Evaluation of the effect of endothelin-1 and characterization of the selective endothelin a receptor antagonist PD155080 in the prostate.

PURPOSE: To evaluate the contractile effect of endothelin-1 (ET-1) on prostatic urethral pressure and to characterize the effect of the selective ETA receptor antagonist PD155080 on ET-1 mediated prostatic urethral pressure. MATERIALS AND METHODS: The effect of intravenous ET-1 administration on canine urethral pressure was determined in the presence and absence of PD155080. The affinity of PD155080 for endothelin-mediated contraction was determined using antagonist dissociation studies. Saturation and competition binding studies were performed using [125I] ET-1 in both human and canine prostate. RESULTS: ET-1 bolus injection elicited shallow and prolonged increases the prostatic urethral pressure. Pretreatment with PD155080 totally abolished the urethral contractile response to ET-1. Specific [125I] ET-1 binding was saturable and of high affinity. Two ET receptor subtypes (ETA receptor, ETB receptor) have been identified in human prostate. The ratio of ETA to ETB receptors was approximately 1.5:1 in both human and canine prostates. Isometric tension studies revealed that PD155080 shifted the ET-1 dose-response curves to the right and exhibited no effect on the ETB receptor selective agonist sarafotoxin dose-response curves. CONCLUSION: ET-1 mediates prostate smooth muscle tone and may play a role in the pathophysiology and treatment of benign prostatic hyperplasia (BPH).

Maximum flow rate--the single uroflowmetric parameter in clinical trials for benign prostatic hyperplasia?

BACKGROUND: Uroflowmetry parameters should be examined for both reliability and optimal test conditions in patients with benign prostatic hyperplasia (BPH), since the difference between one pre- and one post-intervention uroflow rate is usually evaluated in clinical trials of BPH. PATIENTS AND METHODS: Reproducibility of maximum flow rate (Qmax) or its modified forms, and the effects of urinary volume on the reproducibility were examined in terms of Spearman's correlation coefficient (r) in 67 BPH patients. RESULTS: Qmax had a higher r (0.672) as compared to other uroflow rates, such as mathematically modified forms of Qmax and adjusted values of Qmax on nomograms. Reliability was improved by bladder instillation (r = 0.811) or when voided volume was > or = 150 ml or the ratio of volumes was < 2.0 (r = 0.690-0.736). CONCLUSION(S): Qmax, preferably performed with urinary volumes of more than 150 ml or the ratio of volumes less than 2.0, is the most practical single parameter at present in the comparison of two uroflowmetric tests in BPH treatment.

The three-circle single J catheter: a more stable urethral catheter for pressure flow studies.

We describe a single J urethral catheter which has been specially designed to facilitate stabilization during voiding in pressure flow studies. It has a tip with three circles, which prevents the catheter from slipping out even when there is a sudden increase in intra-abdominal pressure.

Response criteria for the therapeutic efficacy of treatment for benign prostatic hyperplasia.

Response criteria for the therapeutic efficacy of treatments for benign prostatic hyperplasia (BPH) were proposed following the International Consultation on BPH held in 1993. In the present study, we validated the criteria and proposed a simplified form, which consists of the responses of three parameters: symptom score and quality of life assessed by the international prostate symptom score and the maximum flow rate. Each of the three individual parameters is evaluated as one of four response grades: excellent, good, fair or poor, and the number of response grade of the three parameters determines the overall response. Excellent and Good responses are regarded as effective, and fair and poor are regarded as not effective. The validity of the response criteria was assessed by comparing the responses determined by these criteria with those made by physicians in charge using a group of 225 patients receiving various treatments. The agreement rates on effectiveness of overall responses between the response criteria and physicians were 77% for a multicenter trial of medical treatment (n = 94), 100% for TURP (n = 23), 92% for laser treatment (n = 47), 80% for thermal treatment (n = 26) and 78% for alpha-blockers (n = 35), respectively. Altogether, 88% (198 of 225 cases) were evaluated accurately regarding effectiveness. Addition of prostate volume to the battery of response parameters made little contribution to diagnostic accuracy. Deletion of any of the other three parameters, however, significantly compromised the quality of assessment. These results suggest that the proposed criteria may be useful as the standard method for the assessment of the clinical efficacy of BPH treatment.

Urinary symptoms and urodynamics in a normal elderly population.

Age-related changes in the lower urinary tract function were investigated by means of symptomatology and urodynamics. In the symptom study subjectively normal 168 males and 101 females aged over 30 were administered a questionnaire regarding urinary symptoms. The prevalence of symptoms gradually advanced with age and nocturia more than 2 times was dramatically increased up to a half in those aged over 70. In the urodynamic study involving 65 males and 51 females with low symptom scores, significant reduction with advancing age was noted for maximum flow rate in both sexes (males: r = -0.295, p < 0.05, females: r = -0.591, p < 0.01) and maximum detrusor pressure in females (r = -0.513, p < 0.01). There was a significant increase in residual urine in males (r = 0.473, p < 0.05); otherwise no consistent changes in cystometry and urethral pressure profile related to aging were detected. These results indicate that urinary symptoms and urodynamic variables may change with age even in "normal" subjects, and warrant a careful interpretation of them in the elderly subjects.

[A clinical classification of severity of benign prostatic hyperplasia].

The grading of severity of benign prostatic hyperplasia (BPH) was attempted by scoring clinical manifestations associated with the disease. The total score (0 to 100 points) is the sum total of subjective and objective one, each of which is 50 points at its maximum. Subjective score is composed of symptom score (0 to 25 points) evaluating 5 each obstructive and irritative symptoms and quality of life (QOL) score (0 to 25 points). Objective score consists of functional and anatomical scores. Functional score (0 to 25 points) is calculated by scoring maximum flow rate and residual urine. Anatomical score (0 to 25 points) is calculated by the score of prostatic volume. Seventy-seven BPH patients have been evaluated by this scoring system. The mean values of 4 kinds of scores (symptom, QOL, functional and anatomical scores) were about 8-9 points and thus comparable each other. The total score was 35.4 +/- 12.3 in the average and divided into 6 grades: Grade 0; < 10, Grade 1; > or = 10, Grade 2; > or = 20, Grade 3; > or = 30, Grade 4; > or = 40, Grade 5; > or = 50. The present scoring and grading systems appear to be appropriately formulated to estimate the global severity of BPH patients. Further studies to apply the system to evaluation of therapeutic responses would be mandatory to examine its validity.