[Medical education and continuing education of physicians in abdominal sonography at German universities. State of the art].
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Education, Medical↗
Biomedical subjects
M Pfeiffer
Publications and source records attributed to M Pfeiffer.
Age-dependence of the anticonvulsant effects of the GABA uptake inhibitor tiagabine in vitro.
Epileptic syndromes frequently start at childhood and therefore it is crucial to test new anticonvulsants at immature stages of the nervous system. We compared the effects of the gamma-aminobutyric acid (GABA) uptake inhibitor tiagabine [(R)-N-(4, 4-bis(3-methyl-2-thienyl)but)3-en-1-yl nipecotic acid] on low-Mg(2+)-induced epileptic discharges in brain slices from rat pups (p 5-8) and juvenile animals (p 15-20). In tissue from rat pups, tiagabine slightly reduced epileptiform activity in hippocampal area CA1 but had no effect in the entorhinal cortex. In juvenile rats, epileptiform discharges were unaffected in CA1 but suppressed by 60% in the entorhinal cortex. While tiagabine increases its efficacy with age, in-situ hybridisation and PCR analysis show that mRNA coding for the neuronal GABA-transporter GAT-1 is already present at p 5. We therefore conclude that the increasing efficacy of tiagabine during ontogenesis is due to functional maturation of GABAergic synapses rather than to up-regulation of GAT-1 expression.
Action Potentials↗
Site-directed spin-labeling reveals the orientation of the amino acid side-chains in the E-F loop of bacteriorhodopsin.
Due to high temperature factors and the lack of considerable electron density, electron microscopy and X-ray experiments on the cytoplasmic E-F loop of bacteriorhodopsin result in a variety of structural models. As the experimental conditions regarding ionic strength, temperature and the presence of detergents may affect the structure of the E-F loop, we employ electron paramagnetic resonance and site-directed spin-labeling to study the structure of this loop under physiological conditions. The amino acid residues at positions 154 to 171 were replaced by cysteine residues and derivatized with a sulfhydryl-specific nitroxide spin label one by one. The conventional and power saturation electron paramagnetic spectroscopy provide the mobility of the nitroxide and its accessibility to dissolved molecular oxygen and membrane-impermeable chromium oxalate in the respective site. The results show that K159 and A168 are located at the water-lipid interface of helices E and F, respectively. The orientation of the amino acid side-chains in the helical regions from positions 154 to 159 and 166 to 171 were found to agree with published structural data for bacteriorhodopsin. In the residue sequence from positions 160 to 165 the EPR data yield evidence for a turned loop structure with the side-chains of M163 and S162 oriented towards the proton channel and the water phase, respectively.
Amino Acids↗
[A scale for measuring symptoms related to degenerative diseases of the cervical spine. A reference in determining indications and evaluating surgical outcome].
A scale for measuring symptoms related to degenerative diseases of the cervical spine is presented. Twenty typical symptoms are listed, e. g., neck pain, dysesthesia, and reduced mobility. Responses are assessed via a 6-point scaling ("did not have symptom" - "had symptom and suffered very strongly".) The cervical spine scale was tested in three samples: patients having undergone cervical spine surgery (n = 70), patients with other orthopedic diagnoses (n = 104), and healthy students (n = 100). The single items of the scale were aggregated into four scores: total number of symptoms, degree of overall symptom distress, functional disability, and pain/psychological distress. Statistical analyses proved the high reliability (Cronbach's alpha = 0.85 to 0.95) and validity (content, convergent, discriminant) of all scores. The scale differs clearly between cervical spine patients, other orthopedic patients and healthy individuals, and between cervical spine patients with different subjective operative outcomes. For applied clinical purposes the cervical spine scale can be included in a quality of life profile (QL-profile); this allows for a readily understandable graphic depiction of individual patients' QL-status.
Activities of Daily Living↗
[Tiagabine and non-convulsive status epilepticus].
A case report is given to draw attention to the risk of the occurrence of nonconvulsive status epilepticus (NCSE) under the anticonvulsant tiagabine in higher doses and doses increases. The patient who had no previous history of status epilepticus developed several NCSE shortly after administration of tiagabine. This represents strong evidence of a causal relationship. Also, in experimental studies it has been shown that in higher doses a disequilibrium between glial and neuronal GABA uptake may aggravate the failure of GABA inhibition thus explaining this adverse side-effect.
Adverse Drug Reaction Reporting Systems↗
Azide reduces the hydrophobic barrier of the bacteriorhodopsin proton channel.
The sensitivity of a nitroxide spin label to the polarity of its environment has been used to estimate the hydrophobic barrier of the proton channel of the transmembrane proton pump bacteriorhodopsin. By means of site-specific mutagenesis, single cysteine residues were introduced at 10 positions located at the protein surface, in the protein interior, and along the proton pathway. After reaction with a methanethiosulfonate spin label, the principle values of the hyperfine tensor A and the g-tensor were determined from electron paramagnetic resonance spectra measured at 170 K. The shape of the hydrophobic barrier of the proton channel is characterized in terms of a polarity index, DeltaA, determined from the variation of the hyperfine coupling constant Azz. The maximum of the hydrophobic barrier is found to be close to the retinal chromophore in the proton uptake pathway. The effect of the asymmetric distribution of charged and polar residues in the proton release and uptake pathways is clearly reflected in the behavior of the hydrophobic barrier. The presence of azide reduces the barrier height of both the cytoplasmic and extracellular channels. This finding supports the view of azide and other weakly acidic anions as catalysts for the formation of hydrogen-bonded networks in proton pathways of proteins.
Azides↗
Combination therapy with tacrolimus and mycophenolate mofetil following cardiac transplantation: importance of mycophenolic acid therapeutic drug monitoring.
BACKGROUND: Interest has recently been expressed in tacrolimus and mycophenolate mofetil (MMF), two potent immunosuppressants, for a variety of transplant indications. The efficacy of this combination was assessed as primary therapy following cardiac transplantation. METHODS: Forty-five patients were enrolled; 15 into Phase I and 30 to Phase II of the study. Intravenous tacrolimus was administered for 2-3 days to all patients prior to conversion to oral therapy; target blood concentrations were 10-15 ng/mL. Treatment also consisted of steroids and MMF. During Phase I, a fixed 2 g/day dose of MMF was given whilst doses were adjusted according to mycophenolic acid (MPA) plasma levels during Phase II (target range 2.5-4.5 microg/mL). Mean follow-up was 696 +/- 62 days and 436 +/- 88 days for Phases I and II, respectively. RESULTS: Phase I: Patient survival was 100%. Rejection was diagnosed in 66.7% of patients (mean number of episodes per patient 1.33 +/- 1.18). Retrospective analyses indicated that whereas mean MPA plasma levels >3.0 microg/mL were not associated with rejection, no correlation was found with tacrolimus blood concentrations. Phase II: A survival rate of 96.7% was evident, one patient having died from aspergillosis. Diagnoses of rejection were made in 10.0% of patients (0.10 +/- 0.31 episodes per patient) and confounding factors were present in all 3 cases. MPA trough levels were 1.0 +/- 0.3 microg/mL at this time. Resolution was apparent following pulse steroid therapy. Steroids were successfully withdrawn from all patients who completed 6 months' treatment. CONCLUSIONS: Combination therapy with tacrolimus and MMF is associated with suppression of acute myocardial rejection; however, this is dependent upon routine therapeutic drug monitoring.
Adolescent↗
Interindividual variation in mitotic recombination.
Mitotic recombination (MR) between homologous chromosomes is a mutational event that results in loss of heterozygosity in half of the segregants at mitosis. Loss of heterozygosity may have important biological consequences. The purpose of this study was to describe human variation in the spontaneous frequency of MR. Using an immunoselection technique for isolating the somatic mutations that result in loss of expression of one of the codominant alleles at the HLA-A locus, we have measured the frequency and molecular basis of somatic mutations in lymphocytes from a population of young adults. Mutations were classified as being the result of intragenic changes, major deletions, or MR. Here we show that the MR mutation frequency in females was significantly greater than that in males but that intragenic mutation frequency showed no association with sex. Individual variation in MR frequency ranged over more than two orders of magnitude and was not normally distributed. Furthermore, the observed number of individuals from whom no mutants resulting from MR were obtained was significantly greater than was expected. The endogenous level of MR may be under genetic control. Given the association of loss of heterozygosity with cancer initiation and progression, low endogenous MR may confer a reduced lifetime risk of cancer, and the converse may apply.
Adult↗
Burden and well-being of caregivers for the severely mentally ill: the role of coping style and social support.
Caregivers of persons with severe mental illness often experience a significant burden in coping with patients' symptoms. Several factors have been hypothesized to mediate the impact of caring for a mentally ill relative, including cognitive appraisal, coping strategies, and social support. The present study examined the relationships between these factors, and subjective burden and well-being in caregivers of persons with a severe mental illness. Higher levels of subjective burden were related to (1) greater perceived frequency of positive and negative symptom behaviors, (2) a tendency to use problem-focused oriented coping for dealing with negative symptom behaviors, and (3) a tendency not to use problem-solving oriented coping for dealing with positive symptom behaviors. Well-being was also related to lower perceived frequency of positive symptom behaviors and social support, but not to coping style. The implications of the findings for interventions designed to reduce caregiver subjective burden are discussed.
Adaptation, Psychological↗
Fusion of two subunits does not impair the function of a [NiFeSe]-hydrogenase in the archaeon Methanococcus voltae.
[NiFe]-hydrogenases generally carry the bimetallic Ni-Fe reaction center on their largest subunit. The [NiFeSe]-hydrogenase Vhu from Methanococcus voltae has an unusual subunit composition. Some of the amino acids participating in the formation of the reaction center are within a separate, very small subunit, called VhuU. It consists of only 25 amino acids and contains the selenocysteinyl residue, a ligand to the Ni atom. We have tested whether the special configuration of the Vhu-hydrogenase is of particular biochemical relevance. We have constructed a fusion subunit derived from the VhuA and VhuU subunits by generating a gene fusion which was inserted into the chromosome of M. voltae by gene replacement. The enzyme was purified and shown to be as active as the wild-type enzyme. M. voltae carries the genetic information for four different [NiFe]-hydrogenases. In addition to the Vhu-hydrogenase, a second selenium-containing enzyme, Fru, has been purified. Two selenium-free enzymes, Vhc and Frc, are homologues of Vhu and Fru, respectively. Their gene groups, vhc and frc are transcribed only upon selenium depletion. The selenium-containing subunit VhuU has been implicated in their negative regulation. However, cells containing the fusion hydrogenase still exhibited normal regulation of the vhc andfrc promoter activities as tested in reporter gene constructs. This indicates that the free VhuU polypeptide is not required for the negative regulation of the vhc or frc genes.
Bacterial Proteins↗
The vhuU gene encoding a small subunit of a selenium-containing [NiFe]-hydrogenase in Methanococcus voltae appears to be essential for the cell.
We developed a general method for the site-specific deletion of gene sequences to obtain new selectable markers in the archaeon Methanococcus voltae. Using a deletion in the hisA gene, a vector was integrated into the chromosome by homologous recombination, thereby reconstituting histidine prototrophy. The vector contained the beta-glucuronidase gene uidA of Escherichia coli as a reporter under the control of an M. voltae promoter that normally drives the expression of a selenium-free [NiFe]-hydrogenase after selenium deprivation. This construct has allowed us to check whether the selenium supply was sufficiently low to induce the transcription of the genes encoding the selenium-free hydrogenases. We tried to introduce a chromosomal deletion of the vhuU gene of the archaeon M. voltae by gene replacement and by keeping the cells under selenium deprivation. The gene vhuU encodes the very small, selenocysteine-containing subunit that is part of the primary reaction center of the Vhu hydrogenase. All transformants bearing the deletion also contained the vhuU wild-type gene. Therefore, the vhuU gene appears to be essential for the cell even under conditions that lead to the induction of the selenium-free homologue Vhc of the Vhu hydrogenase.
Aldose-Ketose Isomerases↗
Validation of an automated enzyme immunoassay for Interleukin-6 for routine clinical use.
Serum levels of Interleukin-6 (IL-6), a proinflammatory cytokine, are increased in early stages of inflammatory diseases such as infection and sepsis. Assay systems which permit its measurement within a few hours and as a single measurement have not been reported so far. We therefore evaluated a now commercially available automated method for IL-6 measurement on the Cobas Core immunological analyzer (Roche Diagnostic Systems) which enables single IL-6 measurement within about 1 hour. The automated assay correlates well with an established, manual microtiter plate assay (Biosource GmbH) which uses the same antibodies and reagents (r=0.98). Accuracy of the automated method was established by adding known amounts of IL-6 international reference preparation. Recovery of the international standard was in the range of 92104%. The automated assay had a precision of singletons below 6% and was linear up to 2800 pg/ml. This automated assay provides a suitable, convenient and time saving method for measurement of IL-6 serum levels in the routine clinical laboratory.
Automation↗
Single-center randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of acute myocardial rejection.
BACKGROUND: To compare the efficacy and safety of tacrolimus and cyclosporine in heart transplantation, this single-center, prospective, randomized, open-label clinical trial was undertaken. METHODS: Seventy-three adult patients were randomly assigned at the time of transplantation to receive either tacrolimus (n=43) or cyclosporine (n=30) as the primary immunosuppressant. Ten of the 43 patients in the tacrolimus group received the drug intravenously in the perioperative period; all other patients received only oral tacrolimus. RESULTS: With a mean follow-up of 27 months, patient survival rates (tacrolimus 83%, cyclosporine 81%) were similar. Fewer patients experienced acute rejection in the tacrolimus group (79%) than in the cyclosporine group (100%), but the difference was not statistically significant. The number of infections and dialysis and insulin requirements were similar for the 2 treatment groups, but the proportion of patients requiring multidrug antihypertensive regimens was lower in the tacrolimus group (12.5% vs 50.0% at month 6; p=.025). The interpatient variance in pharmacokinetic parameters in a subset of 10 patients was much higher after the first oral dose of tacrolimus than at steady-state (eg, first-dose time at which maximal concentration is reached (t(max)): 3.5+/-2.5h, steady-state t(max): 2.0+/-0.7h), and patients treated with intravenous tacrolimus (n=13) rather than oral tacrolimus (n=30) reached target concentrations faster and with less interpatient variability (eg, at day 0: 9.72+/-10.9 ng/mL intravenously vs 3.31+/-8.1 orally). CONCLUSIONS: Tacrolimus was associated with similar efficacy and safety profiles compared with cyclosporine. The higher interpatient variance in absorption associated with oral tacrolimus during the first few days after transplantation would suggest that intravenous tacrolimus should be used during the perioperative period.
Administration, Oral↗
A simple hardware model for the direct observation of voltage-clamp performance under realistic conditions.
A new hardware cell model for electrophysiological recording has been constructed which allows for the assessment of voltage clamp accuracy in different recording situations. Each compartment consists of a capacitor in parallel with a variable resistor and can be connected to other compartments by a variable axial resistance. The simulated membrane resistance can be changed extrinsically by a command voltage input which is optically coupled to the cell without any direct galvanic contact. Each compartment possesses a buffer amplifier which reads out the potential at the simulated membrane element, (e.g. 'somatic' or 'dendritic' potential). The model allows for the direct observation of typical situations and problems arising in electrophysiological experiments. We used the model to monitor deviations between the 'intracellular' and the command voltage, e.g. due to series resistance errors. We also used the model to simulate synaptic currents which were generated by triangular membrane conductance changes. The results demonstrate the strong influence of synaptic location and series resistance on voltage clamp fidelity. The cell model is a new and easy-to-handle tool for the observation of voltage control under realistic experimental conditions.
Animals↗
In vitro testing of a new transpedicular stabilization technique.
The rigidity of a pedicle screw implant is a critical biomechanical variable in lumbar spinal fusions. Sufficient rigidity is required for integration of bone grafts and to promote healing. Osteopenia, stress shielding, and compensatory hypermobility have been described as consequences of excessive rigidity. Little is known about the biomechanical characteristics of "semirigid" compared to "rigid" implants. A new implant, whose rigidity can be varied by selection of different implant components, was tested in vitro under well-defined loading conditions. The three-dimensional load-displacement behavior of all lumbar vertebrae involved in or adjacent to the two-level fusion was evaluated for two fusion modifications: bilateral rigid and bilateral semirigid. Cyclic fatigue loading was subsequently carried out under realistic conditions and motion testing repeated. The rigid device reduced the motion of the L3-4 transfixed segment in the primary movement planes by 87.3% with respect to the intact spine value in flexion/extension (FE), 86.3% in lateral bending (LB), and 76.8% in axial rotation (AR). The semirigid device achieved a reduction in motion of 79.6% (FE), 82.7% (LB), and 51.7% (AR). The semirigid implant was particularly easy to insert, because no bending of rods or plates was necessary. The implants showed no loosening or breakage after the fatigue testing. The results are compared to other available systems and the underlying biomechanics discussed.
Aged↗
The [NiFe] hydrogenases of Methanococcus voltae: genes, enzymes and regulation.
Methanococcus voltae carries genetic information for four [NiFe] hydrogenases. Two of the hydrogenases are predicted to contain selenocysteine on the basis of in-frame TGA codons, while the genes encoding the two other enzymes contain cysteine codons at homologous positions. Their predicted subunit compositions and their electron acceptor specificities are similar to those of the respective selenium-containing enzymes. The selenium-containing hydrogenases have been purified and characterized. Only one of them reduces the deazaflavin F(420). The activity of the F(420)-nonreducing enzyme is exceptionally high. The selenium atom has been shown by EPR spectroscopy to be a ligand to the Ni atom in the primary reaction centers in both enzymes. The spectroscopic analyses also yielded a description of the electronic configuration around the NiFe center at different oxidation states and in the presence of the competitive inhibitor, CO. The genes encoding the selenium-free hydrogenases are expressed only in the absence of selenium. They are linked by an intergenic region in which regulatory cis elements were defined by employing reporter gene constructs and site-directed mutagenesis.
Journal Article↗
Transfusion of platelet-rich plasma from the organ donor during cardiac transplantation.
STUDY OBJECTIVE: To evaluate whether transfusion of platelet-rich plasma from the organ donor during cardiac transplantation can influence the amount of the needed homologous blood products. DESIGN: Randomized, controlled study. SETTING: University hospital. PATIENTS: 16 ASA physical status III patients undergoing orthotopic cardiac transplantation. INTERVENTIONS: Eight patients received donor plasma, while another 8 patients served as a control group. Blood from the organ donor was acquired during cardiac explantation. Thereafter platelet-rich plasma was separated by plasmapheresis (2400 turns per minute). The plasma was then transfused to the organ recipient at the end of the cardiac transplantation. The control group received a similar amount of albumin 5%. MEASUREMENTS AND MAIN RESULTS: In the patients who received donor plasma, the platelet count increased significantly from 98,000 +/- 49,000 mm-3 to 123,000 +/- 55,000 mm-3, the postoperative requirement of packed red blood cells (PRBCs) was 5.8 +/- 4.5 units, which was significantly lower as compared to the control group (10.8 +/- 5.9 units). CONCLUSIONS: Transfusion of platelet-rich plasma from the organ donor to the recipient was confirmed to be feasible, the number of postoperatively transfused PRBCs was reduced.
Blood Transfusion↗
A protocol to evaluate semi-rigid pedicle screw systems.
The objective of the current study was to develop an in vitro testing protocol to evaluate semi-rigid pedicle screw devices. A corpectomy model protocol exists to evaluate rigid spinal implants; however, semi-rigid devices are contraindicated for this condition. This paper describes a technique that simulates more closely the conditions a semi-rigid device would see in vivo. Finally, the new testing protocol is used to evaluate the DDS pedicle screw-cable system. Benefits and shortcomings of the new protocol are discussed.
Bone Screws↗