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Biomedical subjects

D Duboc

Publications and source records attributed to D Duboc.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Brain natriuretic peptide and heart failure].

Brain natiuretic peptide (BNP) is a hormone secreted specifically by the left ventricular myocytes. Its concentration is correlated with the severity of symptomatic or asymptomatic left ventricular dysfunction. The measurement of BNP has several applications from the screening of populations to the monitoring of the effects of treatment and the evaluation of the prognosis of cardiac failure. The emergence of new methods of rapid measurement will enable its usage as a routine investigation in the near future. Large scale clinical trials are, however, required to confirm the hopes raised by this new marker of left ventricular dysfunction.

Animals↗
PubMed2001

[Proximal myotonial myopathy (PROMM): clinical and histology study].

We report 13 French patients with proximal myotonic myopathy. PROMM is a recently delineated multisystem disorder with dystrophic myopathy, myotonia and cataracts. This syndrome is genetically distinct from myotonic dystrophy (DM) by the absence of abnormal CTG repeat expansion. The geographical origin varies but 4 families originated from Poland. Of late onset, muscle weakness is diffuse and predominantly affected proximal and axial muscles. Facial involvement and myotonia were moderate or absent, but in all cases myotonic discharges were detected on EMG. 6 patients suffered from myalgia. Cataracts occurred in 11 patients, mainly indistinguishable from those in DM. Cardiac arrythmia occurred in 7 patients. Muscle biopsy revealed rare structural changes of the muscle fibers and selective type I atrophy, common in DM, could not be found on morphometric analysis. PROMM has a distinct clinical spectrum from DM which includes a predominantly proximal muscle weakness, with troubling pain, a more favourable prognosis and a different histopathological pattern.

Adult↗
PubMed2001

[Transplantation of autologous skeletal myoblasts in ischemic cardiac insufficiency].

Despite medical therapeutic advances, congestive heart failure (CHF), which is the common ultimate consequence of many primary cardiovascular diseases, remains a major and growing public health problem. Although orthotopic heart transplantation is the gold standard, there is now growing evidence that one therapeutic option could be cellular cardiomyoplasty. Autologous adult skeletal myoblast transplantation seems to be the most clinically relevant, compared with other cell types, in that it avoids immunosuppression therapy, availability and ethical issues. Previous experimental studies have documented the efficacy of myoblast transplantation in improving function of infarcted myocardium. Although the mechanisms involved in this improvement are not elucidated, it has been demonstrated convincingly enough to consider ripping to clinical trials.

Animals↗
PubMed2000

High incidence of sudden death with conduction system and myocardial disease due to lamins A and C gene mutation.

We studied 54 living relatives from a large French kindred, among which 17 members presented with a cardiomyopathy transmitted on an autosomal dominant mode. Five of these individuals had clinical manifestations of muscle disease phenotypically consistent with Emery-Dreifuss muscular dystrophy. Genetic analysis of this kindred had demonstrated a nonsense mutation in the LMNA gene located on chromosome 1q11-q23. This gene encodes lamins A and C, proteins of the nuclear lamina located on the inner face of the nuclear envelope. We retrospectively determined the cause of death of 15 deceased family members, 8 of whom had died suddenly, 2 as a first and single manifestation of the disease. The six other cases had histories of arrhythmias and left ventricular dysfunction before dying suddenly, and three of them died despite the prior implantation of a permanent pacemaker. The mean age of onset of cardiac symptoms among affected living family members was 33 years (range 15-47 years), and the first symptoms were due to marked atrioventricular conduction defects or sinus dysfunction, requiring the implantation of permanent pacemakers in seven cases. Myocardial dysfunction accompanied by ventricular arrhythmias developed rapidly in the course of the disease and resulted in severe dilated cardiomyopathy requiring cardiac transplantation in three cases. In conclusion, in patients presenting a life-threatening familial or sporadic cardiac restricted phenotype similar to that described here, mutations in the lamins A and C gene should be looked for. In the genotypically affected individuals, cardiological and electrophysiological follow-up should be performed to prevent sudden death that could occur rapidly in the evolution of such disease.

Adolescent↗
PubMed2000

[Familial myopathy with desmin storage seen as a granulo-filamentar, electron-dense material with mutation of the alphaB-cristallin gene].

Two familial cases of a myopathy remarkable by the presence of a granulo-filamentar, electron dense material were reported in 1978. In a second step, in 1988, it was demonstrated that this material contained an abnormally-phosphorylated desmin. During the last twenty years, the occurrence of new cases in this family confirmed the autosomal dominant inheritance of the disease, and made it potentially informative for molecular genetics studies. This allowed first to map the disease on chromosome11q21-23, and afterwards to identify a mutation within a gene coding for a chaperone protein, alphaBcrystallin. An extensive clinical, pathological and genetic study of this princeps family is herein reported in detail. First, it showed the possible detection of histopathological changes in presymptomatic patients. Second, it allowed to demonstrate the simultaneous occurrence of both alphaBcrystallin and desmin in the granulo-filamentar aggregates. Third, this study provided a precise knowledge of the evolution rate of the disease. The analysis of similar observations reported in the literature clearly shows the clinical, pathological and genetic heterogeneity of this new neuro-muscular disorder.

Actin Cytoskeleton↗
PubMed2000

Clinical and molecular genetic spectrum of autosomal dominant Emery-Dreifuss muscular dystrophy due to mutations of the lamin A/C gene.

Emery-Dreifuss muscular dystrophy (EDMD) is characterized by early contractures of the elbows and Achilles tendons, slowly progressive muscle wasting and weakness, and life-threatening cardiomyopathy with conduction blocks. We recently identified LMNA encoding two nuclear envelope proteins, lamins A and C, to be implicated in the autosomal dominant form of EDMD. Here, we report on the variability of the phenotype and spectrum of LMNA mutations in 53 autosomal dominant EDMD patients (36 members of 6 families and 17 sporadic cases). Twelve of the 53 patients showed cardiac involvement exclusively, although the remaining 41 all showed muscle weakness and contractures. We were able to identify a common phenotype among the patients with skeletal muscle involvement, consisting of humeroperoneal wasting and weakness, scapular winging, rigidity of the spine, and elbow and Achilles tendon contractures. The disease course was generally slow, but we observed either a milder phenotype characterized by late onset and a mild degree of weakness and contractures or a more severe phenotype with early presentation and a rapidly progressive course in a few cases. Mutation analysis identified 18 mutations in LMNA (i.e., 1 nonsense mutation, 2 deletions of a codon, and 15 missense mutations). All the mutations were distributed between exons 1 and 9 in the region of LMNA that is common to lamins A and C. LMNA mutations arose de novo in 76% of the cases; 2 of these de novo mutations were typical hot spots, and 2 others were identified in 2 unrelated cases. There was no clear correlation between the phenotype and type or localization of the mutations within the gene. Moreover, a marked inter- and intra-familial variability in the clinical expression of LMNA mutations exists, ranging from patients expressing the full clinical picture of EDMD to those characterized only by cardiac involvement, which points toward a significant role of possible modifier genes in the course of this disease. In conclusion, the high proportion of de novo mutations together with the large spectrum of both LMNA mutations and the expression of the disease should now prompt screening for LMNA in familial and sporadic cases of both EDMD and dilated cardiomyopathy associated with conduction system disease.

Adolescent↗
PubMed1999

Relationships among electrophysiological findings and clinical status, heart function, and extent of DNA mutation in myotonic dystrophy.

BACKGROUND: Impulse-conduction abnormalities and arrhythmias are common in myotonic dystrophy (MD). This study was performed to determine whether a correlation exists between electrophysiological (EP) testing data and clinical status, heart function, or size of the DNA abnormality (cytosine-thymine-guanine sequence repeat). METHODS AND RESULTS: Eighty-three MD patients underwent invasive EP studies prompted primarily by the presence of asymptomatic conduction abnormalities. AV conduction disturbances were common and mainly distal (HV interval, 66.2+/-14 ms). AV conduction observed from the surface ECG was generally concordant with endocardial measurements. However, 11 of 20 patients with normal surface ECGs had abnormal subhisian conduction. Atrial arrhythmias were inducible in 41% of cases and correlated with prolongation of the AH interval (P=0.02) and a shorter atrial refractory period (P=0.04). Induction of ventricular arrhythmias (18%) correlated strongly with age (P=0. 0003). After adjustment for age, the extent of DNA mutation correlated with the Walton score (P=0.0018) but not with conduction abnormalities or induction of arrhythmias. CONCLUSIONS: Prolongation of the HV interval is the most common conduction abnormality in MD and can be reliably recognized only by invasive EP testing. It raises the issue of prophylactic pacing to limit the incidence of sudden death in MD. Atrial and ventricular arrhythmias are often inducible, although their predictive value remains to be determined. Young age emerged as the most powerful predictor of inducible ventricular tachyarrhythmias. Conversely, we found no relationship between ECG or EP abnormalities recorded during invasive testing and the DNA mutation size or severity of peripheral muscle involvement.

Adult↗
PubMed1999

Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy.

Emery-Dreifuss muscular dystrophy (EDMD) is characterized by early contractures of elbows and Achilles tendons, slowly progressive muscle wasting and weakness, and a cardiomyopathy with conduction blocks which is life-threatening. Two modes of inheritance exist, X-linked (OMIM 310300) and autosomal dominant (EDMD-AD; OMIM 181350). EDMD-AD is clinically identical to the X-linked forms of the disease. Mutations in EMD, the gene encoding emerin, are responsible for the X-linked form. We have mapped the locus for EDMD-AD to an 8-cM interval on chromosome 1q11-q23 in a large French pedigree, and found that the EMD phenotype in four other small families was potentially linked to this locus. This region contains the lamin A/C gene (LMNA), a candidate gene encoding two proteins of the nuclear lamina, lamins A and C, produced by alternative splicing. We identified four mutations in LMNA that co-segregate with the disease phenotype in the five families: one nonsense mutation and three missense mutations. These results are the first identification of mutations in a component of the nuclear lamina as a cause of inherited muscle disorder. Together with mutations in EMD (refs 5,6), they underscore the potential importance of the nuclear envelope components in the pathogenesis of neuromuscular disorders.

Amino Acid Sequence↗
PubMed1999

[Pericardial and myocardial adiastole in rheumatoid polyarthritis].

The authors describe a case of clinical, echocardiographic and haemodynamic adiastole in a man with severe rheumatoid arthritis with a previous history of pericardial effusion. The adiastole was mixed, fibrous pericarditis, confirmed by ultra fast CT scan and at surgery; myocardial adiastole was suspected on finding thickening of the ventricular walls (in the absence of hypertension and coronary artery disease) and, unfortunately, confirmed by the persistence of adiastole despite very satisfactory pericardectomy. The authors underline the involvement of the three cardiac tunics in rheumatoid arthritis and the value of different diagnostic methods in the differentiation between constrictive pericarditis and restrictive cardiomyopathy.

Arrhythmias, Cardiac↗
PubMed1998

Impaired cerebral glucose metabolism in myotonic dystrophy: a triplet-size dependent phenomenon.

Myotonic dystrophy (DM) is caused by an expansion of a CTG triplet repeat sequence in the 3'-noncoding region of a protein kinase gene, yet the mechanism by which the triplet repeat expansion causes disease remains unknown. Impaired glucose penetration into brain tissues has been described in DM patients and is a phenomenon that remains unexplained. The present study shows that altered brain glucose metabolism is triplet repeat dependent. We studied brain glucose metabolism (CMRGlu, mumol/100 g/min) by the use of positron emission tomography and 18F-fluoro-2-deoxy-D-glucose in 11 ambulatory non-obese DM patients and in 11 age and sex matched healthy subjects. All subjects underwent a glucose tolerance test with plasma insulin determinations. The expansion of CTG triplet repeats was analyzed in patients with the probe cDNA25 after EcoRI digestion. As compared to controls, in DM patients, the CMRGlu was significantly decreased (26.26 +/- 5.05 vs. 33.43 +/- 2.18, mumol/100 g/min, P = 0.004), and after oral glucose loading, plasma insulin levels were significantly higher and plasma glucose levels remained unchanged (respectively, F = 11.21, P = 0.004 and F = 0.20, P = 0.66). Subsequently, the glucose/insulin ratio was significantly lower in DM patients (F = 6.25, P = 0.02). The length of the expansion of the CTG repeats correlated negatively with the CMRGlu (r2 = 0.63, P = 0.003) and positively with the area under the curve for insulin changes over time after oral glucose (r2 = 0.49, P = 0.016). We conclude that, in DM patients, the brain metabolism of glucose is impaired in a repeat dependent manner.

Activities of Daily Living↗
PubMed1998

Cardiac involvement in genetically confirmed facioscapulohumeral muscular dystrophy.

In a series of 100 patients exhibiting clinical and molecular features of facioscapulohumeral muscular dystrophy (FSHMD), five patients had conduction defects or arrhythmia in the absence of cardiovascular risk factors--namely, intraventricular conduction delay and supraventricular arrhythmia induced by electrophysiologic investigations (two patients), palpitations associated with supraventricular arrhythmia (one patient), severe atrioventricular block leading to pacemaker implantation (one patient), and ventricular tachycardia related to arrhythmogenic right ventricular cardiomyopathy (one patient). Patients with FSHMD may have cardiac involvement.

Adolescent↗
PubMed1998

[Arrhythmogenic effects of extracorporal lithotripsy in desynchronized mode with a later generation lithotriptor].

Extracorporal lithotripsy has transformed the treatment of renal stones. However, the shock waves can generate arrhythmias which may be severe. To prevent them, the shocks were synchronised to the absolute refractory period of the cardiac cycle with a corollary, an increase in the procedure time. The latest generation of lithotriptors have a number of technical improvements allowing desynchronisation but with a high theoretic risk of arrhythmias. The aim of this study was to assess the arrhythmogenic effects of desynchronised shocks by Holter ECG monitoring during the procedure. This was a prospective randomised study: 25 patients with no previous cardiovascular history were included: 15 men and 10 women with a mean age of 45 years. The originality of this study was the delivery of shock waves in two phases (synchronised versus desynchronised) in a random fashion, the order being unknown to the cardiologist interpreting the recordings. In the synchronised mode, none of the patients developed an arrhythmia. On the other hand, in the desynchronised mode, hyperexcitability was observed in 7 patients, supraventricular in 6 cases (atrial extrasystoles and atrial doublets) and ventricular in 4 cases (VES, ventricular doublets and 1 unsustained ventricular tachycardia). These arrhythmias were asymptomatic and regressed spontaneously. The authors conclude that although they are arrhythmogenic, desynchronised procedures with the latest lithotriptors are acceptable, provided that the patients undergo a cardiological examination beforehand to identify high risk patients and that there is adequate monitoring during the procedure in the presence of an anaesthetist.

Adult↗
PubMed1998

[Functional imaging of human muscle].

Medical imaging is now giving access not only to anatomy but also to functions of organs in the human body. Functional imaging may yield a direct appreciation of the function of a given organ, as is the case when measuring ejection fraction of heart with SPECT. Alternately the approach is indirect. This is the case of cerebral functional imaging, either with PET or NMR, where the perfusion increase induced by neuronal activity is detected. Recent developments of NMR, combining imaging and spectroscopy, allow now to detect modification of physiological parameters induced by muscular activity. Indirect detection of muscle activity is very rich in information alternately requiring invasive techniques. Water shifts resulting from intense exercise are detected either from muscle volume increase or water signal modifications, using simple NMR sequences. Then it is easy to identify which muscle is involved in a given protocol. These water shifts, studied in various muscles and several types of exercise protocols, reflect the perfusion increase induced by exercise, and the contribution of metabolic products such as lactate. In some patients with metabolic myopathies a decreased adaptation of perfusion has been detected. Perfusion measurements, previously performed by using venous occlusion plethysmography or radioactive tracers, now benefit from recently developed MR techniques. Oxygenation of muscle may be measured either by spectroscopy of myoglobin, allowing a time resolution of 1 second, or by spectroscopic imaging allowing a spatial resolution of 1-2 cm in a few minutes. Muscle temperature may be non invasively monitored by diffusion-weighted MR. Direct detection of muscle activity is useful only in those muscles that cannot be directly observed. Ultrafast MR imaging may be used to study vocal cords or oculomotor muscles. More interesting is the measurement of contractility, either in myocardium or skeletal muscle, allowed by MR with spin-tagging. Another contribution of MR to muscle studies is the possibility to quantify muscle cross section and muscle volume, in order to normalize strength or metabolism measurements. Sequences using T1 or T2 differences between muscular and adipose tissue allow to quantify the true muscular volume in patients with neuromuscular disorders. Protocols combining several of these parameters by interleaved NMR measurements of perfusion, phosphorylated metabolites, lactate, myoglobin, now open the way to many comprehensive non-invasive pathophysiological studies.

Body Water↗
PubMed1996

Blunted coronary reserve in myotonic dystrophy. An early and gene-related phenomenon.

BACKGROUND: In myotonic dystrophy (DM), striated muscle is involved in relation to the size of the DNA mutation. Smooth muscle may be similarly impaired at the level of the urinary and digestive apparatus and possibly at the level of small vessels, since microangiopathy has been described in the iris and digital capillaries. Our purpose was to study the function of the myocardial microvasculature in relation to the size of the mutation in DM patients without clinical cardiac involvement and with normal left ventricular dimensions and function and normal large coronary arteries. METHODS AND RESULTS: In 6 control subjects and 10 DM patients, we investigated the coronary blood flow reserve using positron emission tomography with 15O-labeled water. Global and regional flow reserves were obtained from myocardial regions of interest manually drawn on a static FDG image encompassing, respectively, the whole left ventricle and the anterior, septal, and lateral walls. The DNA mutation size was determined on circulating lymphocytes in each DM patient. Compared with control subjects, DM patients had decreased global (2.39 +/- 0.39 versus 4.00 +/- 0.67, P = .00003) and regional (anterior, 2.39 +/- 0.64 versus 3.87 +/- 0.92, P = .002; septal, 2.60 +/- 0.48 versus 4.00 +/- 0.70, P = .0003; lateral, 2.26 +/- 0.58 versus 4.16 +/- 1.11, P = .0005) coronary reserves. In DM patients, the coronary reserve correlated strongly and inversely with the DNA mutation size (r = -.77, P = .009). CONCLUSIONS: The study demonstrated that global and regional coronary reserves are impaired, in relation to the DNA mutation size, in symptom-free DM patients with normal ventricular dimensions and function and normal large coronary vessels. We suggest that a gene-related blunted coronary reserve resulting from an impairment of vascular smooth muscle is an early component of DM cardiomyopathy.

Adult↗
PubMed1996

MR quantification of muscle fatty replacement in McArdle's disease.

McArdle's disease is an energy-dependent disorder of skeletal muscle caused by the inability to break down glycogen. The aim of this study was to quantify fatty replacement in patients with McArdle's disease. Calf and thigh axial spin echo T1-weighted magnetic resonance (MR) images (repetition time 500 ms, echo time 25 ms) were obtained at 0.5 T in nine patients with McArdle's disease (age 51 +/- 16 years, range 26-74) and nine sex- and age-matched healthy subjects (age 52 +/- 16 years, range 29-78) to quantify intramuscular fat. Regions of interest were drawn manually, encompassing the largest cross section of muscle. A fatty replacement index (IF) was determined from histograms of signal in the regions of interest in calf and thigh muscles. In normal subjects, IF = 3.6 +/- 2.8% in calf and 4.9 +/- 2.3% in thigh. In patients, IF = 11 +/- 9.3% in calf and 13.5 +/- 10.4% in thigh, significantly different from IF values in normal subjects (p = .03). IF correlated well with age in patients (p = .03). In older patients, up to 25% of the muscle volume was replaced by fat. Patients with McArdle's disease, usually weakly disabled, exhibit significant muscle fatty replacement on MR images. These findings suggest a progressive muscle loss over time related to the disease process.

Adipose Tissue↗
PubMed1996

[Electroconductive extracorporeal lithotripsy with Sonolith 4000+. A prospective study of the ECG desynchronization using a fixed-rhythm simulator].

INTRODUCTION: Electrohydraulic lithotripters use a R-wave triggering system as episodes of cardiac arrhythmia were observed during early clinical experiments. This study was designed to assess the safety of non triggered shock wave treatments using an external fixed rate device (120/min) on the Sonolith 4000 Plus (*), a non bathtub electroconductive lithotripter. METHODS: Our study is the first prospective evaluation of non-EKG-gated lithotripsy where the patient under continuous Holter monitoring served as his own control during a randomized alternation of periods with or without R-wave triggering. This design allowed for a direct comparison of the effect of EKG-gated and non-EKG-gated lithotripsy respectively. The sequence of the different periods was randomly assigned. The recordings were compared to a pre-treatment recording, the cardiologist ignoring the randomization. RESULTS: 25 consecutive patients without cardiac history have been treated for urinary stones. Ventricular and supraventricular excitability disorders have been noted in 7 patients, always during a non-EKG-triggered period. There was no correlation with stone location. No cardiac rhythm disturbances have been observed during triggered periods in the 25 patients. Auricular extrasystoles (0.1-0.5/min) were observed in 6 patients, and auricular couplets (0.5/min) in one. Ventricular extrasystoles were noted in 4 patients, and ventricular couplets in one. One patient had an asymptomatic non sustained ventricular tachycardia which resolved spontaneously. No clinically significant disorder occurred. Treatment time and analgesics requirements were reduced by non-EKG-triggering. CONCLUSIONS: Non-EKG-triggering lithotripsy has a definite potential for cardiac disturbances, but appeared to be clinically safe in these patients with no cardiac history.

Adult↗