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Biomedical subjects

A Bender

Publications and source records attributed to A Bender.

At least 19 recordsLinked to original sources

In vivo glenohumeral contact forces--measurements in the first patient 7 months postoperatively.

Knowledge of forces in the glenohumeral joint is essential for understanding normal and pathologic shoulder function. It forms the basis for performing fracture treatment or joint replacement surgery, for optimizing implant design and fixation and for improving and verifying analytical biomechanical models of the shoulder. An instrumented shoulder implant with telemetric data transmission was developed to measure six components of joint contact forces and moments. A patient with humeral head arthrosis achieved good joint function after its implantation. During the first 7 postoperative months, the contact force remained below 100% BW (percent body weight) for most activities of daily living. It ranged up to 130% BW for arm positions close to the limits of motion or when acting against external resistance. When the patient tried to turn a blocked steering wheel with maximum effort, the force rose to about 150% BW, the highest level observed thus far. Of great interest were the force directions relative to the humerus, especially those in the sagittal plane, which were not greatly influenced by the type of exercise, the arm position or the external resistance. The moments due to friction in the joint reached 5.2 Nm. The friction-induced shift of contact forces relative to the implant head centre ranged up to 6.3mm. These first worldwide in vivo measurements of glenohumeral contact forces are being continued in more patients and for longer postoperative times.

Follow-Up Studies↗

Creatine supplementation in Parkinson disease: a placebo-controlled randomized pilot trial.

Mitochondrial dysfunction plays a major role in the pathogenesis of Parkinson disease (PD). Creatine (Cr) is an ergogenic compound that exerts neuroprotective effects in animal models of PD. We conducted a 2-year placebo-controlled randomized clinical trial on the effect of Cr in 60 patients with PD. Cr improved patient mood and led to a smaller dose increase of dopaminergic therapy but had no effect on overall Unified Parkinson's Disease Rating Scale scores or dopamine transporter SPECT.

Administration, Oral↗

Diversity oriented synthesis: a challenge for synthetic chemists.

This article covers the diversity-oriented synthesis (DOS) of small molecules in order to generate a collection of pure compounds that are attractive for lead generation in a phenotypic, high-throughput screening approach useful for chemical genetics and drug discovery programmes. Nature synthesizes a rich structural diversity of small molecules, however, unfortunately, there are some disadvantages with using natural product sources for diverse small-molecule discovery. Nevertheless we have a lot to learn from nature. The efficient chemical synthesis of structural diversity (and complexity) is the aim of DOS. Highlights of this article include a discussion of nature's and synthetic chemists' strategies to obtain structural diversity and an analysis of molecular descriptors used to classify compounds. The assessment of how successful one diversity-oriented synthesis is vs another is subjective; therefore we use freely available software (www.cheminformatics.org/diversity) to assess structural diversity in any combinatorial synthesis.

Chemistry, Pharmaceutical↗

Acetic acid-guided biopsies after magnifying endoscopy compared with random biopsies in the detection of Barrett's esophagus: a prospective randomized trial with crossover design.

BACKGROUND: In contrast to standard video endoscopy, magnifying endoscopy after local acetic acid application enables recognition of mucosal surface architecture. OBJECTIVE: To investigate the diagnostic yield of magnifying endoscopy with acetic acid-targeted biopsies compared to random, 4-quadrant biopsies. DESIGN: Prospective randomized trial (ratio 1:1) with crossover design. SETTING: Two referral hospitals in Germany. PATIENTS: Thirty-one patients with Barrett's esophagus or visible columnar-lined lower esophagus. INTERVENTIONS: Patients were randomized to undergo either standard video endoscopy with 4-quadrant biopsies or magnifying endoscopy in conjunction with acetic acid application. All patients were re-examined 14 days after the initial endoscopy with the corresponding procedure. MAIN OUTCOME MEASUREMENTS: Primary outcome analysis (per protocol and per biopsy) was the histological proof of Barrett's epithelium. Secondary outcome analysis was the correlation between the surface architecture and the presence of Barrett's epithelium and the needed number of biopsies to confirm Barrett's epithelium for the 2 different procedures. RESULTS: Magnifying endoscopy enabled the prediction of Barrett's epithelium with a sensitivity of 100% and a specificity of 66%, respectively (accuracy 83.8%). Acetic acid-guided biopsies obtained a significantly higher percentage of tissues containing SCE (78%; 188/241) compared to random biopsies (57%; 159/280). LIMITATIONS: No data on the diagnosis of Barrett's dysplasia. CONCLUSION: Magnifying endoscopy with acetic acid-guided biopsies is superior to standard video endoscopy with random biopsies, and the number of biopsies needed to confirm Barrett's epithelium is half as much when compared to random biopsies.

Acetic Acid↗

Severe tick borne encephalitis with simultaneous brain stem, bithalamic, and spinal cord involvement documented by MRI.

A case of tick borne encephalitis (TBE) is reported, with simultaneous brain stem, spinal cord, and bilateral thalamic involvement confirmed by magnetic resonance imaging (MRI). After exposure to a TBE endemic region, the patient developed a biphasic clinical course with initial flu-like symptoms followed by a severe brain stem syndrome. The diagnosis of TBE was confirmed serologically. Repeated MRI scans showed brain stem, bithalamic, and spinal cord involvement. The outcome was favourable. TBE cases with concomitant myelitis tend to have a more severe clinical course and more likelihood of needing intensive care support. They should therefore be identified early in order to be prepared for life threatening respiratory complications.

Adult↗

Changes in cognitive function after neuronal cell transplantation for basal ganglia stroke.

Reported is the change in cognitive function after neuronal cell transplantation as a treatment for basal ganglia stroke. Nine subjects (two controls, seven transplants), all over 2 years post stroke, completed a comprehensive neuropsychological test battery prior to and 6 months after treatment. Four transplanted subjects who had strokes in the nondominant hemisphere showed marked improvement on the Rey Complex Figure, a test of visuospatial/constructional ability and nonverbal memory.

Aged↗

Sensitivity enhancement in pulse EPR distance measurements.

Established pulse EPR approaches to the measurement of small dipole-dipole couplings between electron spins rely on constant-time echo experiments to separate relaxational contributions from dipolar time evolution. This requires a compromise between sensitivity and resolution to be made prior to the measurement, so that optimum data are only obtained if the magnitude of the dipole-dipole coupling is known beforehand to a good approximation. Moreover, the whole dipolar evolution function is measured with relatively low sensitivity. These problems are overcome by a variable-time experiment that achieves suppression of the relaxation contribution by reference deconvolution. Theoretical and experimental results show that this approach leads to significant sensitivity improvements for typical systems and experimental conditions. Further sensitivity improvements or, equivalently, an extension of the accessible distance range can be obtained by matrix deuteration or digital long-pass filtering of the time-domain data. Advantages and limitations of the new variable-time experiment are discussed by comparing it to the established analogous constant-time experiment for measurements of end-to-end distances of 5 and 7.5 nm on rod-like shape-persistent biradicals and for the measurement of a broadly distributed transmembrane distance in a doubly spin-labeled mutant of plant light harvesting complex II.

Algorithms↗

Adult-onset Leukoencephalopathy with vanishing white matter presenting with dementia.

We report on a case of dementia and extensive cerebral white matter abnormalities seen on magnetic resonance-images which meet the criteria for leukoencephalopathy with vanishing white matter. This is an inherited condition that was first thought to occur only in children. Our patient shows that vanishing white matter should be considered in adult patients with early-onset dementia and extensive white matter changes seen on magnetic resonance images.

Adult↗

Treatment of a cavernous sinus dural arteriovenous fistula by deep orbital puncture of the superior ophthalmic vein.

In a patient with progressive ophthalmological problems, including uncontrolled intraocular pressure related to a cavernous sinus dural arteriovenous fistula, urgent intervention may be necessary to prevent permanent visual loss. We report a case in which inadequate transarterial embolisation and lack of access for transvenous catheterisation, including a direct approach through the superior ophthalmic vein, preceded percutaneous puncture of the superior ophthalmic vein deep within the orbit, permitting venous occlusion without complications. This case demonstrates that deep orbital puncture of the vein is feasible for occlusion of a cavernous sinus dural arteriovenous fistula.

Arteriovenous Fistula↗

Colonic fermentation as affected by antibiotics and acidic pH: Application of an in vitro model.

Antimicrobial substances such as vancomycin or metronidazole suppress normal gut flora, thereby preventing physiological fermentation of colonic substrates that may promote mucosal inflammation. This study was designed to establish an in vitro model of microbial metabolism in the colon under control and disturbed conditions (acidic pH) to investigate specific effects of vancomycin and metronidazole on the production of short chain fatty acids (SCFA), which play a pivotal role in maintaining homeostasis in the colon. The experiments were carried out with the colon simulation technique (Cositec) representing an in vitro model for the semi-continuous incubation of defined colon contents. Inocula and fermentable substrates were sampled from cecal contents of fistulated pigs. Disturbed microbial metabolism was generated by reduction of pH in the fermentation vessels from 6.7 to 5.8 and 5.1. In general, application of either vancomycin or metronidazole resulted in a significant decrease of SCFA production rates indicating substantial disturbance of the homeostasis of microbial metabolism. With low doses of vancomycin acetate and butyrate production rates were reduced and with high doses of the antibiotic propionate production was inhibited to a greater extent. Treatment with metronidazole inhibited butyrate production almost completely. Similarly, low pH caused a reduction in total SCFA production, which was mainly due to respective decrease of acetate synthesis. Metronidazole effects were not consistently changed at low pH. The Cositec system provides an excellent facility to test the effects of different antibiotics under defined conditions. In this study, both vancomycin and metronidazole affected microbial metabolism to a considerable extent. Both substances may thus be responsible for disturbances of colon function in vivo.

Acid-Base Equilibrium↗

Efficient expression of the tumor-associated antigen MAGE-3 in human dendritic cells, using an avian influenza virus vector.

Dendritic cells (DCs) are the most potent inducers of immune reactions. Genetically modified DCs, which express tumor-associated antigens (TAA), can efficiently induce antitumor immunity and thus have a high potential as tools in cancer therapy. The gene delivery is most efficiently achieved by viral vectors. Here, we explored the capacity of influenza virus vectors to transduce TAA genes. These viruses abortively infect DCs without interfering with their antigen-presenting capacity. In contrast to other viruses used for DC transduction, influenza viruses can be efficiently controlled by antiviral pharmaceuticals, lack the ability to integrate into host chromosomes, and fail to establish persistent infections. Genes encoding a melanoma-derived TAA (MAGE-3), or the green fluorescence protein (GFP), were introduced into a high-expression avian influenza virus vector. Monocyte-derived mature DCs infected by these recombinants efficiently produced GFP or MAGE-3. More than 90% of the infected DCs can express a transduced gene. Importantly, these transduced DCs retained their characteristic phenotype and their potent allogeneic T cell stimulatory capacity, and were able to stimulate MAGE-3-specific CD8(+) cytotoxic T cells. Thus influenza virus vectors provide a highly efficient gene delivery system in order to transduce human DCs with TAA, which consequently stimulate TAA-specific T cells.

Animals↗

Mage-3 and influenza-matrix peptide-specific cytotoxic T cells are inducible in terminal stage HLA-A2.1+ melanoma patients by mature monocyte-derived dendritic cells.

Dendritic cell (DC) vaccination, albeit still in an early stage, is a promising strategy to induce immunity to cancer. We explored whether DC can expand Ag-specific CD8+ T cells even in far-advanced stage IV melanoma patients. We found that three to five biweekly vaccinations of mature, monocyte-derived DC (three vaccinations of 6 x 106 s.c. followed by two i.v. ones of 6 and 12 x 106, respectively) pulsed with Mage-3A2.1 tumor and influenza matrix A2. 1-positive control peptides as well as the recall Ag tetanus toxoid (in three of eight patients) generated in all eight patients Ag-specific effector CD8+ T cells that were detectable in blood directly ex vivo. This is the first time that active, melanoma peptide-specific, IFN-gamma-producing, effector CD8+ T cells have been reliably observed in patients vaccinated with melanoma Ags. Therefore, our DC vaccination strategy performs an adjuvant role and encourages further optimization of this new immunization approach.

Antigens, Neoplasm↗

Tissue transition projection (TTP) of the intestines.

Tissue transition projection (TTP) represents a three-dimensional reconstruction technique for volumetric image data sets. To demonstrate the principle characteristics of TTP, a simple phantom consisting of two pipes with a simulated, wall-adherent polyp was scanned with spiral CT, and images were reconstructed by means of volume rendering for both opaque surface reconstructions and TTP. Tissue transition projection was used in 7 patients for reconstruction of the small intestine or the colon. Unlike three-dimensional reconstructions with opaque surfaces, TTP enhances surface transitions while suppressing homogeneous areas, allowing delineation of the bowel wall similar to conventional double-contrast studies.

Adenocarcinoma↗

Transvenous occlusion of dural cavernous sinus fistulas through the thrombosed inferior petrosal sinus: report of four cases and review of the literature.

BACKGROUND: The aim of this study is to describe the technique and results of the endovascular approach through the thrombosed inferior petrosal sinus (IPS) for occlusion of dural cavernous sinus fistulas (DCSFs). METHODS: In four patients presenting with clinically symptomatic DCSFs, the angiogram did not show opacification of the IPS, indicating that it neither drained the arteriovenous fistula nor the cerebral venous outflow. A large volume biplane phlebogram of the jugular bulb was obtained to identify a thrombosed remnant of the IPS. We were able to navigate small hydrophilic catheters and microguide wires through the thrombosed IPS into the ipsi- or contralateral CS. After reaching the fistula site the CS was packed with detachable platinum coils. RESULTS: We were able to reach the fistula site and to achieve a dense packing of coils within the arteriovenous shunting zone in all of the patients. The final angiogram showed subtotal or complete occlusion of the arteriovenous fistula. All four patients recovered completely and showed disappearance of the fistula on follow-up arteriograms. One patient developed a transient sixth nerve palsy. No complications related to the approach were observed. CONCLUSIONS: For endovascular treatment, transvenous occlusion of DCSFs via the IPS is a feasible approach, even when this sinus is partially or completely thrombosed. Gentle handling of recently available, improved hydrophilic microguide wires and microcatheters allows effective and safe catheter navigation into the CS. A phlebogram of the jugular bulb is very useful for identification of a thrombosed IPS.

Aged↗

Carotenoid binding sites in LHCIIb. Relative affinities towards major xanthophylls of higher plants.

The major light-harvesting complex of photosystem II can be reconstituted in vitro from its bacterially expressed apoprotein with chlorophylls a and b and neoxanthin, violaxanthin, lutein, or zeaxanthin as the only xanthophyll. Reconstitution of these one-carotenoid complexes requires low-stringency conditions during complex formation and isolation. Neoxanthin complexes (containing 30-50% of the all-trans isomer) disintegrate during electrophoresis, exhibit a largely reduced resistance against proteolytic attack; in addition, energy transfer from Chl b to Chl a is easily disrupted at elevated temperature. Complexes reconstituted in the presence of either zeaxanthin or lutein contain nearly two xanthophylls per 12 chlorophylls and are more resistant against trypsin. Lutein-LHCIIb also exhibits an intermediate maintenance of energy transfer at higher temperature. Violaxanthin complexes approach a xanthophyll/12 chlorophyll ratio of 3, similar to the ratio in recombinant LHCIIb containing all xanthophylls. On the other hand, violaxanthin-LHCIIb exhibits a low thermal stability like neoxanthin complexes, but an intermediate accessibility towards trypsin, similar to lutein-LHCIIb and zeaxanthin-LHCIIb. Binary competition experiments were performed with two xanthophylls at varying ratios in the reconstitution. Analysis of the xanthophyll contents in the reconstitution products yielded information about relative carotenoid affinities of three assumed binding sites. In lutein/neoxanthin competition experiments, two binding sites showed a strong preference (> 200-fold) for lutein, whereas the third binding site had a higher affinity (25-fold) to neoxanthin. Competition between lutein and violaxanthin gave a similar result, although the specificities were lower: two binding sites have a 36-fold preference for lutein and one has a fivefold preference for violaxanthin. The lowest selectivity was between lutein and zeaxanthin: two binding sites had a fivefold higher affinity for lutein and one has a threefold higher affinity to zeaxanthin.

Apoproteins↗