To assess the intra and interobserver reproducibility of musculoskeletal ultrasonography (US) among rheumatologists in detecting destructive and inflammatory shoulder abnormalities in patients with ...rheumatoid arthritis (RA) and to determine the overall agreement between US and MRI.
A total of 14 observers examined 5 patients in 2 rounds independently and blindly of each other. US results were compared with MRI. Overall agreement of all findings, of positive findings on MRI, as well as intra and interobserver reliabilities, were calculated.
Overall agreement between US and MRI was seen in 79% with regard to humeral head erosions (HHE), in 64% with regard to posterior recess synovitis (PRS), in 31% with regard to axillary recess synovitis (ARS), in 64% with regard to bursitis, in 50% with regard to biceps tenosynovitis (BT), and in 84% for complete cuff tear (CCT). Intraobserver and interobserver kappa was 0.69 and 0.43 for HHE, 0.29 and 0.49 for PRS, 0.57 and 1.00 for ARS, -0.17 and 0.51 for bursitis, 0.17 and 0.46 for BT and 0.52 and 0.6 for CCT, respectively. The intraobserver and interobserver kappa for power Doppler (PD) was 0.90 and 0.70 for glenohumeral signals and 0.60 and 0.51 for bursal signals, respectively.
US is a reliable imaging technique for most shoulder pathology in RA especially with regard to PD. Standardisation of scanning technique and definitions of particular lesions may further enhance the reliability of US investigation of the shoulder.
The inhibition of angiogenesis is considered to be one of the most promising strategies that might lead to the development of novel antineoplastic therapies. This concept is supported by the dramatic ...results of gene inactivation experiments in mice that have identified several vascular endothelium related molecules as rate limiting for embryonic angiogenesis. Likewise, a number of recent animal studies have shown that angiogenesis inhibitors can prevent metastasis and shrink established experimental tumours to small dormant microtumours. In this review, Hellmut Augustin illustrates differences between developmental angiogenesis, physiological angiogenesis in the adult, and pathological angiogenesis in experimental animal tumours and natural human tumours. He then summarizes the experimental approaches to antiangiogenic therapies and finally discusses critical issues that need to be considered in translating these novel therapeutic strategies into clinical practice.
Objective: The aim of the current study was to determine levels of circulating endothelial cell adhesion molecules during preeclampsia and to assess their predictive value as diagnostic markers for ...the early identification of pregnant women at risk of developing preeclampsia.
Study design: Plasma samples were obtained from women with preeclampsia; the syndrome of hemolysis, elevated liver enzymes, and low platelets; uncomplicated pregnancy-induced hypertension; and women with normal pregnancy. In addition, longitudinal plasma profiles of pregnant women were randomly collected to determine individual profiles of circulating endothelial cell adhesion molecules. A sandwich enzyme-linked immunosorbent assay technique was used to quantitate concentrations of soluble intercellular adhesion molecule-1 (CD54), vascular cell adhesion molecule-1 (CD106), E-selectin (CD62E), platelet endothelial cell adhesion molecule (CD31), and P-selectin (CD62P).
Results: Plasma levels of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, and platelet endothelial cell adhesion molecule-1 were significantly elevated in women with preeclampsia compared with healthy control pregnant women. Longitudinal analysis of soluble plasma intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 levels during pregnancy revealed that these molecules (1) show little variation in healthy pregnant women, (2) do not vary during normal pregnancy, and (3) are significantly elevated in women with preeclampsia and the syndrome of hemolysis, elevated liver enzymes, and low platelets compared with control pregnant women and those with uncomplicated pregnancy-induced hypertension. Analysis of soluble intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 levels in longitudinal profiles of pregnant women identified significantly elevated levels of these molecules in the plasma of preeclampsia-prone women 3 to 15 weeks before the onset of clinical symptoms.
Conclusion: Elevated soluble intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 measurements during pregnancy can be considered as major risk factors. Elevated levels of these substances in the plasma of pregnant women with preeclampsia support the concept of a primary endothelial cell involvement in the pathogenesis of preeclampsia. Although currently based on a limited database, significantly elevated levels of soluble intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in the plasma of otherwise healthy pregnant women suggest a very high predictive value of these molecules for the earliest identification of women at risk of developing preeclampsia. (Am J Obstet Gynecol 1997;177:443-9.)
The complexity of the angiogenic cascade limits cellular approaches to studying angiogenic endothelial cells (ECs). In turn, in vivo assays do not allow the analysis of the distinct cellular behavior ...of ECs during angiogenesis. Here we show that ECs can be grafted as spheroids into a matrix to give rise to a complex three-dimensional network of human neovessels in mice. The grafted vasculature matures and is connected to the mouse circulation. The assay is highly versatile and facilitates numerous applications including studies of the effects of different cytokines on angiogenesis. Modifications make it possible to study human lymphangiogenic processes in vivo. EC spheroids can also be coimplanted with other cell types for tissue engineering purposes.
Analysis of endothelial cell (EC) chemokine receptor expression by RT-PCR revealed that EC essentially do not express CC-chemokine receptors whereas they express all known CXC-chemokine receptors. ...Endotheliotropic functions of ligands for CXCR-1, CXCR-2, and CXCR-3 have previously been described. We have consequently performed a detailed analysis of endothelial CXCR-4 expression. CXCR-4 is constitutively expressed by quiescent, resting EC. Cytokine stimulation revealed that bFGF upregulates endothelial CXCR-4 expression, whereas TNFα downregulates endothelial CXCR-4 expression. Expression of CXCR-4 mRNA as well as protein is also upregulated in autocrine activated, migrating bovine aortic endothelial cells (BAEC). Furthermore, migrating BAEC preferentially present CXCR-4 on the cell surface as evidenced by cytochemistry and FACS analysis. Lastly, the monospecific CXCR-4 ligand SDF-1 was found to act as a potent inducer of EC chemotaxis. In summary, the data indicate that the CXCR-4/SDF-1 receptor ligand interaction may be an important regulator of activated endothelial cell functions as they occur during vascular remodeling and angiogenesis.
Transport of glucose into neuronal cells is predominantly mediated by the glucose transporters GLUT1 and GLUT3. In addition, GLUT8 is expressed in some regions of the brain. By in situ hybridization ...we detected GLUT8-mRNA in hippocampus, thalamus, and cortex. However, its cellular and physiological function is still unknown. Thus, GLUT8 knockout (
Slc2a8
−/−
) mice were used for a screening approach in the modified hole board (mHB) behavioral test to analyze the role of GLUT8 in the central nervous system.
Slc2a8
−/−
mice showed increased mean velocity, total distance traveled and performed more turns in the mHB test. This hyperactivity of
Slc2a8
−/−
mice was confirmed by monitoring locomotor activity in the home cage and voluntary activity in a running wheel. In addition,
Slc2a8
−/−
mice showed increased arousal as indicated by elevated defecation, reduced latency to the first defecation and a tendency to altered grooming. Furthermore, the mHB test gave evidence that
Slc2a8
−/−
mice exhibit a reduced risk assessment because they performed less rearings in an unprotected area and showed significantly reduced latency to stretched body posture. Our data suggest that behavioral alterations of
Slc2a8
−/−
mice are due to dysfunctions in neuronal processes presumably as a consequence of defects in the glucose metabolism.
Neuropilin-1 (NRP1) regulates developmental and pathological angiogenesis, arteriogenesis, and vascular permeability, acting as a coreceptor for semaphorin 3A (Sema3A) and the 165-amino acid isoform ...of vascular endothelial growth factor A (VEGF-A165). NRP1 is also the receptor for the CendR peptides, a class of cell- and tissue-penetrating peptides with a specific R-x-x-R carboxyl-terminal motif. Because the cytoplasmic domain of NRP1 lacks catalytic activity, NRP1 is mainly thought to act through the recruitment and binding to other receptors. We report here that the NRP1 intracellular domain mediates vascular permeability. Stimulation with VEGF-A165, a ligand-blocking antibody, and a CendR peptide led to NRP1 accumulation at cell-cell contacts in endothelial cell monolayers, increased cellular permeability in vitro and vascular leakage in vivo. Biochemical analyses, VEGF receptor-2 (VEGFR-2) silencing, and the use of a specific VEGFR blocker established that the effects induced by the CendR peptide and the antibody were independent of VEGFR-2. Moreover, leakage assays in mice expressing a mutant NRP1 lacking the cytoplasmic domain revealed that this domain was required for NRP1-induced vascular permeability in vivo. Hence, these data define a vascular permeability pathway mediated by NRP1 but independent of VEGFR-2 activation.
Angiogenesis occurs during embryogenesis and is a down-regulated process in the healthy adult that is almost exclusively linked to pathological conditions such as tumor growth, wound healing, and ...inflammation. Physiological angiogenic processes in the adult are restricted to the female reproductive system where they occur cyclically during the ovarian and uterine cycle as well as during pregnancy. By systematically analyzing the phenotypic changes of endothelial cells during bovine corpus luteum (CL) formation and regression, we have established a physiological model of blood vessel growth and regression. Quantitation of vessel density, percentage of vessels with lumen, and ratio of Bandeiraea simplicifolia-I to von Willebrand Factor-positive endothelial cells were established as parameters of angiogenesis. Sprouting endothelial cells invade the growing CL and continue to grow throughout the first third of the ovarian cycle. Thereafter the mature CL is characterized by a dense network of vessels with gradually decreasing vessel density. During luteolysis and for several weeks thereafter (regressing and residual CL) all newly formed vessels regress, which is accompanied by gradual foreshortening and rounding of endothelial cells and subsequent detachment. Based on histochemical detection of nucleosomal fragmentation products physiological blood vessel regression in the cyclic CL does not appear to involve endothelial cell apoptosis. Lectin histochemical analysis revealed a distinct alteration of endothelial cell glycoconjugate expression during ovarian angiogenesis comparable with the distinct pattern of hyperglycosylation of cultured migrating endothelial cells (up-regulation of binding sites for Lycopersicon esculentum lectin, wheat germ agglutinin, neuraminidase-treated peanut agglutinin, and Ricinus communis agglutinin-I on sprouting ECs). Northern blot analysis of glycosyltransferases during the different stages of angiogenesis revealed an up-regulation of beta-galactoside alpha 2,6-sialyltransferase and alpha 1,3-galactosyltransferase mRNA expression during the angiogenic stages of CL formation. These data establish the ovarian angiogenesis model as a suitable experimental system to study the functional and phenotypic properties of endothelial cells in sprouting and regressing blood vessels and provide additional evidence for the importance of endothelial cell surface glycoconjugates during angiogenesis.
Aims
Transcatheter mitral valve implantation (TMVI) represents a novel treatment option for patients with mitral regurgitation (MR) unsuitable for established therapies. The CHOICE‐MI registry aimed ...to investigate outcomes of patients undergoing screening for TMVI.
Methods and results
From May 2014 to March 2021, patients with MR considered suboptimal candidates for transcatheter edge‐to‐edge repair (TEER) and at high risk for mitral valve surgery underwent TMVI screening at 26 centres. Characteristics and outcomes were investigated for patients undergoing TMVI and for TMVI‐ineligible patients referred to bailout‐TEER, high‐risk surgery or medical therapy (MT). The primary composite endpoint was all‐cause mortality or heart failure hospitalization after 1 year. Among 746 patients included (78.5 years, interquartile range IQR 72.0–83.0, EuroSCORE II 4.7% IQR 2.7–9.7), 229 patients (30.7%) underwent TMVI with 10 different dedicated devices. At 1 year, residual MR ≤1+ was present in 95.2% and the primary endpoint occurred in 39.2% of patients treated with TMVI. In TMVI‐ineligible patients (n = 517, 69.3%), rates of residual MR ≤1+ were 37.2%, 100.0% and 2.4% after bailout‐TEER, high‐risk surgery and MT, respectively. The primary endpoint at 1 year occurred in 28.8% of patients referred to bailout‐TEER, in 42.9% of patients undergoing high‐risk surgery and in 47.9% of patients remaining on MT.
Conclusion
This registry included the largest number of patients treated with TMVI to date. TMVI with 10 dedicated devices resulted in predictable MR elimination and sustained functional improvement at 1 year. In TMVI‐ineligible patients, bailout‐TEER and high‐risk surgery represented reasonable alternatives, while MT was associated with poor clinical and functional outcomes.
Results from the global CHOICE‐MI registry. CHOICE‐MI, CHoice of OptImal transCatheter trEatment for Mitral Insufficiency; HF, heart failure; MAC, mitral annulus calcification; MR, mitral regurgitation; MVPG, mitral valve pressure gradient; TEER, transcatheter edge‐to‐edge repair.
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