A critical role for Fas/CD-95 dependent signaling pathways in the pathogenesis of hyperoxia-induced brain injury.

OBJECTIVE: Prematurely born infants are at risk for development of neurocognitive impairment in later life. Oxygen treatment has been recently identified as a trigger of neuronal and oligodendrocyte apoptosis in the developing rodent brain. We investigated the role of the Fas death receptor pathway in oxygen-triggered developmental brain injury. METHODS: Six-day-old Wistar rats were exposed to 80% oxygen for various periods (2, 6, 12, 24, 48, and 72 hours), and mice deficient in either Fas (B6.MRL-Tnfrsf6(lpr)) or Fas ligand (B6Smn.C3-Fasl(gld)) and control mice (C57BL/6J) were exposed to 80% oxygen for 24 hours. Polymerase chain reaction, Western blotting, and caspase activity assays of thalamus and cortex tissue were performed. RESULTS: Fas and Fas ligand messenger RNA and protein were upregulated. Furthermore, hyperoxia resulted in induction of downstream signaling events of Fas, such as Fas-associated death domain (FADD), the long and short form of FADD-like interleukin-1beta-converting enzyme (FLICE) inhibitory protein (FLIP-L, FLIP-S), and cleavage of caspase-8 and caspase-3. Injection of a selective caspase-8 inhibitor (TRP801, 1mg/kg) at the beginning of hyperoxia blocked subsequent caspase-3 cleavage in this model. B6.MRL-Tnfrsf6(lpr) mice were protected against oxygen-mediated injury, confirming Fas involvement in hyperoxia-induced cell death. Mice deficient in Fas ligand did not differ from control animals in the amount of cell death. INTERPRETATION: We conclude that neonatal hyperoxia triggers Fas receptor and its downstream signaling events in a Fas ligand-independent fashion. Lack of functional Fas receptors and selective pharmacological inhibition of caspase-8 prevents activation of caspase-3 and provides significant neuroprotection.

Clinical results of arthroscopic meniscal repair using biodegradable screws.

This study was performed to assess the clinical results of meniscus refixation using biodegradable Clearfix meniscal screws. Between July 1999 and June 2001 this technique was performed on 65 patients, of whom 60 (27 women, 33 men; 92%) were followed up by clinical examination after an average of 18 months (range 8-34). The average age of the patients at the time of surgery was 30 years (15-58). Two patients had already undergone a partial meniscectomy at the time of follow up; three patients had had a recurrence of typical clinical signs of a meniscal tear. The other 55 patients rated the overall clinical result as "excellent" (n=21), "good" (n=31) or "satisfactory" (n=3). The average Lysholm score [20] at the time of examination was 93 (49-100) points. The Tegner-Lysholm activity grade [29] preinjury was 5.6 (3-9), compared to a grade of 5.1 (3-9) at the follow-up examination. As a result of our study, biodegradable screws can be recommended as fixation devices with a high rate of good and excellent clinical results.

The influence of limited postoperative weight-bearing on the outcome of drilling in osteochondritis dissecans tali.

INTRODUCTION: This prospective study was performed to assess the influence of limited weight-bearing on the outcome of osteochondral drilling in the treatment of an osteochondritis dissecans tali. MATERIALS AND METHODS: Of a total of 85 patients, 68 (80%; 37 male, 31 female, average age 28 years) were followed up after open or arthroscopic drilling between July 1990 and March 2000. The total outcome of 6 weeks limited postoperative weight-bearing (n=26) was compared with the outcome of 12 weeks limited weight-bearing (n=42). The average follow-up time was 4.8 years after surgery. RESULTS: A significant increase (p<0.01) in the HSS and AOFAS scores was found for the entire study group ranging from HSS: 82 points; AOFAS: 68 points before surgery to HSS: 94 points; AOFAS: 90 points at the time of assessment. The duration of limited weight-bearing did not significantly influence the outcome of surgery. Through osteochondral drilling, the average AOFAS score increased 20 points (73/93) and the HSS score 12 points (84/96) in the 6-week group and the AOFAS score 23 points (65/88) and the HSS score 12 points (80/92) in the 12-week group. The total outcome between the two postoperative treatment regimens showed no significant difference. CONCLUSION: Osteochondral drilling is an adequate therapy for osteochondritis dissecans tali. The postoperative duration of limited weight-bearing does not significantly influence the surgical outcome.