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Biomedical subjects

L S Baskin

Publications and source records attributed to L S Baskin.

At least 19 recordsLinked to original sources

The neuroanatomy of the human scrotum: surgical ramifications.

OBJECTIVE: To define the scrotal nerve origin and distribution with respect to surrounding structures in male human fetuses, by using neuronal-specific markers and three-dimensional (3D) imaging techniques, as the developmental neuroanatomy of the human scrotum has not been studied in detail and an explicit description of nerve derivation and distribution in the human scrotum is germane to genital reconstructive surgery. MATERIALS AND METHODS: Sixteen normal human fetal penile specimens at 17.5-38 weeks of gestation were studied. Specimens were fixed in formalin, embedded in paraffin wax, serially sectioned at 6 micro m and stained with the neuronal marker S-100. All of the specimens contained the whole penis and scrotum from glans to anal verge. The gestational age of the fetuses was determined by fetal heel-to-toe length. 3D-computer reconstruction of serial sections allowed a detailed analysis of the neuroanatomy of the fetal penis and scrotum. RESULTS: The nerves innervating the ventral side of the proximal penis and scrotum originated mainly from the perineal nerves arising from pudendal nerves. The nerves travelling along the ventral side of penis coalesced at the penoscrotal area to be directed into the interscrotal septum. At the penoscrotal junction, nerves on both sides of the ventral penis shifted to the interscrotal septum in a triangular fashion. The interscrotal septum was densely occupied by nerve fibres. Nerves were distributed horizontally to both hemiscrotal walls through this interscrotal septum. Both hemiscrota seem primarily to be innervated separately. CONCLUSION: The interscrotal septum has a dense innervation. Both hemiscrota were innervated mainly by horizontally distributed nerve fibres arising from the interscrotal septum. Any procedure violating the penoscrotal and interscrotal septal area may jeopardize scrotal innervation.

Dissection↗

Urethral seam formation and hypospadias.

Knowledge of the formation of the normal male urethra may elucidate the etiology of hypospadias. We describe urethral formation in the mouse, show the similarities and relevance to human urethral development, and introduce the concept of the epithelial seam formation and remodeling during urethral formation. Three mechanisms may account for epithelial seam formation: (1) epithelial-mesenchymal transformation similar to that described in the fusion of the palatal shelves, (2) apoptosis, and/or (3) tissue remodeling via cellular migration. Urethral development in the embryonic mouse (14-21 days of gestation) was compared with urethral formation in embryonic human specimens (8-16 weeks of gestation) by using histology, immunohistochemistry, and three-dimensional reconstruction. The urethra forms by fusion of the epithelial edges of the urethral folds, giving a midline epithelial seam. The epithelial seam is remodeled via cellular migration into a centrally located urethra and ventrally displaced remnant of epithelial cells. The epithelial seam is remodeled by narrowing approximately at its midpoint, with subsequent epithelial migration into the urethra or penile skin. The epithelial cells are replaced by mesenchymal cells. This remodeling seam displays a narrow band (approximately 30 microns wide) of apoptotic activity corresponding to the mesenchymal cells and not to epithelial cells. No evidence was seen of the co-expression of cytokeratin and mesenchymal markers (actin or vimentin). Urethral seam formation occurs in both the mouse and the human. Our data in the mouse support the hypothesis that seam transformation occurs via cellular migration and not by epithelial mesenchymal transformation or epithelial apoptosis. We postulate that disruption of epithelial fusion remodeling, and cellular migration leads to hypospadias.

Animals↗

Fetal intervention for myelomeningocele: effect on postnatal bladder function.

PURPOSE: Myelomeningocele is the most common congenital malformation of the central nervous system noted on prenatal ultrasound. Due to its significant postnatal sequelae, treatment in utero could potentially have a profound impact on the newborn. Others have reported fetal surgical techniques for in utero repair of myelomeningocele and its potential benefits on motor and neurological function. We report our urodynamic findings in the newborn after in utero repair of spina bifida in an effort to characterize postnatal bladder function. MATERIALS AND METHODS: A retrospective review of the fetal surgery database at University of California San Francisco was performed identifying patients with a diagnosis of myelomeningocele. Prenatal surgical repair of myelomeningocele was considered if a normal karyotype was present, no other significant congenital anomalies were evident and gestational age was less than 24 weeks. The spinal defects were in the lumbar or lumbosacral region. All surgery was performed before 24 weeks of gestations. RESULTS: Fetal surgery to correct myelomeningocele was performed in 6 patients. All patients were born premature at 32 weeks of gestation or less. Videourodynamics performed at age 1 month in 4 patients indicated decreased bladder capacity for weight, increased detrusor storage pressures and significant post-void residual. Hydronephrosis was demonstrated in 4 patients on renal/bladder ultrasound, and moderate vesicoureteral reflux was seen in 3. CONCLUSIONS: Patients with spinal bifida treated in utero appear to have the same changes in urodynamic parameters and anatomical abnormalities in the urinary tract as other children with spinal defects who have undergone standard postnatal care. In utero treatment of spinal bifida may expose the newborn to the effects of prematurity. The long-term effects on bladder function in the fetus after in utero repair of myelomeningocele remain unknown. A randomized controlled trial is necessary to evaluate long-term bladder function as well as other outcome variables in this experimental approach to patients with myelomeningocele.

Female↗

Kidney transplantation in children with urinary diversion or bladder augmentation.

PURPOSE: Urinary tract anomalies or dysfunction leaves the bladder unsuitable for urine drainage in a significant proportion of children presenting for kidney transplantation. We reviewed a multi-institutional experience to determine the ramifications of kidney transplantation in children with bladder augmentation or urinary diversion. MATERIALS AND METHODS: During a 28-year period 18 boys and 12 girls 1.7 to 18 years old (mean age 12.1) received 31 kidney transplants. Cause of end stage renal disease was renal dysplasia in 8 cases, posterior urethral valves in 5, obstructive uropathy in 5, neurogenic bladder/chronic pyelonephritis in 4, spina bifida/chronic pyelonephritis in 3, prune belly syndrome in 3 and reflux in 2. RESULTS: Of the patients 17 had augmented bladder (ileum 9, ureter 5, sigmoid 2 and stomach 1), 12 had incontinent urinary conduits (8 ileum, 6 colon) and 1 had a continent urinary reservoir. Surgical complications included 1 case each of stomal stenosis, stomal prolapse, renal artery stenosis, urine leak, enterovesical fistula and wound dehiscence. Medical complications included urinary tract infection in 21 cases and metabolic acidosis in 5. A bladder stone developed in 1 patient. There was no correlation between the incidence of symptomatic urinary tract infections and type of urinary drainage. Acidosis was more common in patients with augmented bladder (4 of 17 versus 1 of 14) but there was no correlation between the bowel segment used and the occurrence of acidosis. Graft survival was 90% at 1 year, 78% at 5 years and 60% at 10 years. Etiology of graft loss included chronic rejection in 6 cases, noncompliance in 4 and acute rejection in 1. There were no deaths. CONCLUSIONS: Drainage of transplanted kidneys into an augmented bladder or urinary conduit is an appropriate management strategy when the native bladder is unsuitable or absent. Patients with kidney transplants drained into augmented bladder or urinary conduit are at increased risk for urine infection. Graft survival is not adversely affected compared to historical controls when a kidney transplant is drained into a urinary conduit or augmented bladder.

Adolescent↗

Placement of artificial urinary sphincter in children and simultaneous gastrocystoplasty.

PURPOSE: Previous studies have described placement of an artificial urinary sphincter and simultaneous augmentation cystoplasty with a segment of bowel. Conclusions from these studies indicated that infection rates were higher and a staged approach should be undertaken. Others have suggested that concurrent urinary reconstruction with stomach and sphincter placement can be performed safely. Results comparing infection rates of simultaneous sphincter placement and gastrocystoplasty versus staged sphincter placement and augmentation cystoplasty using a segment of ileum or stomach versus sphincter placement alone in a pediatric population have not been previously described to our knowledge. We reviewed these various groups of patients to determine if the difference in infectious complications were clinically and statistically significant. MATERIALS AND METHODS: A retrospective review of medical records from 1986 to 1999 identified 28 pediatric patients (age 18 years or less) who had undergone placement of an AS800dagger artificial urinary sphincter. Data points were collected focusing on etiology of the neurogenic bladder, age at time of surgery, types of surgery performed, length of followup and complication rates. RESULTS: Complete data were available for 27 of the 28 patients. Neurogenic bladder was secondary to myelomeningocele in 25 cases, transverse myelitis in 1 and spinal cord injury in 2. Mean patient age at surgery was 12.7 years (range 6.1 to 18.2) and mean followup was 4.3 years (range 1 month to 13 years). Simultaneous gastrocystoplasty was performed in 7 cases (group 1), staged sphincter placement followed by augmentation cystoplasty with a segment of ileum or stomach was done in 8 (group 2) and 12 did not require bladder augmentation (group 3). Urethral device erosion requiring explantation was the most common complication, occurring in 3 patients in group 1 and 2 in group 3 (p = 0.101). Mean time to erosion was 22.1 months (range 2 to 46.4). Previous surgery (bladder neck or hernia repair) was a common factor in each group with complications. Urine cultures and culture of the explanted device were positive in 2 patients in group 1. CONCLUSIONS: Simultaneous placement of artificial urinary sphincter at the time of gastrocystoplasty can be performed in carefully selected patients, although those undergoing staged procedures did well without complications. Prior bladder neck surgery seems to be a significant risk for infection. A staged approach to lower urinary tract reconstruction would be more advantageous due to the absence of infection and erosion in those undergoing staged sphincter placement and augmentation cystoplasty.

Adolescent↗

Magnetic resonance imaging in the evaluation of congenital anomalies of the external genitalia.

OBJECTIVES: To assess the value of magnetic resonance imaging (MRI) in the anatomic evaluation and management planning of complex congenital genitourinary anomalies. METHODS: Multiplanar T(1) and T(2)-weighted MR images were obtained in 6 pediatric patients with congenital genitourinary anomalies, including aphallia, diphallia, ectopic scrotum, and epispadias. The imaging studies were read by experienced radiologists and discussed with the urologic surgeons in a multidisciplinary conference. RESULTS: Each congenital anomaly was demonstrated in detail by MRI. The MR images of penile agenesis showed hypoplastic corpora cavernosa and a vestigial bulb. In patients with penile duplication, MRI was able to delineate the course of each corporal body and the varying degree of thickness of the tunica albuginea. For the patient with scrotal ectopia, detailed MR images excluded both the possibility of urethral and corporal duplications and the presence of viable testes in the ectopic scrotum. In the case of epispadias, MRI illustrated the precise spatial relationship between the erectile bodies and urethra. Additionally, MRI identified related aberrant pelvic organs and provided images of the external genital structures. CONCLUSIONS: MRI, by rendering excellent anatomic interpretation of complex genital anomalies and associated abnormal pelvic tissues, assists surgeons in conceptualizing the anomalous structures and contributes to their formulation of management approaches.

Adult↗

Hypospadias and endocrine disruption: is there a connection?

Hypospadias is one of the most common congenital anomalies in the United States, occurring in approximately 1 in 250 newborns or roughly 1 in 125 live male births. It is the result of arrested development of the urethra, foreskin, and ventral surface of the penis where the urethral opening may be anywhere along the shaft, within the scrotum, or in the perineum. The only treatment is surgery. Thus, prevention is imperative. To accomplish this, it is necessary to determine the etiology of hypospadias, the majority of which have been classified as idiopathic. In this paper we briefly describe the normal development of the male external genitalia and review the prevalence, etiology, risk factors, and epidemiology of hypospadias. The majority of hypospadias are believed to have a multifactorial etiology, although a small percentage do result from single gene mutations. Recent findings suggest that some hypospadias could be the result of disrupted gene expression. Discoveries about the antiandrogenic mechanisms of action of some contemporary-use chemicals have provided new knowledge about the organization and development of the urogenital system and may provide additional insight into the etiology of hypospadias and direction for prevention.

Androgen Antagonists↗

Fetal surgery for posterior urethral valves: long-term postnatal outcomes.

OBJECTIVE: Fetal intervention for obstructive uropathy was first performed at the University of California, San Francisco in 1981. Indications for treatment were bilateral hydronephrosis with oligohydramnios. Preintervention criteria included fetal urinary electrolytes with beta-microglobulin levels, karyotyping, and detailed sonography specifically looking for renal cortical cysts. We reviewed the outcomes of children who underwent fetal intervention with specific long-term follow-up in patients who were found postnatally to have posterior urethral valves. METHODS: A retrospective review of the University of California, San Francisco fetal surgery database was performed for patients with a prenatal diagnosis of obstructive uropathy. Medical records from 1981 to 1999 were reviewed. Long-term follow-up was documented if the cause of the urinary tract obstruction was posterior urethral valves. We collected data points, focusing on time and type of intervention, fetal urinary electrolytes, appearance of fetal kidneys, present renal function, length of follow-up, and present status of the urinary tract. RESULTS: Forty patients were evaluated for fetal intervention; 36 fetuses underwent surgery during this time period. Postnatal confirmation of posterior urethral valves was demonstrated in 14 patients. All patients had favorable fetal urinary electrolytes. Mean gestational age at intervention was 22.5 weeks. The procedures performed included creation of cutaneous ureterostomies in 1, fetal bladder marsupialization in 2, in utero ablation of valves in 2, and placement of vesicoamniotic catheter in 9. Six deaths occurred before term delivery with premature labor and the newborns succumbing to respiratory failure. One pregnancy was terminated electively because of shunt failure and declining appearance of fetal lungs and kidney. The remaining 8 living patients had a mean follow-up of 11.6 years. Chronic renal disease with abnormal serum creatinine was present in 5 patients. Two patients have undergone renal transplantation, and 1 is awaiting organ donation. Five of the 8 living patients have had urinary diversion with vesicostomy, cutaneous ureterostomy, or augmentation cystoplasty with later reconstruction. CONCLUSIONS: Fetal intervention for posterior urethral valves carries a considerable risk to the fetus with fetal mortality rate of 43%. The long-term outcomes indicate that intervention may not change the prognosis of renal function or be a predictor for possible urinary diversion. Despite all of these patients' having favorable urinary electrolytes, this did not seem to have any implication postnatally. When counseling families about fetal intervention, efforts should be focused on that intervention may assist in delivering the fetus to term and that the sequelae of posterior urethral valves may not be preventable. Fetal surgery for obstructive uropathy should be performed only for the carefully selected patient who has severe oligohydramnios and "normal"-appearing kidneys.

Adolescent↗

Penile anatomy under the pubic arch: reconstructive implications.

PURPOSE: We have previously defined the anatomy of the neurovascular bundle in the normal and hypospadiac penis. These studies were based on analysis of the fetal penis distal to the pubic arch without total inclusion of the crural bodies. To our knowledge the neuroanatomy beneath the pubic arch has not been well described. We defined the nerve distribution under the pubic arch and the relationship of the nerves to the crural bodies, corporeal bodies and urethra of the penis. MATERIALS AND METHODS: Eight normal human fetal penile specimens (at 17.5 to 29 weeks of gestation and 1 hypospadiac specimen at 32 weeks were serially sectioned and stained with Masson's trichrome, and the neuronal markers protein gene product 9.5 and S-100. These specimens were unique in that they contained the whole penis from the glans to the crural bodies beneath the pubic arch. Older specimens were decalcified before fixation. Computer reconstruction with commercially available graphics software allowed 3-dimensional analysis of the nerves and crural bodies in relation to the pubic arch and surrounding structures. RESULTS: The nerves of the penile shaft and glans surrounded the corporeal bodies, extending from the junction of the urethral spongiosum to the classic 11 and 1 o'clock positions with a paucity of nerves at the 12 o'clock position in the dorsal midline. Beneath the pubic arch the nerves to the penis were an extension of the dorsal neurovascular bundle of the prostate. The nerves formed 2 bundles following a path just under the pubic arch in close proximity to the bone, superior to the urethra and medial to the origin of the crural bodies. The nerve bundles joined the corporeal bodies at the proximal origin, where the 2 crural bodies fused together. At this point perforating branches into the corporeal bodies from the cavernous nerves were documented. As the dorsal nerves joined the dorsal aspect of the corporeal bodies, they immediately began to fan out along the surface of the corporeal tissue to the junction of the urethral spongiosum. Three-dimensional reconstruction showed the relationship of the nerves to the pubic arch and urethra in multiple views. CONCLUSIONS: A precise understanding of penile anatomy beneath the pubic arch and at the origin of the crural bodies is important for preserving neuronal structures. This anatomy is especially germane in children undergoing posterior urethral reconstruction secondary to trauma, intersex requiring feminizing genitoplasty and severe hypospadias.

Fetus↗

Plasticity of the urothelial phenotype: effects of gastro-intestinal mesenchyme/stroma and implications for urinary tract reconstruction.

The present study tests the hypothesis that heterotypic stromal-epithelial interactions cause phenotypic changes in urothelium. The rational for the experimental design is to simulate heterotypic stromal-epithelial interactions that are created at the anastomotic site of intestinal-bladder augmentations and internal urinary diversions where the urothelium is in direct contact with the gastro-intestinal tract tissues. Tissue recombination experiments were performed by combining 14-day embryonic rat and mouse rectal mesenchyme with urothelium from embryonic, newborn, and adult mice or rats. All tissue recombinants were grown beneath the renal capsule of athymic mouse hosts for 6-16 weeks. Analyses were performed to detect expression of uroplakins, cytokeratin 7, 14, 19 and mucin secreting epithelial cells via Periodic Acid-Schiff (PAS). The phenotype of both mouse and rat urothelium was changed to a glandular morphology under the influence of rectal mesenchyme. Immunohistochemical staining revealed a loss of the urothelial specific uroplakins and cytokeratins 7, 14, and 19 (characteristic of urothelium). Histologic analysis revealed the presence of mucin secreting glandular structures which stained positive for PAS. The urothelial transdifferentiation into glandular epithelium was not a function of epithelial age and occurred in the embryonic, newborn and adult urothelium. Likewise, rectal mesenchyme from embryonic, neonatal, and adult animals was able to induce glandular differentiation in bladder epithelium. Urothelium exhibits the plasticity to change into an intestinal like epithelium as a result of mesenchymal/stromal stimulation from the gastro-intestinal tract. This experimental result is germane to heterotypic stromal-epithelial interactions that are created in patients with urinary tract reconstructions (intestinal augmentations, de-mucosalized urothelial lined bladder patches, and internal urinary diversion such as ureterosigmoidostomies). We propose that heterotypic stromal-epithelial interactions may play a role in determining histodifferentiation of urothelial cells at the anastomotic site between bowel and bladder tissue in patients with gastro-intestinal urothelial reconstructions.

Animals↗

Anatomical studies of the urethral plate: why preservation of the urethral plate is important in hypospadias repair.

OBJECTIVE: To describe the detailed anatomy of the urethral plate in relation to its controversial role in hypospadias surgery. MATERIALS AND METHODS: A newborn penis with proximal penile hypospadias and two fetal penises with distal shaft hypospadias were included in the study; 30 normal fetal penises served as the control. Specimens were embedded in paraffin and serially sectioned (6 microm) after formalin fixation. Every 10th section was stained with haematoxylin and eosin. Immunohistochemical staining for nerves (S100), smooth muscles (alpha-actin), blood vessels (factor VIII) and epithelium (cytokeratins 7, 14 and 18) were used on selected sections, with particular attention to the urethral plate. Masson's trichrome and Sirius Red stains were used to localize collagen. RESULTS: There were extensive blood vessels, glands and smooth muscle under the urethral plate in the hypospadias specimens. These relatively well organized tissues corresponded to an abnormally formed corpus spongiosum. The glands underneath the urethral plate and adjacent to the normal urethra showed positive staining for cytokeratins 7 and 18, respectively (markers of endodermal origin) but were negative for cytokeratin 14 (a marker of ectodermal origin). Penile skin and urethral plate epithelium stained positively for cytokeratin 14 but not for cytokeratin 7 and 18. The urethral plate has a rich nerve supply, as determined by S100 staining. Collagen intensity under the urethral plate was no different from that in normal areas. Tunica albuginea stained intensely for type I and III collagen. CONCLUSION: These results show that the urethral plate is well vascularized, has a rich nerve supply and an extensive muscular and connective tissue backing. These features may explain the lower complication rate with onlay flaps than with tube flaps. Therefore, from these anatomical findings, we continue to advocate preservation of the urethral plate and the onlay island flap for hypospadias reconstruction.

Case-Control Studies↗

Anatomy of the neurovascular bundle: is safe mobilization possible?

PURPOSE: We have previously defined the anatomy of the neurovascular bundle in the normal and hypospadiac penis. Historical experience suggests that mobilization of the neurovascular bundle is anatomically possible. We attempt to prove whether mobilization of the neurovascular bundle is safe and theoretically sound. Specific questions that will be addressed are does the neurovascular bundle send perforating branches into the corporal bodies; how far lateral does the dissection need to be before nerves are injured and exactly how deep into Buck's fascia must one go. MATERIALS AND METHODS: A total of 35 normal human fetal penile specimens, gestational age 8 to 35 weeks, and 3 hypospadiac specimens, 33 to 41 weeks of gestation, were serially sectioned and stained with Mason's trichrome and the neuronal markers PGP 9.5 or S100. Computer reconstruction using commercial software and National Institutes of Health imaging allowed 3-dimensional analysis of the nerves, corporal bodies and glans. RESULTS: Perforating nerves into the erectile bodies were not documented along the dorsal or lateral aspect of the tunica in any of the specimens studied. Only in the area of the crural bodies on the ventral lateral surface were nerves noted to pierce into erectile tissue. The neural network was extensive from the 11 and 1 to the 5 and 7 o'clock positions corresponding to the erectile tissue and urethral spongiosum junction. At this junction minor nerve branches were noted to perforate into the urethral spongiosum. A microscopic plane exists between the neurovascular bundle and tunica of the corporal bodies measuring 20 to 30 micro. in specimens greater than 30 weeks in gestation. CONCLUSIONS: Perforating branches from the dorsal lateral neurovascular bundle do not exist based on serial step sectioning and microscopic examination of male genital specimens. Surgically it is possible to elevate the neurovascular bundle but the dissection needs to remain directly on top of the tunica albuginea to prevent neuronal injury. Small perforating branches into the urethral spongiosum may be injured with unknown significance. We continue to advocate plication in the nerve-free zone at the 12 o'clock position for correction of penile curvature.

Fetus↗