PubMed Health⌕ Search

Biomedical subjects

M Kaefer

Publications and source records attributed to M Kaefer.

At least 19 recordsLinked to original sources
PubMed2006

What is the need for additional bladder surgery after bladder augmentation in childhood?

PURPOSE: Bladder augmentation has revolutionized the care of children with a neuropathic bladder but it remains a major surgical procedure. However, the need for subsequent bladder surgery has not been well defined in a large series with long-term followup. MATERIALS AND METHODS: We retrospectively reviewed the records of the first 500 bladder augmentations performed from 1978 to 2003 at our institution. Charts were reviewed for complications requiring additional surgery, including malignancy, bladder perforation, repeat augmentation, bowel obstruction and bladder calculi. Mean and median followup was 13.3 years. RESULTS: Complications occurred in 169 patients (34%) resulting in a total of 254 surgeries. The cumulative risk of further surgery at the bladder level was 0.04 operations per patient per year of augmentation. Three patients (0.6%) had transitional cell carcinoma, of whom all presented with metastatic disease and died. Bladder perforation occurred in 43 patients (8.6%) with a total of 53 events. Of the patients 16 (3.2%) required laparotomy for bowel obstruction and 47 (9.4%) required repeat augmentation. Bladder stones were treated in 75 patients (15%), who required a total of 125 surgeries. CONCLUSIONS: Bladder augmentation provides immeasurable improvements in quality of life but it requires lifelong dedication from the patient, family and health care providers. While the requirements for additional surgery are not trivial, 66% of our patients have not required any further surgery in the augmented bladder.

Child↗
PubMed2006

Treatment of the occult tethered spinal cord for neuropathic bladder: results of sectioning the filum terminale.

PURPOSE: Occult tethered cord syndrome applies to patients with signs and symptoms consistent with a caudal spinal cord malformation despite normal neuroimaging. Although several reports of successful surgical treatment exist, controversy remains with respect to patient selection and efficacy. We present a large series with excellent clinical followup, neuroimaging and urodynamic characterization. MATERIALS AND METHODS: We present our experience with 36 patients at a single institution with preoperative clinical findings, neuroimaging and urodynamics available. Postoperative outcomes were assessed clinically and with urodynamics. We determined predictive parameters to improve patient selection. RESULTS: Approximately 0.04% of pediatric urology clinic visits resulted in neurosurgical referral for the potential of an occult tethered cord. They occurred after failure of a mean of 2 years of aggressive medical management. Daytime urinary incontinence was present in 83% of patients and 47% had encopresis. Preoperative urodynamics were markedly abnormal in all patients with mean bladder capacity 55% of expected capacity. Clinical improvement in urinary symptoms was seen in 72% of patients with resolution of incontinence in 42%. Bowel symptoms improved in 88% of cases, including resolution of encopresis in 53% within 3 months of surgery. Urodynamic improvements were demonstrated in 57% of cases. We were unable to determine preoperative factors that were more likely associated with surgical success. CONCLUSIONS: In a highly select population with severe urinary and fecal dysfunction sectioning a normal-appearing filum terminale can result in significant improvement. We were unable to identify factors that may increase the chance of surgical success.

Adolescent↗
PubMed2003

Neonatal scrotal haematoma: mimicker of neonatal testicular torsion.

OBJECTIVE: To describe the clinical features of neonatal scrotal haematoma and distinguish them from those of neonatal testicular torsion. PATIENTS AND METHODS: Five neonates presenting with an acute scrotum and initial diagnosis of neonatal testicular torsion were found to have neonatal scrotal haematoma. In one case the diagnosis was surgical and in four subsequent cases the diagnosis was by colour Doppler ultrasonography, and surgery was avoided. Four of the five children had risk factors associated with neonatal scrotal haematoma, including bleeding diathesis, birth trauma and high birth weight. CONCLUSIONS: The importance of including haematoma in the differential diagnosis of the acute neonatal scrotum is emphasized, as is the value of contemporary Doppler ultrasonography in making this diagnosis.

Diagnosis, Differential↗
PubMed2001

Vascular endothelial growth factor-mediated autocrine stimulation of prostate tumor cells coincides with progression to a malignant phenotype.

Vascular endothelial growth factor (VEGF), which is often produced at high levels by tumor cells, is a well-known mediator of tumor angiogenesis. VEGF receptor tyrosine kinases, KDR/Flk-1 and Flt-1, have been thought to be expressed exclusively by endothelial cells. In this study, we have used a prostate tumor progression series comprised of a differentiated rat prostate epithelial cell line, NbE-1, and its highly motile clonal derivative, FB2. Injection of NbE-1 cells into the inferior vena cava of syngeneic rats indicated that these cells are nontumorigenic. Using the same model, FB2 cells generated rapidly growing and well-vascularized tumors in the lungs. NbE-1 expressed marginal levels of VEGF, whereas high levels of VEGF protein were detected in FB2-conditioned medium and in FB2 tumors in vivo. Analysis of (125)I-VEGF(165) binding to NbE-1 and FB2 cells indicated that only motile FB2 cells expressed the VEGF receptor Flt-1. Consistent with this finding, physiological concentrations of VEGF induced chemotactic migration in FB2 but not in NbE-1 cells. This is the first documentation of a functional Flt-1 receptor in prostate tumor cells. Our results suggest two roles for VEGF in tumor progression: a paracrine role as an angiogenic factor and a previously undescribed role as an autocrine mediator of tumor cell motility.

Animals↗
PubMed2001

Symptomatic ureteropelvic junction obstruction in children in the era of prenatal sonography-is there a higher incidence of crossing vessels?

OBJECTIVES: To determine whether prenatal sonography and early detection and correction of ureteropelvic junction obstruction (UPJO) has changed the incidence of crossing vessels as the etiology of obstruction in older children presenting with symptomatic UPJO. METHODS: We reviewed the medical records of all children and adolescents who underwent pyeloplasty for symptomatic UPJO between 1986 and 1999, during the era of widespread use of prenatal sonography. Operative notes were used to determine which patients had obstruction due to lower pole crossing vessels. RESULTS: Thirty-eight patients were identified who underwent pyeloplasty for symptomatic UPJO. Lower pole vessels were identified in 22 (58%) of 38 patients (P <0.0001 compared with historical controls). All patients underwent dismembered pyeloplasty and remained asymptomatic after surgery, with renal scans demonstrating excellent drainage and preservation of function. CONCLUSIONS: Prenatal ultrasonography has increased the incidence of crossing vessels as the etiology of UPJO in young children and adolescents presenting with symptomatic UPJO compared with the historical incidence of 11% to 15%. This finding may impact treatment recommendations with respect to endourologic management of the obstruction in this patient population. Currently, we recommend open dismembered pyeloplasty for young children and adolescents presenting with symptomatic UPJO.

Child↗
PubMed2001

Nodular Leydig cell hyperplasia in a boy with familial male-limited precocious puberty.

In boys with familial male-limited precocious puberty, an activating mutation of the luteinizing hormone receptor causes Leydig cell hyperplasia, resulting in excess testosterone production. There are no reports of Leydig cell masses in boys with familial male-limited precocious puberty. We describe a 10-year-old boy with familial male-limited precocious puberty who developed Leydig cell nodules.

Child↗
PubMed2001

Tap water and the Malone antegrade continence enema: a safe combination?

PURPOSE: The Malone antegrade continence enema provides independence and improved quality of life in patients with fecal incontinence or intractable constipation. However, isolated reports of fatal hypernatremia after irrigation with normal saline have raised safety concerns about frequent colonic irrigation in children. Significant electrolyte abnormalities have also been reported with hypertonic phosphate and high colonic tap water enemas. Because our patients routinely use tap water for Malone antegrade continence enema irrigations, we examined the safety profile of this practice MATERIALS AND METHODS: In the last 3.5 years 71 patients at our institution have used antegrade tap water enemas for managing fecal incontinence or intractable constipation. Standard serum electrolytes were measured RESULTS: We obtained 101 sets of serum electrolyte measurements in 71 patients at a mean of 8.4 months postoperatively (range 1 to 33). A girl who presented with severe hyponatremia and hypochloremia had not used the Malone antegrade continence enema for several days. The most interesting finding was significantly elevated sodium and chloride in 1 case 6 weeks after surgery that was associated with tap water treated with a home softening system. Electrolytes reverted to normal 1 week after using untreated tap water CONCLUSIONS: We did not detect significant hyponatremia or hypochloremia in any patient using tap water for Malone antegrade continence enema irrigation. Although dangerous electrolyte abnormalities are rare, potential morbidity in those cases warrants periodic evaluation. Due to the elevated sodium content in softened tap water families should be alerted to use untreated tap water for preparing enemas.

Adolescent↗
PubMed2000

Abdominal wall hernia: an uncommon complication of in utero vesicoamniotic shunt placement.

Three cases are reported in which placement of a vesicoamniotic shunt in utero for the treatment of obstructive uropathy led to the rare complication of abdominal wall hernia. All 3 patients underwent vesicoamniotic shunt placement for severe oligohydramnios and a markedly dilated bladder in an effort to preserve renal function and to prevent pulmonary hypoplasia. All three shunts were initially placed at or above the umbilicus. The abdominal wall hernias were closed postnatally at the time of temporary vesicostomy for urethral obstruction. All 3 patients had sufficient pulmonary development, but 2 of 3 had renal failure, requiring dialysis. Management and potential etiology of this rare complication are discussed.

Amnion↗
PubMed2000

The overactive bladder in childhood: long-term results with conservative management.

PURPOSE: Idiopathic detrusor overactivity has not been thoroughly investigated and its natural history remains largely anecdotal. Bladder overactivity resulting from a neurogenic, anatomical or medical condition has been well described. Therefore, we assessed the long-term results of conservative treatment of children with idiopathic symptomatic refractory detrusor instability. MATERIALS AND METHODS: We reviewed the records of 58 patients who had an isolated finding of uninhibited contractions on urodynamics performed for refractory enuresis and daytime wetting between 1988 and 1994. Study exclusion criteria were chronic urinary tract infection, neurological lesion, anatomical abnormality of the lower urinary tract and less than 12 months of followup. RESULTS: Of the 30 children who met our study inclusion criteria 26 (87%) had complete (21) or significant (5) symptom resolution. Average time to resolution was 2.7 years (range 0.2 to 6.6). Patients with a 50% to 90% bladder capacity expected for age were more likely to benefit from therapy than those with a bladder capacity outside of this range. Age and gender were not significant predictors of resolution although girls were more likely to have resolution than boys. CONCLUSIONS: Idiopathic detrusor instability is amenable to conservative management in the majority of patients during a prolonged period. We advocate thorough urological and urodynamic evaluation to identify idiopathic detrusor instability as an etiology of enuresis and daytime wetting in complicated cases.

Adolescent↗
PubMed2000

Genitourinary rhabdomyosarcoma. Treatment options.

Dramatic improvements have occurred in the treatment and prognosis of the child with rhabdomyosarcoma over the past 2 decades. Increased understanding of tumor behavior has improved survival and focused attention on important quality of life issues. Future therapeutic advances will depend largely on an improved molecular understanding of altered cell behavior and the continued efforts of multi-institutional studies.

Child↗
PubMed2000

Sibling vesicoureteral reflux in multiple gestation births.

BACKGROUND: Vesicoureteral reflux (VUR) is the most commonly inherited disease of the genitourinary tract. Although the majority of evidence supports a genetic cause, the tendency for this condition to spontaneously improve over time has made it difficult to determine the actual mode of transmission. We report the incidence of VUR in siblings of multiple gestation births and for the first time compare the relative incidence of reflux between identical and fraternal twins. METHODS: A database consisting of all radionuclide cystograms and voiding cystourethrograms performed between the years 1986 and 1996 was searched for multiple gestation births. The medical records of each patient were evaluated for age at presentation, zygosity, reflux grade, and time to resolution. Children with secondary causes of VUR (eg, posterior urethral valves) were excluded. Triplets were treated as 2 pairs of twins for statistical analysis. RESULTS: Forty-six pairs met the inclusion criteria (31 dizygotic and 15 monozygotic). Overall, 23 (50%) of 46 siblings of index cases had demonstrable VUR. Comparison of VUR prevalence between identical and nonidentical twins was revealing with 80% (12/15) of identical twins and 35% (11/31) of fraternal twins having VUR. When only the youngest individuals in each group were considered, 100% (7/7) of the monozygotics and 50% (5/10) of the dizygotics demonstrated this trait. CONCLUSIONS: High concordance for VUR in identical twin siblings supports a genetic basis for the transmission of this disease. Results obtained from fraternal twin siblings provides convincing evidence that this trait is transmitted in an autosomal dominant fashion.

Child↗
PubMed2000

A nontoxic diphtheria toxin analogue inhibits neonatal bladder smooth muscle cell proliferation.

PURPOSE: The response of the neonatal bladder to infravesical obstruction, such as posterior urethral valves or detrusor-sphincter dyssynergia, may result in structural and functional changes that persist well after obstruction is treated. A pharmacological means of inhibiting smooth muscle cell proliferation would likely serve to halt or reverse this deleterious process. Heparin binding (HB) epidermal growth factor (EGF) is a known smooth muscle cell mitogen, while its membrane bound precursor serves as the diphtheria toxin receptor. We report the effects of the nontoxic diphtheria toxin analogue cross reacting material (CRM) 197 on neonatal sheep bladder smooth muscle cell proliferation. MATERIALS AND METHODS: Neonatal sheep smooth muscle cell cultures were obtained from whole bladder explants. Immunohistochemical staining was performed for desmin and alpha-smooth muscle actin. HB-EGF messenger RNA was detected by reverse transcriptase polymerase chain reaction using primers to the human sequence, while pro-HB-EGF peptide was confirmed using a diphtheria toxin sensitivity assay with incorporation of tritiated leucine. Cells grown in 96 well plates were exposed to 1, 10 and 100 microg./ml. CRM 197 for 5 days, after which relative cell number was determined using an 3-[4,5-dimethylthiazol-2-yl] -2,5-diphenyltetrazolium bromide; thiazolyl blue based assay read at a wavelength of 550 nm. Statistical analysis was performed using Student's t test. RESULTS: Primary cell cultures stained positive for desmin and alpha-smooth muscle actin, confirming a smooth muscle origin. Reverse transcriptase polymerase chain reaction yielded a 453 bp product with 88% homology to human HB-EGF. Total protein synthesis significantly decreased when cells were incubated with diphtheria toxin, confirming the presence of membrane bound pro-HB-EGF. CRM 197 inhibited bladder smooth muscle cell growth in a dose dependent fashion at a concentration of 10 microg./ml., resulting in a 40% decrease in proliferation (p <0.0001). CONCLUSION: CRM 197 inhibits bladder smooth muscle cell proliferation in a dose dependent, nontoxic fashion through its interaction with HB-EGF. These data suggest that molecular strategies designed to inhibit HB-EGF mediated cell growth may prove beneficial for the prevention and/or treatment of detrusor hypertrophy secondary to anatomical or functional bladder outlet obstruction.

Animals↗
PubMed2000

Inhibition of pressure induced bladder smooth muscle cell hyperplasia using CRM197.

PURPOSE: In vivo the effects of sustained hydrostatic pressure on the bladder wall and its components are evident under physiological and pathological conditions. We previously reported that exposure of bladder smooth muscle cells to 20 and 40 cm. H2O hydrostatic pressure for as little as 1 hour resulted in the up-regulation of heparin binding epidermal growth factor messenger RNA in a time dependent fashion as well as in activation of the heparin binding epidermal growth factor growth factor gene. In our current study we investigated the use of CRM197 as an agent for blocking undesirable cellular level events, such as smooth muscle cell hyperplasia, eliminating the irreversible alterations in bladder and kidney function that result from chronic and/or severe bladder outlet obstruction. MATERIALS AND METHODS: Control and experimental neonatal ovine smooth muscle cells were exposed to 0.3 pressure and 8.5 cm. H2O, respectively, for 7 days. We evaluated the mitogenic activity of the supernatant medium from bladder smooth muscle cells exposed to 8.5 cm. H2O for 5 days (conditioned medium) before and after the addition of 0.1 mg./ml. CRM197. Bladder smooth muscle cell apoptosis was also assessed after CRM197 exposure. Statistical analysis was performed using the Student t test with p <0.05 considered significant. RESULTS: Exposing bladder smooth muscle cells to sustained 8.5 cm. H2O hydrostatic pressure for 7 days resulted in increased cell proliferation. Conditioned medium contained mitogenic activity, which was ablated after CRM197 was added. No direct toxic effect of CRM197 on bladder smooth muscle cell growth was appreciated (no apoptosis). CONCLUSIONS: We demonstrated a proliferative response of neonatal bladder smooth muscle cells after exposure to sustained hydrostatic pressure. This response was partially due to the release of heparin binding epidermal growth factor and was blocked by adding CRM197. These data support the potential use of CRM197 in drug targeted therapy for diseases involving bladder outlet obstruction.

Apoptosis↗
PubMed1999

The incidence of intersexuality in children with cryptorchidism and hypospadias: stratification based on gonadal palpability and meatal position.

PURPOSE: The combined findings of cryptorchidism and hypospadias often indicate the existence of an intersex state. Testicular maldescent and incomplete tubularization of the urethral plate occur in a spectrum with the severity of the 2 processes likely dependent on the degree of pathophysiology in the androgenic hormonal axis. The incidence of intersexuality in children with undescended testes, hypospadias and otherwise nonambiguous male genitalia has been reported to be 27%. Although the likelihood of genotypic or gonadal ambiguity has previously been associated with meatal position in this population, to our knowledge our study is the first to evaluate the incidence of intersexuality relative to whether the undescended testis is palpable or nonpalpable. MATERIALS AND METHODS: The database at our hospital was searched for all cases of undescended testes (2,105) and hypospadias (1,057) between 1982 and 1996. Radiographic, histological and karyotypic data were compiled for all patients presenting with both diagnoses. Gonadal palpability (palpable versus nonpalpable) and meatal position (anterior versus mid versus posterior) were recorded and correlated with the likelihood of identifying an intersex condition. Ten boys with a diagnosis of undescended testes subsequent to inguinal hernial repair were excluded from study. Patients with congenital adrenal hyperplasia or complete testicular feminization were also excluded from study due to the clearly female appearance of the external genitalia. Statistical significance was assessed using Fisher's exact test. RESULTS: We identified 79 patients presenting with undescended testes, hypospadias and a phallus that was believed to be a possible penis. Intersex conditions were identified with nearly equal frequency in the 44 cases of unilateral (30%) and 35 of bilateral (32%) cryptorchidism. In the unilateral undescended testes group patients with a nonpalpable testis were at least 3-fold more likely to have an intersex condition than those with a palpable undescended testis (50 versus 15%, p = 0.02). In the bilateral group patients with 1 or more nonpalpable testes were also nearly 3-fold as likely to have an intersex condition than those with bilateral palpable undescended gonads (47 versus 16%, p = 0.07). Meatal position was graded as anterior in 33% of cases, mid in 25% and posterior in 41% with the more posterior location conferring a significantly greater likelihood of an intersex condition (anterior 2 of 26, mid 1 of 20 and posterior 21 of 33). CONCLUSIONS: Gonadal palpability is an important predictor of an intersex state in unilateral and bilateral cases of cryptorchidism with hypospadias. Patients with an undescended testis that cannot be palpated are significantly more likely to have an intersex condition than those in whom the undescended testis may be palpated on physical examination. The severity of hypospadias likewise has a strong positive correlation with an intersex state.

Child↗
PubMed1999

Improved bladder function after prophylactic treatment of the high risk neurogenic bladder in newborns with myelomentingocele.

PURPOSE: High pressure dyssynergic voiding may result in irreversible damage to the urinary tract. Prophylactic therapy in the form of clean intermittent catheterization and anticholinergic medication may significantly decrease the incidence of upper urinary tract deterioration. Whether prophylactic therapy in the high risk bladder may also lead to improved long-term bladder dynamics prompted us to study the effect of early versus late treatment of bladder hypertonicity and detrusor-sphincter dyssynergia on the ultimate need for bladder augmentation. MATERIALS AND METHODS: We retrospectively reviewed urological outcomes in patients with myelodysplasia who were at risk for urological deterioration within year 1 of life based on bladder sphincter dyssynergia and/or high filling or voiding pressure. We recorded the dates when high risk voiding dynamics were initially observed, and when intermittent catheterization and anticholinergic therapy were initiated. Patients in whom treatment began at the time a high risk profile was noted (prophylactic group seen between 1985 and 1990) were compared to controls with the same high risk voiding parameters who did not receive early therapy (observation group seen between 1978 and 1984 with therapy instituted 1 year or longer after high risk was noted). The number of augmentations performed in each group was indexed to the total number of years of followup in the 2 populations, respectively. Patients with less than 2 years of followup were excluded from further analysis. RESULTS: Of the 45 patients at risk clean intermittent catheterization and anticholinergic medication were immediately initiated in 18, while 27 were treated expectantly. Patients in the observation group were followed an average of 4.1 years (range 1.1 to 14) before clean intermittent catheterization and anticholinergic medication were started. Of the 27 children treated expectantly 11 (41%) required augmentation, whereas only 3 of the 18 (17%) treated prophylactically required enterocystoplasty. When the number of augmentations was indexed to total years of followup in each of the 2 groups (296 versus 156 years) patients in the expectant group were nearly twice as likely to require augmentation. CONCLUSIONS: Identification and early proactive treatment of the high pressure, dyssynergic lower urinary tract significantly decreases the need for bladder augmentation as children with neurogenic bladder secondary to myelomeningocele mature.

Adolescent↗
PubMed1999

Urodynamic findings in children with isolated epispadias.

PURPOSE: The exstrophy-epispadias complex represents a spectrum of anomalies with variable implications for upper and lower urinary tract function. Successful treatment of incontinence in this population is challenging and often elusive. To date few studies have focused on urodynamic findings specific to primary epispadias. MATERIALS AND METHODS: We retrospectively reviewed the records of patients presenting with primary epispadias in the absence of bladder exstrophy. We identified 18 boys and 12 girls, of whom 16 underwent formal urodynamic evaluation before (5), after (6) or before and after (5) surgical narrowing of the bladder neck. Bladder capacity was recorded as percent of expected capacity for age. Bladders were considered hypertonic when end filling pressure was greater than 20 cm. water. End filling pressure was defined as the pressure at which urinary leakage was noted or the patient had discomfort. Uninhibited contractions were considered significant when the amplitude was greater than 15 cm water. The ability of the detrusor to generate a voiding contraction at the end of the filling phase was also recorded. Urodynamic studies were performed with a balloon catheter occluding the incompetent bladder neck or with a standard urodynamic catheter after formal bladder neck repair. RESULTS: Before bladder neck repair average bladder capacity was 157 ml (range 55 to 450), corresponding to 52% (range 22 to 100) of expected capacity. Significant uninhibited contractions were noted in 2 patients. In 7 of the 9 evaluable patients (78%) a voiding contraction was generated. In children in whom urodynamic studies were done after surgery mean bladder capacity was 260 ml (range 77 to 660), corresponding to 76% (range 36 to 147) of expected capacity. Hypertonicity and hyperreflexia were noted in 3 and 2 patients, respectively. In 5 of the 11 cases (46%) a voiding bladder contraction was generated. Of the 5 patients who underwent urodynamic evaluation before and after bladder neck repair the percent increase in bladder capacity was significantly greater in the 2 boys (67 and 110%, respectively) than in the 3 girls (-20, 10 and 20, respectively). CONCLUSIONS: The most frequently noted urodynamic pattern before surgical correction of the bladder neck in patients with isolated epispadias is a low capacity, highly compliant bladder with minimal detrusor dysfunction. Postoperatively capacity increases, albeit to a greater extent in boys than in girls, and the incidence of detrusor dysfunction increases as well. In some patients classic bladder neck repair may result in detrimental bladder dynamics due to as yet poorly elucidated mechanisms.

Adolescent↗
PubMed1999

The effects of sustained hydrostatic pressure on select bladder smooth muscle cell functions.

PURPOSE: Normal bladder development is believed to depend on the active work of the bladder for storing and expelling urine. When high urinary diversion is performed in infants and the bladder no longer undergoes normal filling, bladder development may be altered, ultimately resulting in bladder dysfunction. To help better understand this relationship of bladder function with growth at the cellular level we developed a novel laboratory method for applying hydrostatic pressure to cell cultures, and we characterized the response of neonatal bladder smooth muscle cells to physiological levels of sustained hydrostatic pressure. MATERIALS AND METHODS: Neonatal ovine smooth muscle cells staining positive for desmin and alpha-smooth muscle actin were exposed to pressures of 0.3 (controls), 2, 4, 6 and 8.5 cm. water for 1, 3, 5 and 7 days. At the end of the experiments the cells were fixed, stained and counted. Mitogenic activity of the supernatant media from bladder smooth muscle cells exposed to 8.5 cm. water for 5 days (conditioned media) was tested before and after treatments of heating, freezing, passing through a heparin-sepharose affinity chromatography column or after the addition of suramin, a nonspecific growth factor inhibitor. Statistical analysis was performed using Student's t test with p <0.05 considered statistically significant. RESULTS: Exposure of bladder smooth muscle cells to sustained hydrostatic pressures of 4, 6 and 8.5 cm. water resulted in increased cell proliferation. Differences became statistically significant (p <0.05) by day 5. Also, conditioned media contained mitogenic activity that was ablated by heating, freezing, passage through a heparin-sepharose affinity chromatography column or with the addition of suramin. CONCLUSIONS: We have demonstrated a proliferative response of neonatal bladder smooth muscle after exposure to physiological levels of sustained hydrostatic pressure. This response is partially due to 1 or more transferable mitogenic factors. These data support the hypothesis that pressure associated with bladder filling is an important stimulus for detrusor development.

Animals↗