Power Doppler imaging: principles and applications.

Power Doppler Imaging (PDI) is a promising new sonographic technique for evaluating the vascular system. PDI uses special processing to display the amplitude or strength of the Doppler signal, rather than velocity and directional information as in conventional color Doppler. This allows a much greater sensitivity in detecting small vessels and slow-moving blood. Currently PDI is being used only in conjunction with color Doppler, but it has proven valuable in many applications.

Transurethral prostate ablation using saline-liquid electrode introduced via flexible cystoscope.

An interstitial saline-electrode has been developed to couple radiofrequency (RF) energy to prostate tissue in order to produce large lesions quickly and controllably. In this study, we attempted to produce similar results using a flexible catheter introduced transurethrally via a flexible cystoscope. An insulated 4F catheter with an extendable needle electrode (26-gauge, 5-mm exposed metal tip) was introduced through a port of a flexible cystoscope into the urethra of 10 dogs via a small perineal incision (required for the canine U-shaped urethra). Under visual endoscopic guidance, the electrode was placed in the center of the prostate and the needle electrode extended at an angle into the prostate, one lobe at a time. Hypertonic saline (14.6% NaCl) was infused at 2 mL/min through the needle electrode into the tissue for 30 seconds before and during RF application. The energy (50 W, 475 kHz) was delivered for 30, 45, 60, or 90 seconds (RFT System; U.S. Surgical Corporation). Prostate and urethral temperatures were monitored using thermocouples mounted on the catheter. There was an automatic high-temperature shut-off if the urethra reached >42 degrees C or if impedance reached >300 omega during RF energy application. Prostate sizes ranged from 1.4 x 2.0 x 1.4 cm to 5.0 x 4.5 x 4.2 cm. In this group, there were no automatic shut-offs at any of the energy durations, and the lesions produced ranged from 1.3 x 1.3 x 1.1 cm (0.99 cm3) to 1.6 x 2.7 x 2.2 cm (5.03 cm3). The average ablation volumes produced were 1.76 cm3 at 30 seconds' RF application, 2.42 cm3 at 45 seconds, 3.96 cm3 at 60 seconds, and 5.03 cm3 at 90 seconds. Histologic examination revealed typical coagulation necrosis in the treatment zone without tissue desiccation. Introduction of the saline-electrode through a flexible cystoscope provides a minimally invasive procedure that quickly and controllably produces large lesions that may provide effective treatment for benign prostatic hyperplasia with less patient discomfort.

off absorption, pharmacodynamics, metabolism and excretion of 14C-sumatriptan following intranasal administration to the beagle dog.

The pharmacodynamics, pharmacokinetics, metabolism, and excretion of 14C-sumatriptan have been studied in the beagle dog following administration by the intranasal and other routes. The pharmacological response which was monitored, an increase in carotid arterial vascular resistance, correlated with the plasma levels of unchanged sumatriptan following intranasal, intravenous, or intraduodenal administration to the anaesthetised dog. The pharmacokinetics and metabolism of sumatriptan were then confirmed in conscious male and female dogs. Intranasal administration of 14C-sumatriptan resulted in rapid absorption of part of the dose. The overall bioavailability of sumatriptan was 40-50%. Sumatriptan was eliminated from plasma with a half-life of 1.5 or 1.9 h after intravenous or intranasal dosage respectively. Radioactivity was largely excreted in urine (up to 75% of the dose) with small amounts in the bile and faeces after intravenous and intranasal dosing, as sumatriptan and a major metabolite. The results from these studies suggest that intranasal administration provides a viable method for delivering sumatriptan to the systemic circulation.

The efficacy of terazosin, finasteride, or both in benign prostatic hyperplasia. Veterans Affairs Cooperative Studies Benign Prostatic Hyperplasia Study Group.

BACKGROUND: Men with benign prostatic hyperplasia can be treated with alpha 1-adrenergic-antagonist drugs that relax prostatic smooth muscle or with drugs that inhibit 5 alpha-reductase and therefore reduce tissue androgen concentrations. However, the effects of the two types of drugs have not been compared. METHODS: We compared the safety and efficacy of placebo, terazosin (10 mg daily), finasteride (5 mg daily), and the combination of both drugs in 1229 men with benign prostatic hyperplasia. American Urological Association symptom scores and peak urinary-flow rates were determined at base line and periodically for one year. RESULTS: The mean changes from base line in the symptom scores in the placebo, finasteride, terazosin, and combination-therapy groups at one year were decreases of 2.6, 3.2, 6.1, and 6.2 points, respectively (P<0.001 for the comparisons of both terazosin and combination therapy with finasteride and with placebo). The mean changes at one year in the peak urinary-flow rates were increases of 1.4, 1.6, 2.7, and 3.2 ml per second, respectively (P<0.001 for the comparisons of both terazosin and combination therapy with finasteride and with placebo). Finasteride had no more effect on either measure than placebo. In the placebo group, 1.6 percent of the men discontinued the study because of adverse effects, as did 4.8 to 7.8 percent of the men in the other three groups. CONCLUSIONS: In men with benign prostatic hyperplasia, terazosin was effective therapy, whereas finasteride was not, and the combination of terazosin and finasteride was no more effective than terazosin alone.

Multiple forms of cytochrome P450 are involved in the metabolism of ondansetron in humans.

Ondansetron is cleared primarily by metabolism in humans, with hydroxylation of the indole moiety in the 7- and 8-positions being the major identified phase I pathways. In vitro studies using lymphoblastoid cell lines expressing single human cytochrome P450 forms and hepatic microsomes were undertaken to investigate the forms involved in the metabolism of ondansetron in humans. The cell lines that expressed CYP1A1, CYP1A2, and CYP2D6 were shown to be capable of metabolizing [14C]ondansetron. Studies with human hepatic microsomes and the specific inhibitors furafylene, quinidine, and ketoconazole confirmed the role of CYP1A2 and CYP2D6 and also demonstrated the involvement of the CYP3A subfamily. The data in this study collectively indicate that multiple cytochrome P450 forms, including CYP1A1, CYP1A2, CYP2D6, and the CYP3A subfamily, are probably involved in the clearance of ondansetron in humans, with no single form of cytochrome P450 dominating the overall metabolism of ondansetron. The role played by CYP2D6 in the metabolism of [14C]ondansetron by human hepatic microsomes in vitro was shown to be minor. This finding is consistent with the lack of bimodality in the clinical pharmacokinetics of ondansetron. It is therefore concluded that ondansetron is metabolized by multiple forms of cytochrome P450, and this limits the likelihood of a clinically relevant interaction with ondansetron by a modulator of a single form of cytochrome P450.

Lasers for the treatment of benign prostatic hyperplasia.

In our experience, efficacy favors the TURP and safety the laser. Unlike balloon dilatation of the prostate, there are likely to be technologic advancements that will allow more efficient tissue ablation, which will presumably result in more TURP-like efficacy. In addition, each of the many side-firing fibers has different physical properties that require fiber specific dosimetry studies. It is not clear how this will impact clinical efficacy; however, it is presumed that this will optimize efficacy while maintaining safety and minimizing catheterization time and postoperative irritative symptoms. VLAP is the surgical procedure of choice in high-risk patients and is an effective alternative for the treatment of symptomatic BPH. In high-risk patients, other devices such as stents may play an important role. From our assessment, TURP seems to provide greater symptomatic relief and probably is more durable than the VLAP procedure. Patients will often choose VLAP over TURP because of the lower risks of major complications and the perceived advantages of laser therapy over more conventional surgery. Other ablation techniques that are less invasive, more efficient, or do not require anesthesia but have equivalent efficacy could challenge the role of laser devices. Similarly, the continued development of more effective medical therapy will continue to challenge the role of all surgical interventions for BPH. Future investigations will focus on issues of dosimetry, tissue coagulation versus vaporization as well as fiber design and durability. The continued efforts to define the optimal technique reflect the general perception of the urologic community to improve the clinical outcome so that efficacy is more TURP-like. New delivery systems are being investigated as part of the effort to improve outcome. This includes the use of the holmium and diode lasers. The efficacy of these future delivery systems awaits proper study.

Transurethral needle ablation for the treatment of benign prostatic hyperplasia.

The TUNA device is a unique system that uses radiofrequency energy to ablate the obstructing prostate adenoma. Although the clinical data are preliminary, they appear to provide improvement in symptom scores and peak flow rates, although somewhat less than TURP. A prospective, randomized trial comparing TUNA to TURP is under way, which should answer many of the questions regarding the safety and efficacy of this device for BPH. It is a potentially attractive device because of the limited anesthesia requirements, ease of the procedure, and the possibility of making this an office-based technique. The definitive role of this unique device awaits the results of ongoing clinical trials.

Evaluating the cost of lasers for the treatment of benign prostatic hyperplasia.

Cost is an extremely complex equation with many variables, but itemized hospital bills are useful in analysis because they reflect costs as defined by an institution. Using this data source, we found that the total cost of an outpatient visual laser-assisted prostatectomy ($6,872.42) is almost the same as that of transurethral resection with a 3-day hospital stay ($6,925.00). Use of local anesthesia, improvement in the efficiency of tissue vaporization, and increases in fiber durability to permit multiple use would reduce laser prostatectomy costs. The true economic impact of laser prostatectomy awaits a long-term analysis that takes into account the costs of late complications and of reoperation.

A comparison of transurethral prostatectomy with visual laser ablation of the prostate using the Urolase right-angle fiber for the treatment of BPH.

The use of right-angle laser fibers for the treatment of benign prostatic hyperplasia (BPH) has gained widespread acceptance over the past several years. The number of right-angle fibers introduced into the marketplace has continued to grow, but most fibers have not been evaluated thoroughly with properly designed clinical trials. The Urolase fiber has undergone the most extensive clinical trials conducted to date. This report reviews the significant clinical trials with particular emphasis on the comparison of transurethral prostatectomy with visual laser ablation of the prostate. From these initial results, it would appear that laser ablation using the Urolase fiber is a safe and effective surgical therapy for men with symptomatic BPH. From our analysis, it would appear that transurethral prostatectomy provides a greater degree of symptomatic improvement as compared with transurethral resection of the prostate. It is important to consider that these are some of the earliest clinical trials assessing the efficacy of laser prostatectomy and that technological advancements are likely to improve the clinical outcome.

Evaluating the efficacy, safety, and cost of lasers for the treatment of benign prostatic hyperplasia.

This review highlights some of the caveats assessing the available clinical data base for determining the efficacy, safety, and cost of laser systems used to treat benign prostatic hyperplasia. Many new minimally invasive devices have recently been advanced in spite of the limited data base and the lack of properly designed clinical trials. There have been many claims regarding the effectiveness of laser prostatectomy based on the available clinical data. Some important general considerations for interpreting the clinical data base, critically analyzing the study design, and interpreting the data are discussed. Similarly, many claims have been made with respect to the cost of laser prostatectomy; however, insufficient objective data are available for clear determinations of cost. Some of the pertinent issues involved in the cost assessment of laser prostatectomy are also highlighted. It is hoped that this review will provide the reader with some additional insight into the critical assessment of the quality of studies that evaluate the safety, efficacy, and cost of new devices such as the laser.

Perianastomotic injection of autologous fat at the time of radical retropubic prostatectomy.

OBJECTIVES: The present study represents the first attempt to improve urinary continence following radical prostatectomy (RP) by perianastomotic injection of autologous fat at the time of the surgical procedure. METHODS: A total of 15 consecutive men with clinically localized carcinoma of the prostate underwent nerve-sparing radical retropubic prostatectomy (RRP) with perianastomotic injection of autologous fat. The autologous fat was obtained using a liposuction cannula connected to a power aspirator. The fat was harvested from the adipose tissue immediately adjacent to the lower midline incision. After the pelvic floor musculature was perforated, a total of 30 mL of autologous fat was injected through a 12 gauge angiocatheter under cystoscopic guidance. RESULTS: There were no complications resulting from the harvesting or injection of the autologous fat. All of the patients were evaluated for 6 months. Of the 15 patients, 12 (80%) achieved total urinary control within 6 months. The average time required to achieve total urinary continence was 89 days. None of the patients experienced total or nocturnal incontinence. Of the 3 patients with stress urinary incontinence (SUI), 2 required 2 small pads per day and 1 required 3 pads per day. Only 1 patient reported that the level of bother resulting from the incontinence was severe. CONCLUSIONS: The preliminary experiences with the perianastomotic fat injection at the time of RRP are encouraging. Determining the ultimate safety and effectiveness of this technique requires longer follow-up in expanded series of patients.

Right-angle free beam lasers for the treatment of benign prostatic hyperplasia.

When comparing the efficacy of VLAP to TURP, the existing data are not entirely consistent. Several studies conclude that the two procedures have equivalent efficacy with respect to AUA symptom score, peak flow rate, and reduction of postvoid residual urine volume. None of these studies are designed to control for patient or investigator bias and generally only mean values are compared. To date, our study is the only double-blind, randomized trial that compares VLAP to TURP. Although the laser procedure was an effective alternative, it was not as effective as TURP as measured by the AUA symptom score, reoperation rate, or the patients' global assessment of symptomatic improvement. To be a useful procedure, it is not essential that the efficacy be equivalent to TURP, but it is clearly preferred particularly because an anesthetic is usually required. When comparing the efficacy of these two procedures, one cannot help asking an obvious question: What is the chance that the first attempt at a new procedure (VLAP), with relatively little prior testing, would be equally effective to a procedure (TURP) that has been performed hundreds of thousands of times and modified during the past 50 years? It should not be too disappointing or surprising that our data show the TURP to be more effective. These data represent the first attempts at laser treatment for BPH. Although it is an easy procedure for a urologist to learn, the optimal technique has not been defined. It is very likely that improvements in technology and technique will improve the efficacy while maintaining safety.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of the enzyme responsible for the metabolism of sumatriptan in human liver.

Studies have been undertaken to investigate the enzymes responsible for the metabolism of [14C]sumatriptan in man. Oxidative deamination of sumatriptan to form the indole acetic acid derivative is the only phase 1 pathway evident in man and both cytochrome P450 (P450) and monoamine oxidase (MAO) are capable of catalysing this type of reaction. The metabolism of [14C]sumatriptan was therefore investigated in vitro in a preparation derived from human liver, which was shown, by the use of the probe substrates [14C]testosterone (P450), [3H]5HT (MAO-A) and [14C]benzylamine (MAO-B) to be a rich source of both enzyme systems. Incubation with clorgyline and deprenyl, probe inhibitors of MAO-A and MAO-B, respectively, showed that [14C]sumatriptan was metabolized by MAO-A; there was no evidence of P450 involvement in its metabolism. The data in this study therefore indicate that the enzyme MAO-A is the major enzyme responsible for the metabolism of sumatriptan in human liver.

Disposition of sumatriptan in laboratory animals and humans.

Sumatriptan is a new 5HT1-like agonist that has proved a novel and effective treatment for migraine. The disposition of the 14C-radiolabeled drug in laboratory animals and humans after oral and parenteral administration is described. Oral absorption of sumatriptan is essentially complete in dogs and rabbits, but only approximately 50% in rat. In humans, at least 57% of an oral dose is absorbed. Bioavailabilities are species dependent (14, 23, 37, and 58% in humans, rabbits, rats, and dogs) reflecting differing degrees of first-pass metabolism. These data correlate well with hepatic extraction ratios, which are highest in rabbits and humans and lowest in dogs. Renal clearance is significant in all species and exceeds the glomerular filtration rate in rats, rabbits, and humans, but not in dogs. The compound is a weak base that shows widespread tissue distribution, including passage across the placental barrier and into milk, but low CNS penetration. Protein binding of sumatriptan is low in all species. Elimination half-lives of sumatriptan are approximately 1 hr in rats and rabbits, and approximately 2 hr in dogs and humans. In all species the majority of the absorbed dose is renally excreted, predominantly as the indole acetic acid metabolite and unchanged drug. Interesting species differences are evident in the metabolism of sumatriptan. Thus, in humans, the indole acetic acid metabolite is excreted partly as a glucuronide, whereas in animals conjugation of this metabolite is not apparent. In addition, demethylation of the sulfonamide side chain of the drug is evident in rodent and lagomorph species only.

MR imaging of traumatic posterior urethral injury.

To assess the role of magnetic resonance (MR) imaging in defining the surgical approach and in predicting permanent erectile dysfunction in patients with traumatic posterior urethral injury, 27 patients underwent MR imaging before open urethral reconstruction. MR findings were correlated with surgical findings, surgical approach, and sexual potency at 12-month follow-up. MR imaging correctly revealed the length of the urethral injury (allowing for 0.5-cm discrepancy) in 23 of 27 (85%) patients and displacement of the prostatic apex in 19 of 21 (90%) patients. MR findings prompted a change in the clinically planned surgical approach from perineal to combined perineal and transpubic in seven (26%) cases. Significant variables affecting permanent impotence were avulsion of the corpus cavernosum, (P < .001), separation of the corporeal body (P < .05), and superior and/or lateral prostatic displacement (P < .05). When MR imaging findings of both cavernous avulsion and superior and/or lateral prostatic displacement were present, the probability of permanent impotence was 95%. In the absence of these findings, the probability of normal potency was 83%. MR imaging can be performed to help select the most effective surgical approach and to assess permanent erectile dysfunction.

Posttraumatic impotence: magnetic resonance imaging and duplex ultrasound in diagnosis and management.

In 15 patients, impotent as a result of prostatomembranous urethral disruption consequent to pelvic crush injuries, magnetic resonance imaging (MRI) and duplex ultrasound were used to establish anatomical and pathophysiological criteria for accurate diagnosis and appropriate management. All patients were initially treated by suprapubic cystostomy diversion for at least 3 months, after which urethral reconstruction was performed. All men were potent before the pelvic trauma, with loss of sexual function immediately thereafter. Preoperative MRI demonstrated prostatic displacement in 13 cases (86.7%) and cavernous injury in 12 (80%). Duplex ultrasound revealed the cause of erectile failure as vasculogenic in 12 patients (80%) and neurogenic in 3 (20%). Treatment of impotence was deferred for at least 18 months after injury. Of the neurogenic group 2 patients were started on intracavernous injection therapy and 1 refused treatment. Of the vasculogenic group 3 patients underwent successful revascularization, 2 are on injection therapy and 1 had a penile prosthesis inserted. The detailed anatomical information obtainable with pelvic MRI and the functional data provided by duplex ultrasonography enabled us to identify the individual organic components of posttraumatic impotence and to select effective cause-specific therapy.

Magnetic resonance imaging of traumatic posterior urethral defects and pelvic crush injuries.

A total of 18 patients 4 to 71 years old with complete occlusion of the prostatomembranous urethra from pelvic crush injury underwent magnetic resonance imaging (MRI) of the pelvis just before open urethroplasty. MRI studies included T2-weighted sagittal and coronal images as well as transaxial T1 and T2-weighted spin-echo images. Operative findings and erectile function were correlated with MRI findings. All patients underwent conventional cystography and retrograde urethrography. The mean interval from injury to operation was 5.5 months (range 3 to 12 months) and followup averaged 12 months (range 3 to 40 months). Posttraumatic pelvic anatomy can be distorted and imaging in all 3 planes was needed. The severity and direction of prostatourethral dislocation, and the length of the urethral defect could be accurately determined, which often is not possible with conventional radiographic studies. MRI also demonstrated injuries at many locations along the erectile pathway, including sacral and ischial fractures as well as fractures and avulsions of the cavernous bodies. Pelvic MRI can accurately define the pelvic anatomy after crush injury and, therefore, it can provide useful preoperative information that cannot be obtained by conventional radiographic studies. Our results correlating MRI findings of cavernous avulsion with clinical impotence require further study.