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Biomedical subjects

H Lepor

Publications and source records attributed to H Lepor.

At least 127 records · Page 7Linked to original sources
PubMed1992

The response to alpha blockade in benign prostatic hyperplasia is related to the percent area density of prostate smooth muscle.

The objective of the present study was to determine whether the smooth muscle content of the prostate adenoma is related to the clinical response to terazosin, a long-acting selective alpha 1 blocker. Multiple random biopsies of the prostate were obtained from 26 male subjects with symptomatic benign prostatic hyperplasia (BPH) prior to initiating therapy with terazosin. Double immunoenzymatic staining and computer-assisted quantitative color image analysis were utilized to quantify the area density of smooth muscle, connective tissue, glandular epithelium, and glandular lumen. The clinical response to alpha blockade was based upon changes in peak urinary flow rate and the Boyarsky symptom score. A significant direct relationship was observed between the percent area density of smooth muscle and the percent change in peak urinary flow rate. A statistically significant correlation between the percent area density of smooth muscle and the percent change in Boyarsky symptom score was not observed. The percent area density of prostate smooth muscle in the subjects exhibiting a favorable clinical response was 38% greater than the nonresponders (P = 0.068). The clinical response to alpha blockade in BPH is related to the area density of prostate smooth muscle.

Adrenergic alpha-Antagonists↗
PubMed1992

Quantitative morphometry of the adult human bladder.

The primary objective of the present retrospective study was to characterize the effects of aging and BPH on bladder morphometry. Eighty-six bladder specimens were obtained from the autopsy archives of the Milwaukee County Medical Complex. The bladder specimens were divided into 4 groups based upon age and gender: Group I: males between the ages of 35-45 years; Group II: males between the ages of 65-75 years; Group III: females between the ages of 35-45 years; and Group IV: females between the ages of 65-75 years. The age groups were selected in order to identify a group of males with and without BPH. The area density of smooth muscle:connective tissue was determined in bladder specimens using color assisted computer image analysis. Masson-trichrome and double immunoenzymatic staining techniques were used to discriminate the smooth muscle and connective tissue elements of the bladder. The area density of smooth muscle:connective tissue in the Masson-trichrome stained sections was significantly greater in Group I vs. Group II (2.90 +/- 0.22 vs. 2.33 +/- 0.16) and in Group III vs. Group IV (2.85 +/- 0.13 vs. 2.03 +/- 0.20). Aging was associated with a decrease in the area density of smooth muscle:connective tissue ratio in both males and females. The area density of smooth muscle:connective tissue was not significantly different in younger males and females (Group I vs. Group III) and older males and females (Group II vs. Group IV). The present morphometric study suggests that aging and not BPH, is associated with a relative increase in detrusor fibrosis. Infravesical obstruction in BPH may effect bladder function via mechanisms unrelated to the histologic composition of the bladder.

Adult↗
PubMed1992

The effect of obstruction on the developing bladder.

Congenital bladder obstruction causes significant immediate and long-term consequences yet its pathophysiology remains poorly understood. A model of early fetal bladder obstruction in sheep has been developed to study the response of the developing bladder to high grade obstruction, with particular emphasis on the regulation of growth and development. Congenital bladder obstruction was produced in fetal sheep at 60 days of gestation and studied at 95 days of gestation (14 sheep) or term (12 sheep). A total of 24 age-matched normal sheep served as controls. Bladders were analyzed by total weight, stereological estimation of smooth muscle cell size, number and total mass, deoxyribonucleic acid concentration, muscarinic cholinergic receptor density, myosin isoform analysis and/or passive cystometrics. Congenital bladder obstruction caused a 4.6 times increase in bladder weight at term reflecting a 5.8 times increase in smooth muscle mass. This increase was predominantly that of cellular hypertrophy and less so of hyperplasia, based upon increased cell volume, increased protein-to-deoxyribonucleic acid ratio, and no significant increase in total cell number. Muscarinic cholinergic receptor number per smooth muscle cell increased 3.2 times but it did not change relative to myosin content. The ratio of myosin heavy chain isoforms SM1:SM2 is developmentally regulated and was seen to change from 1.6 at 100 days of gestation to 1.13 at term in normals. After 5 weeks of obstruction SM1:SM2 was 1.27 and it was 1.25 at term, indicating an effect on the developmental regulation of smooth muscle. Rapid fill cystometry in vivo measured the rate of stress relaxation to assess accommodative properties. The half-decay time was increased in all 3 obstructed bladders tested to greater than 15 seconds at 50% capacity (normal less than 5 seconds), suggesting reduced compliance. This study shows that an in utero model of bladder obstruction is feasible. Congenital bladder obstruction produces a variety of structural, biochemical and functional changes in the developing bladder indicative of alterations in the regulation of growth and differentiation.

Actins↗
PubMed1992

Binding and functional properties of alpha 1 adrenoceptors and area density of smooth muscle in the canine prostate.

The present study was designed to compare the area density of smooth muscle, and the binding and functional properties of alpha 1 adrenoceptors in 8 different regions of the canine prostate. The area density of smooth muscle, alpha 1 adrenoceptor density, and contractile response to phenylephrine were investigated using immunoenzymatic staining with color assisted computer image analysis, radioligand receptor binding, and isometric tension studies, respectively. The equilibrium dissociation constants (Kd) for 125I-Heat binding and the alpha 1 adrenoceptor densities (Bmax) in the prostatic regions ranged between 138-230 pM and 0.32-0.52 fmol/wet wt., respectively. The maximal tension generated in the presence of phenylephrine (phenylephrine Emax) and phenylephrine EC50s ranged between 0.043-0.129 gm. force/mm.2 CSA and 4.0-11.0 microM, respectively. The differences between Kd, Bmax, Emax, and EC50 were not significantly different between the different regions of the prostate. The percent area density of smooth muscle ranged between 10.6-24.4%. A direct relationship was not observed between alpha 1 adrenoceptor density and phenylephrine Emax, or alpha 1 adrenoceptor density and percent area density of smooth muscle. A direct relationship was observed between the phenylephrine Emax and percent area density of smooth muscle (p = 0.003; r = 0.90). The phenylephrine Emax and percent area density of smooth muscle was threefold and 1.6-fold greater in the peripheral prostate relative to the central prostate, respectively. The morphometrical and isometric tension studies provides evidence that the canine prostate is a heterogeneous gland.

Animals↗
PubMed1992

A randomized, placebo-controlled multicenter study of the efficacy and safety of terazosin in the treatment of benign prostatic hyperplasia.

The clinical manifestations of benign prostatic hyperplasia (BPH) are related primarily to bladder outlet obstruction resulting from enlargement of the prostate gland. Transurethral prostatectomy is the most common treatment currently offered for BPH in the United States. The primary objective of the present randomized placebo controlled multicenter study was to determine the efficacy and safety of terazosin, a selective long-acting alpha 1-blocker, for the treatment of symptomatic BPH. A total of 285 men with symptomatic BPH was randomly assigned in equal proportions to receive placebo, or 2, 5 or 10 mg. terazosin administered once daily. Of the patients 237 completed the 4-week single-blind placebo lead-in and 12-week double-blind treatment periods. The primary outcome parameters were changes in peak and mean urinary flow rates, and changes in the Boyarsky symptom scores. All terazosin treatment groups exhibited significantly greater decreases in total Boyarsky symptom score than the placebo group. The 10 mg. terazosin group exhibited significantly greater increases in peak and mean urinary flow rates than the placebo group. The improvements in symptom scores and urinary flow rates did not reach a plateau within the dose range evaluated, suggesting that further efficacy may be achieved with doses of terazosin exceeding 10 mg. This study unequivocally demonstrates the safety and efficacy of terazosin for the treatment of BPH. Selective alpha 1-blockade is likely to gain widespread acceptance for the treatment of BPH due to its safety and efficacy.

Adrenergic alpha-Antagonists↗
PubMed1992

Randomized double-blind study comparing the effectiveness of balloon dilation of the prostate and cystoscopy for the treatment of symptomatic benign prostatic hyperplasia.

We attempted to determine the effectiveness of balloon dilation of the prostate for the treatment of symptomatic benign prostatic hyperplasia (BPH). A total of 33 men with symptomatic BPH signed informed consent to participate in a randomized, double-blind study comparing balloon dilation of the prostate and cystoscopy. Balloon dilation of the prostate and cystoscopy were performed with the patient under intravenous sedation after intraurethral instillation of viscous lidocaine and infiltration of the autonomic neural innervation of the prostate with 1% lidocaine. Efficacy was based upon improvement in Boyarsky symptom scores, increases in peak urinary flow rates and patient global assessment of symptomatic improvement. Efficacy was assessed at 1 and 3 months after treatment. A study nurse blinded to the randomization scheme administered the symptom score questionnaires and supervised the uroflowmetry studies. The study was randomized, since the mean baseline prostate sizes, peak urine flow rates, obstructive and irritative symptoms scores, post-void residual volumes and patient ages were similar in the 2 groups. The patient perceptions of treatment rendered were similar for the 2 treatment groups, confirming that the study was double-blind. The patients undergoing cystoscopy and balloon dilation of the prostate experienced a statistically significant improvement in the mean total symptom scores at 1 and 3 months. The mean total symptom scores after balloon dilation of the prostate and cystoscopy at 1 and 3 months were not significantly different. The mean peak urinary flow rates 1 and 3 months after balloon dilation of the prostate and cystoscopy were not significantly different from the baseline mean peak urinary flow rates. We demonstrate that balloon dilation of the prostate and cystoscopy are equally effective for the treatment of BPH. Since cystoscopy is considered a diagnostic modality, our study suggests that the efficacy previously observed after balloon dilation of the prostate is primarily placebo-related. The study does not support the indication of balloon dilation of the prostate for the treatment of symptomatic BPH.

Aged↗
PubMed1992

A comparison of the urological complications associated with long-term management of quadriplegics with and without chronic indwelling urinary catheters.

The primary objective of this retrospective study was to compare the incidence of urological complications and renal deterioration in post-traumatic quadriplegic patients managed with or without a chronic indwelling urinary catheter. The charts of 57 consecutive patients who sustained traumatic cervical spinal cord injury between 1970 and 1980 were reviewed. All of the patients received the initial management or rehabilitation therapy at our institution. The unique features of this clinical review are that a large cohort of patients was followed for a minimum of 10 years, none of the 57 consecutive patients was lost to followup and a yearly excretory urogram provided an objective assessment of the renal units. The followup, and mechanism, level and degree of injury for the 32 patients managed with and 25 managed without a catheter were similar. Overall, the incidences of renal and bladder calculi, pyelonephritis, gross hematuria, penile/urethral erosion, urosepsis, urethral stricture, epididymitis and pyonephrosis were not significantly different in the catheterized and noncatheterized groups. The Kaplan-Meier analysis of the most recent excretory urogram demonstrated that the incidence of renal deterioration was also equivalent in the catheterized and noncatheterized groups. Our study suggests that the decision to manage quadriplegics with or without an indwelling catheter should not be based on relative risk of complications or renal deterioration. The decision to avoid an indwelling catheter in these patients should reflect patient comfort, convenience and quality of life.

Adult↗
PubMed1992

Quantifying the smooth muscle content of the prostate using double-immunoenzymatic staining and color assisted image analysis.

The primary objective of the present study was to develop a method for quantifying the smooth muscle content of the prostate adenoma. A double immunoenzymatic staining technique was coupled with color assisted image analysis to determine the area density of the smooth muscle within the prostate adenoma. Eight males with symptomatic BPH underwent transrectal biopsy of the prostate. Four micron thick tissue sections were used for the double immunoenzymatic staining process. Rabbit anti-desmin and mouse anti-human prostatic acid phosphatase antibodies were used to selectively bind smooth muscle and prostatic epithelium, respectively. The two different tissue antigens were identified with peroxidase-antiperoxidase (PAP) and alkaline phosphatase-antialkaline phosphatase techniques. The alkaline phosphatase activity and peroxidase activity were developed with fast red and DAB chromogens. The BQ MEG IV Vista color system image analysis was used to discriminate color differences from the stained tissue sections. The thresholds were set to identify smooth muscle (dark brown), epithelium (red), fibrous tissue (pale brown), and glandular lumina (colorless). The mean area density of smooth muscle, fibrous tissue, glandular epithelium, and glandular lumina was 22%, 54%, 16%, and 9%, respectively. The present study suggests that a significant component of the prostate adenoma is smooth muscle. The application of this technique will be utilized to provide further insights into the role of smooth muscle in the pathogenesis and therapy of BPH.

Aged↗
PubMed1992

The relative proportion of stromal and epithelial hyperplasia is related to the development of symptomatic benign prostate hyperplasia.

The specific features of the prostate adenoma predisposing to the development of symptomatic benign prostatic hyperplasia (BPH) are unknown. Our objective was to determine whether the histological composition of the prostate adenoma is related to the development of symptomatic BPH. Prostate adenomas were obtained from men with asymptomatic BPH undergoing cystoprostatectomy for invasive transitional cell carcinoma, and from men with symptomatic BPH undergoing open prostatectomy, transurethral resection of the prostate and pharmacotherapy. The severity of bladder outlet obstruction was evaluated with the Boyarsky symptom score and uroflowmetry. The percentages of stroma, epithelium and glandular lumen were determined in the prostate adenomas via quantitative image analysis on a computer-assisted morphometry system. The prostate adenomas from the 33 men with symptomatic BPH contained 62 +/- 1%, 15 +/- 1% and 23 +/- 1 of stroma, epithelium and glandular lumen, respectively. The prostate adenomas from 6 men with asymptomatic disease contained 54 +/- 1%, 21 +/- 1% and 25 +/- 1% of stroma, epithelium and glandular lumen, respectively. The ratios of stromal-to-epithelial hyperplasia in the prostate adenomas from men with symptomatic and asymptomatic disease were 4.6 +/- 0.3 and 2.7 +/- 0.1, respectively. The differences in percentage of stroma and epithelium, and the stromal-to-epithelial ratio in the prostate adenomas from men with symptomatic and asymptomatic BPH were statistically significant. Our study suggests that the histological composition of the prostate adenoma is related to the development of symptomatic BPH.

Aged↗
PubMed1992

The safety, efficacy and compliance of terazosin therapy for benign prostatic hyperplasia.

The primary objective of the present interim analysis of an open label study initiated in December 1988 is to provide further insight into the long-term safety, efficacy and compliance of terazosin, a long-acting selective alpha 1-blocker, for the treatment of symptomatic benign prostatic hyperplasia (BPH). A total of 45 normotensive patients with symptomatic BPH was enrolled into this study. The dose of terazosin was titrated to 5 mg. during a 1-month period provided adverse reactions and orthostatic hypotension were not observed. The subjects were maintained on 5 mg. terazosin throughout the 24-month followup. The peak and mean urinary flow rates, obstructive and irritative Boyarsky symptom scores, and systolic and diastolic blood pressures were evaluated at 2, 6, 12, 18 and 24 months after initiation of therapy. Of the 45 subjects 21 (47%) exhibited a durable clinical response with no significant adverse events during the 24-month followup. The obstructive and irritative symptom scores decreased by 63% and 35%, respectively, after 2 months of terazosin therapy. These improvements in obstructive and irritative symptom scores were maintained throughout the 2-year followup. The peak and mean urinary flow rates improved by 42% and 48%, respectively, after 2 months of terazosin therapy. The changes in mean urinary flow rate increased, whereas the changes in peak urinary flow rate decreased during followup. Of the patients 6 (13%) were withdrawn from the study due to an adverse event. Our study demonstrates the safety, efficacy and compliance of terazosin therapy for BPH during a 2-year followup.

Adrenergic alpha-Antagonists↗
PubMed1992

Terazosin in the treatment of benign prostatic hyperplasia: the United States experience.

The rationale for selective alpha 1 blockade in benign prostatic hyperplasia (BPH) is based upon the observations that the prostate adenoma contains between 20% and 40% smooth muscle and the contractile properties of prostatic smooth muscle are mediated by the alpha 1 adrenoceptor. Terazosin is a selective alpha 1 adrenoceptor antagonist that is currently under clinical investigation for the treatment of clinical BPH. The United States experience with this drug is reviewed in the present report. The outcome measures used to assess the efficacy of terazosin in BPH includes Boyarsky symptom scores and uroflowmetry. The total Boyarsky symptom score decreased 55% and the peak urinary flow increased 47% following terazosin therapy in the cumulative open-label and single-blind studies. Three hundred and thirteen subjects with clinical BPH were randomised into a phase III double-blind parallel-group 3-month placebo-controlled study of once-a-day administration of terazosin. The total Boyarsky symptom score decreased 43% and 21% in the 10 mg and placebo treatment groups, respectively. The peak urinary flow increased 37% and 12% in the 10 mg and placebo-treated groups, respectively. The adverse events associated with terazosin were relatively minor and reversible. The United States experience has unequivocally demonstrated the short-term safety and efficacy of terazosin therapy in BPH. Studies are currently under way to determine the long-term safety and efficacy associated with terazosin therapy in BPH.

Adrenergic alpha-Antagonists↗
PubMed1992

Basic epidemiologic and statistical methods in clinical research.

Various study designs and approaches to statistical analysis in clinical research have their own underlying rationales and limitations for interpretation. This information is presented in an intuitive and accessible manner, relying minimally on basic algebra. Epidemiologic concepts of study design and interpretation, bias and confounding, hypothesis testing, and sample size and power are explained. Statistical tests and their appropriate applications are discussed for mean comparisons (t tests and ANOVA), percentages (chi-square), survival analysis, and correlation and regression. Applicable nonparametric tests are also introduced.

Carcinoma, Transitional Cell↗
PubMed1992

Anatomic considerations of the penis and its lymphatic drainage.

A few clinical caveats relevant to penile neurovascular and lymphatic anatomy deserve special emphasis. First, it is clear from the work of Breza and others that the neurovascular anatomy of the penis differs from patient to patient, especially with regard to the arterial supply. It seems prudent to identify an accessory pudendal artery during pelvic lymphadenectomy and nerve-sparing prostatectomy in order to prevent a neurologically intact penis being left with an inadequate corporal blood supply. From an anatomic perspective, it appears that the sentinel lymph node biopsy might be useful in the management of superficial carcinoma of the prepuce or skin of the penis, as these areas drain to the superomedial zone of the superficial inguinal nodes, to which the sentinel node belongs. However, most tumors of the penis involve the glans. Thus, the sentinel node biopsy will not reliably predict nodal involvement for all clinical stage I lesions, as the lymphatics from the glans may bypass the superficial nodes to invade the pelvic nodes directly. Finally, it remains to be determined what impact, if any, the improved understanding of penile anatomy will have for the patient with carcinoma of the penis. The extent of dissection, both in partial penectomy and in nodal dissection, deserves careful consideration. Armed with a clearer understanding of the anatomy of the penis, the urologist can choose a plan of surgical treatment wisely.

Erectile Dysfunction↗
PubMed1991

The efficacy and safety of terazosin for the treatment of symptomatic BPH.

At least 16 clinical investigations have documented the effectiveness of alpha blockade for BPH. In the present review, four clinical studies evaluating the efficacy and safety of terazosin, a selective long-acting alpha 1 blocker, for symptomatic BPH are reviewed. The unique features of these clinical investigations are: the study designs established detailed inclusion and exclusion criteria, the outcome assessments were based upon quantitative outcome parameters, large cohorts of homogeneous patients were enrolled, and appropriate statistical methods were utilized. The dose of terazosin was titrated to maximal doses ranging between 5-20 mg. Only four of the 163 patients developed orthostatic hypotension. Overall, the peak and mean uroflow rates increased 50% and 46%, respectively (P less than 0.001). The cumulative improvement in the mean obstructive, irritative, and total symptom scores was 67%, 35%, and 54%, respectively (P less than 0.001). The present review of terazosin in males with symptomatic BPH supports the following conclusions: (1) the dose of terazosin can be safely titrated to 10 mg in normotensive and hypertensive patients with symptomatic BPH; (2) the adverse events associated with doses of terazosin up to 10 mg are relatively mild and reversible; and (3) the improvements in the outcome parameters (symptom scores and urinary flow rates) are clinically and statistically significant. Although the ultimate role of terazosin for symptomatic BPH will be determined by multi-center randomized placebo-controlled studies, the present review provides further evidence that selective alpha 1 blockers are effective and safe for the treatment of symptomatic BPH.

Adrenergic alpha-Antagonists↗
PubMed1991

The binding and functional properties of voltage dependent calcium channel receptors in pediatric normal and myelodysplastic bladders.

The present study was designed to compare the binding and functional properties of calcium channel receptors in normal and myelodysplastic bladders. Normal bladders were obtained from children with vesicoureteral reflux undergoing ureteral reimplantation. Myelodysplastic bladder specimens were obtained from patients undergoing bladder augmentation. The functional studies included agonist (calcium chloride) dose response experiments and the determination of apparent antagonist dissociation constants for various calcium channel antagonists. The receptor binding studies were performed using the ligand (+)-3H-PN200-110 (specific activity 86.6 Ci./mmol.). The mean maximal response of myelodysplastic bladders to calcium ions was 31% less than normal bladders (p greater than 0.05). The mean EC50 for calcium mediated isometric tension and the mean -log antagonist dissociation constant values of nifedipine, diltiazem and verapamil were similar in normal and myelodysplastic bladders. The radioligand receptor binding studies demonstrated that the equilibrium dissociation constant of (+)-3H-PN200-110 in myelodysplastic bladders was 4-fold greater than in normal bladders. The density of dihydropyridine binding sites in myelodysplastic and normal bladders was similar. Our study demonstrated that the pathophysiology of the poorly compliant hyperreflexic bladder is not related to up regulation of dihydropyridine calcium channel receptors or alterations in the response of detrusor muscle to calcium ions. The relative abundance of calcium channel receptors in the normal and myelodysplastic bladders, and the regulation of detrusor contraction by calcium ions suggest that calcium channel receptors have a meaningful role in detrusor function.

Binding Sites↗
PubMed1991

Bladder wall abnormalities in myelodysplastic bladders: a computer assisted morphometric analysis.

Myelodysplasia represents the most common cause of neurogenic bladder dysfunction in children. The specific histological features associated with myelodysplastic bladders have not been previously characterized. Our objective was to study the relationship between smooth muscle and connective tissue in control and myelodysplastic bladders using classical morphometric analysis with the assistance of an automated image analysis system. Gross histological analysis of the bladder specimens of normal stillborn fetuses showed organized muscle bundles embedded in a small amount of connective tissue. The bladder specimens of myelomeningocele stillborn fetuses showed a marked paucity of muscle bundles as well as a significantly diminished size of the muscle bundles. The myelomeningocele bladder specimens obtained from patients undergoing autopsy and those undergoing augmentation cystoplasty revealed significant interfascicular and pericellular infiltration of the smooth muscle by dense connective tissue. Quantitative morphometric analysis showed that the myelomeningocele stillborn fetuses have a significant increase in the volumetric content of connective tissue compared to control stillborn fetuses. The bladders of myelomeningocele patients who underwent autopsy or augmentation cystoplasty had a 3-fold increase in connective tissue when compared to normal controls. These findings reveal that structural changes in the histological components of the myelodysplastic bladder can be demonstrated not only in patients of varying ages undergoing autopsy or augmentation cystoplasty but also in the developing fetus. These findings enhance our understanding of the relationship of connective tissue proliferation to smooth muscle in the myelodysplastic bladder. We discuss the relationship of these findings to pathological detrusor morphology and detrusor dysfunction.

Child↗
PubMed1991

Comparison of alpha 1 adrenoceptors in the prostate capsule of men with symptomatic and asymptomatic benign prostatic hyperplasia.

The objective of this study was to compare the binding and functional properties of alpha 1 adrenoceptors in prostate capsules obtained from men with symptomatic and asymptomatic benign prostatic hyperplasia (BPH) undergoing simple retropubic prostatectomy and cystoprostatectomy respectively. Saturation experiments using 125I-Heat demonstrated that the density and binding affinity of alpha 1 adrenoceptors in the prostate capsules obtained from men with symptomatic and asymptomatic BPH were similar. Non-cumulative dose response experiments using phenylephrine demonstrated that the magnitude of the contractile response to phenylephrine was 4-fold greater in the prostate capsules from men with symptomatic BPH than from those with asymptomatic BPH. The EC50 of phenylephrine in the prostate capsules of men with symptomatic and asymptomatic BPH was similar. A correlation between alpha 1 adrenoceptor density and phenylephrine Emax was not observed, implying that either alpha 1 adrenoceptors are not localised exclusively to the prostate smooth muscle or that spare alpha 1 adrenoceptors exist. This study suggests that the neuropharmacological properties of the prostate capsule may play a significant role in the development of infravesical obstruction in the ageing male population.

Dose-Response Relationship, Drug↗