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Biomedical subjects

R H Ringert

Publications and source records attributed to R H Ringert.

At least 37 records · Page 2Linked to original sources

[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↗

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↗

Influence of vinblastine on DNA parameters and multidrug resistance in renal cell carcinoma in vitro.

The purpose of this study was to investigate how the vinca alkaloid vinblastine influences DNA parameters and the mechanisms of multidrug resistance in renal cell carcinoma. After exposing cell cultures of human renal carcinoma to progressively increasing concentrations of vinblastine the cell lines were examined by flow cytometric DNA analysis to assess the S-phase and G2/M-phase fraction and by a modified MTT assay. It was shown that the exposed cells became P-glycoprotein-positive by staining the cells with a monoclonal antibody (JSB-1). The flow cytometric analysis revealed, with prolonged vinblastine exposure, correlated increases in the S-phase and G2/M-phase fractions (P = 0.0001). When vinblastine-free medium was used for culturing, the changed DNA characteristics returned to their original values. Comparing the DNA parameters with the IC50 (concentration when cell growth is inhibited by 50%) we found a strong correlation between these parameters (P = 0.0001). In conclusion, DNA analysis of long-term vinblastine exposure may provide insight into events leading to multidrug resistance. Furthermore, analysis of the DNA profile might also be an important investigation before planning therapy with vinblastine for renal cell carcinoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Autologous and allogenic hybrid cell vaccine in patients with metastatic renal cell carcinoma.

OBJECTIVE: To evaluate the safety, acute and long-term toxicity and therapeutic activity of an allogenic and an autologous hybrid cell vaccine in patients with progressive metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: Eleven patients were vaccinated with a lethally irradiated hybrid cell vaccine of allogenic RCC tumour cells fused with major histocompatibility complex class I-matched and class II-unmatched activated allogenic lymphocytes. These patients were then followed for a mean of 11 months. Another 13 patients were vaccinated with a hybrid cell vaccine of autologous tumour cells fused with allogenic activated lymphocytes and followed for a mean of 6 months. RESULTS: Six of the 11 patients receiving the allogenic vaccination showed an initial response, with two complete and two partial responses to date. Only three patients who received autologous vaccination responded to treatment. CONCLUSIONS: Hybrid cell vaccination is a promising new approach in the treatment of patients with advanced RCC.

Cancer Vaccines↗

Metastasis from renal cell carcinoma to the cervix uteri.

We report on a patient with clear cell adenocarcinoma of the left kidney and a solitary metastasis to the cervix uteri. Metastases from renal cell carcinoma to the female genitalia are uncommon and metastatic involvement of the uterus is very rare. To our knowledge, no more then five cases have been published. A review of the literature is given.

Aged↗

Evaluation of seminal plasma parameters in patients with chronic prostatitis or leukocytospermia.

Though detailed cytological and microbiological diagnostic procedures are routinely carried out in male genital tract infection, the correct diagnosis and localization of inflammation or infection is often difficult. In this prospective study, the relevance of the seminal plasma markers PMN elastase, complement C3, CRP, fructose, PSP 94, PSA, and alpha-glucosidase was investigated in 13 patients with chronic prostatitis, 31 patients with significant leukocytospermia, and 58 patients with non-inflammatory diseases (controls). Statistically relevant results were obtained for PMN elastase when comparing chronic prostatitis with controls, leukocytospermia with controls (P < 0.001) and chronic prostatitis with leukocytospermia (P < 0.05); for complement C3 chronic prostatitis and leukocytospermia vs. controls (P < 0.05) and for fructose/ejaculate leukocytospermia vs. controls (P < 0.05). No statistically relevant differences were found for C-reactive protein, alpha-glucosidase, PSA and prostatic secretory protein (PSP 94). To delimit genital tract inflammation from non-inflammatory patients, cutpoint levels for PMN elastase of 230 ng ml-1 and for C3c of 0.01 g l-1 were suggested. PMN elastase was shown to possess the strongest discriminating power. The assessment of a cutpoint for fructose to indicate seminal vesicle dysfunction is not possible as the significance level is weak (P < 0.05).

Adolescent↗

Comparison of questionnaire-based and serological screening for natural latex allergy in children with neurogenic bladder dysfunction.

OBJECTIVE: We evaluated the prevalence of sensitization to natural latex in children with congenital neurogenic bladder dysfunction by patient history and serological examinations. METHOD: 50 consecutive children aged from 6 months to 17 years were included into the study which comprised questionnaires of patient and family histories, serological screening tests for common inhalational allergens (CAP SX1), and determination of total serum immunoglobulin E (IgE) and of latex-specific serum IgE by solid-phase immunoassays. RESULTS: 5 children had a history of allergic reactions to natural latex; a history of atopic disposition or allergic reactions other than to latex was present in 16 children. In 10 children, latex-specific IgE levels were elevated: > 0.35 kU/l; 6 out of these 10 children had no history of allergic reactions to latex. Elevated latex-specific IgE values were statistically correlated with the number of past operations (p < 0.006) and a history of atopic or allergic reactions (p < 0.0067). Clean intermittent catheterization, however, was not associated with an increased risk of latex allergy (p = 0.408). CONCLUSION: When screening children with congenital neurogenic bladder dysfunction for sensitization to natural latex, serological examinations of latex-specific IgE in addition to patient history may better identify patients at risk.

Adolescent↗

[The acute scrotum].

Acute scrotal swelling is a potential urologic emergency. There are many conditions which may present with scrotal swelling including spermatic cord torsion, torsion of testicular appendages, epididymitis, orchitis, incarcerated scrotal hernia, hydrocele, varicocele, trauma, tumor and testicular pain in vasculitis syndromes such as Schoenlein-Hennoch purpura. Testicular torsion is the most important condition that must be proven or ruled out to avoid loss of testicular function. History, physical examination and perhaps color-coded doppler-sonography are the tools to diagnose torsion. Using these tools, three diagnostic categories will be defined: Torsion, non-torsion or equivocal diagnosis. In every doubtful case scrotal evaluation is done surgically. Non-torsion is treated according to the different diseases.

Acute Disease↗

Expression of metalloproteinase 2 and 9 and their inhibitors in renal cell carcinoma.

Degradation of the extracellular matrix is necessary for invasion and metastasis by cancer cells. Two gelatinolytic matrix metalloproteinase enzymes, MMP-2 and MMP-9, are supposed to be key enzymes in this process. The purpose of this study was to correlate the presence of MMP-2, MMP-9 and their inhibitors with the tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2 RNA using reverse transcriptase PCR technique with tumor stage in 17 samples of renal cell carcinoma. The ratio of tissues expressing MMP-2 and MMP-9 to those expressing TIMP-1 and TIMP-2 was defined to be 1 in normal kidney tissue. This MMP:TIMP ratio was significantly increased to 2.43 (standard deviation, SD = 0.8) in locally confined renal cell carcinoma and to 4.86 (SD = 1.1) in advanced carcinoma (p <0.01). In primary tumor cell lines the ratio of MMP:TIMP expression was 3.44 (SD = 0.6). These data suggest that the balance of MMP-2 and MMP-9 to TIMP-1 and TIMP-2 expression is an essential factor in the aggressiveness of renal cell carcinoma.

Carcinoma, Renal Cell↗

In vitro investigations of new therapeutic agents on bladder tumor cell lines.

In this study sensitivity of human transitional cancer cells to the anticancer agent paclitaxel, an antimicrotubular drug, and to gallium nitrate, a group IIIa metal, was compared to that of the standard MVAC (methotrexate, vinblastine, doxorubicin and cisplatin) drugs. The reduction of cell proliferation was evaluated after 48 h of incubation of six different cell lines with each agent using the mean transit time (MTT) assay. We investigated both monolayers and spheroids. Paclitaxel showed significantly higher growth inhibitory effects on monolayers than vinblastine, both agents targeting the antimicrotubular apparatus. This could not be reproduced on spheroids, where a survival fraction of 50% was observed even at high concentrations (10 microM). High concentrations of gallium nitrate were needed to achieve sufficient toxicity. These concentrations are beyond the concentration achievable by systemic application. Our findings suggest that paclitaxel may be a clinically useful agent for systemic and intravesical use in bladder cancer.

Antibiotics, Antineoplastic↗

Electrolyte equilibration of human kidneys during perfusion with HTK-solution according to Bretschneider.

Twelve surgically removed human kidneys (mainly tumor kidneys) were investigated. The investigations comprised perfusion criteria (perfusion flow, perfusion pressure, perfusion resistance, electrolyte equilibration). During perfusion of the kidneys with HTK solution, the perfusion resistance was nearly three times as high in human kidneys as in canine kidneys perfused under the same conditions in previous studies. Beside possible species differences the raised perfusion resistance may be explained by the greater trauma to the human kidneys due to the surgery, the primary ischemic stress which cannot be avoided clinically and the often nonoptimal initial diuresis. Nevertheless definitive perfusion is possible under clinical conditions although pronounced increases of perfusion resistance may occur. As indicated by the raised perfusion resistance of human kidneys under clinical conditions as compared with canine kidneys in an experimental model, electrolyte equilibration of human kidneys was protracted. For this reason, a duration of perfusion of at least 10 min is necessary in clinical application of HTK solution, i.e., longer than in animal experiments.

Glucose↗

[Microproteinuria and enzymuria in fever and pyelonephritis in childhood. A prospective study of 180 children].

In 180 children (87 children belonging to a control group, 68 with fever of non-renal origin, and 25 with pyelonephritis) albumin and immunoglobulin G (markers for glomerular dysfunction), alpha-1-microglobulin and beta-NAG (markers for proximal tubular dysfunction) and apolipoprotein A1 (marker of "postrenal' dysfunction) were measured in second-voided morning urine. In children with fever of non-renal origin, glomerular dysfunction was encountered in 8.8%, tubular dysfunction in 17.6% and mixed glomerular-tubular dysfunction in 14.7% of cases. Among children with pyelonephritis, 28% revealed glomerular dysfunction and 44% mixed glomerular-tubular dysfunction. No case of solitary proximal tubular dysfunction was observed in children with pyelonephritis. There were highly significant differences in presence and expression of glomerular dysfunction between children with fever of non-renal origin and children with pyelonephritis (P < 0.0001), whereas with regard to proximal tubular dysfunction, the differences were only moderately significant (beta-NAG: P < 0.01) or of low significance (alpha-1-microglobulin: P < 0.05). This may indicate that morphologic changes occur during interstitial pyelonephritis due to inflammation of glomeruli, resulting in glomerular dysfunction, while proximal tubular dysfunction may additionally be due to fever-associated function processes.

Acetylglucosaminidase↗

[Influence of DNA ploidy and grading on survival in primary metastatic prostate carcinoma].

An aneuploid pattern of prostatic cancer defined by flow cytometry was shown to be of value in predicting progression rates and patient survival times. We evaluated the long-term value of DNA analysis in prostatic cancer in 61 patients with advanced disease. We performed flow cytometry on 61 fresh prostate specimens obtained-from a transrectal needle biopsy or a transurethral resection. All patients received antihormonal therapy. Time until death was evaluated in all patients. Of the DNA histograms analyzed, 37% showed a diploid pattern, 63% an non-diploid pattern, and 37% a tetraploid or hypertetraploid pattern. Kaplan-Meier plots were generated for analysis of the probability of survival. Mean survival time was 44 months for patients with diploid (range 1-126 months) and 40 months for patients with non-diploid tumors (range 1-96 months). This difference is not statistically significant. However, the combination of non-diploid and low-differentiated (G3) tumors reduced survival time significantly (mean 20 months, range 1-62 months). There was no patient with combination of a diploid and highly differentiated tumor.

Aged↗

Dual-phase helical CT of the kidney: value of the corticomedullary and nephrographic phase for evaluation of renal lesions and preoperative staging of renal cell carcinoma.

OBJECTIVE: Our objective was to evaluate early-phase unenhanced and late-phase contrast-enhanced helical CT in revealing renal lesions and staging renal cell carcinomas. SUBJECTS AND METHODS: Contrast-enhanced helical CT of the kidneys was performed in 145 patients who also underwent unenhanced CT. Contrast-enhanced CT was performed in the corticomedullary phase (CMP) and nephrographic phase (NP). A total of 173 lesions in 96 patients were proven histologically or cytologically. The performance of helical CT in the three study groups was compared: unenhanced and CMP enhancement, group 1; unenhanced and NP enhancement, group 2; unenhanced, CMP enhancement, and NP enhancement, group 3. Among the parameters evaluated were the sensitivity for helical CT of all 173 renal lesions and the sensitivity and specificity for the 90 malignant tumors. Also, the preoperative CT staging of the 76 renal cell carcinomas was correlated with the pathologic specimens. RESULTS: The sensitivity for detection of all renal lesions in group 1 (84%) was significantly less than in groups 2 and 3 (97% and 100%). The specificity and accuracy of helical CT in revealing renal cell carcinomas were significantly higher (p < .05) in group 3 (95% and 95%, respectively) than in groups 1 (93% and 92%, respectively) and 2 (89% and 91%, respectively). Two renal cell carcinomas were overlooked by the interpreters of the helical scans in group 1. The accuracy of preoperative CT staging of renal cell carcinomas was significantly better (p < .05) in group 3 (91%) than in groups 1 (82%) and 2 (86%). CONCLUSION: When patients underwent unenhanced helical CT, CMP helical CT, and NP helical CT, we achieved a better rate of detection and characterization of renal lesions and better preoperative staging of renal cell carcinomas than when we used either CMP helical CT or NP helical CT alone.

Adult↗

Extracellular HTK perfusion and intracellular acidification in ischemic dog kidneys: a 31P NMR spectroscopic study.

PURPOSE: Bretschneider's histidine-tryptophan-ketoglutarate solution (HTK) for organ preservation is in wide clinical use. Its high buffering capacity is its major protective principle. It is assumed that renal ischemic tolerance benefits from this principle. The study was undertaken to determine the degree to which extracellular buffering influences intracellular acid load. MATERIAL AND METHODS: Canine kidneys were investigated for intracellular and extracellular pH changes during a clinically relevant period of ischemia after preperfusion with either HTK or Ringer solution (Ringer) at different temperatures. Extracellular pH (pHe) was measured with ion-sensitive electrodes. Intracellular pH (pHi) was determined with 31P NMRS. Morphologic and functional parameters were assessed in reperfusion experiments. RESULTS: After perfusion with HTK, pHe values of 7.35, 7.25, and 7.30 were determined for 5C, 20C and, normothermia, respectively. The pHe values after 150 minutes were 7.37, 6.84, and 6.76 at the temperatures indicated. The corresponding pHi values 150 minutes after HTK perfusion were 7.20, 6.79 and 6.54. After Ringer perfusion and 150 minutes at 20C and normothermia, pHi values of 6.29 and 5.92 were measured. Reperfusion experiments showed better results in the HTK group. CONCLUSIONS: Preperfusion with HTK considerably decreases ischemic acidification of extracellular and intracellular compartments at 20C and 37C, compared with Ringer. In kidneys preperfused with HTK and kept at 5C, a nearly physiologic pH was maintained during the observation period of 150 minutes and longer, HTK leads to better functional and morphologic preservation compared to Ringer.

Animals↗