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PURPOSE: We investigate the patterns of failure in the treatment of glioblastoma(GBM) based on clinical target volume(CTV) margin size,dose delivered to the site of initial failure,and the use of temozolomide and intensity-modulated radiotherapy(IMRT).METHODS: Between August 2000 and May 2010,161 patients with GBM were treated with radiotherapy with or without concurrent temozolomide.Patients were treated with CTV expansions that ranged from 5 to 20 mm using a shrinking field technique.Patterns of failure and time to progression and overall survival were compared based on CTV margin,use of temozolomide,and use of IMRT.Kaplan Meier analysis was used to estimate survival times,and χ test was used for comparison of cohorts.RESULTS: For patients treated with 5-,10-,and 15-to 20-mm CTV,79%,77%,and 86% experienced failures in the 60 Gy volume,respectively.Forty-eight percent,55%,and 66% of patients with 5-,10-,and 15-to 20-mm CTV experienced failures in the 46 Gy volume,respectively.There was no statistical difference between patients treated with 5-,10-,15-to 20-mm margins with regard to 60 Gy failure(P=0.76),46 Gy failure(P=0.51),or marginal failure(P=0.73).Eighty percent of patients receiving temozolomide experienced failures in the 60 Gy volume.There was no increased likelihood of marginal failures in patients receiving IMRT(P =0.97).CONCLUSIONS: Modern treatment techniques including use of concurrent temozolmide,limited CTV margin size,and IMRT have not greatly changed the patterns of failure of GBM.  相似文献   
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Height has been associated with increased risk of fracture of the neck of femur. However, information on the association of height with fractures at other sites is limited and conflicting. A total of 796,081 postmenopausal women, who reported on health and lifestyle factors including a history of previous fractures and osteoporosis, were followed for 8 years for incident fracture at various sites by record linkage to National Health Service hospital admission data. Adjusted relative risks of fracture at different sites per 10‐cm increase in height were estimated using Cox regression. Numbers with site‐specific fractures were: humerus (3036 cases), radius and/or ulna (1775), wrist (9684), neck of femur (5734), femur (not neck) (713), patella (649), tibia and/or fibula (1811), ankle (5523), and clavicle/spine/rib (2174). The risk of fracture of the neck of femur increased with increasing height (relative risk [RR] = 1.48 per 10‐cm increase, 99% confidence interval [CI] 1.39–1.57) and the proportional increase in risk was significantly greater than for all other fracture sites (pheterogeneity < 0.001). For the other sites, fracture risk also increased with height (RR = 1.15 per 10 cm, CI 1.12–1.18), but there was only very weak evidence of a possible difference in risk between the sites (pheterogeneity = 0.03). In conclusion, taller women are at increased risk of fracture, especially of the neck of femur. © 2015 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).  相似文献   
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We examined the hypothesis that the attention/executive deficits in mild cognitive impairment (MCI) due to Alzheimer’s disease is associated to an abnormal cortical activation, revealed by the method of event-related synchronization/desynchronization (ERS/ERD) in the theta band during a paradigm of temporal orienting of attention. MCI patients (n = 25) and healthy elderly (HE) matched controls (n = 15) performed a task in which periodically omitted tones had to be predicted and their virtual onset time had to be marked by pressing a button. Single-trial theta responses were measured, respectively, before and after the motor response. Then, theta responses were compared to theta power during eyes closed resting state (ERD/ERS method).The temporal course of the task was characterized by two different behavioural conditions: (1) a pre-event epoch, in which the subject awaited the virtual onset of the omitted tone, (2) a post-event (after button pressing) epoch, in which the subject was in a post-motor response condition. The most important findings are summarized as follows: (1) in both groups, the pre-event epoch was characterized by theta ERS on temporal electrodes, but HE had a greater theta ERS compared to that of MCI group; (2) in both groups, during the post-motor condition, there was a theta ERS on prefrontal regions, and, also in this case, HE showed a greater theta enhancement compared to that of MCI patients; (3) HE showed evidence of lateralization: during the waiting epoch, theta ERS was dominant on the right posterior temporal lead (T6), whilst, during the post-motor epoch, theta ERS was greater on the left, as well as the midline prefrontal leads. Compared to the traditional neuropsychological measures for the episodic memory, these theta ERS indicators were less accurate in differentiating MCI patients from healthy elderly. The clinical relevance of these findings is that the weaker theta reactivity in MCI would indicate an early impairment in the temporal orienting of attention in the early stage of the clinical course of this neurodegenerative disease.  相似文献   
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Innes AM, Boycott KM, Puffenberger EG, Redl D, MacDonald IM, Chudley AE, Beaulieu C, Perrier R, Gillan T, Wade A, Parboosingh JS. A founder mutation in BBS2 is responsible for Bardet‐Biedl syndrome in the Hutterite population: utility of SNP arrays in genetically heterogeneous disorders. Bardet‐Biedl syndrome (BBS) is a multisystem genetically heterogeneous disorder, the clinical features of which are largely the consequence of ciliary dysfunction. BBS is typically inherited in an autosomal recessive fashion, and mutations in at least 14 genes have been identified. Here, we report the identification of a founder mutation in the BBS2 gene as the cause for the increased incidence of this developmental disorder in the Hutterite population. To ascertain the Hutterite BBS locus, we performed a genome‐wide single nucleotide polymorphism (SNP) analysis on a single patient and his three unaffected siblings from a Hutterite family. The analysis identified two large SNP blocks that were homozygous in the patient but not in his unaffected siblings, one of these regions contained the BBS2 gene. Sequence analysis and subsequent RNA studies identified and confirmed a novel splice site mutation, c.472‐2A>G, in BBS2. This mutation was also found in homozygous form in three subsequently studied Hutterite BBS patients from two different leuts, confirming that this is a founder mutation in the Hutterite population. Further studies are required to determine the frequency of this mutation and its role, if any, in the expression of other ciliopathies in this population.  相似文献   
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Low-level echogenicity in intraventricular hemorrhage versus ventriculitis   总被引:1,自引:0,他引:1  
Grant  EG; White  EM; Schellinger  D; Rosenbach  D 《Radiology》1987,165(2):471-474
Serial cranial sonograms of 55 neonates with large perinatal intraventricular/intraparenchymal hemorrhages and moderate-to-severe posthemorrhagic hydrocephalus were reviewed. In all 55 patients, the ventricles were initially enlarged and filled with anechoic cerebrospinal fluid, which contained discrete hyperechoic fragments of hematoma. Between 7 and 25 days after the initial hemorrhagic episode, however, diffuse, low-level echogenicity appeared in the ventricles of 34 patients. The low-level echogenicity was transient and persisted for 7-59 days (average, 18 days). In 32 patients, low-level echogenicity was a benign finding associated with prior intraventricular hemorrhage. In two patients, the low-level echogenicity was associated with ventriculitis. Low-level echogenicity appeared, increased, then cleared, but reappeared with the onset of ventriculitis in these two patients. Thickening of the ependyma and abnormal periventricular echogenicity, signs of inflammation, were also present. Although low-level echogenicity may commonly be a benign finding, the possibility of ventriculitis should not be ignored.  相似文献   
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Phorbol esters sensitize platelets to activation by physiological agonists   总被引:2,自引:1,他引:1  
Siess  W; Lapetina  EG 《Blood》1987,70(5):1373-1381
Phorbol esters such as phorbol 12, 13-dibutyrate (PdBu; 40 to 200 nmol/L) or 12-O-tetradecanoyl phorbol 13-acetate (20 to 80 nmol/L) added to aspirinized platelet-rich plasma (PRP) 5 to 15 seconds prior to various platelet stimuli (epinephrine, ADP, prostaglandin endoperoxide analog U44069, collagen, PAF, or vasopressin) potentiate the rate and extent of aggregation and ATP secretion induced by those agonists. Platelet aggregation, but not secretion, is potentiated at low concentrations of agonists; platelet secretion is potentiated at higher concentrations of the platelet stimuli. Potentiation of platelet responses was also observed when the preincubation time with PdBu was extended to 12 minutes and also occurred in washed platelets. The potentiating effect of phorbol esters is not mediated by formation of arachidonate metabolites or by released ADP. The sensitizing effect of PdBu on platelet aggregation induced by epinephrine is unique, since in contrast to the other platelet stimuli it is also found at maximal concentrations of epinephrine and does not diminish with prolonged preincubation of platelets with PdBu. Activation of protein kinase C ranges from 20% to 80% over control after 1 to 10 minutes of platelet pretreatment with PdBu but dramatically increases after subsequent addition of a stimulus such as vasopressin. In contrast, agonist- induced myosin light chain phosphorylation is reduced after platelet pretreatment with PdBu. The results indicate that protein kinase C activation enhances platelet aggregation and dense granule secretion triggered by physiologic stimuli, although it desensitizes agonist- induced myosin light chain phosphorylation.  相似文献   
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