Smoking, obesity, and sedentary lifestyle linked to erectile dysfunction.
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Comment↗
Biomedical subjects
Craig F Donatucci
Publications and source records attributed to Craig F Donatucci.
Biofilm formation on clinically noninfected penile prostheses.
PURPOSE: Biofilms are matrix enclosed bacterial populations that adhere to each other and/or to surfaces of implanted medical devices. Biofilm formation has consistently been demonstrated in association with infected penile prosthetic material. Clinically noninfected patients undergoing revision for mechanical malfunction have a surprisingly high rate of positive intraoperative cultures. After revision replacement prostheses have a higher rate of postoperative infection than first time implants. We characterized biofilm formation on penile prostheses in clinically noninfected patients undergoing revision surgery. MATERIALS AND METHODS: Ten patients undergoing revision or removal of inflatable penile prosthetic devices due to mechanical malfunction were included. Specimens from the corporeal cylinders, scrotal pump and reservoir were analyzed. Bacterial biofilm coverage was detected and characterized using confocal scanning laser microscopy. RESULTS: Bacterial biofilm formation associated with multiple microorganisms was demonstrated on 8 of 10 prostheses. Biofilms consisted of gram-positive rods, cocci and fungal elements. CONCLUSIONS: The degree of biofilm formation on these prosthetic devices suggests that most patients have bacterial coverage on the implant. Host mechanisms to control infection may lead to a homeostatic balance that enables biofilms to exist on the surface of the prosthesis without generating clinical infection. A critical threshold of biofilm extent may exist beyond which clinical infection may occur. These results justify further evaluation of biofilms and penile prosthesis infections. Furthermore, the findings help to explain why strategies such as mini salvage procedures to eliminate subclinical biofilms may decrease the postoperative infection risk in patients undergoing repair or replacement of penile prostheses.
Biofilms↗
Recovery of sexual function after prostate cancer treatment.
PURPOSE OF REVIEW: The estimated disease-free survival rates are approximately equivalent across standard treatments for localized prostate cancer. We aim to review the efforts being made to reduce posttreatment erectile dysfunction, a major morbidity of these therapies. RECENT FINDINGS: Potency as an important factor in a patient's decision about choosing a form of therapy has been demonstrated in the literature. For nerve-sparing surgery, though some proponents of laparoscopic radical prostatectomy believe it may confer an advantage over the open surgical techniques, the published data is scarce and has yet to demonstrate a true difference. Enthusiasm has declined for sural nerve grafting because of the associated complexity of the procedure and inconsistent results. Concurrent implantation of a penile prosthesis is an option for certain patients who already have some baseline erectile dysfunction or are not candidates for nerve-sparing surgery. Agents such as phosphodiesterase inhibitors, immunophilin ligands, and recombinant human erythropoietin have demonstrated potential benefits in early reports of both in-vitro and ongoing clinical trials. SUMMARY: Currently, no standard treatment or prophylaxis exists for posttreatment erectile dysfunction. Neuro-protective and regenerative therapies, including the immunophilin ligands, hold promise to reduce the morbidity of localized prostate cancer therapy.
Erectile Dysfunction↗
Use of negative-pressure dressings and split-thickness skin grafts following penile shaft reduction and reduction scrotoplasty in the management of penoscrotal elephantiasis.
From 1988 to 2005, 8 men who presented with penoscrotal elephantiasis underwent penile shaft degloving and reduction scrotoplasty, followed by transplantation of a split-thickness skin graft (STSG) to the penile shaft. The etiology of elephantiasis in these patients included self-injection of viscous fluid and postsurgical obstructive lymphedema. In the 6 most recent cases, negative-pressure dressings were applied over the STSG to promote graft take, and STSG take rate was 100%. The results of our series corroborate those of a previous report, which showed circumferential negative-pressure dressings to be safe and efficacious in bolstering STSGs to the penile shaft. Furthermore, these results suggest that the use of negative-pressure dressings may improve graft take in this patient population.
Bandages↗
Intracavernosal basic fibroblast growth factor improves vasoreactivity in the hypercholesterolemic rabbit.
PURPOSE: We determined the effects of intracavernosal injection (ICI) of recombinant basic fibroblast growth factor (rbFGF) on corporal tissue in hypercholesterolemic rabbits. METHODS: Twenty New Zealand White rabbits were fed a 1% cholesterol diet for 6 weeks and were randomly divided into four groups. Group 1 (N = 5) received an ICI of phosphate buffered saline solution (PBS) once and again 3 weeks later. Group 2 (N = 4) received an ICI of 2.5 microg rbFGF once and PBS 3 weeks later. Group 3 (N = 6) received an ICI of 2.5 microg rbFGF once and again 3 weeks later. Group 4 (N = 5) received an ICI of 2.5 microg rbFGF once. All animals were maintained on the high cholesterol diet until sacrifice, 3 weeks after last injection. Strips of corporal tissue were submaximally contracted with norepinephrine, and dose-response curves were generated to evaluate endothelial-dependent (acetylcholine, ACH) and endothelial-independent (sodium nitroprusside, SNP) vasoreactivity. Protein levels of bFGF and vascular endothelial growth factor (VEGF) were assessed by enzyme-linked immunosorbent assay. Neuronal nitric oxide synthase (nNOS) protein and mRNA were detected by Western blot and semi-quantitative polymerase chain reaction, respectively. RESULTS: Vasoreactivity was improved by bFGF treatment as shown by higher ED50[-log(M)] of ACH and SNP in Groups 2, 3, and 4. The expression of bFGF protein, VEGF protein, nNOS protein, and mRNA were all increased after bFGF treatment. CONCLUSIONS: ICI of bFGF improved vasoreactivity in hypercholesterolemic rabbit corporal tissue, offering a new direction to explore for the treatment of erectile dysfunction.
Animals↗
Efficacy of tadalafil in men with erectile dysfunction naïve to phosphodiesterase 5 inhibitor therapy compared with prior responders to sildenafil citrate.
INTRODUCTION: Tadalafil, an inhibitor of phosphodiesterase 5 (PDE5), is indicated for treatment of erectile dysfunction. Most tadalafil clinical trials excluded patients with unsuccessful prior treatment with sildenafil citrate (sildenafil). AIM: This retrospective analysis of pooled data from 14 tadalafil clinical trials examines the effect of this exclusion by comparing efficacy results in 1,349 patients without prior sildenafil use (naïve, presumably a mixture of potential responders and nonresponders) with efficacy results in 1,440 patients previously responsive to sildenafil (prior responders). MAIN OUTCOME MEASURES: Efficacy measures included the International Index of Erectile Function (IIEF) erectile function (EF) domain, overall satisfaction (OS), and intercourse satisfaction (IS) domain scores; Sexual Encounter Profile (SEP) diary questions 2 through 5 (SEP2 [successful penetration], SEP3 [successful intercourse], SEP4 (satisfaction with hardness of erection), and SEP5 [overall satisfaction with the sexual experience]); and a Global Assessment Question (GAQ1) (13/14 trials) about erection improvement. Efficacy was compared using analysis of covariance (IIEF and SEP) and logistic regression (GAQ1) models. METHODS: After a 4-week, treatment-free, run-in period, patients in 14 double-blind, placebo-controlled, parallel-group trials were treated with tadalafil 10 mg, tadalafil 20 mg, or placebo for 12 weeks (dosed as needed before sexual activity, no more than once daily). RESULTS: Tadalafil improved erectile function compared with placebo (P < 0.001) in naïve patients and sildenafil prior responders for all efficacy measures. For most efficacy outcomes, responses in the naïve group (probable mix of responders and nonresponders) were not statistically different from responses in the prior-responder group (P >or= 0.10). CONCLUSIONS: The similar responses of these two patient groups observed in this post hoc analysis suggest, but do not confirm, that exclusion of sildenafil nonresponders in previously reported tadalafil clinical trials may not have substantially affected efficacy outcomes. Tadalafil improved erectile function in patients naïve to PDE5 inhibitor therapy and in patients who previously responded to sildenafil therapy.
3',5'-Cyclic-GMP Phosphodiesterases↗
Etiology of ejaculation and pathophysiology of premature ejaculation.
INTRODUCTION: Ejaculation is comprised of three stages of the male sexual response cycle, namely emission, ejection, and orgasm; however, in comparison with erection, which is a well-understood component of male sexual response, the pathophysiology of ejaculation has yet to be fully delineated. Premature ejaculation (PE), the most common sexual disorder in men, while believed to have a multifactorial etiology, is even less well understood. AIM: This article reviews the physiology of ejaculation, and the multifactorial pathophysiology of PE. METHODS: The Sexual Medicine Society of North America hosted a State of the Art Conference on Premature Ejaculation on June 24-26, 2005 in collaboration with the University of South Florida. The purpose was to have an open exchange of contemporary research and clinical information on PE. There were 16 invited presenters and discussants; the group focused on several educational objectives. MAIN OUTCOME MEASURE: Data were obtained by extensive examination of published peer-reviewed literature. RESULTS: Evidence supports that biologic mechanisms associated with neurotransmitters such as norepinephrine, serotonin, oxytocin, Gamma-amino-butyric acid, and nitric oxide (NO) as well as the hormone estrogen play central roles in ejaculation, and subsequently may mediate PE. There is also emerging evidence to show that hyperthyroidism may be a causal factor in PE. Recent data also suggest that psychogenic factors include high level of any experience by some men with PE. CONCLUSIONS: The pathophysiology of both lifelong and acquired PE appears to be both neurobiogenic and psychogenic. While psychogenic factors appear to be contributory to PE, pharmacologic intervention of PE can modify intravaginal ejaculatory latency time (IELT), which suggests that IELT is a biological variable, and is likely biologically dependent upon neurotransmitters and hormones.
Adult↗
Revision washout decreases penile prosthesis infection in revision surgery: a multicenter study.
PURPOSE: Reoperation of penile implants carries a higher risk of infection (7% to 18%). Positive cultures and visible bacterial biofilm have been shown to be present on clinically uninfected inflatable penile prostheses (IPPs) at revision. A salvage irrigation protocol has proved to rescue patients with a clinically infected IPP. During revision surgery for noninfectious reasons we investigated washing out the implant space at revision surgery and using an antibiotic coated replacement prosthesis to determine if it would decrease subsequent infection rates. MATERIALS AND METHODS: At 3 institutions 183 patients with a penile prosthesis underwent revision surgery for noninfectious reasons between June 2001 and October 2003. Of these patients 140 had the entire implant removed and then underwent antiseptic solution lavage of the implant spaces (revision washout), followed by replacement with a 3 piece IPP. This revision washout is a modification of the original Mulcahy salvage procedure. In the remaining 43 patients the implant was removed but they did not undergo antiseptic irrigation before replacement with an antibiotic coated IPP. Patients were followed for 6 to 33 months, while observing for failure. RESULTS: Four of the 140 patients (2.86%) who underwent removal of the entire implant with irrigation of the implant spaces with antiseptic solutions and replacement with an IPP have had infection. In the remaining group 5 of the 43 patients (11.6%) who did not undergo antiseptic irrigation had infection. The difference was statistically significant at the 5% level (Fisher's exact test p = 0.034). CONCLUSIONS: Early results of combining complete implant removal and modified salvage protocol indicate a markedly decreased incidence of infection in patients with a penile prosthesis undergoing revision for noninfectious reasons.
Adult↗
Decreases in corporeal vascular endothelial growth factor expression precede vasoreactivity changes in cholesterol fed rabbits.
PURPOSE: We determined temporal changes in vasoreactivity and angiogenic growth factor levels in corporeal tissue at varying time points after the induction of hypercholesterolemia in rabbits. MATERIALS AND METHODS: A total of 42 New Zealand White rabbits were fed a 1% cholesterol (8 per group) or normal (6 per group) diet for 2, 4.5 or 7.5 weeks. Vascular endothelial growth factor (VEGF) mRNA expression in corpus cavernosum was assessed by real-time polymerase chain reaction analyses for the 3 isoforms VEGF121, VEGF165 and VEGF189. Isometric tension studies were performed and dose response curves were generated to evaluate endothelial dependent and endothelial independent vasoreactivity. RESULTS: Real-time polymerase chain reaction analysis showed 2.2 to 2.5 and 1.5 to 2.7-fold decreases in VEGF121 and VEGF165, respectively, in the corporeal tissues of the high cholesterol group vs the normal diet group at the 2 week time point. At 2 weeks VEGF189 was unchanged but it was decreased 1.5 to 2-fold at 4.5 weeks. Acetylcholine isometric tension studies revealed no difference in mean ED50 (-log [M]) +/- SD until 7.5 weeks of high cholesterol diet (5.10 +/- 0.64 vs 3.95 +/- 1.35, p = 0.0269). The response to sodium nitroprusside was not statistically different at any time point. Endothelial cell and smooth muscle content were decreased for the high cholesterol vs normal diet at 4.5 weeks (endothelial only) and 7.5 weeks (each cell). CONCLUSIONS: Alterations in corporeal tissue levels of VEGF occur before abnormalities in vasoreactivity. The results suggest that VEGF has a role in normal vasoreactivity in corporeal tissue and, thereby, in normal erectile function.
Acetylcholine↗
The prepuce as a donor site for reconstruction of an extravasation injury to the foot in a newborn.
Extravasation injury is a common event in pediatric intensive-care units. This is the first report of successful utilization of the prepuce as a skin graft to reconstruct a full thickness skin necrosis due to a phenobarbital extravasation to the forefoot of a newborn.
Anticonvulsants↗
Cholesterol feeding reduces vascular endothelial growth factor signaling in rabbit corporal tissues.
PURPOSE: Hypercholesterolemia is a major risk factor for erectile dysfunction (ED), but the mechanisms are not completely understood. Vascular endothelial growth factor (VEGF) is reduced in rabbit corporal tissue with cholesterol feeding. VEGF signaling leads to the phosphorylation of Akt and endothelial nitric oxide synthase (p-Akt and p-eNOS). MATERIAL AND METHODS: New Zealand White rabbits (n = 50) were fed a 1% cholesterol (n = 8, 8, 8, 4) or normal (n = 6, 6, 6, 4) diet for 2, 4.5, 7.5, and 12 weeks. Akt, p-Akt, and p-Akt/Akt were measured by enzyme-linked immunosorbent assay. Levels of eNOS, p-eNOS, and neuronal and inducible nitric oxide synthase (nNOS and iNOS) mRNA and protein were assessed by polymerase chain reaction and Western analysis. RESULTS: Cholesterol feeding was associated with a significant decrease in p-Akt/Akt 2.16-fold (P < 0.05), 3.28-fold (P < 0.02), and 3.42-fold (P < 0.02) at 4.5, 7.5, and 12 weeks, respectively. The reduction in p-Akt/Akt with the cholesterol diet at 2 weeks was not significantly different, but the correlation between the duration of cholesterol feeding and the reduction in p-Akt/Akt was high (r( 2) = 0.858). eNOS protein or mRNA did not change with cholesterol feeding, but p-eNOS was significantly decreased at 4.5 weeks and all subsequent time points. nNOS mRNA and protein levels were decreased at 4.5 weeks and all subsequent time points, while iNOS was not different between groups. CONCLUSIONS: Hypercholesterolemia results in decreased VEGF signaling and decreased levels of the active form of eNOS in corporal tissue. Levels of nNOS were reduced by a different mechanism. VEGF signaling may provide a target to modulate ED.
Animals↗
Penile prosthesis cultures during revision surgery: a multicenter study.
PURPOSE: Initial implantation of inflatable penile prosthesis has a 3% risk of infection. Reoperation of penile implants has a higher rate of infection, estimated between 10% and 18%. To explain the higher risk in revision surgery in this prospective study we cultured clinically uninfected prostheses requiring revision. Prosthesis pain was also investigated as a predictor of positive culture. MATERIALS AND METHODS: At 3 institutions cultures were prospectively obtained from 77 clinically uninfected penile prostheses at revision surgery. Immediately upon surgical exposure of the pump cultures were obtained. If a bacterial biofilm was noted on any component it was additionally cultured. All culture isolates positive for a staphylococcus species were tested for sensitivity to rifampin and tetracycline (minocycline). An implant is now available that is coated with these antibiotics. Patient history of chronic prosthesis pain was ascertained. RESULTS: Culture positive bacteria were found in 54 of 77 (70%) patients with clinically uninfected penile prostheses. In some patients more than 1 organism grew and, occasionally, the pump culture was negative but the biofilm was positive. Of 54 patients 49 had positive (90%) culture for staphylococcus genus with 10 different species. All staphylococcal species were sensitive to rifampin and/or tetracycline. We did not find a significant association between prosthesis related pain and culture laboratory results. CONCLUSIONS: The majority of clinically uninfected penile prostheses have organisms growing in the implant spaces at reoperation. Most of these organisms are staphylococcal species that are sensitive to rifampin/minocycline.
Aged↗
Systemic basic fibroblast growth factor induces favorable histological changes in the corpus cavernosum of hypercholesterolemic rabbits.
PURPOSE: Hypercholesterolemia causes erectile dysfunction that is associated with abnormalities in vascular smooth muscle and endothelial cells. We determined the effects of basic fibroblast growth factor (bFGF) on corporeal tissue in hypercholesterolemic rabbits. MATERIALS AND METHODS: A total of 16 New Zealand White rabbits were fed a 1% cholesterol diet for 6 weeks and were randomly divided into 3 groups. Group 1 (5 rabbits) received 2.5 microg recombinant bFGF intravenously once and again 3 weeks later. Group 2 (6 rabbits) received 2.5 microg bFGF intravenously once and placebo 3 weeks later. Group 3 (5 rabbits) received placebo intravenously each time. Rabbits were continuously fed a 1% cholesterol diet and sacrificed 3 weeks after the last treatment. Smooth muscle, endothelial cell and collagen content were assessed by immunohistochemistry and histochemical staining of corporeal tissue. Vascular endothelial growth factor (VEGF) protein and mRNA expression were assessed by enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction. RESULTS: Corporeal smooth muscle content was greater in groups 1 and 2 (35.24% +/- 4.25% and 24.79% +/- 3.39%, p <0.01) vs group 3 (19.68% +/- 2.94%, vs groups 1 and 2 p <0.001 and <0.05, respectively). Endothelial cell and collagen content were similar among the groups. VEGF protein was increased in group 1 vs group 2 (97.90 +/- 26.00 vs 57.03 +/- 14.99 pg/ml, p <0.01) and vs group 3 (39.93 +/- 15.08, p <0.01). There was no statistical difference between groups 2 and 3. VEGF mRNA expression was similar among the groups. CONCLUSIONS: Systemic bFGF increases smooth muscle content and VEGF protein in hypercholesterolemic rabbit corporeal tissue.
Animals↗
Antiandrogens in the treatment of priapism.
Recurrent priapism in young men is a potentially devastating condition that may result in irreversible penile fibrosis. Hormonal manipulation using estrogens and gonadotropin-releasing hormone analogues has been successful in treating episodes of priapism refractory to other treatment forms, but it is associated with significant adverse effects, in particular the loss of libido and erectile function. We present 2 patients with sickle-cell disease and 1 patient with a spinal cord injury who had recurrent and refractory priapism. All 3 patients were successfully treated with low-dose antiandrogens without major side effects. Our observations suggest a role for antiandrogens in the treatment of men with refractory priapism that should be evaluated in the setting of a controlled study.
Adult↗
Erectile dysfunction in early, middle, and late adulthood: symptom patterns and psychosocial correlates.
The prevalence of erectile dysfunction (ED) increases with age. However, it may emerge at any time during the adult years, and may bear a close relationship to ongoing psychosocial issues affecting the patient and his partner. The present study examined ED symptomatology and its associated psychosocial context in 560 men aged 19-87 attending a urology clinic for erectile difficulties. We divided participants into three age groups: early adulthood (age 19-39); middle adulthood (40-59); and late adulthood (60+). They completed a self-report assessment battery evaluating medical, psychological, and lifestyle factors empirically or theoretically related to ED. Results showed that although younger men reported more positive overall ratings of their sex life and better overall erectile functioning relative to older men, they also reported comparatively less relationship satisfaction, greater depressive symptomatology, more negative reactions from partners, and less job satisfaction. Results suggest that older men experience less difficulty than younger men adjusting to life with ED.
Adult↗