Frühmobilisation auf der Intensivstation – Sind robotergestützte Systeme die Zukunft?

Die Anaesthesiologie - Bei etwa 43?% aller Überlebenden der Intensivmedizin wird ein erworbenes Syndrom an Muskelschwäche beobachtet, welches Überleben und Lebensqualität...     

Toward hyperpolarized molecular imaging of HIV: synthesis and longitudinal relaxation properties of 15N‐Azidothymidine

Previously unreported ¹⁵N labeled Azidothymidine (AZT) was prepared as an equimolar mixture of two isotopomers: 1‐¹⁵N‐AZT and 3‐¹⁵N‐AZT. Polarization decay of ¹⁵N NMR signal was studied in high (9.4 T) and low (~50 mT) magnetic fields. ¹⁵N T₁ values were 45 ± 5 s (1‐¹⁵N‐AZT) and 37 ± 2 s (3‐¹⁵N‐AZT) at 9.4 T, and 140 ± 16 s (3‐¹⁵N‐AZT) at 50 mT. ¹⁵N‐AZT can be potentially ¹⁵N hyperpolarized by several methods. These sufficiently long ¹⁵N‐AZT T₁ values potentially enable hyperpolarized in vivo imaging of ¹⁵N‐AZT, because of the known favorable efficient (i.e., of the time scale shorter than the longest reported here ¹⁵N T₁) kinetics of uptake of injected AZT. Therefore, 3‐¹⁵N‐AZT can be potentially used for HIV molecular imaging using hyperpolarized magnetic resonance imaging.     

Impaired vitamin E status in patients with parenchymal liver cirrhosis: relationships with lipoprotein compositional alterations, nutritional factors, and oxidative susceptibility of plasma

Vitamin E is a lipid-soluble vitamin and an important antioxidant that protects lipoproteins and cell membranes from lipid peroxidation. The aims of the present study were to investigate, in patients with parenchymal liver cirrhosis, the following: (1) nutritional and vitamin E status in relation to compositional changes in lipoproteins; and (2) the effects of these alterations on the patients' plasma susceptibility to copper-mediated oxidation. Patients (n = 55) with liver cirrhosis and 25 healthy volunteers had vitamin E in serum and in isolated lipoprotein fractions analyzed by high-performance liquid chromatography (HPLC). Plasma susceptibility to peroxidation was measured by incubation with Cu(2+). Nutritional status was assessed by anthropometry. Vitamin E concentration was significantly decreased (P <.001) in the serum and in very-low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) in cirrhotic patients. The decrease was related to the degree of liver impairment. There were significant correlations between cholesterol and vitamin E concentrations in serum and in all the lipoprotein fractions (r between 0.72 and 0.89; P <.001) in cirrhotic patients, but there were no significant relationships between vitamin E and any of the anthropometric indices of nutritional status. The plasma maximal oxidation rate was significantly increased in cirrhotic patients (P <.01) and was inversely related to the serum concentration of vitamin E (P <.05). We conclude that lipoprotein alterations and not nutritional factors should be regarded as major factors explaining serum vitamin E reduction in patients with parenchymal liver cirrhosis, and that vitamin E depletion is associated with an increased plasma susceptibility to oxidation.     

Kinetic characterization of human hydroxyacid–oxoacid transhydrogenase: Relevance toD-2-hydroxyglutaric and γ-hydroxybutyric acidurias

Summary We investigated the presence of hydroxyacid–oxoacid transhydrogenase (HOT), which catalyses the cofactor-independent conversion of γ-hydroxybutyrate (GHB) to succinic semialdehyde coupled to reduction of 2-ketoglutarate (2-KG) to D-2-hydroxyglutarate (D-2-HG), in human liver extracts employing [²H₆]GHB and 2-KG as substrates. We measured incorporation of ²H in D-[²H]2-HG using GC-MS analyses, providing evidence for HOT activity in humans. Kinetic characterization of HOT was undertaken in forward and reverse directions. We employed [²H₆]GHB and [²H₄]2-KG as cosubstrates in order to develop a HOT activity assay in cultured human fibroblasts derived from patients with D-2-hydroxyglutaric aciduria. HOT activity was quantified in this system by the measurement of D-[²H₅]2-HG production. Fibroblasts derived from patients with D-2-hydroxyglutaric aciduria showed normal HOT activities. Our results provide the first demonstration and preliminary kinetic characterization of HOT activity in human tissues.     

Hypersensitivity pneumonitis in a cluster of sawmill workers: a 10-year follow-up of exposure,symptoms, and lung function

Background:

The long-term prognosis of repeated acute episodes of hypersensitivity pneumonitis (HP) is not well described. We report on a 10-year follow-up of a 10-person cluster from a Norwegian sawmill who had all experienced relapsing episodes of HP.

Objectives:

To evaluate the health symptoms, work-related sick-leave, and lung function of 10 workers exposed to mold in a Norwegian sawmill.

Methods:

Participants were evaluated at baseline and 10 years later at follow-up. A structured interview, measurement of serum IgG antibodies to Rhizopus microsporus (R. microsporus) antigens, lung function tests, high resolution computed tomography (HRCT) of the chest, and personal measurements of exposure to mold spores and dust were completed for each participant.

Results:

At baseline, nearly all workers reported acute episodes of HP more than twice a month. At follow-up, both the frequency and intensity of symptoms had declined. Sick-leave was reduced and gas diffusing capacity improved – paralleling the gradually reduced air levels of mold spores.

Conclusions:

In spite of an initially high occurrence of symptoms, long-term clinical and physiological outcome was good. With reduced exposure to mold spores, symptoms declined and lung function was restored.     

Imaging flow cytometry for automated detection of hypoxia‐induced erythrocyte shape change in sickle cell disease

In preclinical and early phase pharmacologic trials in sickle cell disease, the percentage of sickled erythrocytes after deoxygenation, an ex vivo functional sickling assay, has been used as a measure of a patient's disease outcome. We developed a new sickle imaging flow cytometry assay (SIFCA) and investigated its application. To perform the SIFCA, peripheral blood was diluted, deoxygenated (2% oxygen) for 2 hr, fixed, and analyzed using imaging flow cytometry. We developed a software algorithm that correctly classified investigator tagged “sickled” and “normal” erythrocyte morphology with a sensitivity of 100% and a specificity of 99.1%. The percentage of sickled cells as measured by SIFCA correlated strongly with the percentage of sickle cell anemia blood in experimentally admixed samples (R = 0.98, P ≤ 0.001), negatively with fetal hemoglobin (HbF) levels (R = ?0.558, P = 0.027), negatively with pH (R = ?0.688, P = 0.026), negatively with pretreatment with the antisickling agent, Aes‐103 (5‐hydroxymethyl‐2‐furfural) (R = ?0.766, P = 0.002), and positively with the presence of long intracellular fibers as visualized by transmission electron microscopy (R = 0.799, P = 0.002). This study shows proof of principle that the automated, operator‐independent SIFCA is associated with predictable physiologic and clinical parameters and is altered by the putative antisickling agent, Aes‐103. SIFCA is a new method that may be useful in sickle cell drug development. Am. J. Hematol. 89:598–603, 2014. © 2014 Wiley Periodicals, Inc.