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Biomedical subjects

B A Kogan

Publications and source records attributed to B A Kogan.

At least 73 records · Page 4Linked to original sources

Role of MRI in the evaluation of ambiguous genitalia.

Diagnostic accuracy of magnetic resonance imaging (MRI) interpretation was assessed prospectively in patients with ambiguous genitalia or intersex problems. MRI depiction of the uterus was possible in 93%, the vagina in 95%, the penis in 100%, the testis in 88%, and the ovary in 74% of patients. The strength of MRI lies in the multiplanar capability and tissue characterization by means of T1- and T2-weighted sequences. MRI contributes to accurate morphologic evaluation of müllerian duct structures, the gonads, and the development of the phallus, all of which are essential for appropriate gender assignment and planning of surgical reconstruction.

Adolescent↗

Loss of elasticity in dysfunctional bladders: urodynamic and histochemical correlation.

To store adequate volumes of urine at low safe pressures an elastic bladder wall is required. We developed 2 new techniques to measure this ability in our urodynamic laboratory: pressure specific bladder volume, which measures the bladder capacity at a given pressure, and dynamic analysis of bladder compliance. Recently, morphometric and histochemical techniques have been used to determine the relative volume of connective tissue in the bladder wall and to measure the 2 major types (I and III) of collagen within the bladder wall. These methods quantitate 3 parameters of bladder ultrastructure: 1) relative volume of per cent connective tissue, 2) ratio of connective tissue to smooth muscle and 3) ratio of type III to type I collagen. These parameters have been shown to be abnormally elevated in patients with dysfunctional bladders compared to normals. The purpose of the study was to describe the ultrastructural changes that occur in the wall of dysfunctional bladders and to determine the ability of these new urodynamic techniques to detect reliably the clinical effect of these histological changes. The study included 29 consecutive patients with dysfunctional bladders necessitating bladder augmentation. All patients had upper tract changes and/or were incontinent despite treatment with clean intermittent catheterization and pharmacotherapy. Preoperative urodynamic evaluation included measurement of the total bladder capacity, pressure specific bladder volume and dynamic analysis of bladder compliance. Full thickness bladder biopsies were obtained from the dome of the bladders during augmentation. The per cent connective tissue and the ratio of connective tissue to smooth muscle were determined for all patients, and 4 unselected patients from this group had the ratio of type III to type I collagen determined. These histological results were compared to previously established normal values. All 29 patients had a decreased pressure specific bladder volume and dynamic analysis of bladder compliance, whereas 9 had a normal total bladder capacity. The per cent connective tissue was 35.19 +/- 2.84 and ratio of connective tissue to smooth muscle was 0.60 +/- 0.08 compared to normal values of 10.6 +/- 0.020 and 0.131 +/- 0.021, respectively (p < 0.05). Ratio of type III to type I collagen was also significantly elevated in the 4 samples analyzed (30.53 +/- 1.37 versus 24.00 +/- 2.50, p < 0.05). We conclude that poor storage function of poorly compliant bladders is secondary to an alteration in the connective tissue content of the bladder wall. Furthermore, these pathological ultrastructural changes are universally reflected by an abnormally low pressure specific bladder volume and dynamic analysis of bladder compliance. This strong association validates the use of these parameters and suggests that they are urodynamic indicators of a loss of elasticity in bladder wall.

Adolescent↗

Role of nitric oxide in fetal lower urinary tract function.

We studied the role of nitric oxide (NO) in normal function of the lower urinary tract in fetal lambs. Fetal surgery was performed in pregnant ewes at 118 days' gestation (term 145-days) to place arterial, venous, and double-lumen urachal catheters. Five animals had a catheter secured in the distal urethra (to measure voided volume), and six underwent ligation of the urethra. Urodynamic studies were performed via the urachal catheter under baseline conditions, during systemic blockade of NO synthesis with N omega-nitro-L-arginine, and with systemic NO stimulation by L-arginine 48 hours postoperatively. Nitric oxide blockade caused an 88% mean increase in bladder capacity (volume to initiation of voiding) (p < 0.001) and a 5.8-fold increase in mean postvoid residual volume (p < 0.0001) despite normal maximal bladder pressures, suggesting inadequate sphincteric relaxation. Qualitatively, NO inhibition increased the presence of low-level bladder contractions and caused a trend toward decreased bladder compliance. Increase of NO substrate by L-arginine infusion restored baseline findings if performed after N omega-nitro-L-arginine. Stimulation of NO by L-arginine infusion caused continuous efflux of the infusate secondary to a persistently open sphincter. In conclusion, NO is active in the function of the lower urinary tract in the fetal lamb and appears to influence both sphincter and detrusor activity.

Animals↗

Renal hemodynamic and functional effects of 10 days' partial urinary obstruction in the fetal lamb.

We studied fetal lambs to define the renal pathophysiology of chronic in utero partial bladder outlet obstruction. These fetal lambs, 115 to 120 days gestation (term = 145 days), underwent urethral ligation, placement of a urachal catheter and positioning of an ultrasonic flow transducer around the left renal artery. Partial obstruction was created by placing a narrow connector between the urachal and an amniotic catheter. In control animals a large connector was placed to allow free drainage of the bladder into the amniotic cavity. Renal blood flow was measured daily, and urine was collected at days 5 and 10 to evaluate renal function. In control animals, no significant changes in any parameters were observed. In the partially obstructed fetal lambs, renal blood flow increased to 165% of baseline after 5 days; from 5 to 10 days, it decreased, but remained above baseline values through 10 days (128%). Urine production dropped significantly after 10 days (67%). Glomerular filtration rate increased slightly after 5 days (127%), but decreased after 10 (56%). Filtration fraction steadily decreased after 5 (70%) and 10 days (33%). Fractional and total sodium excretion did not change. Renal blood flow increases, filtration fraction decreases and renal function trends progressively diminish in response to partial bladder outlet obstruction over a period of 10 days in the fetal lamb.

Animals↗

Pediatric ureteropelvic junction obstruction treated with retrograde endopyelotomy.

OBJECTIVES: To determine the feasibility of retrograde endopyelotomy in the management of pediatric ureteropelvic junction (UPJ) obstruction. METHODS: We treated 2 boys aged 4 and 6 years with the Acucise endopyelotomy device for symptomatic ureteropelvic junction obstruction. The Acucise device was placed over a Lunderquist guide wire with fluoroscopic guidance only and routine Double J catheters were left in situ for 6 weeks after the procedure. The morbidity of the treatment and the short-term outcome were assessed. RESULTS: There were no acute complications and short-term follow-up results were satisfactory as determined by intravenous urography and diuretic renography. CONCLUSIONS: Ureteropelvic junction obstruction in children may be treated by retrograde endopyelotomy with the Acucise device. The principal potential advantage of this procedure is reduced morbidity. Our findings suggest that further evaluation is warranted.

Catheterization↗

Urodynamic and clinical follow-up of 28 children after gastrocystoplasty.

OBJECTIVES: To determine the efficacy of gastrocystoplasty in creating a large and compliant urinary reservoir. PATIENTS AND METHODS: Twenty-eight children (14 boys, 14 girls), with a median age of 9 years (range 4-17), were evaluated before and for a median of 2 years and 5 months after gastrocystoplasty. Evaluation included urodynamic and renal function studies and a survey of their post-operative complications and their sense of well-being. Renal function was assessed by ultrasound and serum creatinine, and electrolytes were measured. RESULTS: After gastrocystoplasty bladder size increased, compliance improved, hydronephrosis decreased or was stable, and renal function remained stable. There were minimal complications and the children's subjective impression of their well-being was markedly improved. CONCLUSION: Gastrocystoplasty, using our surgical technique, is a reliable method of creating a large and compliant urinary reservoir. Advantages include the absence of clinical urinary tract infections, the absence of mucus and the preservation of renal function. Complications, such as haematuria, dysuria and hypochloraemic alkalosis, might be avoided by excluding the antrum from the gastrocystoplasty, maintaining the child on a normal salt-containing diet, employing catheterization or buffering the urine in children with normal urethral sensation.

Adolescent↗

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.

Adolescent↗

Effects of endothelium-derived nitric oxide on renal hemodynamics and function in the sheep fetus.

We investigated the effects of the endothelium-derived nitric oxide system on renal hemodynamics and function during the 3rd trimester in a chronically catheterized fetal sheep preparation. Acetylcholine caused a significant decrease in renal vascular resistance (60% of the baseline value) as compared with aortic constriction (142% of the baseline value). The effects of acetylcholine could be blocked by prior administration of N omega-nitro-L-arginine (renal vascular resistance = 102% of baseline). Sodium nitroprusside also caused a significant drop in renal vascular resistance (63% of baseline), but this could not be blocked by N omega-nitro-L-arginine (77% of baseline). Infusion of N omega-nitro-L-arginine with blood pressure maintained at a constant level resulted in a significant increase in renal vascular resistance (148% of the baseline value) as compared with saline alone (94% of baseline). Glomerular filtration rate increased after saline infusion (156% of the baseline value), but this increase was blocked by N omega-nitro-L-arginine (87% of baseline). Sodium excretion also increased (340%), and this increase was blunted by N omega-nitro-L-arginine (235%). We conclude that basal production of endothelium-derived nitric oxide results in ongoing renal vasodilation in 3rd-trimester fetal sheep, maintaining baseline renal blood flow. The endothelium-derived nitric oxide system can also be stimulated to an increased level of activity, and its blockade partially prevents the homeostatic response of the fetus to volume and salt overload.

Animals↗

Acute hemodynamic and endocrinological effects of partial fetal bladder obstruction.

The pathophysiology of fetal urinary obstruction has not been elucidated. Using a unique, reproducible and easily reversible animal preparation, we studied the acute hemodynamic and endocrinological responses to partial fetal bladder obstruction in 16 ovine fetuses at 115 days of gestation (term 147 days). After partial obstruction blood pressure and renal weight increased significantly for at least 72 hours. Renal blood flow trended upwards, particularly from 24 to 72 hours, although this change was not statistically significant. Plasma renin activity was significantly increased during the first 24 hours after obstruction but it returned to baseline thereafter. Plasma cortisol or catecholamine concentrations remained unchanged. The time course and pattern of hemodynamic changes in this fetal sheep preparation of partial urinary obstruction differ significantly from those reported in other preparations.

Animals↗

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.

Administration, Intravesical↗

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.

Age Factors↗

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.

Collagen↗

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.

Collagen↗

Morphology and histochemistry of infant testes in the prune belly syndrome.

Testicular biopsy samples from 3 boys 5.5, 6 and 7 months old with the prune belly syndrome and intra-abdominal testes were examined morphologically and phenotypically for the presence of alkaline phosphatase. Findings were compared with those in age-matched autopsy controls. All patient specimens demonstrated atypical germ cells with large nuclei and prominent nucleoli, and intense alkaline phosphatase staining localized to the cytoplasmic membrane. The presence of these testicular abnormalities suggests that a developmental arrest is fundamental to the pathogenesis of the undescended testes associated with the prune belly syndrome. The similarity of the histological appearance of these testes to that of intratubular germ cell neoplasia suggests that long-term followup of these patients for the development of invasive germ cell tumors is important.

Alkaline Phosphatase↗

Organ preservation in the management of pelvic rhabdomyosarcoma.

The role of exenterative surgical therapy in pelvic rhabdomyosarcoma has been progressively diminishing with the increasing effectiveness of combination chemotherapy. Cooperative studies have demonstrated that, in most instances, the initial surgical procedure should consist of a thorough examination under anesthesia and a biopsy of the mass. Surgery should be repeated to evaluate the therapeutic response to chemotherapy (with or without radiation treatment) so that radical resection, when necessary, is not unduly delayed. In some instances, patients who responded only partially to treatment will, with limited surgical excision, demonstrate a complete response on pathologic examination. The late effects of this multidisciplinary treatment plan must be studied further and long-term follow-up for these children is imperative.

Antineoplastic Combined Chemotherapy Protocols↗