Function of B cells expressing a human immunoglobulin M rheumatoid factor autoantibody in transgenic mice.

We have generated transgenic mice that express the immunoglobulin (Ig)M heavy chain and kappa light chain genes coding for a human IgM rheumatoid factor (RF), Les. Transgenic B cells expressing human IgM RF show striking similarities to their counterparts in normal humans. They comprise a significant proportion of the adult B cell population, but secrete only low levels of RF into the serum. The RF transgene-expressing B cells localize to primary B cell follicles and the mantle zone regions of secondary follicles in the spleen. Using these mice we have been able to show that one of the central functions of normal RF-expressing B cells may be to act as highly efficient antigen-presenting cells for low concentrations of immune-complexed antigen. High levels of secretion of IgM RF can not be induced under normal circumstances, although RF-expressing B cells proliferate well in vitro to both aggregated human IgG and anti-human IgM antibodies. However, these mice are not intrinsically secretion deficient. By crossing the RF transgenic mice with the autoimmune MRL/lpr background, we find a dramatic increase, > 200-fold, in levels of serum RF. The results strongly suggest that a major function of normal resting RF B cells is unrelated to antibody secretion. Rather, the RF B cells in the follicles may play a role in antigen presentation and regulation of immune responses to antibody-bound nonself-, and possibly self-antigens. This physiologic role of RF B cells may be disrupted in RF-associated autoimmune disease

Septal rupture with right ventricular wall dissection after myocardial infarction

BACKGROUND: In patients with inferior myocardial infarction, septal rupture generally involves basal inferoposterior septum, and the communicating tract between left and right ventricle is often serpiginous with a variable degree of right ventricular wall extension. Right ventricular wall dissection following septal rupture related with previous myocardial infarction has been reported in a very few cases, in many of them this condition has been diagnosed in post-mortem studies. In a recent report long-term survival has been achieved after promptly echocardiographic diagnosis and surgical repair. CASE PRESENTATION: We present a case of a 59-year-old man who had a septal rupture with right ventricular wall dissection after inferior and right ventricular myocardial infarction. Transthoracic echocardiography, as first line examination, established the diagnosis, and prompt surgical repair allowed long-term survival in our patient. CONCLUSION: Outcomes after right ventricular intramyocardial dissection following septal rupture related to myocardial infarction has been reported to be dismal. Early recognition of this complication using transthoracic echocardiography at patient bedside, and prompt surgical repair are the main factors to achieve long-term survival in these patients

Aurora B potentiates Mps1 activation to ensure rapid checkpoint establishment at the onset of mitosis

The mitotic checkpoint prevents mitotic exit until all chromosomes are attached to spindle microtubules. Aurora B kinase indirectly invokes this checkpoint by destabilizing incorrect attachments; however, a more direct role remains controversial. In contrast, activity of the kinase Mps1 is indispensible for the mitotic checkpoint. Here we show that Aurora B and Hec1 are needed for efficient Mps1 recruitment to unattached kinetochores, allowing rapid Mps1 activation at the onset of mitosis. Live monitoring of cyclin B degradation reveals that this is essential to establish the mitotic checkpoint quickly at the start of mitosis. Delayed Mps1 activation and checkpoint establishment upon Aurora B inhibition or Hec1 depletion are rescued by tethering Mps1 to kinetochores, demonstrating that Mps1 recruitment is the primary role of Aurora B and Hec1 in mitotic checkpoint signalling. These data demonstrate a direct role for Aurora B in initiating the mitotic checkpoint rapidly at the onset of mitosis

Feasibility, safety and tolerability of accelerated dobutamine stress echocardiography

A continuous infusion of a single high dose of dobutamine has been, recently, suggested as a simple and effective protocol of stress echocardiography. The present study assesses the feasibility, safety, and tolerability of an accelerated dobutamine stress protocol performed in patients with suspected or known coronary artery disease. Two hundred sixty five consecutive patients underwent accelerated dobutamine stress echocardiography: the dobutamine was administered at a constant dose of 50 μg/kg/min for up to 10 minutes. The mean weight-adjusted cumulative dose of dobutamine used was 330 ± 105.24 μg/kg. Total duration of dobutamine infusion was 6.6 ± 2.1 min. Heart rate rose from 69.9 ± 12.1 to 123.1 ± 22.1 beats/min at peak with a concomitant change in systolic blood pressure (127.6 ± 18.1 vs. 167.6 ± 45.0 mmHg). Dobutamine administration produced a rapid increase in heart rate (9.4 ± 5.9 beats/min2). The side effects were similar to those described with the standard protocol; the most common were frequent premature ventricular complexes (21.5%), frequent premature atrial complexes (1.5%) and non sustained ventricular tachycardia (1.5%); among non cardiac symptoms the most frequent were nausea (3.4%), headache (1.1%) and symptomatic hypotension (1.1%). No major side effects were observed during the test. Our data demonstrate that a continous infusion of a single high dose of dobutamine is a safe and well tolerated method of performing stress echocardiography in patients with suspected or known coronary artery disease. This new protocol requires the administration of lower cumulative dobutamine dose than standard protocol and results in a significant reduction in test time

Three-dimensional echocardiography using single-heartbeat modality decreases variability in measuring left ventricular volumes and function in comparison to four-beat technique in atrial fibrillation

BACKGROUND: Three dimensional echocardiography (3DE) approaches the accuracy of cardiac magnetic resonance in measuring left ventricular (LV) volumes and ejection fraction (EF). The multibeat modality in comparison to single-beat (SB) requires breath-hold technique and regular heart rhythm which could limit the use of this technique in patients with atrial fibrillation (AF) due to stitching artifact. The study aimed to investigate whether SB full volume 3DE acquisition reduces inter- and intraobserver variability in assessment of LV volumes and EF in comparison to four-beat (4B) ECG-gated full volume 3DE recording in patients with AF. METHODS: A total of 78 patients were included in this study. Fifty-five with sinus rhythm (group A) and 23 having AF (group B). 4B and SB 3DE was performed in all patients. LV volumes and EF was determined by these two modalities and inter- and intraobserver variability was analyzed. RESULTS: SB modality showed significantly lower inter- and intraobserver variability in group B in comparison to 4B when measuring LV volumes and EF, except for end-systolic volume (ESV) in intraobserver analysis. There were significant differences when calculating the LV volumes (p<0.001) and EF (p<0.05) with SB in comparison to 4B in group B. CONCLUSION: Single-beat three-dimensional full volume acquisition seems to be superior to four-beat ECG-gated acquisition in measuring left ventricular volumes and ejection fraction in patients having atrial fibrillation. The variability is significantly lower both for ejection fraction and left ventricular volumes

Semi-automated quantification of left ventricular volumes and ejection fraction by real-time three-dimensional echocardiography

<p>Abstract</p> <p>Background</p> <p>Recent studies have shown that real-time three-dimensional (3D) echocardiography (RT3DE) gives more accurate and reproducible left ventricular (LV) volume and ejection fraction (EF) measurements than traditional two-dimensional methods. A new semi-automated tool (4DLVQ) for volume measurements in RT3DE has been developed. We sought to evaluate the accuracy and repeatability of this method compared to a 3D echo standard.</p> <p>Methods</p> <p>LV end-diastolic volumes (EDV), end-systolic volumes (ESV), and EF measured using 4DLVQ were compared with a commercially available semi-automated analysis tool (TomTec 4D LV-Analysis ver. 2.2) in 35 patients. Repeated measurements were performed to investigate inter- and intra-observer variability.</p> <p>Results</p> <p>Average analysis time of the new tool was 141s, significantly shorter than 261s using TomTec (<it>p </it>< 0.001). Bland Altman analysis revealed high agreement of measured EDV, ESV, and EF compared to TomTec (<it>p </it>= <it>NS</it>), with bias and 95% limits of agreement of 2.1 ± 21 ml, -0.88 ± 17 ml, and 1.6 ± 11% for EDV, ESV, and EF respectively. Intra-observer variability of 4DLVQ vs. TomTec was 7.5 ± 6.2 ml vs. 7.7 ± 7.3 ml for EDV, 5.5 ± 5.6 ml vs. 5.0 ± 5.9 ml for ESV, and 3.0 ± 2.7% vs. 2.1 ± 2.0% for EF (<it>p </it>= <it>NS</it>). The inter-observer variability of 4DLVQ vs. TomTec was 9.0 ± 5.9 ml vs. 17 ± 6.3 ml for EDV (<it>p </it>< 0.05), 5.0 ± 3.6 ml vs. 12 ± 7.7 ml for ESV (<it>p </it>< 0.05), and 2.7 ± 2.8% vs. 3.0 ± 2.1% for EF (<it>p </it>= <it>NS</it>).</p> <p>Conclusion</p> <p>In conclusion, the new analysis tool gives rapid and reproducible measurements of LV volumes and EF, with good agreement compared to another RT3DE volume quantification tool.</p

Comparison of contrast enhanced three dimensional echocardiography with MIBI gated SPECT for the evaluation of left ventricular function

Background. In clinical practice and in clinical trials, echocardiography and scintigraphy are used the most for the evaluation of global left ejection fraction (LVEF) and left ventricular (LV) volumes. Actually, poor quality imaging and geometrical assumptions are the main limitations of LVEF measured by echocardiography. Contrast agents and 3D echocardiography are new methods that may alleviate these potential limitations. Methods. Therefore we sought to examine the accuracy of contrast 3D echocardiography for the evaluation of LV volumes and LVEF relative to MIBI gated SPECT as an independent reference. In 43 patients addressed for chest pain, contrast 3D echocardiography (RT3DE) and MIBI gated SPECT were prospectively performed on the same day. The accuracy and the variability of LV volumes and LVEF measurements were evaluated. Results. Due to good endocardial delineation, LV volumes and LVEF measurements by contrast RT3DE were feasible in 99% of the patients. The mean LV end-diastolic volume (LVEDV) of the group by scintigraphy was 143 65 mL and was underestimated by triplane contrast RT3DE (128 60 mL; p < 0.001) and less by full-volume contrast RT3DE (132 62 mL; p < 0.001). Limits of agreement with scintigraphy were similar for triplane andfull-volume, modalities with the best results for full-volume. Results were similar for calculation of LV end-systolic volume (LVESV). The mean LVEF was 44 16% with scintigraphy and was not significantly different with both triplane contrast RT3DE (45 15%) and full-volume contrast RT3DE (45 15%). There was an excellent correlation between two different observers for LVEDV, LVESV and LVEF measurements and inter observer agreement was also good for both contrast RT3DE techniques. Conclusion. Contrast RT3DE allows an accurate assessment of LVEF compared to the LVEF measured by SPECT, and shows low variability between observers. Although RT3DE triplane provides accurate evaluation of left ventricular function, RT3DE full-volume is superior to triplane modality in patients with suspected coronary artery disease. © 2009 Cosyns et al; licensee BioMed Central Ltd.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Real-time three-dimensional transthoracic echocardiography in daily practice: initial experience

<p>Abstract</p> <p>Aim of the work</p> <p>To evaluate the feasibility and possible additional value of transthoracic real-time three-dimensional echocardiography (RT3D-TTE) for the assessment of cardiac structures as compared to 2D-TTE.</p> <p>Methods</p> <p>320 patients (mean age 45 ± 8.4 years, 75% males) underwent 2D-TTE and RT3D-TTE using 3DQ-Q lab software for offline analysis. Volume quantification and functional assessment was performed in 90 patients for left ventricle and in 20 patients for right ventricle. Assessment of native (112 patients) and prosthetic (30 patients) valves morphology and functions was performed. RT3D-TTE was performed for evaluation of septal defects in 30 patients and intracardiac masses in 52 patients.</p> <p>Results</p> <p>RT3D-TTE assessment of left ventricle was feasible and reproducible in 86% of patients while for right ventricle, it was (55%). RT3D-TTE could define the surface anatomy of mitral valve optimally (100%), while for aortic and tricuspid was (88% and 81% respectively). Valve area could be planimetered in 100% for the mitral and in 80% for the aortic. RT3D-TTE provided a comprehensive anatomical and functional evaluation of prosthetic valves. RT3D-TTE enface visualization of septal defects allowed optimal assessment of shape, size, area and number of defects and evaluated the outcome post device closure. RT3D-TTE allowed looking inside the intracardiac masses through multiple sectioning, valuable anatomical delineation and volume calculation.</p> <p>Conclusion</p> <p>Our initial experience showed that the use of RT3D-TTE in the assessment of cardiac patients is feasible and allowed detailed anatomical and functional assessment of many cardiac disorders.</p

What is the influence of morphological knowledge in the early stages of reading acquisition among low SES children? A graphical modeling approach

Children from low-SES families are known to show delays in aspects of language development which underpin reading acquisition such as vocabulary and listening comprehension. Research on the development of morphological skills in this group is scarce, and no studies exist in French. The present study investigated the involvement of morphological knowledge in the very early stages of reading acquisition (decoding), before reading comprehension can be reliably assessed. We assessed listening comprehension, receptive vocabulary, phoneme awareness, morphological awareness as well as decoding, word reading and non-verbal IQ in 703 French first-graders from low-SES families after 3 months of formal schooling (November). Awareness of derivational morphology was assessed using three oral tasks: Relationship Judgment (e.g., do these words belong to the same family or not? heat-heater … ham-hammer); Lexical Sentence Completion [e.g., Someone who runs is a …? (runner)]; and Non-lexical Sentence Completion [e.g., Someone who lums is a…? (lummer)]. The tasks differ on implicit/explicit demands and also tap different kinds of morphological knowledge. The Judgement task measures the phonological and semantic properties of the morphological relationship and the Sentence Completion tasks measure knowledge of morphological production rules. Data were processed using a graphical modeling approach which offers key information about how skills known to be involved in learning to read are organized in memory. This modeling approach was therefore useful in revealing a potential network which expresses the conditional dependence structure between skills, after which recursive structural equation modeling was applied to test specific hypotheses. Six main conclusions can be drawn from these analyses about low SES reading acquisition: (1) listening comprehension is at the heart of the reading acquisition process; (2) word reading depends directly on phonemic awareness and indirectly on listening comprehension; (3) decoding depends on word reading; (4) Morphological awareness and vocabulary have an indirect influence on word reading via both listening comprehension and phoneme awareness; (5) the components of morphological awareness assessed by our tasks have independent relationships with listening comprehension; and (6) neither phonemic nor morphological awareness influence vocabulary directly. The implications of these results with regard to early reading acquisition among low SES groups are discussed

Three-dimensional echocardiography for left ventricular quantification: fundamental validation and clinical applications

One of the earliest applications of clinical echocardiography is evaluation of left ventricular (LV) function and size. Accurate, reproducible and quantitative evaluation of LV function and size is vital for diagnosis, treatment and prediction of prognosis of heart disease. Early three-dimensional (3D) echocardiographic techniques showed better reproducibility than two-dimensional (2D) echocardiography and narrower limits of agreement for assessment of LV function and size in comparison to reference methods, mostly cardiac magnetic resonance (CMR) imaging, but acquisition methods were cumbersome and a lack of user-friendly analysis software initially precluded widespread use. Through the advent of matrix transducers enabling real-time three-dimensional echocardiography (3DE) and improvements in analysis software featuring semi-automated volumetric analysis, 3D echocardiography evolved into a simple and fast imaging modality for everyday clinical use. 3DE provides the possibility to evaluate the entire LV in three spatial dimensions during the complete cardiac cycle, offering a more accurate and complete quantitative evaluation the LV. Improved efficiency in acquisition and analysis may provide clinicians with important diagnostic information within minutes. The current article reviews the methodology and application of 3DE for quantitative evaluation of the LV, provides the scientific evidence for its current clinical use, and discusses its current limitations and potential future directions