Inter- and intraexaminer reliability in palpation of the "primary respiratory mechanism" within the "cranial concept".

Inevitable subjectivity makes interexaminer reliability of manual assessment procedures a special matter of concern. The cranial concept (CC), one aspect of osteopathy, deals with very subtle changes that have to be palpated. One of the main principles of the CC is the primary respiratory mechanism (PRM), which is hypothesized to be a palpable physiological phenomenon that occurs in rhythmic cycles, called flexion- and extension-phase, which are independent from cardiac and respiratory rates. Palpation of the PRM is one of the first steps in assessment within the CC. An inter- and intraexaminer reliability study design for repeated measures was used in this study. Forty nine healthy subjects were palpated simultaneously twice, once at the head and once at the pelvis. PRM-frequency (f), the mean duration of the flexion phase and the mean ratio of flexion- to extension-phase were used as the main outcome measures. Inter- and intraexaminer reliability and correlations to the respiratory rates were analysed for all three parameters. Inter- as well as intraexaminer agreement could not be described beyond chance agreement, as the range within the 95% limits of agreement (e.g. for f=6.6 cycles/90 s) for all cases resembled the total range of values (e.g. for f=7 cycles/90 s) that were produced. A significant effect of the examiners' respiration was found for both examiners at the pelvis (P=0.004 for one examiner, P <0.0001 for the other examiner), and for one examiner only at the head (P=0.0017). No correlation could be found for the subjects' respiratory rates. In conclusion, PRM-rates could not be palpated reliably and under certain conditions were influenced by the examiners' respiratory rates. These results do not support the hypotheses behind the PRM. The role of PRM palpation for clinical decision making and the models explaining the PRM should therefore be rethought.

Long-term stability of PBCA nanoparticle suspensions.

In this study, the stability of poly(butyl cyanoacrylate) (PBCA) nanoparticle suspensions was examined for up to 1 year by measuring the nanoparticle sizes. The nanoparticles were prepared with different stabilizers (dextran 70.000, poloxamer 188, or polysorbate 85), and the particle size was determined before and after purification by centrifugation and after dilution with different solutions (0.1 N HCl, 0.01 N HCl, H2O, and PBS). The most constant sizes were with the untreated acidic nanoparticle suspensions. In all other cases, agglomeration of the particles occurred: the extent of this agglomeration and the time at which the agglomeration occurred depended on the experimental conditions. Nanoparticle polymer degradation, as indicated by size decrease, was not observed. Thus, PBCA nanoparticles can be stored as suspensions, making the lyophilization and the sometimes problematic resuspension by ultrasonication, unnecessary, which is advantageous for clinical applications.

Nanoparticle technology for delivery of drugs across the blood-brain barrier.

The Leu-enkephalin dalargin and the Met-enkephalin kyotorphin normally do not cross the blood-brain barrier (BBB) when given systemically. To transport these neuropeptides across the BBB they were adsorbed onto the surface of poly(butylcyanoacrylate) nanoparticles (NPs) and the NPs were coated with polysorbate 80. Central analgesia was measured by the hot plate test in mice. The antidepressant amitriptyline, which normally penetrates the BBB, was used to examine the versatility of the NP method. The concentration of amitriptyline in serum and brain of mice was determined by a gas chromatographic method. Furthermore, NPs were fabricated with different stabilizers. After the adsorption of the peptides on polysorbate 85-stabilized NPs, analgesia was noted after intravenous application when NPs were not coated. The amitriptyline level was significantly enhanced in brain when the substance was adsorbed onto the NP and coated or when the particles were stabilized with polysorbate 85.

Efficacy of oral dalargin-loaded nanoparticle delivery across the blood-brain barrier.

The Leu-enkephalin dalargin normally does not penetrate the blood-brain barrier (BBB) when given intravenously. To transport dalargin across the blood-brain barrier, the peptide was adsorbed onto the surface of poly(butyl)cyanoacrylate nanoparticles and coated with polysorbate 80. After systemic administration the central analgesia was measured by hot plate test. Furthermore, nanoparticles were fabricated with different stabilizers. After the adsorption of the peptide on polysorbate 85 stabilized nanoparticles analgesia was observable after intravenously and oral application even when nanoparticles were not coated. Thus, our data support the usefulness of nanoparticles as a method to deliver drugs to the brain.