4D in vivo quantification of ankle joint space width using dynamic MRI.

Spatio-temporal evolution of joint space width (JSW) during motion is of great importance to help with making early treatment plans for degenerative joint diseases like osteoarthritis (OA). These diseases can affect people of all ages leading to an acceleration of joint degeneration and to limitations in the activities of daily living. However, only a few studies have attempted to quantify the JSW from moving joints. In this paper, we present a generic pipeline to accurately determine the changes of the JSW during the joint motion cycle. The key idea is to combine spatial information of static MRI with temporal information of low-resolution (LR) dynamic MRI sequences via an intensity-based registration framework, leading to a high-resolution (HR) temporal reconstruction of the joint. This allows the temporal JSW to be measured in the HR domain using an Eulerian approach for solving partial differential equations (PDEs) inside a deforming inter-bone area where the HR reconstructed bone segmentations are considered as temporal Dirichlet boundaries. The proposed approach has been applied and evaluated on in vivo MRI data of five healthy children to non-invasively quantify the spatio-temporal evolution of the JSW of the ankle (tibiotalar joint) during the entire dorsi-plantar flexion motion cycle. Promising results were obtained, showing that this pipeline can be useful to perform large-scale studies containing subjects with OA for different joints like ankle and knee.

Temporal resolution enhancement of dynamic MRI sequences within a motion-based framework.

Dynamic MRI has made it possible to non-invasively capture the moving human joints in vivo. Real-time Fast Field Echo (FFE) sequences have the potential to reduce the effect of motion artifacts by acquiring the image data within a few milliseconds. However, the short acquisition times affect the temporal resolution of the acquired sequences. In this paper, we propose a post-processing technique to reconstruct the missing frames of the sequence given the reduced amount of acquired data, which leads to recover the entire joint trajectory outside the MR scanner. To do this, we generalize the Log-Euclidean polyrigid registration framework to deal with dynamic three-dimensional articulated structures by adding the time as fourth dimension : we first estimate the rigid motion of each bone from the acquired data using linear intensity-based registration. Then, we fuse these local transformations to compute the non-linear joint deformations between successive images using a spatio-temporal log-euclidean polyrigid framework. The idea is to reconstruct the missing time frames by interpolating the realistic joint deformation fields in the domain of matrix logarithms assuming the motion to be consistent over a short period of time. The algorithm has been applied and validated using dynamic data from five children performing passive ankle dorsi-plantar flexion.

A comparative study of the relative enzyme inducing properties of anticonvulsant drugs in epileptic patients.

The antipyrine clearance and the urinary excretion of D-glucaric acid (D-GA) were determined in 122 patients receiving chronic anticonvulsant drug treatment and in 21 drug-free control subjects. Patients treated with carbamazepine (CBZ), phenytoin (DPH), primidone (PMD) and phenobarbitone (PB), either alone or in combination, showed higher values of antipyrine clearance and excreted larger amounts of D-GA as compared to controls. While antipyrine clearance values did not differ significantly from one drug group to another, D-GA excretion was significantly higher in patients treated with CBZ than in those treated with DPH. In patients treated with sodium valproate antipyrine clearance did not differ from control values. There was a trend for D-GA excretion to be higher in these patients but the difference was not statistically significant. Significant positive correlations were found between the dosage of CBZ, DPH, PMD and PB and both indices of enzyme induction. These data demonstrate a dose-dependent degree of enzyme induction in patients receiving therapeutic doses of these anticonvulsants. The relative potency at average dose levels for antipyrine clearance was PB (1), DPH (0.92), CBZ (0.84), PMD (0.82) and for log D-GA excretion was PB (1), CBZ (0.96), PMD (0.95), DPH (0.90).

Changes in potential difference across the human buccal mucosa with buffered or unbuffered aspirin and salicylate.

The potential difference (PD) across the gastric mucosa is an index of mucosal integrity, and is lowered by topical application of irritants such as aspirin. There are basic similarities in the PD across the buccal and gastric mucosae, and we have therefore investigated the actions of various salicylates in buffered or un-buffered solution on buccal PD in human subjects. Aspirin (at pH 2) and soluble aspirin (pH 4.4) applied topically reduced buccal PD, but this fall was abolished by buffering to pH 7. Sodium salicylate likewise reduced buccal PD at pH 4 and pH 6, but not when buffered to pH 7. Two other soluble aspirin mixtures also reduced buccal PD, indicating insufficient buffering capacity to prevent topical irritancy. Ingestion of aspirin (600 mg), avoiding topical contact with the buccal mucosa, did not alter buccal PD. Paracetamol applied topically likewise failed to reduce buccal PD. Measurement of buccal PD may be useful in the preliminary assessment of the gastrointestinal irritation provoked by anti-inflammatory and other compounds.

A comparative study of antipyrine and lignocaine disposition in normal subjects and in patients treated with enzyme-inducing drugs.

1 The disposition kinetics of lignocaine and antipyrine were compared in eight normal subjects and in eleven patients receiving chronic therapy with antiepileptic drugs. The urinary excretion of D-glucaric acid (D-GA) was measured in 16 subjects. 2 In patients treated with antiepileptic drugs antipyrine clearance and D-GA excretion were significantly increased, whereas lignocaine biovailability was significantly reduced. 3 When all the subjects included in the study were considered, a significant positive correlation could be found between the apparent oral clearance of lignocaine (Dose/area under the blood concentration curve) and both antipyrine clearance (r = 0.73) and D-GA excretion (r = 0.74). 4 When normal subjects and epileptic patients were considered separately, a significant positive correlation could be confirmed between the apparent oral clearance of lignocaine and both antipyrine clearance (r = 0.71) and D-GA excretion (r = 0.76) in normal subjects, and between antipyrine clearance and D-GA excretion (r = 0.75) in epileptic patients. 5 These results suggest that the reduction of the oral availability of lignocaine in epileptic patients is secondary to induction of first-pass metabolism of the latter drug.

Effects of sodium valproate on the serum protein binding of phenytoin, and on liver enzyme activity.

The effect of a single dose of sodium valproate on the serum protein binding of phenytoin was studied in 6 epileptic patients receiving phenytoin maintenance therapy. Phenytoin was significantly displaced by valproic acid, but the free concentration of phenytoin was unchanged because of redistribution to tissues. As a result of this effect, total serum phenytoin concentration was significantly lowered. Induction of metabolism probably does not play a part in this interaction because antipyrine half-lives and urinary D-glucaric acid excretion were not altered by chronic administration of sodium valproate to 8 patients receiving this drug alone.

Is phenytoin metabolism dose-dependent by enzyme saturation or by feedback inhibition?

The suggestion from animal experiments that phenytoin metabolism may be dose-dependent in man due to feedback inhibition by the major metabolite, 5-(p-hydroxyphenyl)-5-phenylhydantoin, was examined in 3 normal subjects by measuring phenytoin clearance during an intravenous infusion of the metabolite and during a control infusion of solvent. Clearance was measured using both carbon-labeled and unlabeled phenytoin. The infusion of metabolite did not produce any consistent change of phenytoin clearance, suggesting that feedback inhibition does not occur in man.