Biomedical subjects

Alain Lalande

Publications and source records attributed to Alain Lalande.

11 recordsLinked to original sources

PubMed2006

Mutations in myosin heavy chain 11 cause a syndrome associating thoracic aortic aneurysm/aortic dissection and patent ductus arteriosus.

We have recently described two kindreds presenting thoracic aortic aneurysm and/or aortic dissection (TAAD) and patent ductus arteriosus (PDA) and mapped the disease locus to 16p12.2-p13.13 (ref. 3). We now demonstrate that the disease is caused by mutations in the MYH11 gene affecting the C-terminal coiled-coil region of the smooth muscle myosin heavy chain, a specific contractile protein of smooth muscle cells (SMC). All individuals bearing the heterozygous mutations, even if asymptomatic, showed marked aortic stiffness. Examination of pathological aortas showed large areas of medial degeneration with very low SMC content. Abnormal immunological recognition of SM-MHC and the colocalization of wild-type and mutant rod proteins in SMC, in conjunction with differences in their coimmunoprecipitation capacities, strongly suggest a dominant-negative effect. Human MYH11 gene mutations provide the first example of a direct change in a specific SMC protein leading to an inherited arterial disease.

Adult↗

PubMed2005

Mapping of familial thoracic aortic aneurysm/dissection with patent ductus arteriosus to 16p12.2-p13.13.

BACKGROUND: Three loci have been shown to be responsible for nonsyndromic familial thoracic aortic aneurysms (TAAs) and aortic dissections (ADs). We recently described a large family in which TAA/AD associates with patent ductus arteriosus (PDA) and provided genetic arguments for a unique pathophysiological entity. METHODS AND RESULTS: Genome-wide scan was performed in 40 subjects belonging to 3 generations in this large pedigree. Using the 7 TAA/AD cases as affected, we observed positive 2-point LOD scores on adjacent markers at chromosome 16p, with a maximum LOD score value of 2.73 at theta=0, a value that increased to 3.56 when 5 PDA cases were included. Multipoint linkage analysis yielded a maximum LOD score of 4.14 in the vicinity of marker D16S3103. Fine mapping allowed the observation of recombinant haplotypes that delimited a critical 20-cM interval at 16p12.2-p13.13. Automatic determination of aortic compliance with cine MRI showed that all subjects bearing the disease haplotype, even asymptomatic, displayed a very low level of aortic compliance and distensibility. Aortic stiffness was strongly associated with disease haplotype with a marked effect of age, indicating subclinical and early manifestation of the disease. CONCLUSIONS: Genetic analysis of this family identified a unique locus responsible for both TAA/AD and PDA at chromosome 16p12.2-p13.13 with aortic stiffness as an early hallmark of the disease. TAA/AD with PDA is a new monogenic entity among the genetically heterogeneous group of TAA/AD disease.

Aorta↗

PubMed2005

Automatic fuzzy classification of the washout curves from magnetic resonance first-pass perfusion imaging after myocardial infarction.

OBJECTIVES: We sought to investigate the diagnostic ability of cardiac magnetic resonance imaging (MRI) perfusion in acute reperfused myocardial infarction. The study used fuzzy logic to automatically classify signal intensity-time curves from myocardial segments into 3 categories: normal, hypointense, and Hyperintense. MATERIALS AND METHODS: Thirty-eight patients with myocardial infarction underwent short-axis cine-MRI and contrast-enhanced MRI to provide data on wall thickening and the transmural extent of infarction. Of these, 17 had a second cardiac MRI to ascertain the functional recovery in each segment. RESULTS: The fuzzy logic based classification performs well (kappa= 0.87, P < 0.01) in comparison with a visual approach. Segments providing "hypo" curves do not recover (Delta = 0.11 SD = 0.96) whereas segments demonstrating the other curve types recover (Delta = 1 SD = 1.98 for "hyper" curves and Delta = 1.54 SD = 1.77 for "normal" curves). CONCLUSIONS: The proposed automatic signal intensity-time curve classification has a prognostic value when studying the functional recovery of pathologic segments and clearly identifies the no-reflow phenomenon known to induce poor recovery.

Adult↗

PubMed2004

Visual estimation of the global myocardial extent of hyperenhancement on delayed contrast-enhanced MRI.

MRI with paramagnetic contrast agent allows the assessment of the extent of myocardial tissue injury after infarction. Visual segmental scoring has been widely used to define the transmural extent of myocardial infarction, but no attempt has been made to use visual scores in order to assess the percentage of the whole myocardium infarcted. By summing all the segmental scores using a 17-segment model, a global index of the size of the infarcted myocardium is easily obtained. The entire left ventricle of 60 patients with a recent myocardial infarction was scanned using an ECG-gated gradient echo sequence after injection of gadolinium contrast agent. The global score was defined as the sum of the scores on each segment, and expressed as a percentage of the maximum possible score. This index was compared with a planimetric evaluation of hyperenhancement, expressed as a percentage of the left ventricle myocardial volume. There is a good correlation between the two methods (r=0.91; y=1.06x+0.20), and the Bland-Altman plot shows a high concordance between the two approaches (mean of the differences =1.45%). A visual approach based on a 17-segment model can be used to evaluate the global myocardial extent of the hyperenhancement with similar results to planimetry.

Adult↗

PubMed2004

Time course of NAA T2 and ADC(w) in ischaemic stroke patients: 1H MRS imaging and diffusion-weighted MRI.

BACKGROUND AND PURPOSE: Proton spectroscopy and quantitative diffusion-weighted imaging (DWI) were used to investigate the pertinence of N-acetyl aspartate (NAA) as a reliable marker of neuronal density in human stroke. METHODS: The time courses of tissue water apparent diffusion coefficient (ADC(w)) and metabolite T2 were investigated on a plane corresponding to the largest area of cerebral infarction, within and outside the site of infarction in 71 patients with a large cortical middle cerebral artery territory infarction. RESULTS: Significant reductions are seen in NAA T2 deep within the infarction during the period comprised between 5 and 20 days postinfarction; the relaxation times appearing to normalise several months after stroke. After an acute reduction in ADC(w), the pseudonormalisation of ADC(w) occurs at 8-12 days after the ischaemic insult. The minimum in N-acetyl aspartate T2 relaxation times and the pseudonormalisation of ADC(w) appear to coincide. CONCLUSIONS: The data suggest that modifications in the behaviour of the observed proton metabolites occur during the period when the vasogenic oedema is formed and cell membrane integrity is lost. For this reason, NAA may not be a reliable marker of neuronal density during this period.

Aged↗

PubMed2004

The extent of myocardial damage assessed by contrast-enhanced MRI is a major determinant of N-BNP concentration after myocardial infarction.

AIMS: To evaluate the relationship between N-terminal Pro-Brain Natriuretic Peptide (N-BNP) level and contrast-enhanced MRI in patients after acute myocardial infarction (MI). METHODS: Eighty-two patients were studied. Venous blood samples were obtained 3 days after MI and MRI was performed from 2 to 7 days after MI, with determination of left ventricular function and acquisition of perfusion data after injection of gadolinium-DTPA. First-pass images (FPI) and Delayed contrast-enhanced (CE) images were analyzed using a 17-segment model, and the extent of transmurality was determined by a visual score. RESULTS: Univariate analysis showed that age (P<0.001), sex (P<0.02), Left Ventricular Ejection Fraction (LVEF) <45% (P<0.002), creatinine (P<0.05) and delayed CE-MR images (P<0.006) were predictors of a supramedian N-BNP level. FPI was not a predictor in this univariate analysis (P<0.078). In a multivariate model, only age, LVEF <45% and delayed CE-MRI were associated with an increased N-BNP level. CONCLUSION: After MI, high N-BNP levels are dependent on the LVEF but also on the myocardial infarct size derived from the delayed CE-MR images.

Aged↗

PubMed2004

Realignment of myocardial first-pass MR perfusion images using an automatic detection of the heart-lung interface.

Magnetic resonance first-pass imaging of a bolus of contrast agent is well adapted to distinguish normal and hypoperfused areas of the myocardium. In most cases, the signal intensity-time curves in user defined regions of interest (ROI) are studied. As image acquisition is ECG-gated, the images are acquired at the same moment in the cardiac cycle, and the basic shape of the heart is similar from one view to the next. However, superficial respiratory motion can displace the heart in the short-axis plane. The aim of this study is to correct for the respiratory motion of the heart by performing an automatic realignment of the myocardial ROI based on a method tracking the movement of the lung-myocardium interface. Visual and quantitative analyses performed on 120 curves show a very good concordance between two automatic methods and the manual one.

Adult↗

PubMed2004

Microtubule alteration is an early cellular reaction to the metabolic challenge in ischemic cardiomyocytes.

Cytoskeleton damage, particularly microtubule (MT) alterations, may play an important role in the pathogenesis of ischemia-induced myocardial injury. However, this disorganization has been scarcely confirmed in the cellular context. We evaluated MT network disassembly in myoblast cell line H9c2 and in neonatal rat cardiomyocytes in an in vitro substrate-free hypoxia model of simulated ischemia (SI). After different duration of SI from 30 up to 180 min, the cells were fixed and the microtubule network was revealed by immunocytochemistry. The microtubule alterations were quantified using a house-developed image analysis program. Additionally, the tubulin fraction were extracted and quantified by Western blotting. The cell respiration, the release of cellular LDH and the cell viability were evaluated at the same periods. An early MT disassembly was observed after 60 min of SI. The decrease in MT fluorescence intensity at 60 and 90 min was correlated with a microtubule disassembly. Conversely, SI-induced significant LDH release (35%) and decrease in cell viability (34%) occurred after 120 min only. These results suggest that the simulated ischemia-induced changes in MT network should not be considered as an ultrastructural hallmark of the cell injury and could rather be an early ultrastructural correlate of the cellular reaction to the metabolic challenge.

Animals↗

PubMed2004

Familial thoracic aortic aneurysm/dissection with patent ductus arteriosus: genetic arguments for a particular pathophysiological entity.

Thoracic aortic aneurysm and aortic dissection (TAA and AD) are an important cause of sudden death. Familial cases could account for 20% of all cases. A genetic heterogeneity with two identified genes (FBN1 and COL3A1) and three loci (3p24-25 or MFS2/TAAD2, 5q13-q14 and 11q23.2-24) has been shown previously. Study of a single family composed of 179 members with an abnormally high occurrence of TAA/AD disease. A total of 40 subjects from three generations were investigated. In addition to five cases of stroke and three cases of sudden death, there were four cases of AD and four cases of TAA in adults. In all, 11 cases of patent ductus arteriosus (PDA) were observed, two of which were associated with TAA and one with AD. Segregation analysis showed that the distribution of these vascular abnormalities was more likely compatible with a single genetic defect with an autosomal dominant pattern of inheritance. There were no clinical signs of Marfan, Elhers-Danlos vascular type or Char syndromes. Genetic linkage analysis was performed for seven genes or loci implicated in familial TAA/AD disease (COL3A1, FBN1, 3p24-25 or MFS2/TAAD2, 5q13-q14 and 11q23.2-q24), Char syndrome (TFAP2B) or autosomal recessive PDA (12q24). Using different genetic models, linkage with these seven loci was excluded. Familial TAA/AD with PDA is likely to be a particular heritable vascular disorder, with an as yet undiscovered Mendelian genetic basis.

Aortic Dissection↗

PubMed2004

Left ventricular ejection fraction calculation from automatically selected and processed diastolic and systolic frames in short-axis cine-MRI.

The calculation of the left ventricular ejection fraction (LVEF) is dependent upon the accurate measurement of diastolic and systolic left ventricular volumes. Although breath-hold cine magnetic resonance imaging (MRI) allows coverage of the whole cardiac cycle with an excellent time resolution, many authors rely on the visual selection of diastolic and the systolic short-axis slices in order to reduce the postprocessing time. An automatic method was developed to detect the endocardial contour on each image, allowing an automatic selection of the systolic frame. The calculated ejection fraction was compared with radionuclide ventriculography (RNV). Sixty-five patients were examined using an electrocardiogram (ECG)-gated gradient echo sequence. Among these examinations, manual and automatic processing with MRI were compared when the time of the systolic frame concorded. Good correlations have been found between the automatic MRI approach and RNV, and between manual and automatic processing on MRI alone. The results show that the automatic determination of the ejection fraction is feasible, and should constitute an important step toward a larger acceptance of MRI as a routine tool in heart disease imaging. One major benefit of using automatic postprocessing is that it may eliminate the visual choice of the systolic frame, inaccurate in more than 50% of the studied patients.

Adult↗

PubMed2002

Automatic determination of aortic compliance with cine-magnetic resonance imaging: an application of fuzzy logic theory.

RATIONALE AND OBJECTIVES: Aortic compliance is defined as the relative change in aortic cross-sectional area divided by the change in arterial pressure. Magnetic resonance imaging (MRI) is a useful imaging modality for the noninvasive evaluation of aortic compliance. However, manual tracing of the aortic contour is subject to important interobserver variations. To estimate the aortic compliance from cine-MRI, a method based on fuzzy logic theory was elaborated. MATERIALS AND METHODS: Seven healthy volunteers and eight patients with Marfan syndrome were examined using an ECG gated cine-MRI sequence. The aorta was imaged in the transverse plane at the level of the pulmonary trunk. A method based on fuzzy logic was developed to automatically detect the aortic contour. RESULTS: Through our robust automatic contouring method, the calculation of aortic cross-sectional areas allows an estimation of the aortic compliance. CONCLUSION: The aortic compliance can be obtained from a fuzzy logic based automatic contouring method, thereby avoiding the important interobserver variation often associated with manual tracing.

Adolescent↗