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Biomedical subjects

Andreas Wagner

Publications and source records attributed to Andreas Wagner.

At least 55 records · Page 3Linked to original sources
PubMed2003

[Radiochemotherapy with gemcitabine and cisplatin in pancreatic cancer -- feasible and effective].

BACKGROUND: Concomitant radiotherapy and chemotherapy with gemcitabine appears to be a promising tool for the treatment of pancreatic cancer since gemcitabine -- applied as single or combination therapy -- proved to have better efficacy in pancreatic cancer than 5-FU containing schemes and furthermore offers radiosensitizing potential. In the present paper our pilot data of concomitant and sequential chemoradiation with gemcitabine and cisplatin are presented. PATIENTS AND METHODS: A total of 57 patients (f/m 23/34) with pancreatic cancer was treated, of whom 33 patients had irresectable tumors, 19 patients following resection (R1 and/or pN+) and five patients with local recurrent disease. Radiotherapy was delivered in 25 fractions up to a total dose of 45.0 Gy specified according to ICRU reference point (50 patients, 1.8 Gy/fraction) respectively 50.0 Gy to gross tumor volume (seven patients; 45.0 Gy in locoregional lymphatic pathways; 2.0/1.8 Gy/fraction). Concomitant with radiotherapy cisplatin (30 mg/m(2)) and gemcitabine (300 mg/m(2)) were applied on days 1, 8, 22 and 29. After simultaneous chemoradiation two sequential cycles gemcitabine and cisplatin (1000 mg/m(2) and 50 mg/m(2) d 1, 15) were applied. RESULTS: With a median follow-up of 8.2 months the median survival time was 14.8 months (irresectable patients: 10.3 months, postoperative patients, 15.1 months). Within 33 irresectable patients 19 and four partial and complete remissions, respectively, were observed. In 14 patients a secondary resection was possible. Using leveled antiemetics with ondansetron and dexamethasone no gastrointestinal toxicities grade III or IV were observed. Hematologic toxicities were the most grave side effects (leukocytopenia III/IV in 29/five patients and thrombocytopenia III/IV in 21/eight patients), however with minor clinical relevancy (one neutropenic infection, one thrombopenic epistaxis). CONCLUSION: The presented treatment scheme using concomitant and sequential gemcitabine and cisplatin with radiation is feasible with justifiable side effects. To evaluate the promising remission and survival rates, randomized trials of neoadjuvant and primary chemoradiation are started.

Adult↗
PubMed2003

First metatarsophalangeal joint replacement: the method of choice for end-stage hallux rigidus?

Replacement of the first metatarsophalangeal (MTP) joint remains critical because of complex biomechanical conditions and implant fixation. After a 3-year follow-up, most patients who experienced an MTP joint replacement were extremely satisfied with the outcome. Plantar pressure distribution revealed a marked improvement. Nevertheless, recovery of MTP dorsiflexion was limited and joint stability worsened. Radiologically, one-third of the prostheses showed radiolucent lines as a sign of implant loosening. MTP replacement offers distinct advantages in the treatment of end-stage hallux rigidus, but requires further research on implant design and osseous fixation.

Adult↗
PubMed2003

[Effects of a computer-assisted system for nursing care documentation on quality and quantity of nursing care documentation].

The University Hospital in Heidelberg has been gathering experience with the computer based nursing documentationsystem PIK since 1998. Its introduction on four pilotwards was systematically evaluated in an intervention study, gaining data to acceptance issues as well as to the quality of nursing documentation, as the nursing process is often not documented in an appropriate manner. Data to quantity and quality of nursing documentation before and after the intervention was gathered by means of a quality checklist, which was developed on the basis of an intensive literature review. To measure a difference in the quality of nursing documentation 20 documents from each of the four wards were assessed at the three assigned points of time by two nursing experts. The assessors stated a significant improvement in documentation quality due to the increase in formal completeness when documenting the nursing process. The content of the documentation as well as the individualization of the nursing care plan still need to be improved.

Attitude to Computers↗
PubMed2003

Convergent evolution of gene circuits.

Convergent evolution is a potent indicator of optimal design. We show here that convergent evolution occurs in genetic networks. Specifically, we show that multiple types of transcriptional regulation circuitry in Escherichia coli and the yeast Saccharomyces cerevisiae have evolved independently and not by duplication of one or a few ancestral circuits.

Escherichia coli↗
PubMed2003

Induction of antitumour immunity using survivin peptide-pulsed dendritic cells in a murine lymphoma model.

Survivin is overexpressed in several types of haematological malignancies making it an attractive target for therapeutic cytotoxic T-lymphocyte responses. Here, we identify two peptide epitopes derived from the murine survivin protein and demonstrate that Balb/c mice treated with syngeneic dendritic cells pulsed with the survivin epitopes were able to reject an otherwise lethal tumour inoculation of the A20 lymphoma. For the first time, these data provide evidence for the use of survivin peptide epitopes in T cell-based immunotherapeutic concepts against a B-cell lymphoma in vivo.

Animals↗
PubMed2003

Asymmetric sequence divergence of duplicate genes.

Much like humans, gene duplicates may be created equal, but they do not stay that way for long. For four completely sequenced genomes we show that 20%-30% of duplicate gene pairs show asymmetric evolution in the amino acid sequence of their protein products. That is, one of the duplicates evolves much faster than the other. The greater this asymmetry, the greater the ratio Ka/Ks of amino acid substitutions (Ka) to silent substitutions (Ks) in a gene pair. This indicates that most asymmetric divergence may be caused by relaxed selective constraints on one of the duplicates. However, we also find some candidate duplicates where positive (directional) selection of beneficial mutations (Ka/Ks > 1) may play a role in asymmetric divergence. Our analysis rests on a codon-based model of molecular evolution that allows a test for asymmetric divergence in Ka. The method is also more sensitive in detecting positive selection (Ka/Ks > 1) than models relying only on pairwise gene comparisons.

Amino Acid Substitution↗
PubMed2003

Perspective: Evolution and detection of genetic robustness.

Robustness is the invariance of phenotypes in the face of perturbation. The robustness of phenotypes appears at various levels of biological organization, including gene expression, protein folding, metabolic flux, physiological homeostasis, development, and even organismal fitness. The mechanisms underlying robustness are diverse, ranging from thermodynamic stability at the RNA and protein level to behavior at the organismal level. Phenotypes can be robust either against heritable perturbations (e.g., mutations) or nonheritable perturbations (e.g., the weather). Here we primarily focus on the first kind of robustness--genetic robustness--and survey three growing avenues of research: (1) measuring genetic robustness in nature and in the laboratory; (2) understanding the evolution of genetic robustness: and (3) exploring the implications of genetic robustness for future evolution.

Adaptation, Biological↗
PubMed2002

GenomeHistory: a software tool and its application to fully sequenced genomes.

We present a publicly available software tool (http://www.unm.edu/~compbio/software/GenomeHistory) that identifies all pairs of duplicate genes in a genome and then determines the degree of synonymous and non-synonymous divergence between each duplicate pair. Using this tool, we analyze the relations between (i) gene function and the propensity of a gene to duplicate and (ii) the number of genes in a gene family and the family's rate of sequence evolution. We do so for the complete genomes of four eukaryotes (fission and budding yeast, fruit fly and nematode) and one prokaryote (Escherichia coli). For some classes of genes we observe a strong relationship between gene function and a gene's propensity to undergo duplication. Most notably, ribosomal genes and transcription factors appear less likely to undergo gene duplication than other genes. In both fission and budding yeast, we see a strong positive correlation between the selective constraint on a gene and the size of the gene family of which this gene is a member. In contrast, a weakly negative such correlation is seen in multicellular eukaryotes.

Animals↗
PubMed2002

Severe accidental hypothermia with or without hemodynamic instability: rewarming without the use of extracorporeal circulation.

BACKGROUND: The optimal rewarming technique for patients in deep accidental hypothermia with core temperatures below 28 degrees C is not established. Several authors believe that extracorporeal rewarming is essential, especially for patients with hemodynamic instability. Others believe that invasive rewarming ought to be reserved for patients in cardiac arrest. We describe our experience with a strictly conservative technique without the use of invasive rewarming devices in patients with severe accidental hypothermia and a sustained perfusion rhythm. METHODS: A cohort study extending from 1991 to 2000, including all patients received at the emergency department of the University Hospital of Vienna with severe hypothermia, a core temperature of maximum 28 degrees C and no preclinical cardiac arrest. RESULTS: 36 patients with deep hypothermia were included in the study. Their core temperatures ranged from 20.2 degrees C to 28 degrees C; the median temperature was 25.75 degrees C (25th and 75th percentile, 24.2/27.3). Fourteen patients were intoxicated and their multimorbidity was high. All of 19 patients with stable hemodynamics and 14 of 17 patients with unstable hemodynamics were successfully rewarmed to normothermia with warmed infusions, inhalation rewarming and forced air rewarming. The rewarming process took 9.5 hours (8/10.5) and required a volume load of 4820 ml (2735/5770). The rewarming rate was 1.09 degrees C per hour (0.94/1.25). Although 92% of the patients were successfully rewarmed to normothermia, in-hospital mortality was 42%, but was largely related to comorbidity. DISCUSSION: A conservative approach is highly successful in achieving normothermia in patients with deep hypothermia with or without stable hemodynamics. In-hospital mortality of severe accidental hypothermia in urban conditions is high; comorbidity might play a major role. The influence of the rewarming strategy on late in-hospital mortality remains unclear.

Austria↗
PubMed2002

Selection and gene duplication: a view from the genome.

Immediately after a gene duplication event, the duplicate genes have redundant functions. Is natural selection therefore completely relaxed after duplication? Does one gene evolve more rapidly than the other? Several recent genome-wide studies have suggested that duplicate genes are always under purifying selection and do not always evolve at the same rate.

Animals↗
PubMed2002

Plasma endothelin in patients with acute aortic disease.

PURPOSE AND BACKGROUND: We investigated the plasma levels of endothelin 1/2 in patients with acute symptoms relating to a known or newly diagnosed aortic aneurysm in order to investigate the possible role of peptides in the development of the disease. METHODS: Endothelin 1/2 plasma levels were determined in patients admitted to the emergency unit with suspected acute aortic disease. The history, type of aneurysm, outcome and laboratory findings were determined and compared to endothelin 1/2 levels collected on admission. RESULTS: In patients with ruptured aneurysm (n=27) or acute aortic dissection (n=18) the endothelin 1/2 median levels were higher 1.1 (25th and 75th quartile 0.7, 1.7) fmol/ml than in patients (n=20) with pre-existing aneurysm 0.7 (0.4, 1.1) fmol/ml (P=0.013). Patients who died had significantly higher endothelin levels 1.3 (0.8, 1.9) fmol/ml than the survivors 0.8 (0.5, 1.4) fmol/ml (P=0.04). In a logistic regression analysis, only a higher blood pressure on admission was an independent predictor of survival. CONCLUSION: Endothelin 1/2 levels are elevated in patients with acute dissection or ruptured aneurysm, but they are not an independent predictor of survival.

Adult↗
PubMed2002

Long term stability of rh-Cu/Zn-superoxide dismutase (SOD)-liposomes prepared by the cross-flow injection technique following International Conference on Harmonisation (ICH)-guidelines.

The current market position of liposomes as drug carriers is still being discussed with regard to large scale production, product characterisation and the stability of the dispersions. In this study, long term stability of liposomal suspensions with encapsulated rh-Cu/Zn-superoxide dismutase was tested according to the International Conference on Harmonisation (ICH) recommendations. The guidelines of the ICH provide general requirements for stability testing for registration and export in particular. The Institute of Applied Microbiology has examined a process to produce large amounts of pharmaceutical-grade liposomes for the treatment of inflammatory diseases by topical application. For the evaluation of its long-term storage stability, liposomal stability and protein stability were tested under appropriate conditions. Therefore, size alterations of the vesicles, protein release and protein activity were evaluated. During the observation period, neither significant alterations of the liposomes nor any protein degradation could be detected. In the light of these findings our liposomal formulations seem to provide chemical, physical and biological stability according to the definitions of the ICH. Appropriate lipid compounds and environmental factors, in combination with an optimised process and adequate storage conditions, facilitate the production of liposome dispersions suitable as drug carriers on the market.

Drug Stability↗
PubMed2002

Liposomes produced in a pilot scale: production, purification and efficiency aspects.

Intensive efforts have been made to establish a novel, scalable liposomal preparation technique suitable for the entrapment of even large proteins into liposomes. We have developed a new technique based on the principles of the ethanol injection technique. Herein, the principal item is the crossflow injection module, specifically designed for this purpose. This unit has the benefit of defined and characterized injection streams and permits liposome manufacture regardless of production scale, as scale is determined only by the free disposable vessel volumes. Previous publications demonstrated that the crossflow injection technique that we have developed meets all of the above-mentioned requirements. The present paper describes the entire three-step production process, consisting of encapsulation, separation of non-entrapped protein by continuous crossflow filtration, and retrieval of rh-Cu/Zn-SOD by additional filtration. Results of consecutive lots were compared, based on well-defined quality criteria.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2002

The crossflow injection technique: an improvement of the ethanol injection method.

A novel scalable liposome preparation technique for pharmaceutical application is presented. Previous experiments have shown that the concept of continuous crossflow injection is a promising approach. For the characterization of the process, we focus on the influencing parameters like the lipid concentration, the injection hole diameter, the injection pressure, the buffer flow rate, and system performance. These experiments demonstrate that the injection hole diameter and the system performance do not influence the vesicle forming process and that a minimum of buffer flow rate is required to affect batch homogeneity. In contrast, strongly influencing parameters are lipid concentration in combination with increasing injection pressures. After exceeding the upper pressure limit of the linear range, where injection velocities remain constant, the vesicle batches are narrowly distributed, also when injecting higher lipid concentrations. Reproducibility and scalability data show similar results with respect to vesicle size and size distribution and demonstrate the stability and robustness of the novel continuous liposome preparation technique.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2002

Enhanced protein loading into liposomes by the multiple crossflow injection technique.

Methods for encapsulation of a drug into liposomes should preferably result in a high encapsulation efficiency and a high encapsulation capacity. Our studies were focussed on the establishment of an efficient encapsulation procedure of the radical scavenging protein, rh-Cu/Zn-SOD, into liposomes with the cross flow injection method. Limitations to increase the encapsulation efficiency are caused by the enclosed aqueous volume, by the lipid concentration, the aspired vesicle size and the final ethanol concentration. Our research was performed to maximize the encapsulation following several strategies of injecting higher lipid concentrations into the aqueous phase. The one way triple technique, a sophisticated preparation procedure is presented, which enables three times higher encapsulation rates in comparison to standard procedures. Additionally, scalability studies demonstrate reproducibility independent of the preparation volume. Vesicle size distribution and encapsulation efficiency remain constant. Furthermore, special attention is paid on reproducibility of prepared liposomes, scale-up and on long term stability of the lipid vesicles.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2002

Asymmetric functional divergence of duplicate genes in yeast.

Most duplicate genes are eliminated from a genome shortly after duplication, but those that remain are an important source of biochemical diversity. Here, I present evidence from genome-scale protein-protein interaction data, microarray expression data, and large-scale gene knockout data that this diversification is often asymmetrical: one duplicate usually shows significantly more molecular or genetic interactions than the other. I propose a model that can explain this divergence pattern if asymmetrically diverging duplicate gene pairs show increased robustness to deleterious mutations.

Environment↗