Biomedical subjects

C Forslund

Publications and source records attributed to C Forslund.

6 recordsLinked to original sources

PubMed2001

Tendon healing stimulated by injected CDMP-2.

UNLABELLED: Tendon healing stimulated by injected CDMP-2. Med. Sci. Sports Exerc., Vol. 33, No. 5, 2001, pp. 685-687. INTRODUCTION: CDMP-2 is a member of the TFG-beta super-family. It is known to induce bone and cartilage formation but has also been shown under certain conditions to induce a tendon- and ligament-like tissue. The purpose of this study was to find possibilities for improvement of Achilles tendon repair during nonoperative treatment, by local injections of CDMP-2. METHODS: Fifty rats had a 3-mm segment of the Achilles tendon removed. Six hours postoperatively, CDMP-2 was injected locally into the defect at a dose of 0, 2, 10, or 50 microg. Eight days after the operation, the rats were killed and the tensile strength of the repairing tendons was measured with a materials testing machine. RESULTS: After 8 d, the CDMP-2-treated tendons were 39% stronger than the controls (P = 0.0008). CONCLUSION: One single injection CDMP-2 can augment tendon repair. Mechanical stimulation is of great importance for tissue differentiation and tendon repair. The tendons in our model were mechanically loaded during healing and this might explain why CDMP-2 injections induced a strong tendon-like tissue instead of bone or cartilage in this model.

Achilles Tendon↗

PubMed2000

Bone morphogenetic proteins and tendon repair.

Bone repair is controlled by signalling proteins as well as mechanical stimuli. Bone morphogenetic proteins (BMPs), implanted or injected into a fracture site, can enhance bone healing, and so can mechanical stimulation. Possibly, mechanical signals can alter BMP expression, but furthermore, tissue differentiation initiated by an implanted BMP could be guided into the required direction by mechanical signals. Mechanical stimulation also has profound effects on tendon repair. We studied the effects of 3 different BMPs in a rat tendon repair model. One of these, osteogenic protein 1 (OP-1) induced bone formation in the tendon at the expense of mechanical strength and thus overrode any mechanical control system. On the other hand, cartilage derived morphogenetic protein 1 and 2 (CDMP-1 and -2) both made the tendon callus bigger and stronger at an early time point.

Achilles Tendon↗

PubMed1999

Ketoconazole inhibits the metabolism of tolterodine in subjects with deficient CYP2D6 activity.

AIMS: To investigate the pharmacokinetics and safety of tolterodine and tolterodine metabolites after single-and multiple-dose administration in the absence and presence of ketoconazole, an inhibitor of cytochrome P450 (CYP) 3A4, in healthy volunteers with deficient CYP2D6 activity, i.e. poor metabolisers of debrisoquine. METHODS: Eight healthy volunteers received single oral doses (2 mg) of tolterodine l-tartrate. Following a wash-out period of about 3 months, six of the subjects participated in a multiple-dose (1 mg twice daily) phase of the study. Ketoconazole 200 mg was given once daily for 4-4.5 days during both the single and multiple dose tolterodine administration phases. Blood samples were drawn and the pharmacokinetics of tolterodine and its metabolites were determined. RESULTS: A decrease (P<0.01) in apparent oral clearance of tolterodine, from 10- 12 l h-1 to 4.3-4.7 l h-1, was obtained during concomitant administration of ketoconazole, yielding at least a two-fold increase in the area under the serum concentration-time curve after single as well as after multiple doses following single dose administration of tolterodine. The mean (+/-s.d.) terminal half-life increased by 50% from 9.7+/-2.7 h to 15+/-5.4 h in the presence of ketoconazole. CONCLUSIONS: CYP3A4 is the major enzyme involved in the elimination of tolterodine in individuals with deficient CYP2D6 activity (poor metabolisers), since oral clearance of tolterodine decreased by 60% during ketoconazole coadministration. This inhibition resulted in 2.1-fold increase in AUC.

Adult↗

PubMed1999

Enhanced tendon healing with GDF 5 and 6.

Between ruptured tendon ends, undifferentiated mesenchymal cells invade the hematoma and differentiate to form a tendon regenerate. This differentiation is partly directed by mechanical stimuli, which are difficult to apply and control clinically. For example, closed treatment of Achilles tendon ruptures is associated with a risk of rerupture of the regenerate. Improved tendon healing by exogenous growth factors has not previously been reported. Three proteins in the Bone Morphogenetic Protein (BMP) family--namely Growth and Differentiation Factors (GDFs) 5, 6 and 7--have recently been shown to induce a tendon- or ligament-like tissue after intramuscular implantation in rats, indicating a new way to improve tendon healing. We transected the Achilles tendon in 66 rats and denervated the calf muscle. Denervation served to reduce the mechanical stimulation to the tendon callus by eliminating muscle contractions. GDF 5 or 6 were implanted on collagen sponges in the tendon defects in two doses and compared to collagen sponges alone. The rats were killed after 2 weeks and the tensile strength of the tendon regenerate was found to be increased by both proteins in a seemingly dose-dependent manner.

Achilles Tendon↗

PubMed1998

Drug-attributed anaphylaxis.

Allergic type I reactions to medicines range in their clinical presentation from rhinitis and urticaria to severe bronchoconstriction and anaphylactic shock. We examined all cases of suspected drug induced reactions classified as anaphylactic reactions or shock reported in Sweden between 1972 and 1995 with regard to patient characteristics and drug(s) suspected. Some comparisons with drug sales and prescription data were also made. During the study period of a total of 1338 reports concerned anaphylactic/oid shock or reactions with at least a possible causal relation to medicine giving an overall reporting rate of seven cases per million inhabitants per year of drug-induced anaphylaxis. Of these 1338 patients 51 (3.8%) died from their reactions. Among the non-fatal cases, 460 (34.4%) were diagnosed as shock and 827 (61.8%) as anaphylactic reactions. In total 46.3% of all reports concerned men but men were over-represented among the older patients and among the fatal cases (65%). There were 201 different drugs reported as 'suspected' them most common of which were dextrans (418 reports), X-ray contrast media (161 reports) and antibiotics (153 reports). For dextrans the rate of anaphylactic reactions, shock and fatal cases reported were 128,101 and 21 per million bottles respectively. This decreased to 10.3, 9.8, and 0.4 per million bottles after the introduction of preventive treatment with dextran 1 in 1983.The reporting rate for ionic contrast media were 0.14, 0.13 and 0.02 per 1000 l for reactions, shock and fatal cases respectively whilst for non-ionic contrast media they were 0.7/1000 l for reactions, 0.02/1000 l for shock, but there was no report of a fatal case. For phenoxymethylpenicillin the reported rate of anaphylaxis was 0.14 cases per million defined daily doses and for benzylpenicillin it was 3.7 cases per million defined daily doses. During the study period several drugs have been identified as important causes of anaphylaxis and measures have been taken to decrease the risk of anaphylaxis e.g. the introduction of preventive treatment with dextran 1, the shift from ionic to non-ionic contrast media and the abolition of polyethoxylated castor oil as a solvent. Spontaneous reporting of drug-induced anaphylaxis remains an important surveillance model but needs to be complemented by better quantitative methods.

Journal Article↗

PubMed1998

OP-1 has more effect than mechanical signals in the control of tissue differentiation in healing rat tendons.

Although osteogenic protein 1 (OP-1) is best known for its ability to induce bone formation, it is a differentiation factor with diverse functions in the development of non-bony tissues. It is expressed in developing tendon. We therefore hypothesized that OP-1 might stimulate the differentiation of a tendon callus. Rat achilles tendons were transected and a collagen sponge with or without OP-1 was placed in the defect. OP-1 induced the formation of an ossicle, which reduced tendon strength at 2 weeks postoperatively. Abolition of muscle force by tibial nerve transection or reducing load by forefoot amputation reduced tendon strength by almost half during the same period. Thus, traction forces are potent tendon-tissue inducers. OP-1 reduced the strength of denervated tendons even further, but the induced ossicles appeared similar to those in loaded tendons. Thus, both OP-1 and unloading independently reduced tendon strength. In conclusion, the ability of OP-1 to induce bone was greater that the mechanical and environmental signals for a more traction-resistant tissue, indicating that signal proteins may have more direct or stronger effects than mechanical stimuli on tissue differentiation. We also found that a single percutaneous injection of OP-1 reproducibly induced large amounts of bone in this setting, although it is generally believed that BMPs always need to be inserted with a carrier.

Achilles Tendon↗