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PURPOSE: Urinary tract anomalies or dysfunction leaves the bladder unsuitable for urine drainage in a significant proportion of children presenting for kidney transplantation. We reviewed a multi-institutional experience to determine the ramifications of kidney transplantation in children with bladder augmentation or urinary diversion. MATERIALS AND METHODS: During a 28-year period 18 boys and 12 girls 1.7 to 18 years old (mean age 12.1) received 31 kidney transplants. Cause of end stage renal disease was renal dysplasia in 8 cases, posterior urethral valves in 5, obstructive uropathy in 5, neurogenic bladder/chronic pyelonephritis in 4, spina bifida/chronic pyelonephritis in 3, prune belly syndrome in 3 and reflux in 2. RESULTS: Of the patients 17 had augmented bladder (ileum 9, ureter 5, sigmoid 2 and stomach 1), 12 had incontinent urinary conduits (8 ileum, 6 colon) and 1 had a continent urinary reservoir. Surgical complications included 1 case each of stomal stenosis, stomal prolapse, renal artery stenosis, urine leak, enterovesical fistula and wound dehiscence. Medical complications included urinary tract infection in 21 cases and metabolic acidosis in 5. A bladder stone developed in 1 patient. There was no correlation between the incidence of symptomatic urinary tract infections and type of urinary drainage. Acidosis was more common in patients with augmented bladder (4 of 17 versus 1 of 14) but there was no correlation between the bowel segment used and the occurrence of acidosis. Graft survival was 90% at 1 year, 78% at 5 years and 60% at 10 years. Etiology of graft loss included chronic rejection in 6 cases, noncompliance in 4 and acute rejection in 1. There were no deaths. CONCLUSIONS: Drainage of transplanted kidneys into an augmented bladder or urinary conduit is an appropriate management strategy when the native bladder is unsuitable or absent. Patients with kidney transplants drained into augmented bladder or urinary conduit are at increased risk for urine infection. Graft survival is not adversely affected compared to historical controls when a kidney transplant is drained into a urinary conduit or augmented bladder.

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PURPOSE: Percutaneous endopyelotomy has been shown to be effective in the management of ureteropelvic junction obstruction in adults and secondary ureteropelvic junction obstruction in children. There are little published data regarding endopyelotomy as a primary treatment in children. MATERIALS AND METHODS: During 3 years we performed 8 endopyelotomies and 20 open pyeloplasties for primary ureteropelvic junction obstruction and compared the results. Preoperative ureteropelvic junction obstruction was detected by renal ultrasound, excretory urogram (IVP) or renal scan. All patients were followed 1.5 to 3 years postoperatively. The success of the procedure was determined by excretory urogram, renal scan or the absence of clinical findings, with 1 failure in each group. RESULTS: The overall success rates for endopyelotomy and open pyeloplasty were 88% and 93%, respectively. Hospital stays were essentially equal between the groups but operative time and hospital costs were higher for endopyelotomy. CONCLUSIONS: Endopyelotomy may be performed effectively for primary ureteropelvic junction obstruction in children but with increased costs.

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We have developed a technique that reduces the rewarm time during renal transplant vascular anastomoses by supporting the kidney in a slush-filled sterile polyurethane bag. There were no complications related to the use of this technique.

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BCG immunotherapy is very effective in the treatment of superficial transitional cell carcinoma of the bladder, but its significant toxicity may limit its use in some patients. In an effort to find less toxic and potentially more effective treatments we investigated the possible immunotherapeutic potential of combinations of Alpha Interferon (1000 IU) and Gamma Interferon (500 IU) with bacillus Calmette Guerin (BCG) (10(7) cfu), Interleukin-2 (4000 IU), and Keyhole Limpet Hemocyanin (50 micrograms.) in the MBT2 murine bladder cancer model. Significant reductions (p less than 0.05) in tumor incidence relative to the saline control, 83%, Day 35) was observed in groups receiving alpha interferon (42%), Keyhole limpet hemocyanin (42%), interleukin-2 (25%), alpha interferon + Keyhole limpet hemocyanin (17%), alpha interferon + interleukin-2 (33%), gamma interferon + BCG (42%), and gamma interferon + interleukin-2 (17%). All treatment groups with the exception of the group receiving gamma interferon had significantly reduced tumor volume (p less than 0.05) relative to the saline control. Combination treatment groups were significantly more effective than single agent treatments (p = 0.0057). The exhibited anti-tumor effect of these immunotherapeutic agents alone and in combination suggest that they may prove to be effective forms of immunotherapy for transitional cell carcinoma of the bladder.

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With careful attention to patient selection and anesthesia, as well as easy-to-manage dressings and urinary diversions, outpatient surgery for all degrees of hypospadias can be performed safely and economically. By using these techniques over an eighteen-month period all hypospadias operations were performed in the outpatient department. This included thirty-four minor operations as well as twenty-five major hypospadias repairs. Seven complications were encountered in the fifty-nine operations.

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Fluconazole (UK-49,858) is a new oral bis-triazole antifungal agent with demonstrated activity against Candida albicans. Because of the increasing importance of infections due to other species of Candida, we studied the efficacy of fluconazole in a rat model of established systemic candidiasis, using clinical isolates of C. tropicalis, C. glabrata, and C. Krusei. In normal rats, oral fluconazole at both 20 and 80 mg/kg per day for 7 days reduced both kidney and liver titers of C. tropicalis and C. glabrata compared with those in control animals and was only slightly inferior to amphotericin B. Both fluconazole and amphotericin B were ineffective in reducing kidney titers of C. krusei, but amphotericin B was more effective than fluconazole in reducing liver titers. Fluconazole showed no increased efficacy at the higher dose of 80 mg/kg per day compared with 20 mg/kg per day in any experiment. These results suggest that oral fluconazole may be useful in the treatment of established disseminated candidiasis caused by species other than C. albicans. Further in vivo studies are needed, however, to define minimum effective doses and length of therapy and to test additional Candida isolates.

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Fluconazole (UK-49,858), a new oral bistriazole antifungal agent, was compared with amphotericin B in the treatment of established systemic infection with Candida albicans in normal and diabetic rats. In normal rats, oral fluconazole at 10 mg/kg per day for 7 days reduced Candida colony counts in the kidneys and livers as well as amphotericin B did and was nearly as effective as amphotericin B in a 21-day treatment trial. There was no further reduction in Candida colony counts when normal rats were treated with fluconazole at 40 mg/kg twice a day for 7 days. In streptozotocin-induced diabetic rats, fluconazole at 20 mg/kg per day for either 7 or 21 days compared favorably with amphotericin B in efficacy. Results of our study suggest that oral fluconazole may be useful in the treatment of established disseminated candidiasis in normal as well as diabetic hosts.

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The effect of ureteral obstruction on the course of renal candidiasis in a rat model was studied, using both normal and diabetic Sprague-Dawley rats, and a clinical isolate of Candida albicans. Diabetes was induced by streptozotocin injection 1 week prior to inoculation and transabdominal ligation of the left ureter. On day 9 post inoculation, mean titers of Candida were similar in right and left kidneys of obstructed rats. Mean left renal titers for obstructed and control rats were similar (log10 2.68 CFU/g +/- 0.73 (SE) vs. log10 2.21 +/- 0.09, P greater than 0.01). Diabetes produced higher renal titers of Candida, regardless of the presence of ureteral obstruction (log10 5.74 CFU/g +/- 0.57 (SE) vs. log10 2.21 +/- 0.09, P less than 0.01). Animals treated for one week with amphotericin B showed a marked difference in Candida titers between obstructed and control animals (log10 4.14 CFU/g +/- 0.45 (SE) vs. 1.57 +/- 0.38) for both kidneys, and between obstructed and nonobstructed kidneys in the same animals.

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We surveyed 321 patients 1 to 18 years old who were followed at the sickle cell clinic at the Children's Hospital of Philadelphia between 1970 and 1984 for urological complications of the disease. Mean followup was 5 years and all patients exhibited a typical spectrum of hemoglobin types. The urological problems encountered were those cited in the literature, namely hematuria, urinary tract infection and priapism. Surprisingly few of our patients experienced significant renal bleeding. Although the number of patients with infection evaluated radiographically was small, the frequency of renal parenchymal scarring was disturbingly high despite the reported rarity of reflux in black subjects. Our survey and a review of the literature indicate that most sicklemic children with urinary infection are not subjected to urological evaluation. We question the wisdom of that policy. Finally, we found that priapism responds most often to nonsurgical therapy and that it rarely results in impotence in young sickle cell patients.

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Compensatory renal growth is mediated by a substance(s) found in the serum and in urine called renotropin. The interaction of nephrectomy serum and urine antisera upon compensatory renal growth was investigated by administering rat uninephrectomy serum and sham serum and urine to rabbits. The rabbit antisera was given intravenously to uninephrectomy and sham operated rats and kidney weight/body weight ratios were calculated. Antisera against sham serum and urine induced kidney growth as well as antisera against uninephrectomy serum and urine given to sham animals. These results suggest the presence of a circulating antigenic inhibitor to kidney growth and suggest that renotropin is made up of a inhibitory as well as a stimulatory substance.

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The Mayer-Rokitansky-Kuster-Hauser syndrome is composed of vaginal atresia with other variable Müllerian duct abnormalities such as bicornuate or septated uterus. The fallopian tubes, ovaries, and broad and round ligaments are normal. Unilateral renal and skeletal anomalies are associated in 50% and 12% of cases, respectively. Patients have a normal female karyotype and normal secondary sexual development. Previously, one had to rely on radiographic contrast studies and surgical exploration for accurate definition of the reproductive tract anatomy. The authors performed ultrasound (US) examinations on 12 patients, aged 5 days to 18 years, with the Mayer-Rokitansky syndrome. US allowed correct identification of the genitourinary anomalies found in these girls, including eight cases of unilateral renal agenesis; one absent, one rudimentary, and ten duplicated or obstructed uteri; eight duplicated or obstructed vaginas; and associated complications such as endometriosis. Eight of the patients had lower abdominal pain, often cyclical in nature. The findings demonstrate that high-resolution, real-time US in conjunction with water vaginography permits the anatomy of these complex anomalies to be defined.

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Agenesis of the vagina in karyotypic female subjects may be accompanied by other defects of the urogenital system. We describe 8 cases that exemplify nearly all variants in the group of müllerian and renal anomalies that we identify as the Mayer-Rokitansky syndrome. We trace the association of system defects to errors of formation of the wolffian body. This structure is the progenitor of the gonad and wolffian duct, which although temporary in the female subject, gives rise to the ureter and is the path finder of the müllerian system. Errors of formation or premature atrophy of the wolffian duct, or intrinsic müllerian organizers lead to the array of anomalies in this syndrome. Vaginal agenesis was found to be associated with müllerian, renal or ovarian defects in numerous embryological combinations. We propose a müllerian classification, and describe the current diagnostic modalities and techniques of surgery.

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The lateral prostate of the castrate rat has low levels of specific cytosol progesterone binding which can be increased by treatment of the animals with estradiol. Although progesterone alone is a relatively ineffective agonist in either the ventral prostate or the lateral prostate, treatment of animals with a combination of progesterone and estradiol caused selective growth of the lateral prostate. This response did not occur in the ventral prostate which had a very low or undetectable level of specific cytosol progesterone binding which did not respond to treatment with estradiol. The effects of progesterone in the lateral prostate were not mediated via the androgen receptor suggesting that the cytosol progesterone receptor is capable of mediating a growth response to an agonist in the lateral prostate. An endogenous agonist for the cytosol progesterone receptor in the prostate remains to be identified, and its relevance to BPH remains to be defined.

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Estradiol partially maintained the weights of the dorsolateral prostate and seminal vesicles in castrated adult male rats. One group of animals received subcutaneous injections of estradiol (0.01 mg/kg) daily, while a second group of animals received estradiol plus bromocriptine (4.0 mg/kg). Changes in weights of accessory reproductive organs were correlated with serum prolactin levels. Estradiol significantly increased serum prolactin levels while concomitant treatment with bromocriptine caused serum prolactin to remain at castrate levels. Bromocriptine slightly decreased, but did not abolish, the effect of estradiol on weights of the dorsolateral prostate and seminal vesicles. To determine if the effect of estradiol was mediated by androgen receptors in the dorsolateral prostate and seminal vesicles, a third group of animals was treated with flutamide. Flutamide, at a dosage (20 mg/kg) that abolished the effects of dihydrotestosterone on the weights of these tissues, produced no alternation of the effects of estradiol. Treatment of animals with a combination of flutamide, bromocriptine, and estradiol did not significantly alter organ weights from the results obtained with bromocriptine and estradiol. Scatchard plot analysis of the effect of estradiol treatment on cytosol binding of estradiol demonstrated increased quantities of estradiol binding in dorsolateral prostate and seminal vesicles which correlated with the changes in weights noted. Although part of the effect of estradiol on regression of male accessory reproductive organs of castrated rats may be mediated by prolactin, the principal effect appears to be a direct action on responsive tissues.

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Tissue steroid levels in 48 needle-biopsy samples of adenocarcinoma of the prostate were quantified by radioimmunoassay (RIA). Tissue levels of dihydrotestosterone (DHT), estradiol-17 beta, and estrone were correlated with the tumor stage, histologic grade, and patient response to endocrine therapy. All patients with well-differentiated carcinoma of the prostate had tissue DHT content greater than 2.0 ng/g while 35% of patients with moderately differentiated or poorly differentiated tumors had tissue DHT content less than 2.0 ng/g. DHT content appeared to be unrelated to tumor stage. Estradiol and estrone content correlated well with tumor grade but not with tumor stage. DHT levels were measured in 17 patients with symptomatic Stage D2 carcinoma of the prostate. Thirteen patients with DHT content greater than 2.0 ng/g initially had an objective and/or subjective response to endocrine therapy. Four patients with tissue DHT levels below 2.0 ng/g had no response to hormonal therapy. Quantification of tissue DHT content by RIA is a promising method for predicting initial response to hormonal therapy in adenocarcinoma of the prostate.

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