Barry A. Kogan

The Pharmacokinetics of Intravesical and Oral Oxybutynin Chloride

In 8 children with cystometric evidence of bladder instability and marked systemic side effects to oral oxybutynin we investigated the efficacy of intravesical instillation and compared the pharmacokinetics of both routes of delivery. In addition, 4 healthy dogs underwent intravesical instillation for pharmacokinetic studies. Intravesical oxybutynin was well tolerated, efficacious and rapidly absorbed, resulting in plasma concentrations markedly higher than after oral administration. In only 2 patients did this method of instillation result in side effects, and both had previously undergone bladder augmentation. This lack of significant systemic side effects despite high plasma concentrations suggests that a metabolite may be generated after oral administration that is responsible for the side effects. These studies demonstrate that the mode of administration affects the mechanism of action, side effects, pharmacokinetics and metabolism of oxybutynin, and that intravesical instillation is clinically effective and results in minimal side effects.

Collagen and Elastin in the Obstructed Fetal Bladder

Histological findings of muscle, collagen and elastin in obstructed fetal bladders were compared with those of age-matched controls. Muscle thickness was markedly increased, however, the relative collagen content in the muscle was decreased. The ratio of thick-to-thin collagen fibers was markedly increased as was the amount of elastin. These findings suggest that the ratio of thick collagen to elastin has an important role in determining the compliance of the obstructed fetal bladder.

Expressing glomerular filtration rate in children

We have reviewed the studies that provide the current standards of reference for glomerular filtration rate (GFR) in normal children from 14 days to 12 years of postnatal age. These standards currently are presented as ml/min per 1.73 m2, i.e., adjusted to average adult body surface area. Children from birth to 1 year of age have adjusted values below the adult range, making comparisons of observed to reference values difficult. Currently, there is no accepted way of obtaining reference values that vary smoothly with age. An analysis of the absolute GFR values in normal children taken from published studies led to an equation that estimates average GFR in relation to weight and term-adjusted age from-2 months (7 months gestational age) to 12 years in children at least 14 days post delivery. When these data are transformed to percentage of normal (% nl) for age and weight (i.e., percentage of the estimated average), it is possible to describe approximate apparent lower limits of normal GFR as is now done for adults and older children. For children with loss of renal mass, GFR expressed as % nl for age and weight provides a convenient standardization which has several useful applications. First, results expressed as % nl for children of different ages, particularly under 1 year of age, can be combined with those of older children for summary purposes. Second, the course of GFR measured serially in children is more appropriately described using this method for expressing GFR. Reporting GFR in absolute values is also useful, particularly in patients whose body mass is significantly distorted or whose absolute GFR is low.

Neurogenic Bladder Dysfunction Due to Myelomeningocele: Neonatal Versus Childhood Treatment

PURPOSE We sought to determine whether the neonatal institution of treatment of neurogenic bladder dysfunction in myelomeningocele patients at high risk for urinary tract deterioration improves renal and bladder outcome. MATERIALS AND METHODS We reviewed the records of patients with bladder dysfunction believed to be at high risk for renal deterioration based on urodynamic studies. All patients were treated with clean intermittent catheterization. We compared rates of urinary infection, hydronephrosis, reflux, continence and surgical intervention in 46 patients in whom treatment was started in year 1 of life and 52 treated after age 4 years. RESULTS Renal outcome was similar in both groups with persistent hydronephrosis in 6 of 46 patients (13%) and 7 of 52 (14%), respectively. However, significantly fewer bladder augmentation procedures were required in patients started on treatment during year 1 of life (5 of 46, 11% versus 14 of 52, 27%, p < 0.05). CONCLUSIONS In addition to any psychological benefit, early intervention with clean intermittent catheterization in children with neurogenic bladder dysfunction may help to prevent irreversible bladder dysfunction and limit the need for bladder augmentation.

Pediatric Urology: Postoperative Adhesion Formation After Urological Laparoscopy in the Pediatric Population

The risk of intraperitoneal adhesion formation is a concern with transperitoneal laparoscopic surgery. To evaluate the incidence of adhesions after interventional urological laparoscopy, we reviewed 41 pediatric patients who had undergone second-look procedures. The number of adhesions and quantitation of the degree of each adhesion were assessed. Major laparoscopic procedures were performed previously in 8 patients, moderate in 29 and minor in 4. Adhesions were noted in 4 patients (9.8%), including 2 adhesions at the operative site and 2 at trocar sites. The risk of adhesions increased with the extent of dissection. Two adhesions developed after major procedures but the grade and extent of these adhesions were minimal. In the majority of patients re-peritonealization occurred with minimal or no scarring noted. Although adhesions may occur with pediatric urological laparoscopic procedures, the incidence appears lower than what one would expect with open exploration.

Gastrocystoplasty: long-term followup.

PURPOSE Gastrocystoplasty is no longer favored at many institutions due to complications, including the hematuria-dysuria syndrome and metabolic alkalosis. We reviewed our experience to determine the advantages and disadvantages of bladder augmentation using stomach body wall. MATERIALS AND METHODS We retrospectively reviewed the medical records, urodynamic studies, x-rays and laboratory evaluations of 47 children who underwent gastrocystoplasty at our institution between 1986 and June 1997. Parents and patients were contacted by telephone for detailed interviews to validate the medical record and determine whether there had been any changes since the last visit. Followup ranged from 9 months to 11 years (mean 4.4 years). Bladder dysfunction was secondary to spinal dysraphism in 38 children. Other diagnoses included cloacal and bladder exstrophy, posterior urethral valves, a persistent urogenital sinus and bilateral ectopic ureters. RESULTS Preoperative and postoperative ultrasound studies available for 79 renal units demonstrated a stable or improved upper tract in 75 (95%). Preoperative and postoperative serum sodium, potassium and creatinine levels showed no significant changes. Mean serum chloride decreased 2.7 mEq./l. and bicarbonate increased 3.3 mEq./l. In the 3 patients with renal insufficiency serum bicarbonate increased 8 mEq./l. Mean pressure specific bladder volume at less than 20 cm. water increased 177 cc and mean maximum bladder pressure decreased from 35 to 13 cm. water. Two-thirds of the patients had bacilluria and a fourth reported a symptomatic bladder infection. No patients had bothersome mucus or required routine bladder irrigation. Symptoms consistent with the hematuria-dysuria syndrome were present in 27% of the patients. No patients had symptoms more than once weekly. Symptoms occurred in 75% of the patients without a neurogenic bladder, such as exstrophy or posterior urethral valves, and in 14% of those with neurogenic bladder dysfunction. In 1 case a bladder stone developed 8 years after surgery. Five patients required reoperation for complications related to gastrocystoplasty. No patient had perforation. CONCLUSIONS Our data show that even after a mean of 4.4 years gastrocystoplasty has significant advantages over intestinal augmentation, including decreased chloride reabsorption, mucous production and urinary infection, and an extremely low incidence of stones and perforation. The gastric patch is associated with metabolic alkalosis and the hematuria-dysuria syndrome, which may be avoided and medically treated with proper patient selection and close followup. The procedure should be avoided in sensate patients with sufficient bowel.

Stented versus nonstented pediatric pyeloplasty: a modern series and review of the literature.

PURPOSE Dismembered pyeloplasty remains the principal surgical therapy for pediatric ureteropelvic junction obstruction, although the method of postoperative drainage continues to be debated. We compared stented versus nonstented repairs in a modern series. MATERIALS AND METHODS We evaluated 117 pediatric dismembered pyeloplasties performed by 3 pediatric urologists at 2 institutions from 1991 to 2000. Hospital stay, success rate and complication rate were reviewed. Results were compared with 833 evaluable cases in the literature. RESULTS Of the 52 stented repairs urological complications developed in 6 (12%), including symptomatic urinary tract infection in 3 and temporary obstruction in 3. Of the 65 nonstented repairs urological complications developed in 10 (15%), including prolonged leakage in 3, urinoma in 3, obstruction in 3 and urinary tract infection in 1. Mean hospitalization plus or minus standard error was shorter in the stented group (2.1 +/- 0.89 versus 2.6 +/- 1.1 days, p <0.02). We identified 9 previous studies comparing a total of 339 stented with 494 nonstented repairs. Overall the number of complications was almost equal (12% versus 14%) but the stented group had more infections, whereas more leaks occurred in the nonstented group. The nonstented group required more secondary procedures (12 of 339 versus 45 of 494, p = 0.003). Hospital stay was 12 days for stented and 5 days for nonstented repair in these earlier series. CONCLUSIONS In children the outcome of stented pyeloplasty is similar to that of nonstented repair. In contrast to previous reports, using a stent for drainage should not necessitate a longer hospital stay.

Collagen and Elastin in the Normal Fetal Bladder

The development of muscle, collagen and elastic fibers was studied histologically in 15 human fetal bladder specimens. Muscle thickness progressively increased and the relative collagen content in the muscle decreased during gestation. The ratio of thick-to-thin collagen fibers also decreased, whereas elastic fibers increased. These findings document the normal process of maturation of the fetal bladder and serve as a basis for comparison with congenitally obstructed fetal bladders.

Therapeutic laparoscopy for intra-abdominal testes.

Fourteen laparoscopic surgical procedures were performed in 10 children with 11 intra-abdominal testes. In addition to localizing the testes, laparoscopy aided in the surgical approach. In 8 patients, the first phase of a two-stage Fowler-Stephens orchiopexy was performed. Five children underwent an open surgical procedure three months later and have a viable testis in the scrotum after at least nine months of follow-up. In 5 patients (6 testicles), laparoscopy was used to dissect the testis. Three patients underwent the second phase of the two-stage Fowler-Stephens procedure laparoscopically. In all 3 patients, the testicle could be easily mobilized into the scrotum. Two other testicles were mobilized by dissecting the spermatic vessels up to the renal hilum laparoscopically; this allowed the intra-abdominal testes to come into the scrotum without dividing the spermatic vessels. In one teenager with a small intra-abdominal testis and a normal contralateral testis, laparoscopic orchiectomy was performed. We believe laparoscopy has a role both diagnostically and surgically in the treatment of intra-abdominal testes.

Vesicourethral Function in Mice With Genetic Disruption of Neuronal Nitric Oxide Synthase

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