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Nathan J Koewler Katie T Freeman Ryan J Buus Monica B Herrera Juan M Jimenez-Andrade Joseph R Ghilardi Christopher M Peters Lucy J Sullivan Michael A Kuskowski Jack L Lewis Patrick W Mantyh 《Journal of bone and mineral research》2007,22(11):1732-1742
A closed femur fracture pain model was developed in the C57BL/6J mouse. One day after fracture, a monoclonal antibody raised against nerve growth factor (anti-NGF) was delivered intraperitoneally and resulted in a reduction in fracture pain-related behaviors of approximately 50%. Anti-NGF therapy did not interfere with bone healing as assessed by mechanical testing and histomorphometric analysis. INTRODUCTION: Current therapies to treat skeletal fracture pain are limited. This is because of the side effect profile of available analgesics and the scarcity of animal models that can be used to understand the mechanisms that drive this pain. Whereas previous studies have shown that mineralized bone, marrow, and periosteum are innervated by sensory and sympathetic fibers, it is not understood how skeletal pain is generated and maintained even in common conditions such as osteoarthritis, low back pain, or fracture. MATERIALS AND METHODS: In this study, we characterized the pain-related behaviors after a closed femur fracture in the C57BL/6J mouse. Additionally, we assessed the effect of a monoclonal antibody that binds to and sequesters nerve growth factor (anti-NGF) on pain-related behaviors and bone healing (mechanical properties and histomorphometric analysis) after fracture. RESULTS: Administration of anti-NGF therapy (10 mg/kg, days 1, 6, and 11 after fracture) resulted in a reduction of fracture pain-related behaviors of approximately 50%. Attenuation of fracture pain was evident as early as 24 h after the initial dosing and remained efficacious throughout the course of fracture pain. Anti-NGF therapy did not modify biomechanical properties of the femur or histomorphometric indices of bone healing. CONCLUSIONS: These findings suggest that therapies that target NGF or its cognate receptor(s) may be effective in attenuating nonmalignant fracture pain without interfering with bone healing. 相似文献
94.
Defective implant osseointegration under protein undernutrition: prevention by PTH or pamidronate. 总被引:1,自引:0,他引:1
Romain Dayer Isabelle Badoud René Rizzoli Patrick Ammann 《Journal of bone and mineral research》2007,22(10):1526-1533
Protein deficiency is associated with impaired titanium osseointegration. We studied whether systemic treatment with PTH or pamidronate could influence the resistance to pull-out of titanium rods implanted into rats proximal tibia under normal and isocaloric low protein intake. PTH or pamidronate prevented the deleterious effects of protein undernutrition on bone microarchitecture close to the implant and on mechanical fixation. PTH even significantly improved implant osseointegration. INTRODUCTION: Protein deficiency is highly prevalent among elderly patients hospitalized in orthopedic wards. Reduced protein intake impairs titanium osseointegration in rats. Whether stimulator of bone formation or inhibitor of bone resorption could improve implant osseointegration under protein deprivation is not known. We studied the effects of systemic treatment with PTH or pamidronate on the resistance to pull-out of titanium rods implanted into rats proximal tibia under normal and isocaloric low protein intake. MATERIALS AND METHODS: We measured the resistance to pull-out 1-mm-diameter titanium rods implanted into the proximal tibias of 49 adult female rats receiving a normal or an isocaloric low protein diet. After 2 wk on either diet, the implants were inserted, and the rats received PTH(1-34), pamidronate or saline vehicle for 8 wk. The tibias were removed for microCT morphometry, followed by the evaluation of pull-out strength. RESULTS: Pull-out strength was lower in rats fed an isocaloric low protein diet compared with rats fed a normal protein intake (-29%). PTH and pamidronate significantly increased pull-out strength in animals fed a normal or a low protein diet, the effect of PTH being of higher magnitude. The PTH- or pamidronate-mediated increase in pull-out strength was associated with significant increases of relative bone volume, bone-to-implant contact, and trabecular thickness, whereas trabecular spacing was reduced, in the vicinity of the implants. CONCLUSIONS: We confirmed that isocaloric low protein intake impairs titanium implant osseointegration. PTH or pamidronate prevented the deleterious effects of protein undernutrition and even significantly improved the implant osseointegration. These results indicate that systemic administration of PTH or pamidronate could be considered for preventing uncemented arthroplasty loosening in protein undernourished patients. 相似文献
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Plaque composition and its relationship with acknowledged shear stress patterns in coronary arteries. 总被引:2,自引:0,他引:2
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Influence of time elapsed between myocardial infarction and coronary artery bypass grafting surgery on operative mortality. 总被引:1,自引:0,他引:1
Pierre Voisine Patrick Mathieu Daniel Doyle Jean Perron Richard Baillot Gilles Raymond Jacques Métras Fran?ois Dagenais 《European journal of cardio-thoracic surgery》2006,29(3):319-323
OBJECTIVE: Optimal timing for CABG surgery after myocardial infarction (MI) remains controversial. We examined the influence of patient age and time elapsed between MI and isolated CABG surgery on operative mortality. METHODS: Perioperative data of 13,545 patients who underwent isolated CABG surgery from 1991 to 2005 were reviewed. A previous MI was found in 7219 patients, classified among groups A-E whether they underwent surgery less than 6h (A, n=26), between 6 and 24h (B, n=51), between 1 and 7 days (C, n=313), between 8 and 30 days (D, n=917), or more than 30 days (E, n=5912) after the event. Crude percentages and odds ratio estimates of operative mortality were calculated. RESULTS: In patients who had no history of MI, the mortality rate was 1.7%, while it was, respectively, 19.2, 9.8, 8.6, 3.2, and 2.4% in patients from groups A to E. Among 6589 patients over 65 years of age, 3027 had no history of MI. Their mortality was 2.4%, compared to, respectively, 35.7, 13.8, 11.3, 5.1, and 3.9% for those belonging to groups A-E. Overall odds ratio estimates of operative mortality were 3.92 (p=0.19), 5.08 (p=0.002), 4.33 (p=0.0001), 1.50 (p=0.08), and 1.18 (p=0.24) for groups A-E, respectively. CONCLUSIONS: Operative mortality is not influenced by a history of MI sustained more than 30 days prior to isolated CABG surgery, but is highly and most significantly increased between 6h and 1 week after MI, especially in older patients. That critical period should be avoided whenever possible. 相似文献
100.
Patrick Manckoundia France Mourey Pierre Pfitzenmeyer Jacques Van Hoecke Dominic Pérennou 《Clinical neurophysiology》2007,118(4):786-793
OBJECTIVE: We hypothesised that backward disequilibrium (BD), defined by a posterior position of the centre of mass with respect to the base of support, could be caused by a backward tilt in the perception of verticality. METHODS: The relationship between BD, the perception of verticality, and the history of falls in 25 subjects aged 84.5+/-7.4 years was analysed. An original ordinal scale, the BD scale (BDS), was used to quantify BD. Postural (PV) and haptic verticals (HV) were measured in sagittal plane. RESULTS: BDS scores closely correlated with the number of falls (r = 0.81, p =10(-5)). The more the PV was tilted backward, the greater the BDS scores (r = -0.95, p<10(-6)), with a huge backward tilt of about 15 degrees in 4 subjects with severe BD. In these subjects, the tilt in perception of verticality was transmodal since a severe backward HV tilt was also found. CONCLUSIONS: This transmodality suggested high-order cognitive disruption in the construction of the subjective vertical used in postural control by subjects showing BD, which confirmed our hypothesis. SIGNIFICANCE: This study clearly shows that perception and action with respect to gravity are closely related and brings a new insight about fall mechanisms in the elderly. 相似文献