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Biomedical subjects

L Fischer

Publications and source records attributed to L Fischer.

At least 37 records · Page 2Linked to original sources
PubMed2003

[Surgical standard therapy for cancer of the pancreas].

Approximately 150,000 people worldwide and 40,000 people in Europe die each year of pancreatic cancer,making it one of the five leading causes of cancer-related death and one of the most aggressive human tumors. Resection is still the only option that offers a chance of cure for pancreatic cancer patients. Recent studies have highlighted the correlation between the number of pancreatic resections per year and postoperative mortality. Thus, large centers of pancreatic surgery have mortality rates below 5%, whereas centers with lower caseloads have mortality rates exceeding 10%. Standards have been established for the surgical treatment of pancreatic cancer;however, these are often not based on evidence derived from randomized, controlled studies. Resection for pancreatic cancer is carried out if there are no metastases present and if the tumor is locally resectable; i.e., if there is no complex vessel invasion. However, an isolated infiltration of the portal vein is not considered a contraindication for surgery. At present, there are no evidenced-based data available on palliative (R2) resections,which might be a therapeutic option in centers with low morbidity/mortality. Three randomized controlled trials clearly show that the pylorus-preserving Whipple is equal to the classical Whipple in terms of oncological effectiveness, morbidity, and quality of life. Therefore, the pylorus-preserving Whipple is increasingly considered the standard operation for tumors of the pancreatic head. Based on randomized trials, extended lymph node dissection cannot generally be recommended for pancreatic cancer. Further prospective, randomized, multicenter trials have to be carried out in the upcoming years to find new approaches in the therapy of pancreatic cancer and to establish evidence-based treatment strategies for this disease.

Adenocarcinoma↗
PubMed2003

[Evaluation of potential liver living donors. Logistic and financial aspects].

INTRODUCTION: The increasing shortage of cadaveric organs makes living-related liver transplantation a more and more important option. Safety for the donor has the highest priority, and therefore detailed and thorough evaluation is needed. MATERIALS AND METHODS: All potential donors who had been evaluated at our center from January 2001 to March 2002 ( n=100) were included in a retrospective study to analyse the qualitative, logistical, and economic aspects of the evaluation. RESULTS: Seventy-three percent of the potential donors were found to be unsuitable for living donation during the evaluation process. The main reasons were: uncompatible blood group, availability of cadaveric transplant by Eurotransplant, steatosis of more than 10% of hepatocytes in liver biopsy, insufficient liver volume, and psychosocial reasons. The expenditure for all scheduled investigations was 4,469 euro for a complete evaluation. CONCLUSION: While on the one hand, high standards of the evaluation process must be guaranteed, insufficient reimbursement on the other should not lead centers to reduce either quantity or quality of necessary examinations entered in the evaluation protocol.

Adult↗
PubMed2003

Expression of the human homologue of rat NG2 in adult acute lymphoblastic leukemia: close association with MLL rearrangement and a CD10(-)/CD24(-)/CD65s(+)/CD15(+) B-cell phenotype.

The expression of the chondroitin sulfate proteoglycan neuron-glial antigen 2 (NG2) has been demonstrated in association with rearrangement of the mixed lineage leukemia (MLL) gene in acute leukemia, but the frequency of NG2 expression in adult acute lymphoblastic leukemia (ALL) is yet unknown. We evaluated NG2 expression in 313 adult ALL patients by flow cytometry and simultaneously determined MLL rearrangement in 120 adult patients out of them with B-precursor ALL by reverse transcription-polymerase chain reaction and fluorescence in situ hybridization. A total of 57% of pro-B ALL, 2% of common ALL and 20% of pre-B ALL were NG2 positive, but NG2 was absent in T-ALL and mature B-ALL. In B-precursor ALL, NG2 expression was significantly associated with a CD10(-)/CD34(-)/CD24(-)/CD65s(+)/CD15(+)/CD13(-)/CD33(-) phenotype and showed a sensitivity, specificity and positive predictive value of 0.89, 0.89, and 0.93 for MLL rearrangement, respectively. NG2 was positive in three patients without detectable MLL rearrangement and negative in eight patients with MLL-AF4 transcripts. However, NG2 predicted with a 100% accuracy MLL rearrangement among patients disclosing a CD65s(+) and/or CD15(+) immunophenotype. In summary, NG2 adds to a more precise identification of high-risk adult ALL and should therefore be included into diagnostic marker panels. As NG2 is negative in non-malignant hematopoietic cells, this novel antigen might also serve in future studies as a powerful marker in monitoring minimal residual disease.

Adolescent↗
PubMed2003

Genotyping of Clostridium perfringens isolated from domestic and exotic ruminants and swine.

Clostridium perfringens types A, B, C, D and E are known to cause severe enteritis/enterotoxaemia and diseases (especially caused by type A) belonging to the gas oedema complex in many species. Samples from the small intestine as well as faeces of domestic and exotic animals suffering from enterotoxaemic signs or having died within days after first occurance of toxaemia were submitted for typing C. perfringens toxovars by multiplex PCR. The following species have been investigated: domestic sheep (Ovis ammon; n = 10), domestic goat (Capra aegagrus hircus; n = 26), Japanese serow (Capricornis sumatraensis; n = 4), lechwe waterbuck (Hydrotragus leche; n = 1), blackbuck (Antilope cervicapra; n = 1), European reindeer (Rangifer tarandus tarandus; n = 4), domestic swine (Sus scrofa; n = 52), and collared peccary (Tayassu albirostris; n = 1). Interestingly, the predominant C. perfringens toxovar in domestic sheep was type A. This toxovar could also be diagnosed in all reindeer, in three Japanese serows, one lechwe waterbuck and most pigs (n = 47), the majority of those being at suckling age. Type D was the most prevalent toxovar (n = 18) in domestic goats, but also types A and E could be identified as pathogens in this species. Type C could only be found in domestic swine (n = 5) and in one case of clostridiosis in a Japanese serow. Two cases of enterotoxaemia in goats, one case in reindeer, and a single case in blackbuck and collared peccary were caused by C. perfringens type E. Genotyping of C. perfringens is recommended before starting vaccination programmes as it could be shown, that the importance of specific toxovars has been underestimated in specific species and/or age groups.

Animals↗
PubMed2003

[Operative management in the treatment of pancreatic cancer].

The carcinoma of the pancreas is one of the 10 leading causes of death in the Western countries. Because of the resistance of pancreatic cancer against radiation and/or chemotherapy surgery is still the only possibility for cure. However, about 80 % of patients with the diagnosis of pancreatic cancer are no more suitable for curative resection at the time of diagnosis because of local tumor infiltration or the presence of distant metastases. This is one reason for the unsatisfactory situation in terms of 5-year-survival rate of 3 to 24 %. In resectable tumors of the pancreas head the standard Whipple dominates still as the surgical method of choice. However, the pylorus preserving Whipple has been established as a surgical alternative to the classical Whipple. Other surgical procedures like extended or regional pancreatic resections, predominantly done by Japanese surgeons seem to fit the concept of radical resection. But compared to the classical Whipple or the pylorus preserving Whipple resection there is still no clear advantage in terms of long term survival. The prospective European multicenter study ESPAC-1 firstly demonstrated a survival advantage for adjuvant chemotherapy (5-FU and folic acid) but no gain for radiochemotherapy in the treatment of patients with R0 or R1 resected pancreatic cancer in terms of prolongation of mean survival (19.7 months vs. 14.0 months).

Antimetabolites, Antineoplastic↗
PubMed2002

Quantitative analysis of the antigen-specific IFNgamma+ T cell-mediated immune response in conventional outbred pigs: kinetics and duration of the DNA-induced IFNgamma+ CD8+ T cell response.

It is now well established that antigen-specific CD8(+) T cells play a major role in vaccine-induced immunity against intracellular pathogens and tumor cells. The detection of these immune cells in outbred animals has been hampered mainly by the need to generate individual autologous antigen-presenting cells (APCs) due to the high degree of polymorphism of the major histocompatibility complex (MHC) Class I loci. We used individually derived immature porcine dendritic cells infected with a pox-based recombinant viral vector to ex vivo stimulate PBMCs from vaccinated conventional pigs. The frequencies of antigen-specific T cells was determined by the number of IFNgamma-secreting cells in a quantitative enzyme-linked immune spot (ELISPOT) assay. Using this approach we were able to rank different pseudorabies virus (PRV) vaccines strategies for their ability to prime viral-specific IFNgamma(+) T cells. Plasmid DNA has recently emerged as a promising tool with multiple applications in the field of infectious diseases, allergy and cancer. We showed for the first time in this study that DNA immunization induced a long-lived antigen-specific IFNgamma(+) T cells response in conventional pigs. Additional studies allowed us to show that these virus-specific IFNgamma(+) responding cells detected in this ELISPOT assay were MHC-restricted and comprised in the CD8alpha(bright) pig T cell subset. These new data confirm the usefulness of DNA vaccines to control diseases requiring cellular immunity in pigs.

Animals↗
PubMed2002

The effect of virtual reality and training on liver operation planning.

OBJECTIVE: The three-dimensional relation of a liver tumour to the intrahepatic vascular trees is basis of operation planning in liver surgery. Yet it has not been proven whether 3D reconstruction and further computerised processing will enhance precision of operation planning in liver surgery which has been based on the liver segment classification of Couinaud up to now. DESIGN: Our interdisciplinary group (department of Surgery, German Cancer Research Center and Department of Radiology) has developed a new interactive computer-based quantitative 3D operation planning system for liver surgery which is being introduced into the clinical routine. The system quantifies the organ structures semiautomatically, defines resection planes depending on safety margins and the vascular trees, and presents the data in digital movies as well as in quantitative reports. We conducted a clinical trial to evaluate whether 3D reconstruction will lead to an improved operation planning. Data of 7 virtual patients were presented to a total of 81 surgeons in different levels of training. The tumours had to be assigned to a liver segment and subsequently drawn together with the operation proposals into a liver model. The precision of both was measured quantitatively for each surgeon and stratified concerning 2D and different types of 3D presentations. RESULTS: The 3D anatomy can be visualised in high quality which results in good perception of the third dimension (depth). Tumour assignment to liver segments was significantly correlated to the level of training (p < 0.05). There was a significant increase (p < 0.001) in the precision of tumour localisation by 51% and resection proposal from 2D through 3D reconstructions by 13%-21%. Quantitative differences of the simplified Couinaud's classification of the liver segments compared to the true vascular anatomy of up to 40% were found. CONCLUSION: The impact of individual 3D-reconstruction on surgical planning has been proven to be significant and increases precision quantitatively. The merit of Couinaud's classification may be enhanced by individualisation of the segment borders in future.

Hepatectomy↗
PubMed2002

Prevalence of SENV-H viraemia among healthy subjects and individuals at risk for parenterally transmitted diseases in Germany.

The prevalence of a newly described DNA virus (SENV-H) was examined in a population of 599 individuals by polymerase chain reaction (PCR). All individuals were assigned to a nonrisk or a risk group depending on the presence of historical or serological factors indicating an increased risk for parenterally transmitted diseases. In a group of 226 healthy blood donors, 38 (16.8%) were found to be SENV-H viraemic. The highest prevalence of SENV-H viraemia was observed among patients infected by HIV (28 of 63; 44.4%). Contrarily, of 78 individuals on maintenance haemodialysis, only 10 (12.8%) were found positive in the SENV-H PCR. Our results demonstrate that SENV-H viraemia is widespread in the general population. Therefore, it seems to be questionable if parenteral transmission is the main route for spreading SENV-H. The hepatitis-inducing capacity of SENV-H is unclear. However, taking our clinical and epidemiological data into account it seems unlikely that this virus is responsible for hepatitis.

Adolescent↗
PubMed2001

Patients at risk for development of posttransplant lymphoproliferative disorder: plasma versus peripheral blood mononuclear cells as material for quantification of Epstein-Barr viral load by using real-time quantitative polymerase chain reaction.

BACKGROUND: Early diagnosis of Epstein-Barr virus (EBV)-associated posttransplant lymphoproliferative disorder (PTLD) is required to detect a stage of disease that is more likely to respond to treatment. Elevated levels of EBV DNA were found in peripheral blood of patients at the onset of PTLD. METHODS: To compare plasma and peripheral blood mononuclear cells (PBMCs) as material for real-time quantitative polymerase chain reaction (RQ-PCR) measurement of Epstein-Barr viral load, we used two sets of primers and probes specific for the BAM HI-K or BAM HI-W region of the EBV genome. RESULTS: Patients with PTLD had a median viral load of 19,200 EBV genomes/microg DNA (n=9) or 3,225 EBV genomes/100 microl plasma (n=5), being significantly higher compared with immunosuppressed patients with primary (n=9) or reactivated (n=20) EBV infection or immunosuppressed patients without serological signs of active EBV infection (n=67) (P<0.001). Hence, a value of greater than 5,000 EBV genomes/microg PBMC DNA was considered as a diagnostic parameter for PTLD with a sensitivity and specificity of 1.00 or 0.89, respectively. When plasma was analyzed, however, a value of greater than 1,000 EBV genomes/100 microl plasma had both a sensitivity and specificity of 1.00 for the diagnosis of PTLD. During remission of PTLD, viral load was more effectively cleared in plasma compared with PBMCs. In plasma of nonimmunosuppressed individuals, even a qualitative detection of EBV-related sequences was sensitive and specific for the diagnosis of primary EBV infection, whereas for analysis of PBMC DNA a quantitative parameter had to be considered to differentiate healthy individuals (< 100 EBV genomes/microg PBMC DNA) from patients with primary EBV infection (>100 EBV genomes/microg PBMC DNA). CONCLUSION: Although both PBMCs and plasma were useful as material for EBV-specific RQ-PCR in immunosuppressed patients and nonimmunosuppressed individuals, the specificity of analysis seemed to be higher if plasma was taken for analysis.

Adolescent↗
PubMed2001

Testicular germ cell tumor with rhabdomyosarcoma successfully treated by disease-adapted chemotherapy including high-dose chemotherapy: case report and review of the literature.

Treatment and prognosis have not been well characterized in germ cell tumors (GCT) with a malignant nongerm cell component. Patients with a mediastinal tumor, neural or rhabdomyosarcomatous differentiation and distant metastases have the poorest prognosis. We report a rare case of mixed GCT composed of seminoma, teratoma and rhabdomyosarcoma with the rhabdomyosarcomatous component metastasized into the liver and bone marrow (BM) causing hypercalcemia. The patient was treated with differentiation-tailored chemotherapy (CHT) including a disease-adapted high-dose (HD) CHT regimen with purified autologous PBSCT (APBSCT) and pamidronate. To date, remission has lasted for 4 years. Tumor-adapted CHT including HD-CHT with APBSCT can induce long term remissions in high-risk patients with transformed GCT. A review of the literature is given.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

A dominant hepatitis B virus population defective in virus secretion because of several S-gene mutations from a patient with fulminant hepatitis.

There is increasing evidence that certain pathogenic hepatitis B virus (HBV) variants may play a role in the pathogenesis of fulminant hepatitis (FHB). Recently, we isolated from a patient with fulminant recurrent hepatitis B after liver transplantation variants with enhanced replication competence and a possible defect in viral particle secretion. Both viral features may have contributed to the severity of the disease. The aim of this study was to prove the secretion defect of these variants, to analyze the consequences, and to identify the responsible viral mutations. The variant genomes and appropriate wild-type/variant hybrid genomes were functionally characterized after transfection in human hepatoma cells. Two cloned genomes and the polymerase chain reaction (PCR)-amplified mixture of full-length genomes showed a block in viral particle secretion. This was caused by a combination of amino acid changes in the S-protein including the mutation G145R frequently emerging after hyperimmunoglobulin treatment. The mutations induced retention of the surface proteins in an endoplasmic reticulum (ER)-like compartment, but no intracellular accumulation. These data provide evidence for the in vivo existence of a dominant HBV population with a severe defect in viral particle secretion caused by mutations in the S-gene. This viral phenotype in combination with the enhanced replication competence may have contributed to the fulminant clinical course of the infection.

Amino Acid Substitution↗
PubMed2001

Is there still a need for living-related liver transplantation in children?

OBJECTIVE: To assess and compare the value of split-liver transplantation (SLT) and living-related liver transplantation (LRT). SUMMARY BACKGROUND DATA: The concept of SLT results from the development of reduced-size transplantation. A further development of SLT, the in situ split technique, is derived from LRT, which itself marks the optimized outcome in terms of postoperative graft function and survival. The combination of SLT and LRT has abolished deaths on the waiting list, thus raising the question whether living donor liver transplantation is still necessary. METHODS: Outcomes and postoperative liver function of 43 primary LRT patients were compared with those of 49 primary SLT patients (14 ex situ, 35 in situ) with known graft weight performed between April 1996 and December 2000. Survival rates were analyzed using the Kaplan-Meier method. RESULTS: After a median follow-up of 35 months, actual patient survival rates were 82% in the SLT group and 88% in the LRT group. Actual graft survival rates were 76% and 81%, respectively. The incidence of primary nonfunction was 12% in the SLT group and 2.3% in the LRT group. Liver function parameters (prothrombin time, factor V, bilirubin clearance) and surgical complication rates did not differ significantly. In the SLT group, mean cold ischemic time was longer than in the LRT group. Serum values of alanine aminotransferase during the first postoperative week were significantly higher in the SLT group. In the LRT group, there were more grafts with signs of fatty degeneration than in the SLT group. CONCLUSIONS: The short- and long-term outcomes after LRT and SLT did not differ significantly. To avoid the risk for the donor in LRT, SLT represents the first-line therapy in pediatric liver transplantation in countries where cadaveric organs are available. LRT provides a solution for urgent cases in which a cadaveric graft cannot be found in time or if the choice of the optimal time point for transplantation is vital.

Adolescent↗
PubMed2001

Long-term results of percutaneous thrombo-embolectomy in patients with infrainguinal embolic occlusions.

BACKGROUND: The aim of the study was to review early and long term clinical results of percutaneous thrombo-embolectomy in patients with acute embolic occlusions of the infrainguinal arteries. METHODS: Retrospective analysis of consecutive cases. A total of 88 procedures in 84 patients were performed between 1986 and 1996 in a University Hospital (46 men, 42 women; mean age 67.6 +/- 14.4 years). Patients with a history of chronic symptomatic arterial occlusive disease were not included in the analysis. Indications for treatment were severe claudication (n = 45 procedures) and limb threatening ischaemia (n = 43 procedures). Percutaneous thrombo-embolectomy was performed via an ipsilateral approach by means of an end hole aspiration catheter. Local thrombolysis or balloon angioplasty was used as appropriate during the intervention. Follow-up included clinical data, ankle pressure measurements, pulse volume recordings and duplex sonography or angiography if indicated. RESULTS: Technical success was achieved in 85 (96.6%) of the 88 procedures. Two patients (2.3%) suffered major and two patients (2.3%) minor complications. One patient died within 30 days after the procedure. Mean follow-up was 3.7 +/- 2.9 years. Twelve patients (16%) were lost to follow-up. Primary clinical success rate was 88.4% at one and 81.7% at two years and declined to 76.5% at eight years. Out of the 16 interval failures 10 (63%) were due to recurrent embolism to the same leg. They resulted in nine catheter reinterventions and one bypass graft. Six patients were treated conservatively. Cumulative mortality was 11.7% at one year and increased to 29.5% at eight years. CONCLUSIONS: From our single centre experience we conclude that catheter treatment of acute embolic occlusion of infrainguinal arteries is safe and has favourable long-term RESULTS. We therefore regard the technique as a less invasive alternative to surgery.

Aged↗
PubMed2000

Detection and substrate selectivity of new microbial D-amino acid oxidases.

In order to screen for new microbial D-amino acid oxidase activities a selective and sensitive peroxidase/o-dianisidine assay, detecting the formation of hydrogen peroxide was developed. Catalase, which coexists with oxidases in the peroxisomes or the microsomes and, which competes with peroxidase for hydrogen peroxide, was completely inhibited by o-dianisidine up to a catalase activity of 500 nkat ml(-)(1). Thus, using the peroxidase/o-dianisidine assay and employing crude extracts of microorganisms in a microplate reader, a detection sensitivity for oxidase activity of 0.6 nkat ml(-)(1) was obtained.Wild type colonies which were grown on a selective medium containing D-alanine as carbon, energy and nitrogen source were examined for D-amino acid oxidase activity by the peroxidase/o-dianisidine assay. The oxidase positive colonies possessing an apparent oxidase activity > 2 nkat g dry biomass(-)(1) were isolated. Among them three new D-amino acid oxidase-producers were found and identified as Fusarium oxysporum, Verticilium lutealbum and Candida parapsilosis. The best new D-amino oxidase producer was the fungus F. oxysporum with a D-amino acid oxidase activity of about 900 nkat g dry biomass(-)(1) or 21 nkat mg protein(-)(1). With regard to the use as a biocatalytic tool in biotechnology the substrate specificities of the three new D-amino acid oxidases were compared with those of the known D-amino acid oxidases from Trigonopsis variabilis, Rhodotorula gracilis and pig kidney under the same conditions. All six D-amino acid oxidases accepted the D-enantiomers of alanine, valine, leucine, proline, phenylalanine, serine and glutamine as substrates and, except for the D-amino acid oxidase from V. luteoalbum, D-tryptophane, D-tyrosine, D-arginine and D-histidine were accepted as well. The relative highest activities (>95%) were measured versus D-alanine (C. parapsilosis, F. oxysporum, T. variabilis), D-methionine (V. luteoalbum, R. gracilis), D-valine (T. variabilis, R. gracilis) and D-proline (pig kidney). The D-amino oxidases from F. oxysporum and V. luteoalbum were able to react with the industrially important substrate cephalosporin C although the D-amino acid oxidase from T. variabilis was at least about 20-fold more active with this substrate.As the results of our studies, a reliable oxidase assay was developed, allowing high throughput screening in a microplate reader. Furthermore, three new microbial D-amino acid oxidase-producers with interesting broad substrate specificities were introduced in the field of biotechnology.

Journal Article↗
PubMed2000

Monitoring and control of industrial downstream processing of sugar beet molasses.

In present work the determination of several amino acids during the industrial chromatographic desugarisation of molasses is presented. The use of innovative biosensor systems for highly specific detection of serine is described. Using two-dimensional fluorescence spectrometry, a non-invasive method for the determination of several product fractions could be established in an industrial chromatographic procedure.

Biosensing Techniques↗