[Clinical and angiographic parameters affecting the quality of 16 slice spiral CT in the diagnosis of restenosis after stenting the left main coronary artery]. / Paramètres cliniques et angiographiques influant sur la qualité de l'angioscanner spiralé 16 détecteurs dans le diagnostic de resténose après stenting du tronc commun de la coronaire gauche.

The metallic component of coronary stents makes it difficult to study their lumen by angio scanner. The object of this preliminary study was to appreciate the factors influencing the diagnosis of restenosis after stenting the left main coronary artery by 16-slice spiral angio CT. This Monocentric study included 27 patients who underwent 16-slice spiral angio CT six months after stenting of the left main coronary artery. It was possible to assess the stent lumen in 21 patients (78%) and no cases of > 50% restenosis were observed. In 4 patients, hypodense zones adjacent to the stent links were observed suggesting moderate intimal hyperplasia. The tests for ischaemia were normal in 3 of these patients. Coronary angiography and endocoronary ultrasound excluded significant restenosis in the fourth patient. In univariable analysis, the facors associated with good or excellent angioscanner quality (45% of patients) were Ostial stenosis (p = 0.03), no or minimal calcification on initial coronary angiography (p = 0.0S), stent diameters > 3.5mm (p = 0.03), heart rates < 60/min (p = 0.04), absence of extrasystoles (p = 0.05) during acquisition. In multivariable analysis, the only significant factors were absent or minimal calcification and stent diameters > 3.5mm (p = 0.02). The multidetector scanner seems a very promising method of investigating patients who have undergone stenting of the left main coronary artery but this study shows that certain clinical and angiographic parameters are limiting factors of surveillance with a 16-slice angioscanner.

Lack of correlation between plasma DOPEG and urinary MOPEG levels in depressed patients.

Twenty-four-hour urinary excretion of 3-methoxy,4-hydroxyphenylethyleneglycol (MOPEG) and levels of free and conjugated plasma 3,4-dihydroxyphenylethyleneglycol (DOPEG) were measured in 56 depressed patients to find a possible correlation between these two peripheral indices of cerebral noradrenergic activity. Plasma DOPEG was measured at 9:00 AM on the same day that urine was collected for the measurement of MOPEG. All depressed patients were diagnosed as having affective disorders according to DSM-III. No correlation was found between plasma free or conjugated DOPEG levels and urinary MOPEG output. This lack of correlation was found in the total sample of depressed patients (56), in 45 patients diagnosed as having major depressive episodes, and in 24 depressed patients diagnosed as major depressive with melancholia. The authors discuss the significance of this lack of correlation between two peripheral indices of central noradrenergic metabolism.

Litoxetine: a selective 5-HT uptake inhibitor with concomitant 5-HT3 receptor antagonist and antiemetic properties.

The selective 5HT uptake inhibitor, litoxetine (SL 81.0385), currently under development as an antidepressant was shown to have antiemetic properties in the ferret. Litoxetine (at 1 and 10 mg/kg i.v.) dose dependently reduced the number of retches and vomiting as well as the number of emetic episodes induced by cisplatin (10 mg/kg i.v.) and delayed the onset of emesis. Fluoxetine (at 1 or 10 mg/kg i.v.) failed to inhibit cisplatin-induced emetic responses and, in contrast, significantly increased the number of retches and vomiting and accelerated the onset of emesis. The possibility that the antiemetic effects of litoxetine may be mediated through an interaction with 5HT3 receptors was studied using [3H]quipazine or [3H]BRL 43694 to label the 5HT3 receptor. Litoxetine has moderate affinity for cerebral 5HT3 receptors (Ki = 85 nM), while fluoxetine, similar to other 5HT uptake inhibitors, has only negligible affinity for this receptor (Ki = 6.5 microM). It is proposed that litoxetine inhibits cisplatin-induced emetic responses due to its moderate 5HT3 antagonist properties. The clinical use of the majority of serotonergic antidepressants (e.g. fluoxetine, fluvoxamine etc.) is associated with gastrointestinal discomfort (particularly nausea and vomiting) as a major side-effect. If nausea and vomiting associated with the use of 5 HT uptake inhibitors are due to stimulation of 5HT3 receptors, the concomitant 5HT3 antagonism of litoxetine may limit the gastrointestinal side-effects of this novel antidepressant and thus offer an important advantage.

Computer vision approaches for the three-dimensional reconstruction of coronary arteries: review and prospects.

The objective of this article is to define the different stages involved in the 3D reconstruction of arteries and to review, from our experience and from the literature, the solutions already proposed. A full reconstruction framework includes the characterization of the imaging device (in terms of distortion and calibration), the specificity of the image acquisition process, the preprocessing that can be applied, the detection of the vascular structures, the 2D feature formation, the reconstruction itself, and the visualization aspects. They are examined according to a computer vision approach where two or three views are assumed to be available. Their generalization to temporal image sequences are also considered. Some of the material reported here is unpublished. The article allows the reader to identify the true critical issues that are not often clearly mentioned in the literature and the challenges that they convey. A final discussion presents a few perspectives in this area of research.

Reliability of data on haematotoxicity of antidepressants. A retrospective assessment of haematological monitoring in clinical studies on tricyclics.

At the present time, there is some concern over the haematological adverse effects of antidepressants. The present paper examines retrospectively 314 clinical trials in depression which were published in English or French between 1958 and 1986 and which used at least one of the following tricyclics: amitriptyline, clomipramine, imipramine. Two decision tables assess the depth of detail with which haematological monitoring and safety were described by the authors of each study. The results indicate that more than 98% of the papers under scrutiny either provide no information on the subject or do so in a manner which is entirely subjective. Thus, it seems that current knowledge of haematotoxicity of antidepressants is almost entirely the result of spontaneous reports from doctors, with its well-known drawbacks.

A knowledge-based approach for 3-D reconstruction and labeling of vascular networks from biplane angiographic projections.

An approach to the three-dimensional reconstruction of coronary arteries is presented. The principal objective is to show how modeling of a vascular network, together with algorithmic procedures, can lead to accurate 3-D structure and feature labeling. The labeling problem is stated directly within the 3-D reconstruction framework. The reconstruction ambiguities inherent to biplane techniques are solved by means of a knowledge base, modeling of the object, and heuristic rules. Feasibility in near-real situations has been demonstrated. The critical importance of the object 3-D reference to achieving the data and modeling matching is emphasized, and a way to deal with it is pointed out. The overall system implies an incremental development in methodologies and experiments. All of them have been elaborated and tested independently, and the most appropriate ones have been selected for integration into a modular system. All the stages of the process (calibration, segmentation, reconstruction, and display) are discussed, with the main focus on modeling. Examples of automatic reconstruction from a phantom are provided.

Dynamic feature extraction of coronary artery motion using DSA image sequences.

This paper aims to define and describe features of the motion of coronary arteries in two and three dimensions, presented as geometrical parameters that identify motion patterns. The main left coronary artery centerlines, obtained from digital subtraction angiography (DSA) image sequences, are first reconstructed. Thereafter, global and local motion features are evaluated along the sequence. The global attributes are centerline and point trajectory lengths, displacement amplitude, and virtual reference point, while local attributes are displacement direction, perpendicular/radial components, rotation direction, and curvature and torsion. These kinetic features allow us to obtain a detailed quantitative description of the displacements of arteries' centerlines, as well as associated epicardium deformations. Our modeling of local attributes as quasi-homogeneous on a segment analysis, enables us to propose a novel numeric to symbolic image transformation, which provides the required facts for knowledge-based motion interpretation. Experimental results using real data are consistent with cardiac dynamic behavior.

Understanding coronary artery movement: a knowledge-based approach.

The aim of this paper is to describe a knowledge-based system that interprets three-dimensional (3D) coronary artery movement, using data from digital subtraction angiography image sequences. Dynamic information obtained from artery centerline 3D reconstruction and optical flow estimation, is classified according to experimental evidence indicating that artery displacements are quasi-homogeneous by a segment analysis. Characteristic motion features like displacement direction, perpendicular/radial components, rotation direction, curvature and torsion are qualitatively described from an image sequence using symbolic labels. These facts are then related and interpreted using anatomical-functional knowledge provided by a specialist, as well as spatial and temporal knowledge, applying spatio-temporal reasoning schemes. Facts, knowledge and reasoning rules are stated in a declarative form. Detailed examples of local and global interpretation results, using a real reconstructed angiographic biplane image sequence are presented in order to illustrate how our system suitably interprets coronary artery dynamic behavior.

Towards dynamic cardiac scenes interpretation based on spatial-temporal knowledge.

Cardiac motion analysis enables to identify pathologies related to myocardial anomalies or coronary arteries circulation deficiencies. Conventionally, bi-dimensional (2D) left ventricle contour images have been extensively used, to perform quantitative measurements and qualitative evaluations of the cardiac function. Nevertheless, there are other cardiac anatomical structures, the coronary arteries, imaged on routine procedures, upon which complementary motion interpretation can be conducted. This paper presents an experimental methodology to perform dynamic cardiac scenes interpretation, studying three-dimensional (3D) coronary arteries spatial-temporal behavior. Being an alternative way to approach computer assisted cardiac motion interpretation, it reveals a wide range of rarely explored spatial-temporal situations and proposes how to address them. Considering the challenges to achieve dynamic scene interpretation, it is explained how spatial and temporal knowledge, are connected to specialist knowledge and measured parameters, to obtain a dynamic scene interpretation. Global and local motion features are modeled according to cardiac motion and geometrical knowledge, before its transformation into symbols. Anatomical knowledge and spatial-temporal knowledge are applied, along with spatial-temporal reasoning schemes, to access symbols meaning. Experimental results obtained using real data are presented. Complexity of interpretation envisioning is discussed, taking the given results as an example.

A randomized, double-blind study of alpidem vs placebo in the prevention and treatment of benzodiazepine withdrawal syndrome.

The aim of the trial was to assess alpidem efficacy in preventing and treating the benzodiazepine (BZ) withdrawal syndrome (WS). A multicentre, double-blind, randomized versus placebo, parallel group study of six-week duration was carried out in outpatients suffering from generalized anxiety or adjustment disorder with an anxious mood and taking non-hypnotic BZ as continuous course of therapy of at least one-year duration. At the entry, the patients abruptly discontinued BZs and were treated with 50 mg/bid/tid of alpidem or placebo. Withdrawal syndrome diagnosis was (regarding treatment allocation) formulated by an independent psychiatrist, according to DSM-III-R and an appropriate scale, the SESSB. One hundred seventy-three patients were randomized and 148 completed the study. Withdrawal syndrome occurred in 27 patients of the alpidem group (31.0%) and in 38 patients of the placebo group (44.2%). A severe WS was diagnosed in 11.1% of the patients in the alpidem group and in 31.6% of the placebo group. If not having been withdrawn from the market, alpidem could have been useful for the prevention of BZ withdrawal syndrome.

Three-dimensional reconstruction of the coronary arteries using a priori knowledge.

A method for 3D reconstruction of the coronary arteries from two radiographic images is presented. A novel technique for matching image structures is the main contribution of the work. After a comprehensive study of the knowledge required to approach this problem, an automatic method, which includes both numeric and symbolic procedures to solve geometric ambiguities, is developed. In the proposed method, all possible (virtual) reconstructions are first obtained. Their validity is evaluated by means of a priori knowledge about the 3D object and its projections. From the set of chosen possible solutions, the most likely solution is selected. The method is tested using real images and is implemented in a platform that allows further clinical validation.

Biocompatibility of blood tubings.

We studied hemocompatibility of various blood tubings with C3a anaphylatoxin measurement and comparative electron scanning microscopy. The following tubing materials were tested: polyvinylchloride (PVC) plasticised with phthalate (PVC), pvc plasticised with phthalate coextruded with polyurethane (PIV), and two phthalate-free lines: pvc plasticised with trimellitate coextruded with polyurethane (TRI) and pvc plasticised with LT 360 (LTP). Results of C3a generation rate showed a significant activation by all blood tubings, with a reduced rate with PIV when compared to all others. Electron scanning microscopy showed marked alterations of PIV surface on tubings stored for 6 months. Protein deposits on internal surfaces after dialysis were similar whatever tubing material was tested, but adhesive cell number was greater with TRI when compared to PVC and LTP. Hemocompatibility is unchanged with phthalate-free tubings when compared to phthalate plasticised ones. In contrast with phthalate plasticised PVC there is no beneficial effect of polyurethane coextrusion with trimellitate plasticised PVC in regard to C3a generation.

[Comparative risks and benefits of drugs. Methodological problems]. / Risques et bénéfices comparés des médicaments. Problèmes méthodologiques.

A focalizing toxicity is defined here as a specific toxicity which attracts much of the attention devoted to the safety of a drug: the hematotoxicity of "second generation" antidepressants is a typical example of such toxicity. The way in which it is handled is frequently biased, whether this be related to its perception or its reporting; as a result, it hampers the process of assessing the risk/benefit ratio of drugs. An attempt is made here to sketch the principles and methods of the validation of safety data; antidepressants furnish various examples of the different points that we make. Finally, we insist upon the fact that assessment of drug risk/benefit ratio must be global and comparative.

[Study of noradrenaline metabolism in depressed patients by the determination of plasma dihydroxyphenylethylene glycol]. / Exploration du métabolisme de la noradrénaline chez les déprimés par le dosage du dihydroxyphényléthyléneglycol plasmatique.

The plasmatic levels of free, sulfoconjugated and total dihydroxyphenylethyleneglycol (DOPEG), the main deaminated metabolite of noradrenaline, have been measured in thirty DSM3 major depressive inpatients and in thirty healthy controls matched for sex and age. DOPEG levels have been measured by a radioenzymatic assay. Almost fifty per cent of depressed inpatients were D.S.T. non suppressors, thirteen patients were unipolar and thirteen bipolar. Plasmatic DOPEG levels were significantly lower in depressed patients as compared to healthy controls despite a wide interindividual range of DOPEG values. However, the ratio of free over conjugated DOPEG was not statistically different in the two groups. DOPEG levels were slightly higher in the female population of healthy volunteers but not in the depressed patients. In the healthy volunteers, but not in depressed patients, there was a trend for free DOPEG to increase and for conjugated DOPEG to decrease with age. There was no statistical correlation between the DOPEG levels and Hamilton Depression Scores. Also plasmatic DOPEG values were not different in uni or bipolar patients and in DST suppressor or DST non suppressor inpatients. The significance of the decrease of plasmatic DOPEG levels in depressed patients is discussed: this diminution may reflect a deficiency in noradrenaline metabolism in CNS or else may be attributed to other factors e.g. alteration in circadian rhythms, differences in motor activity, in level of anxiety, in sleep and feeding behaviors; cotreatment with benzodiazepine and opiate compounds; monoamine oxidase activity.

[Study of the metabolism of cerebral noradrenaline in depressed patients by the assay of plasma dihydroxyphenylethylene glycol]. / Etude du métabolisme de la noradrénaline cérébrale chez les déprimés par le dosage du dihydroxy-phényl-éthylène-glycol plasmatique.

Dihydroxy-phenyl-ethylene-glycol (DOPEG or DHPG), a deaminated catabolite of noradrenaline formed after presynaptic re-uptake, is a good marker of metabolic activity in noradrenergic pathways. Plasma levels of free, conjugated and total DOPEG were measured by a radioenzymatic method in 45 patients with major depression selected according to the DSM 3 criteria and in 45 matched controls. A significant decrease in man DOPEG levels was observed in all depressive patients. A dexamethasone suppression test performed in these patients showed no difference in DOPEG levels between responders and non-responders, thus failing to support the hypothesis that subjects with low noradrenergic drive escape suppression. There was no correlation between plasma DOPEG levels and urinary excretion of methoxy-hydroxy-phenylglycol (MOPEG), another marker of noradrenaline metabolic activity. Thirty-one patients were treated with a specific monoaminergic antidepressant: maprotiline or indalpine; contrary to urinary MOPEG levels, plasma DOPEG levels had no predictive value concerning the response to this category of antidepressants. The various possible reasons for the fall in DOPEG observed in depressive patients are discussed.

[Towards an automatic classification of psychotropic drugs, based on computerized card-index of their properties]. / Vers une classification automatique des psychotropes à partir d'un fichier informatisé de leurs propriétés.

The authors give the used statistical approach to realize automatic classification on computarized clinical data about 111 psychotropic drugs. Four ways of analyses are used: a reciprocal averaging method to describe and to put together the numerous properties, a cluster analysis and a sequential dynamic clusters method to define groups, a decisionnal method discriminal analysis, to put non classified drugs down these groups. This methodology points out six groups characterized by clinical properties. Others reciprocal averaging analysis part: desinhibitors antipsychotic drugs and sedative antipsychotic drugs, monoamine oxydase inhibitors and others antidepressants, amphetamine drugs and non amphetaminic psychostimulants. This statistical way permits classification of new drugs without a priori.

Intraoperative tracking of aortic valve plane.

The main objective of this work is to track the aortic valve plane in intra-operative fluoroscopic images in order to optimize and secure Transcatheter Aortic Valve Implantation (TAVI) procedure. This paper is focused on the issue of aortic valve calcifications tracking in fluoroscopic images. We propose a new method based on the Tracking-Learning-Detection approach, applied to the aortic valve calcifications in order to determine the position of the aortic valve plane in intra-operative TAVI images. This main contribution concerns the improvement of object detection by updating the recursive tracker in which all features are tracked jointly. The approach has been evaluated on four patient databases, providing an absolute mean displacement error less than 10 pixels (≈2mm). Its suitability for the TAVI procedure has been analyzed.

Understanding the mechanisms amenable to CRT response: from pre-operative multimodal image data to patient-specific computational models.

This manuscript describes our recent developments towards better understanding of the mechanisms amenable to cardiac resynchronization therapy response. We report the results from a full multimodal dataset corresponding to eight patients from the euHeart project. The datasets include echocardiography, MRI and electrophysiological studies. We investigate two aspects. The first one focuses on pre-operative multimodal image data. From 2D echocardiography and 3D tagged MRI images, we compute atlas based dyssynchrony indices. We complement these indices with presence and extent of scar tissue and correlate them with CRT response. The second one focuses on computational models. We use pre-operative imaging to generate a patient-specific computational model. We show results of a fully automatic personalized electromechanical simulation. By case-per-case discussion of the results, we highlight the potential and key issues of this multimodal pipeline for the understanding of the mechanisms of CRT response and a better patient selection.

Personalization of a cardiac electromechanical model using reduced order unscented Kalman filtering from regional volumes.

Patient-specific cardiac modeling can help in understanding pathophysiology and therapy planning. However it requires to combine functional and anatomical data in order to build accurate models and to personalize the model geometry, kinematics, electrophysiology and mechanics. Personalizing the electromechanical coupling from medical images is a challenging task. We use the Bestel-Clément-Sorine (BCS) electromechanical model of the heart, which provides reasonable accuracy with a reasonable number of parameters (14 for each ventricle) compared to the available clinical data at the organ level. We propose a personalization strategy from cine MRI data in two steps. We first estimate global parameters with an automatic calibration algorithm based on the Unscented Transform which allows to initialize the parameters while matching the volume and pressure curves. In a second step we locally personalize the contractilities of all AHA (American Heart Association) zones of the left ventricle using the reduced order unscented Kalman filtering on Regional Volumes. This personalization strategy was validated synthetically and tested successfully on eight healthy and three pathological cases.