Copy-number analysis identified new prognostic marker in acute myeloid leukemia.

Recent advances in genomic technologies have revolutionized acute myeloid leukemia (AML) understanding by identifying potential novel actionable genomic alterations. Consequently, current risk stratification at diagnosis not only relies on cytogenetics, but also on the inclusion of several of these abnormalities. Despite this progress, AML remains a heterogeneous and complex malignancy with variable response to current therapy. Although copy-number alterations (CNAs) are accepted prognostic markers in cancers, large-scale genomic studies aiming at identifying specific prognostic CNA-based markers in AML are still lacking. Using 367 AML, we identified four recurrent CNA on chromosomes 11 and 21 that predicted outcome even after adjusting for standard prognostic risk factors and potentially delineated two new subclasses of AML with poor prognosis. ERG amplification, the most frequent CNA, was related to cytarabine resistance, a cornerstone drug of AML therapy. These findings were further validated in The Cancer Genome Atlas data. Our results demonstrate that specific CNA are of independent prognostic relevance, and provide new molecular information into the genomic basis of AML and cytarabine response. Finally, these CNA identified two potential novel risk groups of AML, which when confirmed prospectively, may improve the clinical risk stratification and potentially the AML outcome.

[Cephalometric study of the velocardiofacial syndrome: Impact of dysmorphosis on phonation]. / Céphalométrie du syndrome vélocardiofacial: les conséquences phonatoires de la dysmorphose.

INTRODUCTION: Velopharyngeal insufficiency is a frequent sign of the velocardiofacial syndrome (VCFS) but its origins are not well-documented. Our aim was to establish a correlation between this functional disorder and regional morphological anomalies. PATIENTS AND METHODS: Twenty-seven of 36 patients presenting with VCFS could be included retrospectively. We measured cavum depth and velum length on lateral orthodontic X-rays, and assessed the relationship between these two measures. We compared these measures to those of reference populations. Postoperative phonation was assessed with an aerophonoscope. RESULTS: The patients presented with a short velum and a deep cavum. Cranium base and upper cervical spine were malformed in 22 of the 27 patients. Seventeen of the 23 assessed patients (66%) improved their phonation after surgery. DISCUSSION: Our data suggests that velopharyngeal insufficiency in VCFS could be the result of a more global craniospinal growth disorder the functional consequences of which remain unclear. The frequent association of morphological anomalies with mental retardation is probably responsible for the failure to normalize phonation.

Genotype phenotype correlation of 30 patients with Smith-Magenis syndrome (SMS) using comparative genome hybridisation array: cleft palate in SMS is associated with larger deletions.

BACKGROUND: Smith-Magenis syndrome (SMS) is rare (prevalence 1 in 25 000) and is associated with psychomotor delay, a particular behavioural pattern and congenital anomalies. SMS is often due to a chromosomal deletion of <4 Mb at the 17p11.2 locus, leading to haploinsufficiency of numerous genes. Mutations of one of these gemes, RAI1, seems to be responsible for the main features found with heterozygous 17p11.2 deletions. METHODS: We studied DNA from 30 patients with SMS using a 300 bp amplimers comparative genome hybridisation array encompassing 75 loci from a 22 Mb section from the short arm of chromosome 17. RESULTS: Three patients had large deletions (10%). Genotype-phenotype correlation showed that two of them had cleft palate, which was not found in any of the other patients with SMS (p<0.007, Fisher's exact test). The smallest extra-deleted region associated with cleft palate in SMS is 1.4 Mb, contains <16 genes and is located at 17p11.2-17p12. Gene expression array data showed that the ubiquitin B precursor (UBB) is significantly expressed in the first branchial arch in the fourth and fifth weeks of human development. CONCLUSION: These data support UBB as a good candidate gene for isolated cleft palate.

[Multislice computed tomography to detect coronary stenosis among asymptomatic patients with cardiovascular risk factors and equivocal prior stress test: preliminary study]. / Apport du scanner multicoupes dans le dépistage des lésions coronaires chez des patients asymptomatiques à risque: étude préliminaire.

UNLABELLED: Multislice computed tomography (MSCT) is a non-invasive and validated technique to detect coronary stenoses. Some questions remain about its accuracy to detect coronary stenoses (CS), especially for asymptomatic patients (P) when a prior stress test isn't conclusive. METHODS: MSCT was performed among 45 asymptomatic men (mean age: 58,3 +/- 16), with a high ten year risk of fatal cardiovascular disease (SCORE 2003 data for low-risk regions of Europe), without any previous coronary history and with previous non conclusive exercise testing. When significant (> 50%) CS was suspected at MSCT, an angiocoronarography (AC) was done. RESULTS: Eighteen MSCT were normal, unsignificant CS (< 50%) were detected on 14 MSCT and significant coronary stenoses (SCS) for 13 P. Among this 13 P, 19 SCS were identified: 2 SCS of left main coronary artery (CA), 9 of the left descending CA, 6 of the right CA and 2 of the left circumflex CA. 13 CS were confirmed at AC. Finally, because of critical angiographic lesions +/- ischemia at nuclear tomoscintigraphy (NT), 9 P had coronary revascularization (7 catheter based, 2 surgical bypass), 4 P had medical treatment. DISCUSSION: Benefits of this preliminary study are obvious: 9 coronary revascularization/45 P. However, the place of MSCT for the screening of CS is uncertain, but may be usefull as a complement for the screening of coronary arterial disease.

[Vasoplegic shock and myocardial infarction during administration of iloprost]. / Choc vasoplégique et infarctus du myocarde lors de l'administration d'iloprost.

INTRODUCTION: The association of vasoplegic shock and myocardial infarction in a patient under iloprost treatment for critical ischemia of the lower limbs has not previously been reported. OBSERVATION: A 56 year-old man suffering from type 2 diabetes, hypertension and dyslipidemia developed critical ischemia of the right leg and was treated with iloprost. On the 19th day of infusion, he developed a vasoplegic shock with myocardial infarction. The shock resolved and he recovered from the infarction. DISCUSSION: This case report indicates the need for reinforced blood pressure and electrocardiographic monitoring in diabetes patients treated with iloprost.

[The heart and aerobatics]. / Coeur et voltige aérienne.

Aerobatics is an aerial sport which has many physiological constraints, principally cardiovascular, with a risk if not adapted of sudden mid-air incapacity which could jeopardise aviation safety, and thus justifies the selection and surveillance of pilots. The aeronautical constraints during flight are multiple, related to the environment traversed, how the aircraft functions and its movements. Those which cause accelerations (+G in particular) pose the problem of haemodynamic tolerance because they can induce loss of consciousness due to cerebral hypoxia. Tolerance of acceleration varies among individuals; it can be improved with training, certain protective manoeuvres, and is reduced by hypoxia, certain medications, dehydration and heat. Moreover, in aerobatics certain tricks require manoeuvres which reduce this tolerance to +G accelerations. This is the "push-pull" effect (_G acceleration immediately followed by +G acceleration). This leads to a risk of sudden loss of consciousness with a load factor much lower than that which the pilot knows he is capable of tolerating. Besides the haemodynamic effects, the existence of an actual acceleration cardiomyopathy has been suggested but has not been proven in man. Finally, while changes in cardiac rhythm during accelerations are usual and relate to changes in vaso-sympathetic balance, ventricular and supra-ventricular rhythm disturbances are rare and are related to the intensity and duration of the acceleration.

[Very long-term outcome of 68 vena cava filters percutaneously implanted]. / Devenir à très long terme de 68 filtres caves implantés par voie percutanée.

Between January 1987 and December 1991, 68 consecutive patients aged 71.5 +/- 12.0 years underwent percutaneous implantation of a vena caval filter, mainly the LGM (N = 64). Fifty seven patients had pulmonary embolism, 61 had deep vein thrombosis of the lower limbs. The average follow-up interval was 4.9 +/- 3.3 years (7.0 +/- 2.7 years for the patients still alive). The follow-up included a telephonic enquiry to determine the date and cause of death, recurrent deep vein thrombosis and/or pulmonary embolism; surviving patients underwent clinical examination, plain abdominal X-ray with a lateral decubitus view and duplex ultrasonography of the lower limb veins to assess the patency of the filter. Fifty three per cent of the patients died. Four predictive factors for mortality were identified: a contra-indication to anticoagulant therapy, chronic post-embolic cor pulmonale, an indication of prophylactic implantation in the elderly and the presence of underlying malignant disease. There were 5.8% recurrences of pulmonary embolism, 26.1% of lower limb deep vein thrombosis and 25% of filter thrombosis. The only predictive factor of thrombosis was a proximal venous thrombus and was associated in 50% of filter thrombosis. Seventy per cent of the plain abdominal X-rays were abnormal with 9 displacements. 9 migrations and 10 closures of the filters. There was a significant correlation between closure on plain abdominal X-ray and caval thrombosis and between recurrent deep vein thrombosis and caval thrombosis. The frequency of long-term complications after implantation of a caval filter in this study suggests that interruption of the vena cava should be reserved for the only validated indications in the presence of a formal contra-indication to or failure of anticoagulant therapy. Other indications require evaluation with prospective randomised trials.

Echocardiographic assessment of the interventricular delay of activation and correlation to the QRS width in dilated cardiomyopathy.

The aim of the study was to define criteria for left ventricular pacing in dilated cardiomyopathy (DCM) using an echocardiographic evaluation of interventricular electromechanical delay (IMD) and a correlation of IMD to QRS duration. Standard 12-lead ECG and echocardiography with pulsed Doppler tissue imaging (DTI) were recorded in 35 DCM patients (mean age 58 +/- 11 years) with QRS duration from narrow (80 ms) to broad (222 ms) patterns. The timefor left ventricular activation was evaluated from the onset of QRS to the onset of aortic flow (Q-Ao) by standard pulsed Doppler (SP) or to the onset of mitral annulus systolic wave (Q-Mit) (DTI). The time for right ventricular activation was determinedfrom the onset of QRS to the onset of pulmonary flow (Q-Pulm) (SP) or to the onset of tricuspid annulus systolic wave (Q-Tri) (DTI). (Q-Ao)-(Q-Pulm) and (Q-Mit)-(Q-Tri) determined IMD for each method, respectively. QRS width and IMD showed correlation coefficients of r = 0.86 ([Q-Ao]-[Q-Pulm]) and r = 0.82 ([Q-Mit]-[Q-Tri]) (P < or = 0.001 ). Mean IMD of 77 +/- 15 ms (SP) and 88 +/- 26 ms (DTI) were noted for QRS width above 150 ms. Left ventricle delayed activation was positively correlated to QRS widening with both methods, (r = 0.90, [Q-Ao]), (r = 0.83, [Q-Mit]) (P < or = 0.001). In conclusion, QRS duration is a good marker of an interventricular mechanical asynchrony. According to IMD correction, left ventricular pacing may be mainly proposed to symptomatic DCM patients with QRS duration > 150 ms.

The human fatty acid transport protein-1 (SLC27A1; FATP-1) cDNA and gene: organization, chromosomal localization, and expression.

Uptake of fatty acids into cells is a controlled process in part regulated by fatty acid transport proteins (FATPs), which facilitate the transport of fatty acids across the cell membrane. In this study the structure of the human FATP-1 (HGMW-approved symbol SLC27A1) cDNA and gene was determined, and the expression of its mRNA in human was characterized. Muscle and adipose tissue have the highest levels of FATP-1 mRNA, small intestine has intermediate levels, and FATP-1 mRNA is barely detectable in liver. The human FATP-1 gene has 12 exons and extends over more than 13 kb of genomic DNA. The FATP gene maps to chromosome 19p13.1 by fluorescence in situ hybridization, a region previously suggested to be implicated in the determination of small dense low-density lipoprotein (LDL). Knowledge of the gene structure and chromosomal localization will allow screening for FATP mutations in humans with metabolic disorders, whereas knowledge of its expression pattern and factors regulating its expression could be of importance in understanding its biology.

Cell-specific mechanisms of estrogen receptor in the pituitary gland.

Analysis of the mechanism of action of estrogen receptor shows protein and mRNA polymorphism within distinct pituitary receptor-positive cells. The lactotropes exhibit unique properties in these mechanisms that distinguish them from gonadotropes. Therefore, this cell type constitutes an especially interesting model in the male as well as in the female for estrogen receptor studies.

[Evaluation of the carriage of Staphylococcus aureus in patients and the personnel of a hemodialysis center for the prevention of infections]. / Evaluation du portage de Staphylococcus aureus chez les malades et le personnel d'un centre d'hémodialyse en vue de la prévention des infections.

With the aim of improving the prevention of Staphylococcus aureus infections in hemodialysis patients, an evaluation of S. aureus nasal carriage was carried out at the hemodialysis center of CHU-Rouen between the 1st of January, 1991 and the 30th of June, 1991. The S. aureus strains were classified according to their antibiotypes, serotypes and lysotypes. The carriage rate appears to be similar to that of the general population but inferior to what has been previously reported in hemodialysis centers. We report our findings on nasal carriage strains. The risk of infection is low. The standards of hygiene, adopted by hospital personnel, seem to be effective although cross colonization may have possibly occurred. Taking into account the different epidemiologic circumstances encountered in each hemodialysis center it is, therefore, necessary to determine the rate of carriage and identify the personnel at risk (persistent carriers, patients with a previous history of S. aureus septicemia, meti-R strains) in order to implement prophylaxis accordingly to epidemic characteristics of each center.