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Biomedical subjects

Gregory A Broderick

Publications and source records attributed to Gregory A Broderick.

14 recordsLinked to original sources

Vardenafil rescue rates of sildenafil nonresponders: objective assessment of 327 patients with erectile dysfunction.

OBJECTIVES: To prospectively investigate whether vardenafil can effectively treat patients for whom sildenafil (100 mg) has failed. The introduction of two new oral phosphodiesterase type 5 inhibitors (tadalafil and vardenafil) raises the question of whether the new agents will permit us to treat sildenafil nonresponders with another oral agent. METHODS: Patients were seen at one institution during a 5-year period. A total of 327 patients complaining of sildenafil-refractory erectile dysfunction underwent intracavernous pharmacologic injection and color duplex Doppler ultrasonography. Subsequently 59 of these men tried vardenafil home dosing. RESULTS: Of the 327 men in whom sildenafil failed, 16% were younger than 50, 21% were 51 to 60, 34% were 61 to 70, and 28% were older than 70 years. The Doppler diagnoses were arterial insufficiency in 154 (47%), mixed vascular insufficiency in 73 (22%), and cavernous venous occlusive disease in 57 (17%). Forty-three men (13%) had normal erectile responses to prostaglandin E1 (10 to 20 microg). Of the 59 men who tried vardenafil, 19% were younger than 50, 17% were 51 to 60, 40% were 61 to 70, and 23% were older than 70 years. The Doppler diagnoses were arterial insufficiency in 28 (42%), mixed vascular insufficiency in 10 (19%), and cavernous venous occlusive disease in 15 (29%). Six men (8%) had normal erectile responses to prostaglandin E1. Only 7 (12%) of the 59 men reported that home vardenafil dosing resulted in successful intercourse. CONCLUSIONS: An appropriate diagnostic evaluation and subsequent treatment algorithm have yet to be established for those for whom phosphodiesterase type 5 inhibitors fail. We found that most sildenafil nonresponders had severe arterial insufficiency and were older, with 62% older than 60 years. Our preliminary experience suggests that only a small percentage (12%) of sildenafil nonresponders can be salvaged with vardenafil.

Adult↗

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↗

Premature ejaculation: on defining and quantifying a common male sexual dysfunction.

INTRODUCTION: Premature ejaculation (PE) and its individual and relationship consequences have been recognized in the literature for centuries. PE is one of the most common male sexual dysfunctions, affecting nearly one in three men worldwide between the ages of 18 and 59 years. Until recently, PE was believed to be a learned behavior predominantly managed with psychosexual therapy; however, the past few decades have seen significant advances in understanding its etiology, diagnosis, and management. There is, as yet, no one universally agreed upon definition of PE. AIM: To review five currently published definitions 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 utilized from the World Health Organization, the American Psychiatric Association, the European Association of Urology, the Second International Consultation on Sexual Dysfunctions, and the American Urological Association. RESULTS: The current published definitions of PE have many similarities; however, none of these provide a specific "time to ejaculation," in part because of the absence of normative data on this subject. While investigators agree that men with PE have a shortened intravaginal ejaculatory latency time (IELT; i.e., time from vaginal penetration to ejaculation), there is now a greater appreciation of PE as a multidimensional dysfunction encompassing several components, including time and subjective parameters such as "control,""satisfaction," and "distress." CONCLUSION: There is a recent paradigm shift away from PE as a unidimensional disorder of IELT toward a multidimensional description of PE as a biologic dysfunction with psychosocial components.

Adult↗

Does indigo carmine prevent early artificial urinary sphincter cuff erosion?

INTRODUCTION: Urethral erosion following artificial urinary sphincter (AUS) placement is hypothesized to be secondary to unrecognized intra-operative urethral injury. Intra-urethral indigo carmine solution (ICS), a blue dye, following urethral mobilization should identify intra-operative urethrotomy and prevent early post-operative cuff erosion. METHODS: Retrospective review was completed of all men undergoing AUS (AMS 800 device) insertion between January 2000 and January 2005 for post prostatectomy stress incontinence at one institution. Operative reports were examined for use of intra-operative injection of ICS as well as documentation of urethral injury. Post-operative course was reviewed for evidence of early cuff erosion. All patients were followed a minimum of 6 months post-operatively. RESULTS: Seventy-eight men underwent AUS placement during the investigative period. Forty-one men received intra-operative ICS injection following urethral mobilization and 37 men did not. ICS identified one intra-operative urethral injury. No urethral injuries were noted in the non-injection group. The ICS group suffered 3 (7.3%) early urethral erosions; the control group had one early urethral erosion (2.7%). CONCLUSION: Intra-operative ICS use is easy, safe, and able to identify urethral injury. However, its use did not preclude the incidence of early cuff erosion. This may postulate the existence of early urethral cuff erosion as a separate entity not dependent on intra-operative urethrotomy.

Aged↗

Systematic transperineal ultrasound-guided template biopsy of the prostate: three-year experience.

OBJECTIVES: To review the technique of transperineal saturation prostate biopsy and to update our results on patients at high risk of prostate cancer. METHODS: A total of 210 men who met the study inclusion criteria underwent systematic transperineal ultrasound-guided template biopsy of the prostate. All patients had previously undergone at least one set of transrectal prostate biopsies and 170 (81%) had undergone two or more. The mean number of prostate cores obtained before the template biopsy was 17.4. A mean of 21.2 cores (range 12 to 41) were obtained at the template biopsy, depending on prostate size. The study inclusion criteria included prostate-specific antigen level of 10 ng/mL or greater, prostate-specific antigen velocity of 0.75 ng/mL per year or greater, or the presence of prostatic intraepithelial neoplasia and/or atypical small cell acinar proliferation on the previous biopsy. RESULTS: Adenocarcinoma was detected in 78 men (37%). Cancer was detected in the transition zone in 60 (77%) of these 78 men, including 36 (46%) in whom cancer was identified uniquely in the transition zone. Gleason sum 6 (range 3 to 9) was the most common biopsy grade. Thirty patients underwent radical prostatectomy, and 27 (90%) had pathologic Stage pT2 disease as the final pathologic stage. Complications from biopsy were limited to postprocedural urinary retention in 11% of patients. CONCLUSIONS: A systematic transperineal template biopsy provides uniform sampling of the entire prostate. This technique appears to enhance the identification of transition zone cancers not detected by previous transrectal prostate biopsy in patients at high risk of prostate adenocarcinoma.

Adenocarcinoma↗

Acute urinary retention after transperineal template-guided prostate biopsy.

PURPOSE: Urinary retention occurs in 5%-36% of patients with prostate cancer after implantation of radioactive seeds for brachytherapy. We used transperineal biopsy as a model to determine the influence of needle trauma on urinary retention. METHODS AND MATERIAL: We retrospectively reviewed medical records of 157 men with high risk of prostate cancer who underwent systematic ultrasound-guided biopsy of the prostate with the transperineal template technique and an 18-gauge automated biopsy device. RESULTS: Eighteen of 157 patients (11.5%; 95% confidence interval, 6.9%-17.5%) had urinary retention within 48 hours after biopsy. Median age was 68.5 years in patients with retention vs. 67.0 years in patients without (p = 0.319); median calculated prostate volume, 76.5 vs. 51.5 mL (p = 0.015); and median number of biopsy cores, 22.0 vs. 20.0 (p = 0.038). Age distribution differed between groups (p = 0.047), with more younger men in the no-retention group. On multivariate analysis, only number of biopsy cores significantly predicted urinary retention (p = 0.003). Four patients required transurethral resection; 1 had an indwelling catheter until radical prostatectomy; and 13 were catheter-free within 1-5 days. CONCLUSIONS: Needle trauma alone may cause urinary retention in men undergoing transperineal procedures. The number of needle incursions and prostate size are predictors of postprocedure urinary retention.

Acute Disease↗

Prediction of genitourinary tract morbidity after brachytherapy for prostate adenocarcinoma.

OBJECTIVE: To investigate whether preoperative genitourinary variables in patients undergoing brachytherapy for localized prostate adenocarcinoma could predict postoperative genitourinary tract morbidity. PATIENTS AND METHODS: We retrospectively reviewed medical records of 105 men who received either iodine 125 or palladium 103 radioactive seed implants with or without external beam radiotherapy or hormone blockade from January 1, 1998, through December 31, 2000, at the Mayo Clinic in Jacksonville, Fla. Patients with one or more of the following were classified as having a high risk of postoperative genitourinary tract morbidity: American Urological Association symptom scores greater than 15, maximum urinary flow rate less than 10 mL/s, postvoid residual urinary volume greater than 100 mL, or prostate volume greater than 40 cm3. Of the 105 men, 59 (56%) were classified as high risk and 46 (44%) as low risk. Mean follow-up after brachytherapy was 23.6 months. Modified Radiation Therapy Oncology Group scores were used to assess postoperative genitourinary tract morbidity. The term significant genitourinary tract morbidity was applied to patients with a Radiation Therapy Oncology Group grade of 3 or 4 after at least 6 months of follow-up. RESULTS: Significant morbidity occurred in 37% of high-risk vs 15% of low-risk patients (P = .006). In high-risk patients, transurethral resection or incision of the prostate was required in 5 patients, urethral dilation in 4, direct-vision internal urethrotomy in 1, and placement of a suprapubic catheter in 1. In low-risk patients, transurethral incision of the prostate was required in only 1 patient. Urinary flow rate was a significant individual predictor of postoperative morbidity (P = .03). CONCLUSIONS: A combination of urinary flow rate, prostate volume, postvoid residual urinary volume, and American Urological Association symptom score can help identify patients with underlying voiding dysfunction. Urinary flow rate was a statistically significant predictor of genitourinary tract morbidity after brachytherapy for localized prostate adenocarcinoma. Patients and physicians should consider these factors before a patient decides to undergo brachytherapy.

Adenocarcinoma↗

Effect of the Bowman-Birk inhibitor (a soy protein) on in vitro bladder neck/urethral and penile corporal smooth muscle activity.

AIMS: The Bowman-Birk inhibitor (BBI), is a serine protease inhibitor derived from soy beans, which is presently being evaluated in clinical trials for its ability to serve as a cancer preventive or anti-inflammatory agent. The form of BBI currently in clinical trials is known as Bowman-Birk inhibitor concentrate (BBIC). There have been anecdotal reports from patients of improved voiding and sexual functions in the ongoing BBIC trials. The objective of this study was to quantify the effect of BBI and BBIC on urethral and corporal smooth muscle activity. METHODS: In vitro muscle strip studies of New Zealand White rabbit urethra/bladder neck and penile corpora in the presence or absence of BBI or BBIC incubation (5 mg/mL) were performed. RESULTS: In dose-response curves to alpha stimulation, BBI mediated a shift to the right (decreased receptor sensitivity in bladder/urethra as well as corpora with no change in the maximal response). Bladder base/ urethra contraction by field stimulation was significantly inhibited by BBI at higher frequencies (1-32 Hz) (12.2 + 0.8 g vs. 6.3 + 0.75 g, P < 0.05). BBI inhibited field stimulated relaxation of corporal muscle at lower frequencies. Muscarinic contraction of the bladder neck/urethra in alpha prestimulated tissue was significantly inhibited by BBI (5.3 + 0.2 g vs. 2.7 + 0.1 g, P < 0.05). BBI has an inhibitory effect on alpha adrenergic dose-response curves in bladder neck/urethral and corpora smooth muscle. BBI also significantly inhibited neurohumoral cholinergic release and in vitro muscarinic contraction of the urethra. The effects on corpora relaxation were less pronounced. CONCLUSIONS: The data suggest that the phytochemical BBI may promote physiologic effects of urethral relaxation and improved voiding by unique mechanisms and deserves further study as a pharmacologic agent for lower urinary tract symptoms.

Adrenergic alpha-Agonists↗

Oral pharmacotherapy and the contemporary evaluation and management of erectile dysfunction.

The introduction of phosphodiesterase-5 (PDE-5) inhibitor therapy for the treatment of erectile dysfunction (ED) marked the beginning of a much greater awareness of this condition and its effects on quality of life. Resulting research has provided much data on the etiologies of ED, the risk factors involved, and the connection between ED and atherosclerotic disease. With the ED patient more frequently seeking treatment from his primary care physician, it behooves both urologists and non-urologist physicians to be familiar with the properties of the PDE-5 inhibitors, as well as those of other oral, sublingual, intracavernosal, and intraurethral ED drugs. This article reviews the diagnostic approach to the ED patient and the mechanisms of PDE-5 inhibition and discusses data from trials of PDE-5 inhibitors and the erectogenic dopaminergic agonist apomorphine.

Journal Article↗

Orthotopic ureterocele masquerading as a bladder tumor in a woman with pelvic pain.

Single system orthotopic ureteroceles often present in adulthood are associated with characteristic radiographic findings. We present the case of a 54 year old woman with 8 months of urgency/frequency and pelvic pain that has the cystoscopic appearance of a bladder tumor. Cystoscopic images, radiographs and intraoperative photos demonstrate the work-up, evaluation, and treatment of this unique single system orthotopic ureterocele containing a calculus. This patient demonstrates the need for cystoscopy accompanied by upper tract imaging in patients with new onset pelvic pain, urgency/frequency, and frequent urinary tract infections.

Cystoscopy↗