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Biomedical subjects

S A Kramer

Publications and source records attributed to S A Kramer.

At least 37 records · Page 2Linked to original sources

Alterations in maternal epidermal growth factor (EGF) effect testicular descent and epididymal development.

OBJECTIVE: (1) To determine the ability of epidermal growth factor (EGF) to reverse antiandrogen-induced cryptorchidism and epididymal abnormalities; (2) to evaluate whether alterations in maternal EGF would result in abnormal testicular descent or mal development of the epididymis. METHODS: Experiment 1: Timed pregnant ICR mice were treated with either flutamide, flutamide plus EGF, or vehicle alone on gestational days 11 through birth. Experiment 2: Maternal EGF was abolished by removing the submandibular glands. Following timed mating, dams were treated with either flutamide, anti-EGF, DHT, or vehicle alone on gestational days 11 through birth. RESULTS: Experiment 1: Treatment with flutamide resulted in a 36 percent (26/72) incidence of undescended testes (UDT), and a 43 percent (31/72) incidence of abnormal epididymides. Rats treated simultaneously with flutamide plus EGF had a reduced incidence of UDT (14%, 6/42) and epididymal anomalies (19%, 8/42); p < 0.01. Experiment 2: The absence of maternal EGF resulted in a significant incidence of cryptorchidism in 11/50 (22%) testes, and epididymal anomalies in 19/50 (38%); p < 0.01. CONCLUSIONS: Our findings suggest that EGF stabilizes the wolffian duct system and partially mediates testicular descent.

Abnormalities, Drug-Induced↗

Infundibulopelvic stenosis: a long-term followup.

We followed 21 patients with congenital infundibulopelvic stenosis, a rare obstructive disorder of the intrarenal collecting system, for a median of 11 years (range 2 to 28 years). Of these patients 19 (90%) had evidence of bilateral renal disease. In particular, 10 patients had bilateral infundibular pelvic stenosis, 6 a contralateral cystic dysplastic kidney and 3 a congenitally absent kidney. Extended observations of the patients with this disorder revealed that end stage renal disease or renal insufficiency developed in 8 patients (37%), all with bilateral renal anomalies. Renal biopsies in patients with end stage renal failure revealed widespread areas of renal dysplasia proximal to the stenotic infundibulum with focal or global glomerulosclerosis of the glomeruli, which was not involved in the dysplastic process. These pathological findings are consistent with the presence of a renal hyperfiltration injury. Our data suggest that the prognosis of infundibulopelvic stenosis is dependent upon the extent of total renal mass involved with the disease process and the duration of followup.

Adolescent↗

Expression of androgen receptor protein within the lumbar spinal cord during ontologic development and following antiandrogen induced cryptorchidism.

One of the leading hypotheses regarding androgenic regulation of testicular descent is that the lumbar genitofemoral nucleus is morphologically altered by testosterone during a specific prenatal period. This hypothesis is based on the unproved assumption that androgen receptor is present in the fetal spinal cord. Using immunohistochemistry we identified androgen receptor in the rat lumbar spinal cord on gestational day 15, a day before the onset of maximal androgenic action for testicular descent. Experiments were performed to determine whether alterations in the morphology of the genitofemoral nucleus are associated with flutamide induced cryptorchidism. Studies revealed a reduction of motoneuron number in rats with flutamide induced cryptorchidism (124.2 +/- 18.9) compared to rats exposed to flutamide without cryptorchidism (269.3 +/- 20.2) and/or male controls (291.0 +/- 14.5, p < 0.01). These findings support the hypothesis that androgens can directly regulate development and morphology of the genitofemoral nucleus.

Animals↗

Epidermal growth factor reverses antiandrogen induced cryptorchidism and epididymal development.

Epidermal growth factor, an androgen responsive paracrine factor, administered to pregnant mice has been reported to result in persistent wolffian ducts in female offspring. This fact led us to investigate whether epidermal growth factor can reverse the undescended testes and epididymal abnormalities associated with time specific flutamide administration. Timed pregnant Sprague-Dawley rats were treated with flutamide (undescended testes 74% and epididymal anomalies 53%) or flutamide plus epidermal growth factor (undescended testes 24% and epididymal anomalies 9%). The decrease in undescended testes and epididymal abnormalities following epidermal growth factor treatment was significant at p < 0.01. We performed immunohistological studies to evaluate whether flutamide alters epidermal growth factor expression in the paratesticular tissues during the time of maximal androgenic activity. These investigations revealed that antiandrogens did not alter epidermal growth factor expression in the fetal testes or epididymides. This finding suggests that epidermal growth factor does not reverse epididymal abnormalities or undescended testes by direct stimulation of the wolffian ducts or fetal testis.

Abnormalities, Drug-Induced↗

Metastatic testicular choriocarcinoma and secondary hyperthyroidism: case report and review of the literature.

We report on a 16-year-old boy with metastatic testicular choriocarcinoma, increased levels of human chorionic gonadotropin and profound hyperthyroidism bordering on thyroid storm. Hyperthyroidism was secondary to elevated human chorionic gonadotropin, with a thyroid-stimulating hormone effect. Management consisted of suppressive therapy for the symptoms of thyrotoxicosis until chemotherapy achieved control of the primary tumor and elevated levels of human chorionic gonadotropin. Review of the urological literature demonstrated a lack of recognition of this potentially serious paraneoplastic syndrome and its management.

Adolescent↗

Hydronephrosis in renal ectopia: incidence, etiology and significance.

The incidence, cause and significance of hydronephrosis in patients with renal ectopia are unknown. Therefore, we conducted a retrospective review of 77 patients with 82 ectopic kidneys. Of 82 kidneys 46 (56%) had hydronephrosis. Dilatation of the renal pelvis was the result of primary ureteropelvic or ureterovesical obstruction in 52%, grade 3, 4 or 5 vesicoureteral reflux in 26% and extrarenal collecting systems with malrotation that produced apparent ureteropelvic junction obstruction in 22%. Surgery was performed in 41 patients, including primary nephrectomy in 18, ureteral reimplantation in 14 and ureteropelvic junction repair in 8. Hydronephrosis was present in 15 of 58 contralateral nonectopic kidneys, and 11 required surgery mostly for vesicoureteral reflux. Solitary ectopic kidneys with no associated obstruction or reflux demonstrated normal renal function. Our data indicate that the prognosis in renal ectopia relates directly to the associated urological disease and timely surgical intervention, not to ectopia alone.

Adolescent↗

Genitourinary polyps in children.

OBJECTIVES: This study was undertaken to review the presenting complaints, diagnostic evaluation, treatment, and natural history of children with genitourinary polyps seen at the Mayo Clinic during the past 35 years. METHODS: We retrospectively reviewed the charts of all children less than 16 years of age with symptomatic genitourinary polyps who were seen at the Mayo Clinic between 1957 and 1992. The age of each patient, clinical presentation, anatomic location of the polyp, diagnostic evaluation, and treatment were reviewed. Long-term follow-up data, including complications, were recorded, and the literature was reviewed. RESULTS: The most common presenting symptoms were hematuria in 9 patients, (gross 7, microscopic 2) and urinary tract obstruction in 9 patients (upper tract 3, lower tract 6). Four children had ureteral polyps. Excretory urography showed hydronephrosis and filling defects in 3 patients and a filling defect without hydronephrosis in 1 child. Two patients underwent segmental ureterectomy, 1 had open excision of the polyp, and 1 had ureteroscopic excision. Urethral polyps were identified in 12 children, most often as a filling defect of the posterior urethra on voiding cystourethrography (5 patients) or during cystourethroscopy (7 patients). All 12 patients were managed successfully by transurethral resection. CONCLUSIONS: Genitourinary polyps in children require a high degree of alertness and can be diagnosed with excretory urography, with voiding cystourethrography, or endoscopically. The biologic activity of these polyps is uniformly benign, and there have been no recurrences following complete excision.

Adolescent↗

Experience with AS 800 artificial sphincter in pediatric and young adult patients.

Congenital or acquired sphincteric urinary incontinence in children and young adults is a severe social and physical burden. As a therapeutic option, we implanted 61 AS 800 artificial sphincters in 59 patients (46 males and 13 females). The mean age of the patients was 17.5 years (range, 6 to 34 years), and mean follow-up was forty-three months (range, 5 to 84 months). In addition to artificial sphincter implantation, intestinal cystoplasty was required in 22 patients to obviate problems of increased detrusor contractility or decreased detrusor compliance, or both. Continence was good in 47 patients (80%) and fair in 8 (14%). Four patients (7%) were awaiting sphincter modification or cystoplasty, or both. Careful and prolonged follow-up is mandatory in all patients managed in this fashion to preclude the deleterious effects of subtle changes in detrusor or ureteral function on the integrity of the upper urinary tracts.

Adolescent↗

Fatty acid profiles, lipogenesis, and lipolysis in lipid depots in finishing pigs treated with recombinant porcine somatotropin.

Thirty-two pigs (average weight, 74 kg) were used to determine the effects of recombinant porcine somatotropin (rpST) and dietary CP concentration on carcass and noncarcass tissues. Pigs were injected intramuscularly with either rpST (50 micrograms.kg BW-1.d-1; n = 16) or vehicle (n = 16) at 0900 for 24 d. Half the treated and control pigs were given ad libitum access to either a 14 or 20% CP corn-soybean meal diet. The left side of the carcass was physically dissected into separable skin, soft tissues, and bone. Tissue samples were obtained for enzyme assays, proximate analysis, and fatty acid profiles. Proximate analysis (fat, water, protein) of adipose tissue (AT) samples indicated that rpST decreased the percentage of ether extractable lipid (P < .01) and increased the percentage of protein and water (P < .05, P < .01) in intermuscular (IM), subcutaneous (SC), and intrafascicular (IF) AT depots and slightly altered fatty acid profiles of longissimus muscle IF and SC AT. Fatty acid synthesis and malic enzyme activity were decreased by rpST (P < .01), suggesting that lipogenesis was decreased; however, lipolysis was unaffected. Pigs fed the high-CP diet (20%) had decreased AT malic enzyme activity (P < .05) and fatty acid synthesis (P < .05). Additionally, pigs fed the high-CP diet had greater kidney weights (P < .01). Heart, liver, and kidney weights were heavier (P < .01) in pigs treated with rpST, whereas skin and total bone weight were unaffected. Neither weights nor lengths of four individual long bones were affected by dietary protein concentration or administration of rpST.

Adipose Tissue↗

Prognosis of patients with unilateral renal agenesis.

The clinical course was reviewed in 157 patients with unilateral renal agenesis and a normal contralateral kidney for the purpose of establishing a prognosis. There were 85 males (54%) and 72 females (46%). The mean age at diagnosis of unilateral renal agenesis was 37 years. The mean years at risk was 56. Proteinuria (> 150 mg/24 h) was found in 19% of the 37 patients tested (P < 0.001), hypertension developed in 47% of the 47 patients tested (P = 0.010), and renal function (adjusted for age and sex) was decreased in 13% of the 32 patients tested (P = 0.001). An increased filtration fraction was found in 7 (54%) of 13 patients evaluated. At the completion of this study, 114 patients (73%) were alive, and the survival rate was similar to that of age-, sex-matched United States life tables. Forty-three patients (27%) died; 6 deaths (4%) were caused by renal failure. Our review indicates that patients with unilateral renal agenesis and a normal solitary kidney are at increased risk of proteinuria, hypertension, and renal insufficiency. Therefore, it is essential to have prolonged and careful follow-up and to employ strategies that maximize renal preservation.

Adolescent↗

Bilateral primary neuroblastomas in the inguinal canal.

The incidental finding of a nodular mass in the inguinal canal in children usually occurs during surgical exploration for an inguinal hernia. We report an unusual occurrence of neuroblastomas bilaterally and simultaneously in the inguinal canals of an infant with no evidence of metastatic disease.

Humans↗

Prognosis of children with solitary kidney after unilateral nephrectomy.

The clinical course of 138 children who underwent unilateral nephrectomy and had a normal contralateral kidney at the time of nephrectomy was reviewed. The diagnosis leading to nephrectomy included obstructive uropathy in 46% of the cases, reflux or pyelonephritis in 30%, Wilms tumor in 15%, hypertension in 4%, dysplastic kidney in 2% and trauma in 2%. Mean age at nephrectomy was 7.3 years and median followup was 24.7 years. Of the 138 patients 121 (88%) are well and 17 died, including 14 secondary to metastatic Wilms tumor and 1 of renal failure. Survival of nonWilms tumor patients was similar to that of an age-matched control group. In 30 patients 24-hour creatinine clearance and 24-hour urinary protein excretion were measured. Proteinuria (greater than 150 mg./24 hours) was found in 8 of the 30 patients (27%) (p less than 0.001), renal insufficiency developed in 9 (30%) (p less than 0.0001) and hypertension occurred in 10% (p greater than 0.10). Children with an acquired solitary kidney are at increased risk for proteinuria and renal insufficiency.

Child↗

Multilocular cysts of kidney. A study of 29 patients and review of literature.

Multilocular renal cyst is a distinct renal tumor whose gross external appearance and absence of normal renal tissue within the septa of loculi distinguish it clearly from other renal cystic lesions. Interlocular septa may contain either (1) fibrous tissue alone or (2) embryonic tissue separating adjacent loculi. Of 29 patients with multilocular renal cysts, 24 underwent a renal-sparing procedure, and only 5 had radical nephrectomy. None of the histologic specimens showed evidence of immature renal tissue or neoplasia. Patients were followed from three months to eight years (mean, 39 months), and no evidence of local recurrence or metastatic disease was found. Because it is difficult to distinguish multilocular renal cyst from cystic Wilms tumor and multicystic clear cell carcinoma on the basis of imaging studies alone, surgical intervention is the only effective method to differentiate multilocular renal cyst from a malignant lesion of the kidney.

Adolescent↗

Administration of growth hormone to pigs alters the relative amount of insulin-like growth factor-I mRNA in liver and skeletal muscle.

The relative amount of insulin-like growth factor-I (IGF-I) mRNA was determined in the liver and skeletal muscle of market weight crossbred barrows (castrated male pigs) using a solution hybridization-nuclease protection assay. Pigs were given either 50 micrograms recombinant porcine GH per kg body weight or vehicle daily for 24 days i.m. They were fed corn-soybean meal diets containing either 140 or 200 g crude protein/kg (low or high protein). The percentage of muscle in the carcasses of pigs given GH was greater (P less than 0.01) than that of controls. Relative to controls, GH increased (P less than 0.05) the amount of liver IGF-I mRNA by 2.7-fold in pigs fed the low protein diet and 3.0-fold in pigs fed the high protein diet. The amount of IGF-I mRNA in the muscles of GH-treated pigs was 77% and 84% of control pigs in those fed the low and high protein diets respectively (P less than 0.08). GH increased (P less than 0.001) the serum concentration of IGF-I 1.6-fold in pigs fed the low protein diet and 2.0-fold in those fed the high protein diet. These results indicate that the administration of GH to pigs influences the relative amount of liver IGF-I mRNA. The increased amount of liver IGF-I mRNA and the increased serum IGF-I concentrations suggest that IGF-I plays an endocrine role in mediating GH-induced muscle hypertrophy in pigs.

Animals↗

Management of pregnancy after augmentation cystoplasty.

We contacted 256 members of the Society for Pediatric Urology to determine their experience with patients who had undergone augmentation cystoplasty and who later became pregnant and delivered a baby. There were 15 pregnancies in 15 patients. Urinary tract infection or pyelonephritis complicated 9 of the 15 pregnancies (60%) and 4 patients experienced premature labor. Serum creatinine levels remained stable throughout pregnancy in 14 patients. Delivery was vaginal in 10 patients, each of whom had the native continence mechanism intact, and by cesarean section in 5, of whom 3 had had prior surgical reconstruction of the vesical neck. There were no intraoperative or postoperative complications. As a consequence of this study, we recommend that patients who have had an enterocystoplasty alone should not be at an increased risk for incontinence from a vaginal delivery. Conversely, patients who have undergone augmentation cystoplasty and either vesical neck reconstruction or placement of an artificial genitourinary sphincter to attain continence should undergo cesarean section delivery to avoid the potential for disruption of the continence mechanism.

Delivery, Obstetric↗

Ureteroscopy in children.

The development of ureteroscopy has led to a dramatic change in the management of ureteral stones as well as other ureteral pathological conditions in adults. Until recently, size limitations have prevented the technique from being used in small children. We have used ureteroscopy for diagnosis and therapy in 4 children less than 10 years old. There was no significant morbidity from the procedure in our patients.

Child↗

Pediatric urological complications with intraoperative radiation therapy.

Intraoperative radiotherapy with variable energy electrons has been used as a supplemental boost to treat 6 children with locally advanced retroperitoneal malignancies. Of the patients 4 had treatment-related injuries to portions of the urinary tract within the intraoperative and external radiation fields. Three patients had significant renal impairment requiring surgical correction. The pathogenesis and management of treatment-induced injury to the urinary tract are discussed.

Adolescent↗

Augmentation cystoplasty utilizing de-epithelialized sigmoid colon: a preliminary study.

The use of bowel segments for bladder replacement or augmentation has been associated with metabolic complications and obstruction due to mucus production. Establishment of a transitional epithelium over the de-epithelialized surface of a segment of intestine might alleviate these complications. Twenty Holstein bull calves underwent sigmoidocystoplasty. Fourteen experimental animals had the epithelium of the sigmoid removed before augmentation. Six calves with intact mucosa served as controls. Fifteen calves survived the study: 11 experimentals and four controls. Cystectomies were performed at four, six, eight, or 12 weeks. Ninety-one percent (10/11) of the experimental calves had almost complete epithelialization of the de-epithelialized graft. All experimental animals had residual colonic mucosa or mucoceles. Nine of 11 experimental calves (82%) had greater than 25% contracture of the sigmoid graft. Two animals had less than 25% graft contracture (1) or formed a wide-mouthed true diverticulum (1) in the grafted segment. All control animals formed a wide-mouthed true diverticulum and had no graft contracture.

Animals↗