Osteoporosis-related vertebral fractures have important health consequences for older individuals, including disability and increased mortality. Because these fractures can be prevented with appropriate medications, recognition and treatment of high-risk patients is warranted. A cross-sectional survey was carried out in a large, regional hospital in New England to examine the frequency with which vertebral fractures are identified and treated by clinicians in a population of hospitalized older women who have radiographic evidence of fractures. The study population consisted of 934 women aged 60 years and older who were hospitalized between October 1, 1995 and March 31, 1997, and who had a chest radiograph obtained. Vertebral fractures in the thoracic region were identified by two radiologists. Discharge diagnoses, medical record notes and radiology reports were compared with the results of the radiologists' readings to determine the frequency with which fractures were identified and appropriate, osteoporosis-preventing medications prescribed. Moderate or severe vertebral fractures were identified for 132 (14.1%) study subjects, but only 17 (1.8%) of the 934 participants had a discharge diagnosis of vertebral fracture. Of these 132, only 17% had fracture noted in the medical record or discharge summary; 50% of contemporaneous radiology reports identified a fracture as present; and 23% of the time it was found in the radiologist's summary impression. Only 18% of medical records indicated that fracture patients had been prescribed calcium, vitamin D, estrogen replacement or an antiresorptive agent. Relatively few hospitalized older women with radiographically demonstrated vertebral fractures were thus identified or treated by clinicians, suggesting a need for improved recognition.
A novel approach for quantifying cerebral blood flow (CBF) is proposed that combines the bookend technique of calculating cerebral perfusion with an automatic postprocessing algorithm. The reproducibility of the quantitative CBF (qCBF) measurement in healthy controls (N ؍ 8) showed a higher intraclass correlation coefficient (ICC) and lower coefficient of variation (COV) when calculated with automatic analysis (ICC/COV ؍ 0.90/0.09) than when compared to conventional manual analysis (ICC/COV ؍ 0.58/0.19). Also, the reproducibility in patients (N ؍ 25) was successfully evaluated with the automatic analysis (ICC/COV ؍ 0.81/0.14). In 175 consecutive clinical scans, we found 3.0% and 7.4% of qCBF decrease per decade in white matter (WM) (21.5 ؎ 6.66 ml/100 g-min) and gray matter (GM) (49.6 ؎ 16.2 ml/100 g-min), respectively. Cerebral blood volume (CBV) showed a significant 3.7% decrease per decade in GM (3.00 ؎ 0.94 ml/100 g) but not in WM (1.69 ؎ 0.40 ml/100 g). Bolus tracking cerebral perfusion has been shown to reflect the underlying pathophysiology in a variety of diseases including cerebrovascular occlusive disease, stroke, central nervous system tumors, and potentially Alzheimer's disease (1-5). Parametric images of cerebral perfusion are calculated by analyzing the tracer kinetics of a known tracer, whether it is: radio-labeled water in positron emission tomography (PET), iodinated contrast agent in computed tomography (CT), spin-labeled water in arterial spin labeling, or a paramagnetic contrast agent in dynamic susceptibility contrast (DSC) MR imaging. While radiolabeled PET is the standard of reference for quantification of cerebral perfusion, the necessity of a cyclotron limits its availability. CT has the potential to quantify perfusion; however, iodinated contrast and large doses of radiation are required. This is particularly problematic for frequent follow-up or in certain populations, such as pediatric patients in which the radiation dose should be minimized MR-based parametric images of relative cerebral blood flow (CBF) and cerebral blood volume (CBV) images using DSC analysis are commonly used to assess changes in cerebral perfusion. The development of quantitative MRbased perfusion (i.e., in ml/100 g-min) has been identified by the American Heart Association as a priority for treatment of acute stroke (6). However, quantitative perfusion MR with DSC analysis has been elusive and challenging (7-10).One approach to quantification of perfusion using MRI has been to assume a population-averaged value for normal white matter (WM) and determine quantitative values relative to "normal-appearing white matter." This method assumes that the average CBF value in WM is not significantly dependent on age, gender, and physiologic conditions, and calculates the population-averaged correction factor by setting WM CBF values to 22 ml/100 g/min (11-13). However, Mukherjee et al. (14) have shown that the individual subject-to-subject correction factor is favored over the population-averaged correction fac...
Lumbar microdecompression is a minimally invasive technique that appears to provide excellent functional outcomes.
Advanced breast cancer is associated with the development of incurable bone metastasis. The two key processes involved, tumour cell homing to and subsequent colonisation of bone, remain to be clearly defined. Genetic studies have indicated that different genes facilitate homing and colonisation of secondary sites. To identify specific changes in gene and protein expression associated with bone-homing or colonisation, we have developed a novel bone-seeking clone of MDA-MB-231 breast cancer cells that exclusively forms tumours in long bones following i.v. injection in nude mice. Bone-homing cells were indistinguishable from parental cells in terms of growth rate in vitro and when grown subcutaneously in vivo. Only bone-homing ability differed between the lines; once established in bone, tumours from both lines displayed similar rates of progression and caused the same extent of lytic bone disease. By comparing the molecular profile of a panel of metastasis-associated genes, we have identified differential expression profiles associated with bone-homing or colonisation. Bone-homing cells had decreased expression of the cell adhesion molecule fibronectin and the migration and calcium signal binding protein S100A4, in addition to increased expression of interleukin 1B. Bone colonisation was associated with increased fibronectin and upregulation of molecules influencing signal transduction pathways and breakdown of extracellular matrix, including hRAS and matrix metalloproteinase 9. Our data support the hypothesis that during early stages of breast cancer bone metastasis, a specific set of genes are altered to facilitate bone-homing, and that disruption of these may be required for effective therapeutic targeting of this process.
These studies uncover mechanisms for food allergy sensitization and anaphylaxis in neonatal mice that are consistent with features of human early-life exposures and genetics in patients with clinical food allergy and demonstrate that changes in barrier function drive development of anaphylaxis to food allergen.
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