Experience with intracavernous injection in the treatment of erectile dysfunction after radical prostatectomy: dose considerations.

We sought to identify factors influencing dose maintenance of intracavernous (IC) injection among patients with ED following radical prostatectomy. A total of 93 patients underwent prostatectomy and received IC treatment for ED, including PGE1 single therapy (n=53) and triple therapy (n=40). In the PGE1-only group, the maintenance dosage was significantly correlated with preoperative sexual function and nerve sparing (NS) (P<0.05). For example, the maintenance dose among patients with no, unilateral and bilateral NS was 10.8 ± 6.6 µg (0.54 ± 0.33 ml), 10.8 ± 3.8 µg (0.54 ± 0.19 ml) and 6.4 ± 4.6 µg (0.32 ± 0.23 ml), respectively. In terms of preoperative sexual function, the maintenance dose among non-ED versus ED patients was 0.38 ± 0.25 ml (7.6 ± 5.0 µg) and 0.59 ± 0.31 ml (11.8 ± 6.2 µg), respectively. No significant correlation was observed between the maintenance dose and NS or preoperative sexual function among the triple-therapy patients or between the maintenance dose and age, body mass index, systemic diseases and initiation of ED treatment among all patients (P>0.05). Thus, maintenance dose of PGE1 therapy could be partly determined by NS status and prior ED of patients.

Oestrogen receptor alpha localisation in the prefrontal cortex of three mammalian species.

Oestrogen modulates cognitive function and affective behaviours subserved by the prefrontal cortex (PFC). Identifying and localising oestrogen receptor (ER)alpha, in human PFC will contribute to our understanding of the molecular mechanism of oestrogen action in this region. Inferences about the site of action of oestrogen in human brain are derived largely from studies performed in nonhuman mammalian species; however, the congruence of findings across species has not been demonstrated. Furthermore, the laminar, cellular, and subcellular localisation of ERalpha in the cortex is debated. Therefore, we compared the distribution of ERalpha in human dorsolateral prefrontal cortex (DLPFC) with that of monkey DLPFC and rat medial PFC. Immunohistochemistry performed on frontal cortex from the three species demonstrated ERalpha positive cells throughout all layers of the PFC, in pyramidal and nonpyramidal neurones, with both nuclear and cytoplasmic immunoreactivity. Western blot analyses and preabsorption studies confirmed that the antibody used recognised ERalpha and not ERbeta. A strong ERalpha immunoreactive band corresponding to the full-length ERalpha protein (65-67 kDa) in the frontal cortex of all three species matched the size of the predominant immunoreactive band detected in breast cancer cell lines known to express ERalpha. Additionally, other ERalpha immunoreactive proteins of varying molecular weight in breast cancer cells, rat ovary and mammalian brain were detected, suggesting that ERalpha may exist in more than one form in the mammalian frontal cortex. The present study provides evidence that ERalpha protein exists in neurones in mammalian PFC and that ERalpha is anatomically well-positioned to directly mediate oestrogen action in these neurones.

Penile prosthesis implantation: past, present and future.

Penile prosthesis implantation is the oldest effective treatment for erectile dysfunction. This review examines the past, present and future of penile prosthesis implantation. Advances in prosthetic design and implantation techniques have resulted today in devices that produce nearly normal flaccid and erect states, and have remarkable freedom from mechanical failure. The future of prosthetic design holds promises for even more improvements.

Risk of infection with an antibiotic coated penile prosthesis at device replacement for mechanical failure.

PURPOSE: The inflatable penile prosthesis is well established as an effective treatment for select patients with organic erectile dysfunction. The risk of prosthetic infection at primary implantation is approximately 2%. However, for revision or replacement procedures the risk of infection has been reported to be as high as 13.3%. To minimize the overall risk of prosthetic infection an antibiotic coated inflatable penile prosthesis (InhibiZone) has been developed. To assess the impact on infection rates we reviewed our experience with the use of this device at prosthesis replacement for mechanical failure. MATERIALS AND METHODS: We retrospectively reviewed the records of all patients undergoing inflatable penile prosthesis replacement for mechanical failure with an antibiotic coated prosthesis between May 2001 and November 2004. Salvage procedures for clinically infected prostheses were excluded from analysis. Chart review was performed with examination of operative notes, all postoperative contacts and microbiological data. RESULTS: A total of 55 patients underwent replacement of an inflatable penile prosthesis for mechanical failure using a device coated with rifampin and minocycline HCL (InhibiZone). In all patients before reimplantation component spaces were irrigated in standard fashion. With a median followup of 32 months (range 12 to 54) postoperative device infection requiring explantation developed in 1 patient (1.8%). Intraoperative cultures from the pump site grew coagulase negative staphylococcus. CONCLUSIONS: Our data suggest that an antibiotic coated inflatable penile prosthesis may lead to decreased infection rates in patients undergoing penile prosthesis replacement for mechanical failure.

Early use of vacuum constriction device following radical prostatectomy facilitates early sexual activity and potentially earlier return of erectile function.

To assess the efficacy of vacuum constriction devices (VCD) following radical prostatectomy (RP) and determine whether early use of VCD facilitates early sexual activity and potentially earlier return of erectile function. This prospective study consisted of 109 patients who underwent nerve-sparing (NS) or non-nerve-sparing (NNS) RP between August 1999 and October 2001 and developed erectile dysfunction following surgery. The patients were randomized to VCD use daily for 9 months (Group 1, N=74) or observation without any erectogenic treatment (Group 2, N=35). Treatment efficacy was analyzed by responses to the Sexual Health Inventory of Men (SHIM) (abridged 5-item International Index of Erectile Function (IIEF-5)), which were stratified by the NS status. Patient outcome regarding compliance, change in penile length, return of natural erection, and ability for vaginal intercourse were also assessed. The mean patient age was 58.2 years, and the minimum follow-up was 9 months. Use of VCD began at an average of 3.9 weeks after RP. In Group 1, 80% (60/74) successfully used their VCD with a constriction ring for vaginal intercourse at a frequency of twice/week with an overall spousal satisfaction rate of 55% (33/60). In all, 19 of these 60 patients (32%) reported return of natural erections at 9 months, with 10/60 (17%) having erections sufficient for vaginal intercourse. The abridged IIEF-5 score significantly increased after VCD use in both the NS and NNS groups. After a mean use of 3 months, 14/74 (18%) discontinued treatment. In Group 2, 37% (13/35) of patients regained spontaneous erections at a minimum follow-up of 9 months after surgery. However, only four of these patients (29%) had erections sufficient for successful vaginal intercourse and rest of patients (71%) sought adjuvant treatment. Of the 60 successful users, 14 (23%) reported a decrease in penile length and circumference at 9 months (range, 4-8 months) compared to 12/14 (85%) among the nonresponders. However, in control group 22/35 reported decrease in penile length and circumference. Early use of VCD following RP facilitates early sexual intercourse, early patient/spousal sexual satisfaction, and potentially an earlier return of natural erections sufficient for vaginal penetration.

Male sexual function improves after ileal pouch anal anastomosis.

PURPOSE: Restorative Proctocolectomy and Ileal Pouch Anal Anastomosis has become the gold standard surgical therapy for the majority of patients with mucosal ulcerative colitis. However sexual functional disturbances after this procedure can be a concern for patients. Therefore the aim of this study was to determine the outcome of sexual-function related quality of life in male patients undergoing restorative proctocolectomy. METHODS: One hundred and twenty-two male patients who underwent restorative proctocolectomy with ileal pouch anal anastomosis between 1995 and 2000 were evaluated by the validated International Index of Erectile Function (IIEF) scoring instrument. This index scale examines sexual function in five categories. These are erectile function, orgasmic function, sexual desire, intercourse satisfaction and overall satisfaction. The IIEF instrument was administered after surgery and then scores before and after RP/IPAA were evaluated and compared. The significance of age at the time of the surgery, type of surgery, type of anastomotic technique (mucosectomy vs stapled) and septic complications on sexual functional outcome were also investigated. RESULTS: Mean age at the time of the surgery was 39.9 +/- 11.5 years. The mean follow-up period (time between pouch surgery and IIEF completed) was 3.6 +/- 1.8 years. There was statistically significant improvement in 4 of 5 categories of sexual function (erectile function, sexual desire, intercourse satisfaction, and overall satisfaction) where patients had improved scores after surgery compared to prior to surgery. The mean erectile function score increased pre to post surgery by 2.12 points (P = 0.02), which indicates better sexual results. Anastomotic technique and septic complication did not influence the results, however, older age had a negative impact on results. CONCLUSIONS: Despite some adverse sexual functions, male patients who undergo RP/IPAA for the surgical management of their colitis may preserve or improve their overall sexual functional outcome.

Antibiotic-coated medical devices: with an emphasis on inflatable penile prosthesis.

One of the most serious complications associated with the use of the inflatable penile prosthesis is infection. This can lead to significant morbidity for the patient, as well as significant health care costs. A number of methods have been used in attempts at minimizing the infection risk, including applying an antibiotic coating to the medical devise. This review aims to evaluate the effectiveness of these products in preventing clinically significant infections.

Bone is a target for the antidiabetic compound rosiglitazone.

Rosiglitazone is an FDA-approved oral antidiabetic agent for the treatment of type 2 diabetes. This compound improves insulin sensitivity through the activation of the nuclear receptor, peroxisome proliferator-activated receptor-gamma (PPAR-gamma). In addition to sensitizing cells to insulin, the PPAR-gamma2 isoform appears to be critical for the regulation of osteoblast and adipocyte differentiation from common mesenchymal bone marrow progenitors. We have demonstrated previously that PPAR-gamma2 activated with rosiglitazone acts as a dominant inhibitor of osteoblastogenesis in murine bone marrow in vitro. Here, we show that in vivo, rosiglitazone administration results in significant bone loss. When rosiglitazone (20 microg/g body weight/d) was given to 6-month-old, nondiabetic C57BL/6 mice for 7 wk, a significant decrease in total body bone mineral density was observed. Analysis of bone microarchitecture, using micro-computed tomography, demonstrated a decrease in bone volume, trabecular width, and trabecular number and an increase in trabecular spacing. Histomorphometric analysis showed a decrease in bone formation rate, with a simultaneous increase in fat content in the bone marrow. Changes in bone morphology and structure were accompanied by changes in the expression of osteoblast- and adipocyte-specific marker genes; the expression of the osteoblast-specific genes Runx2/Cbfa1, Dlx5, and alpha1(I)collagen were decreased, whereas the expression of the adipocyte-specific fatty acid binding protein aP2, was increased. These in vivo data suggest that rosiglitazone therapy may pose a significant risk of adverse skeletal effects in humans.

Cylinder sizing: less is more.

In penile prosthesis implantation traditional cylinder-sizing techniques frequently result in penile cylinders that are too long for the corpora cavernosa. This can result in premature cylinder wear leading to cylinder aneurysm or fluid loss. Additionally, in the case of the length expanding Ultrex penile prosthesis, cylinders that are too long can result in an S-shaped cylinder deformity. We describe a cylinder measurement technique that avoids the problem of oversizing.

Surgical approaches for penile prosthesis implantation: penoscrotal vs infrapubic.

Surgical approaches for implantation of three-piece inflatable penile prostheses include the infrapubic and the penoscrotal. The penoscrotal approach avoids possible injury to the dorsal sensory nerves, provides easier and more complete corporeal exposure, and allows the pump to be anchored in the scrotal pouch. A variant of the penoscrotal approach, the transverse penoscrotal incision, is described.

Long-term efficacy and compliance of intracorporeal (IC) injection for erectile dysfunction following radical prostatectomy: SHIM (IIEF-5) analysis.

Baseline and follow-up data from 102 patients using intracorporeal (IC) injection for erectile dysfunction (ED) following RP were retrospectively collected. We compared baseline International Index for Erectile Function (IIEF) questionnaires with the abridged IIEF-5 questionnaires, referred to as the Sexual Health Inventory of Men (SHIM) to determine drug efficacy. The mean presurgery SHIM score was 21.75+/-5.23, which decreased to 4.23+/-3.48 after surgery and increased to 19.46+/-8.78 post-treatment. Overall, 68% (69/102) of patients achieved and maintained erections sufficient for sexual intercourse and 48% (49/102) of patients continued long-term therapy with a mean use of 3.7+/-1.9 y. In all, 52% (53/102) patients discontinued IC therapy. However when excluding patients who switched to oral therapy, had loss of partner or return of normal erections; the compliance to IC injections was 70.6% (71/102). There was no difference in the SHIM analysis between the nerve sparing (NS) and the non-NS or between the types of medications used. IC injections can provide excellent long-term efficacy and compliance in up to 70% of the patients. This study suggests that IC injections are an excellent salvage option in NS patients who fail oral therapy and a first option in patients with non-NS procedures.

A rat resistance exercise regimen attenuates losses of musculoskeletal mass during hindlimb suspension.

Exposure to microgravity and/or spaceflight causes dramatic losses in both muscle and bone mass. In normal gravity, resistance exercise has been effectively used to increase muscle and bone mass. We tested a novel form of resistance exercise training using flywheel technology as a countermeasure to offset the loss of musculoskeletal mass during 4 weeks of adult rat hindlimb suspension (HS), an unloading model of microgravity. Male, Sprague-Dawley rats (6-month old) were operantly conditioned to perform resistance exercise, and then randomly assigned to groups of sedentary control (CON), HS, and HS with resistance exercise training (HSRT; 2 sets of approximately 21 repetitions, 3 days week(-1) for 4 weeks during suspension). In soleus, HS resulted in lower (P < 0.05) muscle mass to body mass ratio (approximately 50% of controls) and rates of protein synthesis. HSRT significantly attenuated the loss of muscle mass in soleus muscle, and rates of protein synthesis for soleus were similar for HSRT and controls. There were no differences among groups for mass or rates of protein synthesis in extensor digitorum longus. In cancellous regions of the distal femur, HS resulted in significant reductions of bone mineral density (BMD), but this was restored to control levels with HSRT. Cortical regions of the femur were not different among HS, HSRT or control groups. Together, these data suggest that resistance training using flywheel technology may be a promising tool to attenuate losses of the musculoskeletal system during periods of hindlimb unloading.

Peekaboo: a new look at infants' perception of emotion expressions.

Infants' responsiveness to others' affective expressions was investigated in the context of a peekaboo game. Forty 4-month-olds participated in a peekaboo game in which the typical happy/surprised expression was systematically replaced with a different emotion, depending on group assignment. Infants viewed three typical peekaboo trials followed by a change (anger, fear, or sadness) or no-change (happiness/surprise) trial, repeated over two blocks. Infants' looking time and affective responsiveness were measured. Results revealed differential patterns of visual attention and affective responsiveness to each emotion. These results underscore the importance of contextual information for facilitating recognition of emotion expressions as well as the efficacy of using converging measures to assess such understanding. Infants as young as 4 months appear to discriminate and respond in meaningful ways to others' emotion expressions.

Artificial urinary sphincter troubleshooting.

An approach to solving the problem of persistent or recurrent urinary incontinence after artificial urinary sphincter implantation is presented. This practical approach is designed to identify the known causes of this disorder, with treatment being directed to the cause.

Long-term continence and patient satisfaction after artificial sphincter implantation for urinary incontinence after prostatectomy.

PURPOSE: We assess long-term continence and patient satisfaction after implantation of the AMS Sphincter 800 (American Medical Systems, Minnetonka, Minnesota) in men who were incontinent after total and subtotal prostatectomy. MATERIALS AND METHODS: Patients who had an artificial urinary sphincter implanted for urinary incontinence after prostatectomy and a minimum of 20 months of followup were identified from a patient database. The medical records of these 209 patients were reviewed, and a questionnaire was mailed. Telephone contact was attempted with patients who did not respond to the questionnaire. Of the 209 patients 11 (5%) had undergone device removal, 34 (16%) were deceased and an additional 51 (24%) could not be contacted for followup. Our study group consisted of the 113 patients with artificial urinary sphincters who could be contacted for followup. Mean followup was 73 months (range 20 to 170). RESULTS: There were 4 (4%) patients who were dry and continent and 68 (60%) were incontinent using 0 to 1 pad daily. An additional 35 (31%) patients required 2 to 3 pads daily and 5 (4%) used more than 3 daily. There were 14 (12%) patients who had undergone surgical revision of the device. Of the 113 patients 31 (28%) were very satisfied, 50 (45%) satisfied, 20 (18%) neutral, 7 (6%) dissatisfied and 4 (4%) very dissatisfied. One patient was not using his device to control continence. CONCLUSIONS: Artificial urinary sphincter implantation offers men who are incontinent after prostatectomy a reasonable chance for obtaining long-term satisfactory urinary control, although complete continence is unusual.

Penile prosthesis implantation.

The development of effective systemic therapy for the treatment of erectile dysfunction has resulted in a significant increase in the number of men presenting for treatment. Not all men with erectile dysfunction will respond to systemic therapy; those who fail may be candidates for penile prosthesis implantation if second and third lines of treatment also fail or are rejected by the patient and his partner. Penile prosthesis implantation continues to play a role in the treatment of erectile dysfunction. There is a potential for the number of penile prosthesis implantation procedures to actually increase. The ideal penile prosthesis is a three-piece inflatable device that permits good penile flaccidity and increases in size and becomes rigid with inflation.

Quantification of D1B(D5) receptors in dopamine D1A receptor-deficient mice.

The unavailability of selective D1A(D1) or D1B(D5) dopamine receptor ligands has prevented the direct localization of binding sites for these receptors. Thus, receptor autoradiography with long exposure times was used to detect minor D1-like binding sites in the brains of D1A null mutants. Coronal brain sections were prepared from the caudal portion of the prefrontal cortex of homozygous or heterozygous D1A knockout mice or wildtype mice, and labeled with the D1 receptor antagonist [3H]-SCH23390. Slides were dried, and apposed to film with polymer-calibrated standards for 90 days to allow visualization of any low abundance binding sites. No binding was detected in most regions of homozygote (-/-) mouse brains that have high densities of D1 binding in wildtype mice (e.g., the striatum, nucleus accumbens, olfactory tubercles or amygdala). Conversely, small, but detectable amounts of D1-binding were measured in the hippocampus, albeit with a density less than the lowest standard (ca. 20 fmol/mg). Saturation binding of [3H]-SCH23390 in hippocampal homogenates from homozygous mice confirmed a B(max) of 12.3 fmol/mg protein with a K(D) of 0.57 nM. The current work demonstrates directly the presence of D1B(D5) receptors in hippocampus, and also shows that the loss of functional D1A gene products almost completely eliminates detectable D1-binding sites in striatum, as well as in some regions (e.g., the amygdala) where a non-adenylyl cyclase coupled D1 receptor has been reported. This indicates that these non-adenylyl cyclase coupled D1-like receptors represent alternate signaling pathways rather than novel gene products(s).

Report of the American Foundation for Urologic Disease (AFUD) Thought Leader Panel for evaluation and treatment of priapism.

PURPOSE: Patients with priapism often develop permanent erectile dysfunction and personal sexual distress. This report is intended to help educate the public by reviewing the varied definitions and classifications of priapism and limited literature reports of pathophysiology, diagnosis and treatment outcomes of priapism. The AUA priapism guidelines committee is responsible for creating consensus as to appropriate individual patient management of priapism by physicians. MATERIALS AND METHODS: A multidisciplinary panel, consisting of 19 thought leaders in priapism, was convened by the Sexual Function Health Council of the American Foundation for Urologic Disease to address pertinent issues concerning the role of the urologist, primary care providers and other health care professionals in the education of the public regarding management of men with priapism. The panel utilized a modified Delphi method and built upon the peer review literature on priapism. RESULTS: The Thought Leader Panel recommended adoption of the definition of priapism as a pathological condition of a penile erection that persists beyond or is unrelated to sexual stimulation. Priapism is stressed to be an important medical condition that requires evaluation and may require emergency management. The classification system is categorized into ischemic and non-ischemic priapism. Essential elements of the ischemic classification are the inclusion of: (i) clinical characteristics of pain and rigidity; (ii) diagnostic characteristics of absence of cavernosal arterial blood flow; (iii) pathophysiological characteristics of a closed compartment syndrome; (iv) a time limit of 4 h prior to emergent medical care; and (v) a description of the potential consequences of delayed treatment. Essential elements of the non-ischemic classification are the inclusion of: (i) clinical characteristics of absence of pain and presence of partial rigidity; (ii) diagnostic and pathophysiological characteristics of unregulated cavernosal arterial inflow; and (iii) the need for evaluation but emphasizing the lack of a medical emergency. The panel recommended adoption of a rational management algorithm for the assessment and treatment of priapism where the cornerstone of initial assessment includes a careful clinical history, a focused physical examination and selected laboratory and/or radiologic tests. The panel recommended that specific criteria and clinical profiles requiring specialist referral should be identified. The panel further recommended that patient (and partner) needs and education concerning priapism should be addressed prior to therapeutic intervention, however only in the case of chronic management or post acute presentation evaluation should this delay intervention. Treatment goals to be discussed include management of the priapism with concomitant prevention of permanent and irreversible erectile dysfunction and associated psychosocial consequences. The panel recommended that when specific therapies for priapism are required, a step-care treatment approach based upon reversibility and invasiveness should be followed. CONCLUSIONS: The Thought Leader Panel calls for research to expand our understanding of the prevalence and diagnosis of priapism and education to create awareness among the public of the potential urgency of this condition. Critical areas to be addressed include the multiple pathophysiologies of priapism as well as multi-institutional trials to objectively assess safety and efficacy in the various treatment modalities.

Penile prosthesis infections.

In this retrospective review we looked at infection rates and risk factors in penile prosthesis recipients. Computer registry records of patients implanted with three-piece inflatable prostheses from April 1986 to March 1999 were reviewed. Bacteriological culture report data were obtained from the medical records. There were 491 three-piece inflatable penile prosthesis recipients with follow-up ranging from 1 to 168 months (mean 83). All patients were implanted more than 1 y ago. There were 10 infections in 491 recipients (2.0%). In 285 primary prosthesis recipients there were seven infections (2.5%). In 206 secondary prosthesis recipients there were three infections (1.5%). Seven infections occurred in 354 non-diabetics (2.0%) and three infections occurred in 137 diabetics (2.2%). None of these differences were statistically significant. Explants for infection were performed in 8 weeks or less following implantation in eight patients. In two patients explants occurred at 17 and 26 months following implantation. Cultures from the periprosthetic space grew E. coli (four), Proteus mirabilis (two), Staph. aureus (two), and bacteroides (two). Infections occurred in 2.0% of three-piece inflatable penile prosthesis recipients. There were no statistically significant differences in infection rates between first time and repeat prosthesis recipients and between diabetic and non-diabetic recipients. Eight of the 10 infections occurred 8 weeks or less following implantation.

Future considerations: advances in the surgical management of erectile dysfunction.

As treatment options for erectile dysfunction (ED) continue to expand, and with more attractive alternatives such as effective systemic treatment becoming available, the number of men presenting for treatment of ED is increasing exponentially. Since a subset of these men continue to require surgical therapy, there is a potential for the number of operations for the treatment of ED and related disorders to actually increase. Areas in the surgical treatment of ED where improvements are needed are identified, including: measures to prevent penile prosthesis infections, better penile implants, improved penile augmentation procedures, better surgical procedures for the treatment of Peyronie's disease, improved penile revascularization procedures, and new motor and sensory penile nerve grafting procedures. International Journal of Impotence Research (2000) 12, Suppl 4, S140-S143.