AIMS:To assess if the inhibitory potency of nonsteroidal anti-inflammatory drugs (NSAIDs) on cyclooxygenase (COX) isoenzymes, when given therapeutically in humans, can be predicted from their in vitro concentration-response curves using the whole blood assay.METHODS:Twenty-four healthy male volunteers aged 20--27 years were recruited. Inhibition of blood COX isoenzymes was determined in vitro before any drug intake and ex vivo after single and repeated intake of either 7.5 mg meloxicam once, 400 mg ibuprofen three times daily or 75 mg diclofenac SR once, taken in a randomized cross-over design. Production of thromboxane B2 (TXB2) during clotting and of prostaglandin E2 (PGE2) during endotoxin exposure served as indicators of platelet COX-1 and monocyte COX-2 activity, respectively. Drugs were determined in plasma by h.p.l.c., with a chiral separation of ibuprofen and free fractions after equilibrium dialysis.RESULTS:Intra-subject variation for COX-1 and COX-2 at baseline was at 26 +/- 18% and 18 +/- 13% respectively, and intersubject variation at 39% and 36%, respectively. The ratios of IC50s and, at best, of IC80s revealed diclofenac and meloxicam as selective COX-2 inhibitors and ibuprofen as a preferential COX-1 inhibitor in vitro. However, after oral intake, ibuprofen inhibited ex vivo COX-2 by 80% whereas diclofenac inhibited COX-1 by 70%. Meloxicam inhibited COX-1 from 30 to 55% depending on the repetition of the dose and increase in plasma concentrations. Using in vitro dose--response curves, the in vivo inhibitory potency of diclofenac was estimated adequately from its circulating concentration ([-0.18, 0.21] for COX-1 and [-0.13, -0.03] for COX-2) but this was not the case for ibuprofen on COX-2 ([-0.14, 0.27]) and meloxicam on COX-1 ([0.31, 1.05]). The limited predictability of the system was not improved through considering the unbound fraction of the drugs or the variable chiral inversion of ibuprofen.CONCLUSIONS:Assessment of COX-2 selectivity based on in vitro studies and pharmacological modelling has a limited clinical relevance. There is a need to investigate COX selectivity at therapeutic plasma concentrations of NSAIDs using the ex vivo whole blood assay.

AIMS:The efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in rheumatic diseases depends on their concentrations within the joint. We determined piroxicam concentrations in plasma and synovial fluid (SF) after a single oral dose of 20 mg in the form of one tablet of piroxicam-beta-cyclodextrin.METHODS:45 patients, aged 21 to 84 years, presenting with an effusion of the knee, related to degenerative or inflammatory joint disease, were included in this study after having given their written consent. One blood and one SF sample were drawn concomitantly in each patient from 0.5 to 48 h after NSAID administration. Piroxicam assays were performed by high performance liquid chromatography. Pharmacokinetic parameters were obtained from the mean plasma and synovial concentrations measured at various sampling times.RESULTS:The peak concentration was higher in plasma (2.51+/-0.25 microg/ml) than in SF (1.31+/-0.76 microg/ml), but the elimination half-life was much longer in SF (90.7 h) than in plasma (32.5 h). The SF/plasma area under the concentration-time curve ratio (evaluating the quantity of NSAID transferred from the blood to the joint) was equal to 0.39.CONCLUSIONS:Piroxicam contained in piroxicam-beta-cyclodextrin diffused well into the SF where its pharmacokinetic profile corresponded to that of a long half-life NSAID.

Familial articular chondrocalcinosis is a chronic articular disease characterized by acute intermittent attacks of arthritis presence of calcium pyrophosphate dihydrate crystal in synovial fluid cartilage and periarticular soft tissue and by x rays calcium deposition in articular cartilage. A family originating from Alsace, with an autosomal dominant transmission has been studied. As in English and Argentinean families, a linkage to the short arm of chromosome 5p has been found. These results suggest that a defective gene at this location may be related to the chondrocalcinosis in these families.

Familial calcium pyrophosphate dihydrate deposition disease (CPPDD) is a disease of articular cartilage that is radiographically characterized by chondrocalcinosis due to the deposition of calcium-containing crystals in affected joints. We have documented the disease in an Argentinean kindred of northern Italian ancestry and in a French kindred from the Alsace region. Both families presented with a common phenotype including early age at onset and deposition of crystals of calcium pyrophosphate dihydrate in a similar pattern of affected joints. Affected family members were karyotypically normal. Linkage to the short arm of chromosome 5 was observed, consistent with a previous report of linkage of the CPPDD phenotype in a large British kindred to the 5p15 region. However, recombinants in the Argentinean kindred have enabled us to designate a region <1 cM in length between the markers D5S416 and D5S2114 as the CPPDD locus.

Septic sacroiliitis is an uncommon condition that is often diagnosed late. Two cases in the immediate postpartal period are reported. Magnetic resonance imaging contributed decisively to the early diagnosis.

La sacro-iliite septique est rare et son diagnostic reste difficile et souvent retarde. Nous rapportons les cas de deux jeunes femmes chez qui l'infection d'une articulation sacro-iliaque est survenue en post-partum immediat. Nous precisons son aspect semeiologique en IRM qui apporte des arguments determinants au diagnostic et qui n'a fait l'objet que de rares descriptions anterieures.

Insufficiency fractures often occur in the sacrum and pubic rami but have rarely been reported in the ilium, where their frequency may be underestimated. We studied a series of 14 patients with insufficiency fractures of the ilium. Six patients had an oblique fracture through the wing of the ilium (which was bilateral in one case) and nine a supraacetabular fracture, with in one case a superomedial extension into the iliac wing. The initial radiographs were normal, making the diagnosis difficult. A linear area of sclerosis along the fracture line was seen after a few weeks. The radionuclide examination provided early detection and often demonstrated multiple insufficiency fractures (mean 2.1 per patient). Computed tomography missed some of the fractures, whereas magnetic resonance imaging proved a reliable diagnostic tool, especially in patients with supraacetabular fractures, showing the fracture as a line of low signal surrounded by an area of edema whose contours were exactly the same as those of the hyperactive focus on the radionuclide scan. Osteoporosis was a causative factor in all 14 patients and vitamin D deficiency in seven. Also, three patients had a history of fluoride therapy.

The purpose of this paper is to present a pictorial display of osseous and articular lesions of the anterior chest wall. The role of CT and MR imaging in such disorders is emphasized. Imaging of the anterior thoracic wall by plain films is particularly difficult. However numerous disorders may be encountered. They include inflammatory hyperostosis and sclerosis of the clavicle and the sternum, condensing osteitis and post-traumatic osteolysis of the clavicle, radiation osteitis of the sternum and the ribs, septic arthritis of the sternoclavicular joint, primary and secondary tumors of the sternum and the ribs. We illustrate a spectrum of such lesions in which CT and MR imaging provides acute evaluation of both soft tissue and bone details.

Si les fractures par insuffisance osseuse (FIO) concernent souvent le sacrum et les branches pubiennes, leurs localisations iliaques n'ont encore fait l'objet que de rares descriptions et elles demeurent assez meconnues. Nous nous sommes proposes d'en preciser les caracteristiques par l'analyse d'une serie de 14 patients qui regroupent 6 localisations a l'aile iliaque, toutes de type iliaque oblique (dont un cas bilateral) et 9 localisations supra-acetabulaires avec, dans un cas, un prolongement supero-medial du trait de fracture dans l'aile iliaque. Les difficultes de leur diagnostic sont liees a l'absence de signes radiographiques decelables sur les cliches initiaux; la fracture n'est visible que tardivement sous l'aspect d'une condensation osseuse lineaire. Mais, la scintigraphie osseuse permet un diagnostic precoce et la mise en evidence de frequents foyers de FIO associees (en moyenne 2,1 fractures par patient). Si le scanner est parfois pris en defaut, le diagnostic peut etre confirme par l'IRM, en particulier dans les formes supra-acetabulaires. Elle montre, de facon caracteristique, le trait de fracture en hyposignal, entoure d'une zone d'oedeme perifracturaire qui se superpose exactement a l'aire d'hyperfixation scintigraphique. L'analyse des circonstances etiologiques fait valoir, en dehors d'une osteoporose constante, une hypovitaminose D presente sept fois sur quatorze. En outre, un traitement par le fluor est note dans trois cas.

We describe a syndrome combining abnormalities of the pelvis, knee and foot in three related patients with a familial history of small dislocated patellae. The clinical and radiological appearance of the patella and pelvis is consistent with the 'small-patella' syndrome, a rare autosomal dominant disorder. There were also previously unreported deformities affecting the feet.

Unilateral lower extremity hypertrophic osteoarthropathy may be the initial symptom of an infected aortic graft. Knowledge of this uncommon association should lead to early and accurate diagnosis and appropriate surgical management, thus avoiding the development of aortoenteric fistula, a complication that still carries a significant risk of mortality.

Le mot enthese designe la zone d'ancrage dans l'os des tendons, des ligaments et des capsules articulaires. Les enthesiopathies regroupent toutes les alterations de l'enthese, qu'elles soient traumatiques, degeneratives, metaboliques ou inflammatoires. L'exemple le plus acheve des enthesiopathies metaboliques est l'hyperostose squelettique idiopathique diffuse, plus communement appelee maladie de Forestier. Par ailleurs, la spondylarthrite ankylosante, prototype des spondylarthropathies, est l'enthesiopathie inflammatoire la plus commune.