Use of the pentasaccharide fondaparinux as an anticoagulant during haemodialysis

No data about the use of the pentasaccharide fondaparinux, a highly selective indirect inhibitor of factor Xa, in patients treated with haemodialysis are available. Therefore, we investigated the pharmacokinetics and -dynamics of fondaparinux in 12 patients during haemodialysis. The anti-Xa activity (expressed as fondaparinux equivalent) was monitored, a semiquantitative clotting scale (SQCS) ranging from 0 (no visible traces of coagula) to 3 (complete clotting of the dialysis circuit) was applied, and the digital compression time necessary to achieve haemostasis at the puncture site was determined. After an initial period, when the regular heparin dose was replaced once weekly by fondaparinux, 0.05 mg/kg, the pentasaccharide was administered for nine consecutive haemodialysis sessions. Peak anti-Xa activity increased from 0.61 +/- 0.14 microg/l after the first dose to 0.89 +/- 0.24 microg/l after dose 9 (P < 0.001), whereas predialysis anti-Xa activity steadily rose to 0.32 +/- 0.09 microg/l (P < 0.001). A sufficient but slightly less effective anticoagulation with a mean SQCS of 1.19 +/- 0.71 (n = 121) was obtained by fondaparinux as compared with 0.65 +/- 0.58 (n = 60, P < 0.005) by 4,825 +/- 1,703 U of unfractionated heparin. Mean digital compression time rose slightly during fondaparinux from 23.7 +/- 7.4 minutes to 24.8 +/- 7.5 minutes (P < 0.05) and, more important, six of the 12 patients reported minor bleeding problems during the interdialytic interval. Thus, fondaparinux can be used to prevent circuit clotting during haemodialysis; however, accumulation results in an interdialytic increase of anti-Xa activity. Therefore, fondaparinux should be reserved for patients requiring systemic anticoagulation on the days off dialysis.     

Bone marrow stem cell imaging after intracoronary administration

Although feasibility and safety of autologous stem cells administration to the post-infarction heart has been proven it is not known what proportion of cells effectively do home at the damaged site. Therefore, we have labeled autologous bone marrow cells (ABMC's) by radioactive Indium and single photon emission computed tomography (SPECT) tissue distribution has been analyzed. It was detected that up to 10% of the cells were retained within the myocardium while their majority migrated or has been anchored at the spleen and liver. Comparing the number of homed cells to the total number of cells delivered one may postulate the indirect role for few hundred thousands ABMC's at heart regeneration.     

Fibrodysplasia ossificans progressiva: case report

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease characterized by widespread soft tissue ossification and congenital stigmata of the extremities. We report the case of a 33-year-old woman with clinical and radiological features of FOP. She was born with bilateral hallux valgus and at the age of 10 presented swelling and ossification of the left scapula. During the course of the disease numerous crises were observed. In this patient authors noticed FOP exacerbation after a surgical operation.     

Interaction of the Wiskott-Aldrich syndrome protein with sorting nexin 9 is required for CD28 endocytosis and cosignaling in T cells

The Wiskott-Aldrich syndrome protein (WASp) plays a major role in coupling T cell antigen receptor (TCR) stimulation to induction of actin cytoskeletal changes required for T cell activation. Here, we report that WASp inducibly binds the sorting nexin 9 (SNX9) in T cells and that WASp, SNX9, p85, and CD28 colocalize within clathrin-containing endocytic vesicles after TCR/CD28 costimulation. SNX9, implicated in clathrin-mediated endocytosis, binds WASp via its SH3 domain and uses its PX domain to interact with the phosphoinositol 3-kinase regulatory subunit p85 and product, phosphoinositol (3,4,5)P3. The data reveal ligation-induced CD28 endocytosis to be clathrin- and phosphoinositol 3-kinase-dependent and TCR/CD28-evoked CD28 internalization and NFAT activation to be markedly enhanced by SNX9 overexpression, but severely impaired by expression of an SNX9 mutant (SNX9DeltaPX) lacking p85-binding capacity. CD28 endocytosis and CD28-evoked actin polymerization also are impaired in WASp-deficient T cells. These findings suggest that SNX9 couples WASp to p85 and CD28 so as to link CD28 engagement to its internalization and to WASp-mediated actin remodeling required for CD28 cosignaling. Thus, the WASp/SNX9/p85/CD28 complex enables a unique interface of endocytic, actin polymerizing, and signal transduction pathways required for CD28-mediated T cell costimulation.     

Blood vessels and lymphatics in calcific aortic stenosis--in support of its inflammatory pathogenesis

In developed countries, calcific aortic stenosis (CAS) has become the most common acquired valvular disease. It is considered a for of atherosclerosis and, like the latter, of inflammatory origin. Majority of cases of CAS are classified etiologically as either senile ("degenerative")--developing on previously normal aortic valve with three cusps, or based on congenitally malformed--bicuspid aortic valve. Twenty-eight cases of CAS (18 of the senile type, 7 of the bicuspid valve type, and 3 of indeterminable type) were examined by means of histology and immunohistochemistry (CD31 for blood vessels; D2-40 for lymphatics). In the calcified cusps, blood vessels were present in all 28 cases, and lymphatics in 14 of them. Vascularization was associated with lymphocytic infiltrates in 24 cases. There was no difference in the pattern between the two types of CAS. The origin of the cusp vessels is discussed. Our finding in the calcified cusps of both blood and lymphatic vessels together with lymphocytic infiltrates supports the inflammatory theory of the CAS pathogenesis.     

Effect of femoral to tibial varus mismatch on the contact area of unicondylar knee prostheses

In unicondylar knee prostheses, the relative angle and congruency of the femoral against the tibial component is not mechanically constrained and may vary with the surgical implantation technique.The contact area between both components was measured with increasing varus (0–20°) and flexion angles (? 20° to 90°) in five prosthesis models in the laboratory.The contact area varied with the relative position of the components and was critically reduced up to 70% at a varus range between > 5° and < 25°.The importance of relative malpositioning of the femoral and tibial components may be underestimated and reduces the contact area of unicondylar prostheses decisively, independent from the limb axis. This increases local pressure and may thus importantly contribute to increased wear and early loosening.     

Differential patterns of multisensory interactions in core and belt areas of human auditory cortex

The auditory cortex is anatomically segregated into a central core and a peripheral belt region, which exhibit differences in preference to bandpassed noise and in temporal patterns of response to acoustic stimuli. While it has been shown that visual stimuli can modify response magnitude in auditory cortex, little is known about differential patterns of multisensory interactions in core and belt. Here, we used functional magnetic resonance imaging and examined the influence of a short visual stimulus presented prior to acoustic stimulation on the spatial pattern of blood oxygen level-dependent signal response in auditory cortex. Consistent with crossmodal inhibition, the light produced a suppression of signal response in a cortical region corresponding to the core. In the surrounding areas corresponding to the belt regions, however, we found an inverse modulation with an increasing signal in centrifugal direction. Our data suggest that crossmodal effects are differentially modulated according to the hierarchical core-belt organization of auditory cortex.     

Automated segmentation of multiple sclerosis lesion subtypes with multichannel MRI

PURPOSE: To automatically segment multiple sclerosis (MS) lesions into three subtypes (i.e., enhancing lesions, T1 "black holes", T2 hyperintense lesions). MATERIALS AND METHODS: Proton density-, T2- and contrast-enhanced T1-weighted brain images of 12 MR scans were pre-processed through intracranial cavity (IC) extraction, inhomogeneity correction and intensity normalization. Intensity-based statistical k-nearest neighbor (k-NN) classification was combined with template-driven segmentation and partial volume artifact correction (TDS+) for segmentation of MS lesions subtypes and brain tissue compartments. Operator-supervised tissue sampling and parameter calibration were performed on 2 randomly selected scans and were applied automatically to the remaining 10 scans. Results from this three-channel TDS+ (3ch-TDS+) were compared to those from a previously validated two-channel TDS+ (2ch-TDS+) method. The results of both the 3ch-TDS+ and 2ch-TDS+ were also compared to manual segmentation performed by experts. RESULTS: Intra-class correlation coefficients (ICC) of 3ch-TDS+ for all three subtypes of lesions were higher (ICC between 0.95 and 0.96) than that of 2ch-TDS+ for T2 lesions (ICC = 0.82). The 3ch-TDS+ also identified the three lesion subtypes with high specificity (98.7-99.9%) and accuracy (98.5-99.9%). Sensitivity of 3ch-TDS+ for T2 lesions was 16% higher than with 2ch-TDS+. Enhancing lesions were segmented with the best sensitivity (81.9%). "Black holes" were segmented with the least sensitivity (62.3%). CONCLUSION: 3ch-TDS+ is a promising method for automated segmentation of MS lesion subtypes.