Faculty Bibliography

The American Association of Pediatric Urology initiated a Pediatric Urological Manpower Study in 1991. A 24-question survey was distributed to the members of the Society of Pediatric Urology and the American Academy of Pediatrics Section on Urology. The objective of the questionnaire was to obtain information related to fellowship training, regional distribution of pediatric urologists, and practice patterns and attitudes. As of December 31, 1991, 345 questionnaires were distributed, and 244 (71%) were completed and entered into a computer program. The number of pediatric urologists was evenly distributed among 3 consecutive 10-year age groups ranging between age 31 and 60 years. The majority (78%) of urologists practicing 100% pediatric urology were between 31 and 50 years old. Approximately 60% of the responders practiced full-time (100%) pediatric urology and 59% of this group were university based. Pediatric urologists were practicing in 42 states and the District of Columbia. Based upon the United States Department of Commerce 1990 census, the number of pediatric urologists practicing in each state in relation to the total pediatric (less than 18 years old) populations was determined. The number of pediatric urology fellowships has steadily increased since the mid 1950s. Currently, more than 10 fellows are trained annually. Of the 172 responders practicing at least 75% pediatric urology 24% indicated that practice was 'too busy' and 53% indicated that practice was 'just right.' Approximately 44% of the responders were considering adding a partner: 21 indicated that they planned to add a partner in 1 year, 65 in 5 years and 10 in 10 years. Hopefully, the Pediatric Urological Manpower Study will serve as a useful instrument for assessing the pediatric practice patterns and training needs in the United States, thereby enhancing the quality of urological care for children

The objective of the present study was to determine the density and functional properties of alpha 1 adrenoceptors in different regions of the human prostate. Binding and functional studies were performed on eight different topographical regions of the prostate. The contractile response (gm. force/mm.2 cross-sectional area [CSA]) was determined at varying concentrations of phenylephrine, and saturation experiments were performed at seven different concentrations of 125I-Heat. The maximal response to phenylephrine (Emax) ranged from 0.067 to 0.272 gm. force/mm.2 The CSA and the EC50 ranged from 25 to 41 microM. The differences between EC50 and Emax were not significantly different among the eight prostatic regions. A 1.8-fold difference between the Emax for peripheral and central regions of the prostate was statistically significant (p = 0.04). The equilibrium dissociation constant (Kd) of 125I-Heat and the receptor density Bmax were determined from the Scatchard plots. The mean Kd and Bmax ranged from 0.15 to 0.26 nM. and 0.30 to 0.72 fmol. per mg. wet weight, respectively. There were no statistically significant differences between mean Kd and mean Bmax for the eight prostatic regions. The 1.7-fold difference between central and peripheral mean Bmax was not statistically significant (p = 0.07). A direct relationship was not observed between phenylephrine mean Emax and mean Bmax. The present study demonstrates regional differences of the binding and functional properties of prostatic alpha 1 adrenoceptors in the human prostate. These regional differences must be taken into account when investigating the pharmacologic and physiologic properties of the prostate

High affinity alpha 1 adrenoceptors have been characterized in the human prostate. The tension of prostatic smooth muscle is mediated by the alpha 1 adrenoceptor. The present study represents the first characterization of human alpha 1 adrenoceptor subtypes using radioligand receptor binding techniques. Binding studies were performed on tissue homogenates obtained from the human prostate. Competitive inhibition studies were performed in the presence of an 80 pM. 125I-Heat and 16 concentrations of unlabelled 5-methylurapidil (5 MU) or WB-4101 (10(-10) M. to 10(-5) M.). Saturation experiments were also performed with and without chloroethylclonidine (CEC, 10(-5) M.), a compound that selectively inactivates the alpha 1B subtype. The individual displacement plots for WB-4101 and 5-MU in the human prostate were consistently best fit by a 2 binding site model. WB-4101 and 5-MU exhibited a 594- and 186-fold higher affinity for the prostatic alpha 1A binding site relative to the alpha 1B binding site. The ratios of prostatic alpha 1A/alpha 1B binding sites discriminated by WB-4101 and 5-MU were 1.8 and 1.6, respectively. CEC inactivated 44% of the prostatic alpha 1 binding sites. The binding studies suggest that the dominant alpha 1 subtype in the human prostate is the alpha 1A. We are characterizing the functional properties of the alpha 1 subtypes in the human prostate

We have characterized the alpha 1 adrenoceptor subtypes in the human prostate using radioligand receptor binding studies. The objective of the present study was to determine the alpha 1 subtype mediating the tension of prostatic smooth muscle. Fresh human tissue was obtained from 9 males between 50 and 80 years of age undergoing prostatectomy for BPH. The incubation of prostatic tissue with the irreversible antagonist chlorethyclonidine (CEC) resulted in an 80% reduction of the maximal contractile response produced by phenylephrine. However, the alpha 1A-selective antagonists WB-4101 and 5-methylurapidil (5-MU) competitively inhibited the contractile response induced by phenylephrine, with KB = 2.64 and 4.46 nM, respectively, consistent with their affinity at the alpha 1A receptor subtype. The pharmacological profile of the alpha 1-receptor-mediated contractile response of prostate smooth muscle is inconsistent with their classification as either an alpha 1A or alpha 1B subtype. Alternatively, when compared with the properties of the cloned alpha 1 receptors, our results suggest that the alpha 1 receptors involved in the contraction of prostate smooth muscle have some pharmacological properties similar to those encoded by the gene of the bovine alpha 1C receptor subtype. The findings of the present study suggest that efforts should be made to confirm the identity of the alpha 1-receptor subtype expressed by prostate smooth muscle, in order to develop subtype-selective alpha 1 antagonists, and to evaluate their safety and efficacy in benign prostatic hyperplasia (BPH)

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

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

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

There has been limited histological study of the obstructed ureteropelvic junction in patients less than 1 year old. We present our prospective studies on the histomorphometry of the ureteropelvic junction complexes of 35 infants, of whom 23 underwent pyeloplasty for obstruction and 12 were age matched autopsy normals. Qualitatively, the major abnormalities of the pelvic microanatomy in the hydronephrotic obstructed kidneys included a lamina muscularis that was significantly thicker than normal and the presence of collagen fibers between muscle fascicles. Additionally, variable amounts of elastin were present in the adventitia and lamina muscularis. At the ureteropelvic junction the abnormalities were an increase in the number of inner longitudinal muscle bundles, collagen between muscle bundles (p less than 0.016) and elastin in the adventitia. Quantitatively, for the pelvis the lamina muscularis was significantly thicker in 18 obstructed kidneys compared to 7 controls (1,075 +/- 79 mu. versus 420 +/- 63 mu., mean +/- standard error of mean, p less than 0.001). The percentage area density of smooth muscle in the obstructed versus normals was increased (45.1% versus 35.2%, p less than 0.039). The percentage area density of collagen in the obstructed specimens versus normal showed an upward trend (38.6% versus 27.6%), which was not significant. In conclusion, the obstructed ureteropelvic junction complexes of kidneys in asymptomatic infants show significant qualitative and quantitative differences from normal

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