RESUMEN
Assessment of peripheral perfusion and comparison of surface and body core temperature (BST; BCT) are diagnostic cornerstones of critical care. Infrared non-contact thermometers facilitate the accurate measurement of BST. Additionally, a corrected measurement of BST on the forehead provides an estimate of BCT (BCT_Forehead). In clinical routine BCT is measured by ear thermometers (BCT_Ear). The PiCCO-device (PiCCO: Pulse contour analysis) provides thermodilution-derived Cardiac Index (CI_TD) using an arterial catheter with a thermistor tip in the distal aorta. Therefore, the PiCCO-catheter might be used for continuous BCT-measurement (BCT_PiCCO) in addition to intermittent CI-measurement. To the best of our knowledge, BCT_PiCCO has not been validated compared to standard techniques of BCT-measurement including measurement of urinary bladder temperature (BCT_Bladder). Therefore, we compared BCT_PiCCO to BCT_Ear and BCT_Bladder in 52 patients equipped with the PiCCO-device (Pulsion; Germany). Furthermore, this setting allowed to compare different BSTs and their differences to BCT with CI_TD. BCT_PiCCO, BCT_Ear (ThermoScan; Braun), BCT_Bladder (UROSID; ASID BONZ), BCT_Forehead and BSTs (Thermofocus; Tecnimed) were measured four times within 24h. BSTs were determined on the great toe, finger pad and forearm. Immediately afterwards TPTD was performed to obtain CI_TD. 32 (62%) male, 20 (38%) female patients; APACHE-II 23.8 ±8.3. Bland-Altman-analysis demonstrated low bias and percentage error (PE) values for the comparisons of BCT_PiCCO vs. BCT_Bladder (bias 0.05 ±0.27° Celsius; PE = 1.4%), BCT_PiCCO vs. BCT_Ear (bias 0.08 ±0.38° Celsius; PE = 2.0%) and BCT_Ear vs. BCT_Bladder (bias 0.04 ±0.42° Celsius; PE = 2.2). While BCT_PiCCO, BCT_Ear and BCT_Bladder can be considered interchangeable, Bland-Altman-analyses of BCT_Forehead vs. BCT_PiCCO (bias =-0.63 ±0.75° Celsius; PE = 3.9%) Celsisus, BCT_Ear (bias = -0.58 ±0.68° Celsius; PE = 3.6%) and BCT_Bladder (bias = -0.55 ±0.74° Celsius; PE = 3.9%) demonstrate a substantial underestimation of BCT by BCT_Forehead. BSTs and differences between BCT and BST (DCST) significantly correlated with CI_TD with r-values between 0.230 and 0.307 and p-values between 0.002 and p < 0.001. The strongest association with CI_TD was found for BST_forearm (r = 0.307; p < 0.001). In a multivariate analysis regarding CI_TD and including biometric data, BSTs and and their differences to core-temperatures (DCST), only higher temperatures on the forearm and the great toe, young age, low height and male gender were independently associated with CI_TD. The estimate of CI based on this model (CI_estimated) correlated with CI_TD (r = 0.594; p < 0.001). CI_estimated provided large ROC-areas under the curve (AUC) regarding the critical thresholds of CI_TD ≤ 2.5 L/min/m2 (AUC = 0.862) and CI_TD ≥ 5.0 L/min/m2 (AUC = 0.782). 1.) BCT_PiCCO, BCT_Ear and BCT_Bladder are interchangeable. 2.) BCT_Forehead significantly underestimates BCT by about 0.5° Celsius. 3.) All measured BSTs and DCSTs were significantly associated with CI_TD. 4.) CI_estimated is promising, in particular for the prediction of critical thresholds of CI.
Asunto(s)
Hemodinámica , Termodilución , Boston , Catéteres , Femenino , Alemania , Humanos , Masculino , Reproducibilidad de los Resultados , TemperaturaRESUMEN
Phosphoinositide (PI) lipids are intracellular membrane signaling intermediates and effectors produced by localized PI kinase and phosphatase activities. Although many signaling roles of PI kinases have been identified in cultured cell lines, transgenic animal studies have produced unexpected insight into the in vivo functions of specific PI 3- and 5-kinases, but no mammalian PI 4-kinase (PI4K) knockout has previously been reported. Prior studies using cultured cells implicated the PI4K2alpha isozyme in diverse functions, including receptor signaling, ion channel regulation, endosomal trafficking, and regulated secretion. We now show that despite these important functions, mice lacking PI4K2alpha kinase activity initially appear normal. However, adult Pi4k2a(GT/GT) animals develop a progressive neurological disease characterized by tremor, limb weakness, urinary incontinence, and premature mortality. Histological analysis of aged Pi4k2a(GT/GT) animals revealed lipofuscin-like deposition and gliosis in the cerebellum, and loss of Purkinje cells. Peripheral nerves are essentially normal, but massive axonal degeneration was found in the spinal cord in both ascending and descending tracts. These results reveal a previously undescribed role for aberrant PI signaling in neurological disease that resembles autosomal recessive hereditary spastic paraplegia.
Asunto(s)
Axones/patología , Degeneración Nerviosa/metabolismo , Fosfotransferasas (Aceptor de Grupo Alcohol)/deficiencia , Transducción de Señal/fisiología , Médula Espinal/citología , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Axones/metabolismo , Análisis Químico de la Sangre , Ratones , Ratones Noqueados , Antígenos de Histocompatibilidad Menor , Transducción de Señal/genética , Médula Espinal/patologíaAsunto(s)
Encéfalo/fisiología , Simulación por Computador , Modelos Neurológicos , Neurociencias/métodos , Animales , HumanosRESUMEN
Valproic acid (VPA) is used to treat epilepsy and bipolar disorder and to prevent migraine. It is also undergoing trials for cancer therapy. However, the biochemical and molecular biological actions of VPA are poorly understood. Using the social amoeba Dictyostelium discoideum, we show that an acute effect of VPA is the inhibition of chemotactic cell movement, a process partially dependent upon phospholipid signaling. Analysis of this process shows that VPA attenuates the signal-induced translocation of PH(Crac)-green fluorescent protein from cytosol to membrane, suggesting the inhibition of phosphatidylinositol-(3,4,5)-trisphosphate (PIP(3)) production. Direct labeling of lipids in vivo also shows a reduction in PIP and PIP(2) phosphorylation following VPA treatment. We further show that VPA acutely reduces endocytosis and exocytosis-processes previously shown to be dependent upon PIP(3) production. These results suggest that in Dictyostelium, VPA rapidly attenuates phospholipid signaling to reduce endocytic trafficking. To examine this effect in a mammalian model, we also tested depolarization-dependent neurotransmitter release in rat nerve terminals, and we show that this process is also suppressed upon application of VPA and an inhibitor of phosphatidylinositol 3-kinase. Although a more comprehensive analysis of the effect of VPA on lipid signaling will be necessary in mammalian systems, these results suggest that VPA may function to reduce phospholipid signaling processes and thus may provide a novel therapeutic effect for this drug.