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Biomedical subjects

H Lepor

Publications and source records attributed to H Lepor.

At least 19 recordsLinked to original sources
PubMed1995

Benign prostatic hyperplasia specific health status measures in clinical research: how much change in the American Urological Association symptom index and the benign prostatic hyperplasia impact index is perceptible to patients?

PURPOSE: We assessed the relationship between changes in scores for the American Urological Association (AUA) symptom index and benign prostatic hyperplasia (BPH) impact index with patient global ratings of improvement in a large Veterans Affairs trial comparing different pharmacological therapies for BPH. MATERIALS AND METHODS: The primary analyses compared absolute score changes from baseline with global ratings of improvement at 13 weeks for 1,218 men. RESULTS: Subjects who rated themselves as being slightly improved had a mean decrease in AUA symptom index and BPH impact index scores of 3.1 and 0.4 points, respectively. However, the baseline scores strongly influenced this relationship. CONCLUSIONS: These data provide guidance for investigators using the AUA symptom index and BPH impact index as outcome measures.

Health Status↗
PubMed1995

Long-term efficacy and safety of terazosin in patients with benign prostatic hyperplasia. Terazosin Research Group.

OBJECTIVES: To evaluate long-term efficacy and safety of terazosin, a selective alpha 1 blocker, in the treatment of benign prostatic hyperplasia (BPH). METHODS: This was a long-term (42 months), open-label, multicenter study with patients evaluated at 1- to 6-month intervals. Twenty-three outpatient clinics throughout the United States and Canada participated in the study. A total of 494 men with symptomatic BPH, lacking absolute indications for surgery, were enrolled in this study; 298 were transferred into the study from randomized, placebo-controlled studies of terazosin and 196 had no prior terazosin therapy. Terazosin was given starting at 1 mg/d and titrated upward until symptoms were relieved or a maximum dose of 20 mg/d was achieved, whichever came first. RESULTS: Peak urinary flow rates at all visits were significantly higher than baseline values, with mean improvements ranging from 1.0 to 4.0 mL/s. At 3 months, 40% of patients exhibited a 30% or greater improvement in peak flow rate; this improvement was maintained through 42 months. Boyarsky symptom scores improved significantly at all visits; mean total score improved by at least 4.0 points (40%) at all visits beyond 3 months. The most common adverse events resulting in premature termination from the study were dizziness (6.7%), asthenia (3.8%), and somnolence (2.0%). CONCLUSIONS: This study suggests that terazosin is well tolerated and effective in longterm treatment of patients with BPH.

Adrenergic alpha-Antagonists↗
PubMed1995

Characterization and localization of nitric oxide synthase in the human prostate.

OBJECTIVES: To characterize nitric oxide synthase (NOS), which catalyzes nitric oxide (NO) production, in the human prostate using biochemical and immunohistochemical techniques. METHODS: NOS catalytic assay and NOS immunohistochemistry were performed on histologically verified nonmalignant prostate tissue obtained from the peripheral and transition zones of seven radical prostatectomy specimens. RESULTS: Biochemical analysis revealed NOS activity in the human prostate, with a greater amount in the peripheral zone than in the transition zone (P < 0.01). In both prostate zones, NOS was immunohistochemically localized to nerve fibers and ganglia coursing throughout the smooth musculature of the stroma and to subepithelial nerve plexuses. NOS immunoreactivity was also localized to glandular epithelium. CONCLUSIONS: The presence, activity, and distribution of NOS were described in two regions of the human prostate. The present evidence implicates NO in the automatic innervation and physiology of the human prostate. It is proposed that NO may modulate smooth muscle tone and secretory functions in the human prostate, although functional studies are needed to support these hypotheses.

Amino Acid Oxidoreductases↗
PubMed1995

Effects of nitric oxide on human and canine prostates.

OBJECTIVES: To determine whether nitric oxide (NO) is a mediator of prostatic smooth muscle activity. METHODS: Pharmacologic experiments using electrical field stimulation (EFS) were performed on strips of human and canine prostate. RESULTS: EFS alone elicited frequency-dependent contractions in preparations of human and canine prostates. The greatest contractile activity was achieved at 30 Hz. In the presence of 10(-5) M guanethidine (GUA) and 2 x 10(-6) M atropine (ATR), EFS elicited relaxation of canine prostate strips relative to baseline tension. A weak biphasic response consisting of initial relaxation and subsequent contraction relative to baseline tension was observed in the human prostate strips exposed to similar conditions. The smooth muscle activity observed in the presence of GUA plus ATR was attributed to nonadrenergic, noncholinergic (NANC) nerve transmission. 10(-4) M L-NG-nitroarginine methylester (NAME) significantly increased EFS-elicited NANC smooth muscle activity both in human and canine prostates. L-arginine, 10(-2) M, reversed the effect of L-NAME in human and canine prostates. Sodium nitroprusside, 10(-4) M, a donor of NO, caused relaxation of both human and canine prostates. The mean magnitude of the relaxant response/cross-sectional area in human prostate (2.64 +/- 0.4 g/cm2) was significantly greater than in the canine prostate (1.09 +/- 0.17 g/cm2) (P < 0.005). CONCLUSIONS: These results provide compelling evidence that NO plays a role in mediating contractile function of human and canine prostates.

Animals↗
PubMed1995

A prospective randomized comparison of transurethral resection to visual laser ablation of the prostate for the treatment of benign prostatic hyperplasia.

OBJECTIVES: Transurethral resection of the prostate (TURP) represents the accepted standard of surgical therapy for the management of symptomatic bladder outlet obstruction due to benign prostatic hyperplasia (BPH). However, this is a major operative procedure associated with significant perioperative morbidity. Visual laser ablation of the prostate (VLAP) utilizing a neodymium:yttrium-aluminum-garnet laser represents a new technologic approach to the surgical management of BPH. We compared the relative safety and efficacy of these two surgical approaches in a prospective, randomized trial. METHODS: At 6 investigational sites in the United States, 115 men with symptomatic BPH more than 50 years of age and not in retention, were randomly assigned to undergo either TURP (59 patients) of VLAP (56 patients). VLAP patients received a mean of 10,200 J of energy delivered in a mean of 5.5 intraprostate laser applications. At preoperative baseline, 3 months, 6 months, and 1 year postoperatively, all patients underwent clinical evaluations, including ultrasonic prostatic volume determination, standardized American Urological Association (AUA)-6 symptom score, peak urine flow, postvoid residual urine volume, and quality-of-life assessment. RESULTS: Compared to TURP, the VLAP procedure required less time (23.4 versus 45.2 minutes; P < 0.01) and shorter hospitalization (1.8 versus 3.1 days, P < 0.01). VLAP was associated with a significantly lower rate of serious treatment-related complications compared to TURP (10.7% versus 35.6%; P < 0.01). Only One (2.2%) patient undergoing VLAP experienced a greater than 2.2 g/dL decrease in hemoglobin compared to 40% of TURP patients (P = 0.01). No patient in the VLAP group required blood transfusion compared with 3.4% of those undergoing TURP. Of the 115 patients, clinical outcomes measured at 1 year showed a mean improvement in AUA-6 symptom scores of -9.0 for VLAP compared with -13.3 for TURP (P < 0.04), mean increase in peak urinary flow rate of 5.3 cc/s for VLAP compared with 7.0 cc/s for TURP (P = 0.27), and mean decrease in postvoid residual urine volume of -55.4 cc for VLAP compared with -138.8 cc for TURP (P < 0.01). At 1 year, 78.2% of patients undergoing VLAP indicated that their quality of life was improved compared with 93.0% of patients undergoing TURP (P = 0.03). When compared with TURP, treatment of BPH with VLAP is associated with less hemoglobin decrease, a lower likelihood of serious complication, and requires less procedure time and a shorter hospital stay. Through a 1-year follow-up, VLAP produced significant improvement over baseline in objective and subjective outcome measures. However, for 1-year improvement in AUA-6 symptom score, postvoid residual urine volume, and quality of life, VLAP was less effective than TURP. CONCLUSIONS: In this initial study in the United States, with relatively low-energy laser applications, VLAP did not result in as complete a removal of prostatic tissue as did TURP. Considering the lower morbidity, shorter procedure and hospitalization times, and the degree of effectiveness that was achieved even at the low-energy doses used in this study, VLAP appears to be a viable and safe alternative to standard TURP.

Aged↗
PubMed1995

Localization of the alpha 1A-adrenoceptor in the human prostate.

PURPOSE: We determined the tissue localization of the alpha 1a-adrenoceptor in the human prostate. MATERIALS AND METHODS: Autoradiographic localization of the alpha 1a-adrenoceptor in the human prostate was determined by performing competitive displacement experiments on slide mounted tissue sections using the ligand 125iodine-2-(-[4-hydroxyphenyl]-ethyl-aminomethyl)tetralone (125I-Heat), and the alpha 1-antagonists WB-4101 (4 x 10(-8) M.) and 5-carboxamido-2,6-diethyl-1,4-dihydro-3-[N-(3-[4-hydroxy-4-phenylpipe ridin- yl]propyl)]carboxamido-4-(4-nitrophenyl) (SNAP 5272, 3 x 10(-7) M.). Under these experimental conditions, WB-4101 and SNAP 5272 are selective alpha 1a/alpha 1d-adrenoceptor and alpha 1a-adrenoceptor antagonists, respectively. The autoradiographs were quantitatively analyzed using a computer image analysis system. RESULTS: Specific 125I-Heat binding associated with the epithelium and stroma were independently analyzed. WB-4101 and SNAP 5272 inhibited 100% of the specific 125I-Heat binding in the stroma, suggesting that all of the stromal alpha 1-adrenoceptors are of the alpha 1a subtype. WB-4101 inhibited none of the specific 125I-Heat binding in the epithelium, suggesting that the alpha 1-adrenoceptor in the epithelium is of the alpha 1b subtype. SNAP 5272 displaced only 25% of the specific 125I-Heat binding in the epithelium, suggesting that a relatively small percentage of the epithelial alpha 1-adrenoceptor is of the alpha 1a subtype. CONCLUSIONS: To our knowledge, our study represents the first cellular localization of the alpha 1-adrenoceptor subtypes in the human prostate using highly selective alpha 1-adrenoceptor antagonists and is consistent with the physiological observation that the activity of prostatic smooth muscle is mediated by the alpha 1a-adrenoceptor.

Adrenergic alpha-Antagonists↗
PubMed1995

Pathophysiology of clinical benign prostatic hyperplasia.

The pathophysiology of clinical BPH has been attributed to bladder outlet obstruction resulting from the enlarged prostate. A direct relationship does not exist between prostate size, symptom severity, or bladder outlet obstruction. The pathophysiology of prostatism is most likely multifactorial. Elucidating the factors contributing to symptoms will likely provide the foundation for the development of new pharmacological alternatives for the medical treatment of BPH.

Humans↗
PubMed1995

Alpha blockade for the treatment of benign prostatic hyperplasia.

Randomized double-blind placebo controlled studies have consistently demonstrated the safety and effectiveness of selective alpha 1 blockers for the treatment of clinical BPH. Selective alpha 1 blockers relieve the symptoms of prostatism and decrease bladder outlet obstruction. The advantages of this class of drugs for the medical treatment of BPH include the extremely rapid onset of action, statistically and clinically significant effects on relevant outcome measures, adverse experiences that are generally infrequent, mild, and reversible, serum PSA levels are not affected, and hypertension is also effectively treated. The long-term effectiveness of selective alpha 1 blockers has recently been reported. Prostate smooth muscle tension is mediated by the alpha 1a (previously defined as alpha 1c) AR. The pharmaceutical industry is aggressively pursuing development of alpha 1a "prostate" selective AR antagonists.

Adrenergic alpha-Antagonists↗
PubMed1995

Combination medical therapy for benign prostatic hyperplasia.

Preliminary clinical observations suggest that the efficacy of combination therapy (alpha 1 blockade + androgen suppression) is superior to the individual monotherapies. Several randomized double-blind multicenter placebo controlled studies are being done to define the efficacy and safety of combination therapy relative to the monotherapies. The ultimate role of combination therapy in clinical practice depends on a critical assessment of relative efficacy, safety, and cost.

Drug Therapy, Combination↗
PubMed1995

The treatment of benign prostatic hyperplasia: a glimpse into the future.

The treatment of BPH has changed dramatically over the last decade. Industry has recognized the potential market for BPH therapies. Urologists have accepted and embrace the development of alternative treatment strategies. The combined resources and talents of industry and academic urology will lead to exciting future advances in this field. The optimal treatment of BPH requires not only new technology but a better understanding of the pathophysiology and natural history of this disease. Urologists are presently engaged in studies to better define these fundamental aspects of the disease process. The end result of these investigative efforts will be to the advantage of patients afflicted with BPH.

Humans↗
PubMed1995

Randomized double-blind study comparing the efficacy of terazosin versus placebo in women with prostatism-like symptoms.

PURPOSE: We attempt to determine whether terazosin is effective therapy for the treatment of prostatism-like symptoms in women. MATERIALS AND METHODS: A total of 29 women 47 to 79 years old with prostatism-like symptoms entered a randomized double-blind study comparing terazosin (14) versus placebo (15). The salient inclusion and exclusion criteria consisted of an American Urological Association (AUA) symptom score of 8 or more, post-void residual volume less than 300 ml. and absence of stress urinary incontinence. RESULTS: The baseline and final visit AUA symptom scores were 12.7 and 10.7 respectively, in the placebo group, and 16.4 and 13.6, respectively, in the terazosin group. The differences between the change in AUA symptom score in the placebo and terazosin groups were not clinically or statistically significant. CONCLUSIONS: Our study demonstrates that terazosin is not effective for the treatment of prostatism-like symptoms in aging women.

Adrenergic alpha-Antagonists↗
PubMed1994

Detection of prostate cancer in males with prostatism.

The present study was designed to compare the prostate cancer detection rate, sensitivity, specificity, and positive predictive value of digital rectal examination (DRE) and serum prostatic specific antigen (PSA) in a consecutive cohort of males presenting to a single institution with clinically significant prostatism. The study population was comprised of 224 consecutive males with clinically significant prostatism referred to the Prostate Center at the Medical College of Wisconsin between June 1990 and December 1991. Subjects were considered to have clinically significant prostatism if they elected to pursue medical or surgical therapy following exclusion of carcinoma of the prostate. The initial examination consisted of a Boyarsky symptom score assessment, DRE, uroflowmetry, postvoid residual determination, serum PSA level, and transrectal prostatic ultrasonography. Subjects with an abnormality on DRE or serum PSA > 4 ng/dl were advised to undergo transrectal prostatic biopsy. Of the 224 subjects, 40 (17.9%) had an abnormal DRE and 57 (25.4%) had an elevated serum PSA > 4 ng/dl. The overall detection rate of prostate cancer in the study population was 6.7%. The prostate cancer detection rates for PSA alone and DRE alone were 5.8% and 5.3%, respectively. The sensitivity, specificity, and positive predictive values of PSA alone were 86.7%, 80.9%, and 25.0% and of DRE alone 80.0%, 86.3%, and 30.0%, respectively. Receiver operator characteristic (ROC) curves were constructed for the entire study population in order to compare the screening measures serum PSA and PSA density. The area under the curves was 0.88 for both tests, indicating that these screening tests for prostate cancer were not significantly different. The present study demonstrated that males with clinically significant prostatism represent a high risk cohort for detecting prostate cancer. DRE and PSA are equally effective measures for detecting prostate cancer. PSA density does not offer any advantage over serum PSA in screening for prostate cancer, except in the subset of patients with a normal DRE and serum PSA levels between 4.0 and 9.9 ng/dl.

Adult↗
PubMed1994

Effects of alpha-adrenergic agonist on neobladder water and electrolyte transport.

OBJECTIVE: Nocturnal urinary incontinence and nocturia are problematic for patients with continent neobladders. Clonidine, an alpha 2-adrenergic agonist, increases water absorption across rabbit ileum; human intestine contains a substantial density of alpha 2-adrenergic receptors. We studied the effect of neobladder clonidine instillation and catheterization (to reduce urine-bowel contact time) on nocturnal water and electrolyte reabsorption. METHODS: A total of 8 patients with Indiana neobladders constructed after radical cystectomy were studied at a mean of 11.3 months postoperatively under standardized diet and fluid intake. RESULTS: Topical clonidine or catheterization failed to alter nocturnal urine volume, free-water clearance, or absolute excretions of electrolytes in Indiana neobladders; however, the absolute excretion of urine urea nitrogen and osmoles was significantly increased in the catheterized urine collections compared with the baseline urine collections (paired t-test, p = 0.0022 and 0.0091, respectively). CONCLUSIONS: Bowel comprising neobladders loses its capacity to significantly alter urinary electrolyte composition by prolonged contact, which may explain the rarity of significant acid-base disturbances in patients with continent neobladders. Unfortunately, topical clonidine does not diminish nocturnal urine volumes, but increased excretion of urea and osmoles with overnight neobladder catheterization may prove beneficial in patients who suffer azotemia or hyperosmolarity.

Adult↗
PubMed1994

Relationship between prostatic epithelial volume and serum prostate-specific antigen levels.

OBJECTIVES: The present study was designed to determine the relationship between serum prostate-specific antigen (PSA) levels and prostatic epithelial volumes. METHODS: Forty-two men between the ages of 50 and 79 years of age with either an abnormal digital rectal examination (DRE) or a serum PSA level > 4 ng/dL underwent transrectal ultrasonography (TRUS) and ultrasound-guided random systematic biopsy of the prostate. The volumes of the peripheral zone (PZ) and transition zone (TZ) were calculated, assuming that the total prostate and TZ are ellipsoidal structures. Six random systematic biopsies were directed into the PZ and four random systematic biopsies were directed into the TZ under ultrasound guidance. Among the 42 patients undergoing prostatic biopsy, adenocarcinoma of the prostate was identified in 21 (50%). Tissue sections obtained from the biopsy specimens of the subjects without histologic evidence of prostate cancer were stained with Mallory trichrome stain, and the percentage area density of epithelium in the biopsy cores was determined using computer-assisted color image analysis. The relationships between serum PSA and total, PZ, and TZ epithelial volumes, and serum PSA and total, PZ, and TZ prostatic volumes were determined using regression analysis. RESULTS: The difference between the mean percentage epithelial density of the PZ (17.79 +/- 1.40%) and TZ (10.32 +/- 0.82%) was statistically significant (p < 0.0001). The mean volumes of epithelium in the PZ and TZ were 4.25 +/- 0.47 cc and 3.39 +/- 0.45 cc, respectively. The p and r2 values for the relationship between serum PSA and total prostatic volume were 0.016 and 0.260, respectively. Statistically significant correlations were also observed between serum PSA levels and TZ epithelial volumes (p = 0.0009; r2 = 0.449) and serum PSA levels and TZ volumes (p = 0.007; r2 = 0.329). Statistically significant correlations were not observed between serum PSA levels and the following parameters: PZ volume, PZ epithelial volume, and total prostatic epithelial volume. CONCLUSIONS: Although the PZ contains a significantly greater area density and absolute volume of epithelium than the TZ, the serum PSA level is most strongly correlated only with the volume of epithelium in the TZ.

Age Factors↗
PubMed1994

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.

Adipose Tissue↗