals who underwent vaginoplasty from May 1985 to December 1988. Followup from 5 to 48 months was available for 14 patients. Our patients comprised a well educated, mostly employed, law abiding group with a low incidence of drug use. Most patients were able to develop strong support systems and showed a marked decrease in suicidal tendencies postoperatively. Functionally, the majority of the patients were able to lubricate the neovagina and have painless intercourse with a potential for orgasm. The cosmetic result was judged to be good, with no patient reporting being discovered of having had a prior operation by the sexual partner. We experienced a 21% rate of vaginal stenosis with 40% of these patients fully functional after a corrective operation.

A case of unilateral ureteral obstruction owing to extensive pelvic endometriosis is presented. There was complete resolution of ureteral obstruction following treatment with synthetic progestin. Sequential assessment of renal function was provided by renal imaging and renograms. It would appear that selected patients with obstructive uropathy may respond favorably to medical management, which would allow for preservation of reproductive capabilities and restoration of renal excretory function.

The etiology of impotence, which affects 50 per cent of the men with diabetes, is unknown. The neurotransmitter (norepinephrine) released from adrenergic neurons is thought to be the most direct regulator of vascular smooth muscle. We have measured the norepinephrine content of the erectile tissue of diabetic men. Our results indicate the presence of a dual neural regulator mechanism of the corpora that controls penile erection.

Of 276 patients who underwent evaluation to determine the cause of hypertension 2 were found to have unsuspected renal cell carcinoma. This prevalence of 0.73 per cent is 16 times higher than expected for an age-matched population. Both patients exhibited abnormalities of plasma renin activity before radical nephrectomy but they remained hypertensive postoperatively. The data suggest an unexplained association between hypertension and renal cell carcinoma. Furthermore, abnormalities on excretory urograms in hypertensive people should be defined by selective renal arteriography.

We evaluated 70 patients for male sexual dysfunction in our center during its first 6 months of operation. The results of the analysis demonstrated that 55 per cent had organic impairment. Several important findings should be emphasized. There was mild elevation of serum prolactin in 6 cases, none of which was the direct cause of the impotence. A total of 15 patients had a diagnosis of either impaired glucose tolerance or overt diabetes (7 with organic and 8 with psychogenic disease). Therefore, the diagnosis of diabetes or impaired glucose tolerance, whether known previously or not, should not be accepted as confirming the organicity of impotence. Also, nocturnal penile tumescence alone confirmed the diagnosis of psychogenic impotence only when a rigid erection 5 minutes in duration occurred. The absence of nocturnal erections cannot be interpreted as conclusive evidence of organic impotence. Finally, a definitive diagnosis of psychogenic impotence was made based only on visual sexual stimulation in 6 patients. Our results emphasize further that etiologic factors of organic or psychogenic impotence are complex and that a multidisciplinary approach should be used.

One to 4 years after penile prosthesis implantation 52 men and 22 partners were interviewed personally. All except 4 patients were having intercourse on a regular basis. A quarter of the patients reported restriction in intercourse positions, possibly because of a smaller penis postoperatively, and 15 per cent reported decreased orgasm intensity. Six men had an undiagnosed prosthesis malfunction or they used an inadequate pumping technique, suggesting that prosthesis patients should be followed on a continuing basis. The 52 men had experienced 10 malfunctions with the prosthesis. Partial erections were reported by 69 per cent of the patients but this could be confirmed in only 1 of 10 with visual sexual stimulation testing. It is suggested that differences between prosthesis models are more a result of psychological, relationship and health factors than mechanical factors. Of the patients 79 per cent would undergo the operation again but only 59 per cent of the partners had no hesitations. The longer the postoperative period the more hesitations. A satisfaction score was used to measure patient satisfaction.