[Natalizumab as induction therapy in multiple sclerosis]. / Traitement d'induction dans la sclérose en plaques: place du natalizumab.

BACKGROUND: Current treatment options for first-line immunotherapy in relapsing-remitting multiple sclerosis (MS) are recombinant interferon-ß and glatiramer acetate. However, these therapies are only partially effective and certain patients may fail to respond. For this reason, it is important to elaborate alternative treatment strategies. Induction therapy represents a more aggressive approach in which powerful drugs are used right from the beginning to tackle the disease process hard and early. Natalizumab is a powerful monoclonal antibody approved for the treatment of relapsing-remitting MS and is known to silence disease activity. METHODS: We describe here the early outcome at 1 month and at 6 months of three patients treated with natalizumab for relapsing-remitting MS. RESULTS: All three patients had a high disease activity before the initiation of natalizumab, with 4, 8 and 5 gadolinium-enhancing lesions on brain MRI respectively. On the MRI scans made at 1 month after the first infusion, and at 6 months, there was no more gadolinium-enhancement and no new T2-lesion. Clinically, they did not experience any relapse. DISCUSSION: In these three cases, natalizumab showed a dramatic efficacy: the patients became "disease activity free" right from the first infusion. To our knowledge, natalizumab is not classically used as an induction therapy, unlike mitoxantrone. However, this treatment has potential hematological and cardiac toxicity and its use can be limited. Thus, in JC virus negative patients, natalizumab could be an interesting alternative treatment. CONCLUSION: Our report suggests that induction strategy with natalizumab may be applicable in patients with aggressive multiple sclerosis. A study of more similar cases may be interesting to confirm these preliminary results.

Current Clinical Application of Intracardiac Flow Analysis Using Echocardiography

In evaluating the cardiac function, it is important to have a comprehensive assessment of structural factors, such as the myocardial or valvular function and intracardiac flow dynamics that pass the heart. Vortex flow that form during left ventricular filling have specific geometry and anatomical location that are critical determinants of directed blood flow during ejection. The formation of abnormal vortices relates to the abnormal cardiac function. Therefore, vortex flow may offer a novel index of cardiac dysfunction. Intracardiac flow visualization using ultrasound technique has definite advantages with a higher temporal resolution and availability in real time clinical setting. Vector flow mapping based on color-Doppler and contrast echocardiography using particle image velocimetry is currently being used for visualizing the intracardiac flow. The purpose of this review is to provide readers with an update on the current method for analyzing intracardiac flow using echocardiography and its clinical applications.

Quantification of left ventricular mechanics using vector-velocity imaging, a novel feature tracking algorithm, applied to echocardiography and cardiac magnetic resonance imaging / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Tagged magnetic resonance imaging (MRI) is the non-invasive golden standard to measure myocardial deformity. Tissue Doppler Imaging can be used to assess myocardial deformity, however, it has the limitation of angle-dependence. Our study aimed to compare left ventricular torsion and strains measured by velocity-vector imaging (VVI) using echocardiography (echo-VVI) and MRI (MRI-VVI), and to validate them against harmonic phase tagged MRI (HARP MRI).</p><p><b>METHODS</b>A total number of 34 subjects (14 normal and 20 patients) were evaluated. Apical and basal image of left ventricular short axis view were acquired for measurements of apical and basal rotation, circumferential and radial strain using both echo-VVI and MRI-VVI. An apical four-chamber view was obtained for measuring the distance between the apical and basal levels.</p><p><b>RESULTS</b>The correlations of segmental rotations, circumferential and radial strains were high between echo-VVI and HARP MRI, while the agreement of apical rotation was poor. Left ventricular torsion showed much better correlation and agreement between echo-VVI and HARP MRI than apical rotation: the coefficient was 0.97, P < 0.001. The correlation between MRI-VVI and HARP MRI in quantifying rotational parameters and strains was similar with echo-VVI and HARP MRI. Echo-VVI could discriminate normal and dysfunctional ventricles on either hypertensive or dilated cardiomyopathy.</p><p><b>CONCLUSION</b>The data from this study show that (1) it is feasible to quantify left ventricular torsion and myocardial strain using echo-VVI and MRI-VVI in normal subjects, patients with left ventricular global systolic dysfunction and segment systolic dysfunction; (2) the agreement among all mechanical parameters derived from echo-VVI, MRI-VVI, and HARP MRI remained with clinically acceptable ranges.</p>

[Demyelinating disease affecting both central and peripheral nervous system]. / Maladie démyélinisante du système nerveux central et périphérique.

INTRODUCTION: Demyelinating disease affecting both the central and the peripheral nervous systems has rarely been reported. CASE REPORT: A 30-year-old man, presented with ataxia and diffuse areflexia due to polyneuropathy fullfilling demyelination criteria. His medical history was notable for central nervous system demyelination compatible with multiple sclerosis. He improved transiently with intravenous immunoglobulin and then stabilized with methotrexate. CONCLUSION: This case report distinguishes a new kind of inflammatory disease affecting both central and peripheral nervous system. It seems to be different from multiple sclerosis and chronic immune demyelinating polyneuropathy, because of high hyperproteinorachia and absence of oligoclonal bands in the cerebrospinal fluid.

The nature and origin of binucleate cells in human preimplantation embryos: relevance to placental mesenchymal dysplasia.

Cleavage-stage embryos often have nuclear abnormalities, one of the most common being binucleate blastomeres, which may contain two diploid or two haploid nuclei. Biopsied cells from preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS) cycles were studied to determine the relative frequency of binucleate cells with two haploid versus two diploid nuclei. The frequency of mononucleate haploid biopsied blastomeres was also recorded. In the chromosomal PGD cycles 45.2% of the biopsied binucleate cells were overall diploid and 38.7% were overall tetraploid, compared with 50.0% and 29.2% for the PGS group, respectively. Placental mesenchymal dysplasia is a rare condition associated with intrauterine growth restriction, prematurity and intrauterine death. Recent work suggests that androgenetic diploid/haploid mosaicism may be a causal mechanism. There are two possible origins of haploid nuclei, either the cell contained only one parental genome initially or they may be derived from the cytokinesis of binucleate cells with two haploid nuclei. Binucleate formation therefore may be a way of doubling up the haploid genome, to produce diploid cells of androgenetic origin as seen in placental mesenchymal dysplasia.

Variable aneuploidy mechanisms in embryos from couples with poor reproductive histories undergoing preimplantation genetic screening.

BACKGROUND: Preimplantation genetic screening (PGS) is used to determine the chromosome status of human embryos from patients with advanced maternal age (AMA), recurrent miscarriage (RM) or repeated implantation failure (RIF). METHODS: Embryos from 47 such couples were investigated for chromosomes 13, 15, 16, 18, 21 and 22 using fluorescence in situ hybridization with two rounds of hybridization. The investigation included parental lymphocyte work-up, the screening of blastomeres on day 3 and full follow-up on day 5/6 of untransferred embryos. RESULTS: The outcome of 60 PGS cycles is described, in which 523 embryos were biopsied; 91% gave results, of which 18% were diploid for all the chromosomes tested and 82% were abnormal. The pregnancy rate per cycle that reached the biopsy stage was 27%, and 30% per embryo transfer. Satisfactory follow-up was obtained from 353 embryos; all those diagnosed as abnormal were confirmed as such, although two false-positives were detected in relation to specific chromosome abnormalities. Meiotic errors were identified in 16% of embryos. Between the RM, AMA and RIF groups, there was a significant difference in the distribution of embryos that were uniformly abnormal and of those with meiotic errors; with an almost 3-fold increase in meiotic errors in the first two groups compared with the RIF group. CONCLUSIONS: This complete investigation has identified significant differences between referral groups concerning the origin of aneuploidy in their embryos.