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Biomedical subjects

M Wendt

Publications and source records attributed to M Wendt.

At least 19 recordsLinked to original sources
PubMed2006

Metronidazole improves intestinal microcirculation in septic rats independently of bacterial burden.

To explore the effects of metronidazole (Me) on intestinal microcirculation in septic rats, intravital microscopy (IVM) following 16 hours of colon ascendens stent peritonitis (CASP model) was used. Four groups of animals were studied: control group (sham operation) and CASP group, each with and without Me treatment (10 mg/kg i.v.). In order to investigate the substance-specific effects of Me independently of the antibacterial effects within a pathologically altered microcirculation, a second experimental series with lipopolysaccharide challenge (LPS model) was carried out. The LPS model consisted of the four groups (control animals and LPS animals (15 mg/kg i.v. LPS from E. coli) with and without Me). IVM in the LPS experiments was performed following a two hour observation period. Me treated CASP or LPS animals, as compared with untreated, demonstrated significant improvement of functional capillary density (FCD) of the intestinal wall. The increase in the number of leukocytes firmly adhered to the endothelium (leukocyte sticking) in the untreated CASP or LPS animals within the V1 venules of the intestinal submucosal layer, was significantly reduced in the Me treated animals. In conclusion, Me exerts beneficial anti-bacterial and anti-inflammatory effects within the septic microcirculation.

Animals↗
PubMed2004

[PercuTwist dilational tracheostomy. Prospective evaluation of 54 consecutive patients].

BACKGROUND: Percutaneous dilational tracheostomy (PDT) is considered to be an accepted method in intensive care patients. In 2002 Frova and Quintel described a method of dilation that employed controlled rotation of the PercuTwist dilational device. The goal of the present study was to evaluate the new technique employed by an experienced team. PATIENTS AND METHODS: Prospective, observational clinical study in 54 intensive care patients who required PDT. All tracheostomies were accompanied by bronchoscopic control. Vital parameters and perioperative complications were registered. RESULTS: In all 54 consecutive PercuTwist tracheostomies no severe complications were noted. Accidental tracheal ring fracture was noted in 7 patients while bleeding that needed surgical care occurred in 1 patient. CONCLUSION: The PercuTwist tracheostomy is a safe procedure for intensive care patients. More prospective studies that would compare the PercuTwist tracheostomy with the other PDT methods are necessary.

APACHE↗
PubMed2004

[The prevalence of Actinobaculum suis in boars of breeding herds in the Omsk region (Russian Federation) by indirect immunofluorescence technique].

Actinobaculum suis (Corynebacterium suis, Eubacterium suis, Actinomyces suis) was detected in the preputial diverticulum of 64,8% of 162 boars investigated in 8 districts of the region Omsk (Russian Federation) by indirect immunofluorescent technique. Until yet no informations were available about the prevalence of Actinobaculum (A.) suis in swine herds of the Russian Federation. The study shows that A. suis, as a main aetiological factor of cystitis and pyelonephritis in sows, is widely spread among the boars of the region Omsk. Prevalence of A. suis was not influenced by housing conditions, age or breed of investigated boars. Indirect immunofluorescent technique for detection of A. suis provides a good method for screening investigations with high numbers of samples.

Actinomyces↗
PubMed2004

[Establishment of an immunological labelling of pigs using synthetic peptides].

The objective of this study was to develop a suitable combination consisting of synthetic peptides, carrier protein and adjuvant for immunological labelling of pigs. Specific antibody titres were evaluated by ELISA technique. From 9 peptides 4 were excluded from following investigations showing cross reactivity or low immunogenic effects, sufficient anti-peptide titres were achieved by 5 peptides. Labelling control is possible after 7 days at the earliest and can be used for the whole fattening period after single immunization using an effective carrier-adjuvant-combination. Mixing of peptides in one labelling dose had no negative influence on titres against single peptides. Different combinations of 4 carriers (keyhole limpet haemocyanin (KLH), palmitic-acid-3-cystein-acid (Pam3Cys), palmitic acid (Pam) and dextran) and 4 adjuvants (Montanide IMS 1313, Montanide ISA 25, Quil A and Diluvac forte) were tested. Optimal labelling could be seen by combination of 50 nmol peptide, KLH as carrier and Montanide IMS 1313 as adjuvant. Generally after booster injection titres were higher, however, a booster dose was not necessary using most effective adjuvants. A less immunogenic, but cost effective alternative for short time labelling (7 weeks) was a peptide-Pam3Cys-conjugate (75 nmol) combined with Quil A as an adjuvant (2 mg/ml). Immunological labelling of pigs is recommended as a good method for tracing back the origin of animals and meat products. It may be also used for vaccine labelling to prove vaccination of pigs.

Adjuvants, Immunologic↗
PubMed2003

Detection of antibodies in sera of weaned pigs after contact infection with Sarcoptes scabiei var. suis and after treatment with an antiparasitic agent by three different indirect ELISAs.

Three commercial enzyme-linked immunosorbent assays (ELISAs) were compared for the detection of antibodies to Sarcoptes scabiei var. suis using experimental sera of six 8-week-old pigs after contact infection with Sarcoptes scabiei var. suis. Six non-infected pigs were monitored as a control group. Blood sera were taken once a week from all animals. After successful infection the pigs were treated with an antiparasitic agent (12 weeks post infection (p.i.)) and the antibody titres were monitored until they were negative. The antibody levels of the experimental pigs reached the cut-off level 5 weeks after introduction of an infected animal to the group and were positive by both the Sarcoptes-ELISA 2001 PIG and the Acar-Test P-ELISA. Four weeks after treatment mean results showed optical densities (% OD) below the cut-off level in the Sarcoptes-ELISA 2001 and 8 weeks after treatment in the Acar-Test P-ELISA. In the Chekit Sarcoptest pigs had elevated antibody levels in comparison to control animals, but ODs remained below the given cut-off level at all times. In a second examination with Chekit Sarcoptest (different lot) and at a lower cut-off level, the sera of most of the piglets tested positive. Eight weeks after treatment, four from six pigs still had positive OD values. Therefore this investigation showed a higher sensitivity for the Sarcoptes-ELISA 2001 and the Acar-Test P-ELISA than for the Chekit Sarcoptest. Different test sensitivities must be considered when serologic methods are used for the diagnosis of swine sarcoptic mange, especially for monitoring and controlling eradication programs.

Animals↗
PubMed2003

[A head-mounted display system for augmented reality: initial evaluation for interventional MRI].

PURPOSE: To discuss the technical details of a head mounted display with an augmented reality (AR) system and to describe a first pre-clinical evaluation in interventional MRI. METHOD: The AR system consists of a video-see-through head mounted display (HMD), mounted with a mini video camera for tracking and a stereo pair of mini cameras that capture live images of the scene. The live video view of the phantom/patient is augmented with graphical representations of anatomical structures from MRI image data and is displayed on the HMD. The application of the AR system with interventional MRI was tested using a MRI data set of the head and a head phantom. RESULTS: The HMD enables the user to move around and observe the scene dynamically from various viewpoints. Within a short time the natural hand-eye coordination can easily be adapted to the slightly different view. The 3D perception is based on stereo and kinetic depth cues. A circular target with a diameter of 0.5 square centimeter was hit in 19 of 20 attempts. In a first evaluation the MRI image data augmented reality scene of a head phantom allowed good planning and precise simulation of a puncture. CONCLUSION: The HMD in combination with AR provides a direct, intuitive guidance for interventional MR procedures.

Computer Graphics↗
PubMed2002

Generation of GW radiation pulses from a VUV free-electron laser operating in the femtosecond regime.

Experimental results are presented from vacuum-ultraviolet free-electron laser (FEL) operating in the self-amplified spontaneous emission (SASE) mode. The generation of ultrashort radiation pulses became possible due to specific tailoring of the bunch charge distribution. A complete characterization of the linear and nonlinear modes of the SASE FEL operation was performed. At saturation the FEL produces ultrashort pulses (30-100 fs FWHM) with a peak radiation power in the GW level and with full transverse coherence. The wavelength was tuned in the range of 95-105 nm.

Journal Article↗
PubMed2002

Microscopic and ultrastructural lesions of the ureter and renal pelvis in sows with regard to Actinobaculum suis infection.

Tissues from ureter and renal pelvis of 18 sows naturally (n = 15) and experimentally (n = 3) infected with Actinobaculum suis (former Actinomyces, Eubacterium suis) were studied using light and scanning as well as transmission electron microscopy. The results were compared with the findings from 11 clinically healthy sows as controls. The lesions in both the ureter and renal pelvis of naturally and experimentally infected animals were similar. In severe cases there were necrotizing ureteritis and pyelitis with accumulation of bacterial colonies in some cases. Several superficial epithelial cells were found phagocytosing necrotic debris. In mild cases the main lesions included epithelial cell hyperplasia, desquamation of the superficial epithelial cells and goblet cell metaplasia with intraepithelial cyst formation. The goblet cells were found in the superficial as well as in the intermediate cell layers. Generally, it was observed that severe purulent ureteritis and pyelitis/ pyelonephritis in sows were to be expected only in mixed infection of A. suis with other bacteria. The findings were compared and discussed with the changes in the infected urinary bladder of sows and the alterations induced by urinary tract infection in man.

Actinomyces↗
PubMed2001

Species specificity of amidine-based urokinase inhibitors.

Inhibition of the proteolytic activity of urokinase has been shown to inhibit the progression of tumors in rodent models and is being investigated for use in human disease. Understanding the rodent/human species-specificity of urokinase inhibitors is therefore critical for interpretation of rodent cancer progression models that use these inhibitors. We report here studies with a panel of 11 diverse urokinase inhibitors in both human and mouse enzymatic assays. Inhibitors such as amiloride, B428, and naphthamidine, that occupy only the S1 subsite pocket were found to be nearly equipotent between the human and the murine enzymes. Inhibitors that access additional, more distal, pockets were significantly more potent against the human enzyme but there was no corresponding potency increase against the murine enzyme. X-ray crystallographic structures of these compounds bound to the serine protease domain of human urokinase were solved and examined in order to explain the human/mouse potency differences. The differences in inhibitor potency could be attributed to four amino acid residues that differ between murine and human urokinases: 60, 99, 146, and 192. These residues are Asp, His, Ser, and Gln in human and Gln, Tyr, Glu, and Lys in mouse, respectively. Compounds bearing a cationic group that interacts with residue 60 will preferentially bind to the human enzyme because of favorable electrostatic interactions. The hydrogen bonding to residue 192 and steric considerations with residues 99 and 146 also contribute to the species specificity. The nonparallel human/mouse enzyme inhibition observations were extended to a cell-culture assay of urokinase-activated plasminogen-mediated fibronectin degradation with analogous results. These studies will aid the interpretation of in vivo evaluation of urokinase inhibitors.

Amidines↗
PubMed2001

Radial keyhole sequences for low field projection reconstruction interventional MRI.

Interventional magnetic resonance imaging (IMRI) is a rapidly emerging application for MRI in which diagnostic and therapeutic procedures are performed with MR image guidance. Real-time or near-real-time image acquisition and relative insensitivity to motion are essential for most intraoperative, therapeutic, and diagnostic procedures performed under MR guidance. The purpose of this work was to demonstrate the development and utility of two alternative rapid acquisition strategies during IMRI that are analogous to computed tomography fluoroscopy or keyhole MRI in a radial rather than rectilinear coordinate frame. The two strategies discussed here, interleaved projection reconstruction and continuous projection reconstruction, are compared and the feasibility of their application in experimental interventional applications is studied. J. Magn. Reson. Imaging 2001;13:142-151.

Animals↗
PubMed2001

Two-step navigatorless correction algorithm for radial k-space MRI acquisitions.

A new way to correct magnetic resonance image artifacts resulting from view-dependent phase variations and view-dependent variations in rigid body object translation is presented by exploiting basic properties of the trajectory of radial k-space acquisitions. Simulations, phantom studies, and in vivo experiments are used to demonstrate the feasibility and the utility of this method. While somewhat analogous to navigator echo correction, in which special gradients are interleaved into the imaging sequence so echoes at the center of k-space can be acquired prior to or after collection of the image data, the current method does not require additional new gradient structures within the pulse sequence or increases in scan time. The new method uses the phase information from all collected radial k-space data points rather than only the navigator echo, which permits correction of multiple sources of view-dependent phase variation in the image data. The resultant effect is improved image quality in radial MRI acquisitions. Magn Reson Med 45:277-288, 2001.

Algorithms↗
PubMed2001

A multielement RF coil for MRI guidance of interventional devices.

Accurate localization of minimally invasive devices is critical to the success of interventional procedures. Device orientation and tip position are two of the most important pieces of information needed to define device location for magnetic resonance imaging (MRI)-guided interventional procedures. While a single one-element micro coil incorporated into an interventional device has proven to be effective in some applications, it can only supply tip position information. However, multiple positions on the device are necessary to also determine its orientation. For this purpose, a novel single micro coil design with three separate winding elements that provides both the device orientation and tip position is described in this study. Definition of MR scan planes, by using the device orientation and the target tissue location, permits automatic tracking of the insertion of the device. Furthermore, devices that include this coil design are permitted to bend to a limited extent. This makes the micro coil design appropriate for many flexible interventional devices. Reliable near-real-time tracking of three points on an interventional device is demonstrated on a 0.2T MRI system with modest gradient performance. Phantom and in vivo animal experiments are used to demonstrate the utility of this new coil design.

Animals↗
PubMed2001

A method for fast 3D tracking using tuned fiducial markers and a limited projection reconstruction FISP (LPR-FISP) sequence.

This work demonstrates the feasibility of using wireless, tuned fiducial markers with a limited projection reconstruction-fast imaging with steady-state free precession sequence (LPR-FISP) to accurately obtain tracking information necessary for interactive scan plane selection in magnetic resonance imaging (MRI). The position and orientation of a rigid interventional device can be uniquely determined from the 3D coordinates of three fiducial markers mounted in a known configuration on the device. Three fiducial markers were tuned to the proton resonant frequency in a 0.2T open MR scanner and mounted to the surface of a cylindrical water phantom. An LPR-FISP sequence was developed to suppress the water phantom signal while preserving that of the fiducial markers through a nonselective low-tip-angle excitation and a dephaser gradient applied prior to data acquisition. A localization algorithm was developed to accurately calculate the 3D coordinates of the fiducial markers using four LPR-FISP projections in two orthogonal scan planes. The sequence repetition time (TR = 21 msec) and the limited projection set resulted in fast LPR-FISP coordinate acquisition times of approximately 170 msec with an accuracy (max error) of 3 mm on a 0.2T MR system. This fast, accurate tracking method provides the fundamental technology for interactive MRI scan plane definition for rigid interventional devices without the need for stereotactic cameras or reference frames.

Algorithms↗
PubMed2001

Antioxidants and endothelial dysfunction in hyperlipidemia.

Endothelial function is abnormal in a variety of diseased states such as hypercholesterolemia and atherosclerosis. This may be secondary to decreased synthesis of nitric oxide (NO) and/or increased degradation of NO due to interaction with superoxide anions. More recent experimental observations demonstrate increased production of superoxide in hyperlipidemia, suggesting that endothelial dysfunction in these states is in part secondary to increased NO metabolism. Enzymes proposed to be involved in increased superoxide production may include xanthine oxidase, the NO synthase, and the NAD(P)H oxidase. Superoxide rapidly reacts with NO to form peroxynitrite (ONOO-), a highly reactive intermediate with cytotoxic properties. Despite experimental evidence for the oxidative stress concept in causing endothelial dysfunction, the results of recent randomized trials to test the influence of antioxidants on coronary event rates and prognosis in patients with coronary artery disease were very disappointing. In all of these studies the use of vitamins such as vitamin E failed to improve the prognosis. In contrast, treatment with angiotensin converting enzyme inhibitors or cholesterol- lowering drugs improved endothelial dysfunction, prevented the activation of superoxide-producing enzymes in cholesterol-fed animals, reduced coronary event rates, and improved prognosis in patients with coronary artery disease. Therefore, inhibition of superoxide production at the enzymatic level rather than symptomatic superoxide scavenging may be the better choice of treatment.

Animals↗
PubMed2001

[Comparison of susceptibility artefacts of different radiofrequency electrodes at O.2 T. Influence of electrode positioning, pulse sequence and image reconstruction methods].

PURPOSE: Interventional MRI procedure monitoring requires small but accurate susceptibility artifacts of the instruments used. In this investigation, susceptibility artifacts of different RF-electrode designs were compared using a variety of pulse sequences and k-space acquisition methods. METHODS: 4 different 18-gauge RF-electrodes (with three single electrodes made of stainless steel, copper, inconal, and a triple-clustered electrode configuration made of inconal) were placed in a 0.2 T MR-scanner perpendicular to the main magnetic field. Pulse sequences used included: TSE T2, FISP, true-FISP, PSIF, and a temperature sensitive ES-GRE sequence. In addition to the 2D Cartesian k-space trajectory with Fourier transformation (2DFT), projection reconstruction (PR) was used with the FISP, true-FISP and PSIF sequences. RESULTS: The best tip accuracy was achieved with the combination of inconal electrodes and TSE T2. The usefulness of the tested sequences was found to be: TSE T2 > PSIF > FISP/true-FISP > ES-GRE. In general 2DFT provided better or equal tip accuracy than PR. The apparent shaft width was smaller using the copper electrode compared to the inconal electrode. However, the "match shaped" tip artifact of the copper probe led to a higher error in tip accuracy. CONCLUSIONS: TSE-T2 sequences and Cartesian 2DFT acquisitions should be used for accurate tip positioning at 0.2 T. Further, artifact size of the electrode shaft prevents the use of inconal for temperature sensitive sequences. Copper electrodes can be used for these purposes, although copper is not considered to be biocompatible at present.

Artifacts↗
PubMed2001

A rapid look-up table method for reconstructing MR images from arbitrary K-space trajectories.

Look-up tables (LUTs) are a common method for increasing the speed of many algorithms. Their use can be extended to the reconstruction of nonuniformly sampled k-space data using either a discrete Fourier transform (DFT) algorithm or a convolution-based gridding algorithm. A table for the DFT would be precalculated arrays of weights describing how each data point affects all of image space. A table for a convolution-based gridding operation would be a precalculated table of weights describing how each data point affects a small k-space neighborhood. These LUT methods were implemented in C++ on a modest personal computer system; they allowed a radial k-space acquisition sequence, consisting of 180 views of 256 points each, to be gridded in 36.2 ms, or, in approximately 800 ns/point. By comparison, a similar implementation of the gridding operation, without LUTs, required 45 times longer (1639.2 ms) to grid the same data. This was possible even while using a 4 x 4 Kaiser-Bessel convolution kernel, which is larger than typically used. These table-based computations will allow real time reconstruction in the future and can currently be run concurrently with the acquisition allowing for completely real-time gridding.

Algorithms↗
PubMed2000

Structure-directed discovery of potent non-peptidic inhibitors of human urokinase that access a novel binding subsite.

BACKGROUND: Human urokinase-type plasminogen activator has been implicated in the regulation and control of basement membrane and interstitial protein degradation. Because of its role in tissue remodeling, urokinase is a central player in the disease progression of cancer, making it an attractive target for design of an anticancer clinical agent: Few urokinase inhibitors have been described, which suggests that discovery of such a compound is in the early stages. Towards integrating structural data into this process, a new human urokinase crystal form amenable to structure-based drug design has been used to discover potent urokinase inhibitors. RESULTS: On the basis of crystallographic data, 2-naphthamidine was chosen as the lead scaffold for structure-directed optimization. This co-crystal structure shows the compound binding at the primary specificity pocket of the trypsin-like protease and at a novel binding subsite that is accessible from the 8-position of 2-napthamidine. This novel subsite was characterized and used to design two compounds with very different 8-substituents that inhibit urokinase with K(i) values of 30-40 nM. CONCLUSIONS: Utilization of a novel subsite yielded two potent urokinase inhibitors even though this site has not been widely used in inhibitor optimization with other trypsin-like proteases, such as those reported for thrombin or factor Xa. The extensive binding pockets present at the substrate-binding groove of these other proteins are blocked by unique insertion loops in urokinase, thus necessitating the utilization of additional binding subsites. Successful implementation of this strategy and characterization of the novel site provides a significant step towards the discovery of an anticancer clinical agent.

Binding Sites↗