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Die Anaesthesiologie - Die intraoperative Dosierung von Opioiden stellt eine Herausforderung im anästhesiologischen Alltag dar; insbesondere, da potenzielle Effekte einer intraoperativen...     

Despite Equivalent Outcomes,Men Receive Neoadjuvant Chemotherapy Less Often Than Women for Lymph Node-Positive Breast Cancer

Annals of Surgical Oncology -     

Misaligned spinal rods can induce high internal forces consistent with those observed to cause screw pullout and disc degeneration

BACKGROUND CONTEXTManual contouring of spinal rods is often required intraoperatively for proper alignment of the rods within the pedicle screw heads. Residual misalignments are frequently reduced by using dedicated reduction devices. The forces exerted by these devices, however, are uncontrolled and may lead to excessive reaction forces. As a consequence, screw pullout might be provoked and surrounding tissue may experience unfavorable biomechanical loads. The corresponding loads and induced tissue deformations are however not well identified. Additionally, whether the forced reduction alters the biomechanical behavior of the lumbar spine during physiological movements postoperatively, remains unexplored.PURPOSETo predict whether the reduction of misaligned posterior instrumentation might result in clinical complications directly after reduction and during a subsequent physiological flexion movement.STUDY DESIGNFinite element analysis.METHODSA patient-specific, total lumbar (L1–S1) spine finite element model was available from previous research. The model consists of poro-elastic intervertebral discs with Pfirrmann grade-dependent material parameters, with linear elastic bone tissue with stiffness values related to the local bone density, and with the seven major ligaments per spinal motion segment described as nonlinear materials. Titanium instrumentation was implemented in this model to simulate a L4, L5, and S1 posterolateral fusion. Next, coronal and sagittal misalignments of 6 mm each were introduced between the rod and the screw head at L4. These misalignments were computationally reduced and a physiological flexion movement of 15° was prescribed. Non-instrumented and well-aligned instrumented models were used as control groups.RESULTSPulling forces up to 1.0 kN were required to correct the induced misalignments of 6 mm. These forces affected the posture of the total lumbar spine, as motion segments were predicted to rotate up to 3 degrees and rotations propagated proximally to and even affect the L1–2 level. The facet contact pressures in the corrected misaligned models were asymmetrical suggesting non-physiological joint loading in the misaligned models. In addition, the discs and vertebrae experienced abnormally high forces as a result of the correction procedure. These effects were more pronounced after a 15° flexion movement following forced reduction.CONCLUSIONSThe results of this study indicate that the correction of misaligned posterior instrumentation can result in high forces at the screws consistent with those reported to cause screw pullout, and may cause high-tissue strains in adjacent and downstream spinal segments.CLINICAL SIGNIFICANCEProper alignment of spinal posterior instrumentation may reduce clinical complications secondary to unfavorable biomechanics.     

Quantification and preservation of lectin binding by isolated cardiomyocytes

During preparation of cells for experimentation a considerable amount of bound substance is lost. Our aim was to develop a protocol which retained lectin binding to an extent similar to living cells. This procedure would use fixation procedures suited for fluorescent lectin conjugates and gold-conjugates to be visualized by light- and electron microscopy, respectively. We tested glutaraldehyde and paraformaldehyde in different concentrations before and after lectin binding, different buffers and divalent cations, as additives, to determine the effects on preservation of lectin binding. Lectin binding was visualized and semiquantitatively evaluated by image analysis in the light microscope after silver enhancement of lectin-gold conjugates and by using tetramethyl rhodaminyl isothiocyanate (TRITC)-conjugated lectins. Preservation of lectin binding was best visualized with fluorescent lectin conjugates, whereas during silver enhancement procedures of gold-conjugated lectins, a considerable amount of bound lectins was lost. In general, lectin binding to living cells followed by fixation is superior to fixation before lectin binding. Unfavourable combinations of fixatives and buffers can cause a loss of more than 90% bound lectin. In our experiments with freshly isolated guinea pig cardiomyocytes, lectin binding was best when we used Na-cacodylate buffer with glutaraldehyde fixation (0.1%) after binding of lectins to the living cells.     

Cationic-amphiphilic arpromidine-derived guanidines and a histamine trifluoromethyl-toluidide derivative may activate pertussis toxin-sensitive G-proteins by a receptor-independent mechanism

Formyl peptides activate superoxide anion (O₂ ^–) formation in human neutrophils and in HL-60 cells via pertussis toxin (PTX)-sensitive guanine nucleotide-binding proteins (G-proteins), and histamine (HA) mediates inhibition of O₂ ^– formation via H₂-receptors. We have studied the effects of lipophilic arpromidine-derived guanidines, which are potent, full H₂-receptor agonists in the guinea pig atrium, on O₂ ^– formation and on activation of G-proteins in HL-60 membranes and on purified G-proteins. We have also studied the effects of a HA trifluoromethyl-toluidide derivative (HTMT), a cationic-amphiphilic HA derivative which activates O₂ ^– formation in HL-60 cells through a mechanism which is independent of known HA receptor subtypes, on G-protein activation. Guanidines, at concentrations, up to 30 mol/l inhibited and, at concentrations above 30 mol/l, enhanced formyl peptide-induce O₂ ^– formation in neutrophils. In HL-60 cells, guanidines per se activated O₂ ^– formation. The stimulatory effects of guanidines on O₂ ^– formation were not inhibited by H₁- or H₂-receptor antagonists. In HL-60 membranes, guanidines and HTMT, activated high-affinity GTPase in a PTX-sensitive manner. These substances also increased GTP hydrolysis effected by transducin and G_i/G_o-proteins. Our data suggest that lipophilic guanidines and HTMT may act as receptor-independent activators of PTX-sensitive G-proteins, resulting in stimulation of O ₂ ^– formation.     

Urinary excretion of adenosine deaminase binding protein in neonates treated with tobramycin

The potential tubulotoxicity of tobramycin and cefotaxim were assessed in neonates by measuring the urinary level of adenosine deaminase binding protein (ABP) and urinary ₁-microglobulin and ₂-microglobulin. In a prospective study, 33 neonates who received tobramycin and cefotaxim for suspected neonatal sepsis were compared with 48 untreated newborns during the first 10 days of life. The urinary concentrations of ABP and its excretion rates, corrected for body weight and body surface area, were significantly increased from the 1st day of treatment. Urinary ₁-microglobulin and ₂-microglobulin were not elevated under tobramycin and cefotaxim during the first 2 days of treatment. We conclude that ABP may be a sensitive marker for the detection of proximal renal tubular injury during tobramycin and cefotaxim treatments of neonates. The increase in urinary ABP which occurs before an elevation of urinary ₁-microglobulin and ₂-microglobulin may reflect earlier structural than functional alterations. However, since none of the treated infants had signs of electrolyte disorders or glomerular dysfunction, the clinical relevance of ABP measurement should be reevaluated.     

Tonic inhibition of neuronal calcium channels by G proteins removed during whole-cell patch-clamp experiments

The barium current through voltage-dependent calcium channels was recorded from cultured rat cortical neurons with the whole-cell configuration of the patch-clamp technique. The maximal current evoked by depolarising pulses from –80 mV to 0 mV was divided into inactivating and non-inactivating fractions. During the first minutes of whole-cell recording, the amplitude of the inactivating fraction increased from less than 0.1 nA to an average value of 1 nA, whereas the amplitude of the non-inactivating component remained essentially the same. This increase in amplitude was prevented when the perforated-patch technique was used, suggesting that some intracellular factor that inhibited the barium current was lost or destroyed during conventional whole-cell experiments. When GTP[-S] or GTP was added to the pipette solution, no increase or only a weak rise of the inactivating current was seen, whereas GDP[-S] accelerated its increase. The results suggest that some of the calcium channels expressed in cultured cortical neurons are inhibited by a G protein even in the absence of added neurotransmitter. The current increase observed during whole-cell recordings may be due to a loss of intracellular GTP and the subsequent inactivation of an inhibitory G protein.     

Ventricular remodeling after acute myocardial infarction

The term ventricular remodeling has been coined to describe the geometrical changes in size and shape of the left ventricle occurring after large myocardial infarcts. We do not exactly know what initiates this process. Slipping of myofilaments following destruction of connective tissue--probably due to metalloproteinase activation--could be the initial event. As a consequence, wall stress is increased triggering deleterious adaptation processes, such as: - intracardiac angiotensin II generation; - cardiac endothelin formation and release; - pro-apoptotic signals for cardiomyocytes; - hypertrophic signals for fibroblasts and cardiomyocytes. This cascade of events is not only observed in the process of remodeling following myocardial infarction but is also operating during the progression of heart failure. Therapeutic principles therefore are similar in both conditions: - reduction of wall stress (pharmacological or mechanical unloading of the heart); - blockade of angiotensin II generation or of AT1-receptors (ACE-inhibitors or AT1 antagonists); - blockade of endothelin receptors (ET(A)-blockers); - blockade of adrenergic receptors (preferably beta1-adrenergic receptor blockers). Better understanding of the molecular mechanisms of the remodeling process already has fueled the search for new therapeutic interventions (such as endothelin receptor blockers, aldosterone antagonists and growth hormone application). Continuous research in this field may be especially rewarding if we will succeed in identifying the very first step in the cascade.