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991.
992.
Jon Power Kenneth ES Poole Rutger van Bezooijen Michael Doube Ana M Caballero‐Alías Clemens Lowik Socrates Papapoulos Jonathan Reeve Nigel Loveridge 《Journal of bone and mineral research》2010,25(8):1867-1876
Remodeling imbalance in the elderly femoral neck can result in thin cortices and porosity predisposing to hip fracture. Hip osteoarthritis protects against intracapsular hip fracture. By secreting sclerostin, osteocytes may inhibit Wnt signaling and reduce bone formation by osteoblasts. We hypothesised that differences in osteocytic sclerostin expression might account for differences in osteonal bone‐formation activity between controls and subjects with hip fracture or hip osteoarthritis. Using specific antibody staining, we determined the osteocytic expression of sclerostin within osteons of the femoral neck cortex in bone removed from subjects undergoing surgery for hip osteoarthritis (hOA: 5 males, 5 females, 49 to 92 years of age) or hip fracture fixation (FNF: 5 males, 5 females, 73 to 87 years of age) and controls (C: 5 males, 6 females, 61 to 90 years of age). Sclerostin expression and distances of each osteocyte to the canal surface and cement line were assessed for all osteonal osteocytes in 636 unremodeled osteons chosen from fields (~0.5 mm in diameter) with at least one canal staining for alkaline phosphatase (ALP), a marker of bone formation. In adjacent sections, ALP staining was used to classify basic multicellular unit (BMUs) as quiescent or actively forming bone (ALP+). The areal densities of scl? and scl+ osteocytes (number of cells per unit area) in the BMU were inversely correlated and were strong determinants of ALP status in the BMU. In controls and hip fracture patients only, sclerostin‐negative osteocytes were closer to osteonal surfaces than positively stained cells. Osteon maturity (progress to closure) was strongly associated with the proportion of osteonal osteocytes expressing sclerostin, and sclerostin expression was the chief determinant of ALP status. hOA patients had 18% fewer osteocytes per unit bone area than controls, fewer osteocytes expressed sclerostin on average than in controls, but wide variation was seen between subjects. Thus, in most hOA patients, there was increased osteonal ALP staining and reduced sclerostin staining of osteocytes. In FNF patients, newly forming osteons were similar in this respect to hOA osteons, but with closure, there was a much sharper reduction in ALP staining that was only partly accounted for by the increased proportions of osteonal osteocytes staining positive for sclerostin. There was no evidence for a greater effect on ALP expression by osteocytes near the osteonal canal. In line with data from blocking antibody experiments, osteonal sclerostin appears to be a strong determinant of whether osteoblasts actively produce bone. In hOA, reduced sclerostin expression likely mediates increased osteoblastic activity in the intracapsular cortex. In FNF, full osteonal closure is postponed, with increased porosity, in part because the proportion of osteocytes expressing sclerostin increases sharply with osteonal maturation. © 2010 American Society for Bone and Mineral Research 相似文献
993.
Kenneth ES Poole Paul M Mayhew Collette M Rose J Keenan Brown Philip J Bearcroft Nigel Loveridge Jonathan Reeve 《Journal of bone and mineral research》2010,25(3):482-491
The anatomic distribution of cortical and cancellous bone in the femoral neck may be critical in determining resistance to fracture. We investigated the effects of aging on femoral neck bone in women. In this cross‐sectional study, we used clinical multidetector computed tomography (MDCT) of the hips to investigate aging effects in 100 female volunteers aged 20 to 90 years. We developed a clinically efficient protocol to measure cortical thickness (C.Th) and cortical, trabecular, and integral bone mineral density (CtBMD, TrBMD, and iBMD in mg/cm3) in anatomic quadrants of the femoral neck. We used a nested ANOVA to evaluate their associations with height, weight, location in the femoral neck, and age of the subject. Age was the principal determinant of both cortical thickness and BMD. Age had significantly different effects within the anatomic quadrants; compared with young women, elderly subjects had relative preservation of the inferoanterior (IA) quadrant but strikingly reduced C.Th and BMD superiorly. A model including height, weight, and region of interest (and their interactions) explained 83% of the measurement variance (p < .0001). There were marked C.Th and BMD differences between age 25 and age 85 in the already thin superior quadrants. At 25 years the predicted C.Th of the superoposterior quadrant was 1.63 mm, whereas at 85 years it was 0.33 mm [?1.33 mm, 95% confidence interval (CI) of difference over 60 years ?1.69 to ?0.95]. By contrast, at 25 years mean C.Th of the IA quadrant was 3.9 mm, whereas at 85 years it was 3.3 mm (?0.6 mm, 95% CI ?0.83 to ?0.10). CtBMD of the IA region was equivalent at 25 and 85 years. In conclusion, elderly women had relative preservation of IA femoral neck bone over seven decades compared with young women but markedly lower C.Th and BMD in the other three quadrants. The IA quadrant transmits mechanical load from walking. Mechanical theory and laboratory tests on cadaveric femurs suggest that localized bone loss may increase the risk of fracture in elderly fallers. It remains to be determined whether this MDCT technique can provide better prediction of hip fracture than conventional clinical dual X‐ray absorptiometry (DXA). © 2010 American Society for Bone and Mineral Research 相似文献
994.
Rivera N Ramnanan CJ An Z Farmer T Smith M Farmer B Irimia JM Snead W Lautz M Roach PJ Cherrington AD 《The Journal of clinical investigation》2010,120(12):4425-4435
In individuals with type 1 diabetes, hypoglycemia is a common consequence of overinsulinization. Under conditions of insulin-induced hypoglycemia, glucagon is the most important stimulus for hepatic glucose production. In contrast, during euglycemia, insulin potently inhibits glucagon's effect on the liver. The first aim of the present study was to determine whether low blood sugar augments glucagon's ability to increase glucose production. Using a conscious catheterized dog model, we found that hypoglycemia increased glucagon's ability to overcome the inhibitory effect of insulin on hepatic glucose production by almost 3-fold, an effect exclusively attributable to marked enhancement of the effect of glucagon on net glycogen breakdown. To investigate the molecular mechanism by which this effect comes about, we analyzed hepatic biopsies from the same animals, and found that hypoglycemia resulted in a decrease in insulin signaling. Furthermore, hypoglycemia and glucagon had an additive effect on the activation of AMPK, which was associated with altered activity of the enzymes of glycogen metabolism. 相似文献
995.
996.
Medical civil military operations (MCMO) are part of military civil capacity-building efforts within the full spectrum of military operations, from war to military operations other than war. In 2008-2009 during Operation Iraqi Freedom, the Division Surgeon's Section (DSS) of the 25th Infantry Division (25ID) and Multinational Division-North developed an innovative MCMO program in northern Iraq. The program centered on understanding and mapping key relationships, empowering brigade-level programs, and leveraging technology to identify and share best practices. The DSS mapped the critical relationships within and between the three entities affecting MCMO: the government of Iraq (GOI), Department of State (DOS), and the Department of Defense (DOD). A division MCMO working group was then created along with processes to facilitate MCMO project execution and program management. The structure and organization of the 25ID MCMO program lend themselves to other operational environments requiring synchronization of medical capacity-building efforts. 相似文献
997.
Safety,Pharmacokinetics, Pharmacodynamics,and Antitumor Activity of Necuparanib Combined with Nab‐Paclitaxel and Gemcitabine in Patients with Metastatic Pancreatic Cancer: Phase I Results 下载免费PDF全文
998.
999.
Background
Prostate cancer is the sixth leading cause of death from cancer among men worldwide. We have previously reported that prostate cancer survival rates for Caribbean-born males in the US was similar to survival rates of African-Americans and was higher than their counterparts diagnosed in the Caribbean. However, it is not clear whether differences in mortality could be attributed to differences in treatment.Methods
This current analysis seeks to further explore reasons for the geographic variation of prostate cancer survival for Caribbean-born men. This analysis included 2,554 Black newly diagnosed prostate cancer cases (960 cases diagnosed in the US and 1,594 cases diagnosed in the Caribbean). Clinical data were extracted from the cancer registry and clinical charts.Results
There were noted differences in the pattern of treatment for each place of birth category when stratified according to disease stage at diagnosis. Among the patients diagnosed with early-intermediate disease (stage I-III) the majority of US-born Brooklyn men were treated with surgery only (31%) and a similar pattern was observed for Caribbean-born Brooklyn men (35%). In contrast, the majority of Caribbean-born Trinidad &; Tobago men were treated with hormone therapy (31%).Caribbean-born men diagnosed in the Caribbean had a significantly higher risk of death from prostate cancer (Adjusted Hazard [AdjHR]: 3.7, 95% Confidence Interval [CI]: 2.8-5.0) when compared with the risk of death for Caribbean-born males diagnosed in the US. This observation was consistent for each treatment group with the exception of the cases treated with hormone therapy only. For these cases, there was no difference in the risk of death between Caribbean-born males diagnosed in the Caribbean (AdjHR: 1.4, 95% CI: 0.8-2.6) compared to Caribbean-born males diagnosed in the US.Conclusions
In addition to difference in access and utilization of screening, differences in treatment strategy may also be a strong predictor of outcome for Caribbean-born males diagnosed with prostate cancer. Further studies are needed to confirm these findings. In addition, other environmental factors related to survival that was not considered in this analysis also need to be investigated.1000.
Raoul P Kloppenborg Edo Richard Marieke ES Sprengers Dirk Troost Piet Eikelenboom Paul J Nederkoorn 《Journal of neuroinflammation》2010,7(1):18
Cerebral amyloid angiopathy (CAA) is a common but often asymptomatic disease, characterized by deposition of amyloid in cerebral
blood vessels. We describe the successful treatment of CAA encephalopathy with dexamethasone in a patient with CAA-related
inflammation causing subacute progressive encephalopathy and seizures, which is an increasingly recognized subtype of CAA.
The two pathological subtypes of CAA-related inflammation are described and a review of the literature is performed concerning
immunosuppressive treatment of CAA-related inflammation with special attention to its pathological subtypes. Immunosuppressive
therapy appears to be an appropriate treatment for CAA encephalopathy. 相似文献