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Biomedical subjects

J Ohayon

Publications and source records attributed to J Ohayon.

At least 19 recordsLinked to original sources
PubMed2006

Relationship between inflammatory lesions and cerebral atrophy in multiple sclerosis.

OBJECTIVE: To investigate the temporal relationship between inflammation and cerebral atrophy in a longitudinal study of 19 patients with relapsing-remitting multiple sclerosis (RRMS) using serial monthly contrast enhanced MRI examinations and monthly measurements of brain fractional volume (BFV) for an average of 4 (range 2.4 to 10) years. METHODS: In this retrospective study, all patients had an active MRI scan at entry with a minimum of two new contrast enhancing lesions (CEL) on baseline MRI examinations. Patients were followed for a minimum of 3 months during a baseline (pretreatment) phase and subsequently followed during treatment with recombinant interferon beta (IFN) and various other immunomodulatory agents. Pre- and post contrast axial images were obtained using 3-mm slice thickness and a gadolinium contrast dose of 0.1 mmol/kg. Monthly CEL were sequentially numbered on hardcopy films and monthly BFV was determined on precontrast T1W images using a semiautomated program. For BFV measurements, all T1W scans were registered to the entry examination, which served as a mask image. Cerebral atrophy was measured as percent brain fractional volume change (PBVC) compared to the entry baseline scan. RESULTS: The results demonstrate that cerebral atrophy paralleled that of contrast enhancing lesion accumulation. The correlation between cumulative CEL and PBVC ranged from R2 = 0.47 to 0.81. Immunomodulatory agents that effectively reduced CEL accumulation also slowed the rate of atrophy. CONCLUSIONS: The correlation between contrast enhancing lesions (CEL) and atrophy suggests that patients who are not responding to therapy with a decrease in CEL may also be at risk for developing increased atrophy.

Adult↗
PubMed2005

Non-linear elastic properties of the lingual and facial tissues assessed by indentation technique. Application to the biomechanics of speech production.

This paper aims at characterizing the mechanical behavior of two human anatomical structures, namely the tongue and the cheek. For this, an indentation experiment was provided, by measuring the mechanical response of tongue and cheek tissues removed from the fresh cadaver of a 74 year old woman. Non-linear relationships were observed between the force applied to the tissues and the corresponding displacements. To infer the mechanical constitutive laws from these measurements, a finite element (FE) analysis was provided. This analysis aimed at simulating the indentation experiment. An optimization process was used to determine the FE constitutive laws that provided the non-linear force/displacements observed during the indentation experiments. The tongue constitutive law was used for simulations provided by a 3D FE biomechanical model of the human tongue. This dynamical model was designed to study speech production. Given a set of tongue muscular commands, which levels correspond to the force classically measured during speech production, the FE model successfully simulated the main tongue movements observed during speech data.

Aged↗
PubMed2005

MRI as a marker for disease heterogeneity in multiple sclerosis.

BACKGROUND: Whereas recent data from imaging studies challenge the prevailing notion that multiple sclerosis (MS) is purely an inflammatory disease, pathologic studies suggest differences in the disease processes between individual patients with MS. The ability to dissect the pathophysiologic disease heterogeneity, if it indeed exists, by methodologies that can be applied in vivo is important both for the development of new therapeutics and for the ability to identify the optimal therapy for an individual patient. OBJECTIVE: To design a stratification algorithm for patients with MS based on accepted MRI measurements reflective of inflammation and axonal damage/tissue loss and to assess if such MS subgroups retain their intergroup differences long term. METHODS: Mathematical modeling was used to select three discriminatory MRI measures for clinical outcome based on the cross-sectional analysis of 71 patients with untreated MS and tested general applicability of the stratification scheme on the independent longitudinal cohort of 71 MS patients. RESULTS: By consecutive employment of MRI measures reflective of inflammation and tissue loss, the authors were able to separate MS patients into four clinically meaningful subgroups. The analysis of the longitudinal confirmatory cohort demonstrated persistence of the intergroup differences in selected MRI measures for 8 years. CONCLUSIONS: The inflammatory activity and destructiveness of the multiple sclerosis process are to some degree independent of each other, and the successive evaluation of both of these variables can strengthen prediction of clinical outcome in individual patients.

Adult↗
PubMed2001

In-vivo prediction of human coronary plaque rupture location using intravascular ultrasound and the finite element method.

BACKGROUND: Spontaneous rupture of atherosclerotic plaques is known to be involved in the mechanism leading to acute coronary syndromes. Means to detect plaques prone to rupture and predict rupture location would then be very valuable for clinical diagnosis. DESIGN: In this study, finite element (FE) analysis based on intravascular ultrasound (IVUS) images of atherosclerotic arteries was used to predict in-vivo plaque rupture locations. In four patients with coronary artery diseases, IVUS images were recorded before and after balloon angioplasty. Pre-angioplasty images were recorded after injection of ATP. This caused a brief drop of arterial blood pressure down to values of about 20 mmHg, and thus allowed the recording of the unloaded configurations of arteries used to initiate FE analysis. Plaque rupture was triggered by balloon inflation (coronary angioplasty). FE simulations were performed under physiological loading conditions. Stress distributions within the plaque and the arterial wall were determined. The corresponding stress maps are presented. RESULTS: Circumferential tensile peak stress areas were compared with plaque rupture locations on postangioplasty IVUS images. They were found to coincide in all four studied cases. CONCLUSION: Our results agreed with those reported in previous studies based on ex-vivo postnecropsic data and showed the feasibility of in-vivo prediction of atherosclerotic plaque rupture location.

Aged↗
PubMed2000

[Qualitative and quantitative descriptions of the mechanisms of action of the angioplasty balloon on coronary stenosis. An endovascular ultrasonic study].

The barotrauma induced by inflation of the balloon on an obstructive atherosclerotic plaque induces several distinct, complex effects. The object of this study was to describe these mechanisms based on endovascular echographic sections of coronary stenoses before and after balloon angioplasty. The 32 lesions analysed were richly cellular (81.2%) and associated with calcifications in 31% of cases. The remodelling index before angioplasty was used to individualize a majority of lesions with chronic arterial constriction (56.2%). The modelling of the plaque (dilatation or constriction) had no effect on the final luminal result. Global analysis of the endoluminal gain (4.38 +/- 2.28 mm2) showed that it was mainly due to reduction of plaque surface (78.2% of gain) without prejudging the mechanism, and less due to expansion of the global arterial surface (21.8% of the gain). The type of remodelling affected the mechanisms of action of balloon angioplasty. Dissection was present in 53.1% of cases. Fragmentation of the plaque with embolisation is a common phenomenon (28% of cases). The authors conclude that there are four mechanisms which coexist: 1) Reduction of plaque thickness cannot physically correspond to simple compression of tissue. The plaque is redistributed longitudinally. 2) Arterial expansion only plays a minor part in endoluminal gain. 3) Plaque rupture is directly related to the acute increase in wall stress often exceeding the thresholds of rupture of its components. Finally, 4) embolisation by parietal fragmentation, a mechanism often unknown or ignored which plays an essential part in the potentially deleterious effects.

Angioplasty, Balloon↗
PubMed1991

Myo-inositol and D-glucose transport in rat glomerular and cultured mesangial cells.

Myo-inositol (MI) is the precursor of membrane-bound phosphoinositides important for transmembrane signaling. This study examines whether freshly isolated whole glomeruli can be used to characterize intact cell transport kinetics for MI and D-glucose. Transport properties of cultured mesangial cells are compared. Glomeruli greater than 95% tubule free were isolated from Sprague-Dawley rat kidney cortex by means of selective sieving. Scanning electron microscopy revealed substantial damage of glomerular epithelial cells, whereas endothelial and mesangial cells remained intact. Specific [3H]MI uptake (7-180 min, 37 degrees C) was observed in presence of 5.5 mM D-glucose when L-[14C]glucose was used as a marker of nonspecific uptake. With ouabain (3 mM), or when Na was replaced with N-methyl-D-glucamine, choline, or Li, specific MI uptake was reduced by 95%. A single high-affinity, Na-dependent MI transport site on glomerular cells with Km of 16.5 +/- 1.4 (SE) microM and Vmax of 947 +/- 56 (SE) fmol.mg protein-1.min-1 was observed for 0.75-100 microM MI. D-glucose competitively inhibited MI transport. Specific D-[3H]-glucose transport was Na independent. Phlorizin inhibition of D-glucose and MI uptake was in keeping with Na-independent D-glucose transport. Km and Vmax for MI uptake in cultured mesangial cells were 42.7 +/- 7.1 microM and 1,474 +/- 192 fmol.mg protein-1.min-1, respectively. We conclude that freshly isolated glomeruli can be used to study cellular transport function that may be modified in disease states.

Animals↗
PubMed1991

A modelized distribution of actomyosin interactions in the vertebrate cardiac muscle.

Preliminary assumption of this model is that interactions between actin and myosin presupposes an exact three-dimensional geometrical correspondence between sites, due to the very short time constants present under physiological conditions. Only small and controlled torsions of the actin filaments are accepted. The model uses geometrical information concerning orientations and dimensions of myosin crossbridges and actin monomeres to modelize the distribution of their inter-actions. An orientation map of actin sites in the cross-section perpendicular to the filament axis is proposed, adapted to the specific filament array of vertebrate muscle. Orientation of myosin crossbridges follows Luther's rules. According to the model, any interaction between actin and myosin implies the superimposition of their respective cross-sectional planes. The axial length of actin monomere is 55 A; the distance between two crossbridges along the myosin filament axis is 143 A. The following properties are derived: 1) The shortening step of the sliding actin filament must be a multiple of 11 A (highest common factor). Taking into account the staggered disposition of the two actin strands and the presence of two heads for each cross-bridge, the most probable value for this shortening step is equal to 99 A. A specific scheme is proposed to describe the shortening process. The behavior of the modelized crossbridge does not need any elastic structure--2) Planes situated at 715 A (lowest common multiple) of actin and myosin coinciding planes are also in coincidence. In a hemi-sarcomere the maximal number of these planes, referred to as simultaneously activable planes, is 10 (20 if both myosin heads are considered). The proportion of interactions authorized by the site orientations is 1/12. In the model, the concept of randomly recruited crossbridges is replaced by a discretized recruitment, based on geometrical properties at an ultrastructural level. The proposed distribution is homogeneous: it can be extended radially in the sarcomere and authorizes the actin filament sliding in the whole physiological range under the control of a dual activation function, reproducing Ca++ temporal and spatial distribution.

Actins↗
PubMed1990

Phasic regional myocardial inflow and outflow: comparison of theory and experiments.

We developed a theory for regional blood flow in the beating heart and validated it with measurements of coronary arterial inflow and venous outflow in the open-chest anesthetized dog. The model used measured aortic, left ventricular, and coronary sinus pressures as input data under control conditions and during long diastoles induced by vagal stimulation. A nonlinear two-compartment lumped model for each transmural layer was obtained by spatial averaging a continuum description of the myocardial microcirculation based on morphometric measurements and appropriate fluid and vascular mechanics principles. The chief results and conclusions of the study are 1) an intramyocardial time constant on the order of 1 s is required to explain the phase opposition between inflow and outflow; 2) capillary and venous perfusion are in phase with arterial pressure, and arterial flow is out of phase with arterial pressure except in superficial intramural layers; 3) subendocardial retrograde systolic flow increases with increased contractility and time constants and decreased arterial pressure; and 4) endocardial capillary and venule volume change by 5.5 and 10%, respectively, during the control cardiac cycle.

Animals↗
PubMed1989

Wall-thickness and midwall-radius variations in ventricular mechanics.

A fluid-fiber-collagen stress tensor is used to describe the rheology of the left ventricle of the heart. Linear theory is used to find the equilibrium solutions for the end-diastolic and end-systolic states of general axisymmetric shapes that are small perturbations of a thick-walled finite cylinder. The general problem can be studied by superposing the effects of variable midwall radius but constant wall thickness with those of variable wall thickness but constant midwall radius. A Fourier series representation is used to describe the midwall radius and thickness functions. Numerical calculations are performed to determine the deformed geometry and spatial distributions of tissue pressure, stresses, and fiber strains. The calculations proved to be highly accurate when compared to an analytical solution obtained for the special case of no fibers. The results show significant longitudinal differences when compared to results for the cylindrical geometry, with more sensitivity to variation in wall thickness than to variation in midwall radius.

Animals↗
PubMed1988

Effects of collagen microstructure on the mechanics of the left ventricle.

The microstructure of the collagen sheath or weave surrounding a myocyte and the collagen struts interconnecting neighboring myocytes is incorporated into a fluid-fiber-collagen continuum description of the myocardium. The sheaths contribute to anisotropic elasticity, whereas the struts contribute to an isotropic component. Elastic moduli of the composite myocyte-sheath complex and the strut matrix are estimated from existing passive biaxial loading data from sheets of canine myocardium. The contribution of the sheath to the elasticity of the myocyte-sheath complex is critically dependent on the helical pitch angle. Calculations for a cylindrical model of the left ventricle using both a fluid-fiber and fluid-fiber-collagen stress tensor show that the collagen strut matrix tends to limit muscle fiber lengthening; increase myocardial tissue pressure during systole, with endocardial tissue pressure exceeding left ventricular pressure; decrease tissue pressure during diastole, and thus facilitate myocardial blood flow; and aid filling during ventricular relaxation by providing a suction effect that relies on a release of stored elastic energy from the previous contraction. Calculations show that this energy is stored mostly in the collagen struts.

Animals↗
PubMed1988

Theoretical analysis of the effects of a radial activation wave and twisting motion on the mechanics of the left ventricle.

The mechanical effects resulting from the normal transmural delay of electrical depolarization of the myocardium are investigated. An activation sequence having a finite radial propagation velocity is introduced into the equations of ventricular mechanics. The resulting system of coupled integral equations is solved using a perturbation method based on the small ratio of transmural propagation time to cardiac period. Numerical calculations are performed using cavity pressure and volume waveforms characteristic of the canine left ventricle (LV), for both simultaneous and delayed activation of fiber layers. The results show that a finite transmural electrical propagation velocity tends to: (i) equalize the transmural distribution of sarcomere length during systole; (ii) equalize the transmural distribution of fiber external work/vol; and (iii) insignificantly affect myocardial tissue pressure. Calculations are also performed to investigate the mechanical effects resulting from the application of an externally applied moment that prevents LV torsion. Those results are highly dependent on the transmural distribution of sarcomere length in the stress-free reference state (unloaded diastole). When we assume a uniform distribution, then normal torsion acting with normal activation delay tends to: (i) increase the magnitude of fiber strain in the subendocardium and decrease it in the subepicardium; (ii) equalize the transmural distribution of fiber external work/vol; and (iii) lower myocardial tissue pressure. The normally occurring transmural delay of activation tends to lessen endocardial O2 demand, while the normally occurring torsion further lessens that demand and improves O2 supply.

Animals↗
PubMed1987

[Refractory unstable angina. Emergency treatment by coronary artery angioplasty under aortic counterpulsion].

We report our experience of 15 transluminal coronary angioplasties performed in an emergency in 13 patients (mean age 67 +/- 8 years) with refractory unstable angina. The procedures were conducted under diastolic counterpulsation effected by means of an intra-aortic balloon. The angina was of the threatening infarction type on 11 occasions and of the threatening extended infarction on 4 occasions. Electrocardiographic abnormalities were recorded in the anterior (11 cases) or in the inferior (4 cases) territory. Three patients had a very alarming haemodynamic status, with acute pulmonary oedema in two and cardiogenic shock in one. After intra-aortic counterpulsation was installed and the clinical signs were stabilized, coronaro-ventriculography was performed, leading to a decision of immediate angioplasty since age, underlying diseases, myocardial function and diffused lesions made most of the patients unsuitable for surgery. In multiple vessel patients electric and angiographic data were used to locate the tight stenosis (92% in all cases) responsible for the acute coronary ischaemia. The stenosis was found to affect the anterior interventricular artery in 9 cases, the circumflex artery in 2 cases, the right coronary artery in 2 cases and a saphenous shunt on the anterior interventricular artery in 2 cases. Immediate arteriographic and clinical success was obtained in 12 out of 15 cases (80%); there were 3 failures with 2 transmural infarctions. Later on, 2 patients underwent aorto-coronary bypass and 1 died of myocardial failure and pulmonary superinfection 3 weeks after the procedure. Ten of our 13 patients were stabilized and were discharged under medical treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1987

[Hemodynamic effects of a new alpha-1 antagonist, AR-C 239 administrated in intravenous bolus, in patients with cardiac insufficiency].

A new specific alpha-1 antagonist was studied in 16 patients with left ventricular failure. In Group I (8 patients) the drug was given as a 40 micrograms/kg intravenous bolus, and in Group II (8 patients) at the dose of 80 micrograms/kg. A thermodilution Swan-Ganz catheter, a Millar microtransducer introduced via the femoral artery were relayed to a SYSCOMORAM system to record the systemic artery pressures (SAP), pulmonary artery pressures (PAP), left ventricular pressures, and to calculate cardiac output and systemic and pulmonary arterial resistances (SAR, PAR) over a 30 minute period. In Group I (40 micrograms/kg), administration of AR-C 239 led to a significant decrease in PAP and SAP (-24 +/- 17 p. 100, p less than 0.02) with a fall in time-tension index (-20 +/- 19 p. 100, p less than 0.05) and a significant increase in LV stroke volume (+23 +/- 12 p. 100, p less than 0.01). At 80 micrograms/kg there was also a fall in LV filling pressures (-29 +/- 25 p. 100, p less than 0.05) and PAP (-38 +/- 28 p. 100, p less than 0.02) and an improvement in LV compliance (Gaaschisk -43 +/- 19 p. 100, p less than 0.01). These results show that AR-C 239 is a powerful vasodilator without secondary beta mimetic effects or influence on LV contractility; it may provide an effective means of treating cardiac failure.

Adult↗
PubMed1987

[Obstruction of the left coronary branch. Ergometric, hemodynamic and angiographic findings].

The authors present 6 personal cases of complete obstruction of the left main stem coronary artery and review the main epidemiological, clinical, ergometric, haemodynamic, angiographic and therapeutic data concerning this condition which is uncommon (0.66% of patients who underwent coronary angiography for angina in this series). This series had a number of special features. Clinical symptoms were moderate, consisting of exercise-induced aggravated angina, except in one patient with a history of anterior infarction complicated by regressive initial heart failure with residual angina. For this reason, all patients were able to perform a standard exercise-test on an ergometric bicycle without any problem. As the exercise test revealed major abnormalities, extreme precautions were observed when coronary angiography was performed, but no incident occurred in any of the 6 patients. Haemodynamic data were normal in 4 cases and altered in 2 cases. The important role played by collateral circulation must be stressed; it is probably under evaluated at arteriography. The absence of lesion of the right coronary artery is thought to facilitate the development of a collateral vascular network. Five patients were operated upon, made an uneventful recovery and were followed up for 19, 42, 17, 5 and 2 months respectively: all were symptom-free under medical treatment. In 3 out of these 5 patients who underwent a post-operative exercise-test all parameters showed excellent results; however, the 4th patient proved unadaptable to exercise, and ECG showed persistent ischaemia due to a very poor distal coronary bed; in the 5th patient, under diltiazem, the results on ischaemia and on the circulatory signs of heart failure were very good.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1986

Quantitative frame by frame analysis of regional contraction and lengthening on left ventricular cineangiograms: application to the study of normal left ventricles and left ventricles with mitral valve prolapse.

This work attempted to study the segmental wall motion on left ventriculograms, in terms of segmental shortening, velocity of segmental shortening, and temporal sequences of various events in systole as well as in diastole. The ability of such a method to characterize patterns of normal regional wall motion and to detect mild abnormalities such as isolated asynchronisms, was tested on two groups of patients. Group I included 25 patients presenting evidence of a normal left ventricle (LV) after left heart catheterization. Group II consisted of 21 patients suffering from an isolated pure idiopathic mitral valve prolapse (MVP), with no mitral insufficiency and with an unaffected global LV function. In all patients left ventriculography was filmed in the right anterior oblique view at a rate of 50 frames/s. For each patient a cycle was chosen, distant from any premature beat, with acceptably contrasted outlines, and a quantitative frame by frame study of the motion of 10 segments was performed using a semiautomated method derived from the Stanford method. In the control group (Group I), analysis of the segmental motion by means of this method demonstrates a mild nonuniformity of the normal wall motion. This is principally marked by a stronger and faster contraction in anterolateral segments (segments 7, 8, 9) and by a shorter duration of the contraction in this region. In contrast the MVP group (Group II), exhibited a frank asynergy of the anterolateral region occurring from end systole to early diastole.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗