Search PubMed⌕ Search

Biomedical subjects

B A Kogan

Publications and source records attributed to B A Kogan.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1998

Length of stay for specialized pediatric urologic care.

BACKGROUND: Pediatric urologic specialists have been excluded from many recent managed care contracts because they are believed to be more expensive and of no better quality than general urologists in managing common urologic problems in children. We believed this to be inaccurate. OBJECTIVES: To compare the length of stay at the University of California, San Francisco Medical Center for 2 common pediatric urologic operative procedures with data from other northern California hospitals and to document our results and patient satisfaction. DESIGN: Retrospective analysis of HCIA statewide database (HCIA Inc, Orange, Conn). SETTING: Northern California, 1995. SUBJECTS: Children younger than 12 years undergoing surgery for repair of an obstruction of the ureteropelvic junction or vesicoureteral reflux. MAIN OUTCOME MEASURE: Length of stay. RESULTS: The length of stay in our hospital was similar to that observed in other hospitals in which other full-time pediatric urologic specialists practiced and was significantly less than that observed in other northern California hospitals, even when adjusted for risk. In fact, a savings of 279 hospital days would have been realized if all patients had the same length of stay as that achieved at University of California, San Francisco Medical Center. In the 38 patients operated on at our center, there was uniform surgical success. Of the parents, 92% (11/ 12) were satisfied with their child's care and 92% (11/ 12) believed they received enough information to know what to expect and how to care for their child at home. There were no data available evaluating quality from other northern California hospitals for comparison. CONCLUSIONS: Our finding that actual and risk-adjusted length of stay were shorter when patients were treated by full-time pediatric urologists, while excellent quality was maintained, suggests that these specialists achieve their results with more efficiency and lower resource utilization than do general urologists. The implication of these results is that exclusive contracting that prevents patients from receiving care from full-time specialists results in overuse of valuable resources and possibly reduced quality. If our results are generalizable, they have important implications for health care reform in the United States.

Academic Medical Centers↗
PubMed1998

Gastrocystoplasty: is there a consensus?

The problems encountered with ileal and colocystoplasty have led to the use of the stomach for bladder augmentation, termed gastrocystoplasty. The advantages of gastrocystoplasty over intestinal segment augmentation include reduced chloride reabsorption, decreased mucus production, decreased urinary infection in the presence of acid urine, extremely low incidence of stones, and avoidance of complications from short bowel syndrome. The gastric patch provides comparable improvements in bladder volume, pressure, and continence. The thick muscular wall of the stomach facilitates ureteric reimplantation as compared with the small intestine, but the rate of stenosis and reflux may not be superior. The disadvantages of the gastric patch include complications of severe systemic alkalosis, which is usually manifest in dehydrated, renal compromised patients, and the hematuria-dysuria syndrome (HDS), which is more prevalent in patients with renal insufficiency, normal pelvic sensation, and urinary incontinence. The postoperative complication rate of gastrocystoplasty is comparable with that of other augmentation procedures and similarly warrants proper selection and close follow-up of patients. In this report we review the literature and present the results, including a discussion of the technique and the pathophysiology of its complications.

Bacteriuria↗
PubMed1998

Neonatal management. Role for early intervention.

Although performing pyeloplasty on an infant with a relatively healthy kidney prior to the onset of renal damage is not as well-accepted as "aggressive observation," the authors argue that early intervention is the more "conservative" or safe method of treatment for infants with ureteropelvic junction (UPJ) obstruction. Using experimental and clinical data, the authors demonstrate that prolonged partial UPJ obstruction in the developing kidney causes significant renal morbidity with time.

Animals↗
PubMed1998

Neuroanatomical changes in the rat bladder after bladder outlet obstruction.

OBJECTIVE: To investigate the histological changes in bladder innervation in response to partial bladder outlet obstruction in a rat model. MATERIALS AND METHODS: Forty-eight adult female rats had their bladder outlet partially obstructed by ligating the proximal urethra over a 20 G angiocatheter; 18 shamoperated rats served as controls. Animals were killed after 1, 2 and 4 weeks, and their bladders evaluated using computerized morphometry. Immunohistochemical staining for neuronal protein gene-product 9.5 (PGP, a general neuronal marker) and enzyme histochemical staining of acetylcholinesterase, adrenergic fibres and nitric oxide synthase were performed. RESULTS: Bladder wall changes after obstruction consisted of a six- to sevenfold increase in bladder volume and weight. Smooth muscle hypertrophy was evident equally at all sample times. Cystometry showed functional alterations in bladder capacity and voided pressures; obstructed animals had markedly increased bladder capacities and higher voiding pressures (obstructed, 80-100 cmH2O; normal, 30-40 cmH2O). Neuronal changes in the obstructed bladder were most dramatic within the cholinergic and adrenergic neurotransmitter systems within and surrounding the smooth muscle bundles, where there was less staining than in control animals. PGP immunoreactivity increased slightly. The L-arginine-nitric oxide pathway appeared unperturbed after obstruction. CONCLUSIONS: These histological findings suggest that neuropathic changes in the bladder after outlet obstruction, including detrusor instability, are mainly the result of anatomical perturbations in the cholinergic and adrenergic pathways.

Animals↗
PubMed1998

Renal hemodynamic changes after complete and partial unilateral ureteral obstruction in the fetal lamb.

PURPOSE: Complete and partial ureteral obstruction decreases ipsilateral renal blood flow in neonatal and adult animals. However, the effects of obstruction that develops during gestation may be different from those in neonatal or adult animals. We determine whether complete or partial ureteral obstruction decreases ipsilateral renal blood flow in fetal sheep. MATERIALS AND METHODS: We positioned an ultrasonic flow transducer around both renal arteries in 21 fetal sheep at 123 to 125 days of gestation. Unilateral ureteral obstruction was created in 16 fetuses, including complete and partial obstruction in 7 and 9, respectively. There were 5 controls. Renal blood flow and arterial blood pressure were measured daily for a minimum of 7 days. RESULTS: All obstructed kidneys had hydronephrosis, partially obstructed kidneys had less obstruction and contralateral kidneys had none. Renal weight was similar in obstructed and contralateral kidneys in the sham operated, partial and complete obstruction groups. After partial ureteral obstruction renal blood flow in obstructed and contralateral kidneys was increased compared to that in sham operated kidneys up to 11 days after obstruction was created. After complete ureteral obstruction the blood flow in obstructed kidneys was significantly lower than in the unobstructed counterparts but it remained 124% of initial renal blood flow at 10 days. Elevated ureteral pressure was maintained in obstructed kidneys throughout the study period. CONCLUSIONS: In our experiment partial ureteral obstruction in the fetus did not decrease renal blood flow to the ipsilateral kidney even after 7 days. Complete obstruction decreased blood flow in the affected kidney but not to same magnitude as that in previous adult animal studies. Our findings suggest that during gestation renal blood flow is maintained in the presence of obstruction.

Animals↗
PubMed1998

Neonatal hydronephrosis.

With fetal abnormalities diagnosed during maternal ultrasound becoming more commonplace, the management of neonatal hydronephrosis has become one of the most interesting and controversial subjects in pediatric urology. Although it is recognized that obstruction must be treated, it is also clear that hydronephrosis may well exist without significant obstruction. Numerous experimental and clinical studies of the urinary tract have failed to lead to a clear consensus. Our approach consists of careful observation of patients with moderate hydronephrosis in well functioning kidneys. In patients with reduced function or a renal pelvic diameter of greater than 3 cm and dilated calyces, we lean more towards surgical intervention. Overall, an individualized approach is necessary.

Journal Article↗
PubMed1998

Multicenter experience with the Mitchell technique for epispadias repair.

PURPOSE: We present a multicenter experience using the Mitchell epispadias technique to determine if satisfactory results could be obtained by various pediatric urologists at multiple centers using the same technique to repair epispadias. This particular technique involves complete disassembly of the penis into 2 separate hemicorporeal glandular bodies and a separate urethral plate, and relies on the unique blood supply to the epispadiac phallus. MATERIALS AND METHODS: A total of 17 boys 11 months to 21 years old underwent the Mitchell procedure for epispadias at 4 institutions by 6 different surgeons between 1994 and 1996. One patient in this group had undergone prior epispadias repair, which had failed. RESULTS: At followup (mean 13.5 months) 3 boys had pinpoint penopubic fistulas, which resolved spontaneously in 2. The 21-year-old patient had a complete wound dehiscence. All boys with intact repairs have straight erections, orthotopic meatus and satisfactory appearances. There were 15 boys with a conical glans appearance and 1 exhibiting glandular disproportion. There was 1 episode of postoperative pyelonephritis. CONCLUSIONS: The Mitchell technique for repair of epispadias is reproducible and successful in the hands of pediatric urologists from different centers. Chordee is reliably corrected, erectile function preserved, the urethra ventrally situated in an anatomically precise fashion and satisfactory cosmesis achieved.

Adolescent↗
PubMed1998

Long-term benefits of early neurosurgery for lipomyelomeningocele.

PURPOSE: Our previous experience with early neurosurgery for lipomyelomeningocele revealed that patients undergoing repair before age 1.5 years were more likely to have normal bladder function. We evaluate the durability of the urological benefits in patients with lipomyelomeningocele with longer followup. MATERIALS AND METHODS: A retrospective chart review was performed on all patients who underwent urodynamic testing before and after primary neurosurgical repair of lipomyelomeningocele. A total of 43 patients presented between 1983 and 1995 with at least 12 months of followup (median 68, range 15 to 167). RESULTS: Of the 43 patients 36 (84%) maintained stable clinical and urodynamic function, and 7 (16%) had late deterioration, which occurred between 9 months and 8 years postoperatively. Of 19 patients with normal urodynamic studies preoperatively 14 (74%) maintained normal function. Overall, 14 of 43 patients (33%) with lipomyelomeningocele had normal bladder and sphincter function during followup. The principal predictor of long-term normal bladder function was preoperative urodynamic status, since urodynamic studies were preoperatively normal in 13 of 14 patients (93%) who maintained normal bladder and sphincter function. Late neurosurgery was equally efficacious if urodynamic studies were normal. CONCLUSIONS: Our data continue to support early diagnosis and neurosurgical intervention in patients with lipomyelomeningocele, since there is a higher likelihood of normal preoperative function that can be preserved. Furthermore, the results are durable in 84% of cases. However, close followup is necessary, since deterioration can occur up to 8 years postoperatively.

Adolescent↗
PubMed1998

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.

Child↗
PubMed1997

Plexiform neurofibroma involving the genitourinary tract in children: case reports and review of the literature.

We report extensive genitourinary neurofibroma in two children who presented with massive bilateral hydroureteronephrosis and a thick-walled bladder. The best radiologic technique to stage the disease and determine treatment is magnetic resonance imaging. Management of extensive genitourinary neurofibroma is controversial. Based upon our experience and a review of the literature, aggressive surgery should be approached cautiously.

Humans↗
PubMed1997

Hemodynamic changes after complete unilateral ureteral obstruction in the young lamb.

PURPOSE: We studied renal hemodynamic changes after complete acute unilateral ureteral obstruction in the young lamb. MATERIALS AND METHODS: Seven 4-week-old lambs underwent unilateral complete ureteral obstruction and renal blood flow was monitored in both kidneys with ultrasonic flow transducers. Ureteral and arterial blood pressure was measured. RESULTS: In the obstructed kidney renal blood flow was stable for 5 hours and then decreased thereafter to 71% of baseline at 5 days (p < 0.05). In the contralateral kidney the pattern of renal blood flow constituted a mirror image, although the magnitude of the increase was decreased (122% of baseline at 5 days, not statistically significant). Mean arterial blood pressure did not change in 5 days. Mean ureteral pressure increased from a baseline of 9 to 37 mm. Hg (p < 0.001) 2 hours after obstruction but gradually decreased to 24 mm. Hg after 24 hours and remained elevated for 5 days (p < 0.001). CONCLUSIONS: The pattern of renal blood flow and ureteral pressure response to obstruction in the young lamb is different from that previously reported. Renal blood flow does not increase after obstruction and it is relatively preserved at 5 days. This unexpected response may be a result of the compound caliceal sheep kidney, immaturity of the young vascular system or development differences in the mechanism of spontaneous decompression of the collecting system.

Age Factors↗
PubMed1997

Smooth and striated muscle development in the intrinsic urethral sphincter.

PURPOSE: The intrinsic urethral sphincter is composed of adjacent striated and smooth muscle. We studied the sequential expression of smooth and striated muscle proteins to gain insight into the ontogeny of intrinsic sphincter development. MATERIALS AND METHODS: The intrinsic urethral sphincters of timed Fischer 344 rat embryos at 14, 16 and 18 days of gestation, neonates on postnatal day 1 and adult animals were examined. Serial sections of the urethra and adjacent levator ani muscles were studied histologically with hematoxylin and eosin, anti-alpha-smooth muscle actin, anti-alpha-sarcomeric actin and antistriated muscle myosin heavy chain antibodies. RESULTS: The intrinsic urethral sphincter was identified within the periurethral mesenchyma as early as day 14 of gestation. Although striated myotubules were identified within the urethra by hematoxylin and eosin staining starting on postnatal day 1, striated muscle myosin heavy chain protein was absent in the embryonic and neonatal development of the sphincter, and it was expressed only in the mature myotubule of adults. alpha-Smooth muscle actin was expressed throughout the urethral sphincter of embryonic and neonatal animals. In adults alpha-smooth muscle actin was confined to the smooth muscle component of the urethra. Co-expression of alpha-smooth and alpha-sarcomeric muscle actin by the striated sphincter myotubule was noted only in neonates. CONCLUSIONS: Development of the intrinsic urethral sphincter is characterized by sequential expression of well characterized muscle marker proteins. The co-expression of smooth and striated muscle markers by developing sphincter myotubule suggests the possibility that trans-differentiation of smooth to striated muscle occurs in the developing genitourinary tract.

Animals↗
PubMed1997

Changing the technique of background subtraction alters calculated renal function on pediatric mercaptoacetyltriglycine renography.

PURPOSE: Although many operative decisions are based on apparent changes in function detected by serial diuretic renography, the reliability of relative renal function data has been questioned. We investigated the effect of background subtraction on calculated renal function. MATERIALS AND METHODS: We reviewed 23 pediatric mercaptoacetyltriglycine renograms. Regions of interest for background subtraction were redrawn and relative renal function values were recalculated. RESULTS: In patients with left hydronephrosis left differential renal function was consistently underestimated by 7.3% compared to the superior and 4.7% compared to the average background subtraction technique. In patients with right hydronephrosis, when considering lower pole background activity only, right differential renal function was consistently overestimated by 15.8% compared to the superior and 2.4% compared to the average background subtraction technique. In patients younger than 1 year at the time of study these differences were exaggerated. CONCLUSIONS: Because of overlapping hepatic background activity, the position of regions of interest for background subtraction may greatly influence calculated renal function. We recommend that the preferred method of calculating background subtraction to minimize error be based on a region of interest surrounding the whole kidney. This method is especially pertinent in patients with right hydronephrosis and in those younger than 1 year. Reported relative renal function data should be interpreted with caution.

Child↗
PubMed1997

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.

Animals↗
PubMed1997

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.

Age Factors↗