Abuse liability of oxycodone as a function of pain and drug use history.

The relationship between pain and prescription opioid abuse is poorly understood. Determining whether a patient is seeking additional opioid medications in order to alleviate pain or to abuse the drugs can be difficult. The present study was designed to evaluate two variables that may influence the abuse liability of opioids: drug use history and the presence or absence of experimentally induced pain. Eighteen healthy participants completed this outpatient study. One group was abusing prescription opioids (N=9) and one group had used prescription opioids medically but did not abuse them (N=9). All participants completed twelve sessions during which the effects of orally delivered oxycodone (0, 15, 30mg/70kg, PO) were examined. One dose was tested per day under double-blind conditions and sessions were separated by at least 48h. During the first "sample" session each week, participants were given $10 and the dose that was available later that week. During the second "choice" session, participants could self-administer either money or the previously sampled dose. Six sessions involved repeated hand immersions in cold water (4 degrees C) and six sessions involved immersions in warm water (37 degrees C). Most of the positive subjective effects of oxycodone were similar between the groups, but oxycodone self-administration significantly differed between groups. Non-abusers self-administered active doses of oxycodone only when they were in pain while abusers self-administered oxycodone regardless of the pain condition. These data suggest that an assessment of the reinforcing effects of opioids may be a sensitive method for differentiating opioid abusers from non-abusers.

Xanthan and gellan degradation by bacteria of activated sludge.

Owing to increasing amounts of xanthan and gellan in food, cosmetics and pharmaceuticals, as well as in some technical spheres, studies were carried out on the xanthan and gellan degrading bacteria present in activated sludge. The activated sludge used in the study was able to degrade both carbohydrates over 7 days, with levels of xanthan and gellan utilizing microbes estimated at 10(5) cells/g of dry sludge weight. Isolating key degrading bacteria revealed the important role of genus Paenibacillus in xanthan degradation and prosthecate bacterium Verrucomicrobium sp. GD, which was capable of gellan utilization. Further tests performed with both strains showed they were able to degrade other types of carbohydrate polymers, and that Verrucomicrobium sp. GD did not possess extracellular free gellan depolymerase.

[Anterior luxation of the humerus complicated by thrombosis of the axillary artery--a case review]. / Prední luxace humeru komplikovaná trombózou arteria axillaris--kazuistika.

The authors report on a rare complication of humeral luxations, thrombosis of the axillary artery. They present a literature overview to discuss possible causes and mechanisms of venous complications. Although humeral luxations are very frequently diagnosed in traumatological departments, vascular complications are rare. Therefore, thorough examination of every single patient is a must, taking the above possibility into consideration.

Full-body gaze control mechanisms elicited during locomotion: effects of VOR adaptation.

We have previously shown that multiple, interdependent, full- body sensorimotor subsystems aid gaze stabilization during locomotion. In the present study we investigated how the full-body gaze control system responds following exposure to visual-vestibular conflict known to adaptively modify vestibulo-ocular reflex (VOR) function. Subjects (n = 14) walked (6.4 km/h) on a motorized treadmill before and after they were exposed to 0.5X minifying lenses worn for 30 minutes during self-generated sinusoidal vertical head rotations performed while seated. Results indicate that, following the exposure the major changes that subjects showed were to: 1) decrease the amplitude of head pitch and vertical translation of the torso movement with respect to space; 2) increase the amount of knee and ankle flexion during the initial stance phase of the gait cycle. A correlation analysis showed that: 1) changes in the head pitch significantly co-varied with that of the vertical torso translation 2) changes in the knee flexion significantly co-varied with that of the ankle flexion during the initial stance phase of the gait cycle 3) changes in the vertical torso translation significantly co-varied with that of the ankle flexion during the initial stance phase of the gait cycle. Thus we infer that the changes in the magnitude after VOR adaptation in comparison to their pre adaptation responses serve to aid gaze stabilization during locomotion. The significant covariation of the changes between subsystems provides further evidence that the full body contributes to gaze stabilization during locomotion, and its different functional elements are subject to adaptive reorganization following exposure to visual-vestibular conflict.

The association of perceived health, clinical status, and initiation of HAART (highly active antiretroviral therapy) in adolescents.

PURPOSE: To examine factors associated with the initiation of highly active antiretroviral therapy (HAART) in adolescents to understand better how current National Institutes of Health (NIH) Guidelines are being used in practice. METHODS: HIV infected and HAART-naive adolescents seen at 15 REACH clinical sites were selected. Repeated measures methodology using generalized estimating equations was applied to identify associations between subject demographic characteristics, risk behaviors, perceived health, and clinical status with the outcome measure of HAART initiation during the first 24 study months. RESULTS: A total of 219 subjects were eligible for analysis; HAART was prescribed in 115 (53%). Significant univariate associations with HAART prescription included lower CD4(+) T cell counts (OR = 1.7, 95% CI: 1.1-2.6), higher viral loads (OR = 2.7, 95% CI: 1.5-5.0), and calendar year of HAART prescription (OR as high as 2.4, 95% CI: 1.1-5.2). Multivariate results showed that after controlling for CD4(+) T cell counts below 500 cells/mm(3), higher plasma HIV-1 RNA (

Natural killer cell enumeration and function in HIV-infected and high-risk uninfected adolescents.

This is the first report of natural killer cell enumeration and function in HIV-infected and high-risk uninfected adolescents. We examined the association of demographic characteristics of this cohort with three outcomes: CD16+ cell absolute count, lytic units per peripheral blood mononuclear cell (PBMC), and lytic units per natural killer (NK) cell. We also examined the association of CD4, CD38, and antiretroviral therapy (ART) use with these outcomes in the subset of HIV-infected adolescents. Adolescents participating in an on-going longitudinal study (the REACH study) were sampled for CD16+ cell count and NK function. This cross-sectional analysis was performed on 412 subjects with NK cell data available. HIV-positive males had higher numbers of CD3-/CD16+/CD56+ NK cells than HIV-positive females. However, for the HIV-negative subjects, we did not observe a gender-related effect for absolute NK cell numbers. Gender, however, was a significant covariate for the analysis, using lytic units per PBMC as the unit of measurement, with males showing higher values than females. Age was not a predictive covariate for any of the three assessments of NK cell number and function examined. Our observations concerning the HIV-positive individuals indicate that reduced CD4+ T cell counts were associated with decreased circulating CD3-/CD16+/CD56+ NK cells. We also observed an association between elevation of CD8+/CD38+/DR+ lymphocytes and lower NK lytic units per PBMC. The results of our multivariate models indicate that there is a reduced number of NK cells and reduced lytic units per PBMC in patients receiving single or multidrug antiretroviral therapy. There are changes in circulating NK cell number and function in HIV-infected adolescents, in comparison with high-risk HIV-negative adolescents. The data suggest that these changes may occur early in the course of HIV disease but that quantitative changes continue to occur with advancing depletion of the CD4+ T cell pool.

Stabilization/solidification of salt from a waste incinerator.

A laboratory procedure was developed and verified for stabilizing salt produced by an industrial waste incinerator. This procedure is based on salt stabilization by means of an asphalt binder. Conductivity values and relevant anion contents in leachates of stabilized waste with an asphalt coating were near zero. The pH value of these leachates equaled the pH value of the water used, so that the stabilized waste salt represented inert material, posing no environmental hazard. An unusually significant reduction in the volume of processed salt occurred during stabilization. After compacting under 10.4 MPa pressure, the volume of test specimens was almost 55% smaller than the initial salt volume. In practice, this would mean more than a doubling of landfill waste capacity. Volume reduction was successfully explained by means of a mathematical model.

Pharmacokinetics and pharmacodynamics of the leukotriene B4 receptor antagonist CP-105,696 in man following single oral administration.

AIMS: CP-105,696, (+)-1-(3S,4R)-[3-(4-phenylbenzyl)-4-hydroxy-chroman-7-yl] cyclopropane carboxylic acid is a potent, novel LTB4 receptor antagonist advanced to clinical trials to determine its efficacy in inflammatory diseases. The pharmacokinetics and pharmacodynamics of CP-105,696 were investigated in healthy male volunteers following oral administration of single doses of 5 to 640 mg. METHODS: Forty-eight subjects participated in a randomized, double-blind, parallel group study. Plasma and urine concentrations of CP-105,696 were determined at intervals after drug administration. As an indication of LTB4 receptor antagonism following oral administration of CP-105,696, the inhibiton of LTB4-induced upregulation of the neutrophil cell surface complement receptor (CR3), CD11b/CD18, was monitored at 4 h following drug administration using an ex vivo whole blood flow cytometry assay. RESULTS: Cmax and AUC(0, infinity) increased in a dose-related manner. Respective mean Cmax values were 0.54 to 30.41 microg ml(-1) following doses of 5 to 640 mg. Respective mean AUC(0, infinity) values were 1337 to 16819 microg ml(-1) h for the 40 to 640 mg dose groups. Plasma concentrations declined in a monoexponential manner, with terminal elimination half-lives ranging from 289 to 495 h. Group mean terminal elimination half-lives were dose-independent. Urinary excretion of unchanged drug accounted for < 1% of the administered dose. A linear relationship was observed between CP-105,696 plasma concentrations and inhibition of LTB4-mediated CD11b upregulation on human neutrophils in whole blood. CP-105,696 plasma concentrations of 5-6 microg ml(-1) were necessary to elicit a two-fold shift to the right of the LTB4 concentration response curve for CD11b upregulation. CONCLUSIONS: These studies demonstrate pharmacologically significant LTB4-receptor antagonism following a single dose of CP-105,696 and pharmacokinetics consistent with once-daily dosing.

The neutral products formed during backbone fragmentations of protonated peptides in tandem mass spectrometry.

Collisionally activated dissociation (CAD) of the protonated polyalanines Ala-Ala,Ala-Ala-Ala, and Ala-Ala-Ala-Ala causes breakup of the peptide bonds leading to sequence-indicative fragment ions. The neutral molecules eliminated during these reactions are identified here using neutralization-reionization mass spectrometry (NRMS). N-terminal acylium ions (bn) arise after the C-terminus is lost as an intact amino acid or peptide; further loss of CO leads to immonium ions (an). Upon generation of C-terminal sequence ions (yn), a hydrogen atom attached to a nitrogen rearranges from the N-terminal to the C-terminal side yielding a protonated amino acid (y1) or peptide (y > or = 2) as the ionic fragment; the complementary neutral fragment is an aziridinone if the N-terminal amino acid is cleaved and a diketopiperazine if two N-terminal amino acid units are eliminated. Detection of neutral dissociation products can reveal valuable structure information, as demonstrated with the tetrapeptides Val-Gly-Ser-Glu and Val-Gly-Asp-Glu.

Ergonomics: the investment of the '90s.

Repetitive strain injuries, headaches and backaches are growing faster than any other occupational injury as a by-product of our computerized work environment. Many of these injuries can be avoided in an ergonomically designed office. This professional paper will provide a summary reference in the correct design of a "human-friendly" medical office group.