Assessment of respiratory system compliance with electrical impedance tomography using a positive end-expiratory pressure wave maneuver during pressure support ventilation: a pilot clinical study.

INTRODUCTION: Assessment of respiratory system compliance (Crs) can be used for individual optimization of positive end-expiratory pressure (PEEP). However, in patients with spontaneous breathing activity, the conventional methods for Crs measurement are inaccurate because of the variable muscular pressure of the patient. We hypothesized that a PEEP wave maneuver, analyzed with electrical impedance tomography (EIT), might be suitable for global and regional assessment of Crs during assisted spontaneous breathing. METHODS: After approval of the local ethics committee, we performed a pilot clinical study in 18 mechanically ventilated patients (61 ± 16 years (mean ± standard deviation)) who were suitable for weaning with pressure support ventilation (PSV). For the PEEP wave, PEEP was elevated by 1 cmH2O after every fifth breath during PSV. This was repeated five times, until a total PEEP increase of 5 cmH2O was reached. Subsequently, PEEP was reduced in steps of 1 cmH2O in the same manner until the original PEEP level was reached. Crs was calculated using EIT from the global, ventral and dorsal lung regions of interest. For reference measurements, all patients were also examined during controlled mechanical ventilation (CMV) with a low-flow pressure-volume maneuver. Global and regional Crs(low-flow) was calculated as the slope of the pressure-volume loop between the pressure that corresponded to the selected PEEP and PEEP +5 cmH2O. For additional reference, Crs during CMV (Crs(CMV)) was calculated as expired tidal volume divided by the difference between airway plateau pressure and PEEP. RESULTS: Respiratory system compliance calculated from the PEEP wave (Crs(PEEP wave)) correlated closely with both reference measurements (r = 0.79 for Crs(low-flow) and r = 0.71 for Crs(CMV)). No significant difference was observed between the mean Crs(PEEP wave) and the mean Crs(low-flow). However, a significant bias of +17.1 ml/cmH2O was observed between Crs(PEEP wave) and Crs(CMV). CONCLUSION: Analyzing a PEEP wave maneuver with EIT allows calculation of global and regional Crs during assisted spontaneous breathing. In mechanically ventilated patients with spontaneous breathing activity, this method might be used for assessment of the global and regional mechanical properties of the respiratory system.

[Acute kidney injury--prevention, risk stratification and biomarkers]. / Akutes nierenversagen--prävention, risikostratifizierung und biomarker.

Acute kidney injury influences negatively morbidity and mortality of the critically ill patient and causes increased costs by prolonged length of stay in the intensive care unit. At present the diagnosis and classification of acute kidney injury is derived from the RIFLE and AKIN criteria based on serum creatinine and urine output. The possible pre-, intra- and postrenal causes of acute kidney injury are the starting points of preventive therapy and risk stratification.Because of the unreliability of serum creatinine in critically ill patients the development of new biomarkers raises hope. But none of the promising candidates is used in clinical routine up to now. For evaluation of clinical benefit the results of large prospective multicenter studies have to be awaited.

In vitro characterization of the thyroidal uptake of O-(2-[(18)F]fluoroethyl)-L-tyrosine.

OBJECTIVES: Positron emission tomography (PET) using O-(2-[(18)F]fluoroethyl)-l-tyrosine (FET) has been successfully employed in the diagnostic workup of brain tumors. Knowledge on the mechanisms of the uptake of radiolabeled amino acids into thyroidal tissues and well-differentiated thyroid carcinomas is limited. We therefore studied several factors potentially governing the uptake of FET in the rat thyroid cell line FRTL-5 in comparison with thyroid tumor cell lines of human origin. METHODS: FET uptake was determined in thyroid-stimulating hormone (TSH)-stimulated and TSH-deprived FRTL-5 cells, as well as in the cell lines U-138 MG (human glioblastoma), Onco DG-1 (human papillary thyroid carcinoma) and ML-1 (human follicular thyroid carcinoma). The TSH responsiveness of cells was measured by the incubation of TSH-treated and untreated control cells with 2-[(18)F]fluoro-2-deoxyglucose (FDG). All cellular tracer uptake values were related to total protein mass and expressed as percentage per milligram. For countertransport studies, FRTL-5 cells were exposed to 10-300 microM tyrosine methyl ester. TSH-stimulated and TSH-deprived FRTL-5 cells were incubated with 100 kBq/ml FET for 20 min. 2-Aminobicyclo-[2,2,1]heptane-2-carboxylic acid (BCH), alpha-(methylamino)-isobutyric acid, L-serine and tryptophan were used as competitive inhibitors of FET uptake. All inhibition experiments were repeated with the human thyroid carcinoma cell lines to obtain comparative FET uptake values. RESULTS: The FET uptake was 155+/-30%/mg in FRTL-5 cells (n=6), 108+/-14%/mg in U-138 MG cells (n=6), 194+/-60%/mg in ML-1 cells (n=9) and 64+/-23%/mg in Onco DG-1 cells (n=6) under identical incubation conditions. Preloading with tyrosine methyl ester increased cellular FET uptake dose dependently in FRTL-5 cells (165+/-25%, n=6). While TSH increased the uptake of FDG in FRTL-5 cells by sixfold, there was no TSH effect on FET accumulation. FET uptake by TSH-treated FRTL-5 cells was sodium independent and significantly inhibited by BCH (91.4+/-3.0%, n=9), tryptophan (94.8+/-1.6%, n=8) and serine (83.2+/-10.8%, n=12). TSH-starved FRTL-5 cells had a sodium-dependent component with a similar inhibition pattern. Onco DG-1 mainly confirmed the inhibition pattern of FET uptake in FRTL-5 cells, reflecting System-L-mediated FET uptake that was blocked by BCH and serine (72-85%, n=9). ML-1 cells revealed a pronounced sodium-dependent FET uptake that was inhibited by tryptophan (70+/-10%, n=9, P<.05) in the presence and in the absence of sodium, suggesting a contribution of alternative amino acid carriers. CONCLUSION: FET uptake by FRTL-5 cells is not TSH dependent. FET uptake by FRTL-5 cells seems to be mainly mediated by a carrier exhibiting the characteristics of the System L amino acid transporter. FET uptake in thyroid cells and thyroid carcinoma cells was in the same range as that in a glioblastoma cell line. This encourages further research efforts towards the clinical evaluation of FET for the diagnostic workup of well-differentiated thyroid carcinomas.

In vitro studies on the signal transduction of thyroidal uptake of 18F-FDG and 131I-Iodide.

UNLABELLED: Glucose metabolism in radioiodine-negative metastases of differentiated thyroid carcinomas (DTC) may still be increased by thyroid-stimulating hormone (TSH) as demonstrated by PET with 18F-FDG. The mechanisms of signal transduction involved in that process are as yet not completely understood. Therefore, the aim of this study was to investigate the effects of TSH, of an analog of cyclic adenosine monophosphate (dibutyryl cyclic AMP (Bu)2cAMP), and of inhibitors of the phosphatidylinositol 3-kinase (PI3-kinase) and of the protein kinase A (PKA) on 18F-FDG and radioiodide uptake in the thyroid cell line FRTL-5. METHODS: FRTL-5 cells were cultured in the presence of hormones with or without 1 mU/ mL TSH. Glucose carrier (GLUT-1) was determined by Western blot analysis. Cells were incubated with 0.5-1.0 MBq/mL 18F-FDG for 1 h or 18-37 kBq/mL 131I for 45 min, respectively, and tracer uptake was related to protein concentration. (Bu)2cAMP (1 mmol/L) was used as cAMP enhancer, H89 (0.25-25 micromol/L) as selective PKA inhibitor, and wortmannin (1 micromol/L) as inhibitor of PI3-kinase. RESULTS: TSH induced a 2.6-fold +/- 0.5 increase of radioiodide uptake in FRTL-5 cells (P < 0.001, n = 8). The use of wortmannin inhibited TSH-induced uptake of 131I only moderately by 21.1% +/- 3.5% (P < 0.05, n = 8), whereas H89 markedly blocked the effect of TSH by 53.8% +/- 16.7% (P < 0.001, n = 8). TSH enhanced GLUT-1 concentration of FRTL-5 cell membrane preparations by a factor of 1.6 (n = 3). TSH-treated cells showed a 2.6-fold increased uptake of 18F-FDG (P < 0.001, n = 20). Stimulation by (Bu)2cAMP analogously increased 18F-FDG uptake (P < 0.001, n = 20). Wortmannin, but not H89, significantly inhibited TSH- and (Bu)2cAMP-stimulation of 18F-FDG uptake by 42% +/- 25% (P < 0.001, n = 20) and 42% +/- 31% (P < 0.001, n = 20), respectively. CONCLUSION: The effect of TSH and cAMP on 18F-FDG uptake by FRTL-5 cells is mediated by PI3-kinase and not by PKA, thus differing from the mechanism of radioiodide accumulation of this cell line. This observation is one possible explanation for the persistence of TSH-dependent 18F-FDG uptake in radioiodine-negative metastases of DTC.