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.     

Elektrische und Chemische Deutung von Lebensvorgängen

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

Caring for the patient with fibromyalgia: the rehabilitation nurse's role.

Fibromyalgia (FM) is a chronic, potentially disabling, cluster of symptoms that manifests as pain for 3 months or more and pain with pressure on 11 of 18 tender points throughout the body. Because there is no known cause, and therefore, no cure, treatment focuses on the control or relief of symptoms. Many patients are referred to rehabilitation settings for physical or exercise therapy. While exercise is helpful in the control of the pain, stiffness, fatigue, sleep disorders, and mood changes, a holistic approach to treatment is more effective. Rehabilitation nurses provide major support for patients with FM. Validation of the patients' experiences is essential for achieving quality of life. Many patients have a history of being undertreated because of a lack of credibility and invisibility of the illness. This article provides background information about FM, summarizes the FM trajectory, reviews approaches to management, and discusses the role of rehabilitation nurses in a holistic approach to care of clients with FM.     

Effect of dialyzer geometry on granulocyte and complement activation

During hemodialysis with cuprophan membranes, the complement system as well as leukocytes become activated. In order to clarify the role of dialyzer geometry, the effect of hollow-fiber versus flat-sheet dialyzers and of different surface areas on C3a generation and leukocyte degranulation was investigated. Plasma levels of leukocyte elastase in complex with alpha 1-proteinase inhibitor were significantly increased after 1 h (+55%) and 3 h (+62%) of hemodialysis with flat-sheet dialyzers as compared to hollow-fiber devices. In addition, plasma levels of lactoferrin, released from the specific granules of leukocytes during activation, were significantly higher (+42%) 3 h after the onset of dialysis treatment with flat-sheet than with hollow-fiber dialyzers. With respect to surface area, larger dialyzers tended to cause more release of leukocyte elastase as compared to dialyzers with smaller surface areas, irrespectively of the configuration of the dialyzer used. On the other hand, activation of the complement system, as measured by the generation of C3a-desarg, did not differ with both types of configurations. The same held true for leukopenia, which was almost identical for hollow-fiber and flat-sheet dialyzers. From these findings two lines of evidence emerge: First, not only the type of membrane material used in a dialyzer may influence its biocompatibility, but the geometry of the extracorporeal device also determines the degree of compatibility. Hence, the extent of leukocyte activation correlated with both configuration of the dialyzer and surface area of the membrane.(ABSTRACT TRUNCATED AT 250 WORDS)