Human pharmacokinetics and CSF penetration of clavulanic acid

Clavulanic acid, a product of Streptomyces clavuligerus with β-lactam structure, is a potent inhibitor of several β-lactamases. To study its pharmacokinetic and CSF penetration in patients without meningeal inflammation, a single oral dose of 250 mg of clavulanic acid was given to 21 patients. One patient was studied in a multiple dose schedule. Fifteen of these 21 patients had a diagnostic lumbar puncture and 3 neurosurgical patients had a continuous CSF drainage. Serum and urine concentrations of clavulanic acid were available from 22 patients. The mean peak serum concentration was 4·3 mg/l and individual peak serum concentrations ranged from 0·1-9·5 mg/i between 40 and 60 mm after ingestion of clavulanic acid. Urinary recovery between 300 and 400 mm ranged from 0·8-54·3% of the administered dose. The mean absorption half life was 0·26 h and the mean elimination half life was 0·9 h. Considerable degradation of clavulanic acid occurred in vitro at 37°C. In pooled human serum, phosphate buffer pH 7 and 5, an hourly loss of activity of about 10, 7 and 10% respectively, was observe

The Illusion of Being Located in Dynamic Virtual Environments. Can Eye Movement Parameters Predict Spatial Presence?

Attention allocation towards the mediated environment is assumed to be a necessary precondition to feel localized in a virtual world. In presence research, however, the potential of eye movement research has not been fully exploited so far. In this study, participants (N=44) rode on a virtual roller coaster simulation. We compare participants scoring high versus low on presence. During the ride, the eye movements and subjective ex post presence judgments were assessed. We found high sensations of presence to be associated with fewer fixations and a tendency towards longer fixation durations. In contrast to the immersive tendency trait, eye movement parameters can predict presence

Long-term (10 years) prognostic value of a normal thallium-201 myocardial exercise scintigraphy in patients with coronary artery disease documented by angiography

In order to assess the prognostic significance of normal exercise thallium-210 myocardial scintigraphy in patients with documented coronary artery disease, we studied the incidence of cardiac death and non-fatal myocardial infarction in 69 symptomatic patients without prior Q wave myocardial infarction, who demonstrated one or more significant coronary lesions (stenosis ≤70%) on an angiogram performed within 3 months of scintigraphy (Group 1). These patients were compared to a second group of 136 patients with an abnormal exercise scintigram, defined by the presence of reversible defect(s) and angiographically proven coronary artery disease (Group 2), and to a third group of 102 patients with normal exercise scintigraphy without significant coronary lesions (stenosis ≥30%) or with normal coronary angiography (Group 3). In contrast to coronary lesions observed in Group 2, patients in Group I presented more frequently with single- vessel disease (83% vs 35%, P>0·0001) and with more distal lesions (55% vs 23%, P>0·0001). Over a mean follow-up period of 8·6 years, one fatal and eight non-fatal cases of myocardial infarction were observed in Group 1. The majority of patients in Group 1 were treated medically: only 24 (35%) underwent myocardial revascularization, usually by coronary angioplasty. There was no significant difference in the incidence of combined major cardiac events (cardiac death, non-fatal myocardial infarction) in patients with normal exercise scintigraphy, with or without documented coronary artery disease (Groups 1 and 3), while the incidence was higher in Group 2. However, while the mortality remained very low in Group 1, the incidence of non-fatal myocardial infraction was not different from that of Group 2, where most patients underwent revascularization procedures. In conclusion, patients with coronary artery disease and a normal exercise thallium-201 myocardial scintigram usually have mild coronary lesions (single-vessel disease, distal location) and good long-term prognosis, with a low incidence of cardiac deat

Beurteilung der aldosteronantagonistischen Wirkung eines Diuretikums

Peer Reviewe

Predictive Value of Bronchoalveolar Lavage in Excluding a Diagnosis of Pneumocystis carinii Pneumonia During Prophylaxis with Aerosolized Pentamidine

We assessed the negative predictive value of bronchoalveolar lavage (BAL) for Pneumocystis carinii pneumonia (PCP) during prophylaxis with aerosolized pentamidine. On the basis of the assumption that undiagnosed and untreated PCP would progress and become clinically apparent, for 3 months we prospectively followed 34 consecutive cases in which BAL had not detected PCP. All patients were immunodeficient, had a symptomatic human immunodeficiency virus infection, and were evaluated for possible PCP during prophylaxis with aerosolized pentamidine. No transbronchial biopsies were performed. In 32 of 34 cases, a diagnosis of PCP could be excluded because of other definite diagnoses or improvement during the follow-up. Despite negative results of an examination of their BAL fluid, two patients received empirical treatment that was active against PCP; these patients were regarded as possibly having undiagnosed PCP. Thus, the negative predictive value of BAL alone was at least 94% (32 of 34 cases) in excluding a diagnosis of PCP during prophylaxis with aerosolized pentamidin

On the state dependency of fast feedback processes in (palaeo) climate sensitivity

Palaeo data have been frequently used to determine the equilibrium (Charney) climate sensitivity $S^a$, and - if slow feedback processes (e.g. land ice-albedo) are adequately taken into account - they indicate a similar range as estimates based on instrumental data and climate model results. Most studies implicitly assume the (fast) feedback processes to be independent of the background climate state, e.g., equally strong during warm and cold periods. Here we assess the dependency of the fast feedback processes on the background climate state using data of the last 800 kyr and a conceptual climate model for interpretation. Applying a new method to account for background state dependency, we find $S^a=0.61\pm0.06$ K(Wm$^{-2}$)$^{-1}$ using the latest LGM temperature reconstruction and significantly lower climate sensitivity during glacial climates. Due to uncertainties in reconstructing the LGM temperature anomaly, $S^a$ is estimated in the range $S^a=0.55-0.95$ K(Wm$^{-2}$)$^{-1}$.Comment: submitted to Geophysical Research Letter

Evaluation of boundary layer cloud parameterizations in the ECHAM5 general circulation model using CALIPSO and CloudSat satellite data

Three different boundary layer cloud models are incorporated into the ECHAM5 general circulation model (GCM) and compared to CloudSat and CALIPSO satellite observations. The first boundary layer model builds upon the standard Tiedtke (1989) parameterization for shallow convection with an adapted convective trigger; the second is a bulk parameterization of the effects of transient shallow cumulus clouds; and lastly the Dual Mass Flux (DMF) scheme adjusted to better represent shallow convection. The three schemes improved (Sub)Tropical oceanic low-level cloud cover, however, the fraction of low-level cloud cover remains underestimated compared to CALIPSO observations. The representation of precipitation was improved by all schemes as they reduced the frequency of light intensity events <0.01 mm d-1, which were found to dominate the radar reflectivity histograms as well as be the greatest source of differences between ECHAM5 and CloudSat radar reflectivity histograms. For both lidar and radar diagnostics, the differences amongst the schemes are smaller than the differences compared to observations. While the DMF approach remains experimental, as its top-of-atmosphere radiative balance has not been retuned, it shows the most promise in producing nonprecipitating boundary layer clouds. With its internally consistent boundary layer scheme that uses the same bimodal joint distribution with a diffusive and an updraft component for clouds and turbulent transport, the ECHAM5_DMF produces the most realistic boundary layer depth as indicated by the cloud field. In addition, it reduced the frequency of large-scale precipitation intensities of <0.01 mm d-1 the greatest

Faster Correlation Attack on Bluetooth Keystream Generator E0

Abstract. We study both distinguishing and key-recovery attacks against E0, the keystream generator used in Bluetooth by means of correlation. First, a powerful computation method of correlations is formulated by a recursive expression, which makes it easier to calculate correlations of the finite state machine output sequences up to 26 bits for E0 and allows us to verify the two known correlations to be the largest for the first time. Second, we apply the concept of convolution to the analysis of the distinguisher based on all correlations, and propose an efficient distinguisher due to the linear dependency of the largest correlations. Last, we propose a novel maximum likelihood decoding algorithm based on fast Walsh transform to recover the closest codeword for any linear code of dimension L and length n. It requires time O(n + L · 2 L) and memory min(n, 2 L). This can speed up many attacks such as fast correlation attacks. We apply it to E0, and our best key-recovery attack works in 2 39 time given 2 39 consecutive bits after O(2 37) precomputation. This is the best known attack against E0 so far.