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Biomedical subjects

D M Barrett

Publications and source records attributed to D M Barrett.

At least 19 recordsLinked to original sources

Rationale for combination therapy of intraurethral prostaglandin E(1) and sildenafil in the salvage of erectile dysfunction patients desiring noninvasive therapy.

Corpus cavernosum smooth muscle relaxation and hence penile erection are regulated in part by increases in smooth muscle synthesis of the second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). The object of this study was to determine 30-month follow-up results in motivated patients desiring noninvasive medical therapy using sildenafil citrate (Viagra) in combination with intraurethral prostaglandin E(1) (PGE(1)) (Medicated Urethral System for Erection [MUSE]). Twenty-eight patients (mean +/- s.d. age, 59 +/-7.3 y; 17 who had undergone radical prostatectomy and 11 who had a diagnosis of organic erectile dysfunction) were included in this study. Detailed history taking and physical examinations were performed and vascular risk factors noted. In these patients, treatment with either 100 mg of sildenafil citrate and/or 1000 microg of MUSE had failed. None of these patients desired intracavernosal injection. Duplex Doppler ultrasonography after redosing was carried out on all patients. Dynamic infusion corpus cavernosography/cavernosometry was obtained in 17 of 28 patients, and combination therapy was initiated using 100 mg of sildenafil citrate orally 60 min before intercourse and 500 microg of MUSE intraurethrally immediately before intercourse. Independently, either 100 mg of sildenafil citrate or 1000 microg of MUSE was not efficacious in inducing an erection sufficient for vaginal penetration in any of the 28 patients. After initiating a combination therapy, at 30 months, all 28 patients were reporting erections sufficient for vaginal penetration, with 3.6 intercourse episodes per month. None of the patients crossed over to intracavernosal therapy or penile prosthesis. During therapy, eight of 28 patients reduced the dose of sildenafil citrate to 50 mg. Combination therapy with MUSE and sildenafil may be more efficacious in the salvage of patients who desire noninvasive therapy but in whom single-treatment modalities fail. Although both cAMP- and cGMP-mediated vasodilation can lead to penile erection, combining therapies that incorporate both pathways may succeed when single therapies fail.

Aged↗

Does nocturnal deactivation of the artificial urinary sphincter lessen the risk of urethral atrophy?

OBJECTIVES: To compare nocturnal deactivation with nocturnal activation of the artificial urinary sphincter (AUS) to determine whether nocturnal deactivation reduces the risk of urethral atrophy and subsequent recurrent incontinence. To the best of our knowledge, no review comparing these two approaches has been performed. METHODS: At the Mayo Clinic, all patients are instructed to deactivate their AUS at night; at Baylor, all patients keep their AUS activated all the time. At each institution, a group of consecutive men with comparable severe urinary incontinence after radical retropubic prostatectomy were selected; 61 and 46 patients from the Mayo Clinic and Baylor, respectively, were available for review. All Mayo Clinic patients strictly adhered to nocturnal deactivation of their AUS and all 46 patients from Baylor kept their AUS activated at all times, except during voiding. Each patient was reviewed for the long-term risk of subsequent reoperation, especially regarding recurrent incontinence due to urethral atrophy. RESULTS: Seventeen (27.8%) of the 61 patients from Mayo (mean follow-up 40 months) required a repeated operation. Of the 17 AUS failures, 6 (35%) were due to urethral atrophy. Of the 46 patients from Baylor (mean follow-up 28 months), 16 (34.7%) required a repeated operation. Of the 16 AUS failures, 10 (62%) were due to urethral atrophy. Overall, the patients who nocturnally deactivated their AUS had a 10% risk of atrophy-related incontinence compared with a 21% risk in the nocturnally activated group. CONCLUSIONS: Although not statistically significant, nocturnal deactivation appears to decrease the risk of urethral atrophy and recurrent incontinence (10% versus 21%). Nocturnal deactivation should be considered in men who are dry at night and have sufficient motivation to lessen the risk of urethral atrophy secondary to cuff compression.

Atrophy↗

Colorimetric method for the determination of lipoxygenase activity.

A colorimetic assay for lipoxygenase activity has been developed. The assay is based on the detection of the lipoxygenase reaction product, linoleic acid hydroperoxide, by the oxidative coupling of 3-methyl-2-benzothiazolinone (MBTH) with 3-(dimethylamino)benzoic acid (DMAB) in a hemoglobin-catalyzed reaction. This test reaction is rapid and sensitive, and it offers advantages over other methods for detecting lipoxygenase activity. The assay is capable of detecting activity in a number of crude vegetable homogenates and should be particularly useful where a rapid visual determination of lipoxygenase activity is desired.

Aminobenzoates↗

Low-density lipoprotein antioxidant activity of phenolic compounds and polyphenol oxidase activity in selected clingstone peach cultivars.

The antioxidant potential of eight clingstone peach cultivars was investigated by determining phenolic compounds and inhibition of low-density lipoprotein (LDL) oxidation. Cultivars low in polyphenol oxidase (PPO) were also selected to minimize enzymatic browning. Inhibition of LDL oxidation varied from 17.0 to 37.1% in peach flesh extract, from 15.2 to 49.8% in whole peach extract, and from 18.2 to 48.1% in peel extract. Total phenols were 432.8-768.1 mg/kg in flesh extract, 483.3-803.0 mg/kg in whole extract, and 910.9-1922.9 mg/kg in peel extract. The correlation coefficient between relative LDL antioxidant activity and concentration of total phenols was 0.76. Peel PPO activity was higher than flesh activity in most cultivars. The lowest PPO and specific activities were found in the Walgant cultivar, followed by Kakamas and 18-8-23. These three cultivars combine the desirable characteristics of strong antioxidant activity, low PPO activity, and lower susceptibility to browning reactions.

Antioxidants↗

Success of de novo reimplantation of the artificial genitourinary sphincter.

PURPOSE: We evaluate our experience with de novo reimplantation of the artificial genitourinary sphincter with a particular emphasis on mechanical and nonmechanical failure rates. De novo reimplantation is defined as implantation of an artificial sphincter following removal of a previously placed sphincter for erosion and/or infection and a waiting period of several months. MATERIALS AND METHODS: A retrospective analysis of more than 400 patients with an artificial sphincter revealed 23 who underwent de novo reimplantation between January 1983 and October 1998. All patients were men with a mean age of 66.5 years (range 16 to 88) and all had a urethral cuff. Reasons for cuff removal were erosion in 12 cases (52.2%), infection in 10 (43.5%) and intraoperative urethral injury in 1 (4.3%). Mean waiting period was 6.8 months (range 1.5 to 32) between explantation and de novo reimplantation. Mean followup was 32.6 months (range 1 to 108). RESULTS: Of the 23 patients 20 (87%) had no mechanical or nonmechanical failures and 3 (13%) had nonmechanical failures, including 2 patients (8.7%) whose cuff eroded into the urethra and 1 (4.3%) who had recurrent urinary incontinence which was successfully treated with implantation of a tandem cuff. There were no mechanical failures or infections in this group of patients. CONCLUSIONS: Our study suggests that de novo artificial sphincter reimplantation is an excellent treatment option. It is safe and associated with complication rates that are comparable to those of primary implantation.

Adolescent↗

High power potassium-titanyl-phosphate laser vaporization prostatectomy.

PURPOSE: We prospectively studied a cumulative cohort of men with obstructive benign prostatic hyperplasia who underwent potassium-titanyl-phosphate (KTP) laser vaporization prostatectomy to determine the safety and efficacy of this procedure. MATERIALS AND METHODS: A total of 55 men with symptomatic bladder outlet obstruction due to benign prostatic hyperplasia were treated with a 60 W. KTP laser produced by a prototype Laserscopedagger generator and delivered through a side-deflecting fiber with a 22Fr continuous flow cystoscope. Sterile water was used for irrigation. The prostatic lobes were vaporized to within capsular fibers. Mean lasing time plus or minus standard deviation was 44 +/- 19 minutes. RESULTS: Mean prostate volume plus or minus standard deviation was 43 +/- 14 ml. No patient had any significant blood loss or fluid absorption, or required blood transfusion. Foley catheters did not require irrigation and were removed less than 24 hours postoperatively. All patients remained satisfied with voiding outcome, which changed significantly (p <0.0001). Mean improvement in American Urological Association symptom score at 3, 6, 12 and 24-month intervals was 75%, 79%, 82% and 82%, respectively. Mean increase in peak flow rate at the same intervals was 250%, 242%, 255% and 278%, respectively. Complications included mild transient dysuria in 7%, bladder neck contracture in 2% and delayed hematuria in 4% of patients. None of the patients required re-catheterization or reoperation, or had incontinence or newly developed impotence. Of the sexually active patients 15% and 9% had retrograde ejaculation at 1 and 2 years, respectively. CONCLUSIONS: Our observation in a 2-year period indicates that 60 W. KTP laser vaporization prostatectomy is safe and effective for quickly relieving bladder outlet obstruction with minimal postoperative complications, a high rate of patient satisfaction and, to date, a generally good outcome.

Aged↗

Artificial urinary sphincter implantation using a bulbous urethral cuff: perioperative care.

Urinary incontinence is a common problem encountered by clinicians and nursing staff. An artificial genitourinary sphincter (AGUS) placed around the bulbar urethra or bladder neck has become one of the gold standards for treating urinary incontinence due to sphincteric incompetence. It is imperative not only for physicians but also the nursing staff to have a working knowledge of the mechanics, risks, benefits, and durability of the AGUS to provide care for those patients encountered with an AGUS.

Humans↗

Repeated pressure-flow studies in the evaluation of bladder outlet obstruction due to benign prostatic enlargement. Finasteride Urodynamics Study Group.

Test-retest reliability of repeated voids in pressure-flow studies and the influence on maximum flow rate (Q(max)pQ), detrusor pressure at maximum flow rate (p(det)Qmax), voided volume, and residual urine were studied. Also the agreement in interpretation of pressure-flow tracings between investigators and a single blinded central reader acting as a quality control center (QCC) were assessed. In addition, correlations between p(det)Qmax and patient age, International Prostate Symptom Score (IPSS), free maximum flow rate (Qmax), and prostate volume were calculated. Using suprapubic pressure recording, 216 men with lower urinary tract symptoms (LUTS) due to benign prostatic enlargement (BPE) were investigated in 11 centers. In each pressure-flow study, three sequential voids were performed, and quality controlled recordings were analyzed for Q(max)pQ and p(det)Qmax by the QCC. Trans rectal ultrasound was used to measure the prostate volume. Mean Q(max)pQ did not change, but p(det)Qmax decreased significantly in the second and third sequential voids. Using the Abrams-Griffiths nomogram definition of obstruction, 125 patients (67%) were classified as obstructed from the first void, but only 111 patients (59%) from the third void. The agreement between the investigator assessment and that of a single blinded reader was good. There was no significant correlation between p(det)Qmax and patient age, IPSS, and Qmax, whereas a modest correlation was found between p(det)Qmax and prostate volume. In summary, there was no significant change in Q(max)pQ, but p(det)Qmax decreased for the three consecutive voids, which can be explained by a decrease in outlet resistance. The agreement between the investigator and QCC interpretations shows the value of a standardized technique, supporting the feasibility of multicenter urodynamic studies. There is a modest, but statistically significant, correlation between detrusor pressure and prostate size, supporting the hypothesis that prostate size is a contributing factor in symptomatic BPH.

Adult↗

A new temporary catheter (ContiCath) for the treatment of temporary, reversible, postoperative urinary retention.

OBJECTIVES: To describe the initial experience of a newly designed temporary urethral catheter, ContiCath, as an aid in the management of postoperative or temporary outflow obstruction. In patients with normal detrusor and sphincter function, this catheter allows volitional voiding while maintaining an open prostatic urethra. METHODS: In a pilot study, 64 nonconsecutive patients with postoperative or temporary urinary retention, at eight clinical trial sites, were enrolled for the placement of this temporary catheter. Three patients did not have the catheter placed because of placement failure because of either a large median lobe or a urethral stricture. The remaining 61 patients were divided into three groups: those with non-neuropathic causes of retention and retention for 1 week or less (37 patients), those with non-neuropathic causes of retention and retention for longer than 1 week (19 patients), and those with neuropathic causes of retention and retention for longer than 1 week (5 patients). The ContiCath is placed in the office setting, in the same fashion as a Foley catheter. A blue prolene tether extends from the bulbar urethra to the meatus to assist in the removal of the device. Patients were then reassessed at 3 hours, and at 7, 14, 21, and 28 days, at which point the device was removed. RESULTS: In patients with a neuropathic cause for their retention (5 patients) and those with non-neuropathic causes of retention and retention for longer than 1 week (19 patients), only 3 patients were able to void after the catheter was placed. Of the 37 patients with a non-neuropathic cause and retention 1 week or less, controlled voiding was seen in 33 patients (89%). Controlled voiding was defined as the patient's volitional ability to initiate and stop his urinary stream. There were no complications with catheter placement; however, 8 patients (24.2%) had minor adverse experiences of frequency/urgency (n = 3), incontinence (n = 3), migration of the catheter (n = 1), and pain (n = 1). CONCLUSIONS: ContiCath offers an alternative to an indwelling Foley catheter in men with temporary bladder outlet obstruction and urinary retention.

Aged↗

Continued improvement in pressure-flow parameters in men receiving finasteride for 2 years. Finasteride Urodynamics Study Group.

OBJECTIVES: To assess the long-term effects of finasteride on pressure-flow parameters in men with urodynamically documented bladder outflow obstruction (BOO). METHODS: One hundred twenty-one men with benign prostatic enlargement (BPE) and lower urinary tract symptoms (LUTS) underwent a pressure-flow study (PFS) at 1 of 11 clinical centers. The PFS technique was standardized, and all tracings were read by a single reader unaware of the treatment group. Patients who were obstructed according to a modified Abrams-Griffiths nomogram were randomized to 5 mg finasteride (n = 81) or placebo (n = 40) for 12 months; all patients continuing into an open extension received finasteride during the second 12 months of therapy. Results of the initial 12-month study demonstrated the benefit of finasteride treatment on PFS parameters. To examine the continuing effects over time, an analysis of the data from 54 patients who completed 24 months of treatment with finasteride is provided. RESULTS: Detrusor pressure at maximum flow (PdetQmax) continued to decrease during the second 12 months of therapy (decreases of 5.3 and 11.7 cm H2O at months 12 and 24, respectively). The percentage of patients obstructed by Abrams-Griffiths classification decreased from 76.2% at baseline to 66.7% at month 12 and 59.6% at month 24. An intention-to-treat analysis yielded similar results. CONCLUSIONS: Finasteride improves urodynamic measures of obstruction in men with BPE and LUTS, with continued improvement during the second 12 months of therapy.

Double-Blind Method↗

Transforming growth factor-beta1 (TGF-beta1) is sufficient to induce fibrosis of rabbit corpus cavernosum in vivo.

PURPOSE: The pleotropic cytokine TGF-beta1 which induces connective tissue synthesis, and inhibits the growth of smooth muscle cells, has been implicated in corpus cavernosum fibrosis. The objective of this study was to determine the dose and time dependence of TGF-beta1 as an active agent in penile corporal fibrosis in an animal model. MATERIALS AND METHODS: A time release method of delivery was developed using sodium alginate microspheres containing recombinant human (rh) TGF-beta1. New Zealand White rabbits were injected intracorporally with a single alginate microsphere either with or without rh-TGF-beta1. Dosage was varied from 325 to 1500 ng./bead. Animals were sacrificed at either three or five days post injection and the penises removed en bloc, examined, and processed for quantitative histomorphometric analysis, staining the sections with Masson's trichrome. RESULTS: Alginate microspheres containing [125I]-rh-TGF-beta1 showed slow-release kinetics (t1/2 = 10.5 hours). Histomorphometric analysis of 60 sets of high powered fields/treatment/ animal showed dose dependent decreases in percentage of corporal smooth muscle with TGF-beta1 treatment (750 to 1500 ng./bead). Placebo (alginate microspheres alone) had trabecular smooth muscle content comparable to values previously reported for untreated rabbit corpus cavernosum. CONCLUSIONS: This study confirms that TGF-beta1 induces fibrosis in situ by altering connective tissue synthesis and hence the structure of the corpus cavernosum. Injection of rh-TGF-beta1 impregnated alginate microspheres into the corpus cavernosum resulted in dose-dependent decreases in percentage of corporal smooth muscle.

Animals↗

Pharmacotherapeutic advances in the treatment of erectile dysfunction.

An estimated 20 million to 30 million American men have erectile dysfunction (ED). The past 2 decades of research defining erectile physiology and investigating the pathogenesis of ED have led to the recognition of a predominantly vascular basis for organic male sexual dysfunction. These scientific advances have laid the foundation for the advent of pharmacotherapies. The Food and Drug Administration approval of intracavernosal, intraurethral, and oral pharmacotherapeutics for ED has revolutionized non-surgical management of this condition. The primary care physician is faced with the challenges of diagnosis and treatment of ED, as well as referral of patients to urologists. In this article, erectile physiology and pathophysiology are reviewed, and pharmacotherapeutics are classified and discussed by their mechanisms of action and the means of administration. A thorough understanding of these new therapeutic options is key to the accurate diagnosis and successful treatment of ED and maximal patient satisfaction and care.

Adrenergic alpha-Antagonists↗

Improvement of pressure flow parameters with finasteride is greater in men with large prostates. Finasteride Urodynamics Study Group.

PURPOSE: We assess the effect of finasteride, a 5alpha-reductase inhibitor, on objective voiding parameters in men with lower urinary tract symptoms and benign prostatic enlargement on digital rectal examination (known as clinical benign prostatic enlargement) in a double-blind placebo controlled multicenter study using strict standard pressure flow study techniques. MATERIALS AND METHODS: A modification of the Abrams-Griffiths nomogram was used by 1 reader to ensure that all patients met objective criteria for bladder outlet obstruction at baseline. After performing a pressure flow study patients with obstruction were randomized 2:1 to receive 5 mg. finasteride (81) or placebo (40) daily. A second pressure flow study was performed at month 12. At baseline and month 12 free urinary flow studies and transrectal ultrasound were performed, and International Prostate Symptom Score questionnaires were completed. Patients were treated between May 1994 and July 1996. RESULTS: Finasteride caused a significant decrease (-8.1 cm. water) in detrusor pressure at maximum flow (p <0.05 versus placebo p = 0.02), increase (+1.1 ml. per second) in maximum flow rate (p <0.05 versus placebo p = 0.02) and decrease (-22.8%) in prostate volume (p <0.05 versus placebo p <0.001). Men with prostates larger than 40 cc had greater improvement in detrusor pressure at maximum flow (between group difference -14.5 cm. water, 95% confidence interval -26.2 to -2.6, p = 0.02) and maximum flow rate (mean treatment effect +1.6 ml. per second, 95% confidence interval -0.2 to 3.0, p = 0.02) compared to those with prostates 40 cc or less (between group differences not significant). CONCLUSIONS: Finasteride treatment resulted in improvements in urodynamic parameters, which were greater in men with large prostates.

Aged↗

The artificial urinary sphincter in the female: indications for use, surgical approach and results.

Female urinary incontinence is a common problem. Among the many treatment options a few patients may be suitable candidates for the artificial urinary sphincter (AUS). The indications for placement of an AUS are much more common in males: however, we review the indications, technique and potential complications of the AUS in the female population. Although few indications exist for the placement of an AUS in women, if proper patient selection is made, with strict adherence to proper surgical technique, it can be a suitable treatment option for those suffering from sphincteric incontinence.

Female↗

High-power potassium-titanyl-phosphate (KTP/532) laser vaporization prostatectomy: 24 hours later.

OBJECTIVES: To study the feasibility and immediate postoperative outcome of vaporization prostatectomy by high-power potassium-titanyl-phosphate (KTP/532) laser in 10 men with bladder outlet obstruction due to benign prostatic hyperplasia (BPH) and to evaluate their clinical and voiding outcome 24 hours postoperatively. METHODS: The KTP/532 laser at 60 W was produced by a prototype Laserscope generator and delivered through a side-deflecting fiber with a 22F continuous-flow cystoscope. Sterile water was used for irrigation. The prostatic lobes were readily vaporized to within capsular fibers. The mean lasing time was 29 +/- 8 minutes, during which a mean of 104.6 +/- 30 kJ of energy was delivered. RESULTS: The prostate volumes ranged from 22 to 60 mL (mean 38.4 +/- 9.7). None of the 10 patients had any significant blood loss or any fluid absorption. Foley catheters were removed in less than 24 hours postoperatively. All patients were satisfied with their voiding outcome. The mean peak urine flow rate increased from 8 +/- 1.3 mL/s preoperatively to 19.4 +/- 8.4 mL/s (142%, P = 0.003266) 24 hours postoperatively. Postvoid residual volumes remained essentially unchanged from their preoperative levels, as expected (P = 0.767423). One patient had urgency, but none had dysuria, hematuria, or incontinence or required recatheterization. Three patients have returned for 3-month follow-up; all 3 patients have had excellent results and are very satisfied with the outcome. CONCLUSIONS: Our very early and limited experience indicates that high-power KTP/532 laser vaporization prostatectomy is feasible and appears to be safe and effective for quickly relieving bladder outlet obstruction due to BPH. Larger randomized clinical trials to compare this technique with standard transurethral resection of the prostate and more follow-up data are needed to determine its long-term efficacy and durability.

Aged↗

Postprostatectomy urinary incontinence: a comparison of the cost of conservative versus surgical management.

OBJECTIVES: Post-radical prostatectomy stress incontinence occurs in up to 20% of patients. Postprostatectomy incontinence is initially treated with undergarments, pads, or drip collectors. Patients with persistent leakage are often treated with a transurethral bulking agent (Contigen) or placement of an artificial genitourinary sphincter (AGUS). We have compared the direct costs of each treatment at our institution over 10 years. METHODS: The Mayo Clinic estimating office provided the Medicare and non-Medicare charges for patients receiving both collagen injection (outpatient) and AGUS placement (2-day hospitalization) during August 1995. The Mayo Store provided the current price of all undergarments, pads, and drip collectors carried. Two local grocery stores provided the cost of Depends undergarments. RESULTS: The following items were the least expensive carried at the Mayo Clinic Store: Entrust undergarments, Active Style pads, and Conveen drip collectors at $0.99, $0.52, $1.05 each, respectively. The average cost of Depends undergarments was $0.52 each. The cost of wearing 5 of the least expensive undergarments or pads per day for 10 years is $9497. The average estimated Medicare and non-Medicare cost for outpatient (general anesthesia) collagen injection is $4300 and $5625, respectively. The average Medicare and non-Medicare cost for AGUS placement is $15,400 and $20,300, respectively. Factoring in our current 22.4% reoperation rate, the average per patient Medicare and non-Medicare cost for AGUS placement is $18,850 and $24,847, respectively. CONCLUSIONS: The cost of the AGUS placement compares favorably with the cost of transurethral collagen injection (under general anesthesia) in patients requiring several (more than three) collagen injection treatments or requiring the continued use of undergarments after collagen injection. Whereas the cost of transurethral collagen injection, when effective, compares favorably with conservative treatment, AGUS placement is significantly more expensive than conservative management for almost all patients except the exceedingly rare patient wearing more than 9 undergarments or pads per day. When the psychosocial benefit of urinary continence is considered, however, transurethral injection of collagen or AGUS placement often becomes the preferred treatment.

Ambulatory Surgical Procedures↗