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Biomedical subjects

M Neumann

Publications and source records attributed to M Neumann.

At least 37 records · Page 2Linked to original sources

Microscopic self-dynamics in liquid hydrogen and in its mixtures with deuterium.

We have measured the dynamic structure factor of liquid parahydrogen, pure and mixed with deuterium, in various thermodynamic conditions using incoherent inelastic neutron scattering. The experiments were carried out on TOSCA-II, a new time-of-flight, inverse-geometry, crystal-analyzer spectrometer. After an accurate data reduction, the high-energy parts of the neutron spectra recorded in backward scattering were studied through the modified Young and Koppel model, from which the mean kinetic energy values for a hydrogen molecule were estimated. In addition the low-energy parts of the neutron spectra recorded in forward scattering were analyzed in the framework of the Gaussian approximation and fitted through a Levesque-Verlet model for the velocity autocorrelation function. Thus various physical quantities are determined and compared with accurate path integral Monte Carlo simulations. Despite the excellent quality of these fits, the velocity autocorrelation functions derived from the forward-scattering data appear totally unable to properly describe the backward-scattering ones. These findings prove an unquestionable breakdown of the Gaussian approximation in semiquantum liquids. The present results appear of great interest and suggest further investigation on the limits of the widely used Gaussian approximation.

Journal Article↗

Breast cancer: patient information needs reflected in English and German web sites.

Individual belief and knowledge about cancer were shown to influence coping and compliance of patients. Supposing that the Internet information both has impact on patients and reflects patients' information needs, breast cancer web sites in English and German language were evaluated to assess the information quality and were compared with each other to identify intercultural differences. Search engines returned 10 616 hits related to breast cancer. Of these, 4590 relevant hits were analysed. In all, 1888 web pages belonged to 132 English-language web sites and 2702 to 65 German-language web sites. Results showed that palliative therapy (4.5 vs 16.7%; P=0.004), alternative medicine (18.2 vs 46.2%; P<0.001), and disease-related information (prognosis, cancer aftercare, self-help groups, and epidemiology) were significantly more often found on German-language web sites. Therapy-related information (including the side effects of therapy and new studies) was significantly more often given by English-language web sites: for example, details about surgery, chemotherapy, radiotherapy, hormone therapy, immune therapy, and stem cell transplantation. In conclusion, our results have implications for patient education by physicians and may help to improve patient support by tailoring information, considering the weak points in information provision by web sites and intercultural differences in patient needs.

Breast Neoplasms↗

Large-scale homogeneous molecular templates for femtosecond time-resolved studies of the guest-host interaction.

Self-assembled monolayer films based on iodobenzoyloxy-functionalized resorc[4]arenes were prepared on gold substrates to serve as model systems for future time-resolved studies of molecular recognition, a mechanism of outstanding importance in bioorganic systems. The film properties were tested using X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM) and imaging ellipsometry. An apparatus for time-resolved electron spectroscopy utilizing femtosecond soft X-ray pulses is capable of detecting iodine core-level photolines and the photoinduced dissociation after ultraviolet illumination. The developed technique holds promise for tracking the temporal evolution of chemical shifts of atomic markers as local probes for the dynamics of the guest-host interaction.

Benzoates↗

[Caloric stimulation of the vestibular organ after cochlear implant surgery].

BACKGROUND: Alterations of the vestibular organ after intracochlear insertion of the electrode array in cochlear implant (CI) surgery are estimated in the literature to be more than 30 % . By performing a most atraumatic electrode insertion following the "soft surgery technique" as described by Lehnhardt , the risk of postoperative vestibular dysfunction should be minimised. METHODS: In the present study we compared pre- and postoperative results of the caloric stimulation test in cochlear implant patients and analysed the influence of untimely opening of the perilymphatic space under cochleostomy. In addition we used a non-validated questionnaire, asking for continuous postoperative vertigo after cochlear implant surgery. RESULTS: From patients with preoperative normal or hyperfunction on the implanted ear (n = 32) approximately 16 % showed a hypofunction or nonfunction on the implanted side postoperatively, independent of the technique of the cochleostomy. Only 12 % (n = 98) of the patients who were without vestibular problems preoperatively described postoperative vertigo longer than two days in the questionnaires. CONCLUSIONS: Although we found no significant difference regarding the influence of the technique of the cochleostomy on the preservation of vestibular function, we conclude that the concept of an atraumatic electrode insertion reduces the risk of vestibular dysfunction after CI-surgery.

Adolescent↗

[Laparoscopic cholecystectomy. Training on a bio-simulation model with learning success documented using score-cards].

The possibilities of gaining theoretical knowledge in surgery are virtually unlimited. To acquire practical skills,however, the availability and willingness of the patient are the limiting factors. With the development of training tools and structured courses, experience can be gained independently of the clinical situation. To objectify and record individual performance and improvement, and to define further potential, a scoring system is necessary. Using the example of laparoscopic cholecystectomy, a training program was combined with an evaluation system and the beginners' learning curves were recorded during the course of a training week. The present study shows that first experiences and measurable improvements can be reliably assessed within one week's structured training on a simulation model.

Animals↗

Cell type selective accumulation of mercaptoundecahydro- closo-dodecaborate (BSH) in glioblastoma multiforme.

BACKGROUND: Boron uptake in glioblastoma tissue for boron neutron capture therapy is of great importance for the clinical outcome of the treatment. METHODS: The cell type specific distribution of mercaptoundecahydro-closo-dodecaborate (BSH) in glioblastoma multiforme tissue sections of seven patients having received BSH prior to surgery was investigated by light and fluorescence microscopy. FINDINGS: With use of specific antibodies against different tumour specific epitopes and BSH, BSH was found predominantly (approx. 90%) in the cytoplasm of GFAP-positive cells of all but two patients. The latter were younger (33 and 38 years versus 46-71 (mean 60) years). There was no correlation between BSH uptake and expression of EGFR, p53, CD44 and Ki-67. INTERPRETATION: GFAP-positive cells appear to be the primary cell type for BSH uptake in primary glioblastoma, and an important cell type for localisation of BSH in secondary glioblastoma. The molecular basis and the selective uptake mechanism require further work. If a correlation between histologically distinct patterns and clinical outcome for patients undergoing boron neutron capture therapy could be derived, prognostic factors for the treatment could be developed.

Adult↗

Diagnostic and neural analysis of skin cancer (DANAOS). A multicentre study for collection and computer-aided analysis of data from pigmented skin lesions using digital dermoscopy.

BACKGROUND: Early detection of melanomas by means of diverse screening campaigns is an important step towards a reduction in mortality. Computer-aided analysis of digital images obtained by dermoscopy has been reported to be an accurate, practical and time-saving tool for the evaluation of pigmented skin lesions (PSLs). A prototype for the computer-aided diagnosis of PSLs using artificial neural networks (NNs) has recently been developed: diagnostic and neural analysis of skin cancer (DANAOS). OBJECTIVES: To demonstrate the accuracy of PSL diagnosis by the DANAOS expert system, a multicentre study on a diverse multinational population was conducted. METHODS: A calibrated camera system was developed and used to collect images of PSLs in a multicentre study in 13 dermatology centres in nine European countries. The dataset was used to train an NN expert system for the computer-aided diagnosis of melanoma. We analysed different aspects of the data collection and its influence on the performance of the expert system. The NN expert system was trained with a dataset of 2218 dermoscopic images of PSLs. RESULTS: The resulting expert system showed a performance similar to that of dermatologists as published in the literature. The performance depended on the size and quality of the database and its selection. CONCLUSIONS: The need for a large database, the usefulness of multicentre data collection, as well as the benefit of a representative collection of cases from clinical practice, were demonstrated in this trial. Images that were difficult to classify using the NN expert system were not identical to those found difficult to classify by clinicians. We suggest therefore that the combination of clinician and computer may potentially increase the accuracy of PSL diagnosis. This may result in improved detection of melanoma and a reduction in unnecessary excisions.

Adult↗

Score card endoscopy: a multicenter study to evaluate learning curves in 1-week courses using the Erlangen Endo-Trainer.

BACKGROUND AND STUDY AIMS: The present study was carried out in the context of current discussions concerning ways in which simulation systems can be integrated sensibly and effectively into clinical educational structures, in order to shorten the training period for assistants and reduce potential risks for the patient. In our study, a number of centers used a standardized training approach, in 1 week courses, to investigate the learning curve improvement that can be achieved with a group of beginners in upper gastroduodenal endoscopy. MATERIALS AND METHODS: The multicenter study used the Erlangen Endo-Trainer, with specially prepared biological specimens from pigs. Using this, the individual steps of diagnostic upper gastrointestinal endoscopy with biopsy can be carried out following a score-card system. After a theoretical introduction and a demonstration of the examination by an experienced endoscopist, an initial evaluation score for each participant was obtained on day 1. On the following days, the program consisted of 2 hours' training by a tutor, followed by a test run for each participant. On days 1, 2, 3, 4, and 5 the test run was directly followed by a self-assessment. In addition, on days 1, 3, and 5 the test run for each beginner was recorded on video, with each video assigned an encrypted code number. All the end of the study week, control assessments of these videos were carried out by an experienced endoscopist. RESULTS: Both the self-assessments and the control assessments showed significant improvements in the endoscopic parameters tested during the course (days 1-5; all parameters P < 0.001, Wilcoxon-test). However, it was found that the trainees tended to give themselves better marks than the marks given by experienced endoscopists. CONCLUSION: During 1 week of training, using the model and following the score card, a significant improvement in the learning curve was achieved in the beginners' group for the individual steps involved in diagnostic upper gastrointestinal endoscopy. When this approach is used with trainees who are also provided with the necessary theoretical background, this type of preparation may lead to a better, lower-risk start to supervised practical endoscopic examinations in patients.

Animals↗

Scorecard endoscopy: a pilot study to assess basic skills in trainees for upper gastrointestinal endoscopy.

BACKGROUND: The development of training models and structured training courses for endoscopic techniques provides practical experience. To assess individual performance and progress in this training we developed and tested a scorecard system. METHODS: Three test groups were compared: group 1, ten physicians without previous endoscopic experience; group 2, ten students, without endoscopic experience; group 3, a control group of experienced endoscopists. Groups 1 and 2 underwent 1 week of training with a theoretical introduction and practical demonstrations. They were assessed by the scorecard daily by an experienced tutor. The individual scores and learning curves of the two beginner groups were compared with those of the expert group using a biosimulation model was used. RESULTS: Each participant improved significantly during the 1-week course. Mean scores on the first day in groups 1-3 were, respectively, 26.7+/-10.7, 33.4+/-5.3, and 72.0+/-5.8, and on day 6 they were 62.2+/-6.6, 63.4+/-7.6, and 86.6+/-4.3. The difference between group 3 and the other two groups was significant but not that between groups 1 and 2. CONCLUSIONS: Training in endoscopy can be assessed using our training model and our scorecard protocol, which distinguishes between various levels of experience. In physicians beginning in the field of gastrointestinal endoscopy this approach could help to reduce risks to patients, shorten learning curves, and exclude unskilled individuals from further fruitless interventions.

Animals↗

Tau protein and 14-3-3 protein in the differential diagnosis of Creutzfeldt-Jakob disease.

BACKGROUND: Diagnosis of Creutzfeldt-Jakob disease (CJD) is made according to the typical clinical picture and can be supported by a positive 14-3-3 CSF immunoblot. Promising results for the diagnostic sensitivity and specificity of tau-protein measurement in CSF already have been described in a smaller group of patients. Both tests in a larger group of patients with the differential diagnosis of CJD were evaluated. METHODS: CSF of 297 patients under the differential diagnosis of CJD (109 definite, 55 probable, 39 possible; 85 others, 1 iatrogenic, 8 genetic), 23 nondemented control subjects, and 15 non-CJD patients with positive 14-3-3 immunoblots were analyzed. The 14-3-3 immunoblot bands were semiquantitatively rated as strong, medium, and weak. Tau-protein was analyzed using a commercially available ELISA. In addition, patients were neuropathologically classified according to prion protein type and polymorphism at codon 129. RESULTS: A diagnostic sensitivity of 94%, a diagnostic specificity of 90%, and a positive predictive value of 92% were achieved for tau-protein at a cut-off of 1,300 pg/mL. These results are comparable with those of the 14-3-3 immunoblot. For patients with type II prion protein and methionine/valine or valine/valine polymorphism at codon 129, tau-protein has a higher diagnostic sensitivity than 14-3-3 protein. Tau-protein levels were significantly higher in patients with higher-rated 14-3-3 immunoblot bands. CONCLUSION: The differential diagnostic significance of the 14-3-3 immunoblot is similar to that of the tau-protein ELISA. The advantage of the tau-protein ELISA is that it is easy to use in routine laboratories. Patients with a negative 14-3-3 immunoblot already have measurable tau-protein levels. This increases information on 14-3-3-negative patients with CJD and especially on patients with other diseases.

14-3-3 Proteins↗

Generating p53-specific cytotoxic T lymphocytes by recombinant adenoviral vector-based vaccination in mice, but not man.

Mutations and aberrant expression of the p53 tumor suppressor protein are the most frequent molecular alterations in human malignancy. Peptides derived from the wild-type (wt) p53 protein and presented by major histocompatibility complex (MHC) molecules for T lymphocyte recognition are believed to serve as universal tumor-associated antigens for cancer immunotherapy. We studied the immunogeneicity of a recombinant replication-defective adenoviral vector encoding human full-length wt p53 (rAd/hup53) in human leukocyte antigen (HLA)-A2K(b)-transgenic (Tg) mice and man. The generation of p53 epitope-specific cytotoxic T lymphocytes (CTLs) in p53-proficient and p53-deficient A2K(b)-Tg mice was affected by self-tolerance and a selective inability of rAd/hup53 to induce p53.264-272 peptide-reactive effector cells. To extend this study into a pilot clinical trial, six advanced-stage cancer patients received sequential injections of rAd/hup53. The treatment was well tolerated. To date, no evidence for objective tumor responses was observed. An amplification of humoral and cellular anti-adenoviral immune responses was demonstrated in all patients following rAd/hup53 vaccination. However, p53-reactive antibodies and HLA-A*0201 (A2.1)-restricted CTLs specific for wt p53 epitopes were not generated. Tailoring p53-based cancer immunotherapy thus requires the interference with p53-specific self-tolerance and the induction of the entire repertoire of p53-reactive T lymphocytes.

Adenoviridae↗

A score card for upper GI endoscopy: Evaluation of interobserver variability in examiners with various levels of experience.

BACKGROUND: In most European countries, training in GI endoscopy has largely been based on hands-on acquisition of experience in patients rather than on a structured training programme. With the development of training models systematic hands-on training in a variety of diagnostic and therapeutic endoscopy techniques was achieved. Little, however, is known about methods of objectively assessing trainees' performance. We therefore developed an assessment 'score card' for upper GI endoscopy and tested it in endoscopists with various levels of experience. The aim of the study was therefore to assess interobserver variations in the evaluation of trainees. METHODS: On the basis of textbook and expert opinions a consensus group of eight experienced endoscopists developed a score card for diagnostic upper GI endoscopy with biopsy. The score card includes an assessment of the single steps of the procedure as well as of the times needed to complete each step. This score card was then evaluated in a further conference including ten experts who blindly assessed videotapes of 15 endoscopists performing upper GI endoscopy in a training bio-simulation model (the 'Erlangen Endo-Trainer'). On the basis of their previous experience (i. e. the number of endoscopies performed) these 15 endoscopists were classified into four groups: very experienced, experienced, having some experience and inexperienced. Interobserver variability (IOV) was tested for the various score card parameters (Kendall's rank-correlation coefficient 0.0-0.5 poor, 0.5-1.0 good agreement). In addition, the correlation between the score card assessment and the examiners' experience levels was analysed. RESULTS: Despite poor IOV results for all the parameters tested (Kendall coefficient < 0.3), the assessment parameters correlated well when the examiners' different experience levels were taken into account (correlation coefficient 0.59-0.89, p < 0.05). The score card parameters were suitable for differentiating between the four groups of examiners with different levels of endoscopic experience. CONCLUSIONS: As expected with scores involving subjective assessment of performance, the variability between reviewers was substantial. Nevertheless, the assessment score was capable of distinguishing reliably between different experience levels in terms of a good individual observer consistency. The score card can therefore be used to document both training status and progress during endoscopy training courses using bio-simulation models, and this might be able to provide improved quality assurance in GI endoscopy training.

Animals↗

Surfactant in children with malignancies, immunosuppression, fever and pulmonary infiltrates.

In children with malignancies and immunosuppression, significant morbidity and mortality result from respiratory complications. The aim of the present study was to investigate whether or not this is associated with altered surfactant components or functions. Bronchoalveolar lavage fluid from 24 children with malignancies, immunosuppression, pulmonary infiltrates and fever unresponsive to empirical antibiotic treatment were compared to that from 24 healthy children. Levels of surfactant protein (SP) A and D and their binding capacity for Pseudomonas aeruginosa, as well as levels of SP-B and SP-C, were assessed by enzyme-linked immunosorbent assay. The large and small surfactant aggregate forms were separated and the biophysical activity of large surfactant aggregates was determined using a pulsating bubble surfactometer. Compared to healthy controls, SP-A levels were increased four-fold, the increase being most pronounced in those children with pathogens recovered from their bronchoalveolar lavage fluid. In children with malignancies, levels of SP-C were increased two-fold and of small surfactant aggregates five-fold. No differences were observed in levels of SP-B or SP-D, binding capacity of SP-A or SP-D or the surface activity of large surfactant aggregates. The increased levels of surfactant protein A, particularly in children with recovered microorganisms, and unchanged binding capacity of surfactant protein A are consistent with upregulated local host defence mechanisms. Increased surfactant protein A and C may also be responsible for the conserved biophysical activity of surfactant in children with malignancies, immunosuppression, pulmonary infiltrates and fever.

Adolescent↗

Signal-specific and phosphorylation-dependent RelB degradation: a potential mechanism of NF-kappaB control.

RelB is an unusual member of the Rel/NF-kappaB family of transcription factors which are involved in oncogenic processes. Due to a relaxed control by the IkappaBs, the cytosolic NF-kappaB inhibitors, RelB is constitutively expressed in the nuclei of lymphoid cells. We show here that RelB is inducibly degraded upon activation of T cells in a fashion similar to the IkappaBs. However, RelB degradation differs from that of IkappaBs since it is not induced by TNFalpha but only by T cell receptor or TPA/ionomycin stimulation. Moreover, RelB degradation occurs in three steps: (i) after stimulation RelB is rapidly phosphorylated at amino acids Thr84 and Ser552 followed by (ii) an N-terminal cut and, finally, (iii) the complete degradation in the proteasomes. Since mutation of the two phosphoacceptor sites to non-acceptor sites abolished RelB phosphorylation in vivo and led to the stabilization of the mutated RelB(DM), site-specific phosphorylation appears to be a necessary prerequisite for RelB degradation. RelB is a crucial regulator of NF-kappaB-dependent gene expression. Thus, the signal-induced degradation of RelB should be an important control mechanism of NF-kappaB activity.

Animals↗

Estrogen effects in the myocardium: inhibition of NF-kappaB DNA binding by estrogen receptor-alpha and -beta.

We have previously shown that estrogen effects in the heart include direct hormone effects on the myocardium. In a recent study we found that one beneficial effect of estradiol on the myocardium is the inhibition of apoptosis in cardiac myocytes. This effect was associated with a reduction of NF-kappaB activity. In the present study we have analyzed the functional mechanism of NF-kappaB inhibition in the myocardium by estrogen receptors-alpha and -beta. Despite the previous finding that 17-beta-estradiol (10 nM) inhibited the staurosporine-induced binding of p65/p50 NF-kappaB complexes to their cognate DNA elements in cultured rat cardiac myocytes, myocyte extracts showed no change in expression or cellular localization of p65, p50, and IkappaB upon staurosporine or estradiol treatment. Addition of either estrogen receptor-alpha or estrogen receptor-beta as recombinant protein was sufficient to inhibit staurosporine-dependent p65/p50 DNA binding in cardiac myocytes. 17-beta-Estradiol inhibits staurosporine-induced p65/p50 DNA binding associated with apoptotic cell death of cardiac myocytes via estrogen receptors-alpha and -beta. This is not associated with changes in p65, p50 and IkappaB expression or subcellular localization. Thus, inhibition of NF-kappaB activity by estrogenic compounds might inhibit NF-kappaB dependent gene expression such as pro-inflammatory cytokines in the myocardium.

Animals↗