Bladder Outlet Obstruction In Men Research Articles

PROTEINURIA AND RENAL FUNCTION DURING AND AFTER ACUTE URINARY RETENTION

Purpose Benign prostatic hyperplasia is the most common neoplasm as well as the main cause of bladder outlet obstruction in men. It may progress to involve a risk of urinary retention. We investigated the effects of acute urinary retention on renal function. Materials and Methods We evaluated renal function using biochemical markers in 25 men with a mean age of 69 years in whom an episode of acute urinary retention a mean of 31 hours in duration was due to bladder outlet obstruction. Patients were followed for 6 months after acute retention was relieved. Patients were not known to have had any renal disease previously. Results During acute urinary retention at presentation, and after 1 and 6 months we noted albuminuria in 100, 92 and 54% of patients, elevated alpha 1-microglobulin excretion in 54, 39 and 58%, and elevated beta 2-microglobulin excretion in 17, 19 and 9%. Serum creatinine or creatinine clearance did not predict proteinuria. All parameters became normal at 6 months in only 2 cases. Conclusions Acute urinary retention affects glomerular and tubular renal function. After acute urinary retention was relieved increased glomerular permeability and tubular damage persisted in the majority of patients. This condition may have been partially due to previous long-term bladder outlet obstruction. Our findings stress the importance of the rapid recognition and treatment of acute urinary retention.

DIAGNOSING BLADDER OUTLET OBSTRUCTION IN WOMEN

There are no universally accepted urodynamic criteria for diagnosing female bladder outlet obstruction. When accepted criteria for men are applied to women, the diagnosis of obstruction may often be missed, which is most likely due to differences in voiding dynamics. We propose video urodynamic criteria for diagnosing obstruction in women, and describe the urodynamic findings in those with and without obstruction. We reviewed the charts of 331 women who underwent multichannel video urodynamics for nonneurogenic voiding dysfunction. Of these women 261 (mean age 55.8 years) had evaluable voiding pressure flow studies with simultaneous video fluoroscopy of the bladder outlet during voiding. At video urodynamics cases were classified as obstructed if there was radiographic evidence of obstruction between the bladder neck and distal urethra in the presence of a sustained detrusor contraction. Strict pressure flow criteria were not used. Maximum flow rate, detrusor pressure at maximum flow rate, post-void residual, bladder capacity and the incidence of detrusor instability were compared between obstructed and unobstructed cases. A total of 76 women met the criteria for obstruction (mean age 57.5 years), while 184 (mean age 55) did not. Causes of obstruction were dysfunctional voiding in 25 cases, cystocele in 21, primary bladder neck obstruction in 12, iatrogenic from incontinence surgery in 11, urethral stricture in 3, uterine prolapse in 2, urethral diverticulum in 1 and rectocele in 1. Obstructed cases had lower mean maximum flow rate (9 versus 20.2 ml. per second, p <0.0001), higher mean detrusor pressure at maximum flow rate (42.8 versus 22.1 cm. water, p <0.0001) and higher mean post-void residual (157 versus 33 ml., p <0.0001). There was no difference in bladder capacity (381 versus 347 ml.) or incidence of detrusor instability (45 versus 41%). Using the proposed video urodynamic criteria obstructed cases had significantly higher voiding pressures, lower flow rates and higher post-void residual than unobstructed cases, as expected. However, absolute values, especially for voiding pressure, are not as dramatic in women as in men. Pressure flow studies alone may fail to diagnose obstruction but simultaneous imaging of the bladder outlet during voiding greatly facilitates diagnosis.

Treatment of nocturia in the elderly.

The aging process, behavioural habits and a multitude of pathological conditions are the main contributors to the development of nocturia in the elderly. Age-related physiological changes can alter the regular pattern of urine excretion and lead to increased nocturnal frequency of voiding. In addition, aging is associated with anatomical and physiological changes of the urinary tract itself that predispose to increased urinary frequency without affecting urine volume. Several urinary and extra-urinary tract conditions may have nocturia as a prominent symptom. These conditions can be grouped as those associated with bladder overactivity, bladder outlet obstruction, bladder hypotonicity and an increased urine volume. A detailed assessment that gathers clues from the medical history, physical examination and laboratory is of utmost importance in identifying the specific causes. Overactive bladder can be idiopathic or associated with different triggers such as UTI, bladder stones, bladder tumours and CNS diseases that disrupt the normal inhibitory signals to the bladder. It may be cured by the successful elimination of the trigger conditions. Therapeutic modalities include behavioural therapies with scheduled voiding, anticholinergic drugs and in women the use of transvaginal electrical stimulation. Benign prostatic hyperplasia is the most common cause of bladder outlet obstruction in men. Different drug classes (e.g. peripheral alpha-adrenoceptor blockers and 5 alpha-reductase inhibitors) are now available for the treatment of mild to moderate symptoms. Surgery is reserved for patients with severe symptoms or with complications, with new and less invasive surgical techniques being preferred. Bladder hypotonicity is usually caused by peripheral neuropathies, spinal cord lesions and the indiscriminate use of drugs with anticholinergic actions. Treatment involves discontinuation of implicated drugs, short term use of cholinergic drugs and urinary catheterisation. Increased urine volumes and nocturia are frequently seen in hyperosmolar and oedematous states. Excessive ingestion of fluids, caffeinated or alcoholic beverages are habits that commonly produce nocturia. Although more definitive studies are awaited, low dose loop diuretics given a few hours prior to bedtime and desmopressin nasal spray or tablets may be useful alternatives for the control of nocturic symptoms in elderly patients with nocturnal polyuria syndrome. Whenever nocturia is present, clinicians should try to identify its causes by means of a thorough history, physical examination and pertinent complimentary tests. Once the specific cause or causes are found, most cases can be satisfactorily managed with behavioural, pharmacological or surgical therapies.

The ICS-'BPH' Study: uroflowmetry, lower urinary tract symptoms and bladder outlet obstruction.

To explore the relationship between uroflow variables and lower urinary tract symptoms (LUTS): to define performance statistics (sensitivity, specificity, positive and negative predictive values) for maximum urinary flow rate (Qmax) with respect to bladder outlet obstruction (BOO) at various threshold values; and to investigate the diagnostic value of low-volume voids. The study comprised 1271 men aged between 45 and 88 years recruited from 12 centres in Europe, Australia, Canada, Taiwan and Japan over a 2-year period. Symptom questionnaires, voiding diaries, uroflowmetry and pressure-flow data were recorded. The relationship between uroflow variables and symptoms, Qmax and BOO, and the diagnostic performance of low volume voids were analysed. The relationship between symptoms and uroflow variables was poor. The mean difference between home-recorded and clinic-recorded voided volumes was -48 mL. Qmax was significantly lower in those with BOO (9.7 mL/s for void 1) than in those with no obstruction (12.6mL/s; P<0.001) and Qmax was negatively correlated with obstruction grade (Spearman's correlation coefficient -0.3, P<0.001), even when controlling for the negative correlation between age and Qmax (Spearman's partial correlation coefficient -0.29, P<0.001). A threshold value of Qmax of 10 mL/s had a specificity of 70%, a positive predictive value (PPV) of 70% and a sensitivity of 47% for BOO. The specificity using a threshold Qmax of 15 mL/s was 38%, the PPV 67% and the sensitivity 82%. Those voiding <150 mL (n=225) had a 72% chance of BOO (overall prevalence of BOO 60%). In those voiding >150 mL the likelihood of BOO was 56%. The addition of a specific threshold of 10 mL/s to these higher volume voiders improved the PPV for BOO to 69%. While uroflowmetry cannot replace pressure-flow studies in the diagnosis of BOO. it can provide a valuable improvement over symptoms alone in the diagnosis of the cause of lower urinary tract dysfunction in men presenting with LUTS. This study provides performance statistics for Qmax with respect to BOO: such statistics may be used to define more accurately the presence or absence of BOO in men presenting with LUTS, so avoiding the need for formal pressure-flow studies in everyday clinical practice, while improving the likelihood of a successful outcome from prostatectomy. This study also shows that low-volume uroflowmetry can provide useful diagnostic information and that, as such, the data from such voids should not be discarded.

DETRUSOR CONTRACTION DURATION AS A URODYNAMIC PARAMETER OF BLADDER OUTLET OBSTRUCTION FOR EVALUATING MEN WITH LOWER URINARY TRACT SYMPTOMS

Purpose Recent studies suggest that detrusor contraction duration increases with bladder outlet obstruction and correlates with the American Urological Association (AUA) symptom index. Since the detrusor contraction duration may also depend on detrusor contractility and bladder volume, its use alone in characterizing bladder outlet obstruction is debatable. Therefore, we studied the relationship between detrusor contraction duration and bladder outlet obstruction, bladder capacity, detrusor contractility and symptoms to determine whether detrusor contraction duration is a useful parameter for characterizing bladder outlet obstruction in men with lower urinary tract symptoms. Materials and Methods Pressure-flow studies were performed in men with lower urinary tract symptoms. Bladder outlet obstruction was defined as passive urethral resistance relation greater than grade II and contractility was determined from Schafer's nomogram. Detrusor contraction duration was defined as the contraction time elapsed between the first rise in detrusor pressure from baseline to the time at which detrusor pressure returned to baseline at the end of voiding. AUA symptom index was attained from each patient and categorized as mild (0 to 7), moderate (8 to 19) and severe (20 to 35). Results Detrusor contraction duration was determined from 58 consecutive pressure-flow studies. This parameter was not significantly different among 23 patients with mild (116.7 +/− 34.0 seconds), 15 with moderate (102.7 +/− 61.9 seconds) and 9 with severe (89.2 +/− 44.4 seconds) AUA symptom index scores. AUA symptom index, as well as irritative and obstructive scores did not significantly correlate with detrusor contraction duration. Detrusor pressure at maximal flow was weakly correlated with detrusor contraction duration (r = 0.322, p = 0.014). However, detrusor contraction duration in 27 obstructed patients (111.6 +/− 53.7 seconds) was not significantly different from that of 31 nonobstructed patients (91.5 +/− 41.5 seconds) and it did not increase with the severity of bladder outlet obstruction. Detrusor contraction duration in 40 patients with good contractility (94.3 +/− 49.2 seconds) was significantly lower than in 18 patients with poor contractility (115.5 +/− 43.3 seconds). Detrusor contraction duration was significantly lower in nonobstructed patients with good contractility (72.0 +/− 21.7 seconds) compared with either nonobstructed patients with poor contractility (118.4 +/− 47.7 seconds) or obstructed patients with good contractility (112.5 +/− 58.0 seconds). There was no difference in detrusor contraction duration between nonobstructed patients with poor contractility and obstructed patients with good contractility. Multiple regression analysis showed that detrusor contraction duration can be best predicted by a combination of detrusor pressure at maximal flow, bladder capacity and contractility (r = 0.576). Conclusions Our study showed that detrusor contraction duration cannot distinguish patients with from those without bladder outlet obstruction, and it does not correlate with the severity of symptoms. Since our results also showed that detrusor contraction duration depends on several factors related to detrusor and outlet function, it cannot be used as a reliable parameter to diagnose bladder outlet obstruction.

NOVEL STAGING TOOL FOR LOCALIZED PROSTATE CANCER: A PILOT STUDY USING GENETIC ADAPTIVE NEURAL NETWORKS

An estimated $1.5 billion is spent annually for direct medical expenses and an additional $2.5 billion for indirect costs for the management of prostate cancer. Today there are several procedures for staging prostate cancer, including lymph node dissection. Despite these procedures, the accuracy of predicting extracapsular disease remains low (range 37 to 63, mean 45%). Use of multiple staging procedures adds significantly to the costs of managing prostate cancer. Recently artificial intelligence based neural networks have become available for medical applications. Unlike traditional statistical methods, these networks do not assume linearity or homogeneity of variance and, thus, they are more accurate for clinical data. We applied this concept to staging localized prostate cancer and devised an algorithm that can be used for prostate cancer staging. Our study comprised 1,200 men with clinically organ confined prostate cancer who underwent preoperative staging using serum prostate specific antigen, systematic biopsy and Gleason scoring before radical prostatectomy and lymphadenectomy. The performance of the neural network was validated for a subset of patients and network predictions were compared with actual pathological stage. Mean patient age was 62.9 years, mean serum prostate specific antigen 8.1 ng./ml. and mean biopsy Gleason 6. Of the patients 55% had organ confined disease, 27% positive margins, 8% seminal vesicle involvement and 7% lymph node disease. Of margin positive patients 30% also had seminal vesicle involvement, while of seminal vesicle positive patients 50% also had positive margins. The sensitivity of the network was 81 to 100%, and specificity was 72 to 75% for various predictions of margin, seminal vesicle and lymph node involvement. The negative predictive values tended to be relatively high for all 3 features (range 92 to 100%). The neural network missed only 8% of patients with margin positive disease, and 2% with lymph node and 0% with seminal vesicle involvement. Our study suggests that neural networks may be useful as an initial staging tool for detection of extracapsular extension in patients with clinically organ confined prostate cancer. These networks preclude unnecessary staging tests for 63% of patients with clinically organ confined prostate cancer.

Overview: role of stents in urology.

Catheterization of the urinary tract for drainage is the mainstay of urologic manipulations. Although the material of which the catheters are made changed during the years, they all remained external communicating devices, causing ascending infections and discomfort. A concept of completely internal catheters for use in urology developed during the last few decades. Although the first self-retaining internal ureteral catheters (stents) were developed for use in open surgical procedures or on malignant obstructions, later, they caused a considerable leap in the development of minimally invasive endourologic procedures. The development of intraurethral stents also started to change some of the approaches to the management of bladder outlet obstruction. This paper summarizes the subject of urologic stents, which is presented in detail in this special issue of the Journal of Endourology.

High-energy visual laser ablation of the prostate in men with urinary retention: Pressure-flow analysis

Objectives. To assess the efficacy of high-energy visual laser ablation of the prostate (VLAP) in men withurinary retention, using subjective and objective data. Methods. Seventeen men in urinary retention underwent high-energy VLAP. The mean patient age was 69years, and the mean follow-up was 12 months. All men were urodynamically obstructed by pressure-flow analysis with a functioning detrusor muscle. Interviews assessed retrograde ejaculation and patient satisfaction. Results. The mean total energy applied was 71,088 J (range 27,556 to 110,294). The mean peak noninvasive urine flow rates increased from 2.1 to 18.1 cc/s, and the mean postvoid residual volumes decreased from 550.0 to 39.0 cc. The mean detrusor pressure at peak flow decreased from 66.4 to 41.9 cm H 2O, and the mean maximal detrusor pressure decreased from 72.2 to 49.2 cm H 2O. Ten men (59%) voided to completion within 1 week post-VLAP. The mean postoperative International Prostate Symptom Score was 6. Nine men (53%) reported new retrograde ejaculation, and 14 men (82%) were satisfied with their outcome. Conclusions. High-energy VLAP is an effective procedure for relief of bladder-outlet obstruction in men with urinary retention.

Alpha 1-adrenoceptors in human prostate: Characterization and binding characteristics of alpha 1-antagonists

The role of alpha 1-adrenoceptors in the mediation of autonomic functions, particularly in the control of the cardiovascular system, is widely known. It has been shown that alpha 1-adrenoceptors localized in human prostate mediate the contraction of prostatic smooth muscles which produces an increase in the intraurethral pressure and thus, these receptors are important in the regulation of bladder outlet resistance. Alpha 1-antagonists such as prazonin relieve the symptoms of bladder outlet obstruction in men with symptomatic benign prostatic hypertrophy (BPH) by blocking alpha 1-adrenoceptors, thereby decreasing prostatic tone and urethral resistance. Thus, alpha 1-adrenergic stimulation may be one of the most important factors in the development of urinary obstruction in BPH. Alpha 1-adrenoceptors in human prostate have been identified and characterized extensively by functional, radioligand binding and molecular biological techniques. These studies provide evidence in support of the concept that the alpha 1-subtype forms the majority of alpha 1-adrenoceptors in human prostatic smooth muscles. It has been shown that YM617 (tamsulosin) and naftopidil have higher affinities to alpha 1-adrenoceptors in the prostate than in the aorta. Some alpha 1-antagonists, such as prazosin and terazosin, are not selective with respect to alpha 1-adrenoceptor subtypes, while others, such as 5-methylurapidil and indoramin, show higher potencies for alpha 1C-adrenoceptors and much lower potencies for alpha 1A-and alpha 1B-subtypes. In conclusion, the recent findings from pharmacological and molecular biological studies indicate that selective antagonists of alpha 1C-adrenoceptors could be effective in the treatment of urinary obstruction in symptomatic BPH with fewer cardiovascular side effects.

Relationship of Symptoms of Prostatism to Commonly Used Physiological and Anatomical Measures of the Severity of Benign Prostatic Hyperplasia

In previous studies the severity of symptoms of prostatism in men with benign prostatic hyperplasia have not correlated well with prostate size, degree of bladder trabeculation, uroflowmetry or post-void residual volume. As part of a prospective cohort study of benign prostatic hyperplasia treatment effectiveness in 4 university-based urology practices, we correlated symptom severity and these commonly used measures of disease severity. Symptom severity was quantified using the American Urological Association symptom index. Analyses were based on 198 outpatients completing a standardized evaluation (84 of these men have completed 6 months of followup after treatment with prostatectomy, balloon dilation, terazosin or watchful waiting). At baseline, symptom severity was not correlated with uroflowmetry, post-void residual, prostate size and degree of bladder trabeculation. However, symptom severity was much more strongly related to overall health status than the other measures. Reduction in symptoms with treatment did correlate with improvements in uroflowmetry. This poor baseline correlation with symptoms may reflect unreliability in measurement of the physiological/anatomical variables. Alternatively, these parameters may be measuring different pathophysiological phenomena.

Development of the Eagle-Barrett (prune belly) syndrome and a thickened, poorly functional bladder wall after early second-trimester decompression of fetal megacystis.

The management of bladder outlet obstruction in the fetus remains a debated issue. Recent data suggest the use of cystocentesis for the possible relief of the bladder neck obstruction or for the opening of posterior urethral valves. This case report adds further support for the use of cystocentesis and observation prior to the placement of an indwelling bladder shunt. The case further demonstrates that relief of the megacystis may not prevent prune belly syndrome, bladder dysfunction or renal damage. Finally, the case demonstrates that severe oligohydramnios in the second trimester need not invariably result in pulmonary hypoplasia.

The management of bladder outlet obstruction due to prostate cancer, untreated and after endocrine treatment.

The management of bladder outlet obstruction due to prostate cancer, untreated and after endocrine treatment.

Transurethral Resection Versus Transurethral Incision of the Prostate

A new operation, transurethral incision of prostate (TUIP), performed on 846 patients in 20 years, is offered primarily for the management of bladder outlet obstruction in young, middle-aged, and those old men with small prostates who otherwise would be subjected for years to dilatation, massage, and drugs with only partial and temporary relief. In matched cases, results and complications are the same for TUIP and TURP except for the troublesome bladder neck contracture and the higher incidence of reflex into the seminal vesicles and sexual complications after resection of the prostate. Transurethral incision is unsuitable for large prostates. As for economics, compassion and wisdom in fee collection are justified. Cost reduction in health care may be necessary, but it hurts everyone involved. There is no such thing as unnecessary surgery when the critics are charged with decision making about the health and life of the patient before surgery. Finally, before the advent of the third-party payment, operations were avoided because of the financial burden. The surgeon, the patient, and the relatives silently consented to no care. This "silent consent" did not improve the quality of life but did contain costs--as well as longevity.

Autonomic Receptors in Human Prostate Adenomas

Radioligand receptor binding techniques were used to characterize alpha1 adrenergic, alpha2 adrenergic and muscarinic cholinergic (MCh) binding sites in human prostate adenomas obtained from men with symptomatic and asymptomatic benign prostatic hyperplasia (BPH). Prostate adenoma specimens were obtained from nine men with asymptomatic BPH undergoing cystoprostatectomy, 11 men with symptomatic BPH undergoing open prostatectomy, and 11 men with symptomatic BPH undergoing transurethral resection of the prostate (TURP). A quantitative symptoms score analysis and urinary flow rate determinations documented the absence of bladder outlet obstruction in men undergoing cystoprostatectomy and confirmed the presence of bladder outlet obstruction in men undergoing prostatectomy. The mean equilibrium dissociation constants (Kd) and the mean densities of 125I-Heat (alpha1 adrenergic) and 3H-NMS (MCh) binding sites were similar in tissue homogenates obtained from men with asymptomatic and symptomatic BPH. The mean Kd of 3H-Rauwolscine (3H-Ra) was significantly greater in the prostatectomy specimens obtained from men with symptomatic BPH compared to the specimens obtained from men with asymptomatic BPH (p < 0.05). The density of 3H-Ra (alpha2 adrenergic) binding sites was significantly greater in the prostate adenomas obtained from men with symptomatic BPH compared to the prostate adenomas obtained from men with asymptomatic BPH (p < 0.05). The difference in alpha2 adrenoceptor density was accounted for by an increased receptor density in the open prostatectomy specimens. There was no significant correlation between alpha2 adrenergic, alpha1 adrenergic, and MCh receptor densities and prostate weight or patient age. This study indicates that the development of infravesical obstruction in men with BPH is not related to upregulation or altered binding affinity of alpha1 adrenergic or MCh receptor binding sites. The significance of the observed upregulation of alpha2 adrenoreceptors in the prostate adenomas obtained from men undergoing open prostatectomy is unknown, and requires further investigation.

Contractile properties of human prostate adenomas and the development of infravesical obstruction

The contractile response of human prostate adenomas to KCl, phenylephrine (alpha 1 adrenergic agonist), UK 14304 (alpha 2 adrenergic agonist), and carbachol (muscarinic cholinergic agonist) was evaluated in tissue specimens obtained from men with symptomatic and asymptomatic BPH. Prostate specimens were obtained from 5 men with asymptomatic BPH undergoing cystoprostatectomy, 11 men with symptomatic BPH undergoing open prostatectomy, and 11 men with symptomatic BPH undergoing transurethral resection of the prostate (TURP). Quantitative symptom score analysis and urinary flow rate determination documented the absence of bladder outlet obstruction in men undergoing cystoprostatectomy and confirmed the presence of bladder outlet obstruction in men undergoing prostatectomy. The magnitude of the contractile response (Emax) and the potency of phenylephrine-induced contractions (EC50) in prostatic preparations obtained from men with symptomatic and asymptomatic BPH were similar. The IC50 for the inhibition of phenylephrine-induced contractions by prazosin was 3.2 nM, confirming that phenylephrine-induced contraction in the human prostate is mediated by the alpha 1 adrenoceptor. The contractile responses of prostate adenomas to muscarinic cholinergic and alpha 2 agonists were negligible. This study demonstrates that the development of bladder outlet obstruction in men with BPH is not related to alterations in the functional response of the smooth muscle component of the prostate adenoma.

The Effect of Electrocautery on Neurotransmitter Receptor Binding Assays in the Canine Prostate

The purpose of this study was to determine whether resection of the prostate with electrocautery alters the binding properties of various neurotransmitter ligands. Prostate glands were removed from four adult male dogs. The prostates were divided in the midsaggital plane and one half of the prostate was resected using a resectoscope. Saturation experiments were performed on the resected and control prostatic tissue using 3H-NMS, 125I-Heat, and 3H-rauwolscine.The mean equilibrium dissociation constants (Kd) and the mean densities of 3H-NMS,125I-Heat, and 3H-Rauwolscine binding sites were similar in tissue homogenates obtained from control and resected portions of the prostate (p> 0.05). Resection of the prostate using electrocautery did not alter the binding properties of various neurotransmitter ligands for characterizing and quantifying muscarinic cholinergic, alpha1 adrenergic, and alpha2 adrenergic binding sites in the canine prostate. Approximately 90% of prostatectomies for symptomatic BPH (benign prostatic hyperplasia) are performed transurethrally. The ability to accurately measure neurotransmitter receptor densities in prostate tissues obtained following transurethral resection is imperative for our future studies designed to elucidate the role of alpha adrenergic receptors in the development of bladder outlet obstruction in men with BPH. (J. Urol., 140: 668–671, 1988)

Alpha2 Adrenergic Receptors in Canine Prostate: Biochemical and Functional Correlations

The sympathetic innervation of human prostate adenomas has been previously demonstrated using fluorescence microscopy and in vitro isometric studies. A clinical implication of these observations is that bladder outlet obstruction in men with benign prostatic hypertrophy may be subject to pharmacologic manipulation using adrenergic drugs. Randomized clinical trials have demonstrated the efficacy of alpha adrenergic antagonists for symptomatic BPH.We have previously characterized the alpha1 and alpha2 adrenergic receptors in the human prostate using [3H]prazosin and [3H]rauwolscine, respectively. The mean alpha1 and alpha2 receptor densities in the adenomas studied were equivalent. The effect of alpha2 adrenergic drugs on prostatic urethral pressure has not been examined in the human or in an animal model. In this study a canine model was used to define the effect of alpha2 drugs on prostatic urethral pressure. Intravenous administration of clonidine, a selective alpha2 agonist, resulted in a dose dependent increase in prostatic urethral pressure. The maximal increase in urethral pressure ranged between 18 to 30cm. H20. The maximal response to clonidine was approximately 50% less than the response to epinephrine, indicating that clonidine acts as a partial agonist. Pretreatment with yohimbine, a selective alpha2 adrenergic antagonist, abolished the effects of clonidine and epinephrine. The alpha2 adrenergic receptors were then studied in the canine prostates using [3H]rauwolscine. The equilibrium dissociation constant, Kd, ranged between 0.68 to 1.80nM and the receptor density ranged between 14.8 to 69.3fmol./mg. protein. The receptor density was homogeneous in specimens obtained from the proximal, midportion, and distal canine prostate suggesting that the effect of alpha2 drugs is not sphincter mediated. These in vitro and in vivo studies provide the basis for investigating the effects of alpha2 antagonists in men with symptomatic BPH.

Characterization of Alpha1 Adrenergic Receptors in Human Benign Prostatic Hyperplasia

Bladder outlet obstruction in men with benign prostatic hyperplasia is decreased following administration of prazosin, a selective alpha1 adrenergic antagonist. Prazosin presumably binds and antagonizes alpha1 adrenergic receptors on the smooth muscle cells of the prostatic adenoma. This study represents the first identification and characterization of alpha1 adrenergic receptors in the prostate using radioligand receptor binding methods.The binding of [3H] prazosin in homogenates obtained from human prostatic adenomas was saturable and a single high affinity prazosin binding site was identified (Kd = 0.29 ± 0.09nM). The alpha1 adrenergic receptor concentration in these homogenates ranged between 0.28 to 2.05fmol./mg. wet wt. prostate. The equilibrium dissociation constant and density of prazosin binding sites were similar in different regions of an enucleated prostate suggesting homogeneity of receptor density and receptor binding sites within an adenoma. The receptor density was not directly proportional to the weight of the surgically removed adenoma. The pharmacology of the prazosin binding sites was characterized by competitive binding experiments using [3H] prazosin and several unlabelled adrenergic analogs. The IC50’s determined from competitive binding experiments using [3H] prazosin and alpha-methylnorepinephrine, rauwolscine and corynanthine were characteristic of alphai adrenergic receptor binding.

Thoughts on sphincteric function and comments on management of bladder outlet obstruction in the female.

SUMMARY The mode of action of the bladder sphincter is not known but it seems to be more than a simple mechanical valve and may depend at least in part on some orderly pattern of muscular contraction, possibly of peristaltic nature, under autonomic control. A minor procedure for dealing with meatal stricture is described. Bougies a boule have been found of great assistance in the investigation of the female urethra, and passage of these bougies has been found to be the best method for demonstrating and locating a stricture. Very little mechanical strength is required to narrow the urethra and the fact that no stricture is detected by the passage of a cylindrical instrument is not valid evidence of the absence of a stricture. In the cine cystourethrogram a narrowing, with dilatation above, suggests the presence of a stricture, but strictures are not always displayed by this technique. In the short term, internal urethrotomy appears to be a most useful procedure for dealing with strictures, but it will be many years before its long term value will be fully assessed. The operation is simple and appears to be remarkably safe. YV-plasty should not be performed on the adult female except after the most careful and extensive investigation.