Determinants of daily pain trajectories and relationship with pain acceptability in hip and knee osteoarthritis. A national prospective cohort study on 886 patients

Objectives

To study daily pain trajectories (DPT) in patients with knee (KOA) and hip osteoarthritis (HOA) over a one-month period and identify relationships with patients characteristics and acceptability.

Summary of knowledge gaps related to quality and efficacy of current influenza vaccines

Influenza viruses are a public health threat, as they are pathogenic, highly transmissible and prone to genetic changes. For decades vaccination strategies have been based on trivalent inactivated vaccines, which are regulated by specific guidelines. The progress in scientific knowledge and the lessons learned from the A(H1N1)2009 pandemic have highlighted further the need to improve current guidelines, including the immunogenicity criteria set by the CHMP in 1997, and to promote the discussion on the shortcomings encountered, e.g. the evaluation of vaccine efficacy in the paediatric and elderly populations, the measurement of the naivety of a population, the impact of prior immunity on subsequent vaccinations, and the technical issues with the serological assays for detection of immunity and immunogenicity.     

Comparison of tissular disposition of pentamidine mesylate in the rat after aerosol or parenteral administration

The tissular distribution of pentamidine mesylate (4 mg/kg as free base) after intravenous, intramuscular, and aerosol administration in healthy rats was examined. Pentamidine levels in the plasma, lungs, liver, kidneys, and other organs were determined by high-performance liquid chromatography. Pentamidine was undetectable in the plasma after day 5. At day 1, the injected groups had high concentrations of the drug in the kidneys (32-34 micrograms/g) and spleen with much lower concentrations in the lungs and the liver (3.12-5.70 micrograms/g and 1.64-2.19 micrograms/g, respectively). Aerosol delivery of pentamidine produced negligible extrapulmonary drug levels (3.29 micrograms/g in kidneys at day 1) and high sustained pulmonary levels throughout the 60 d of the study (range 5.42-19.62 micrograms/g). The half-time of elimination was longer in the lungs and kidneys (29-45 d) than in the liver (1.4-7.0 d) regardless of the mode of administration.     

Modification of cefixime bioavailability by nifedipine in humans: involvement of the dipeptide carrier system.

We studied the action of nifedipine on the bioavailability of cefixime, a molecule absorbed via the gut wall dipeptide carrier system in the rat, and on the bioavailability of D-xylose, which is absorbed via a pH (and Na(+)-)-dependent transporter. Each compound was administered alone or in combination with 20 mg of nifedipine to eight healthy male volunteers. Nifedipine significantly increased the absorption rate of cefixime (20.7 +/- 4.3 versus 16 +/- 3.5 mg/h in the absence of nifedipine). The absolute bioavailability of cefixime alone was 31% +/- 6% compared with 53% +/- 1% (P < 0.01) in the presence of nifedipine. The observed peak concentrations in serum were significantly different (2.5 +/- 0.3 mg/liter without nifedipine and 3.7 +/- 1.1 mg/liter with nifedipine; P < 0.02). In contrast, nifedipine induced no significant differences in the pharmacokinetic profile of xylose following oral administration. We conclude that (i) cefixime is absorbed in humans by an apparently active process which can be enhanced by a calcium channel blocker, in this case, nifedipine; and (ii) nifedipine does not modify the activity of the pentose transporter.     

High-performance liquid chromatography of a new 2-amino-2-oxazoline: application to pharmacokinetic studies in dogs

5-(1'-Phenyl-4'-piperazinomethyl)-2-amino-2-oxazoline (1; COR3224), a derivative of 2-amino-2-oxazolines with antidepressant properties in rats, was assayed in plasma by high-performance liquid chromatography. After back extraction, 1 and a ortho-O-methyl derivative of 1 as the internal standard were separated by reversed-phase liquid chromatography and measured by UV detection (235 nm). The method is rapid and specific: the detection was linear in the range 125-1000 micrograms.L-1, with a detection limit of 50 micrograms.L-1. This method allowed the determination of pharmacokinetic parameters in six beagle dogs after intravenous and oral administration of 14C-labeled 1 ([14C]1) in a crossover study. The comparison of the results obtained from total radioactivity counting and unchanged product evaluated by HPLC-UV suggest the presence of metabolites.     

Health security--GMOs in therapeutics

The recent progress in human therapeutics has been made possible thanks to molecular biology and its use in producing proteins having the same sequence and structure as that of human proteins. The use of GMOs allows production of proteins with high added value in therapeutics, which are of satisfactory quality. GMOs may also be directly administered to patients as gene therapy vectors. However, the use of GMOs in therapeutics must take into consideration some risks, particularly those of microbiological contamination, of neo-antigenicity as well as environmental risks with regard to the way of use of the GMO. Nevertheless, those risks are taken in due consideration in the development of these new medicinal products; solutions have been found to allow their use in therapeutics with a very positive benefit/risk ratio. Medicinal products from biotechnology have enabled considerable therapeutic progress without compromising health security.     

Role for magnetic resonance imaging in coccydynia with sacrococcygeal dislocation

Sacrococcygeal dislocation is among the many causes of coccydynia. The etiological diagnosis of this fairly rare condition is difficult. Dynamic imaging is the only means of documenting the dislocation. We describe two cases of sacrococcygeal dislocation in patients presenting with coccydynia. Both patients reported a history of trauma in the more or less remote past, with no clear correlation with pain onset. Magnetic resonance imaging (MRI) of the sacrococcygeal junction showed local inflammatory lesions (bursitis, sacrococcygeal arthritis), providing a rationale for a local procedure. Analgesic therapy was inadequately effective and a local glucocorticoid injection into the sacrococcygeal junction was therefore recommended. One of the patients accepted this procedure and subsequently reported complete resolution of the symptoms.