Summary. Childhood acute lymphoblastic leukaemia (ALL) is a malignancy with the potential to infiltrate the liver, spleen, lymph nodes and brain. Such extramedullary presentation is important for understanding the biology of childhood ALL and also for developing new prognostic parameters. A potential mechanism in the trafficking of leukaemia cells is the interaction of the chemokine receptor CXCR4, which is expressed on ALL cells, and its ligand stromal cell-derived factor-1 (SDF-1), produced by stromal cells in bone marrow and extramedullary organs. Functionality of CXCR4 was demonstrated by a high correlation between cell surface density of CXCR4 and transendothelial migration of leukaemia blasts towards a gradient of SDF-1 (r 0´73, P 0´001). Inhibition of SDF-1-induced migration by an anti-CXCR4 monoclonal antibody (78´33^23´86% inhibition) evidenced the specificity of CXCR4 to SDF-1. In order to evaluate clinical significance of CXCR4 expression, lymphoblasts from the bone marrow of 73 patients with and without extramedullary organ infiltration were compared. Multiparameter flow cytometry revealed that lymphoblasts from patients with high extramedullary organ infiltration, defined as ultrasonographically measured enlargement of liver or spleen, expressed the CXCR4 receptor at higher fluorescence intensity (median 66´12^66´17) than patients without extramedullary organ infiltration (median 17´56^19´29; P , 0´001). Consequently, high expression of CXCR4 was strongly predictive for extramedullary organ involvement, independently of the peripheral lymphoblast count. Highest CXCR4 expression was seen in mature B ALL (median 102´74^92´13; P , 0´003), a disease characterized by a high incidence of extramedullary bulky disease. As high expression of the chemokine receptor CXCR4 predicts extramedullary organ infiltration in childhood ALL, we suggest that CXCR4 and its ligand play an essential role in extramedullary invasion.
Malposition of the acetabular component is a risk factor for post-operative dislocation after total hip replacement (THR). We have investigated the influence of the orientation of the acetabular component on the probability of dislocation. Radiological anteversion and abduction of the component of 127 hips which dislocated post-operatively were measured by Einzel-Bild-Röentgen-Analysis and compared with those in a control group of 342 patients. In the control group, the mean value of anteversion was 15 degrees and of abduction 44 degrees. Patients with anterior dislocation after primary THR showed significant differences in the mean angle of anteversion (17 degrees), and abduction (48 degrees) as did patients with posterior dislocation (anteversion 11 degrees, abduction 42 degrees). After revision patients with posterior dislocation showed significant differences in anteversion (12 degrees) and abduction (40 degrees). Our results demonstrate the importance of accurate positioning of the acetabular component in order to reduce the frequency of subsequent dislocations. Radiological anteversion of 15 degrees and abduction of 45 degrees are the lowest at-risk values for dislocation.
To assess the frequency and prognostic impact of Ep-CAM and Her-2/neu overexpression in patients with breast cancer and to determine its relationship with other prognostic markers, 205 breast cancer patients with a median follow-up of 10.8 years were enrolled in this retrospective study. Overexpression of Ep-CAM and Her-2/neu in tumor tissue samples was assessed by immunohistochemistry. Tumors presenting a Her-2/neu 2؉ staining were additionally analyzed by FISH to exclude false positive results. Ep-CAM and Her-2/neu overexpression was found in 35.6% and 19.5% of the tumor samples, respectively. Both Ep-CAM and Her-2/neu overexpression were predictive for poor disease-free (DFS) and disease-related overall survival (DROS). Concurrent Ep-CAM and Her-2/neu overexpression was present in 13.2% of tumor specimens and had an additive negative impact on DFS and DROS. This minority of patients had a median time to relapse of only 34 months, whereas the median time to relapse was not reached in the patient population without Her-2/neu and Ep-CAM overexpression. By multivariate analysis Ep-CAM overexpression proved to be an indicator of poor prognosis, independent of tumor size, histologic grade, hormone receptor expression and Her-2/neu overexpression. In conclusion, overexpression of Ep-CAM and Her-2/neu complement each other as predictors for poor prognosis in patients with invasive breast cancer. Determination of these tumor markers should help in assigning breast cancer patients to 1 of 3 distinct risk categories.
The collection of detailed consumption data through smart metering has led to privacy concerns. Aggregating the consumption data over a number of smart meters can be used to strike a balance between functional and privacy requirements. A number of contributions have proposed the use of differential privacy in smart metering to perturb aggregates in order to provide a proven privacy property for end consumers. However, as differential privacy has originally been proposed for very large datasets, the applicability in real-world smart metering is not guaranteed. In this paper, the effect of differential privacy on real smart metering data is studied, especially with respect to balancing utility and privacy requirements. The main finding is that even after some improvements of the basic method the aggregation group size must be of the order of thousands of smart meters in order to have reasonable utility.
In patients with secondarily generalized tonic-clonic seizures (sGTCS) an asymmetric termination of the clonic phase can be observed. The authors systematically analyzed this phenomenon in patients with temporal lobe epilepsy (TLE). Thirty-nine sGTCS from 29 patients with TLE who underwent successful epilepsy surgery were analyzed, in addition to a prospectively collected group of 28 patients with TLE who had 35 sGTCS. The clonic phase of sGTCS did not end synchronously in 65.7% of all patients and in 59.4% of all seizures. In 79.3% to 80% this was ipsilateral to the hemisphere of seizure onset, and there was excellent interobserver agreement.
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