Etanercept (ETN), which is a recombinant human soluble tumor necrosis factor (TNF) receptor that inhibits TNF activity, is effective in the treatment of rheumatoid arthritis. We investigated the effect of ETN on recombinant human bone morphogenetic protein-2 (rhBMP-2)-induced ectopic bone formation in vivo. A block copolymer composed of poly-D,L-lactic acid with random insertion of p-dioxanone and polyethylene glycol (PLA-DX-PEG polymer) was used as the delivery system. Polymer discs (6 mm, 30 mg) containing 5 microg rhBMP-2 were implanted into the left dorsal muscle pouch of mice (n = 50). In the systemic administration groups (n = 5 per group), ETN was subcutaneously injected (25 mg/human = 12.5 microg/mouse) twice per week in a dose-dependent manner (placebo, 12.5 x 10(-3), 12.5 x 10(-1), 12.5, 125 microg), whereas a single dose of ETN (placebo, 12.5 x 10(-3), 12.5 x 10(-1), 12.5, 125 microg) was embedded in each rhBMP-2 polymer disc in the local administration groups (n = 5 per group). Three weeks after implantation, the mice were killed and the implants were analyzed. Implants in the optimally dosed groups had increased radiodensity, which was consistent with a significant increase in bone mineral content of the ossicles. Bone histomorphology revealed a significant increase in bone volume/total volume, number of osteoblasts, osteoblast surface/bone surface, and a significant decrease in the number of osteoclasts, osteoclast surface/bone surface in the optimal dosed systemic and locally administered groups. These data suggest that the optimal dose of ETN, administered either systemically or locally, enhanced the bone-inducing capacity of BMP with no apparent adverse systemic effects.
To investigate new methods that can decrease the duration of bone transport (BT) distraction osteogenesis, we injected composite materials containing recombinant human bone morphogenetic protein-2 (BMP-2) and induced the generation of a callus bridge by rapid segmental transport (4 mm/day) in a rabbit bone defect model. The composite materials consisted of BMP-2 (0, 30, or 100 mg), btricalcium phosphate powder (bTCP, 100 mg/animal; particle size, <100 mm), and polyethylene glycol (PEG; 40 mg/animal). A paste of equivalent composition was percutaneously injected at the lengthening and the docking sites after surgery and after BT, respectively. The radiographic, mechanical, and histological examinations 12 weeks post-operative revealed that the generation of bridging callus in the presence and in the absence of BMP-2 was significantly different. The callus mass in the bone defect region was adequately and consistently developed in the presence of 100 mg of BMP (administered for 6 weeks), and the bones were consolidated in 12 weeks. Such an adequate callus formation was not observed in the control animals without BMP-2 treatment. The result of this experimental study suggests the potential application of BMP-2 in accelerating callus formation and in enabling rapid bone transporting, thereby shortening the treatment period for the repair of diaphyseal bone defects by distraction osteogenesis. ß
Purpose: To assess the ease of fibrescope-assisted tracheal intubation while the patient's head and neck were placed in the neutral or the manual in-line position, and to determine if the intubating laryngeal mask facilitated fibreoptic intubation in these positions. Methods:In 84 patients, the patient's head and neck were placed in the neutral position (pillow placed under occiput), and in another 40 patients the head and neck were stabilized by the manual in-line method (no pillows under occiput). In both groups, after induction of anesthesia with 2.0 -2.5 mg·kg -1 propofol, 50 -100 µg fentanyl and 1.0 mg·kg -1 vecuronium, patients were allocated randomly into two groups: in Group C tracheal intubation was attempted using only a fibrescope, whereas in Group L fibreoptic intubation through the intubating laryngeal mask was attempted.Results: In group C the success rate of fibreoptic tracheal intubation within two minutes was higher in the neutral position (31 of 42 patients (73%)) than in the manual in-line position (8 of 20 patients (40%)). In contrast, in group L the success rate was similar between the two positions. Tracheal intubation was easier in group L than in group C (P < 0.01 or 0.001) and the time for intubation was shorter in group L than in group C in both head and neck positions.Conclusions: Fibreoptic tracheal intubation was more difficult in the manual in-line position than in the neutral position. The intubating laryngeal mask facilitated fibreoptic intubation in both positions.Objectif : Évaluer la facilité de l'intubation endotrachéale fibroscopique alors que la tête et le cou du patient sont en position neutre ou en position en ligne manuelle. Déterminer aussi si le masque laryngé d'intubation facilite l'intubation fibroscopique dans ces positions.Méthode : Chez 84 patients, la tête et le cou ont été placés en position neutre (un oreiller sous l'occiput) et chez 40 autres patients, la tête et le cou ont été stabilisés manuellement par la méthode en ligne (sans oreiller). Après l'induction de l'anesthésie avec 2,0 -2,5 mg·kg -1 de propofol, 50 -100 µg de fentanyl et 1,0 mg·kg -1 de vécuronium, les patients ont été répartis au hasard en deux groupes : le groupe C où l'intubation endotrachéale a été tentée en utilisant seulement le fibroscope, tandis que dans le groupe L, l'intubation fibroscopique a été réa-lisée au travers du masque laryngé d'intubation.Résultats : Dans le groupe C, le taux de succès de l'intubation endotrachéale fibroscopique, réalisée en moins de deux minutes, a été plus élevé chez les patients en position neutre (31 des 42 patients ou 73 %) que chez les patients en ligne (8 des 20 patients ou 40 %). Par ailleurs, dans le groupe L, le taux de succès a été similaire pour les deux positions. L'intubation endotrachéale a été plus facile dans le groupe L que dans le groupe C (P < 0,01 ou 0,001) et le temps nécessaire à l'intubation a été plus court dans le groupe L que dans le groupe C pour les deux positions.Conclusion : L'intubation endotrachéale fibroscopique a été plus dif...
Background and purpose Osteochondral defects have a limited capacity for repair. We therefore investigated the effects of tumor necrosis factor (TNF) signal blockade by etanercept (human recombinant soluble TNF receptor) on the repair of osteochondral defects in rabbit knees.Material and methods Osteochondral defects (5 mm in diameter) were created in the femoral patellar groove in rabbits. Soon after the procedure, a first subcutaneous injection of etanercept was performed. This single injection or, alternatively, 4 injections in total (twice a week for 2 weeks) were given. Each of these 2 groups was divided further into 3 subgroups: a low-dose group (0.05 μg/kg), an intermediate-dose group (0.4 μ g/kg), and a high-dose group (1.6 μ g /kg) with 19 rabbits in each. As a control, 19 rabbits were injected with water alone. The rabbits in each subgroup were killed 4 weeks (6 rabbits), 8 weeks (6 rabbits), or 24 weeks (7 rabbits) after surgery and repair was assessed histologically.Results Histological examination revealed that the natural process of repair of the osteochondral defects was promoted by 4 subcutaneous injections of intermediate-dose etanercept and by 1 or 4 injections of high-dose etanercept at the various time points examined postoperatively (4, 8, and 24 weeks). Western blot showed that rabbit TNFα had a high affinity for etanercept.Interpretation Blocking of TNF by etanercept enabled repair of osteochondral defects in rabbit knee. Anti-TNF therapy could be a strategy for the use of tissue engineering for bone and cartilage repair.
Long-term sequelae of the coronavirus disease (COVID-19) constitute Long COVID. Although Long COVID has been reported globally, its risk factors and effects on quality of life (QOL) remain unclear. We conducted a cross-sectional study using questionnaires and electronic medical records of COVID-19 patients who were diagnosed or hospitalized at five facilities in Japan. Responses were obtained from 285 out of 1,150 patients. More than half of the participants reported Long COVID symptoms of varying severity 1 year after COVID-19. Common sequelae included fatigue, dyspnea, alopecia, concentration problems, memory problems, sleeplessness, and joint pain, which often significantly reduced their QOL. COVID-19 severity was strongly associated with sputum production, chest pain, dyspnea, sore throat, and diarrhea, but not with fatigue, dysgeusia, anosmia, alopecia, and sleeplessness. Fatigue, dysgeusia, anosmia, alopecia, and sleeplessness affected the QOL among participants with asymptomatic or mild COVID-19 during the acute phase. Moreover, these sequelae persisted for prolonged periods.
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