751 research outputs found
High-performance liquid chromatography analysis of mezlocillin, piperacillin, their degradation products, and of ioxitalamic acid in plasma and urine of healthy volunteers
In plasma and urine of 10 healthy volunteers after intravenous administration of 4 g mezlocillin and piperacillin, respectively, the parent compounds as well as degradation products were assayed by high-performance liquid chromatography. Ioxitalamic acid, a renal contrast medium, was administered simultaneously, in order to measure the glomerular filtration rate, and to control the collection of 24-h urine. As metabolite of mezlocillin the corresponding penicilloic acid only was found, whereas in the case of piperacillin a further degradation product was observed. Half of the doses given was recovered in the urine as unchanged drugs, and in addition 5-10% as metabolites. No differences were found in the pharmacokinetic behaviour of both antibiotics
Thirty-fold: Extreme gravitational lensing of a quiescent galaxy at
We report the discovery of eMACSJ1341-QG-1, a quiescent galaxy at
located behind the massive galaxy cluster eMACSJ1341.92442 (). The
system was identified as a gravitationally lensed triple image in Hubble Space
Telescope images obtained as part of a snapshot survey of the most X-ray
luminous galaxy clusters at and spectroscopically confirmed in
ground-based follow-up observations with the ESO/X-Shooter spectrograph. From
the constraints provided by the triple image, we derive a first, crude model of
the mass distribution of the cluster lens, which predicts a gravitational
amplification of a factor of 30 for the primary image and a factor of
6 for the remaining two images of the source, making eMACSJ1341-QG-1 by
far the most strongly amplified quiescent galaxy discovered to date. Our
discovery underlines the power of SNAPshot observations of massive, X-ray
selected galaxy clusters for lensing-assisted studies of faint background
populations
Probabilistic Search for Object Segmentation and Recognition
The problem of searching for a model-based scene interpretation is analyzed
within a probabilistic framework. Object models are formulated as generative
models for range data of the scene. A new statistical criterion, the truncated
object probability, is introduced to infer an optimal sequence of object
hypotheses to be evaluated for their match to the data. The truncated
probability is partly determined by prior knowledge of the objects and partly
learned from data. Some experiments on sequence quality and object segmentation
and recognition from stereo data are presented. The article recovers classic
concepts from object recognition (grouping, geometric hashing, alignment) from
the probabilistic perspective and adds insight into the optimal ordering of
object hypotheses for evaluation. Moreover, it introduces point-relation
densities, a key component of the truncated probability, as statistical models
of local surface shape.Comment: 18 pages, 5 figure
Quantum chaos in nanoelectromechanical systems
We present a theoretical study of the electron-phonon coupling in suspended
nanoelectromechanical systems (NEMS) and investigate the resulting quantum
chaotic behavior. The phonons are associated with the vibrational modes of a
suspended rectangular dielectric plate, with free or clamped boundary
conditions, whereas the electrons are confined to a large quantum dot (QD) on
the plate's surface. The deformation potential and piezoelectric interactions
are considered. By performing standard energy-level statistics we demonstrate
that the spectral fluctuations exhibit the same distributions as those of the
Gaussian Orthogonal Ensemble (GOE) or the Gaussian Unitary Ensemble (GUE),
therefore evidencing the emergence of quantum chaos. That is verified for a
large range of material and geometry parameters. In particular, the GUE
statistics occurs only in the case of a circular QD. It represents an anomalous
phenomenon, previously reported for just a small number of systems, since the
problem is time-reversal invariant. The obtained results are explained through
a detailed analysis of the Hamiltonian matrix structure.Comment: 14 pages, two column
Anomalous quantum chaotic behavior in nanoelectromechanical structures
It is predicted that for sufficiently strong electron-phonon coupling an
anomalous quantum chaotic behavior develops in certain types of suspended
electro-mechanical nanostructures, here comprised by a thin cylindrical quantum
dot (billiard) on a suspended rectangular dielectric plate. The deformation
potential and piezoelectric interactions are considered. As a result of the
electron-phonon coupling between the two systems the spectral statistics of the
electro-mechanic eigenenergies exhibit an anomalous behavior. If the center of
the quantum dot is located at one of the symmetry axes of the rectangular
plate, the energy level distributions correspond to the Gaussian Orthogonal
Ensemble (GOE), otherwise they belong to the Gaussian Unitary Ensemble (GUE),
even though the system is time-reversal invariant.Comment: 4 pages, pdf forma
Casimir force between integrable and chaotic pistons
We have computed numerically the Casimir force between two identical pistons
inside a very long cylinder, considering different shapes for the pistons. The
pistons can be considered as quantum billiards, whose spectrum determines the
vacuum force. The smooth part of the spectrum fixes the force at short
distances, and depends only on geometric quantities like the area or perimeter
of the piston. However, correcting terms to the force, coming from the
oscillating part of the spectrum which is related to the classical dynamics of
the billiard, are qualitatively different for classically integrable or chaotic
systems. We have performed a detailed numerical analysis of the corresponding
Casimir force for pistons with regular and chaotic classical dynamics. For a
family of stadium billiards, we have found that the correcting part of the
Casimir force presents a sudden change in the transition from regular to
chaotic geometries.Comment: 13 pages, 10 figure
Pharmacokinetics of tigecycline in critically ill patients with liver failure defined by maximal liver function capacity test (LiMAx)
Background:
In critically ill patients, tigecycline (TGC) remains an important therapeutic option due to its efficacy against multiresistant Gram-positive and Gram-negative bacteria. TGC is metabolized and eliminated predominantly by the liver. Critical illness-induced liver failure may have a profound impact on the pharmacokinetic of TGC. In the present study, we aimed to establish a link between the degree of liver dysfunction and TGC plasma concentration using the novel maximum liver function capacity (LiMAx) test, as a dynamic liver function test.
Materials/methods:
The prospective study included 33 patients from a surgical ICU with the clinical indication for antibiotic therapy with TGC. The patients received 100 mg loading dose of TGC followed by intermittent standard doses of 50 mg q12. Blood samples for TGC plasma concentration were collected at 0.3, 2, 5, 8 and 11.5 h in a steady-state condition after at least 36 h post-standard dosage. The results were analyzed by means of a high-performance liquid chromatography (HPLC) method. Within the same day, the LiMAx test was carried out and routine blood parameters were measured.
Results:
Peak plasma concentrations of TGC were significantly higher in patients with severe liver failure (LiMAxââ300 ”g/kg/h). The pharmacokinetic curves revealed higher values in severe liver failure at any measured point. Moreover, LiMAx and total bilirubin were the only liver-related parameters that correlated with TGC Cmax.
Conclusions:
The present study demonstrates a high variability of TGC plasma concentrations in critically ill patients. The results show a significant correlation between the degree of liver dysfunction, measured by the LiMAx test, and TGC Cmax. LiMAx test may be a helpful tool beyond others for adjusting the required dosage of hepatic metabolized antibiotics in critically ill patients.
Trial registry DRKSâGerman clinical trials register; Trial registration number: DRKS00008888; Date of registration: 07-17-2015; Date of enrolment of the first participant to the trial: 12-10-201
Pharmacokinetics and pharmacodynamics of antifungals in children and their clinical implications
Invasive fungal infections are a significant cause of morbidity and mortality in children. Successful management of these systemic infections requires identification of the causative pathogen, appropriate antifungal selection, and optimisation of its pharmacokinetic and pharmacodynamic properties to maximise its antifungal activity and minimise toxicity and the emergence of resistance. This review highlights salient scientific advancements in paediatric antifungal pharmacotherapies and focuses on pharmacokinetic and pharmacodynamic studies that underpin current clinical decision making. Four classes of drugs are widely used in the treatment of invasive fungal infections in children, including the polyenes, triazoles, pyrimidine analogues and echinocandins. Several lipidic formulations of the polyene amphotericin B have substantially reduced the toxicity associated with the traditional amphotericin B formulation. Monotherapy with the pyrimidine analogue flucytosine rapidly promotes the emergence of resistance and cannot be recommended. However, when used in combination with other antifungal agents, therapeutic drug monitoring of flucytosine has been shown to reduce high peak flucytosine concentrations, which are strongly associated with toxicity. The triazoles feature large inter-individual pharmacokinetic variability, although this pattern is less pronounced with fluconazole. In clinical trials, posaconazole was associated with fewer adverse effects than other members of the triazole family, though both posaconazole and itraconazole display erratic absorption that is influenced by gastric pH and the gastric emptying rate. Limited data suggest that the clinical response to therapy may be improved with higher plasma posaconazole and itraconazole concentrations. For voriconazole, pharmacokinetic studies among children have revealed that children require twice the recommended adult dose to achieve comparable blood concentrations. Voriconazole clearance is also affected by the cytochrome P450 (CYP) 2C19 genotype and hepatic impairment. Therapeutic drug monitoring is recommended as voriconazole pharmacokinetics are highly variable and small dose increases can result in marked changes in plasma concentrations. For the echinocandins, the primary source of pharmacokinetic variability stems from an age-dependent decrease in clearance with increasing age. Consequently, young children require larger doses per kilogram of body weight than older children and adults. Routine therapeutic drug monitoring for the echinocandins is not recommended. The effectiveness of many systemic antifungal agents has been correlated with pharmacodynamic targets in in vitro and in murine models of invasive candidiasis and aspergillosis. Further study is needed to translate these findings into optimal dosing regimens for children and to understand how these agents interact when multiple antifungal agents are used in combination
Increased human defensine levels hint at an inflammatory etiology of bisphosphonate-associated osteonecrosis of the jaw: An immunohistological study
<p>Abstract</p> <p>Background</p> <p>Human ÎČ-defensins (hBD) are antimicrobial peptides that are an integral part of bone innate immunity. Recently, it could be shown that expression of hBD-1, -2 and -3 were upregulated in cases of osteomyelitis of the jaws. In order to gain insight into the possible impairment of hBD metabolism in bisphosphonate-associated osteonecrosis of the jaws (BONJ), the present exploratory study was designed so as to determine the qualitative and quantitative expression of afore mentioned hBDs in BONJ and infected osteoradionecrosis (ORN), both of which represent inflammatory bone diseases.</p> <p>Methods</p> <p>Bone samples were collected from patients with BONJ (n = 20) and ORN (n = 20). Non-infected healthy bone samples (n = 20) were included as controls. Immunohistological staining in an autostainer was carried out by the (Strept-ABC)-method against hBD-1,-2,-3. Specific positive vs. negative cell reaction of osteocytes (labeling index) near the border of bony resection was determined and counted for quantitative analysis. Number of vital osteocytes vs. empty osteocytes lacunae was compared between groups.</p> <p>Results</p> <p>hBD-1,-2 and -3 could be detected in BONJ as well as ORN and healthy bone samples. Immunoreactivity against hBD-2 and -3 was significantly higher in BONJ than in ORN and healthy jaw bone samples. Number of empty osteocyte lacunae was significantly higher in ORN compared with BONJ (<it>P </it>= 0.001).</p> <p>Conclusion</p> <p>Under the condition of BONJ an increased expression of hBD-1,-2,-3 is detectable, similarly to the recently described upregulation of defensins in chronically infected jaw bones. It remains still unclear how these findings may relate to the pathoetiology of these diseases and whether this is contributing to the development of BONJ and ORN or simply an after effect of the disease.</p
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