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Biomedical subjects

P Wagner

Publications and source records attributed to P Wagner.

At least 19 recordsLinked to original sources
PubMed2007

[Experiments on prosody perception with cochlear implants].

BACKGROUND AND OBJECTIVE: Prosody has a myriad of linguistic functions and involves specific aspects of speech, such as stress, intonation and pauses. The underlying acoustic quantities (amplitude envelope, pitch frequency, and temporal structure) can be processed and transmitted by cochlear implants (CI) only to a limited extent. At present, no adequate tests are available in the German-speaking world for evaluation of the perception of prosodic elements. Different experiments have been conducted to address several prosodic cues, and the results are to be used as a basis for appropriate tests. METHODS: Various prosodic materials were used for the experiments. Discrimination was measured for minimal pairs differing in frequency and/or duration, accents in words and phrases, questions versus statements and phrasing. Measurements were performed in ten normal-hearing subjects and five with cochlear implants. RESULTS AND CONCLUSIONS: In all test modules, the subjects with normal hearing proved to have high discrimination rates of 96-100%. The test of word stresses was problematic because the results were influenced by different confounders. The other measurements did prove to be basically suitable for use in the subjects with implants. Early results revealed that the subjects with CI had few problems with prosodic cues based on the temporal structure, the outcome being similar to that of the subjects with normal hearing in these tests. In contrast, the performance of subjects with CI in perceiving prosodic cues based on amplitude variations and, especially, on alterations in pitch frequency was worse, even though some of them achieved very good results in these tests too. These preliminary tests can form the basis for development of a German-language prosody test battery with a limited number of subtests addressing different prosodic cues.

Acoustic Stimulation↗
PubMed2006

EDC-mediated DNA attachment to nanocrystalline CVD diamond films.

Chemical vapour deposited (CVD) diamond is a very promising material for biosensor fabrication owing both to its chemical inertness and the ability to make it electrical semiconducting that allows for connection with integrated circuits. For biosensor construction, a biochemical method to immobilize nucleic acids to a diamond surface has been developed. Nanocrystalline diamond is grown using microwave plasma-enhanced chemical vapour deposition (MPECVD). After hydrogenation of the surface, 10-undecenoic acid, an omega-unsaturated fatty acid, is tethered by 254 nm photochemical attachment. This is followed by 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide (EDC)-mediated attachment of amino (NH(2))-modified dsDNA. The functionality of the covalently bound dsDNA molecules is confirmed by fluorescence measurements, PCR and gel electrophoresis during 35 denaturation and rehybridisation steps. The linking method after the fatty acid attachment can easily be applied to other biomolecules like antibodies and enzymes.

Biosensing Techniques↗
PubMed2005

Microtubule Associated Protein (MAP)-Tau: a novel mediator of paclitaxel sensitivity in vitro and in vivo.

Microtubule binding protein Tau was recently identified through gene expression analysis of human breast cancer tissues as a novel marker of response to paclitaxel. This article reviews these recent findings and provides additional information to support the role of Tau as an emerging marker and mediator of paclitaxel sensitivity. Low expression of Tau is associated with increased sensitivity to paclitaxel in human breast cancer as well as in a broad range of cell lines. Down regulation of Tau in cell lines by siRNA increases their sensitivity to paclitaxel but not to anthracycline chemotherapy. We propose that this is due to increased paclitaxel binding to microtubules when microtubules are assembled in the presence of low concentrations (or absence) of Tau compared to microtubules that are formed in the presence of physiological (or higher) levels of Tau.

Alternative Splicing↗
PubMed2005

Impedimetric immunosensors based on the conjugated polymer PPV.

In the work reported here, we investigated the interaction between the semiconducting polymer MDMO-PPV and antibodies against the fluorescent dyes fluorescein isothiocyanate (FITC) and Cy5. The antibodies are adsorbed physically onto thin polymer films on gold electrodes, as seen in AFM images of these films. By tuning the antibody concentration, the contact angle of distilled water with the film can be made to vary between 95 degrees and 50 degrees, showing that different surface densities of antibody can be obtained. That these biosensor films specifically bind their antigenic fluorescent molecules from PBS buffer solution is demonstrated by confocal fluorescence microscopy. Specific antigen-antibody recognition is demonstrated by lack of cross-sensitivity between the two antibodies and their antigens. In a biosensor prototype based on differential impedance spectroscopy, these polymer films show a clear response to 1 ppb antigen solution, with a time constant of 2-3 min.

Antigens↗
PubMed2005

[Psychological abnormalities in patients with complex regional pain syndrome (CRPS)].

QUESTION: Do comorbid psychological disorders, dysfunctional pain processing, and psychosocial pain coping occur with complex regional pain syndrome (CRPS) and is a connection between clinical and psychological manifestations apparent? METHODS: In addition to securing information on case histories and performing clinical neurological examinations of chronic CRPS patients, the structured clinical interview (SCID), pain perception scale, and the Kiel Pain Inventory were employed. RESULTS: The structured clinical interview revealed evidence of a depressive episode in 65% of CRPS patients. Pain perception is similar to neuropathic pain syndromes and patient history revealed a slightly increased frequency of anxiety and affective disorders. Depressive syndrome occurred significantly more often in right-sided CRPS; otherwise, there were no significant correlations between medical history, clinical examination, and frequency of psychological disorders. However, CRPS patients with allodynia manifest clinical signs of special psychological distress. CONCLUSION: In chronic CRPS depressive syndrome frequently develops and psychological treatment can be recommended.

Comorbidity↗
PubMed2005

Group B streptococcus disease in neonates: to screen or not to screen?

An audit was undertaken of the prevention of early-onset Group B streptococcus (EOGBS) disease in neonates. The prevention strategy in use involved offering Intra-partum Antibiotic Prophylaxis (IAP) to mothers with identified risk factors, which include maternal fever in labour > 38 degrees C, previous baby with GBS disease, prolonged rupture of membranes > 18 h, pre-term labour, GBS urinary tract infection and known GBS carriage. The most common risk factor identified was GBS carriage (41%) which was known ante-partum but logistical problems prevented these mothers from receiving adequate prophylaxis 4 h before delivery and so were classified as at risk of GBS disease. We found an incidence of GBS in our unit of 0.55 per 1,000 births over the study period. One neonate developed EOGBS disease and the mother had no identifiable risk factor ante-partum/intra-partum. Recent recommendations from the Royal College of Obstetricians and Gynaecologists (RCOG) could reduce the number of babies having sepsis screens performed as the time interval from beginning IAP to delivery has been shortened to 2 h and routine surface cultures or blood cultures are not recommended in well newborns. The evidence is lacking at this point to recommend universal screening for GBS in all pregnant women but patients are increasingly aware of this option and may request anogenital swabs to assess GBS carriage.

Adolescent↗
PubMed2005

A single-gene biomarker identifies breast cancers associated with immature cell type and short duration of prior breastfeeding.

The pathogenesis of breast cancers that do not express estrogen receptors or Her-2/neu receptors (ER-/HER2- phenotype) is incompletely understood. We had observed markedly elevated gene expression of gamma-aminobutyric acid type A (GABA(A)) receptor subunit pi (GABApi, GABRP) in some breast cancers with ER-/HER2- phenotype. In this study, transcriptional profiles (TxPs) were obtained from 82 primary invasive breast cancers by oligonucleotide microarrays. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was used to measure GABApi gene expression in a separate cohort of 121 invasive breast cancers. GABApi gene expression values from TxP and RT-PCR were standardized and compared with clinicopathologic characteristics in the 203 patients. GABApi gene expression was increased in 16% of breast cancers (13/82 TxP, 20/ 121 RT-PCR), particularly in breast cancers with ER-/HER2- phenotype (60%), and breast cancers with basal-like genomic profile (60%). The profile of genes coexpressed with GABApi in these tumors was consistent with an immature cell type. In multivariate linear regression analysis, the level of GABApi gene expression was associated with ER-/HER2- phenotype (P < 0.0001), younger age at diagnosis (P = 0.0003), and shorter lifetime duration of breastfeeding (< or = 6 months) in all women (P = 0.017) and specifically in parous women (P = 0.013). GABApi gene expression was also associated with combinations of high grade with ER-/HER2- phenotype (P = 0.002), and with Hispanic ethnicity (P = 0.036). GABApi gene expression is increased in breast cancers of immature (undifferentiated) cell type and is significantly associated with shorter lifetime history of breastfeeding and with high-grade breast cancer in Hispanic women.

Biomarkers, Tumor↗
PubMed2004

Acute effects of monounsaturated fatty acids with and without omega-3 fatty acids on vascular reactivity in individuals with type 2 diabetes.

AIMS/HYPOTHESIS: We examined the acute postprandial effects of meals containing unsaturated fatty acids on flow-mediated dilation (FMD) of the brachial artery and triacylglycerols in individuals with type 2 diabetes. We hypothesised that consumption of omega-3 fatty acids would enhance vascular function. Saturated fat reduces FMD for several hours, but there is inconsistent evidence about whether foods containing unsaturated fats impair FMD acutely. Little is known about the acute effects of omega-3 fatty acids on vascular reactivity. METHODS: We measured FMD before and 4 h after 3 test meals (50 g fat, 2,615 kJ) in 18 healthy adults with type 2 diabetes. The monounsaturated fatty acids (MUFA) meal contained 50 g fat from high oleic safflower and canola oils. Two additional meals were prepared by replacing 7% to 8% of MUFA with docosahexaenoic acid and eicosapentaenoic acid from sardine oil or alpha-linolenic acid from canola oil. RESULTS: In the sample as a whole, FMD was increased 17% at 4 h vs. the fasting baseline. After the MUFA meal, subjects with the largest increases in triacylglycerols had the largest FMD decreases. The opposite pattern was observed after meals containing docosahexaenoic acid and eicosapentaenoic acid or alpha-linolenic acid. In subjects with high fasting triacylglycerols, meals containing 3 to 5 g of omega-3 fatty acids increased FMD by 50% to 80% and MUFA alone had no significant effects on FMD. CONCLUSIONS/INTERPRETATION: Endothelium-dependent vasodilation was not impaired 4 h after meals containing predominantly unsaturated fatty acids. The fatty acid composition of the meal and the metabolic status of the individual determine the vascular effects of a high-fat meal.

Blood Flow Velocity↗
PubMed2004

Biological correlates of day-to-day variation in flow-mediated dilation in individuals with Type 2 diabetes: a study of test-retest reliability.

AIMS/HYPOTHESIS: Dysfunction of the vascular endothelium is commonly observed in Type 2 diabetes, and endothelial function may be an important outcome for clinical trials in diabetic samples. However, the most commonly used non-invasive test of endothelial function (flow-mediated dilation [FMD]) is technically challenging to perform, and no previous studies have carefully examined the reproducibility of FMD measurements in individuals with Type 2 diabetes. In this study, we tested the hypothesis that larger day-to-day changes in insulin and glucose are associated with larger fluctuations in FMD. METHODS: Ultrasound was used to measure the FMD (% change from baseline diameter) of the brachial artery in 18 healthy adults with Type 2 diabetes on three separate occasions, in the absence of changes to diet, activity level or medications. The CV and mean deviations between pairs of FMD scores in the same individual were used as the primary outcome variables. RESULTS: The CV for FMD (29.7%) was higher than the level traditionally accepted for biochemical assays. However, this CV estimate is within the low range of published values for FMD in healthy individuals. FMD scores were not significantly correlated with glucose or insulin levels. However, subjects with the largest variability in FMD also showed the largest fluctuations in glucose ( r=0.52), insulin ( r=0.47) and heart rate ( r=0.48) ( p</=0.05). CONCLUSIONS/INTERPRETATION: FMD can be reliably measured in individuals with Type 2 diabetes, and population-specific data on reliability is critical for the design of adequately powered studies of endothelial function.

Adult↗
PubMed2004

Nuclear stopping from 0.09A to 1.93A GeV and its correlation to flow.

We present a complete systematics (excitation functions and system-size dependences) of global stopping and side flow for heavy ion reactions in the energy range between 0.09A and 1.93A GeV. For the heaviest system, Au+Au, we observe a plateau of maximal stopping extending from about 0.2A to 0.8A GeV with a fast drop on both sides. The degree of stopping, which is shown to remain significantly below the expectations of a full stopping scenario, is found to be highly correlated to the amount of side flow.

Journal Article↗
PubMed2004

Expression of sigma 1 receptor in human breast cancer.

The sigma 1 receptor (S1R) represents a unique drug-binding site that is distinct from any other receptors. We examined S1R expression in human breast cancer and assessed the activity of S1R ligands in breast cancer cell lines. One-hundred nine breast specimens from normal breast, benign breast disease and cancer were examined with immunohistochemistry or RT-PCR and six different cell lines were also evaluated. S1R mRNA overexpression was detected in 64% of breast cancers compared to normal breast tissue. Immunohistochemistry showed positive epithelial cell staining in 60% of invasive and 41% of in situ cancers, 75% of ductal hyperplasia and in 33% of normal breast. The pattern of expression was more diffuse in invasive breast carcinoma compared to other conditions (p = 0.02). S1R expression was neither a prognostic nor a predictive factor for efficacy of adjuvant chemotherapy but the study only included 58 cancer patients and therefore the statistical power is limited. MDA-MB-361, MDA-MB-435, BT20 and MCF7 cells all expressed S1R protein by Western blot. The non-specific S1R ligands haloperidol, reduced haloperidol and progesterone produced a dose-dependent inhibition of the growth at high (>10 microM) concentrations. Reduced haloperidol also showed additive cytotoxic effects when combined with doxorubicin, vinorelbine , paclitaxel and docetaxel in vitro. The S1R-specific ligand, SKF 10047 demonstrated the least growth inhibitory activity and showed no interaction with chemotherapy. These results demonstrate that some normal and most neoplastic breast epithelial cells and cell lines commonly express S1R. High concentrations of haloperidol inhibit the growth of these cells and potentiate the effect of chemotherapy in vitro.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

The TATGARAT box of the HSV-1 ICP27 gene is essential for immediate early expression but not critical for efficient replication in vitro or in vivo.

We constructed a recombinant virus containing a promoter mutation altering the immediate-early expression of the HSV-1 ICP27 transcript, ICP27DeltaSma, which contains a deletion of the "TATGARAT" and surrounding sequences, but retains the rest of the ICP27 promoter. This mutant does not exhibit immediate-early expression of ICP27 using criteria of expression in the absence of de novo protein synthesis and earliest expression in the kinetic cascade. While transcript abundance at 1h after infection at 0.1 PFU/cell in mouse embryo fibroblasts was significantly altered compared to infections with wt -rescues, by 4 h after infection these differences were diminished or absent. Consistent with this observation, levels of some critical proteins were reduced in the mutant as compared to rescue infections at the earliest times tested, but were equivalent by 8-12 h pi. Further, both single and multi-step virus replication was equivalent with both mutants and rescues. Thus, altering the immediate early kinetics of ICP27 leads to a sub-optimal quantitative lag-phase in gene expression but without consequence to replication fitness in vitro . Infections in vivo also revealed the ability of mutant and rescue virus to invade the CNS of mice following footpad injections was equivalent. The nature of the role of immediate-early ICP27 expression is discussed in light of these observations.

Animals↗
PubMed2003

Quantitative assessment to the structural basis of water repellency in natural and technical surfaces.

Many plant surfaces are water-repellent because of a complex 3-dimensional microstructure of the epidermal cells (papillae) and a superimposed layer of hydrophobic wax crystals. Due to its surface tension, water does not spread on such surfaces but forms spherical droplets that lie only on the tips of the microstructures. Studying six species with heavily microstructured surfaces by a new type of confocal light microscopy, the number, height, and average distance of papillae per unit area were measured. These measurements were combined with those of an atomic force microscope which was used to measure the exposed area of the fine-structure on individual papillae. According to calculations based upon these measurements, roughening results in a reduction of the contact area of more than 95% compared with the projected area of a water droplet. By applying water/methanol solutions of decreasing surface tension to a selection of 33 water-repellent species showing different types of surface structures, the critical value at which wetting occurs was determined. The results impressively demonstrated the importance of roughening on different length scales for water-repellency, since extremely papillose surfaces, having an additional wax layer, are able to resist up to 70% methanol. Surfaces that lack papillae or similar structures on the same length scale are much more easily wetted.

Cell Surface Extensions↗
PubMed2002

[Intracanalicular trabeculostomy with the Er:YAG laser].

PURPOSE: To develop a new ab externo technique for glaucoma trabecular surgery using the infrared Er:YAG laser radiation (2.9 micrometer) guided into Schlemm's canal by an optical fiber. MATERIAL AND METHODS: In order to create a drainage canal to the anterior chamber, a quartz fiber (core diameter: 100 micrometer) coupled to an Er:YAG laser was shielded by a metal canula (diameter: 280 micrometer) bent in conformance to the curvature of Schlemm's canal. A 45 degrees -mirror enabled the laser radiation to exit the canula perpendicular to the fiber axis. The complete surgery device was tested on agar medium and enucleated human eyes. RESULTS: Using the unshielded quartz fiber, eight pulses of 8 mJ (frequency: 7 Hz, pulse duration: 150 microseconds) were sufficient to perforate the trabecular meshwork of the human eye. Histology showed a rippled canal with 50 micrometer average diameter and a surrounding necrosis zone of 15-35 micrometer. The complete device could be easily inserted into Schlemm's canal similar to the classic trabeculostomy probe and a conical-shaped canal with a length of 2-3 mm could be created in agar medium within a few seconds. CONCLUSIONS: Initial experience in an experimental set-up show the ab externo creation of a draining canal between Schlemm's canal and the anterior chamber with only minimal irritation of the surrounding tissue. Further refinements of the laser parameters and the biomechanical set-up resulted in a new hand-held device with improved function. The Er:YAG laser intracanalicular trabeculostomy could become a new ab externo technique for minimal invasive therapy of open angle glaucoma.

Equipment Design↗
PubMed2002

[Sedation analgesia in interventional radiology].

PURPOSE: Development of a save and effective protocol for analgosedation of patients undergoing painful interventional procedures. MATERIAL AND METHODS: In a prospective trial a consecutive series of 72 adult patients underwent analgosedation during painful interventions. A radiologist performed the analgosedation, the patients received a combination of a shortly effective piperidine derivative (Alfentanil [Rapifen(R)]; 7.5 - 15 microgram/kg body weight) and Benzodiazepine (midazolam [Dormicum(R)]; 20 microgram/kg body weight). After pre-procedure oxygenation patients were continuously monitored. Pain and discomfort were scored using an established visual-analog pain score (0 - 10). A control group (n = 24) had received midazolam, pentazocine or fentanyl according to the study protocol. RESULTS: All procedures could be carried out by an interventional radiologist and a nurse and/or technologist only. In 69/72 cases adequate analgosedation could be achieved. Injection of alfentanil was titrated, with a rapid onset and short acting effect of the analgesia. Patients reported an average pain score of 2.6 vs. 4.5 in the control group. Over 55 % experienced no or mild pain (score 0 - 3), in the control group only 8 % reached this level. CONCLUSION: A combination of shortly effective alfentanil and midazolam allows interventional radiologists to perform major procedures alone under effective analgosedation. This medication scheme is superior to the medication upon demand.

Adjuvants, Anesthesia↗
PubMed2001

Headways in traffic flow: remarks from a physical perspective.

Traffic flow can be understood as a realization of a broad class of one dimensional physical systems, where a hard core repulsive interaction competes with a longer ranged attraction between the particles. It can be shown rigorously that the statistical properties of such systems in thermal equilibrium are well described by a family of distributions that stems from the random matrix theory. Analyzing the traffic data from different sources, we show that traffic on real roads belongs to that class of random matrix distributions. Also, various traffic simulation models show a similar behavior. It is demonstrated in such a way that the headway distribution of a highway traffic, that serves usually as a paradigm of systems driven far from equilibrium, is reasonably well described by a distribution originating from equilibrium statistical physics.

Journal Article↗