Update PONV – Was gibt es Neues bei der Prophylaxe und Therapie von postoperativer Übelkeit und postoperativem Erbrechen?

Die Anaesthesiologie - Auch wenn für Anästhesiologen über Jahrzehnte die Prophylaxe und Therapie postoperativer Schmerzen im Rahmen des postoperativen Patientenkomforts an vorderster...     

Increasing the efficiency of Monte Carlo cohort simulations with variance reduction techniques.

The authors discuss techniques for Monte Carlo (MC) cohort simulations that reduce the number of simulation replications required to achieve a given degree of precision for various output measures. Known as variance reduction techniques, they are often used in industrial engineering and operations research models, but they are seldom used in medical models. However, most MC cohort simulations are well suited to the implementation of these techniques. The authors discuss the cost of implementation versus the benefit of reduced replications.     

In vivo targets of recombinant human tumour necrosis factor-alpha: blood flow, oxygen consumption and growth of isotransplanted rat tumours

The impact of recombinant human tumour necrosis factor-alpha (1 microgram kg-1 to 1 mg kg-1; 6.6 x 10(6) U mg protein-1) on blood flow, oxygen consumption and growth of a moderately TNF-sensitive rat tumour (DS-carcinosarcoma) was studied. Tumour growth was stimulated at low TNF doses (1 and 10 micrograms kg-1) and significantly retarded at higher TNF dose levels (0.1 and 1 mg kg-1). Growth changes were concomitant with variations in oxygen consumption, lactate release and acidification of the metabolic micromilieu. Both single and repeated application of low TNF doses (1-10 micrograms kg-1 i.v.) increased tumour perfusion whereas single administration of high TNF dose levels (0.1-1 mg kg-1 i.v.) reduced tumour blood flow. After repeated application of high TNF doses tumours shrank to such small sizes that perfusion measurements could not be performed within the observation period of two weeks. It is concluded that TNF effects on solid tumours are at least partially mediated by changes in tumour perfusion. Thus, an altered tumour sensitivity towards other treatment modalities, e.g. irradiation, chemotherapy or hyperthermia, can be expected after TNF therapy. A beneficial TNF effect would critically depend on the dose level employed and on the sequence and timing of various combination regimes.     

Formation of mitochondrial phospholipid adducts by nephrotoxic cysteine conjugate metabolites.

Nephrotoxic cysteine conjugates derived from a variety of halogenated alkenes are enzymatically activated via the beta-lyase pathway to yield reactive sulfur-containing metabolites which bind covalently to cellular macromolecules. Mitochondria contain beta-lyase enzymes and are primary targets for binding and toxicity. Previously, mitochondrial protein and/or DNA have been considered as molecular targets for cysteine conjugate metabolite binding. We now report that metabolites of nephrotoxic cysteine conjugates form covalent adducts with rat kidney mitochondrial phospholipids. Rat kidney mitochondria were incubated with the 35S-labeled conjugates S-(1,1,2,2-tetrafluoroethyl)-L-cysteine (TFEC), S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine (CTFC), S-(1,2-dichlorovinyl)-L-cysteine, and S-(1,2,3,4,4-pentachlorobutadienyl)-L-cysteine. Quantitation of metabolite binding to whole mitochondria and to mitochondrial protein and lipid fractions revealed that as much as 42% of the 35S-label associated with the mitochondria was found in the lipid fraction. Total lipids were also extracted from 35S-treated mitochondria and separated by thin-layer chromatography. 35S-Containing metabolites were found in the lipid fractions from mitochondria treated with each of the conjugates. Lipids from both [35S]CTFC- and [35S]-TFEC-treated mitochondria contained major 35S-labeled lipid adducts which had similar mobility by thin-layer chromatography. Fatty acid analysis, 19F and 31P NMR spectroscopy, and mass spectrometric analyses confirmed that the major TFEC and CTFC adducts are thioamides of phosphatidylethanolamine.     

Differential Regulation of RGS-2 by Constant and Oscillating PTH Concentrations

PTH has diverse effects on bone metabolism: anabolic when given intermittently, catabolic when given continuously. The cellular mechanisms underlying the varying target cell response are not clear yet. PTH induces RGS-2, a member of the Regulator of G-protein Signaling protein family, via cAMP/PKA, and inactivates PKC-mediated signaling. To investigate intracellular signaling pathways with different PTH concentration-time patterns, we treated UMR 106-01 osteoblast-like cells in a perfusion system. PTH was administered intermittently (4 min/h, 10⁻⁷ M) or continuously at an equivalent cumulative dose (6.6 × 10⁻⁹ M). cAMP was measured using radioimmunoassay, mRNA levels using real-time rtPCR and ribonuclease protection assay, and protein levels using Western immunoblotting. A single PTH pulse transiently increased cAMP levels by 2000% ± 1200%. In contrast to continuous PTH exposure, cAMP induction remained unchanged with intermittent PTH, ruling out desensitization of the PTH receptor. In continuously perfused cells, RGS-2 abundance was three to five times higher than in cells intermittently exposed to PTH for up to 12 h. MKP-1 and -3 were significantly less induced with pulsatile PTH; exposure-mode-dependent differences in MMP-13 and IGFBP-5 were small. Pulsatile but not continuous PTH administration prevents PTHrP receptor desensitization and accumulation of RGS-2 in osteoblasts, which should preserve PKC-dependent signaling.     

Three-Dimensional Soft Tissue Prediction Using Finite Elements

Abstract Background and Aim: The prediction of soft tissue esthetics is important for achieving an optimal esthetic outcome in orthodontic treatment planning. Applicable procedures have so far been restricted to two-dimensional profile predictions that have not proven to be very reliable. The goal of this investigation was therefore to develop a novel finite element-based procedure that allows a three-dimensional, easily visualized, quantitative analysis and prediction of soft tissue behavior for the clinician. The procedure to be developed should be easy to handle and not entail any additional radiation exposure for the patient. Material and Methods: Using a three-dimensional scanner, the facial surfaces of 20 probands were digitalized and individual FEM models were generated. Results: After reduction of data redundancy via several conversion steps, a patient-specific simulation model was prepared consisting of 20,000 to 40,000 individual elements to which specific physical properties could be assigned. The average time required for generating a virtual model was 50 minutes. Problems occurring during model generation were rare (mainly shadowing phenomena and movement artifacts). Conclusion: The procedure outlined herein makes the reliable generation of patient-specific simulation models possible for facial soft tissue prediction in orthodontics.     

Three-Dimensional Soft Tissue Prediction Using Finite Elements

BACKGROUND AND AIM: The goal of this study was to analyze the validity and prediction accuracy of a newly-developed procedure for three-dimensional soft tissue prediction based on Finite Element Method, and to compare the results with prediction produced using an existing two-dimensional prediction program (Dentofacial Planner Plus). PATIENTS AND METHODS: In twelve patients who underwent combined surgical-orthodontic treatment, profile prediction was generated using both procedures preoperatively and then compared at predefined measurement points with the patient's actual postoperative soft tissue status. RESULTS: The deviations observed depended on the facial region, whereby the prediction errors for both procedures were much greater in the lower facial third than in the midfacial third. Calculating in all the measurement points, the mean horizontal prediction error was 0.32 mm for the Finite Element Method and 0.75 mm for the Dentofacial Planner Plus. Overall, we were able to demonstrate the new procedure's superior validity and quality of visualization. In addition to profile prediction, the procedure allows a differentiated three-dimensional assessment of esthetically important regions such as the cheeks, nasolabial folds and the nasal wings. Additional X-radiation is not necessary in this risk-free and stress-free procedure. CONCLUSION: Three-dimensional soft tissue prediction employing finite element modeling is a useful aid for implementing esthetically-optimized treatment planning.     

Elektrische und Chemische Deutung von Lebensvorgängen

Ohne ZusammenfassungNach einem Vortrag, gehalten am 10. Dezember 1940 vor der Medizinischen Gesellschaft in Gießen.