Compact cryogenic source of periodic hydrogen and argon droplet beams for relativistic laser-plasma generation

We present a cryogenic source of periodic streams of micrometer-sized hydrogen and argon droplets as ideal mass-limited target systems for fundamental intense laser-driven plasma applications. The highly compact design combined with a high temporal and spatial droplet stability makes our injector ideally suited for experiments using state-of-the-art high-power lasers in which a precise synchronization between the laser pulses and the droplets is mandatory. We show this by irradiating argon droplets with multi-terawatt pulses.     

Cyclin A1 is predominantly expressed in hematological malignancies with myeloid differentiation

OBJECTIVE: To document the frequency of conduction defects and their influence on prognosis in a large series of patients with acute myocardial infarction who underwent coronary care during a period when thrombolytic therapy was in common usage. BACKGROUND: Conduction defects have been associated with an adverse prognosis following acute myocardial infarction, but there are few data on the incidence and outcome of conduction defects since the introduction of thrombolytic therapy. PATIENTS AND METHODS: The study group comprised 1225 consecutive patients with acute myocardial infarction treated in the coronary care unit from 1 January 1988 to 31 December 1994. Conduction defects were recorded prospectively and were classified as follows: complete atrioventricular node block associated with narrow complex escape rhythms; left or right bundle branch block; bifascicular block; complete heart block involving both bundle branches. RESULTS: Electrocardiographic data were available in 1220 patients. Complete atrioventricular node block occurred in 65 (5.3%), left and right bundle branch block in 29 (2.4%) and 44 (3.6%) bifascicular block in 36 (2.9%) and complete heart block involving both bundle branches in 20 (1.6%). The more advanced degrees of block in the bundle branches occurred more commonly in patients with diabetes, previous infarction. Q-wave infarction, anterior infarction and left ventricular failure. Survival analysis showed an increased short- and long-term cardiac mortality in patients with conduction defects, prognosis worsening as the severity of the conduction defect increased. CONCLUSION: Conduction defects complicated acute myocardial infarction in 16% of cases and had a graded impact on the short- and long-term prognosis, patients with advanced bundle branch involvement faring worst. The data showed a small decline in the rate of severe conduction defects compared with previous studies, possibly reflecting the beneficial effects of thrombolytic therapy on infarct size.     

A table for the calculation of d' and BETA.

The methodology of signal detection theory is a preferred technique for assessing an S's ability to discriminate the occurrence of discrete binary events. A compact table is presented which will permit precise calculation of signal detection parameters, d' (discrimination index) and BETA (response bias), for hit and false alarm rate combinations in the range from .01-.99. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Metabolism of dynorphin A1-13 in human CSF

In-vitro incubation of human cerebrospinal fluid (CSF) obtained from patients ranging from 22-78 years with 10 microM of dynorphin A1-13 (Dyn A1-13) resulted in several cleavage products. Dyn A1-12 and A2-13 were identified as the major CSF metabolites by matrix-assisted laser desorption mass spectrometry (LD-MS). Further metabolites were Dyn A1-6, A2-12 and A4-12. LD-MS further suggested the formation of Dyn A1-8, A1-7, A1-10, A7-10, A3-12, A7-12, A3-13, A7-13 and A8-13. The metabolic half-life of Dyn A1-13 at 37 degrees C was approximately 2.5 h (range 1.75-8.5 h), compared to less than one minute in plasma. The half-life of Dyn A1-13 decreased markedly with age or age-associated processes (n = 20, r2 = 0.498). Noncompartmental kinetic analysis in the absence or presence of enzyme inhibitors (leucinethiol 10 microM, captopril 100 microM and GEMSA 20 microM) suggested that Dyn A1-13 is mainly metabolized by carboxypeptidase to A1-12 (51%) and by aminopeptidases to A2-13 (35%). The generation of A1-6 (13%) was only detected under enzyme inhibition. The extent of conversion into the main metabolites did not follow an age-associated trend, thus over-all enzyme levels but no specific enzymatic systems are elevated with age.     

Pharmacokinetic/pharmacodynamic evaluation of systemic effects of flunisolide after inhalation

The pharmacokinetics and pharmacodynamics of flunisolide were studied in healthy volunteers after inhalation. In the morning on the day the study began, volunteers inhaled 0.5 mg of flunisolide with and without oral administration of charcoal, or 1 mg, 2 mg, and 3 mg of flunisolide with concomitant administration of charcoal. A placebo group was used to assess the endogenous cortisol, granulocyte, and lymphocyte baseline levels. Flunisolide plasma levels were determined by high-performance liquid chromatography using a tandem mass spectrometer as detector (HPLC/MS/MS). Cortisol plasma levels and differential white blood cell counts were obtained over 12 hours. An integrated pharmacokinetic/pharmacodynamic (PK/PD) model was applied to link the flunisolide plasma concentrations with the effects on lymphocytes, granulocytes, and cortisol. Maximum concentration levels of 3 to 9 ng/mL of flunisolide were observed after 0.2 to 0.3 hours for all of the investigated doses. The terminal half-life ranged from 1.3 to 1.7 hours. There was no statistical difference between treatments in the presence or absence of orally administered charcoal. The pharmacokinetic/pharmacodynamic (PK/PD) models satisfactorily described the time-courses of the effects on granulocytes, lymphocytes, and cortisol suppression. The resulting E50-values (concentrations to induce 50% of the maximum effect) concurred with the reported values of in vitro receptor binding affinities. The duration of the systemic effects were short because of the short half-life of the drug. Cumulative cortisol suppression increased with dose administration and ranged from 20% to 36%. The PK/PD simulations resulted in a smaller degree of cortisol suppression for the drug administered at 10 PM. The cumulative change from baseline was slightly smaller for the effects on granulocytes and lymphocytes than those on cortisol. This information promotes the comparison with other inhaled glucocorticoids.     

Pharmacokinetic/pharmacodynamic aspects of aerosol therapy using glucocorticoids as a model

Glucocorticoids are predominantly prescribed in asthma therapy as aerosols to achieve high pulmonary effects with reduced systemic spill-over and pronounced pulmonary selectivity. A variety of pharmacokinetic parameters are potentially important for determining pulmonary selectivity. The intent of this article, is to provide a practice-relevant theoretical approach to put the importance of these parameters on pulmonary targeting using pharmacokinetic/pharmacodynamic modeling as a tool in perspective. The applied pulmonary pharmacokinetic/pharmacodynamic model revealed that, in addition to recognized parameters such as systemic clearance, oral bioavailability, and efficiency of pulmonary deposition, other factors, such as the pulmonary release (dissolution) rate and dose, are relevant. However, the volume of distribution (for effect parameters not undergoing a diurnal rhythm) and the receptor affinity of a given glucocorticoid are not important for achieving lung targeting.     

Pharmacokinetics of methylprednisolone and prednisolone after single and multiple oral administration

The pharmacokinetics of methylprednisolone and prednisolone were evaluated in 24 healthy men after oral administration of single and multiple doses for 3 days. For each drug, 6 different administration regimens with doses ranging from 1 to 80-mg of methylprednisolone and 1.25 to 100-mg of prednisolone, and administration intervals ranging from 3 to 24 hours for both were investigated. Plasma was assayed using a normal phase high-performance liquid chromatography (HPLC) method. Methylprednisolone showed linear pharmacokinetics with no apparent dose or time dependency. Prednisolone showed marked dose dependency with higher clearance and volume of distribution for higher doses. This can be explained by its saturable protein binding of plasma, because unbound clearance and unbound volume of distribution were not dose-dependent. After multiple administration, prednisolone showed significant time-dependent pharmacokinetics with increased unbound clearance and increased unbound volume of distribution. Due to the complicated pharmacokinetic properties of prednisolone, it is extremely difficult to determine the dose needed to obtain a desired target concentration. The pharmacokinetics of methylprednisolone are more predictable because methylprednisolone concentrations are proportional to dose, and no determination of plasma protein binding is needed.     

Perceptual repetition blindness effects.

Repetition blindness (RB) may reveal a new limitation on human perceptual processing. Recently, however, researchers have attributed RB to postperceptual processes. The standard rapid serial visual presentation (RSVP) paradigm used in most RB studies is open to such objections. The "single-frame" paradigm introduced by J. C. Johnston and B. L. Hale (1984) allowed investigation of RB with minimal memory demands. Participants made a judgment about whether 1 masked target word was the same or different than a posttarget probe. Confidence ratings permitted use of signal detection methods. In the critical condition for RB, a precue of the posttarget word was provided prior to the target stimulus so that the required judgment amounted to whether the target did or did not repeat the precue word. In control treatments, the precue was an unrelated word or a dummy. Results showed that perceptual sensitivity was significantly reduced in the RB condition relative to baseline control conditions. The data showed that RB can be obtained under conditions in which memory problems are minimal and perceptual sensitivity is assessed independently of biases. RB therefore can be a perceptual phenomenon. (PsycINFO Database Record (c) 2010 APA, all rights reserved)