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Biomedical subjects

H Rübben

Publications and source records attributed to H Rübben.

At least 127 records · Page 7Linked to original sources

Identification of G protein-coupled receptors potently stimulating migration of human transitional-cell carcinoma cells.

The expression of G protein-coupled receptors inducing calcium mobilization and stimulating cell migration was examined in human transitional-cell carcinoma (J82) cells. Measurements of cytoplasmic Ca2+ concentration ([Ca2+]i) and phospholipase C activity indicated that these cells express several calcium-mobilizing receptors, including those for lysophosphatidic acid (LPA), thrombin, bradykinin, bombesin and histamine, of which only the LPA response was sensitive (approximately 50%) to pertussis toxin (PTX). Migration of J82 cells was strongly stimulated by LPA and thrombin, by 5- to 20-fold, whereas bradykinin, bombesin and histamine were ineffective. Migration induced by either LPA or thrombin was inhibited by the actin cytoskeleton-disrupting agent, cytochalasin B, by the Rho protein-inactivating Clostridium difficile toxin B, by preventing [Ca2+]i transients with an intracellular calcium-chelating agent, and by the phorbol ester, phorbol 12-myristate 13-acetate, which also blocked the LPA- and thrombin-induced [Ca2+]i increases. On the other hand, ADP-ribosylation of Gi type G proteins by PTX abrogated the migratory response to LPA, without affecting the thrombin effect. Similarly, raising cAMP levels inhibited, by about 50%, the LPA- but not the thrombin-induced J82 cell migration. In conclusion, human transitional-cell carcinoma (J82) cells express various G protein-coupled, calcium-mobilizing receptors, out of which only those for LPA and thrombin stimulate cell migration, indicating that phospholipase C-derived second messengers per se are not sufficient for initiating this response. The complex signal transduction processes leading to LPA- and thrombin-stimulated motility of these human carcinoma cells apparently involve several common, essential factors, such as [Ca2+]i changes and Rho protein-regulated reorganization of the cytoskeleton, as well as some distinct components, most notably distinct subtypes of heterotrimeric G proteins and apparently also distinct cAMP-sensitive targets.

Calcium↗

[Long-term results of wall stent implantation in benign prostatic hyperplasia and high risk status].

The implantation of a Wallstent prosthesis is a minimally invasive alternative to conventional TUR-P for the treatment of infravesical obstruction owing to benign prostatic hyperplasia. We report on the long-term follow-up of 37 patients with a high-risk status for TUR-P who have been implanted since May 1990. The ASA status was: ASA I: 0, ASA II: 2, ASA III: 17 and ASA IV: 18 patients. The median follow-up is now 38.5 months. Directly after implantation, a medium increase in the maximum flow-rate from 7.5 ml/s to 16.9 ml/s was documented. Residual urine was reduced from 120 to 24.2 ml on average. After 12, 18, 24 and 36 months, average maximum flow rates of 16.1, 16.7, 12.0 and 11.6 ml/s were evaluated. The corresponding residual urine was 50.3, 121.1, 56.8 and 65 ml, respectively. Also, micturition frequency decreased from 12.4 preoperatively to 8.3, 7.6, 8.0, and 8.4 per day on average. Nearly all patients reported perineal discomfort in the 1st weeks after implantation. For this reason, the stent had to be removed in 1 patient on the 45th postoperative day. In addition, a dislocated stent had to be replaced in 2 patients. Six of 15 retention patients presented with persisting detrusor dysfunction after implantation and were therefore discharged with a suprapubic tube. Endoscopic controls showed complete urothelial coverage in 78% of our patients after 6 months. After 18 months all stents were completely covered. Long-term follow-up showed reobstruction in 6 of 37 patients (16.7%) and signs of incontinence in 4 of 37 (10.8%). The late complication rate is therefore calculated at 27.5%. Stent-related deaths could not be found. We conclude that Wallstent implantation into the prostatic urethra is an alternative to TUR-P for patients at high risk from surgery. The good postoperative results also remain stable during long-term follow-up.

Aged↗

[Treatment and follow-up of patients with squamous epithelial carcinoma of the penis].

Since squamous cell carcinoma of the penis is rare, prospective trials do not exist. Therefore, new treatment strategies have to be developed. Based on our experience with the treatment of 22 patients with penile squamous cell carcinoma, we describe our therapeutic approaches. Ten patients with superficial disease (T1-2N0M0) were treated with partial penectomy. The 3-year survival rate amounted to 90%. In patients with extensive disease (T3-4 or N1-3) a partial or total penectomy was performed. After initial antibiotic therapy for 4 weeks, patients underwent inguinal lymph-node dissection and if the nodes were positive, additional pelvic lymph-node dissection. In patients with ulcerous inguinal lymph-node metastases surgical resection was performed, covering the wound with a musculocutaneous flap (tensor fascia lata flap n = 2; rectus abdominis flap n = 1). The 3-year survival rate of patients with T1-2N1 tumours (n = 4) was 67% and with T3-4N1-3 (n = 8) 25%. Patients with distant metastases received inductive systemic chemotherapy with cisplatin, methotrexate and bleomycin. Objective responses occurred in 22% (1 CR, 1 PR) of 9 patients. These results suggest that immediate radical surgery with lymph-node dissection is the best treatment for squamous cell carcinoma of the penis.

Adult↗

[Post-traumatic priapism in a 10-year-old boy].

The case of a 10-year-old boy with post-traumatic priapism after perineal trauma is presented. Interdisciplinary treatment using angiography and selective catheter embolization for juvenile high-flow priapism is demonstrated. The literature and the diagnostic possibilities resulting from color duplex sonography are discussed.

Arteriovenous Fistula↗

[Burkitt lymphoma as a rare cause of hydronephrosis].

Involvement of the genitourinary tract by lymphoproliferative disorders is rare. Rapid proliferating Burkitt's lymphomas could mimic acute diseases. Due to the extreme chemosensitivity, the lymphoma is cureable and surgery should be done only for histology. Initial surgery should be restricted to acute abdominal complications or complete removal of localised resectable disease. In any case a multiagent chemotherapy is necessary.

Adult↗

[Therapy with mitomycin C, folic acid and 5-fluorouracil in treatment of metastatic, refractory urinary bladder carcinoma--phase II study].

We performed a phase II trial with second-line chemotherapy in patients with refractory, metastatic cancer of the bladder. Second-line therapy consists of 2.6 cycles of mitomycin-C, 5-fluorouracil and folic acid. Two patients suffered from WHO grade III side effects (nephrotoxicity, leukocytopenia). We did not find any complete or partial remission. Four patients had a stable disease; 3.3 months after therapy, patients developed tumor progression with a median survival of 9 months. Four patients reported an improvement in quality of life. Since all patients received supportive care, improvement in quality of life cannot be related to chemotherapy alone. In conclusion, second-line chemotherapy with mitomycin-C, 5-fluorouracil and folic acid has no effect on refractory, metastatic cancer of the bladder and is no alternative for cisplatin and methotrexate-based chemotherapy.

Aged↗

[Long-term outcome of surgical therapy of metastatic non-seminomatous germ cell tumor in advanced tumor stages].

We present long-term results (minimum follow-up 5 years) in 145 patients with advanced non-seminomatous germ cell tumours, who underwent radical retroperitoneal lymphadenectomy (RPLA) after chemotherapy. We correlated patients' outcomes (death of disease) to different kinds of chemotherapy and to intraoperative findings. We found that patients who were treated by a modified Einhorn scheme with cisplatin, etoposide and bleomycin have a good prognosis. In all, 90% showed no evidence of disease (NED). The NED rate was significantly lower in patients who were treated by sequential alternative chemotherapy (DOD = 37%). We determined the following prognostic factors which predict a poor outcome: salvage RPLA in the case of progressive disease or tumour marker increase during chemotherapy (DOD = 89%, P < 0.0001) residual tumour in multiple-organ systems (DOD = 41%, P = 0.0006) vital tumour in RPLA specimen (DOD = 53%, P < 0.0001) residual tumour mass > 5 cm (DOD = 41%, P = 0.0188). We found that histopathological findings of the primary tumour and tumour stage IIc-IIIc according to the Lugano classification have no prognostic significance for death of disease.

Adult↗

Management of neurogenic fecal incontinence in myelodysplastic children by a modified continent appendiceal stoma and antegrade colonic enema.

OBJECTIVES: Antegrade colonic enemas for neurogenic fecal incontinence via reverse reimplanted appendices (Mitrofanoff principle) have been primarily reported by Malone and coworkers in 1990. We used a modification of the described surgical technique and treated the first 10 patients with neurogenic fecal incontinence due to spina bifida. The surgical procedure and the results are reported. METHODS: Since November 1991, we have used a surgical procedure similar to the appendiceal continence mechanism in urinary diversion to establish a continent colonic cutaneous stoma for antegrade enemas in 10 myelodysplastic patients (4 females, 6 males; median age 13.2 years [range 6 to 26]) with severe neurogenic fecal incontinence. The average follow-up is now 26.4 months (range 12.5 to 50). All patients had neurogenic bladder dysfunction successfully managed by clean intermittent catheterization, anticholinergic drugs, or artificial sphincter implantation. The surgical technique for fecal incontinence included the partial orthotopic submucosal imbedding of the appendix into a cecal tenia and the fixation of the ileocecal region at the inner side of the abdominal wall after creation of an appendicocutaneous catheterizable stoma. RESULTS: All patients reached fecal continence for at least 38 hours (median 45.3) by using antegrade colonic enemas with 1.5% saline solution (n = 9) or GoLYTELY solution (n = 1), 0.5 to 1.5 L every 2 to 3 days. All other therapies (diet, oral medication, rectal purgative, or enema) to reach fecal continence had previously failed. There were only two complications seen at the follow-up. One boy with an artificial urinary sphincter presented with infection of the sphincter system, which led to explantation. Another boy presented 15 months after creation of the colonic appendiceal stoma with saline intoxication possibly due to a homemade saline solution. CONCLUSIONS: We conclude that the antegrade colonic enema via an orthotopic continent appendiceal stoma is a safe and highly effective treatment modality for fecal incontinence in patients with neurogenic bowel dysfunction if nonsurgical management has failed.

Adolescent↗

Bladder autoaugmentation in adult patients with neurogenic voiding dysfunction.

Bladder autoaugmentation offers an alternative to enterocystoplasties for patients with low capacity high pressure bladders caused by non-malignant pathology. In particular for patients with neuropathic hyperreflexive bladders, refractory to less invasive therapy, bladder autoaugmentation will attain comparable results with less impact on life quality compared to other bladder augmentation procedures. The procedure does not preclude later enterocystoplasty or deafferentations. Over the last 7 years, 50 patients were treated by this method, some of them for other than neurogenic voiding dysfunction. Substantial increase of bladder capacity and compliance resulted, at the cost of increased residual urine and the need for intermittent catheterisation in most patients. Some patients are able to perform complete voiding at will. The time lapse between surgery and functional rehabilitation of the bladder (substantial increase of capacity and detrusor compliance) cannot be predicted yet. In most patients this amelioration was observed 1-6 months after surgery, but in some the effect was equivocal for a year or longer. Low-dose anticholinergics appear to speed up the therapeutic effect. One patient had enterocystoplasty and one deafferentation later, one had rupture of the bladder, probably from the use of an artificial sphincter, and two are rated as failures because of psychogenic bladder-centred problems. Bladder autoaugmentation is a favourable treatment for patients who are motivated to wait possibly longer for functional changes to occur and are willing to perform intermittent catheterisation afterwards.

Adolescent↗

Phase II study: adjuvant single-agent carboplatin therapy for clinical stage I seminoma.

OBJECTIVE: Though para-aortal and ipsilateral iliacal radiation is the established adjuvant treatment for clinical stage I seminoma, promising results have been reported on adjuvant single-agent carboplatin therapy. PATIENTS AND METHODS: We treated 43 patients with clinical stage I seminoma according to this option. They received 2 courses of single-agent carboplatin (400 mg/m2) at an intervall of 3 weeks. Therapy could be performed on an outpatient basis within 2 h. RESULTS: Therapy was well tolerated. Apart from minor gastrointestinal disorders and mild myelosuppression, no adverse reactions were observed. The median follow-up is 28 months. Up to now no recurrences have been noted. CONCLUSIONS: If the recurrence rate remains as low as after adjuvant radiotherapy, which should be proved in a phase III study, single-agent carboplatin therapy will be an alternative adjuvant approach for clinical stage I seminoma.

Adult↗

Improved prognosis assessment for patients with bladder carcinoma.

Urothelial carcinomas are heterogeneous diseases with an aggressive clinical potential. To date, the most used prognostic factors for bladder carcinomas are grade and stage, which are based on histopathological parameters that are often not reliable in predicting a clinical outcome. Here, we evaluated the clinical outcome of 100 patients with urothelial carcinomas with follow-up information for more than 2 years after surgery in relation to the expression of two cell surface antigens, ie, E-cadherin and autocrine motility factor receptor (AMF-R, gp78). Frozen bladder tissues were serially cut, stained either with hematoxylin and eosin for grading, with the anti-gp78 antibodies, or with anti-E-cadherin antibodies to determine level of expression. Of 63 patients presented at the time of diagnosis with pathological loss of E-cadherin associated with increased gp78 expression, 39 (62%) succumbed to tumor progression or death. Of 37 patients with normal E-cadherin and gp78 expression positive and negative, respectively, 36 (97%) had favorable disease outcomes (P < 0.0001). The results suggest that in bladder carcinomas abnormal expression of both E-cadherin and gp78 results in a poor disease outcome, independent of tumor stage and grade.

Age Factors↗

Microbeam MOMeNT: non-contact laser microdissection of membrane-mounted native tissue.

The analysis of tissue-specific genetic alterations depends on the selective procurement of homogeneous cell populations. Microbeam microdissection of membrane-mounted native tissue (MOMeNT) permits the rapid, selective, and low-contamination procurement of tumor or other cells from histological sections by non-thermic non-contact laser microdissection. Tissue sections are mounted on a specifically designed ultrathin transparent supporter membrane. Tissue together with the membrane are then dissected with an ultraviolet (337-nm) pulsed laser microbeam coupled into a robot-stage microscope. The ultraviolet laser causes dissection by cold photolysis due to the high photon density of the microbeam rather than by local heating. The track of the laser microbeam can be preselected freely on a video screen, and the size and form of the dissectates can thus be adapted to the histological features of the section with a delineation accuracy in the micron range. Polymerase chain reaction amplification of DNA from the dissectates is not impaired, and tumor-specific loss of heterozygosity of the APC gene as well as homozygous deletion of the MTS1 gene are demonstrated in bladder carcinomas. Taken together, microbeam MOMeNT is a novel technique that utilizes membrane-based microdissection by an ultraviolet laser microbeam, thus providing a flexible, easy-to-use high-performance tool for the molecular pathologist.

Carcinoma, Transitional Cell↗

Selective loss of human leukocyte antigen class I allele expression in advanced renal cell carcinoma.

The expression of human leukocyte antigen (HLA) class I alleles was analyzed in 65 renal cell carcinomas using one-dimensional isoelectric focusing. Normal organ tissue and peripheral blood lymphocytes were used as controls. The patients were serologically typed using the standard microcytotoxicity test. Forty-two patients were staged as pT1 or pT2, and 23 patients had advanced tumor stages (pT3/pT4). In all cases the HLA-A,B phenotypes were confirmed using one-dimensional isoelectric focusing. The expression of HLA expression was reduced in two tumors [1 x HLA-A1(pT2); 1 x HLA-A28 (pT2)]. In three carcinomas the expression of HLA-A1 was lost. One tumor showed a combined loss of HLA-A2 and HLA-B38. These selective losses occurred in tumor stage pT3 (n = 1) or pT4 (n = 3; P = 0.013, Fisher's exact test). This leads to the conclusion that the loss of HLA expression is predominantly present in advanced tumor stages.

Adult↗

A randomized multicenter trial of adjuvant therapy in superficial bladder cancer: transurethral resection only versus transurethral resection plus mitomycin C versus transurethral resection plus bacillus Calmette-Guerin. Participating Clinics.

PURPOSE: A randomized multicenter trial was done to compare transurethral resection only to transurethral resection plus adjuvant mitomycin C and bacillus Calmette Guerin (BCG) instillation for treatment of superficial bladder cancer (stage pTa/1 grades 1 to 3 except primary stage pTa grade 1). MATERIALS AND METHODS: Included in the study were 337 patients with superficial stage pTa/1 grades 1 to 3 bladder cancer except primary stage pTa grade 1 tumors. One group underwent transurethral resection alone. Mitomycin C (20 mg./50 ml. sodium chloride) was given every 2 weeks during year 1 and once a month during year 2. BCG (120 mg/50 ml. sodium chloride was instilled once a week for 6 weeks and once a month for 4 months. RESULTS: At a median followup of 20.2 months, a decrease in recurrence rate was noted for both drug instillations compared to transurethral resection only. The relative risk of recurrence was 0.508 after mitomycin C and 0.618 after BCG instillation compared to transurethral resection alone. There was no significant difference between the mitomycin C and BCG instillations. The progression rate was comparable in all 3 therapy groups, with an estimated common progression rate of 4.22% per year. Side effects occurred most frequently during or after BCG instillation, most often consisting of cystitis. One patient required cystectomy because of ulcerating cystitis and a prostatic abscess subsequent to unsuccessful tuberculostatic therapy. There were no systemic complications. CONCLUSIONS: Our study showed a positive effect of adjuvant chemotherapy and immunotherapy on decreasing tumor recurrence rate. No influence was observed concerning progression rate, which was low overall.

Adjuvants, Immunologic↗