Use of recombinant human osteogenic protein-1 for the repair of subchondral defects in articular cartilage in goats.

The objective of this pilot study was to examine in vivo the potential of recombinant human osteogenic protein-1 (rhOP-1, also called bone morphogenetic protein-7, BMP-7) for treatment of subchondral lesions by induction of new hyaline cartilage formation. Subchondral left knee defects in 17 mature goats were treated with fresh coagulated blood mixed with (1) rhOP-1 combined with collagen (OP-1 device, 400 microgram/mL); (2) rhOP-1 alone (OP-1 peptide, 200 microgram/mL); (3) OP-1 device with small particles of autologous ear perichondrium; (4) OP-1 peptide with small particles of autologous ear perichondrium; or (5) autologous ear perichondrium alone (controls). rhOP-1 was combined with either collagen (OP-1 device) or not (OP-1 peptide). The defects were closed with a periosteal flap. The formation of cartilage tissue was studied by histologic and biochemical evaluation at 1, 2, and 4 months after implantation. One and 2 months after implantation there were no obvious differences between control and rhOP-1-treated defects. Four months after implantation, only one out of three controls (without rhOP-1) showed beginning signs of cartilage formation while all four rhOP-1-treated defects were completely or partly filled with cartilage. A significant linear relationship was found between rhOP-1 concentration and the total amount of aggrecan in the defects. These results suggest that implantation of rhOP-1 promotes cartilage formation in subchondral defects in goats at 4 months after implantation. Therefore, rhOP-1 could be a novel factor for regeneration of cartilage in articular cartilage defects.

Late failure of the polyethylene liner fixation in an uncemented total hip arthroplasty.

We report on the failure of fixation of a polyethylene liner of a Harris/Galante first-generation cementless acetabular component (Zimmer, Warsaw, IN). The failure was diagnosed 9 years after implantation. The polyethylene liner was partly dissociated in its metal shell, resulting in nearly complete wearing through of the metal caused by the femoral head. This wearing contributed to severe metallosis and osteolysis around both the femoral and the acetabular component. The possible failure mechanisms are described, and a complete review of the literature is given.

Osteogenic protein (OP-1, BMP-7) stimulates cartilage differentiation of human and goat perichondrium tissue in vitro.

The objective of this study was to examine in vitro the influence of recombinant human osteogenic protein-1 [rhOP-1, or bone morphogenetic protein-7 (BMP-7)] on cartilage formation by human and goat perichondrium tissue containing progenitor cells with chondrogenic potential. Fragments of outer ear perichondrium tissue were embedded in clotting autologous blood to which rhOP-1 had been added or not added (controls), and the resulting explant was cultured for 3 weeks without further addition of rhOP-1. Cartilage formation was monitored biochemically by measuring [35S]-sulphate incorporation into proteoglycans and histologically by monitoring the presence of metachromatic matrix with cells in nests. The presence of rhOP-1 in the explant at the beginning of culture stimulated [35S]-sulphate incorporation into proteoglycans in a dose-dependent manner after 3 weeks of culture. Maximal stimulation was reached at 40 microg/mL (human explants: +148%; goat explants: +116%). Histology revealed that explants treated with 20-200 microg/mL of rhOP-1, but not untreated control explants, contained areas of metachromatic-staining matrix with chondrocytes in cell nests. It was concluded that rhOP-1 stimulates differentiation of cartilage from perichondrium tissue. The direct actions of rhOP-1 on perichondrium cells in the stimulation of chondrocytic differentiation and production of cartilage matrix in vitro provides a cellular mechanism for the induction of cartilage formation by rhOP-1 in vivo. Thus rhOP-1 may promote early steps in the cascade of events leading to cartilage formation and could prove to be an interesting factor in the regeneration of cartilage in articular cartilage defects.

Hypokalaemia in healthy volunteers after single and multiple doses of formoterol or salbutamol.

A specific beta(2)-adrenoceptor-mediated effect, hypokalaemia, was studied in healthy volunteers after single as well as multiple dosages of the long-acting agonist formoterol and the short-acting agent salbutamol. The purpose of the study was to test with simple methodologies if rapidly induced tachyphylaxis for this well known systemic effect can be shown and if it will then be more pronounced for the long-acting compound. Hypokalaemia induced by inhalation of, respectively, 72microg formoterol and 1200microg of salbutamol was studied before and after 1 week of medication. Potassium-time curves were described by a biexponential equation and also analysed with a deconvolution technique. Both drugs induced a statistically significant hypokalaemia, the duration of this effect being considerably shorter for salbutamol than for formoterol (p < 0.05 with both methods of analysis). After multiple doses for 1 week, both maximal hypokalaemia and the area under the curve of the hypokalaemic effect had decreased after inhalation of formoterol (p < 0.05) but not after inhalation of salbutamol.It was concluded that plasma potassium as an effect measurement can be used to study in a simple but reproducible way differences of pharmacological interest between various beta(2)-adrenoceptor agonists.