Faculty Bibliography

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

Anti-desmin and anti-actin are commercially available antibodies that bind to smooth muscle. The present study was designed to compare the staining properties of anti-desmin and anti-actin in the human prostate in order to determine the optimal antibody for quantifying the smooth muscle content of the human prostate. Nineteen male subjects with symptomatic BPH underwent needle biopsy of the prostate. Double-immunoenzymatic staining was performed with peroxidase-anti-peroxidase (PAP) and alkaline phosphatase-anti-alkaline phosphatase (APAAP) techniques. Rabbit anti-desmin:mouse anti-human prostatic acid phosphatase and mouse anti-actin:rabbit anti-human prostatic acid phosphatase were utilized. Computer assisted color image analysis was performed using the Bioquant image analysis system. The percent area density of stroma and epithelium was independent of the antibodies used. The percent area density of smooth muscle in the anti-actin stained tissue sections was twofold greater than the anti-desmin stained tissue sections. A direct relationship was observed for the area density of smooth muscle (r = 0.71; P = 0.0006) and the area density of connective tissue (r = 0.82; P less than 0.001) determined from anti-desmin and anti-actin stained tissue sections. Anti-actin represents the optimal antibody for quantifying the area density of prostate smooth muscle. The reproducibility of the immunoenzymatic staining technique is inferred from the direct relationship observed for area density of epithelium between the different staining techniques

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

The objective of the present study was to characterize the alpha 1-adrenoceptor binding properties of terazosin and its enantiomers in human prostate and canine brain. Human prostate adenomas were obtained from 7 males undergoing prostatectomy for symptomatic BPH and canine cerebral cortices were obtained from 6 male beagles. Competitive displacement experiments were carried out on these tissue homogenates in the presence of a constant concentration ([180 pM]) of 125I-Heat and varying concentrations of unlabelled terazosin and its enantiomers. The Ki of terazosin and its enantiomers were determined from these binding studies. The mean Ki of rac-terazosin, R(+)-terazosin, and S(-)-terazosin in human prostate was 3.6 nM, 3.8 nM, and 2.8 nM, respectively. The differences between these mean Ki values were not statistically significant. The mean Ki of rac-terazosin, R(+)-terazosin, and S(-)-terazosin in canine brain were 6.7 nM, 8.4 nM, and 5.6 nM, respectively. The differences between these mean Ki values were not significantly different. The mean Ki of terazosin and its enantiomers were consistently lower in the human prostate compared to canine brain (P less than 0.05). The present study does not provide any evidence suggesting differential effects of terazosin enantiomers on the human prostate. The twofold difference between the Ki values in the prostate and brain suggests that different subtypes of the alpha 1-receptor might be present in these tissues

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

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

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

We describe seven female patients with deficient abdominal wall musculature and urinary tract and genital anomalies that represent the female equivalent of the prune belly syndrome. Urethral atresia, uterine duplication, and anorectal anomalies occurred frequently. The perinatal mortality rate was high; of the four surviving patients, renal failure developed in two and renal transplantation was required. The analysis of these cases suggests that urethral obstruction is an important factor contributing to the development of the prune belly syndrome in females

Percutaneous endopyelotomy has been shown to be successful in treating ureteropelvic junction obstruction in adults. Little data have been published regarding this procedure in children. We describe 4 patients 6.5 weeks to 5.5 years old who underwent percutaneous endopyelotomy to treat ureteropelvic junction obstruction following failed open dismembered pyeloplasty. Preoperative obstruction was demonstrated by a nephrostogram, diuretic renogram and/or ultrasonography. Percutaneous endopyelotomy was successful in relieving the obstruction in all 4 patients, although 2 required secondary endoscopic procedures. One patient had persistent obstruction 40 days after endopyelotomy at the ureteropelvic junction and, subsequently, required percutaneous resection of a persistent flap of obstructing tissue. In another patient a ureterovesical stricture was noted at the time of stent removal, which was treated by endoscopic incision. All patients have been followed from 1.5 to 3 years postoperatively. Followup diuretic renograms, ultrasound and/or excretory urography demonstrated a patent ureteropelvic junction in all patients and all have remained asymptomatic. Endopyelotomy appears to be safe and effective in treating secondary ureteropelvic junction obstruction in children.

Conjoined twins occur once in 50,000 births. Only 6% of conjoined twins are of the ischiopagus type in which the twins are joined symmetrically at the pelvis and fusion begins at the level of the common umbilicus. The longitudinal axis extends in a straight line in opposite directions and the genitourinary and gastrointestinal tracts are shared. Tetrapus is a subtype in which all 4 lower extremities are present and oriented at right angles to the axis of the common trunk. Two sets of female ischiopagus tetrapus twins were born in 1977 and successfully separated at the St. Louis Children's Hospital in the following year. We describe the genitourinary and associated anomalies, surgical separation and long-term urological followup of these 2 sets of ischiopagus tetrapus twins