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O Dubourg

Publications and source records attributed to O Dubourg.

At least 37 records · Page 2Linked to original sources
PubMed2003

[Negative D-dimers and peripheral pulmonary embolism].

The measurement of D-dimers is a recent addition to the diagnostic strategy of pulmonary embolism and has been shown to be a valuable tool with excellent sensitivity. However, there have been rare reports of patients with pulmonary embolism but negative D-dimer tests. The object of this study was to study patients with pulmonary embolism but negative D-dimers and to compare them with a population of patients with pulmonary embolism and raised D-dimers. One hundred and fifty consecutive patients admitted for pulmonary embolism were included in this study. All underwent measurement of D-dimers (normal <500 ng/ml) by an ELISA technique. The data of clinical examination and complementary investigations were analysed with respect to the D-dimers result. The sensitivity of raised D-dimers for pulmonary embolism was 96% (6 patients had results <500 ng/ml). The finding of chest pain was statistically greater in the group with negative D-dimers (p=0.01). In these cases, the emboli were all distal (p=0.0003), the average Miller index was significantly lower than in patients with high D-dimers (p=0.04) and the diagnostic value of ultrasound investigations (echocardiography, ultrasonography of lower limb veins) was less (p<0.0001). The authors conclude that measurement of D-dimers by the ELISA method may be non-diagnostic in distal pulmonary embolism and one explanation could be the less extensive thromboembolic process. In cases with negative D-dimers, a strong clinical suspicion of pulmonary embolism should lead to the request for further investigations.

Adult↗
PubMed2002

[Incidence of acute cor pulmonale and deep venous thrombosis in acute pulmonary embolism].

OBJECTIVE: Ultrasounds are a useful tool when looking for indirect evidence in favor of pulmonary embolism. The aim of this study was to determine the incidence of acute cor pulmonale and deep venous thrombosis revealed by ultrasonographic techniques in a population of patients presenting with pulmonary embolism. METHODS: 96 consecutive patients with a mean (+/- SD) age of 65 +/- 15 years, admitted to our hospital for pulmonary embolism were included in this study. The diagnosis of pulmonary embolism was made either by spiral computed tomography or selective pulmonary angiography. Each patient subsequently underwent both trans-thoracic echocardiography and venous ultrasonography. The diagnostic criterion used for defining acute cor pulmonale by echocardiography was the right to left ventricular end-diastolic area ratio over (or equal to) 0.6. Diagnosis of deep venous thrombosis was supported by the visualization of thrombi or vein incompressibility and/or the absence of venous flow or loss of flow variability by venous ultrasonography. RESULTS: Using ultrasounds, an acute cor pulmonale was found in 63% of our patients while 79% were found to have deep venous thrombosis and 92% of the patients had either acute cor pulmonale or deep venous thrombosis or both. All of the patients with proximal pulmonary embolism had acute cor pulmonale and/or deep venous thrombosis. The presence of acute cor pulmonale on echocardiography was significantly higher in patients with proximal pulmonary embolism (p < 0.0001). CONCLUSION: This study emphasizes the potential value of ultrasonographic techniques in the diagnosis of acute pulmonary embolism.

Acute Disease↗
PubMed2002

[Isolated and asymptomatic Brugada syndrome. A case report].

The case report of a 32-year-old man with a Brugada syndrome is presented. He was asymptomatic and without familial history of sudden death or syncope. Diagnosis criteria for Brugada syndrome were 1--a pattern of right bundle branch block and ST-segment elevation in leads V1 and V2 on the ECG, 2--no cardiac structural anomalies. Symptomatic patients with this electrical anomaly are at high risk of sudden death and need an automatic implantable defibrillator. The outcome and the treatment of asymptomatic patients are a matter of debate and are discussed in this report.

Adult↗
PubMed2002

Efficacy of very low dose perindopril 2 mg/indapamide 0.625 mg combination on left ventricular hypertrophy in hypertensive patients: the P.I.C.X.E.L. study rationale and design.

The PICXEL study is designed to evaluate the effects of long-term administration of very low-dose combination perindopril 2 mg/indapamide 0.625 mg (Per/Ind) vs enalapril in reducing left ventricular hypertrophy (LVH) in hypertensive patients. This multicentre, controlled, randomised, double-blind, parallel group study is carried-out to assess the variation of left ventricular mass index (LVMI) after treatment, using a centralised control of M-mode echocardiography determinations, and a dedicated software for semi-automatic measurement. Following a 4-week placebo run-in period, hypertensive outpatients aged >/=18 years, with LVH (LVMI >120 and 100 g/m(2) for men and women, respectively), are randomised to receive once daily, over 52 weeks, either Per/Ind or enalapril. According to blood pressure levels, the dose may be adjusted. In addition to clinical examinations, ECG, blood pressure, heart rate and laboratory assessments echocardiographic determinations are performed for selection, at baseline, after 24 weeks and at the end of the study. The main outcome criteria is the change from baseline in LVMI which is considered the primary efficacy criterion; changes in blood pressure and echo-Doppler parameters constitute secondary criteria. Two-sided Student's t-test for independent samples will be used to differentiate the effects of the treatment between groups with alpha = 5%, and the inter-group difference of LVMI variation will be analysed with a power of 90%. A sample size of 500 patients is required making it necessary to randomise at least 550 patients, based on a 10% proportion of potentially non-assessable patients. The results of this study, obtained after applying strict methodological procedures and requirements, are expected to provide valuable and reliable information on the effects of long-term administration of Per/Ind on LVH, and on its potential superiority over enalapril.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2002

Relation between QT duration and maximal wall thickness in familial hypertrophic cardiomyopathy.

BACKGROUND: QT abnormalities have been reported in left ventricular hypertrophy and hypertrophic cardiomyopathy. OBJECTIVE: To determine the relation between left ventricular hypertrophy and increased QT interval in familial hypertrophic cardiomyopathy. METHODS: The QT interval was measured in 206 genotyped adult subjects with familial hypertrophic cardiomyopathy from 15 unrelated families carrying mutations in the beta myosin heavy chain (beta-MHC) gene (five families, n = 68) or the cardiac myosin binding protein C (MyBPC) gene (10 families, n = 138). Subjects were classified as genetically unaffected (controls, n = 112), affected with left ventricular hypertrophy (penetrants, n = 58), or affected without left ventricular hypertrophy (non-penetrants, n = 36). RESULTS: There was a significant increase in QTmax and QTmin from controls to non-penetrants and penetrants for both the MyBPC group (p < or = 0.001 and p < or = 0.001, respectively) and the beta-MHC group (p < or = 0.001 and p < or = 0.001, respectively). In the MyBPC group, the increase in the QT interval could be explained by increased left ventricular hypertrophy. In the beta-MHC group, non-penetrants had a significantly longer QTmax than controls despite the absence of left ventricular hypertrophy, and a similar QT interval to penetrants despite a lesser degree of left ventricular hypertrophy. CONCLUSIONS: In familial hypertrophic cardiomyopathy, genetically affected subjects without left ventricular hypertrophy may have a prolonged QT duration, which depends not only on the degree of left ventricular hypertrophy, when present, but also on the causative mutation.

Adult↗
PubMed2002

Genetic testing and genetic counselling in hypertrophic cardiomyopathy: the French experience.

AIMS: A major breakthrough in the molecular genetics of hypertrophic cardiomyopathy (HCM) has made genetic testing now available in clinical practice, raising new questions about its implications, potential benefits, and the organisation of the procedure. The aim of this work was (1) to discuss the different questions related to genetic testing in HCM, and propose guidelines for the different situations, (2) to report our preliminary experience with a specific procedure. METHODS AND RESULTS: The main questions asked by patients and relatives concern presymptomatic diagnosis and prenatal counselling/diagnosis, while clinicians sometimes discuss diagnostic and prognostic testing. To take into account the complex medical and psychological implications of this new approach, we developed a specific, multidisciplinary, and multiple step procedure, including a cardiologist, a geneticist, and a psychologist. Seventy subjects were examined, including (1) 29 adults for presymptomatic diagnosis (of whom 10 left the procedure after the first visit and 19 continued, among whom six had a mutation and two experienced negative psychological impact, observed during follow up), (2) nine couples of parents for presymptomatic diagnosis in their children (the procedure was stopped after the first visit in eight and continued in one), (3) 22 couples for prenatal counselling (no prenatal genetic testing was asked for after the first visit), and (4) 10 subjects for diagnostic testing. We decided to perform no prognostic testing. CONCLUSION: Our preliminary experience confirms the complexity of the situation and suggests the necessity for a specific procedure to ensure good practice in genetic testing of HCM.

Adolescent↗
PubMed2002

[Long-term outcome of a patient with hypertrophic obstructive cardiomyopathy treated by alcohol septal transcoronary ablation].

We report here the long term follow-up of the first french case, at our knowledge, of alcohol septal transcoronary ablation in March 1998 in Clinique Ambroise Paré in an 76 year-old woman. This patient was in NYHA III-IV functional class and at control outflow gradient was 100 mmHg. She was prior treated with high dosis of beta-blockers then DDD-pacemaker with no effects on symptoms. The technique used was the one described by Sigwart and al., with injection of 3 cm3 of ethyl alcohol in the first septal branch, after checking decrease of gradient during occlusion of septal branche with balloon angioplasty. After alcohol ablation, the gradient decreased immediately to 15 mmHg and disappeared at long-term follow up. Three years and half after the procedure, no complication occurred, the patient remains asymptomatic and the control echocardiography shows interventricular septal reduction of thickness from 22 to 12 mm.

Aged↗
PubMed2002

[Reflexion of French experts on the key points of the symposium].

The French experts present at the Eutherapy Symposium held in Prague confirmed the importance of left ventricular hypertrophy (LVH) and microalbuminuria as major independent risk factors for cardiovascular disease. Factors that must be considered for the treatment of hypertension in patients, particularly with type 2 diabetes. Professor J.M. Mallion stressed the contribution of thiazide and thiazide-like diruetics as indapamid, especially the 1.5 mg SR formulation. Professor F. Forette and Doctor O. Hanon recalled that the HYVET study is expected to confirm the beneficial effect of this same treatment on morbidity and mortality in very elderly patients. Professor O. Dubourg recalled the beneficial effect of indapamid SR on LVH demonstrated in the LIVE study. Likewise, Professor M. Marre emphasized its important impact on microalbuminuria as shown in the NESTOR study.

Adult↗
PubMed2001

Human Connexin 32, a gap junction protein altered in the X-linked form of Charcot-Marie-Tooth disease, is directly regulated by the transcription factor SOX10.

Mutations in SOX10, a transcription modulator crucial in the development of the enteric nervous system (ENS), melanocytes and glial cells, are found in Shah-Waardenburg syndrome (WS4), a neurocristopathy that associates intestinal aganglionosis, pigmentation defects and sensorineural deafness. Expression of MITF and RET, two genes that play important roles during melanocyte and ENS development, respectively, are controlled by SOX10. The observation that some WS4 patients present with myelination defects of the central and peripheral nervous systems correlates with the recent finding that P(0), a major component of the peripheral myelin, is another transcriptional target of SOX10. These phenotypic features suggest that SOX10 could regulate expression of other genes involved in the myelination process as well. Thus, we tested the ability of SOX10 to regulate expression of MBP, PMP22 and Connexin 32, three major proteins of the peripheral myelin. Our study shows that this factor, in synergy with EGR2, strongly activates Cx32 expression in vitro by directly binding to its promoter. In agreement with this finding, SOX10 and EGR2 mutants identified in patients with peripheral myelin defects fail to transactivate the Cx32 promoter. Moreover, we show that a mutation of the Cx32 promoter previously described in a patient with the X-linked form of Charcot-Marie-Tooth (CMTX) disease impairs SOX10 function. In addition to providing new insights into the molecular mechanisms underlying some of the peripheral myelin defects observed in CMTX disease, these results further extend the spectrum of genes that are regulated by SOX10.

Binding Sites↗
PubMed2001

Acute cor pulmonale in massive pulmonary embolism: incidence, echocardiographic pattern, clinical implications and recovery rate.

OBJECTIVE: The indications for the use of thrombolytic agents in massive pulmonary embolism (MPE) remain controversial and it has been suggested that transthoracic echocardiographic (TTE) examination, which is able to detect an associated right ventricular dysfunction, may cast light on this question. The goal of this study was to examine the incidence of acute cor pulmonale (ACP) in MPE, diagnosed on the basis of TTE criteria, its clinical implications and its resolution rate. DESIGN: Ten-year retrospective clinical study. SETTING: A medical and a coronary intensive care unit, university hospital. PATIENTS: One hundred sixty-one patients with proven MPE. INTERVENTIONS: Acute cor pulmonale was defined as right ventricular end-diastolic area / left ventricular end-diastolic area (RVEDA/LVEDA) ratio in the long axis greater than 0.6 associated with septal dyskinesia in the short axis. ACP patients were divided into three groups according to circulatory status: 32 patients without circulatory failure constituted group 1, 32 patients with circulatory failure requiring inotropic support, but free of metabolic acidosis, constituted group 2 and 34 patients in whom circulatory failure was associated with metabolic acidosis (defined by a base deficit >5 mEq/l) constituted group 3. RESULTS: Acute cor pulmonale was present in 61% of patients with MPE and carried a 23% mortality, but this mortality was very different in stable patients (groups 1 and 2, 64 patients, 3% mortality) and in unstable patients (group 3, 34 patients, 59% mortality). A multivariate logistic regression analysis showed that the TTE results were not predictive of the risk of death. Conversely, the same analysis showed that the presence of metabolic acidosis was a powerful predictor of death. CONCLUSION: Because none of the TTE measurements in ACP could be used to stratify the severity of MPE, TTE was of no help in deciding on medical thrombolysis. However, depending on its severity, metabolic acidosis could justify a large cooperative study to assess the impact of thrombolytic therapy on mortality rate in this specific group.

Acidosis↗
PubMed2001

The SOX10 transcription factor: evaluation as a candidate gene for central and peripheral hereditary myelin disorders.

The SOX10 transcription factor is involved in development of neural crest derivatives and fate determination in glial cells. SOX10 mutations have been found in patients with intestinal aganglionosis and depigmentation with deafness (Waardenburg-Hirschsprung). Associated neurological signs have been reported in some cases, including a patient exhibiting a central and peripheral myelin deficiency. Therefore, we screened for SOX10 mutations in a large cohort of patients with peripheral and central myelin disorders. 56 were affected by classical demyelinating Charcot-Marie-Tooth disease without identified mutations in the genes encoding PNS myelin proteins (PMP22, P0), connexin 32 and the zinc-finger transcription factor, EGR2. 88 patients with undetermined leukodystrophy were selected from a large European prospective study. Associated clinical, magnetic resonance imaging and electrophysiological signs were consistent with a defect in CNS myelination in 83 and with an active degeneration of the CNS myelin in 5. No abnormalities in the proteolipid protein gene (PLP) were found. The absence of SOX100 mutation in this large cohort of patients suggests that this gene is not frequently involved in peripheral or central inherited myelin disorders.

Charcot-Marie-Tooth Disease↗
PubMed2001

The frequency of 17p11.2 duplication and Connexin 32 mutations in 282 Charcot-Marie-Tooth families in relation to the mode of inheritance and motor nerve conduction velocity.

The 17p11.2 duplication and Connexin 32 (Cx32) mutations are the most frequent gene mutations responsible for Charcot-Marie-Tooth diseases. We classified 282 Charcot-Marie-Tooth families according to the median motor nerve conduction velocity of the index patient and the mode of inheritance, and screened them for 17p11.2 duplication and Cx32 mutations. Forty-seven percent of the Charcot-Marie-Tooth families had median motor nerve conduction velocity under 30 m/s (group 1), 15% between 30 and 40 m/s (group 2), and 28% over 40 m/s (group 3). Spinal Charcot-Marie-Tooth (group 4) was observed in 7% of the families. Modes of inheritance were not similarly represented among the different groups. The 17p11.2 duplication was detected in index patients of group 1 only, and accounted for 83% of the familial cases and 36% of the isolated cases. In contrast, 21 Cx32 mutations were detected to variable degrees in groups 1-3, but were most numerous by far in dominant families of group 2 (44%). This systematic approach was taken to estimate the frequency of 17p11.2 duplication and Cx32 mutations in the different Charcot-Marie-Tooth subgroups, in order to propose a practical strategy for molecular analysis.

Adult↗
PubMed2001

Clinical, electrophysiological and molecular genetic characteristics of 93 patients with X-linked Charcot-Marie-Tooth disease.

X-linked dominant Charcot-Marie-Tooth (CMTX) disease is a motor and sensory neuropathy caused by mutations in the connexin 32 (CX32) gene. In this study we report the clinical, electrophysiological and genetic features of 93 patients (41 males, 52 females) from 37 unrelated families with CMTX. Age at onset was 15.4 +/- 9.6 years in males (range 1-40 years) and 18.7 +/- 13.1 years in females (range 1-56 years) (P = 0.22) and the duration of disease at the time of examination was 18.3 +/- 14.6 years in males and 23.9 +/- 13.7 years in females (P = 0.11). Males were more severely affected than females, with significantly more frequent muscle weakness, amyotrophy, proprioception loss, upper limb areflexia and pes cavus. Females were more frequently asymptomatic, whereas high functional disability scores were more frequently encountered in males. The electrophysiological studies showed that motor nerve conduction velocities in CMTX females, but not males, were heterogeneous between nerves compared with Charcot-Marie-Tooth type 1A (CMT1A) patients and controls. The terminal latency index (TLI) for the median nerve was 0.37 +/- 0.08; it was similar in men and in women and a little higher than those observed in CMT1A and controls. The range of values for median TLI was wider in both male and female CMTX patients than in controls, but was similar to that of CMT1A patients, suggesting that motor conduction was relatively homogeneous within a given nerve. Twenty-seven different CX32 mutations, including missense (n = 23), nonsense (n = 2) and frameshift mutations (n = 1) and one entire deletion of the CX32 coding sequence, were observed in the 37 families. Four of these mutations are described for the first time. The phenotype of the patients, especially age at onset, is discussed in relation to the functional consequences of CX32 mutations, analysed in vitro in Xenopus oocytes and mammalian cells. CMTX patients with age at onset in the first decade mostly presented non-functional mutations, suggesting that the physiological consequences of the mutations affect age at onset in CMTX.

Adolescent↗
PubMed2001

New CT index to quantify arterial obstruction in pulmonary embolism: comparison with angiographic index and echocardiography.

OBJECTIVE: This study was designed to define and evaluate a specific index to quantify arterial obstruction with helical CT in acute pulmonary embolism. MATERIALS AND METHODS: Fifty-four patients (mean age, 56 years) with proven pulmonary emboli among 158 consecutive patients, who had undergone both CT and pulmonary angiography for clinically suspected pulmonary embolism, were eligible for the study. The CT obstruction index was defined as (n. d) (n, value of the proximal clot site, equal to the number of segmental branches arising distally; d, degree of obstruction scored as partial obstruction [value of 1] or total obstruction [value of 2]). We compared the CT obstruction index with pulmonary arterial obstruction on angiography (assessed by the Miller index), using linear regression, and correlated it with findings on echocardiography. Interobserver variability was determined for both CT and pulmonary angiography indexes. RESULTS: The CT obstruction index (29% +/- 17%) and the Miller index (43% +/- 25%) were well correlated (r = 0.867, p < 0.0001) with an excellent concordance between investigators for both the CT index (r = 0.944, p < 0.0001) and the Miller index (r = 0.904, p < 0.0001). A CT obstruction index greater than 40% identified more than 90% of patients with right ventricular dilatation. CONCLUSION: The degree of arterial obstruction in pulmonary embolism may be quantified by a specific CT index that appears reproducible and highly correlated to the previously described index with pulmonary angiography. Further evaluations are needed to investigate the usefulness of the CT obstruction index for stratification of patient risk and determining therapeutic options.

Angiography↗
PubMed2001

[Coronary steal syndrome by systemic pulmonary hypervascularization fed by a mammary-left anterior descending artery bypass. Treatment by embolization].

We report a case of coronary-steal syndrome which occurred after coronary bypass surgery. It was related to systemic hypervascularization of the lung caused by a bronchopathy. The steal syndrome was fed by an ectopic bronchial artery arising from the internal mammary--left anterior descending artery bypass graft. The myocardial ischemia disappeared after hyperselective embolization of the ectopic bronchial artery. The authors outline the rarity of this syndrome and its pathophysiology. They insist on the necessity to perform broncho-systemic arteriography for candidates to coronary surgery, in patients with thoracic diseases which can induce systemic hypervascularization of the lung.

Bronchial Arteries↗
PubMed2000

Phenotypic and genetic study of a family with hereditary sensory neuropathy and prominent weakness.

We report the clinical and electrophysiological features of six members of a French family with a dominantly inherited motor and sensory neuropathy. Mean age at onset was 33.6 +/- 9.1 years. Mean age at examination was 55.5 +/- 13.3 years. Clinical presentation combined symptoms of hereditary sensory and autonomic neuropathy type I (HSAN-I) with prominent distal muscle weakness. Five male patients presented with sensory symptoms involving the distal part of the limbs, especially the legs. All but one had histories of trophic alterations, consisting of poorly healing foot ulcers. Muscle weakness and wasting were always present, often severe, and mainly affected dorsiflexion of the toes and feet. One obligate female carrier aged 65 was clinically asymptomatic. Electrophysiological findings were consistent with a distal axonal motor and sensory neuropathy. Results of linkage analysis excluded the Charcot-Marie-Tooth 2A (CMT2A) and CMT2B loci and suggested the possibility of a linkage to HSAN-I locus on 9q22.1-q22.3.

Adult↗
PubMed2000

Homozygotes for a R869G mutation in the beta -myosin heavy chain gene have a severe form of familial hypertrophic cardiomyopathy.

UNLABELLED: Familial Hypertrophic Cardiomyopathy (FHC) is an autosomal dominant disease characterised by ventricular hypertrophy, with predominant involvement of the interventricular septum. It is a monogenic disease with a high level of genetic heterogeneity (nine genes and more than 110 mutations reported so far). We describe a family with a new R869G mutation in the beta -myosin heavy chain gene (MYH7). This mutation was found in the heterozygous status in both parents and in the homozygous status in the two children. A haplotype analysis on the MYH7 locus with microsatellite markers showed that the same haplotype is transmitted within the family, suggesting a founder effect. Clinically, the father was asymptomatic with mild left ventricular hypertrophy on echocardiography. The mother had a mild form of hypertrophic cardiomyopathy and remained asymptomatic until 60 years old when an atrial fibrillation occurred. For the two children, clinical diagnosis was performed at 12 and 8 years and atrial fibrillation occurred at 17 years. For both children, the evolution was characterized by left ventricle (LV) systolic dysfunction and a severe dilatation of the left atrium before 40 years of age. CONCLUSIONS: In this family, a new R869G mutation in the MYH7 gene was found. Interestingly, a mutation was found at the homozygous status for the first time in FHC. This finding suggests that this particular mutation is compatible with life, but for homozygous subjects, age at onset of symptoms was earlier and the disease much more severe than in the heterozygous subjects, suggesting a gene-dose effect.

Adult↗