Beta-1 integrins in renal cell carcinoma--an immunohistochemical study.
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Biomedical subjects
Publications and source records attributed to R Ackermann.
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The accuracy of computed tomography (CT) in staging of pelvic lymph nodes in bladder cancer was investigated in 50 patients. All patients underwent pelvic lymph node dissection and cystectomy. The results of preoperative CT findings were compared with the histopathological findings in the dissected lymph nodes. Normal lymph nodes free of tumour cells were found in 32 patients. In 6 patients, single lymph node involvement was detected, while in 12 patients two or more lymph nodes were found to be positive for tumour infiltration. CT results were confirmed in 38 patients (76%). Specificity of CT was 100%, but the sensitivity of this method was only 33%. Based on these results, it appears that CT evaluation of pelvic lymph nodes in bladder cancer patients should have only a limited impact on decision making in patient management.
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Frozen sections of primary and metastatic human renal cell carcinoma (RCC) were analyzed for the expression of endogenous binding sites for carbohydrates. Fluorescent neoglycoproteins, carrying chemically linked carbohydrate residues on bovine serum albumin as a carrier protein, were applied to 44 primary tumor specimens. In the majority of specimens, accessible binding sites with specificity for maltose and N-acetylgalactosamine were detected. In specimens of normal kidney no specific binding of carbohydrate ligands was observed under these experimental conditions. Specimens of both the primary tumor and a metastasis were available in 10 cases. When the expression of specific binding sites of primary tumors and metastases was compared, the respective patterns were similar with no clear gain or loss of certain lectins in the metastases. We conclude that binding sites with specificity for maltose and N-acetylgalactosamine are present on human RCC and their corresponding metastases.
Rehabilitation of athletes following surgical reconstruction of complex instabilities of the knee joint focuses on four goals: 1. the restoration of ligament stability, 2. the restoration of muscular stabilisation ability, 3. the restoration of coordinative muscular function in sport specific kinesiology, 4. the retention and improvement of the general state of fitness. These aims can only be reached by a close cooperation between physician, physiotherapist, trainer, and coach. In order not to put the rehabilitation process at risk, everybody involved has to have knowledge about functional anatomy, surgical technique, and biology of the transplant as well as knowledge about the long duration thereof that cannot substantially be shortened by knee ortheses. No athlete should compete until he has demonstrated sufficient fitness, strength, and coordination for his sport under laboratory conditions.
In a prospective study of 302 ureteroscopic procedures, 161 were commenced and 133 completed without the use of general or regional anaesthesia. In 15 patients ureteroscopy (URS) was performed with lignocaine jelly in the urethra only, and in 118 with additional intravenous analgesia. Alfentanil, a synthetic morphine derivative, was used for intravenous analgesia. Ureteroscopy was performed prior to extracorporeal shock wave lithotripsy in 46 patients, for stone basketing in 40, for stone fragmentation in 29, for diagnostic purposes in 14 and for cold knife ureterotomy in 4. Ureteric lesions were observed in 9 patients (6.8%) treated under intravenous sedoanalgesia. This percentage is within the range reported in other series of patients treated under general anaesthesia. The findings suggest that URS, when performed without general or regional anaesthesia, does not increase the risk of complications or compromise the results of treatment.
To establish a quantitative dual-parameter flow cytometry (FCM) analysis of cell surface antigens, possible obstacles caused by contaminated leucocytes in a specimen and staining and measuring conditions were investigated using human bladder cancer cell lines, 5637, T24 and SW1710. The first monoclonal antibody (MoAb) used to select urothelial cells in a specimen was applied with the second MoAb used to discriminate between normal and transformed urothelial cells. MoAbs Due AUT 2 and CD45 appeared to be suitable for the selection of urothelial cells, while Due ABC 3 and Due ABC 5 were applied to detect transformed cells. Tumor cell-leucocyte suspension was simultaneously stained with combinations of these MoAbs. The results demonstrated that Due AUT 2 and CD45 effectively eliminated contaminated leucocytes by means of positive and negative selection of the urothelial cells, respectively. Based on these experiments, dual-parameter FCM analyses of bladder washing from 5 patients with bladder cancer were performed using MoAbs Due AUT 2 and Due ABC 3. The results indicated that by dual-parameter FCM distinct antigenic features of transitional cells could be investigated even if considerable amounts of contaminated leucocytes were present. The clinical impact of this approach is a subject of ongoing trials.
A new two-step technique for percutaneous nephrostomy with a newly designed nephrostomy set is described. The technique combines the advantages of the a direct introducing method (one-step nephrostomy) with an introducing trocar and the "three-step" technique with an initial puncture by a needle and insertion of a rigid guide wire. Evaluation of the different techniques in 195 patients revealed no disadvantage of the new technique compared with the three-step technique.
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To investigate the pharmacokinetics and the disposition of levoprotiline after i.v. and p.o. administration and to assess the absolute bioavailability, 12 healthy volunteers (11 women, 1 man) were given a 10 min i.v. infusion of 15 mg and a p.o. dose of 75 mg in a two-way crossover study. Blood and urine samples were collected after each dose. Unchanged levoprotiline and the sum of unchanged and glucuronidated levoprotiline (= total levoprotiline) were determined by a specific gas chromatographic-mass spectro-metric method. Intravenous levoprotiline was rapidly and extensively distributed into extravascular sites of the body; the steady-state volume of distribution was 18.81 kg-1. The elimination of levoprotiline from blood was independent of the dosing route, the half-life being 18.8 h. Only 1.8 and 0.6 per cent of the i.v. and p.o. dose, respectively, were excreted unchanged in the urine, whereas 57 per cent of each dose were renally excreted as total levoprotiline. The absolute bioavailability of p.o. levoprotiline was 40 per cent. About 60 per cent of the dose was subject to a first-pass effect in the liver. The systemic blood clearance of levoprotiline, determined after i.v. dosing, was 885 ml min-1, the renal blood clearance after i.v. and p.o. dosing was only 16.0 and 14.2 ml min-1, respectively. Presystemic and systemic clearance of levoprotiline occurred predominantly by direct glucuronidation.
The development of the hybridoma technology allows the identification of tumor associated antigens with monoclonal antibodies (mAbs). Employing this technology mAb Due ABC 3 was obtained by immunization of a BALB/c mouse with bladder tumor cell line SW 1710 and subsequent cell fusion of spleen cells with P3. X63.Ag8.653 mouse myeloma cells. MAb Due ABC 3, an IgM antibody, was found to recognize an antigen present in the membrane of tumor cells in 25 out of 28 (89%) transitional cell carcinoma specimens but rarely (three out of 25 specimens, 12%) on normal urothelial cells. Cross reactions were seen with proximal tubular epithelium of the kidney and seven out of 12 renal cell carcinomas examined. Furthermore, the antigen was expressed by granulocytes, some gastrointestinal epithelia, ovarian and breast carcinoma. The antigen recognized by mAb Due ABC 3 was stable to fixation with formaldehyde and paraffin emmbedding, different proteases, alkaline treatment and heat exposure up to 70C. Antigenicity was abandoned by incubation with periodate but not with neuraminidase treatment. The antigen could be extracted with chloroform/methanol suggesting the involvement of a glycolipid. Immuno-thin layer chromatography revealed a single lipid band reacting with mAb Due ABC 3 but not with anti-CD15, directed against the Lewis X antigen. Although not tumor-specific, mAbs directed against differentiation antigens may be of value for the investigation of cell transformations as well as for diagnostic use.
Thirty men who presented with erectile impotence to the urological department underwent a thorough urological, angiological, and neurological examination with complementary neurophysiological tests of somatosensory and sympathetic and parasympathetic function. Most had vascular and neurological abnormalities. Clinical findings and electrophysiological tests for autonomic dysfunction had the highest yield of abnormal results. Nerve conduction studies and pudendal nerve somatosensory evoked potentials were far less informative. The lack of correlation between vascular and general neurological abnormalities emphasises that patients must be screened for both vascular and neurological dysfunction to prevent unrewarding vascular operation in impotent men.
To determine the HLA class-I antigen expression in renal cell carcinoma, the expression of beta-2-microglobulin (beta 2-m) was analyzed. 20 renal tumor specimens and 20 normal renal tissues were examined for beta 2-m expression by immunofluorescence. Homogenous staining of all normal renal tissues was observed, as expected. From the panel of 20 tumors, 17 also had a strong expression of beta 2-m. Furthermore, two newly established renal cancer cell lines exhibited a normal distribution of beta 2-m at two different passages. From these results we conclude that in most cases malignant transformation in renal cancer is not associated with a loss of HLA class-I antigens. This could be a favorable explanation for the restricted results of interferon-gamma in renal cell carcinoma, the main function of which is probably to enhance major histocompatibility complex class-I expression.
Advanced renal cell carcinoma (RCC) is almost completely resistant to conventional therapeutic approaches such as chemotherapy or radiotherapy. There is growing evidence that few patients may be cured from metastatic RCC by immunotherapy. Unlike 20 years ago, current immunotherapeutic regimens are set up with pure drugs, such as recombinant cytokines. Immunotherapy interferes with a complicated network of cellular immune effectors, e.g., T-lymphocytes, macrophages and natural killer cells. The activity of immune effectors cells is regulated and fine-tuned by a variety of cytokines, e.g., interleukins and interferons which are produced predominantly by the immune effector cells themselves. It is reasonable to expect that in the near future more patients will benefit from immunotherapy for RCC as the knowledge on regulation of the immune response to tumors is rapidly increasing.
The high incidence of benign prostatic hyperplasia (BPH), together with the wide variability in its clinical manifestations and in the natural course of disease, requires a careful evaluation of the patient. Technical progress and continuing development of established methods mean that a wide range of diagnostic procedures is available and an "objective" correlate of infravesical obstruction can be obtained. In addition to these objective criteria, the patient's subjective perception of the impact of the symptoms on his quality of life also affects the decision as to whether therapeutic intervention should be attempted and the degree of success that can be attained, as is becoming increasingly evident. The diagnostic methods available for the routine assessment of patients with BPH is reviewed, and their relative value as a basis for deciding on therapeutic intervention is analysed.
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