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Biomedical subjects

S C Müller

Publications and source records attributed to S C Müller.

At least 19 recordsLinked to original sources
PubMed2006

New agents for treatment of advanced transitional cell carcinoma.

The prognosis for any patient with progressive or recurrent invasive transitional cell carcinoma remains poor. In this context, the focus of clinical research in these invasive cancers concentrates on identifying systemic treatment options and new agents in order to improve survival of patients. Cisplatin-based chemotherapy is standard treatment of patients with metastatic urothelial cancer; however, despite regimens as the cisplatin-gemcitabine combination, the overall response rates vary between 40% and 65%, with complete response in 15%-25% with survivals up to 16 months. This survival is frequently achieved with severe and life-threatening side effects. None the less, almost all responding patients relapse within the first year; therefore, the need for development of new and tolerable agents is urgent. This review highlights some new active chemotherapeutic as new platinum compounds (oxaliplatin, lobaplatin), gallium nitrate, ifosfamide, the antifolates piritrexim and pemetrexed (Alimta, LY231514), vinflunine and molecular targeting agents such as farnesyltransferase inhibitors (lonafarnib, R115777, SCH66336), ribozyme (RPI.4610), histone deacetylase inhibitor (CI-994) and monoclonal antibodies (epidermal growth factor receptor, Her 2/neu).

Antibodies, Monoclonal↗
PubMed2006

Electrical stimulation of the energy metabolism in yeast cells using a planar Ti-Au-electrode interface.

We report on the influence of dielectric pulse injection on the energy metabolism of yeast cells with a planar interdigitated electrode interface. The energy metabolism was measured via NADH fluorescence. The application of dielectric pulses results in a distinct decrease of the fluorescence, indicating a response of the energy metabolism of the yeast cells. The reduction of the NADH signal significantly depends on the pulse parameters, i.e., amplitude and width. Furthermore, the interface is used to detect electrical changes in the cell-electrolyte system, arising from glucose-induced oscillations in yeast cells and yeast extract, by dielectric spectroscopy at 10 kHz. These dielectric investigations revealed a beta(1)-dispersion for the system electrolyte/yeast cells as well as for the system electrolyte/yeast extract. In agreement with control measurements we obtained a glycolytic period of 45 s for yeast cells and of 11 min for yeast extract.

Electric Conductivity↗
PubMed2006

Interleukin-2/interferon-alpha2a/13-retinoic acid-based chemoimmunotherapy in advanced renal cell carcinoma: results of a prospectively randomised trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN).

We performed a prospectively randomised clinical trial to compare the efficacy of four subcutaneous interleukin-2-(sc-IL-2) and sc interferon-alpha2a (sc-IFN-alpha2a)-based outpatient regimens in 379 patients with progressive metastatic renal cell carcinoma. Patients with lung metastases, an erythrocyte sedimentation rate < or =70 mm h(-1) and neutrophil counts < or =6000 microl(-1) (group I) were randomised to arm A: sc-IL-2, sc-IFN-alpha2a, peroral 13-cis-retinoic acid (po-13cRA) (n=78), or arm B: arm A plus inhaled-IL-2 (n=65). All others (group II) were randomised to arm C: arm A plus intravenous 5-fluorouracil (iv-5-FU) (n=116), or arm D: arm A plus po-Capecitabine (n=120). Median overall survival (OS) was 22 months (arm A; 3-year OS: 29.7%) and 18 months (arm B; 3-year OS: 29.2%) in group I, and 18 months (arm C; 3-year OS: 25.7%) and 16 months (arm D; 3-year OS: 32.6%) in group II. There were no statistically significant differences in OS, progression-free survival, and objective response between arms A and B, and between arms C and D, respectively. Given the known therapeutic efficacy of sc-IL-2/sc-INF-alpha2a/po-13cRA-based outpatient chemoimmunotherapies, our results did not establish survival advantages in favour of po-Capecitabine vs iv-5-FU, and in favour of short-term inhaled-IL-2 in patients with advanced renal cell carcinoma receiving systemic cytokines.

Adult↗
PubMed2006

Aggressive angiomyxoma of the prostate mimicking benign prostatic hyperplasia.

Aggressive angiomyxoma (AAM) is a locally invasive soft tissue tumor with a high risk of local recurrence but without metastatic spread. The mesenchymal tumor is relatively site-specific and has a peak incidence in females in their 2nd or 4th decade. Only few cases in males have been reported in the literature. We describe what we think is the first case of an aggressive angiomyxoma arising in the prostate presenting with classical symptoms of benign prostatic hyperplasia.

Biomarkers, Tumor↗
PubMed2006

[MR techniques for noninvasive diagnosis of prostate cancer].

The diagnosis of prostate cancer is suggested on the basis of an elevated PSA level, abnormal digital exam, and abnormal transrectal ultrasound. US-guided biopsy is used to confirm the diagnosis, but up to 30% of prostate cancer may be missed with this approach. Meanwhile MR imaging and proton MR spectroscopy have emerged as the most sensitive additional tools for the noninvasive evaluation of prostate cancer. This article reviews the clinical indications for MRI of the prostate and summarizes new techniques such as high field strength (3 tesla) and dynamic contrast-enhanced MRI.

Biomarkers, Tumor↗
PubMed2006

[Plasma-deposited carbon coating on urological indwelling catheters: Preventing formation of encrustations and consecutive complications].

BACKGROUND: Any material placed in the urinary tract is susceptible to the formation of encrustations of crystalline bacterial biofilms. These biofilms cause severe complications in some cases. The strategies used so far for reduction of these complications by surface modifications of the implant material failed to show the expected results. PATIENTS AND METHODS: In this study, we investigated amorphous carbon coatings (a-C:H) for their ability to effectively reduce or to repress the progressive formation of infection-enhancing crystalline biofilms as new functional surface coatings. In nine patients suffering for several years from stenting, a-C:H-coated ureteral stents were tested in treatment attempts. The current replacement intervals amounted to a mean of 77 days; the principle cause for early replacement was massive stent encrustations associated with symptomatic urinary tract infections. RESULTS: In total, 20 coated ureteral stents were tested spanning indwelling times between 3 and 4 months. No stent-related complications occurred. In all cases extraordinarily facile handling, less pain during replacement, and markedly increased tolerance were observed. Symptomatic urinary tract infections were reduced by more than 50%. The stents remained virtually free of encrustations. CONCLUSION: a-C:H coatings are a novel strategy leading to an enhancement of long-term applicability of ureteral stents and catheters and to improved patient comfort.

Adult↗
PubMed2006

[Technical limits of PET/CT with 18FDG in prostate cancer].

There is increasing evidence that (18)FDG-PET is not useful for the imaging of primary prostate cancer. The aim of this examination was to prove whether or not these poor results are due to technical deficiencies of the examination method like older image reconstruction techniques, extensive (18)FDG-tracer activity in the bladder or improper contrast staining of the rectum. We examined three patients with primary prostate cancer using a modern combined PET/CT system, continuous irrigation of the bladder and an air-inflated rectal balloon catheter. PET/CT images show an exact depiction of both the prostate and all surrounding anatomic structures but no enhanced uptake of radiotracer in the tumour. Therefore, the mentioned poor results of (18)FDG-PET seem not to be due to technical deficiencies.

Adenocarcinoma↗
PubMed2006

[Extended metabolic diagnosis of urolithiasis].

PURPOSE: In Germany, urolithiasis, with a frequency of 5 % and a continuously increasing incidence, must be considered as a widespread disease. Ever growing socio-economic expenses have become the focus of attention. The present treatment strategies provide only limited support for the practitioner in evaluating the often complex causes of urolithiasis and in assessing the chosen treatment. A successful treatment with minimal effort requires a general improvement of existing options in prophylaxis as well as metaphylaxis of urolithiasis. For this purpose, detailed examination and interpretation of a stone-former's urinary composition are essential. MATERIAL AND METHODS: The following two novel and significant methods with rapid and uncomplicated application procedures are presented: 1) The easy-to-perform and accurate determination of the calcium oxalate crystallisation risk from a urine sample using the BONN risk index (BRI) for the most frequently occurring stone type (75 %). 2) Consideration of the chemical depletion of lithogenic components in a urine sample due to in-vivo growing uroliths. This phenomenon, the so-called depletion effect, can be of considerable clinical relevance due to possible determination of false normal urinary parameters. RESULTS: This review article explains the theoretical background of these methods and the many applications of the novel methods in practice. CONCLUSIONS: New strategies in stone prevention can help to reduce the extent of urolithiasis in a patient. The BRI enables the practitioner to optimise patient treatment without major effort. Consideration of the stone growth-related alteration of composition improves the interpretation of urine analysis.

Calcium Oxalate↗
PubMed2006

Reducing recurrence and costs in superficial bladder cancer: preclinical evaluation of osmotic cytolysis by distilled water vs. mitomycin.

Transurethral resection followed by instillation of chemotherapeutic agents such as mitomycin is considered as standard therapy in recurrent superficial bladder cancer. However, incidence of bladder cancer is increasing, and contrariwise resources to finance the health care systems are decreasing. Therefore, effective alternatives to expensive chemotherapeutics are necessary. Recurrence of bladder cancer after transurethral resection is mostly promoted by reimplantation of dissolved tumour cells which are therapeutical purpose of any intravesically instillated agent. Monolayer cultures of human RT112, RT4, T24 and TCC SUP bladder cancer cells were incubated and exposed to mitomycin or distilled water. Cell survival was determined by microculture tetrazolium assay. Distilled water led to significant cytolysis in all tumour cells. This effect was comparable to exposition to mitomycin. Distilled water and mitomycin have comparable in vitro effects in bladder cancer cells. These findings have to be substantiated by an animal model emphasising the aspect of larger tumour cell compounds or possible damage to healthy bladder tissue.

Antibiotics, Antineoplastic↗
PubMed2005

Frequency-locking phenomena of propagating wave fronts in reaction-diffusion systems.

We observe N:(N-1)(N>/=2) frequency-locking phenomena of propagating wave fronts when increasing the light intensity in a spatially extended system. The experiments were carried out using the light-sensitive form of the Belousov-Zhabotinsky reaction with Ru(bpy)(2+)3 as a catalyst. By constructing a mapping function, the characteristic devil's staircase can be reproduced when plotting wave period versus light intensity, in agreement with the experimental data.

2,2'-Dipyridyl↗
PubMed2005

Surgical outcome following radical nephrectomy in cases with inferior vena cava tumour thrombus extension.

AIM: To report our experience with extensive surgery in patients with and without metastatic renal cell carcinoma and gross venous tumour thrombus. MATERIAL AND METHODS: Twenty-seven patients with unilateral renal cell carcinoma and tumour thrombus into the vena cava underwent radical nephrectomy and thrombectomy. Eight patients presented with metastatic disease at the time of surgery. Mean follow-up was 17 months (1-54 months, median 9 months). Follow-up was available for 26 patients (96%). RESULTS: Thirteen patients were alive at the time of the study; 11 without evidence of disease with a mean follow-up of 25 months and two (one with and one without metastasis at surgery) with distant metastasis at 16 and 36 months. Eleven patients have died of progressive disease. Mean survival in patients (19 patients) without metastatic disease at time of surgery was 15.2 months; patients (seven patients) with metastatic disease at surgery had a mean survival of 6.7 months. CONCLUSION: Radical nephrectomy and vena caval tumour thrombectomy can be performed in selected patients with an acceptable complication rate. Patients without metastatic disease have a better prognosis than patients with metastatic disease.

Adult↗
PubMed2005

Bioavailability and pharmacokinetics of caffeoylquinic acids and flavonoids after oral administration of Artichoke leaf extracts in humans.

Extracts from artichoke leaves are traditionally used in the treatment of dyspeptic and hepatic disorders. Various potential pharmacodynamic effects have been observed in vitro for mono- and dicaffeoylquinic acids (e.g. chlorogenic acid, cynarin), caffeic acid and flavonoids (e.g. luteolin-7-O-glucoside) which are the main phenolic constituents of artichoke leaf extract (ALE). However, in vivo not only the genuine extract constituents but also their metabolites may contribute to efficacy. Therefore, the evaluation of systemic availability of potential bioactive plant constituents is a major prerequisite for the interpretation of in vitro pharmacological testing. In order to get more detailed information about absorption, metabolism and disposition of ALE, two different extracts were administered to 14 healthy volunteers in a crossover study. Each subject received doses of both extracts. Extract A administered dose: caffeoylquinic acids equivalent to 107.0 mg caffeic acid and luteolin glycosides equivalent to 14.4 mg luteolin. Extract B administered dose: caffeoylquinic acids equivalent to 153.8 mg caffeic acid and luteolin glycosides equivalent to 35.2 mg luteolin. Urine and plasma analysis were performed by a validated HPLC method using 12-channel coulometric array detection. In human plasma or urine none of the genuine target extract constituents could be detected. However, caffeic acid (CA), its methylated derivates ferulic acid (FA) and isoferulic acid (IFA) and the hydrogenation products dihydrocaffeic acid (DHCA) and dihydroferulic acid (DHFA) were identified as metabolites derived from caffeoylquinic acids. Except of DHFA all of these compounds were present as sulfates or glucuronides. Peak plasma concentrations of total CA, FA and IFA were reached within 1 h and declined over 24 h showing almost biphasic profiles. In contrast maximum concentrations for total DHCA and DHFA were observed only after 6-7 h, indicating two different metabolic pathways for caffeoylquinic acids. Luteolin administered as glucoside was recovered from plasma and urine only as sulfate or glucuronide but neither in form of genuine glucosides nor as free luteolin. Peak plasma concentrations were reached rapidly within 0.5 h. The elimination showed a biphasic profile.

Administration, Oral↗
PubMed2005

Transition from an excitable to an oscillatory state in dictyostelium discoideum.

Under conditions of starvation, populations of the amoebae Dictyostelium discoideum aggregate are mediated by chemical excitation waves of cAMP. Two types of waves can be observed, either spiral or circular-shaped ones. We investigate transitions from rotating spirals to circular shaped waves (target patterns). Two different experiments demonstrating this phenomenon are presented. In the first case a continuous transition from the spiral type pattern to target waves was observed at the later stages of aggregation. In the second case the transition was induced by annihilation of waves by a spatially homogeneous cAMP pulse. Instead of the originally present spiral waves, oscillating spots bearing target patterns emerged. On the basis of a model for Dictyostelium aggregation, we provide a theoretical explanation for such transitions. It is shown that cell density can be an effective bifurcation parameter. Under certain conditions, the system is shifted from the excitable to the oscillatory state while the frequency of oscillations is proportional to the square root of the cell density. Thus, the regions with the highest cell density during the early stages of the spatial rearrangement of the cells become pacemakers and produce target patterns. The analytic results were confirmed in numerical simulations of the model.

Animals↗
PubMed2004

GSTP1 hypermethylation as a molecular marker in the diagnosis of prostatic cancer: is there a correlation with clinical stage, Gleason grade, PSA value or age?

OBJECTIVES: Epigenetic events such as promoter hypermethylation have been implicated in prostate carcinogenesis. We present a real-time, methylation specific protocol to detect hypermethylation in the promoter region of the GSTP1 gene in benign hyperplasia and adenocarcinoma of the prostate. METHODS: In our preliminary study, 31 prostate cancer and 5 benign prostatic hyperplasia (BPH) tissue samples were analyzed. Genomic DNA was isolated from formalin-fixed and paraffin-embedded specimens and subjected to sodium bisulfite modification, followed by real-time, methylation specific PCR. Patients with prostatic cancer were also subdivided according to their Gleason score, PSA, age and TNM Staging. Prostate cancer cell lines (LNCaP, DU145, PC3) and a BPH cell line (BPH-1) were also tested as controls. RESULTS: GSTP1 promotor hypermethylation was detected in 28 of the 31 prostate cancer cases (90.3%) and none of the five (0%) BPH cases. Statistical analysis did not reveal a significant correlation between GSTP1 hypermethylation and Gleason score, PSA, age or TNM staging. All prostate cancer cell lines were testes positive for GSTP1 promotor hypermethylation, whereas the BPH cell line (BPH-1) was tested negative. CONCLUSION: GSTP1 promotor hypermethylation occurs during carcinogenesis and is considered to be a major event of prostate carcinogenesis. Our data support this thesis and shows that GSTP1 hypermethylation reliably distinguishes between prostate cancer and BPH . Although it is not yet clear at what time during carcinogenesis hypermethylation of the GSTP1 promotor occurs it seems to provide valuable information for prostate cancer screening and diagnosis. Larger studies are underway to determine the potential role for GSTP1 hypermethylation in clinical settings.

Adenocarcinoma↗
PubMed2004

Stabilization of reaction-diffusion pulses by external forcing.

A pulse velocity equation under forcing is derived and the conditions for stationary waves (pinning conditions) are considered. It is found that there are two types of stationary pulses with symmetric and asymmetric parameter sets in the phase-amplitude diagram. The pulses with a symmetric set are always unstable, whereas the pulses with an asymmetric set may be stable. The stability criteria are presented.

Journal Article↗
PubMed2004

Superselective embolization of arterial bleeding as a late complication 3 months after nephron sparing surgery for renal cell carcinoma.

To our knowledge, this is the first case of an arterial bleeding as a late complication 3 months after nephron sparing surgery of renal cell cancer, presumably originating from an arteriocalyceal fistula. Superselective embolization of the feeding arterial branch was chosen for treatment of the hemorrhage and proved successful. The high efficacy of superselective embolization as a minimally invasive procedure in this and other cases of bleeding Vessels should be the preferred method instead of open surgery.

Carcinoma, Renal Cell↗
PubMed2004

Interleukin-2- and interferon alfa-2a-based immunochemotherapy in advanced renal cell carcinoma: a Prospectively Randomized Trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN).

PURPOSE: We conducted a prospectively randomized clinical trial to compare the efficacy of three outpatient therapy regimens in 341 patients with progressive metastatic renal cell carcinoma. PATIENTS AND METHODS: Patients were stratified according to known clinical predictors and were subsequently randomly assigned. Treatment arms were: arm A (n = 132), subcutaneous interferon alfa-2a (sc-IFN-alpha-2a), subcutaneous interleukin-2 (sc-IL-2), and intravenous (IV) fluorouracil; arm B (n = 146): arm A treatment combined with per oral 13-cis-retinoic acid; and arm C (n = 63), sc-IFN-alpha-2a and IV vinblastine. RESULTS: Treatment (according to the standard 8-week Hannover Atzpodien regimen) arms A, B, and C yielded objective response rates of 31%, 26%, and 20%, respectively. Arm B, but not arm A, showed a significantly improved progression-free survival (PFS) compared with arm C (P =.0248). Both arm A (median overall survival, 25 months; P =.0440) and arm B (median overall survival, 27 months; P =.0227) led to significantly improved overall survival (OS) compared with arm C (median OS, 16 months). All three sc-IFN-alpha-2a-based therapies were moderately or well tolerated. CONCLUSION: Our results established the safety and improved long-term therapeutic efficacy of sc-IL-2 plus sc-INF-alpha-2a-based outpatient immunochemotherapies, compared with sc-INF-alpha-2a/IV vinblastine.

Adult↗