Diamniotic twin gestation discordant for renal dysplasia and oligohydramnios.

Severe oligohydramnios and renal dysplasia were detected in one of diamniotic, monochorionic twins at 19 weeks' gestation. At birth (37 weeks), the affected twin had only minimal extrarenal Potter's features and mild pulmonary hypoplasia, despite severe renal dysplasia due to posterior urethral valves. The effects of virtual absence of amniotic fluid during the latter half of gestation from bilateral renal dysplasia were ameliorated by the presence of a normal co-twin and its normal amniotic fluid levels, even though the affected twin did not share the same amniotic fluid.

Neuroanatomical changes in the rat bladder after bladder outlet obstruction.

OBJECTIVE: To investigate the histological changes in bladder innervation in response to partial bladder outlet obstruction in a rat model. MATERIALS AND METHODS: Forty-eight adult female rats had their bladder outlet partially obstructed by ligating the proximal urethra over a 20 G angiocatheter; 18 shamoperated rats served as controls. Animals were killed after 1, 2 and 4 weeks, and their bladders evaluated using computerized morphometry. Immunohistochemical staining for neuronal protein gene-product 9.5 (PGP, a general neuronal marker) and enzyme histochemical staining of acetylcholinesterase, adrenergic fibres and nitric oxide synthase were performed. RESULTS: Bladder wall changes after obstruction consisted of a six- to sevenfold increase in bladder volume and weight. Smooth muscle hypertrophy was evident equally at all sample times. Cystometry showed functional alterations in bladder capacity and voided pressures; obstructed animals had markedly increased bladder capacities and higher voiding pressures (obstructed, 80-100 cmH2O; normal, 30-40 cmH2O). Neuronal changes in the obstructed bladder were most dramatic within the cholinergic and adrenergic neurotransmitter systems within and surrounding the smooth muscle bundles, where there was less staining than in control animals. PGP immunoreactivity increased slightly. The L-arginine-nitric oxide pathway appeared unperturbed after obstruction. CONCLUSIONS: These histological findings suggest that neuropathic changes in the bladder after outlet obstruction, including detrusor instability, are mainly the result of anatomical perturbations in the cholinergic and adrenergic pathways.

The effect of testosterone on androgen receptors and human penile growth.

PURPOSE: Recent rat studies suggest that early exposure to exogenous testosterone accelerates the loss of androgen receptors and compromises eventual penile length. In humans we hypothesize that down regulation of the androgen receptor is not the mechanism that stops penile growth. To test this hypothesis we investigated the effects of androgen deprivation and supplementation on the developing human penis. MATERIALS AND METHODS: A total of 15 normal human fetal penises at 7 to 19 weeks of gestation (mean plus or minus standard deviation 12 +/- 4.5) was divided in half sagittally. Specimens were grafted beneath the renal capsule of male athymic nude mice or nude rats. Three groups of host animals were prepared, including 10 with no testosterone that were castrated at grafting, 15 with testosterone and 5 with super testosterone in which 50 mg. testosterone propionate pellets were implanted subcutaneously at grafting. Each fetal penile specimen was its own control, since half was implanted into an intact animal and the other into a castrated or super testosterone host. Six weeks after grafting the specimens were analyzed for gross size (length), histology and expression of androgen receptors. RESULTS: All human fetal penile specimens grew from the nadir size and appeared as white exophytic growths on the surface of the host kidneys. Normal grafts were larger than castrate specimens (mean 6.9 +/- 2.1 versus 3.9 +/- 2.1 mm., p = 0.014). Mean length of the super testosterone specimens (7.3 +/- 2.3 mm.) was not significantly greater than that of normal specimens (p = 0.797). Histological analysis revealed that all specimens were composed of viable penile tissue. Cellular density of the castrate penises was approximately 2 times greater than that of the normal and super testosterone specimens (40.6 +/- 5.9 versus 25.1 +/- 2.8 cells per cm.2, p > 0.001), as calculated on enlarged micrographs. Supraphysiological doses of testosterone did not change the histology compared to controls. Immunohistochemical localization revealed androgen receptors expressed throughout the corporeal bodies, surrounding stroma and penile skin with intracellular localization to nucleus. The mean proportion of cells expressing androgen receptors was higher in the castrate (29.4 +/- 5.2 cells per cm.2) than in the normal (24.0 +/- 3.7) and super testosterone (24.7 +/- 4.5) grafts (p = 0.005). However, in regard to growth there was no change in the proportion of androgen receptor positive cells among the groups. CONCLUSIONS: Testosterone influences penile growth, possibly as a result of extracellular stromal expansion. The number of androgen receptor positive cells in the human fetal penis did not change among the castrate, normal and super testosterone hosts. These experiments support the hypothesis that penile growth cessation is mediated by mechanisms other than down regulation of the androgen receptor. Furthermore, these data support the hypothesis that early administration of androgen to prepubertal male individuals does not result in a shorter phallus in adulthood.

Growth factors in bladder wound healing.

INTRODUCTION: Surgical and traumatic injuries to the bladder initiate a complex series of biological processes that result in wound healing. This process involves cellular proliferation, migration and differentiation; removal of damaged tissue; and production of extracellular matrix all of which may be controlled by growth factors. In skin, keratinocyte growth factor (KGF) is induced following incisional injury. We hypothesize that in bladder wound healing KGF and other growth factors are induced to modulate tissue repair. METHODS: We have created a model of surgical bladder injury in the rodent. At 12, 24 and 48 hrs and 5 and 7 days after injury, the bladder was bisected and total RNA extracted from the anterior or wounded half and posterior or non-wounded half. Histological analysis of the bladder wound was performed with Mason's Trichrome and immunohistochemistry against smooth muscle alpha actin. RNase protection assays were performed to examine the expression of KGF, transforming growth factor (TGF)alpha and TGF beta 2 and 3 as well as the receptors for KGF and epidermal growth factor (EGF). Lastly, the effects of the exogenous administration of KGF on the bladder was tested on neonatal mice by daily injections of 5 micrograms KGF per gram body weight for 5 days. RESULTS: At 12 hours after injury KGF mRNA expression in the anterior wounded bladder half and posterior non-wounded bladder half was 8 and 6 times higher respectively, compared to unoperated control bladders. A similar response was seen for TGF alpha, where the 12 hour mRNA expression was 4.5 times higher in the anterior wounded bladder half and 3.5 times higher in the posterior non-wounded bladder half compared to unoperated control bladders. The nadir mRNA expression for both KGF and TGF alpha occurred at 7 days after bladder injury and was the same as in unoperated control bladders. EGFR mRNA expression was approximately 2 times higher in both the anterior wounded and posterior non-wounded bladder halves compared to the nadir levels which occurred at 24 hours after injury. TGF beta 2 and beta 3 mRNA levels did not significantly change in either the anterior wounded or posterior non-wounded bladder halves. Exogenous KGF stimulation resulted in a marked urothelial proliferation when compared to age matched control animals. CONCLUSION: During the early phases of bladder wound healing (12-24 hours post injury), mRNA for KGF and TGF alpha increased, whereas TGF beta 2 and beta 3 and the KGFR and EGFR remain unchanged. Additionally, exogenous KGF has a direct effect on urothelial proliferation. KGF and TGF alpha warrant further study as potential mediators of bladder wound healing.

Vesicourethral function in mice with genetic disruption of neuronal nitric oxide synthase.

PURPOSE: Nitric oxide is thought to play an important role in neuromodulation of the lower urinary tract. We therefore studied the lower urinary tract function of mice in whom the gene encoding for neuronal nitric oxide synthase had been disrupted (nNOS knockout). METHODS: Female mice, both control and nNOS knockout, underwent voiding, urodynamic and muscle strip testing as well as histologic studies. Neuronal mechanisms assessed histologically included nitric oxide, cholinergic, adrenergic, vasoactive intestinal polypeptide (VIP), and nonspecific neuronal protein (protein gene product 9.5 [PGP 9.5]). RESULTS: No differences in voiding were observed between normals and nNOS knockout mice. On urodynamic studies, bladder capacity was higher in the experimental than in the normal animals (25.3 +/- 11.8 vs. 17.4 +/- 5.6 ml./gm. x 1000, p < 0.05) as was the maximal bladder pressure at leakage (70.1 +/- 15.9 vs. 59.5 +/- 12.8 cm. H20, p < 0.05). After treatment with L-NAME or L-Arginine, there was no significant difference between the groups. Muscle bath studies showed no differences in bladder contractility or relaxation after chemical and electrical stimulation. Histologic studies confirmed virtually no nNOS or nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase in the nNOS knockout mice, but no difference in the total number of nerves (PGP 9.5) and of cholinergic, adrenergic or VIP-staining nerves was detected between groups. CONCLUSIONS: Despite disruption of the main pathway for synthesis of neuronal nitric oxide, nNOS knockout mice voided normally, demonstrate normal muscle bath responses, and have normal numbers of all nerves studied (except those staining for NO). Further studies are underway to elucidate the compensatory mechanisms in these animals.

The role of type IV collagenases in rat bladder development and obstruction.

The role of type IV collagenases during rat bladder development and in response to partial bladder outlet obstruction was evaluated. Gelatinase gel zymography was performed on developing rat bladders (gestation d 16 and 19, at birth, 5, 10, 15, 20, 30, and 75 d postnatally), after partial obstruction of the bladder outlet in young adults and after separation of the epithelium from the mesenchyme in young adults. Bladder function was assessed by cystometry in obstructed animals. During development, the 72-kD type-IV collagenase [matrix metalloproteinase (MMP)-2, both latent and activated] was maximally expressed in the fetal period and decreased with age; whereas the 92-kD gelatinase (MMP-9) was not expressed in developing or adult bladders. MMP-2 was localized to the bladder mesenchyme and was undetectable in isolated epithelium. In 46 obstructed rats, there was an 8-fold increase in bladder volume and weight along with smooth muscle hypertrophy (mean smooth muscle cell diameter 7.09 +/- 0.11 microns versus 4.65 +/- 0.05 microns in normal animals, p < 0.001). Obstructed rats had increased quantities of latent and activated MMP-2 and MMP-9 compared with sham-operated and normal controls. These findings suggest that expression and activation of type IV collagenases (MMP-2 and 9) are developmentally regulated and play a role in bladder remodeling during developmental morphogenesis and after partial outlet obstruction.

Clean intermittent catheterization in boys using the LoFric catheter.

PURPOSE: We compared a recently developed hydrophilic catheter to the standard polyethylene catheter in regard to hematuria, infection and patient satisfaction. MATERIALS AND METHODS: A hydrophilic LoFric or standard Mentor catheter was assigned at random to 17 and 16 boys, respectively, who were skilled in intermittent self-catheterization. They were evaluated by weekly urinalysis and a questionnaire. RESULTS: Significantly fewer episodes of microscopic hematuria occurred in the LoFric than Mentor catheter group (9 episodes in 6 subjects versus 19 episodes in 11, p < 0.05). There were also fewer episodes of bacteriuria in the LoFric group but the difference was not statistically significant. Mean scores plus or minus standard deviation on a visual analogue scale with 0 equal to most and 10 equal to least favorable were LoFric 3.3 +/- 2.8 versus Mentor 4.9 +/- 2.7 for catheter convenience and 2.7 +/- 2.4 versus 4.2 +/- 2.6 for insertion comfort, significantly favoring the LoFric group (p < 0.05 for both). Of the 16 LoFric subjects 13 preferred to continue its use, particularly those with a history of urethral trauma or sphincteric spasm. CONCLUSIONS: In boys the LoFric catheter appears to cause less trauma. Although it is not reusable and is more expensive than the standard catheter, satisfaction is higher with the LoFric device and for select patients it has significant advantages.

Therapeutic laparoscopy for the nonpalpable testicle.

Laparoscopy is playing an increasingly important role in the management of boys with nonpalpable testes. We describe our technique of laparoscopy and laparoscopically assisted orchidopexy. Our early results in 24 patients with nonpalpable intraabdominal testes have encouraged us to recommend this option as the procedure of choice.

Regeneration of bladder urothelium, smooth muscle, blood vessels and nerves into an acellular tissue matrix.

PURPOSE: To study the cellular events occurring during bladder development and regeneration we developed an in vivo model of bladder augmentation with an acellular tissue graft. We propose that the extracellular matrix orchestrates the regenerative capacity of host bladder cells (urothelium, smooth muscle, blood vessels and nerve cells) after bladder augmentation with acellular tissue matrix. MATERIALS AND METHODS: A total of 40 adult rats underwent partial cystectomy and augmentation with a patch of extracellular matrix representing the full thickness of rat gastric or bladder tissue. Sections were examined histologically to assess urothelial, smooth muscle and neuronal invasion of the graft. RESULTS: A total of 32 rats was evaluated 1 day to 26 weeks after grafting. Epithelialization occurred by day 4, accompanied by granulocytic infiltration. Smooth muscle regenerated 2 weeks after grafting in juxtaposition to epithelial surfaces and it matured into normal sized bundles by 26 weeks. Neovascularity was noted 2 weeks postoperatively. Neural elements formed around developing smooth muscle bundles as early as 4 weeks after grafting. CONCLUSIONS: We demonstrated the regeneration of urothelium, smooth muscle, blood vessels and nerves within a full thickness grafted acellular tissue matrix scaffold in the rat. The spatial orientation of these elements suggests that mesenchymal-epithelial interactions occur during phenotypic regeneration of the bladder. Urothelium appears to regulate the early forming smooth muscle. This in vivo model provides a suitable method to study cellular events during regeneration.

The effect of prepubertal androgen exposure on adult penile length.

PURPOSE: Recent studies in the rat suggest that early exposure to exogenous testosterone accelerates the loss of androgen receptors and compromises eventual penile length. To determine whether this is true in men we measured adult penile length of patients treated in childhood for sexual precocity. MATERIALS AND METHODS: We examined 21 men with sexual precocity due to true precocious puberty (12) or congenital adrenal hyperplasia (9) who had been followed at our institution since childhood. Penile lengths were compared with data from normal men. RESULTS: Mean stretched penile length plus or minus standard deviation was 12.7 +/- 2.6 cm. in all patients, 12.1 +/- 2.6 cm. in those with true precocious puberty and 13.6 +/- 1.6 cm. in those with congenital adrenal hyperplasia. These lengths were not significantly different from those of normal men (12.4 +/- 2.7 cm.). CONCLUSIONS: In contrast to findings in rats, exposure to endogenous testosterone during gestation and/or childhood does not reduce adult penile length in men. Thus, the use of testosterone to treat childhood genitourinary anomalies would likely not compromise mature penile size.

Growth factors and receptors in bladder development and obstruction.

During fetal and neonatal development and experimental obstruction, the bladder wall undergoes changes in both the amount and composition of the urothelium, extracellular matrix, and smooth muscle. We hypothesize that cell-cell signaling among the different layers of the bladder wall mediates these changes. Growth factors likely to be involved in this process are keratinocyte growth factor (KGF) and transforming growth factor (TGF)-alpha, -beta 2, and -beta 3. Whole rodent bladders were analyzed by RNase protection assays for KGF, KGF receptor, TGF alpha, epidermal growth factor receptor, and TGF beta 2 and -beta 3 transcripts at Fetal Day 14 (before smooth muscle differentiation) and Fetal Day 18 (after smooth muscle differentiation), at birth, and 60 days postnatal. Growth factor transcripts were also analyzed in partially obstructed rodent bladders and in sham-operated animals. TGF beta 2 and -beta 3 mRNA expression decreased as a function of gestational age, whereas TGF alpha mRNA increased. KGF mRNA was low before smooth muscle differentiation at 14 days' gestation, then increased. The mRNA of receptors for KGF and EGF remained essentially unchanged throughout bladder development. In bladders subjected to partial urethral outlet obstruction, there was a 2-fold increase in mRNA for TGF beta 2, a 5-fold increase in TGF beta 3, and a 10-fold increase TGF alpha mRNA. In contrast, there was no change in transcripts for either KGF or receptors for KGF and epidermal growth factor. Immunohistochemical localization of the protein for these growth factors showed selective localization to the epithelium and/or smooth muscle for TGF beta 2 and -beta 3, whereas TGF alpha and the epidermal growth factor receptor localized throughout the bladder wall. In conclusion, growth factor mRNA expression is modulated in bladder development and obstruction, which implies a possible mechanistic role of growth factors for the observed changes in the bladder wall and extracellular matrix.

The prune-belly syndrome: current insights.

The prune-belly syndrome comprises a constellation of well-established physical findings, yet the cause and management remain controversial. This review focuses on the current understanding of its pathogenesis and characterizes the fetal and neonatal diagnosis and management. Other associated anomalies are discussed to understand better the factors affecting treatment and prognosis as these patients grow into childhood and beyond.

Hernia after dorsal incision into lumbar region: a case report and review of pathogenesis and treatment.

Because of few associated complications and rapid recovery, dorsal incision into lumbar region has experienced a resurgence in popularity for the treatment of a variety of renal and upper ureteral disorders. We report a case of pyelolithotomy via the dorsal approach in which a symptomatic lumbar incisional hernia subsequently developed, which to our knowledge is a previously unreported complication of this approach. Reconstruction of this lumbar hernia defect necessitated the application of synthetic mesh graft sandwiched by mobilized muscle flaps. The entire repair was then sutured inferiorly to the iliac crest using drill holes. Outcome was durable and successful. The pathogenesis and treatment of this complication are discussed.

Effect of terfenadine on urination.

Anticholinergic side effects of commonly used antihistamines are known to aggravate voiding difficulties in older men with benign prostatic hypertrophy. Newer antihistamines, such as terfenadine (Seldane), with less anticholinergic side effects may not have such an effect on voiding. We performed a randomized, double-blind, placebo-controlled, crossover study in eight normal male volunteers (phase I) and in 11 patients with documented benign prostatic hypertrophy (phase II) to study the effect of terfenadine on voiding. Subjects received either 60 mg of terfenadine or an identical placebo twice daily for 1 week each. After a 1-week washout period, they were crossed over to receive the other drug. Evaluation took place on days 0, 7, 14, and 21. Prick skin testing was performed with serial threefold dilutions of histamine to assess efficacy and degree of compliance. Uroflowmetry and urinary symptom assessment were also done. In phase I, after 1 week of terfenadine, mean skin test suppression was 83.8% compared with -0.5% with placebo (P < .01). Urinary peak flow increased 10.4% on terfenadine and 9.7% on placebo (P = NS). In phase II, the mean prick skin test suppression was 87.8% compared with 12.0% for placebo (P < .002). Urinary peak flow was decreased 0.1% from baseline on terfenadine and increased by 18.7% for placebo (P = NS). None of the subjects noted alterations in voiding symptom scores. We conclude that the commonly recommended dose of terfenadine does not significantly alter voiding characteristics in normal men or in patients with documented benign prostatic hypertrophy.

Carney's complex in a patient with hormone-producing Sertoli cell tumor of the testicle.

Carney's complex is an unusual disorder consisting of a variety of endocrinological and urological manifestations. The characteristic gonadal and adrenal features of Carney's complex should become familiar to urologists. A patient was evaluated for obesity, cushingoid features, hyperlipidemia, glucose intolerance, coronary artery disease, a left adrenal mass, bilateral testicular masses and cardiac myxomas. Pathological evaluation revealed the testicular tumors to be of Sertoli cell origin, the adrenal mass to be an adrenocortical adenoma and intracardiac lesions consistent with myxomas. The features of Carney's complex are discussed.

Ventral preputial onlay island flap and proximal flip-flap technique for the repair of epispadias: a case report.

Use of the ventral preputial island flap technique for repair of epispadias has yielded satisfying functional and cosmetic results. We report a modification of this technique in a patient with proximal penile epispadias without exstrophy. We used the Duckett modification of the onlay island flap using ventral preputial skin and coupled it with a proximal flip-flap of perimeatal skin without division of the urethral plate. This achieved an excellent result.

Renal artery stenosis after renal transplantation: the impact of the hypogastric artery anastomosis.

A review of 402 renal allotransplants performed during a 5-year period revealed 25 cases of transplant renal artery stenosis in 377 evaluable patients. To our knowledge this is the first large study of this transplant complication in which all patients received cyclosporine immunotherapy. The incidence of transplant renal artery stenosis was 6.6%. The mean internal from transplantation to onset of transplant renal artery stenosis was 11 months. No significant differences in atherosclerotic risk factors were detected between the groups with and without transplant renal artery stenosis. The incidence of acute allograft rejection was not increased in the stenosis group. There was no difference in the incidence of transplant renal artery stenosis following end-to-end (hypogastric artery) or end-to-side (common or external iliac artery) arterial anastomoses. Among patients having end-to-end hypogastric artery anastomoses the incidence of transplant renal artery stenosis was significantly greater (p < 0.01) when endarterectomy was required to render the hypogastric artery suitable for use. Percutaneous transluminal angioplasty was performed in 20 patients and open repair was performed in 18. After percutaneous transluminal angioplasty of hypogastric artery anastomoses, more additional procedures were required and there was a higher allograft loss rate when compared to percutaneous transluminal angioplasty of the external iliac artery. These data suggest that treatment of transplant renal artery stenosis in patients with end-to-end hypogastric artery anastomosis is more difficult and results in a higher morbidity rate than treatment in the external iliac artery group.

Endopyelotomy associated ureteral necrosis: complete ureteral replacement using the Boari flap.

A case of an adolescent who sustained necrosis of the entire ureter after attempted endopyelotomy for congenital ureteropelvic junction obstruction is presented. Successful reconstruction of a neoureter was performed easily with the Boari bladder flap coupled with nephropexy and a psoas hitch. Although repair of upper ureteral injuries with the Boari flap has been described in the literature, to our knowledge its use in the pediatric population has not. Our case exemplifies how the Boari flap repair is particularly suitable in children for bridging significant segments of injured ureters, not just the lower third.

Primary carcinoid tumor of the testicle: a case report and management schema.

A case of primary testicular carcinoid is presented in which extensive testing for peptide hormones was done. None was found suggesting that such tumors may be nonfunctional. A systematic approach to the evaluation and treatment of testicular carcinoid is presented.