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Biomedical subjects

L S Baskin

Publications and source records attributed to L S Baskin.

At least 37 records · Page 2Linked to original sources
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

Hypospadias and urethral development.

PURPOSE: Hypospadias is a common congenital anomaly that may be treated with surgical reconstruction. In the majority of cases the etiology remains elusive. Although androgens are clearly critical for penile development, defects in androgen metabolism and/or the androgen receptor explain only a small subset of cases of hypospadias. Strategies are presented for understanding the etiology of hypospadias. MATERIALS AND METHODS: Current scientific reports on the etiology of hypospadias were reviewed, and the embryology and possible mechanisms of urethral and penile formation are presented. RESULTS: A new theory of glandular human urethral development via endodermal cellular differentiation is proposed to replace the classic explanation of ectodermal intrusion. CONCLUSIONS: Careful studies of penile and urethral development have led to a better understanding of genital embryology. Future areas of study, such as endocrine disrupters, mesenchymal-epithelial interactions and mechanisms of penile growth, are proposed to explain the etiology of hypospadias.

Animals↗
PubMed2000

High urinary flow accelerates renal injury in young rats with partial unilateral ureteral obstruction.

PURPOSE: We studied the effect of dietary manipulation and high urine flow on neonatal partial ureteral obstruction in a weanling rat preparation. MATERIALS AND METHODS: A total of 40, 3-week old Sprague-Dawley rats underwent unilateral ureteral obstruction by burial of the right ureter in the psoas muscle and 13 underwent sham operation. Low, high and normal salt, and high sucrose diets were administered for 2 months. The glomerular filtration rate of each kidney was measured by iothalamate clearance. Intrapelvic pressure and renal blood flow were measured before and after acute volume loading. RESULTS: Fluid intake and urine output were 8 to 10-fold greater in animals on high salt and high sucrose diets compared to those in rats on normal and low salt diets. Hydronephrosis was observed only in rats with partial obstruction and high urine flow. No difference in renal weight was noted. Relative glomerular filtration rate of the partially obstructed kidney was maintained when urine flow was normal but decreased significantly with high urine flow. Total glomerular filtration rate also decreased with high urine flow. Intrapelvic pressure was elevated significantly at baseline in partially obstructed kidneys with high urine flow. All kidneys with partial obstruction had significantly increased intrapelvic pressure with volume loading. Renal blood flow was not significantly decreased in rats with high urine flow. CONCLUSIONS: Chronic high urine flow causes loss of renal function in partially obstructed weanling rat kidneys. Research should be done to determine whether human infants with hydronephrosis and partial ureteral obstruction would benefit from the prevention of increased fluid and salt intake.

Animals↗
PubMed2000

Urethral development in the fetal rabbit and induction of hypospadias: a model for human development.

PURPOSE: To determine whether the development of the rabbit phallus would be an appropriate model of human phallic development, we evaluated the formation of the fetal rabbit phallus and attempted to induce hypospadias pharmacologically. MATERIALS AND METHODS: New Zealand rabbit fetuses were obtained on gestational days 20 to 24, 26, 28 and 31. Sex was determined by gonadal morphology, and 6 fetuses were obtained at each age. The perineum was dissected, fixed, sectioned and stained with hematoxylin and eosin, and monoclonal antibodies against neuronal specific enolase. Two pregnant rabbits were treated with 10 mg./kg. finasteride orally daily between gestational days 19 and 28. The development of the external genitalia was compared in treated and untreated control rabbits. RESULTS: The rabbit phallus contains 2 corpora cavernosa and dorsolateral nerves similar to the human. In male and female fetuses fusion of the urethral folds progressed in a proximal to distal sequence forming a seam at the point of ventromedial fusion. In male fetuses urethral fold and ventral preputial fusion continued more distally toward the glans compared to females. Thus, in mature males the urethral meatus and ventral prepuce extended to the tip of the phallus, whereas in females the urethral meatus opened on the proximal phallus and the prepuce was deficient ventrally forming a dorsal hood. Male offspring had a significantly larger anogenital distance postnatally than female offspring. In male fetuses exposed to finasteride urethral fusion did not extend distally and the prepuce was deficient ventrally. Also, male offspring exposed to finasteride in utero had a significantly shorter anogenital distance than females and untreated control males at all ages (p <0.05). CONCLUSIONS: Fetal development of the rabbit phallus and urethra is homologous to the human. Although the gestational period is significantly shorter, the temporospatial pattern of external genitalia development is analogous in these species. Feminization of the rabbit urethra, hypospadias, can be induced by inhibiting 5alpha-reductase. Use of this animal model will allow further study of molecular mechanisms involved in urethral fusion and the evaluation of the pathophysiological processes of hypospadias.

Animals↗
PubMed1999

Ultrastructural smooth muscle ontogeny of the rat bladder.

The transmission electron microscope characteristics of developing rat bladder smooth muscle are described at 14 and 18 days of gestation, birth, and adulthood. Caveolae, microfilaments, and dense bodies increase during smooth muscle development. Collagen content in the extracellular matrix also increases. These changes may reflect increased bladder emptying in the rat, and also allow for comparison of smooth muscle cells in studies of bladder wound healing and tissue substitutes.

Aging↗
PubMed1999

Anatomical studies of the human clitoris.

PURPOSE: Endogenous or exogenous testosterone exposure to the fetus during gestation may result in masculinization of the external genitalia. Surgical correction requires a clear understanding of normal female anatomy. We report observations from our anatomical dissections on which we base our approach to reduction clitoroplasty. MATERIALS AND METHODS: A total of 14 normal human fetal clitoral specimens at 8 to 24 weeks of gestation were serially sectioned after formalin fixation. Every tenth section was stained with Masson's trichrome, smooth muscle alpha-actin and the neuronal markers PGP 9.5 or S-100. Computer reconstruction using imaging software permitted 3-dimensional analysis of the nerves, corporeal bodies and glans clitoris. These specimens were compared with 2 obtained postnatally at feminizing genitoplasty. RESULTS: The normal fetal clitoris consists of 2 corporeal bodies with a midline septum. The ultrastructure of the female corporeal bodies is similar to that of the male counterpart. The glans clitoris forms a cap on top of the distal end of the narrowed corporeal bodies. There is a midline septum starting on the ventral aspect and extending approximately halfway into the glans. Large bundles of nerves course along the corporeal bodies with the highest density on the dorsal aspect or top. No nerves were noted at the 12 o'clock position, although nerves extend completely around the tunica in a fashion similar to that of the fetal penis. Glans innervation is provided by multiple perforating branches entering at the dorsal junction of the corporeal body and glans. The lowest density of nerves in the glans is on the ventral aspect in juxtaposition to the glans septum. In surgical specimens obtained from patients with congenital adrenal hyperplasia nerves were adjacent to the excised tunica of the corporeal bodies, especially on the lateral aspect. CONCLUSIONS: A clear understanding of the anatomy of the human clitoris is important for surgical reconstruction. As in the human penis, nerves in the clitoris form an extensive network around the tunica of the corporeal body with a nerve-free zone at the midline 12 o'clock position. Care should be taken to preserve all nerves. Reduction of the glans clitoris should not violate the extensive innervation that predominates on the dorsal aspect of the glans. The normal clitoris has corporeal bodies that are smaller but analogous to those of the penis. One may consider their function when extensive resection is considered.

Clitoris↗
PubMed1999

Understanding bladder regeneration: smooth muscle ontogeny.

PURPOSE: We determined the origin of smooth muscle cells in acellular bladder matrix grafts. MATERIALS AND METHODS: A total of 15 female Sprague-Dawley rats underwent partial cystectomy and grafting with an acellular matrix derived from rat bladder. The grafts were examined 1, 2, 3 and 4 weeks after grafting by immunohistochemical studies for smooth muscle markers and by transmission electron microscopy for smooth muscle morphology. Bladder matrix and bladder epithelium recombinants were created and grafted subcutaneously and under the renal capsule in nude mice. Recombinants were examined 1, 2, 3 and 4 weeks postoperatively by immunohistochemical studies for bladder epithelium and bladder smooth muscle. RESULTS: Smooth muscle ingrowth into acellular matrix was initially seen at 2 weeks. The immunohistochemical and electron microscopic characteristics of the cells were similar to those of fetal smooth muscle 2 weeks and newborn smooth muscle 4 weeks after grafting. Matrix epithelium recombinants displayed mature bladder epithelium with 3 to 7 layers but they did not support the ingrowth of smooth muscle cells. CONCLUSIONS: Mature bladder smooth muscle cells undergo dedifferentiation, migration and redifferentiation to repopulate an acellular matrix graft. It is unlikely that adult fibroblasts from the surrounding tissue are induced by epithelium and matrix to form smooth muscle. The contractile behavior of bladder substitute materials likely reflects the properties of the host bladder.

Animals↗
PubMed1999

Child sexual abuse: what the urologist needs to know.

PURPOSE: We define what the urologist needs to know regarding child sexual abuse. MATERIALS AND METHODS: Based on our experience in treating numerous child victims of sexual assault and a review of the contemporary literature, the data concerning child sexual abuse incidence, risk factors, clinical presentation, child interview, physical examination and management were analyzed. RESULTS: It is estimated that at least 1 in 4 girls and 1 in 10 boys will suffer victimization by age 18 years. There are no predicting socioeconomic factors. In legally proved cases of child sexual abuse the majority of victims have no diagnostic physical findings. Examination findings change depending on the position of the child, degree of relaxation, amount of labial traction and time to perform the evaluation. Findings that are consistent but not independently diagnostic of abuse include chafing, abrasions or bruising of inner thighs or genitalia, scarring, tears or distortion of the hymen, a decreased amount of or absent hymenal tissue, scarring of the fossa navicularis, injury to or scarring of the posterior fourchette/posterior commissure and scarring or tears of the labia minora. In all 50 states physicians are mandated by law to report to child protection services whenever they suspect that a child has been sexually abused. CONCLUSIONS: The urologist must routinely examine the anogenital area of children during routine urethral evaluation and include child sexual abuse as part of the routine urological history.

Adolescent↗
PubMed1999

Ontogeny of the male urethra: theory of endodermal differentiation.

The most widely accepted mechanism of male urethral development proposes that the urethral plate is elevated by urethral folds which fuse ventrally in a proximal-to-distal sequence. Unlike its proximal counterpart, the urethra which forms within the glans is lined by a stratified squamous epithelium and has a more controversial development. One theory supports the idea that fusion of the urethral folds extends all the way to the tip of the glans. Another theory suggests that a solid ectodermal in-growth of epidermis canalizes the glandar urethra. We hypothesized that the use of immunohistochemical staining and tissue recombinant grafting would delineate the epithelia involved and lend clues to their origin. Thirty-six human fetal phallic specimens of gestational ages 5-22 weeks were sectioned and stained immunohistochemically with antibodies raised against different cytokeratins. Evaluation of the sections showed that the urethral plate, an extension of the urogenital sinus, extended to the tip of the phallus and maintained patency and continuity throughout the process of urethral development. The entire urethra, including the glans portion, was formed by dorsal extension and disintegration of the urethral plate combined with ventral growth and fusion of the urethral folds. Sections of the distal glandar urethra showed no evidence of a solid ectodermal ingrowth. Rather, immunostaining results at different ages suggested differentiation of the endodermal urethral plate into a stratified squamous epithelium. To determine whether urothelium could be induced to express a stratified squamous phenotype, mouse fetal bladder epithelium was combined with rat fetal genital tubercle mesenchyme and grown under the renal capsule of athymic mice. The bladder epithelium differentiated into a stratified squamous epithelium. Thus, proper mesenchymal signaling may induce differentiation of urothelium into a stratified squamous phenotype, such as during development of the urethra of the glans penis.

Animals↗
PubMed1999

Epithelial-mesenchymal interactions in development of the mouse fetal genital tubercle.

Epithelial-mesenchymal interactions play a central role in the development of urogenital organs. We hypothesized that normal development of the external genitalia depends upon proper mesenchymal-epithelial signaling. The mesenchyme of the adult mouse penis consists of a corpus cavernosum and proximal and distal bones. The differentiation of penile mesenchyme into bone and cartilage begins after birth and can be accelerated by androgens. After determining the sex, genital tubercles of fetal mice at gestational day 15 were removed. The genital tubercles were trypsinized and microdissected to remove the epidermis and urethra from the mesenchyme. Recombinant specimens were created by combining genital tubercle mesenchyme with genital tubercle epithelium, bladder epithelium or tail epidermis. Tissues were grafted under the renal capsule of male athymic mice. After 3 weeks of growth, grafts were removed from the kidney, weighed and stained with hematoxylin and eosin, Alcian blue and peanut agglutinin. Male and female grafts showed no difference in growth or differentiation. Intact grafts and recombinant grafts, irrespective of the epithelial source, grew significantly more than grafts of the mesenchyme only. Recombinant grafts demonstrated a significantly higher prevalence of cartilage formation and mesenchymal differentiation compared to grafts of the mesenchyme without epithelium. Since heterologous epithelium is able to induce equivalent growth and differentiation of phallic mesenchyme, epithelium carries a permissive, but critical, role in genital mesenchyme development.

Animals↗
PubMed1999

Growth factor expression in the obstructed developing and mature rat kidney.

The purpose of this study is to evaluate the role of keratinocyte growth factor (KGF), transforming growth factor-alpha (TGF-alpha), and their receptors in altered renal growth caused by complete ureteral obstruction in the developing kidney. Neonatal and adult rats underwent complete unilateral ureteral ligation or sham operation. The kidneys were harvested at 1, 5, 10, 20, and 30 days after obstruction. Renal growth and development was assessed by histology and immunohistocytochemical localization of vimentin, cytokeratin and smooth muscle-alpha actin. Cellular proliferation was measured by [3H]thymidine labeling index of all cells. RNase protection assays were used to quantify mRNA encoding for KGF, KGF receptor, TGF-alpha, and epidermal growth factor (EGF) receptor. Ureteral obstruction in the developing kidneys resulted in decreased DNA synthesis, rapid parenchymal loss, myofibroblast proliferation in the interstitium, decreased tubular epithelial cells formation, and development of cystic dysplasia. In comparison, obstruction in the mature kidneys resulted in transient growth in the medullary ductal cells, parenchymal loss, and myofibroblast proliferation at a later time, lymphocytic infiltration in the interstitium but not cystic dysplasia. KGF and KGF receptor mRNA levels were increased in obstructed neonatal kidneys. Similarly, TGF-alpha and EGF receptor mRNA levels were increased. Delayed and more moderate increases in KGF, KGF receptor, and TGF-alpha expression were also seen in the obstructed mature kidneys. Of importance, the amount of EGF receptor mRNA was not increased in the obstructed compared with the contralateral or sham-operated adult kidneys. This study suggests that obstruction alters the normal expression pattern of KGF, TGF-alpha, and their receptors in renal development. These changes may be responsible for the impaired renal growth and altered development seen in ureteral obstruction of the kidneys. Although some changes are similar to those seen in the adult kidney, the increased expression of TGF-alpha and cystic dysplasia are unique to neonatal obstruction.

Aging↗
PubMed1999

Expression of the Wnt gene family during late nephrogenesis and complete ureteral obstruction.

Because the Wnt-4, -7b, and -11 genes are expressed in metanephric kidneys and code for secreted glycoproteins that may serve as mediators of the transformation of renal mesenchyme to epithelium, we investigated the pattern of Wnt gene expression in late metanephrogenesis and after ureteral obstruction. Newborn and 10-, 20-, and 60-day-old rats underwent complete unilateral ureteral ligation or sham operation. The kidneys were collected bilaterally 1, 5, 10, 20, or 30 days later. RNase protection assays were used to quantify the amounts of mRNA encoding Wnt-4, -7b, and -11, E-cadherin, and cytokeratin-19. Renal development was assessed by histologic characterization of vimentin, cytokeratin, E-cadherin, and beta-catenin distribution. During normal development, the amounts of mRNA encoding Wnt-4 and Wnt-11 increased during gestation and then abruptly decreased after the completion of metanephrogenesis, 15 days after birth. In contrast, the amounts of mRNA encoding Wnt-7b, E-cadherin, and cytokeratin-19 increased during development and into adulthood. In neonatally obstructed kidneys, the expression of Wnt-4 was abnormally maintained when obstruction was induced before the completion of renal development and was reactivated when obstruction was induced after the completion of metanephrogenesis. Wnt-7b expression was minimally affected and Wnt-11 expression was only transiently affected by obstruction. In neonatally obstructed kidneys, the differentiation of mesenchyme to epithelium failed to proceed normally, with the majority of cells maintaining vimentin expression and some differentiated epithelial cells reverting to vimentin expression. In addition, the expression of E-cadherin and cytokeratin was increased in epithelial cells. Changes in the expression of Wnt genes were correlated with histologic changes. This study suggests that Wnt-4 and -11 are likely to be important mediators of the transformation of mesenchyme to epithelium in the kidney. Obstruction induced during metanephrogenesis disrupts the normal pattern of Wnt-4, -7b, and -11 expression and interferes with the normal transformation process in developing kidneys, by maintaining the mesenchymal component and inducing the transformation of epithelium to mesenchyme.

Aging↗