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Biomedical subjects

C Röder

Publications and source records attributed to C Röder.

At least 19 recordsLinked to original sources
PubMed2005

The rationale for a spine registry.

In the discussion about the rationale for spine registries, two basic questions have to be answered. The first one deals with the value of orthopaedic registries per se, considering them as observational studies and comparing the evidence they generate with that of randomised controlled trials. The second question asks if the need for registries in spine surgery is similar to that in the arthroplasty sector. The widely held view that randomised controlled trials are the 'gold standard' for evaluation and that observational methods have little or no value ignores the limitations of randomised trials. They may prove unnecessary, inappropriate, impossible, or inadequate. In addition, the external validity and hence the ability to make generalisations about the results of randomised trials is often low. Therefore, the false conflict between those who advocate randomised trials in all situations and those who believe observational data provide sufficient evidence needs to be replaced with mutual recognition of their complementary roles. The fact that many surgical techniques or technologies were introduced into the field of spine surgery without randomised trials or prospective cohort comparisons makes obvious an even increased need for spine registries compared to joint arthroplasty. An essential methodological prerequisite for a registry is a common terminology for reporting results and a sophisticated technology that networks all participants so that one central data pool is created and accessed. Recognising this need, the Spine Society of Europe has researched and developed Spine Tango, the first European spine registry, which can be accessed under www.eurospine.org.

Arthroplasty↗
PubMed2005

SSE Spine Tango--content, workflow, set-up. www.eurospine.org-Spine Tango.

The Spine Tango registry is now accessible via the SSE webpage under www.eurospine.org-Spine Tango. Links to the Swiss/International, German and Austrian modules are provided as well as information about the philosophy, methodology and content. Following the links, the users are taken to the respective national modules for registration or log-in and data entry. The Swiss/International module, also accessible under www.spinetango.com, is used by all Swiss and international users, who do not have a separate national module. The physician administered forms for surgery, staged surgery and follow-up can be downloaded as PDFs.The officially recommended Spine Tango patient forms are also available. All forms were implemented in an online version and as scannable optical mark reader forms which can be ordered from the corresponding author.

Databases as Topic↗
PubMed2003

Multiple and synergistic deregulations of apoptosis-controlling genes in pancreatic carcinoma cells.

Inability to die by apoptosis is one of the reasons for the deregulated growth of tumour cells and the frequently observed failure of chemotherapy. In this study we thought to identify the common and functionally important characteristics responsible for the apoptosis resistance of pancreatic tumour cells. We analysed cell surface expression level of death receptors CD95 and TRAIL-R1-4 as well as the expression profile of sixteen apoptosis-relevant proteins in five pancreatic carcinoma cell lines Capan1, Colo357, PancTuI, Panc89 and Panc1. These data were evaluated in the context of sensitivity towards anti-CD95 and TRAIL-mediated apoptosis. Here we report that except for resistant Panc1 cells, which only marginally expressed CD95, all other cell lines showed comparable levels of CD95 and TRAIL receptors irrespectively of their apoptotic phenotype. Interestingly, we found that the elevated expression of FLIP, Bcl-x(L) and IAP in parallel with a downregulation of FADD and Bid was common for the resistant cell lines. Consequently, stable overexpression of XIAP, Bcl-x(L) or dominant negative FADD in sensitive cells significantly reduced the death receptor mediated apoptosis while the overexpression of Bid rendered the resistant cells sensitive.

Adenocarcinoma↗
PubMed2003

Mucin 7 and cytokeratin 20 as new diagnostic urinary markers for bladder tumor.

PURPOSE: We determine the sensitivity and specificity of cytokeratin 20 (CK-20) and mucin 7 (MUC7) gene expression in voided urine samples taken from patients with bladder tumor and from control groups to investigate putative, noninvasive urinary markers for bladder tumor detection and monitoring. MATERIALS AND METHODS: Voided urine samples were collected from 50 patients with histologically proven bladder neoplasms (pTaN0M0G1-3 in 19 and pTisN0M0G3-pT4pN1M1G3 in 31), 20 patients with urolithiasis, 20 patients with urinary tract infection, 20 patients with other urological neoplasms and 20 healthy volunteers. Total RNA was extracted from exfoliated cells collected from 200 ml. voided urine. All RNA samples were investigated by a specific CK-20 and MUC7 nested reverse transcriptase polymerase chain reaction. RESULTS: The overall sensitivity of CK-20 gene expression in voided urine samples for the detection of bladder neoplasms was 78%. In contrast, voided urine samples from control patients and healthy volunteers showed a high rate of false-positive CK-20 detection resulting in a low specificity of 36%. The overall sensitivity of the MUC7 test for all bladder tumor cases was 66%. The sensitivity for papillary urothelial neoplasms (pTaN0M0G1-3) was 42% whereas analysis of the carcinoma in situ and invasive bladder cancer group (pTisN0M0G3-pT4pN1M1G3) yielded a sensitivity of 81%. The overall specificity of the MUC7 nested reverse transcriptase polymerase chain reaction method in the control groups was 80%. CONCLUSIONS: A high positive CK-20 detection rate was found not only in voided urine samples from patients with bladder tumor, but also in urine specimens from control groups. Therefore, CK-20 is not a reliable urinary tumor marker for bladder neoplasms. In contrast to CK-20, analysis of MUC7 demonstrated a high sensitivity and high specificity for carcinoma in situ and invasive bladder cancer, thus fulfilling the criteria of a urinary tumor marker.

Adult↗
PubMed2003

Reliability of quantitative reverse-transcriptase-PCR-based detection of tumour cells in the blood between different laboratories using a standardised protocol.

Differences in methods of reverse-transcriptase (RT)-polymerase chain reaction (PCR)-based detection of tumour cells in the blood gives rise to conflicting results, and standardisation is urgently needed. This pilot study aimed to assess the variation of RT-PCR-based detection of tumour cells in blood between four different laboratories using a commercially available kit with a standardised protocol. This kit allows comparison of results from different laboratories and facilitates the investigation of the influence of pre-analytical parameters. All laboratories analysed identical sets of blood samples spiked with tumour cells in a concentration range of 1-100 tumour cells/ml. To study at which level variation was introduced, three kinds of sample sets were generated in which (i) tumour cell RNA was spiked in the RNA of mononuclear cells (MNC), (ii) tumour cells were spiked in isolated MNC, and (iii) tumour cells were spiked in blood. Real-time quantitative RT-PCR was used to detect and quantify cytokeratin 20 (CK20) expression, which is indicative for the presence of epithelial tumour cells. All laboratories were able to detect CK20 expression in all spiked-RNA samples with limited variation in expression levels between laboratories. There was a positive correlation between the amount of spiked tumour cell RNA and CK20 expression level. RT-PCR analysis of spiked-MNC samples resulted in more variation in the CK20 expression levels between laboratories, however again all spiked samples were reported to be positive by all of the laboratories. The evaluation of spiked-blood samples gave rise to considerable quantitative and qualitative variation between the laboratories. Our results underline the importance and need for standardisation and extended quality control studies in the field of pre-analytics.

HT29 Cells↗
PubMed2003

The validity of clinical examination in the diagnosis of loosening of components in total hip arthroplasty.

We analysed follow-up data from 18,486 primary total hip arthroplasties performed between 1967 and 2001 to assess the validity of clinical procedures in diagnosing loosening of prosthetic components. Sensitivity, specificity and predictive values were estimated with the radiological definition of loose or not loose as the 'gold standard'. The prevalence of acetabular loosening increased from 0.6% to 13.9% during the period of the study and that of femoral loosening from 0.9% to 12.1%. Sensitivities and positive predictive values were low, suggesting that clinical procedures could not replace radiological assessment in the identification of loose prostheses. Specificities and negative predictive values were constantly above 0.86. The possibility of there being a prosthesis which is not loose in asymptomatic patients was consequently very high, particularly during the first five to six years after operation. The necessity of periodic clinical and radiological follow-up examinations of asymptomatic patients during the first five to six years after operation remains questionable. Symptomatic patients, however, require radiological assessment.

Acetabulum↗
PubMed2002

A European spine registry.

New joint replacement registries are being widely implemented across national and international organizations. The need for a continuous long-term post-market surveillance of implants has been recognized, and has become increasingly important to ensure the quality of prosthetic components. Registry data with large case numbers represent an acceptable alternative to controlled randomized clinical trials, which are often difficult to conduct in orthopedic surgery. The variety of implants and procedures in spinal surgery not only induces the same need for long-term monitoring of post-surgical product performance as in the joint replacement subspecialties, but also renders essential the establishment of a comprehensive spine registry for all major pathologies and interventions. In cooperation with the M.E. Müller Institute for Evaluative Research in Orthopedic Surgery (MEM-CED) at the University of Berne, Switzerland, the Spine Society of Europe (SSE) has launched Spine Tango: the first modular and multilevel European online registry for spinal surgery. Within Spine Tango, the major challenge in registry design and structure is the definition of and agreement upon a core set of questions as a common European dataset. Additional questions for national or individual interest can also be dynamically added to the core dataset. An automated implant tracking system has also been setup, which allows highly precise product documentation without additional work for clinical staff members.

Europe↗
PubMed2001

CD95 and TRAIL receptor-mediated activation of protein kinase C and NF-kappaB contributes to apoptosis resistance in ductal pancreatic adenocarcinoma cells.

The molecular alterations in tumour cells leading to resistance towards apoptosis induced by CD95 and TRAIL-receptors are not fully understood. We report here that the stimulation of the CD95- and TRAIL-resistant human pancreatic adenocarcinoma cell line PancTuI with an agonistic anti-CD95 antibody or TRAIL resulted in activation of protein kinase C and NF-kappaB. Inhibition of protein kinase C by Gö6983 sensitized these cells to apoptotic challenges and strongly diminished activation of NF-kappaB by anti-CD95 and TRAIL. Similarly, inhibition of NF-kappaB by MG132 or by transient transfection with a dominant negative mutant of IkappaBalpha restored the responsiveness of PancTuI cells to both death ligands. In the CD95 and TRAIL-sensitive cell line Colo357 the induction of protein kinase C and NF-kappaB following activation of CD95 and TRAIL-R was very moderate compared with PancTuI cells. However, pre-incubation of these cells with PMA strongly reduced their apoptotic response to anti-CD95 and TRAIL. Taken together, we show that activation of protein kinase C operates directly in a death receptor-dependent manner in PancTuI cells and protect pancreatic tumour cells from anti-CD95 and TRAIL-mediated apoptosis by preventing the loss DeltaPsim and Cytochrome c release as well as by induction of NF-kappaB.

Adenocarcinoma↗
PubMed2001

Cytokeratin-20 reverse-transcriptase polymerase chain reaction as a new tool for the detection of circulating tumor cells in peripheral blood and bone marrow of bladder cancer patients.

OBJECTIVES: Systemic progression is the prevalent form of bladder tumor recurrence after radical cystectomy. The ability to detect circulating tumor cells in peripheral blood or bone marrow could be of prognostic value for the disease with the consequence of early adjuvant chemotherapy. We established a sensitive and specific method using a double cytokeratin-20 (CK-20) reverse-transcriptase polymerase chain reaction (RT-PCR) to detect circulating bladder cancer cells in venous blood and bone marrow MATERIAL AND METHODS: The sensitivity of the detection method was determined by a serial dilution of bladder cancer cells from the cell line HT1376 in whole blood. Bone marrow from 20 bladder cancer patients was drawn prior to radical cystectomy and CK-20 cDNA was amplified by RT-PCR. Additionally, pre- and postoperative venous blood samples from 11 of these patients with bone marrow aspirates and 9 patients undergoing only transurethral resection of the bladder as well as blood samples of 25 healthy volunteers were investigated by CK-20 RT-PCR. RESULTS: The detection limit of the method was 2 bladder cancer cells/ml whole blood containing one million peripheral blood mononuclear cells. The positive detection rate in bone marrow was 7 of 20 (35%) for bladder cancer patients of all stages. However, investigation of the preoperatively collected venous blood samples from 20 patients revealed onyl 2 positive findings, belonging to advanced tumor stages pT4pN0M0 and pT3pN2M0. In contrast, CK-20 was detected in 3 of 20 postoperatively collected venous blood samples from patients with low tumor stages (pTaNXM0 and pT1NXM0) as well as from 1 patient with pelvic lymph node metastases (pT3apN2M0). All venous blood samples of the control group (n = 25) were negative for CK-20. CONCLUSION: The detection of circulating bladder tumor cells in venous blood and bone marrow by the CK-20 RT-PCR is a promising approach that could improve risk assessment and the identification of bladder cancer patients who would benefit from adjuvant chemotherapy.

Adult↗
PubMed2000

A method for the production of cryopreserved aliquots of antigen-preloaded, mature dendritic cells ready for clinical use.

Dendritic cells (DC) are increasingly used as a vaccine. Unfortunately, a satisfactory cryopreservation of DC in the absence of FCS is not yet available, so that laborious repeated generation of DC from fresh blood or frozen peripheral blood mononuclear cells for each vaccination has been required to date. We now aimed at developing an effective cryopreservation method, and by testing several variables found that it was crucial to combine the most advantageous maturation stimulus with an improved freezing procedure. We generated monocyte-derived DC from leukapheresis products by using GM-CSF and IL-4 and showed that amongst several known maturation stimuli the cocktail consisting of TNF-alpha+IL-1 beta+IL-6+PGE(2) achieved the highest survival of mature DC. We then systematically explored cryopreservation conditions, and found that freezing matured DC at 1 degrees C/min in pure autologous serum+10% DMSO+5% glucose at a cell density of 10x10(6) DC/ml gave the best results. Using this approach 85-100% of the frozen DC could be recovered in a viable state after thawing (Table 1). The morphology, phenotype, survival as well as functional properties (allogeneic mixed leukocyte reaction, induction of influenza matrix or melan A peptide-specific cytotoxic T cells) of these thawed DC were equivalent to freshly prepared ones. The addition of CD40L or TRANCE/RANKL further improved DC survival. Importantly, we demonstrate that DC can effectively be loaded with antigens (such as Tetanus Toxoid, influenza matrix and melan A peptides) before cryopreservation so that it is now possible to generate antigen-preloaded, frozen DC aliquots that after thawing can be used right away. This is an important advance as both the generation of a standardized DC vaccine under GMP conditions and the carrying out of clinical trials are greatly facilitated.

Antigens↗
PubMed2000

Mage-3 and influenza-matrix peptide-specific cytotoxic T cells are inducible in terminal stage HLA-A2.1+ melanoma patients by mature monocyte-derived dendritic cells.

Dendritic cell (DC) vaccination, albeit still in an early stage, is a promising strategy to induce immunity to cancer. We explored whether DC can expand Ag-specific CD8+ T cells even in far-advanced stage IV melanoma patients. We found that three to five biweekly vaccinations of mature, monocyte-derived DC (three vaccinations of 6 x 106 s.c. followed by two i.v. ones of 6 and 12 x 106, respectively) pulsed with Mage-3A2.1 tumor and influenza matrix A2. 1-positive control peptides as well as the recall Ag tetanus toxoid (in three of eight patients) generated in all eight patients Ag-specific effector CD8+ T cells that were detectable in blood directly ex vivo. This is the first time that active, melanoma peptide-specific, IFN-gamma-producing, effector CD8+ T cells have been reliably observed in patients vaccinated with melanoma Ags. Therefore, our DC vaccination strategy performs an adjuvant role and encourages further optimization of this new immunization approach.

Antigens, Neoplasm↗
PubMed1999

Vaccination with mage-3A1 peptide-pulsed mature, monocyte-derived dendritic cells expands specific cytotoxic T cells and induces regression of some metastases in advanced stage IV melanoma.

Dendritic cells (DCs) are considered to be promising adjuvants for inducing immunity to cancer. We used mature, monocyte-derived DCs to elicit resistance to malignant melanoma. The DCs were pulsed with Mage-3A1 tumor peptide and a recall antigen, tetanus toxoid or tuberculin. 11 far advanced stage IV melanoma patients, who were progressive despite standard chemotherapy, received five DC vaccinations at 14-d intervals. The first three vaccinations were administered into the skin, 3 x 10(6) DCs each subcutaneously and intradermally, followed by two intravenous injections of 6 x 10(6) and 12 x 10(6) DCs, respectively. Only minor (less than or equal to grade II) side effects were observed. Immunity to the recall antigen was boosted. Significant expansions of Mage-3A1-specific CD8(+) cytotoxic T lymphocyte (CTL) precursors were induced in 8/11 patients. Curiously, these immune responses often declined after the intravenous vaccinations. Regressions of individual metastases (skin, lymph node, lung, and liver) were evident in 6/11 patients. Resolution of skin metastases in two of the patients was accompanied by erythema and CD8(+) T cell infiltration, whereas nonregressing lesions lacked CD8(+) T cells as well as Mage-3 mRNA expression. This study proves the principle that DC "vaccines" can frequently expand tumor-specific CTLs and elicit regressions even in advanced cancer and, in addition, provides evidence for an active CD8(+) CTL-tumor cell interaction in situ as well as escape by lack of tumor antigen expression.

Adult↗
PubMed1999

Hollow-spheres: a new model for analyses of differentiation of pancreatic duct epithelial cells.

We discovered a unique feature of a subclone of the pancreatic carcinoma cell line A818. A818-1-derived hollow-spheres developed under three-dimensional growth conditions. Hollow-spheres consist of a single layer of 50-200 epithelial cells surrounding an inner lumen. In contrast to A818-1, the subclone A818-4 and all other pancreatic tumor cell lines tested (n = 5), formed spheroids as the only three-dimensional phenotype. A dramatically reduced proliferation rate compared to the corresponding monolayer was observed in hollow-spheres when bromodeoxyuridine (BrdU) incorporation was measured. This finding was confirmed by immunostaining using the MIB-1 antibody. Mechanically disrupted hollow-spheres not only attached but also grew as monolayer with the same doubling time as the founder cells. Hollow-spheres developed in fetal calf serum (FCS) containing RPMI 1640 medium without additionally added cytokines. A818-1 hollow-sphere formation and integrity was influenced by interferon-gamma. Tumor necrosis factor-alpha (TNF-alpha) led to cell death. Exogenously added hepatocyte growth factor (HGF) showed no effect neither on hollow-sphere formation nor on the integrity of completely developed hollow-spheres. Moreover, no changes were observed when cells were treated with a neutralizing antibody for HGF. Interestingly, hollow-spheres showed intensive immunoreactivity for the HGF-receptor (c-met) and its ligand (HGF). Immunostaining for the biliary glycoprotein (BGP), the non-specific cross-reacting antigen 95 (NCA95) and beta-catenin revealed a polar organization of hollow-spheres. Immunhistochemically, hollow-spheres were negative for the carcinoembryonic antigen (CEA). When hollow-spheres were embedded into matrigel, duct-like tubes grew out. Taken together, A818-1 hollow-spheres resemble normally differentiated duct-like structures and will serve as an excellent model to study differentiation of human pancreatic epithelial cells.

Aged↗
PubMed1999

Generation of large numbers of fully mature and stable dendritic cells from leukapheresis products for clinical application.

Dendritic Cell (DC)-based vaccination approaches in man require a reproducible DC generation method that can be performed in conformity with GMP (Good Manufacturing Practice) guidelines and that circumvents the need for multiple blood drawings to generate DC. To this end we modified our previously described method to generate mature DC from CD14 + monocytes by a two step method (priming in GM-SF + IL-4 followed by maturation in monocyte conditioned medium) for use with leukapheresis products as a starting population. Several adaptations were necessary. We established, for example, a modified adherence step to reliably enrich CD14 + DC precursors from apheresis mononuclear cells. The addition of GM-CSF + IL-4 at the onset of culture proved disadvantageous and was, therefore, delayed for 24 h. DC development from apheresis cells occurred faster than from fresh blood or buffy coat, and was complete after 7 days. Monocyte conditioned medium when added on day 6 resulted in fully mature and stable DC (veiled, highly migratory and T cell sensitizing cells with a characteristic phenotype such as 85% CD83 + , p55/fascin + , CD115/M-CSF-R - , CD86 + ) already after 24 h. The mature DC progeny were shown to remain stable and viable if cultured for another 1-2 days in the absence of cytokines, and to be resistant to inhibitory effects of IL-10. Freezing conditions were established to generate DC from frozen aliquots of PBMC or to freeze mature DC themselves for later use. The approach yields large numbers of standardized DC (5-10 x 10(8) mature CD83 + DC/leukapheresis) that are suitable for performing sound DC-based vaccination trials that can be compared with each other.

Cell Adhesion↗
PubMed1999

Expression of laminin alpha1, alpha2, alpha4, and alpha5 chains, fibronectin, and tenascin-C in skeletal muscle of dystrophic 129ReJ dy/dy mice.

The dy/dy mouse is an animal model for human merosin-negative congenital muscular dystrophy (CMD), which has been reported to have reduced or no expression of the basement membrane protein laminin alpha2. We here investigate various myogenic and nonmyogenic tissues of mature dy/dy and control 129ReJ mice histologically and for laminin alpha2 expression. In addition, expression patterns of laminin alpha1, alpha2, alpha4, and alpha5 chains, the interstitial proteins fibronectin and tenascin-C, and the adhesion molecules VCAM-1, ICAM-1, and alpha4 integrin were characterized in skeletal muscle of 1- and 7-day and mature (>6 weeks old) dy/dy and control 129ReJ mice. The laminin alpha2 chain remained detectable in myogenic tissues of dy/dy mice by immunofluorescence using two different monoclonal antibodies and by Northern blot analysis. However, laminin alpha2 expression was significantly reduced or not detectable in nonmyogenic tissues of dy/dy mice, including skin, lung, kidney, brain, thymus, and eye. Focal lesions were observed in mature skeletal muscle only, characterized by necrotic tissue, isolated VCAM-1- and ICAM-1-positive cells indicative of inflammatory processes, and regenerating muscle fibers surrounded by intense tenascin-C and fibronectin expression. In contrast to studies on human CMD muscle, laminin alpha1 was not detectable in either dy/dy or control skeletal muscle using immunofluorescence or Northern blot analysis. Immunofluorescence localized laminin alpha4 to basement membranes of blood vessels, the endoneurium of the intramuscular nerves, and the neuromuscular junction in skeletal muscle of 1- and 7-day-old dy/dy and control mice. In mature muscle, laminin alpha4 expression shifted to the perineurium of intramuscular nerves in both dy/dy and control mice. Furthermore, strong upregulation of laminin alpha4 in the basement membranes of blood vessels, the perineurium of intramuscular nerves, and of isolated regenerating muscle fibers in the dy/dy mice was apparent. Investigation of 1-day-old animals revealed expression of laminin alpha5 in skeletal muscle fiber basement membranes of dy/dy but not control animals. This difference between dy/dy and control animals was no longer apparent at 7 days after birth, indicating a temporary shift in expression pattern of laminin alpha5 in dy/dy animals. Analysis of the extracellular matrix components of 1- and 7-day-old dy/dy and control skeletal muscle revealed an early onset of the dystrophy, even before histopathological features of the disease were evident. Our data confirm the absence of laminin alpha1 chain in myogenic tissues of both dy/dy and control mice and suggest compensation for reduced laminin alpha2 in dy/dy skeletal muscle by laminin alpha4 and, in early development, also laminin alpha5. These results have significant ramifications in the diagnosis of human merosin-negative CMD.

Age of Onset↗
PubMed1999

Photoallergic skin reaction to ribavirin.

A 65-yr-old woman with chronic hepatitis C was treated with three million units interferon-alpha t.i.w. and 1000 mg ribavirin daily. At wk 16 of combination therapy the patient developed an itchy eczematous erythema, partly of urticarial character, which was almost confined to ultraviolet (UV)-exposed sites. Histopathological examination of the skin lesions was consistent with a photoallergic reaction. The minimal erythematous dose for UVA and UVB was assessed on healthy skin. After 24 h, a distinct erythema at the UVB irradiated site was found, whereas no reaction was seen with UVA provocation up to a dose of 10 J/cm2. Correspondingly, determination of the absorption spectrum of ribavirin revealed maximum absorption within UVB at 282.5 nm. Ribavirin was stopped, and the cutaneous lesions and pruritus completely disappeared without subsequent hyperpigmentation. This case indicates that ribavirin is a potential photosensitizer for UVB, which may become increasingly relevant in patients with chronic hepatitis C undergoing combination therapy for 6-12 months with interferon-alpha and ribavirin.

Aged↗