PubMed Health⌕ Search

Biomedical subjects

L S Baskin

Publications and source records attributed to L S Baskin.

At least 91 records · Page 5Linked to original sources

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.

Animals↗

Role of mesenchymal-epithelial interactions in normal bladder development.

PURPOSE: To assess the role of cell-cell interactions in the development of bladder smooth muscle. MATERIAL AND METHODS: Bladders from 14-day rat fetuses (prior to smooth muscle differentiation) were isolated and digested with trypsin to separate the mesenchyme and epithelium. Three types of specimens were prepared for grafting under the renal capsule of syngeneic adult hosts: a) intact bladder (BL) which had been isolated from fetuses of timed pregnant rats by surgical methods alone; b) bladder mesenchyme (BLM) alone (urothelium removed following trypsinization); and c) isolated BLM recombined with bladder urothelium (BLM + BLE). After 2 weeks of in vivo growth the grafts were assessed by immunocytochemical techniques for the expression of smooth muscle cells markers (actin, myosin, vinculin, laminin and desmin). The same experiments were repeated in vitro. In the final experiment, the induction of bladder smooth muscle was elicited in situ across species lines. Fourteen-day rat BLM was grafted onto the proximal ureter of an athymic nude mouse after ipsilateral nephrectomy. RESULTS: Grafts of intact BL and BLM + BLE recombinants expressed smooth muscle differentiation. In contrast, grafts of BLM alone remained devoid of smooth muscle. This was also true for the in vitro studies in which, after 5 days of growth, BLM + BLE recombinants (n = 12) showed clear evidence of smooth muscle differentiation. In contrast, cultures of BLM alone (n = 12) exhibited poor growth without smooth muscle differentiation. In the final experiment testing the induction of smooth muscle across species, after 1 month in vivo growth the urothelium of the cut end of the ureter had invaded the grafted BLM. The BLM grafts (n = 3) had increased 30 times in size, and immunocytochemical staining showed clear expression of smooth muscle markers in the grafted BLM in proximity to the urothelium. CONCLUSION: We have shown that the differentiation of smooth muscle in the rat bladder is dependent upon an inductive interaction with the epithelium.

Animals↗

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.

Adolescent↗

Recurrent Staphylococcus aureus renal abscess in a child positive for the human immunodeficiency virus.

A 10-year-old girl with the human immunodeficiency virus was found to have a Staphylococcus aureus renal abscess with perinephric extension. The abscess was drained first percutaneously and then surgically, and the patient received a 6-week course of intravenous antibiotics. Three months later, the abscess recurred, necessitating a nephrectomy. The extended morbidity and difficulty of eradicating S aureus suggest that, in immunocompromised patients, early aggressive surgical management is indicated.

AIDS-Related Opportunistic Infections↗

Contradictory renal function measured with mercaptoacetyltriglycine diuretic renography in unilateral hydronephrosis.

PURPOSE: We studied apparently supranormal renal function in hydronephrotic kidneys, as measured by 99mtechnetium mercaptoacetyltriglycine renography. MATERIALS AND METHODS: We retrospectively reviewed the clinical history, ultrasonography and renography of 29 children. RESULTS: Of the 29 children 7 had greater than 50% relative function in the hydronephrotic kidney. This finding was independent of patient age, gender, degree of hydronephrosis or obstructive pattern. Of these 7 cases 6 occurred on the right side (p < 0.05 versus a large registry). CONCLUSIONS: In most cases supranormal renal function is caused by a technical problem, likely the inadequate background subtraction of mercaptoacetyltriglycine in the liver.

Child↗

Buccal mucosal urethral replacement.

Graft substances, such as skin and bladder mucosa, have been previously used for urethral replacement when local epithelial tissue was not available. However, these substances have been associated with meatal prolapse, stricture and fistula formation. We have used buccal mucosa as a tissue for urethral substitution in these situations during the last 8 years. We review our clinical experience in 18 urethral reconstructions performed for urethral replacement in 4 cases of exstrophy/epispadias, 12 complex hypospadias repairs and 2 cases of complex bulbar urethral strictures. There have been 5 cases of meatal stenosis (2 requiring operative revision) but none of meatal eversion. There has also been 1 urethrocutaneous fistula and 1 mid graft stricture. Mean followup was 27 months and minimum followup was 6 months. Histological examination of the buccal mucosal graft compared to grafts of skin showed that the full thickness of the dermis or lamina propria is thinnest while the native vascular supply is greatest in the buccal mucosa. These 2 factors are associated with improved graft take and may explain the encouraging clinical results.

Cheek↗

Primary dilated megaureter: long-term followup.

Previously, we reported on the changing concepts in the management of 35 neonates with primary obstructive megaureters, 25 of whom were observed without surgery for a mean of 28 months while 10 were surgically treated. We report the long-term outcome of the 25 patients who were managed without surgery. This group consists of 19 male and 6 female neonates with 19 unilateral and 6 bilateral dilated ureters. Of the patients 17 presented with an antenatal diagnosis of hydronephrosis, 2 with infection and 6 with incidental findings. None of the patients had vesicoureteral reflux. Followup serial imaging (2 or more studies per case) consisted of excretory urography in 18 of the 25 cases, diethylenetriaminepentaacetic acid renal scan in 16 and/or sonogram in 10. Mean followup was 7.3 years (range 4.8 to 12.4) for 24 patients and 1 was lost to followup after 1.5 years. Excretory urography showed improvement in urinary tract dilatation in 12 cases and stable dilatation in 6. Renal scans demonstrated expected interval increases in the glomerular filtration rate with age without any deterioration in per cent of renal function in all 16 cases. None of the patients had stones, pain or pyelonephritis. We conclude that it is safe to follow a select group of patients with primary dilated megaureters in the absence of vesicoureteral reflux. We recommend antibiotic prophylaxis and serial urinary tract imaging to confirm renal growth and preservation of renal function.

Dilatation, Pathologic↗

Type III collagen decreases in normal fetal bovine bladder development.

In normal fetal bovine bladder development we have shown that compliance increases at approximately the same time that urine production first occurs. The late first trimester fetal bladders are relatively stiff with a progressive increase in bladder compliance peaking in the newborn period. From the newborn period through adulthood, we documented a relatively modest decrease in bladder compliance, which may result from the normal aging process. To account for these changes, we have used the bovine model to perform biochemical analyses of the major structural collagens that are found in the bladder (types I and III). These results show that the per cent of type III collagen decreases in the developing bladder from the end of the first trimester until the newborn period. Comparing the newborn bladder to that of a mature adult, we documented a relatively modest increase in the amount of type III collagen. We demonstrated that the ratio of type III-to-type I collagen parallels the normal compliance changes in the developing fetal and mature bovine bladder.

Aging↗

Changing concepts of hypospadias curvature lead to more onlay island flap procedures.

From 1987 through 1992, 1,109 primary hypospadias operations were performed at our hospital, of which 374 (33%) were onlay island flap procedures. In contrast, from 1982 to 1987 only 66 of 657 primary hypospadias repairs (10%) were onlay island flaps. The increase in this type of repair stems from the observation that in most cases of hypospadias the urethral plate is not the cause of penile curvature. Intraoperative artificial erection after skin take down revealed that only 50 of the 374 patients (13%) still had a significant bend. After experience demonstrated that the residual bend was not due to a fibrous urethral plate, but rather to a generally mild (20 to 30 degree) corporeal disproportion, correction was achieved by dorsal tunica albuginea plications. We conclude that better healing of the onlay flap to spongiosum supported urethral plate may account for the lower fistula rate (6%) observed with the onlay island flap hypospadias repair, and even in severe cases of hypospadias the urethral plate is usually healthy and it does not require division to produce a straight penis.

Child↗

Dorsal tunica albuginea plication for hypospadias curvature.

A systematic approach is described to correct congenital penile curvature using intraoperative artificial erection, preservation of the urethral plate when possible, tunica albuginea plication to straighten the penis and island flap urethroplasty (onlay and tube) when needed. After many years of experience we recognize that curvature correction is not necessarily enhanced by division of a healthy urethral plate. To correct inherent congenital curvature or corporeal disproportion we use a modification of the Nesbit dorsal tunica albuginea plication.

Follow-Up Studies↗

Nonoperative management of blunt pediatric major renal trauma.

Although algorithms exist for the management of renal trauma in adults, guidelines have not been established in children. Of 1,175 patients entered into our Trauma Registry between 1987 and 1991, 61 (5.2%) presented with gross or microscopic hematuria. Eight of the 58 patients (13.8%) who had blunt abdominal trauma had major renal injuries. Gross hematuria (n = 10) was a significant predictor of major renal injury (n = 5) (p < 0.001). All 3 patients with microscopic hematuria and a major renal injury also had evidence of multisystem trauma. Admission blood pressure, hemoglobin, and trauma score were not predictors of major renal trauma. All cases were managed nonoperatively except for 1 patient who required a partial nephrectomy for continued hemorrhage. These data suggest that hematuria of any degree should be evaluated in the pediatric population, since major injuries can occur with even microscopic hematuria or in the absence of shock. Nonoperative management in this series resulted in no morbidity or delayed complications and suggests that surgical exploration be reserved for ongoing bleeding.

Adolescent↗

Biochemical characterization and quantitation of the collagenous components of urethral stricture tissue.

The collagenous composition of normal and strictured human urethral tissue was analyzed qualitatively by immunohistochemistry and quantitatively by 2-dimensional gel electrophoresis of cyanogen bromide digested tissue. Histological comparison of the normal and strictured urethral tissue showed that the normal urethral spongiosum was replaced by densely packed connective tissue fibers interspersed with fibroblasts in the strictured tissue. The immunohistochemical analysis of urethral tissue identified the presence of types I and III collagen fibers in normal spongiosum and in the connective tissue scar of strictured tissue. Estimation of the collagen type III:I ratio using scanning densitometry revealed a CB5:CB8 peptide ratio of 0.357 +/- 0.058 in the normal tissue, while the urethral stricture tissue had a CB5:CB8 ratio of 0.203 +/- 0.079 (p = 0.010). Total collagen content, as determined by hydroxyproline analysis, revealed no statistically significant differences between control and strictured tissue. Therefore, the normal urethral spongiosum was comprised of 75.1% type I collagen and 24.9% type III collagen. In contrast, the type I collagen in urethral stricture tissue was increased (83.9%), with a corresponding decrease in type III collagen (16.1%). This alteration in the ratio of collagen type III:I may explain the fibrotic noncompliant nature of urethral stricture scar tissue.

Adolescent↗

Culture of urethral fibroblasts: cell morphology, proliferation and extracellular matrix synthesis.

The in vitro morphology and proliferative activity of urethral fibroblasts were characterized from primary isolates of fetal bovine urethral spongiosum. Cells were identified as fibroblastic based on their spindle-shaped morphology and lack of expression of phenotypic markers characteristic of either urethral smooth muscle or epithelial cells. Urethral fibroblasts proliferated at a steady rate and did not exhibit contact-inhibition of growth in a culture medium of Medium 199 supplemented with 10% newborn calf serum. Both immunohistochemistry and metabolic labeling analyses of extracellular matrix synthesis demonstrated the presence of collagen types I and III, and fibronectin. Quantitation of the collagenous components of the cell medium revealed that urethral fibroblasts synthesize 85% type I collagen, 14% type III collagen and < 1% type V collagen. In contrast, the urethral fibroblast cell layer matrix consisted of 98% type I collagen, < 1% type III and < 1% type V collagen.

Animals↗

Bladder smooth muscle cells in culture: I. Identification and characterization.

This report documents the growth and culture characteristics of human and fetal bovine bladder smooth muscle cells in vitro. Bladder smooth muscle cell strains have been identified by their spindle shaped morphology, noncontact inhibited growth characteristics and the expression of smooth muscle cell specific alpha-actin. Extracellular matrix protein biosynthesis by these cells in vitro has been characterized by metabolic labeling of proteins with [14C] radiolabeled proline and analysis by SDS gel electrophoresis. These studies demonstrate that bladder smooth muscle cells synthesize predominantly types I and III collagen, and fibronectin. In addition type III collagen exists in both a partially processed (pN alpha 1[III]) form and processed form. Complementary immunohistochemical studies show localization of type I, III, and IV collagens, and fibronectin to bladder smooth muscle cell extracellular matrix. We conclude that both fetal bovine and human smooth muscle bladder cells are capable of secreting the classic components of the surrounding connective tissue.

Animals↗

Childhood urethral injuries: perspectives on outcome and treatment.

To elucidate the history of childhood urethral injuries, we undertook a retrospective review of 19 male patients comprising 2 groups: those requiring surgical intervention in adulthood and those with complete disruption of the posterior urethra requiring acute intervention (cystostomy drainage). Group 1 patients (n = 12) ranged in age from 17 to 63 years, had sustained urethral injury between the ages of 3 to 15 years and underwent initial surgery from 9 to 18 years after injury. In all 12 patients the strictures developed in the bulbar urethra. All now report continence and normal voiding and none is impotent. Group 2 patients (n = 7) ranged in age from 4 to 16 years and underwent delayed primary reconstruction of the urethral rupture defect. Six patients are now continent with a good stream but the seventh has required repeat optical urethrotomy. One patient with erectile capability at the time of injury was rendered impotent and remains so.

Adolescent↗