Biomedical subjects

R H Ringert

Publications and source records attributed to R H Ringert.

At least 19 recordsLinked to original sources

PubMed2002

Bladder dysfunction in children with bilateral single ectopic ureters.

BACKGROUND: Single ectopic ureters are a rare malformation in children. Therapy consists of ureteral reimplantation. However, in case of bilateral single ectopic ureters, subsequent malformation of the bladder trigone and bladder neck may result in additional voiding dysfunction, and ureteral reimplantation alone may not solve the urologic problems. METHODS: The authors report their experience with 2 girls, in whom bilateral single ectopic ureters were treated by ureteral reimplantation in early childhood and who did not gain adequate bladder control during following years. RESULTS: Videourodynamic evaluation was done in both girls. No bladder overactivity was found during the urodynamic studies. However, cystography showed a widely open bladder neck during filling with no sufficient bladder neck closure shown by urethral pressure profile studies. When blocking the bladder outlet by balloon catheters, adequate bladder filling volume was achieved. Incontinence was cured by implantation of an AMS 800 artificial sphincter system in a 10-year-old girl. A 7-year-old girl was regarded to be too young for sphincter implantation and is waiting for surgery within the next years. CONCLUSION: Insufficient development of trigone and bladder neck with subsequent urinary incontinence has to be kept in mind when deciding on surgical procedures in children with bilateral single ectopic ureters.

Abnormalities, Multiple↗

PubMed2001

Prognostic impacts of cytogenetic findings in clear cell renal cell carcinoma: gain of 5q31-qter predicts a distinct clinical phenotype with favorable prognosis.

To evaluate the prognostic significance of cytogenetic findings in clear cell renal cell carcinoma (RCC), cytogenetic results of 118 primary RCCs were evaluated in relation to classical indicators of prognosis and overall survival. Losses in 3p (98.3%) were most prevalent and included 32 (27.6%) monosomies of chromosome 3 and 84 (72.4%) structural aberrations involving 3p, of which 36 were unbalanced translocations, der(3)t(3;5)(p11-p22;q13-q31), resulting in duplication of 5q sequences. Patients with gain of 5q31-qter resulting from either polysomies or structural rearrangements of 5q, the most frequent of which was der(3)t(3;5), had a significantly better outcome than those without this aberration (P = 0.001). There was no association between gain of 5q or der(3)t(3;5) and any of the well-known variables for prognosis, including low versus high clinical stage and grade of malignancy. Among additional chromosomal aberrations, loss of chromosome 9/9p was associated with distant metastasis at diagnosis (P = 0.006). The data indicate that gain of 5q identifies a clinically favorable cytogenetic variant of clear cell RCC and demonstrate the impact of specific chromosome aberrations as additional prognostic indicators in clear cell RCC.

Adenocarcinoma, Clear Cell↗

PubMed2001

Differences in cortical microcirculation in the kidneys of unilaterally congenital hydronephrotic rats.

The surgically induced split hydronephrotic kidney has been generally accepted as a valid model for the assessment of renal microcirculation by means of intravital microscopy. Whereas nearly all previous work on this issue has been done with a transillumination technique, we used an epiillumination model that is suitable for investigation of microvascular perfusion in both normal and hydronephrotic kidneys without surgical manipulation of the ureter. By means of the congenital unilaterally hydronephrotic Tauchi rat, microcirculation of the hydronephrotic and that of the nonhydronephrotic kidney were compared. For that purpose both the hydronephrotic and the nonhydronephrotic kidneys of Tauchi rats were exteriorized on a specially designed microscopy stage. After injection of FITC-dextran and rhodamine 6G, microvascular perfusion was assessed in both kidneys. The new model allowed visualization of arterioles, capillaries, and postcapillary venules in both the hydronephrotic and the nonhydronephrotic kidneys. Glomeruli could only be regularly seen in the hydronephrotic kidney, but also in some normal kidneys. Capillary blood cell velocity was significantly higher in the hydronephrotic kidneys (0.67 +/- 0.03 mm/s) compared to the normal kidney (0.32 +/- 0.05 mm/s; P < 0.05), whereas capillary diameters were smaller (4.2 +/- 0.02 microm vs. 5.7 +/- 0.2 microm; P < 0.05). In addition, the hydronephrotic kidney showed a significantly lower density of perfused microvessels compared to the normal controls. Epiillumination intravital microscopy allows assessment of the cortical microcirculation in both the hydronephrotic and the nonhydronephrotic kidneys without surgical induction of hydronephrosis. The hydronephrotic kidney shows significant microcirculatory differences compared to normal kidneys that should be taken into account when using a hydronephrotic model for pharmacological testing.

Animals↗

PubMed2001

Vascular endothelial growth factor expression, angiogenesis, and necrosis in renal cell carcinomas.

Rapidly growing tumors often develop necrosis. In the present study the expression of vascular endothelial growth factor (VEGF) was investigated and compared to microvessel density and necrosis of renal cell carcinomas. In the tumor-host interface the microvessel density was significantly increased compared to central tumor areas. Tumor necrosis was associated with a decrease of microvessel density and an increase of the VEGF protein expression within the perinecrotic rim. VEGF protein was focally upregulated in vital tumor tissue. An increase of the apoptotic rate of endothelia and vital tumor tissue in tumors with necrosis could not be detected. VEGF(121,165) mRNA was decreased in proliferatively active carcinomas compared to less proliferative tumors. Multicellular renal cell cancer spheroids as a model of chronic hypoxia developed central apoptosis but no necrosis. VEGF was upregulated in the spheroid. Tumor microvessels expressed matrix metalloproteinase -2 and -9 and an incomplete pericyte covering in comparison to tumor-free tissue indicating immature active angiogenesis. We conclude that highly proliferative renal cell carcinomas outgrow their vascular supply and develop chronic hypoxia inducing a decrease of proliferation and an increase of VEGF expression. However, chronic hypoxia does not cause significant necrosis or apoptosis. Tumor necrosis is more likely induced by acute hypoxia due to immature microvessels. Furthermore, VEGF expression associated with concomitant tumor necrosis may help identify renal cell carcinomas susceptible to antiangiogenic therapy.

Antigens, Nuclear↗

PubMed2001

Impaired nephrogenesis in rats with congenital obstructive uropathy.

PURPOSE: Alterations caused by renal obstruction in developing kidneys are of particular interest in basic research of congenital obstructive uropathy. In rats nephrogenesis mainly occurs 7 to 10 days postnatally. Therefore, surgically induced neonatal ureteral obstruction in rats has been suggested to be analogous to congenital obstruction in the fetus. An attempt less prone to surgical artifacts and assessing even earlier developmental stages is to monitor the development of obstructed kidneys in rats with congenital obstructive uropathy. MATERIALS AND METHODS: Rats from an inbred strain with congenital renal obstruction in 70% of their littermates were observed. Morphologically, significant hydronephrosis was not detected before day 5 post partum and progressed with age. Unilateral obstructed kidneys were compared with contralateral kidneys and kidneys from healthy control animals at ages of 1, 5, 10, 18 and 32 days. A total of 72 renal units were investigated. The renal messenger RNA expression of renin and transforming growth factor-beta1 (TGF-beta1) was quantified by competitive quantitative reverse transcription polymerase chain reaction using a gene specific complementary RNA standard. RESULTS: In controls the gene expression of renin decreased from day 1 to day 18 and remained stable. TGF-beta1 expression increased during the first 10 days and then decreased again. Renin expression of the obstructed kidneys was reduced (p <0.05) on day 1, increased to a maximum versus controls (p <0.01) on day 10 and decreased to an unchanged elevated level (p <0.01) on days 18 and 32. Renin expression of the contralateral kidneys showed no significant alterations to control kidneys. Messenger RNA expression of TGF-beta1 of obstructed kidneys stayed decreased during the first 10 days (p <0.05), then increased excessively on day 18 (p <0.01) and slightly decreased on day 32. TGF-beta1 expression of the contralateral kidneys was parallel to controls on a slightly elevated level, increased on day 18 and returned to control level on day 32. CONCLUSIONS: Within the postpartum period of nephrogenesis gene expression of renin and TGF-beta1 was decreased in obstructed kidneys compared to controls. As the renin angiotensin system and TGF-beta1 have important functions in normal kidney development, these results suggest impaired nephrogenesis of congenital obstructed kidneys even before the onset of morphological signs of hydronephrosis. These features differ from surgical induced unilateral ureteral obstruction at birth and promise new insights into the pathophysiology of congenital obstructive uropathy.

Animals↗

PubMed2001

Differential expression of the lung resistance-related protein/major vault protein in the histological compartments of nephroblastomas.

Nephroblastomas (Wilms' tumors) are curable with survival rates above 80%. Some tumors, however, fail to respond to therapy and those patients have a poor prognosis. In a search for molecular markers of drug resistance, we investigated the expression of lung resistance protein (LRP) in tissue samples from 32 children with nephroblastoma by means of immunohistochemistry. LRP is a human major vault protein (MVP) and is associated with multidrug resistance of tumors. LRP/MVP expression was found in the blastemal and epithelial compartments but to a significantly lesser extent in the stromal compartment of Wilms' tumors. Expression was generally heterogeneous with respect to staining intensity and percentage of positive cells. We found significant relationships between LRP/MVP expression and chemotherapeutic pre-treatment of tumors and tumor stage. The immunohistochemical results were validated with a real-time RT-PCR technique and a significant association between protein and mRNA expression was observed.

Antibiotics, Antineoplastic↗

PubMed2001

Differential expression of the multidrug resistance-related protein MRP1 in the histological compartments of nephroblastomas.

Nephroblastomas (Wilms' tumors) are curable with survival rates above 80%. Some tumors, however, fail to respond to therapy and those patients have a poor prognosis. In a search for prognostic markers, we investigated the expression of the multidrug resistance-related protein 1 (MRP1) in 32 nephroblastomas by means of immunohistochemistry. The immunohistochemical results were validated with a real-time RT-PCR technique. MRP1 expression was heterogeneous and predominantly found in the blastemal and epithelial compartments compared to the stromal elements of nephroblastomas. We found significant relationships of MRP1 expression to survival of patients and to expression of p53, HSP70, and LRP/MVP. The relationship between MRP1 and p53 expression is a clue that the transcriptional control of MRP1 by p53 reported for other tumor types may also take place in nephroblastomas. The correlation of MRP1 to other drug resistance genes, e.g. HSP70 and LRP/MVP in nephroblastomas indicates that the co-expression of different drug resistance genes may be under a common regulation of still unknown transcription factors.

ATP-Binding Cassette Transporters↗

PubMed2000

["False positive" testicular perfusion in testicular torsion in power Doppler ultrasound].

We report about a patient with acute scrotal pain. Power Doppler sonography demonstrated arterial testicular perfusion. As no amelioration was achieved by conservative treatment, surgical exploration was done after 7 days. Intraoperatively, we found a partial testicular torsion with a 180 degrees rotation of the testis at the rete testis. This case demonstrates, that the detection of intratesticular arterial blood flow cannot exclude testicular torsion.

Adult↗

PubMed2000

Histologic and molecular evidence of obstructive uropathy in rats with hereditary congenital hydronephrosis.

Partial obstruction of the upper urinary tract, a frequent challenge for the pediatric urologist, leads to renal damage, if deobstruction is delayed. Several but sometimes unsatisfactory animal models have been developed to study this phenomenon. Obstruction created by surgical manipulation lacks adequate correlation with a developing congenital obstruction. In some animals with congenital hydronephrosis, evidence of renal obstruction is absent. A study of the renal morphology of rats with hereditary unilateral hydronephrosis has exhibited clear evidence of renal obstruction distinguishable from renal dilatation. The renal mRNA expression of renin and transforming-growth factor-beta1 (TGF-beta1) was measured by a semiquantitative RT-PCR technique. In hydronephrotic kidneys, a marked loss of parenchyma, atrophy and dilation of tubuli and collecting ducts and interstitial fibrosis was observed. The mRNA expression of renin was increased significantly in comparison to controls, whereas the contralateral kidneys showed renin activity below control levels. TGF-beta1 expression was markedly increased in hydronephrotic kidneys, whereas contralateral kidneys did not differ significantly from control values. These data suggest the presence of renal obstruction and not only renal dilatation in these rats with congenital hydronephrosis. This colony seems to be a representative animal model to study congenital renal obstruction even in the fetal period without the need of surgical manipulation.

Actins↗

PubMed2000

Regression of human metastatic renal cell carcinoma after vaccination with tumor cell-dendritic cell hybrids.

Reports of spontaneous regressions of metastases and the demonstration of tumor-reactive cytotoxic T lymphocytes indicate the importance of the host's immune system in controlling the devastating course of metastatic renal cell carcinoma. Recent research indicates that immunization with hybrids of tumor and antigen presenting cells results in protective immunity and rejection of established tumors in various rodent models. Here, we present a hybrid cell vaccination study of 17 patients. Using electrofusion techniques, we generated hybrids of autologous tumor and allogeneic dendritic cells that presented antigens expressed by the tumor in concert with the co-stimulating capabilities of dendritic cells. After vaccination, and with a mean follow-up time of 13 months, four patients completely rejected all metastatic tumor lesions, one presented a 'mixed response', and two had a tumor mass reduction of greater 50%. We also demonstrate induction of HLA-A2-restricted cytotoxic T cells reactive with the Muc1 tumor-associated antigen and recruitment of CD8+ lymphocytes into tumor challenge sites. Our data indicate that hybrid cell vaccination is a safe and effective therapy for renal cell carcinoma and may provide a broadly applicable strategy for other malignancies with unknown antigens.

Aged↗

PubMed1999

[Langerhans-cell histiocytosis of the penis].

Involvement of the male genitalia by langerhans cell histiocytosis ist very rare. It has been reported in only three cases yet. We present a patient with recurrent disease of the skin of the penis and by proliferation involvement of the distal urethra and the corpus cavernosum. An overview of the disease and its therapy is given.

Adolescent↗

PubMed1999

Polyploidization and losses of chromosomes 1, 2, 6, 10, 13, and 17 in three cases of chromophobe renal cell carcinomas.

Clonal chromosome aberrations identified after short-term culture are presented for three cases of chromophobe renal cell carcinomas (RCC). All tumors revealed abnormal karyotypes with a varying proportion of polyploid tumor cells. Common numerical abnormalities were combined losses of chromosomes 1, 2, 6, 10, 13, and 17. Clonal karyotypic evolution was demonstrated in one case in which several related clones could be identified. An additional balanced translocation t(3;14)(p24;q22) observed in this case proved to be of constitutional nature by cytogenetic analysis of normal kidney cells and peripheral blood lymphocytes. These cytogenetic findings provide further evidence that chromophobe renal cell carcinomas are characterized by a highly specific combination of chromosomal losses most commonly including chromosomes 1, 2, 6, 10, 13, and 17.

Adenocarcinoma↗

PubMed1999

Erectile dysfunction caused by sacral gun-shot injury.

A 22-year-old man suffering from isolated erectile dysfunction associated with damage to the right spinal nerve S2 caused by sacral gun-shot injury. He has no loss of bladder innervation. Treatment has been implantation of a penile prosthesis.

Adult↗

PubMed1999

Helical computed tomography of renal lesions.

Helical computed tomography is a new technique that acquires a volumetric data set of both kidneys within a single breath-hold. It has proved to be superior to conventional computed tomography. Multiphasic helical computed tomography after the administration of contrast material shows advantages concerning the detection and characterization of renal lesions and the preoperative staging of renal cell carcinomas. The proper scan protocol for a sufficient examination of the kidneys is described as well as its diagnostic value. The characteristic computed tomography morphology of benign and malignant renal lesions is reviewed and the advantages of helical computed tomography are illustrated.

Animals↗

PubMed1999

Outcome after repair of congenital penile malformations.

Penile malformations seen and treated during childhood may result in voiding disorders and sexual malfunction in adults. Preputial synechia and phimosis will seldom be the reason for these problems, although some men do seek treatment to correct radical circumcision. Little is known about the satisfaction of men with neonatal or childhood circumcision. Congenital penile curvature is seen in 0.4-0.6% of men. Slight bends do not need any operative treatment and young men should be given advice and counselling accordingly. If treatment is needed, a standard Nesbit procedure or one of its modifications is used in order to avoid urethral manipulation. A hypospadiac position of the urethral meatus together with a more or less prominent ventral bending of the penis is seen in another 0.3-0.5% of boys. Reports on more than 200 operations to correct this deformity have been published. Between 5 and 25% of early complications such as fistula formation, stenosis of the neourethra and skin problems result from hypospadias repair. Long-term follow-up studies have shown that adulthood satisfaction with respect to voiding and sexual function is achieved in 2/3 and some degree of dissatisfaction in 1/3 of cases. Epispadias repair is a much more complicated procedure and long-term results are seldom reported. Nevertheless, quite good results with respect to continence (approximately 80%) and sexual function may be achieved.

Adolescent↗

PubMed1998

Push and smash increases success rates in treatment of ureteric calculi by ESWL.

During a 3-year period 105 patients underwent attempted retrograde manipulation for ureteric calculi into the renal pelvis prior to extracorporeal shock wave lithotripsy (ESWL). The success rate of this group was compared to 93 patients receiving ESWL of ureteric calculi in situ. The method of retrograde manipulation was recorded prospectively. Retrograde flushing with a 5 F Tiemann ureteral catheter was performed after coating the proximal ureter and renal pelvis with a mixture of saline and lidocaine gel. Success rate of calculi push was 91.4%. Mean number of ESWL treatments in this group of patients was 1.4, compared to 2.1 in patients with in situ treatment. Reposition of ureteric calculi prior to ESWL treatment increases successful initial treatment and can be performed easily.

Anesthetics, Local↗

PubMed1998

[Treosulfan displays cytotoxic effect on spheroids of primary cell cultures of renal cell carcinoma independent of p-glycoprotein expression].

Therapy of advanced renal cell carcinoma remains difficult. New therapeutic schemes besides cytokine treatment should be evaluated. The following study analyzes the in vitro toxicity of treosulfan on spheroids of 8 primary cultures of renal cell carcinoma cells. these data were compared to the toxicity of vinblastine. All investigations were performed in regard to the P-glycoprotein (Pgp) expression of the cells, which is one of the main causes of multidrug resistance. Four Pgp positive and four Pgp negative spheroids were incubated with the drugs in increasing doses. Toxicity was measured using the MTT toxicity assay as well as trypan blue exclusion. Significantly higher toxicity of treosulfan compared to vinblastine could be demonstrated. In addition, the effects of treosulfan were not related to Pgp expression. These results are encouraging and a phase II study analyzing the efficacy of treosulfan in patients with advanced renal cell carcinoma has been initiated in our institution.

Antineoplastic Agents, Alkylating↗

PubMed1998

Treatment of transplant ureteral stenosis with Acucise endoureterotomy.

Treatment of ureteral stenosis has been attempted in many patients with transplanted kidneys. Treatment with the Acucise catheter system is a new approach for such patients. Published results of the approach in eight patients promise safety, effectiveness, and low perioperative morbidity. We report two cases of transplant ureteral stenosis treated with Acucise. One patient with stenosis of the pyeloureteral junction was treated successfully and has been free of recurrence for 9 months. The other patient had long-distance stenosis of the lower portion of the transplant ureter. Acucise incision was successful, but the patient had to undergo uretero-neocystostomy because of a ureteroperitoneal fistula. We use these cases to illustrate the disadvantages of endourological ureteral surgery as a standard therapeutic approach after renal transplantation. We suggest that Acucise is reliable when used in patients with uncomplicated short-distance ureteral stenosis; however, patients with long-distance stenosis or stenosis caused by heavily scarred periureteral tissue will not profit from it because of a higher complication rate.

Adult↗