Addition or removal of concomitant methotrexate alters adalimumab effectiveness in rheumatoid arthritis but not psoriatic arthritis.

Objective: Randomized trials have shown that concomitant methotrexate (MTX) augments the effectiveness of tumour necrosis factor (TNF) inhibitors in rheumatoid arthritis (RA), but its benefit in psoriatic arthritis (PsA) has not been demonstrated. The goal of this study was to examine whether the impact of concomitant MTX on therapeutic outcomes in patients with PsA was similar to its effects in RA. Methods: We used data from highly comparable and concurrent observational studies of patients with PsA (N = 1424) or RA (N = 3148) who initiated adalimumab therapy during routine clinical care. The 28-joint Disease Activity Score (DAS28) and patient-reported pain scores were evaluated in patients who received 24 months of continuous treatment with adalimumab monotherapy or adalimumab + MTX and in patients who initiated or stopped concomitant MTX during ongoing adalimumab therapy. Results: Twenty-four months of continuous treatment with adalimumab + MTX was superior to adalimumab monotherapy in RA patients, while no significant difference was observed in patients with PsA. RA patients who added MTX during the study showed significant individual improvements in DAS28 and pain scores at 6 months after the change in therapy, while those who removed MTX had slight increases in disease activity. In contrast, in patients with PsA, neither initiation nor removal of MTX during continuous adalimumab therapy had a significant effect on therapeutic outcomes. Conclusion: Addition of MTX to adalimumab confers further therapeutic benefit in patients with RA, but not in those with PsA, suggesting differences in MTX effects in these two patient populations. Clinicaltrials.gov NCT01078090, NCT01077258, NCT01111240.

MAO-A inhibition in brain after dosing with esuprone, moclobemide and placebo in healthy volunteers: in vivo studies with positron emission tomography.

OBJECTIVE: The aim of the study was to investigate whether or not esuprone binds substantially to MAO-A in the human brain. METHODS: In a randomised double-blind placebo-controlled study 16 male healthy volunteers were examined with positron emission tomography (PET) with [11C]harmine. Eight of the volunteers were given daily doses of 800 mg esuprone, four were given bi-daily doses of 300 mg moclobemide, and four volunteers were given placebo tablets. PET was performed before initiation of a 7-day treatment period. On day 7, one investigation was made immediately before administration of the drug, representing 23 h after the previous day's treatment for esuprone and 11 h after the last tablets of moclobemide. Further investigations were made 4 h and 8 h after the morning dose on day 7. RESULTS: PET showed a high degree of binding of [11C]harmine, a high-affinity ligand for MAO-A, before the start of treatment, and a marked and similar reduction after treatment with esuprone and moclobemide. A slight tendency for normalisation of enzyme binding was observed at the last time point. In the placebo group no change was observed. Plasma kinetics of esuprone showed a rapid elimination with a half-life of about 4 h. CONCLUSION: The study demonstrates that esuprone was comparable to moclobemide in its effect on MAO-A inhibition in the brain at the doses given. This is an illustration of the potential of PET to monitor drug effects directly on target biochemical systems in the brain in human volunteers, and the possibility of using these data, rather than pharmacokinetic data, for the determination of dosing intervals.

Osteochondroma: review of the literature and case report.

Osteochondroma is the most common bone tumor of the foot. The podiatric surgeon should have an organized protocol to diagnose and treat suspicious osseous lesions in order to prevent undertreatment of malignant lesions, or overtreatment of benign lesions. The presence of a solitary osteochondroma is not sufficient indication for surgical removal. Surgical removal is indicated if the tumor produces pain, has radiographic features of malignancy, or shows abnormal increase in size. This case involves an osteochondroma of the fifth digit that was treated by digital amputation.

Closing base wedge osteotomy.

The authors have completed a retrospective study on closing base wedge osteotomies. This review includes preoperative and postoperative clinical and radiographic evaluation. A total of 61 procedures were evaluated on 47 patients. All procedures were performed at The Podiatry Hospital of Pittsburgh. Subjective analysis of patient acceptance is included, as well as an in-depth discussion of surgical technique, with emphasis on fixation.

Pharmacokinetic-dynamic study on different oral biperiden formulations in volunteers.

The pharmacodynamic and kinetic profiles of two oral biperiden formulations (tablet with instant-release and sugar-coated tablet with slow-release) were studied in a total of 12 healthy subjects after the administration of a 4 mg dose and compared in part to placebo. Biperiden as slow-release formulation showed much slower absorption than the instant-release tablet; whereas plasma levels peaked as early as 1-2 h after administration of the tablet, with the slow-release formulation a first peak was seen approximately 4.5 h after intake in the majority of the subjects. In some subjects this was followed by a trough, in others by formation of a shoulder at around 0.5 ng/ml. In all subjects a peak of about 1.0 ng/ml was reached after 10-12 h. The instant-release tablet and the slow-release formulation showed comparable bioavailability. Plasma concentrations for the slow-release formulation at 24 h were around 0.5 ng/ml, about twice as high as those for the instant-release formulation. The ratio of peak to 24 h values showed the marked reduction which is characteristic for a slow-release formulation compared with the instant-release tablet. The subjective well-being of the volunteers was not influenced by the slow-release formulation, whereas after the instant-release tablet slight CNS effects (dizziness, drowsiness and fatigue) were reported up to 6 h after ingestion. Furthermore, objectively quantifiable pharmacodynamic ocular parameters (near-point accomodation, pupil size) and the secretion of saliva proved to be less affected by the slow-release formulation than by the instant-release tablet, or not affected at all.

Bioscience experiments in the German Spacelab mission D-1: introduction and summary.

The German Spacelab mission D-l was performed from 30 October through 6 November 1985. Payload operation in orbit was managed by DFVLR for the Federal Ministry of Research and Technology. The scientific program of the mission placed emphasis on microgravity research. In bioscience, the role of gravity in vital functions of biological systems was investigated, such as intracellular and intercellular interactions, developmental processes as well as regulation and adaptation in highly organized systems including human beings. In addition, the biological significance of cosmic radiation or altered zeitgeber within the complex matrix of all relevant spaceflight components were studied. Most of the experiments were accommodated in the following three payload elements: The Bioscience Experiment Package, and the ESA facilities Vestibular Sled and BIORACK. The information gained from the individual experiments will be compiled to help answer pending questions of space bioscience.

Comparison of the effects of sequential or simultaneous administration of salbutamol and beclomethasone dipropionate.

The effect of the simultaneous administration of salbutamol and beclomethasone dipropionate, from a combination inhaler, was compared with the same doses given with an interval of 10 min, from separate inhalers, in a group of 40 asthmatic females. The double-blind parallel-group study was well balanced and lasted 4 weeks. Both groups showed a similar improvement in thrice-weekly lung function values and daily symptoms in week 4 compared to week 1. There were no other differences and no adverse reactions. The combination inhaler is a useful alternative for maintenance treatment in patients who require an inhaled steroid.

Biperiden effects and plasma levels in volunteers.

The pharmacokinetics of biperiden was studied and compared with pharmacodynamics (pupil size, accommodation, self-rating mood scale) in 6 healthy volunteers. A single-blind cross-over design was employed with placebo and biperiden (4 mg as commercially available tablets). After a lag time of 0.5 h, biperiden was rapidly absorbed with a half-life of 0.3 h, plasma peak levels of 5 ng/ml being reached after 1.5 h. Biperiden showed good tissue penetration (distribution half-life 0.6 h; ratio of total to central distribution volume 9.6), the terminal half-life time of plasma concentration was 18 h, and the oral clearance was 146 l/h. The pharmacodynamic maximum lagged behind the plasma peak concentration by 1 (self-rating) to 4 h (accommodation).

Beta-blocking and electrophysiological effects of propafenone in volunteers.

The chemical structure of propafenone (P) and certain experimental findings suggest that this antiarrhythmic compound could possess beta-blocking properties. To evaluate the clinical relevance of the latter cardiovascular effects of P during exercise were studied. After oral administration of P 150 and 300 mg in solution, six healthy volunteers were subjected to graded exercise. These doses of P, which are usually effective against arrhythmias, decreased exercise-induced tachycardia, whereas the systolic blood pressure was lowered but only at rest, and the diastolic pressure was slightly raised. However, taking into account dose ratio, and the intensity and duration of the reduction in exercise tachycardia, this effect of P was only about 5% at its maximum compared to propranolol and similar active beta-blocking compounds. The reduction in heart rate produced by P was not correlated with the plasma level nor did it show dose dependency, in contrast to beta-blocking agents, and also in contrast to its electrophysiological effects on the PQ interval.

[Testing of lung function after theophylline inhalation (author's transl)]. / Lungenfunktionsprügungen nach Theophyllininhalation.

In the pharmacological therapy of obstructive airway syndrome, a combined therapy with pharmaca of different effective principles often is necessary. In comparison to the systemical therapy equal effects with less substance are to be obtained by application of the medicament as an aerosol. We report about results of a clinical experimental study: In patients suffering from obstructive airway syndrome, body plethysmographic measures of the lung function were made after inhalation of theophylline as an aerosol, given in different doses. At the same time serum levels of theophylline were measured. We report about the results.