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Biomedical subjects

D Duboc

Publications and source records attributed to D Duboc.

At least 55 records · Page 3Linked to original sources
PubMed1995

Impairment of the exercise-induced increase in muscle perfusion in McArdle's disease.

In McArdle's disease (myophosphorylase deficiency) exercise intolerance is generally attributed to a lack of glycogenolysis, which decreases energy production during exercise. Magnetic resonance imaging data have recently suggested an impairment of the increase in muscle perfusion during exercise in these patients. We have tested this hypothesis by direct measurement of local muscle perfusion increase. Increase in muscle perfusion was assessed by positron emission tomography with oxygen-15 labelled water in five patients with McArdle's disease and five age- and sex-matched healthy volunteers. Radioactivity was measured in both forearms before and after exercise of the right forearm. The exercise intensity was biochemically assessed by in vivo phosphorus-31 magnetic resonance spectroscopy. The estimated increase in muscle perfusion with exercise was 5.7+/-5.5-fold in the patients (range 1.5-12.8) and 22.3+/-12.0-fold in the healthy subjects (range 10.1-37) (P=0.022). The results show a significant impairment of increase in muscle perfusion with exercise in McArdle's disease. Thus patients may suffer not only from a direct lack of glycogenolysis but also from indirectly impaired vasodilation.

Adult↗
PubMed1995

Transient expression of genes transferred in vivo into heart using first-generation adenoviral vectors: role of the immune response.

Gene therapy for heart diseases requires availability of an efficient vector for gene transfer into myocardium. Recombinant adenovirus expressing the Escherichia coli beta-galactosidase (beta-Gal) gene was shown to infect rat cardiocytes efficiently in vivo. However, a time course of gene expression showed that transgene expression was maximal during the first week following injection, then declined and disappeared by day 21. An immunosuppressive treatment prolonged beta-Gal expression for at least 21 days. On the contrary, a preimmunization of the animals by two intraperitoneal injections of the vector led to a decreased transgene expression 48 hr after intramyocardial injection and to a barely detectable expression at the sixth day. Appearance of adenovirus neutralizing antibodies in preimmunized animals could have contributed to such a refractoriness to further adenoviral infection. Finally, a neonatal intrathymic injection of the vector was able to induce long-term LacZ expression for more than 2 months after heart injection, although neutralizing as well as anti-beta-Gal antibodies were detected in sera of the animals. These results indicate that an immune response against first-generation replication-defective adenoviral vectors is a major cause of transient transgene expression, a cellular response being most probably responsible for ablation of transgene expression in immunocompetent animals.

Adenoviridae↗
PubMed1994

[Severe cardiomyopathy revealing amylopectinosis. Two cases in adolescents from the same family].

Type IV glycogen storage disease, also termed Andersen's disease or amylopectinosis, is a rare autosomic recessive hereditary disease usually caused by a deficit in glycogen branching enzyme. We report our observation of two siblings with type IV glycogen storage disease who had normal branching enzyme activity. The initial symptom was severe heart failure. A 14-year-old boy, born to consanguinous parents, was seen for severe global heart failure. Growth retardation had been diagnosed since the age of 6 and abnormal fatigability since the age of 12. Muscle and endomyocardium biopsies revealed abnormal glycogen storage with normal branching enzyme activity. The patient's condition improved after symptomatic treatment, but death occurred due to infectious complications after orthoptic heart transplantation. One year later, the proband's 12-year-old sister, with an uneventful personal medical history, was hospitalized for severe left ventricular failure. Muscle and liver biopsies demonstrated the same anomalies, again without branching enzyme deficiency in the liver. Heart failure was controlled with symptomatic care and the patient's current condition remains satisfactory. This observation demonstrates the clinical expression of familial type IV glycogen storage disease in patients with normal branching enzyme activity. Age at onset is quite variable, reported from 5 to 70 years, as is the clinical course before diagnosis.

Adolescent↗
PubMed1994

Myocardial viability assessment in ischemic cardiomyopathy: benefits of coronary revascularization.

Patients with ischemic heart disease, congestive heart failure, and low ejection fraction are usually referred for orthotopic heart transplantation. Based on results of myocardial viability assessment, we have prospectively used either coronary artery bypass grafting or orthotopic heart transplantation. From January 1990 to June 1992, among 50 patients initially referred for heart transplantation, 46 showing myocardial viability underwent bypass grafting. Forty-five of these 46 patients were men, and the mean age was 58 +/- 12 years (range, 40 to 70 years). Congestive heart failure was present in all patients, and dyspnea was the main symptom in 80% (37/46). Patients were selected according to three criteria. (1) Myocardial viability was primarily assessed by thallium scintigraphy for up to 24 hours (28/46 patients). When results were negative, patients underwent positron emission tomography (20/46 patients). (2) Regional left ventricular function was assessed using gated blood pool single-photon emission computed tomography combined with (3) full hemodynamic evaluation. Results were as follows: end-diastolic volume, 129 +/- 35 mL/m2; ejection fraction, 0.23 +/- 0.06; cardiac index, 2.4 +/- 0.62 L.min-1.m-2; mean pulmonary artery pressure, 26 +/- 0.90 mm Hg; and mean pulmonary capillary wedge pressure, 16 +/- 1.10 mm Hg. Operative mortality was 2.17% (1/46). During follow-up (mean duration, 18 months), there were three late cardiac-related deaths (arrhythmias) and two noncardiac-related deaths. The 40 long-term survivors are in New York Heart Association class II. Angiography (15 patients) or gated blood pool single photon emission tomography (32) showed improvement in mean ejection fraction to 0.39 +/- 0.13 (range, 0.22 to 0.46).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Correlation between decreased myocardial glucose phosphorylation and the DNA mutation size in myotonic dystrophy.

BACKGROUND: Myotonic dystrophy, the most common form of adult dystrophy, has been shown to be caused by amplification of CTG triplet repeat in the 3' untranslated region of a protein kinase gene located on chromosome 19. Impaired glucose metabolism has been suggested as a possible explanation of brain and skeletal muscle involvement in this multisystem disease. We investigated whether myocardial glucose metabolism is impaired in myotonic dystrophy and whether this impairment is related to the size of the mutation. METHODS AND RESULTS: The myocardial metabolic rate for glucose (MMRGlu, mumol.min-1.g-1), K1 (blood-to-tissue transfer constant), k2 (tissue-to-blood transfer constant), and k3 (phosphorylation rate constant) were determined in 7 control subjects and 12 patients with myotonic dystrophy by using parametric images generated from dynamic cardiac positron emission tomography (PET) and 18F-fluoro-2-deoxy-glucose studies. The expansion of the CTG triplet repeats was analyzed in patients with the probe cDNA25 after EcoRI digestion. Nonparametric tests were used to compare quantitative variables between control subjects and patients. The correlations between the size of the mutation and PET parameters were studied by linear regression. MMRGlu and k3 were significantly decreased in patients compared with control subjects (0.39 +/- 0.20 versus 0.64 +/- 0.25, P = .03, and 0.09 +/- 0.07 versus 0.24 +/- 0.21, P = .03, respectively), whereas K1 and k2 were not statistically different between control subjects and patients. MMRGlu and k3 correlate inversely with the length of the CTG triplet repeat (r = -.65 and P = .03 for MMRGlu, and r = -.85 and P = .001 for k3, respectively). CONCLUSIONS: In myotonic dystrophy, the observed reductions in MMRGlu and phosphorylation are inversely linked to the length of the mutation. This observation suggests that impaired modulation of a protein kinase involved in myocardial hexokinase activation may give a pathophysiological schema to relate the molecular defect and the abnormal myocardial metabolism in myotonic dystrophy.

Adult↗
PubMed1993

Coronary surgery can be an alternative to heart transplantation in selected patients with end-stage ischemic heart disease.

Patients with ischemic heart disease (IHD) low ejection fraction (EF), and congestive heart failure (CHF), are usually referred for orthotopic heart transplantation (OHT). This study reports our experience with coronary artery bypass grafting (CABG) in patients initially referred for OHT, and suggests guidelines to facilitate the choice of procedure (OHT or CABG). Between January 1990 and December 1991, 32 patients with IHD, proposed for OHT, underwent CABG 31/32 patients were male, the mean age was 58 +/- 12 years (40 to 70). Congestive heart failure was present in all patients and was the main symptom. The mean EF was 23 (14 to 31%), mean cardiac index (CI) 2.4 l/min per m2 (1.6 to 3.1 l/min per m2), mean pulmonary artery mean pressure (MPAP) 26 (20 to 37 mmHg) and mean pulmonary wedge pressure 16 (12 to 22 mmHg). Every patients underwent a myocardial viability study by thallium scintigraphy (n = 32) and/or by positron emission tomography (n = 10). The perioperative mortality was 9.3% (3/32). All long-term survivors (n = 27) are in NYHA Class II with a complete follow-up (mean 18 +/- 6 months). Ejection fraction control either by angiography (n = 15) or by single photon emission computed tomography (n = 12) showed an increase of up to 38% (22%-46%). Three determinant factors influenced the choice of CABG. 1) CI > 21/min per m2, 2) MPAP < 35 mmHg. 3) Detection of myocardial viability.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

MR imaging as a potential diagnostic test for metabolic myopathies: importance of variations in the T2 of muscle with exercise.

OBJECTIVE: Most metabolic myopathies (like glycogenoses and mitochondrial myopathies) are related to inborn errors of muscle energy metabolism and often present clinically as exercise intolerance (inability to sustain normal exercise). We investigated whether the previously observed absence of normal exercise-induced variation in the T2 of muscle in McArdle's disease (a metabolic myopathy caused by muscle phosphorylase deficiency) was specific for this disease and whether the variations in T2 could be used for screening patients suspected of having metabolic myopathy. SUBJECTS AND METHODS: Exercise-induced variations in proton MR signal and in intracellular pH were studied in the forearm flexor muscles of nine healthy subjects and 49 patients with exercise intolerance due to muscle pain, suggesting a metabolic myopathy. The relative increase in T2, delta T2/T2, was measured from MR spin-echo images before and after exercise. Phosphocreatine (used as a control of the degree of exercise) and intracellular pH were measured from phosphorus-31 spectra before and during exercise. The progressive 4.5-min handgrip exercise reached maximal exertion capability at the end of exercise and decreased phosphocreatine to less than 50% of its rest value. RESULTS: Variations in T2 and end-exercise pH were correlated. The nine healthy subjects showed a delta T2/T2 ranging from +19% to +44% (but little T1 variation). Ten patients with McArdle's disease showed only slight delta T2/T2 (0-10%). There was no overlap with values for healthy subjects, but there was some with values for other patients. Of the 21 subjects with a delta T2/T2 less than 19%, 19 had a metabolic myopathy. The other two had a congenital neuromuscular disorder (one central core disease, one nemaline myopathy) with type I fiber predominance (type I muscle fibers are characterized by a high oxidative metabolism and a low lactic acid production). CONCLUSION: The altered increase in T2 was sensitive but not specific for McArdle's disease. However, as variations in T2 reflect variations in pH, they seem to be specific for myopathies in which there is little exercise-induced decrease in pH (some metabolic myopathies and congenital neuromuscular disorders with type I fiber predominance) among patients in whom exercise intolerance is the main symptom. Our results suggest that MR imaging might be useful as a screening test for these diseases.

Adolescent↗
PubMed1993

[Cardiac involvement in certain muscular diseases. Apropos of 216 cases].

Myopathy may be associated with very variable cardiac involvement, the expression of which is related to the type of neuromuscular disease and also to the individual. This retrospective study, performed between 1986 and 1991, was undertaken to determine the prevalence of cardiac involvement in myopathy. A total of 216 subjects with an average age of 34 years were reviewed by clinical examination, ECG, echocardiography and Holter ECG monitoring. Some patients also underwent complementary radionuclide (scintigraphy, angiography) and electrophysiological investigations. The results confirmed cardiac disease in over a half of patients. Although 3/4 of the patients were asymptomatic from the cardiac point of view at the time of evaluation, the severity of certain lesions led to a number of specific therapeutic interventions. This suggests that simple, non-invasive cardiac diagnostic procedures should be undertaken systematically in the early stages of myopathic disease.

Adolescent↗
PubMed1993

[Left pulmonary artery originating from the ascending aorta in tetralogy of Fallot. Therapeutic strategy].

The authors report the rare case of a 12 year old child with an anomalous origin of the left pulmonary artery from the ascending aorta associated with Tetralogy of Fallot. This complex congenital malformation was treated surgically by a Deleval anastanosis between the right subclavian and right pulmonary arteries. The result was good with a 9 year follow-up, the patient having only Grade II effort duspnoea and cyanosis. The authors discuss the advantages and drawbacks of the different possible surgical approaches to this problem in the light of the outcome of this case and a review of the literature.

Anastomosis, Surgical↗
PubMed1992

Decreased cerebral glucose utilization in myotonic dystrophy.

To test the hypothesis that cerebral metabolism is altered in myotonic dystrophy (MyD), we investigated cerebral glucose kinetics and utilization in 11 adult patients with MyD and 14 healthy controls, using 18F-labeled 2-fluoro-2-deoxy-D-glucose (FDG) and dynamic positron emission tomography. Estimation of rate constants in MyD revealed a reduction of FDG delivery to the brain. Cortical glucose utilization rate was reduced by about 20% in MyD. These findings may be related to the presence of neurologic impairment in MyD and prompt further investigations on the metabolic and clinical features of brain dysfunction in this disease.

Adult↗
PubMed1992

[Mechanism of cellular action of nitrate derivatives].

Nitrate derivatives have to undergo metabolic activation in the smooth muscle cell or in the plasma with a sulflydryl radical. This transformation results in the formation of nitric oxide and/or S-nitrosothiols. These products stimulate an enzyme, the soluble guanylate cyclase in the sarcoplasm of the smooth muscle cell; giving rise to the formation of intracellular cyclic GMP from GTP. The cyclic GMP activates a kinase protein which in turn activates a number of other protein enzymes involved in the recaptation of calcium by the sarcoplasmic reticulum and in the extrusion of calcium from the cell. In addition, cyclic GMP reduces the level of phosphorylation of the myosin light chain, thereby reducing the sensitivity of the contractile proteins to intracellular calcium. All these phenomena cause smooth muscle relaxation so explaining most of the vasodilator effect of nitrate derivatives.

Cyclic GMP↗
PubMed1992

Prognostic value of cardiac metaiodobenzylguanidine imaging in patients with heart failure.

The prognostic value of 123I-metaiodobenzylguanidine (MIBG) imaging was compared with that of other noninvasive cardiac imaging indices in ninety patients (mean age = 52 +/- 7 yr) suffering from either ischemic (n = 24) or idiopathic (n = 66) cardiomyopathy. Patients had different measurements taken: cardiac MIBG uptake, radionuclide left ventricular ejection fraction, x-ray cardiothoracic ratio and echographic M-Mode data. Cardiac MIBG uptake was assessed as the heart-to-mediastinum activity ratio measured on the chest anterior view image obtained 4 hr after intravenous injection. The patients then had follow-up for 1-27 mo, at which time 10 patients had transplants, 22 had died and 58 were still alive. Data from patients with transplants were not used in the analysis, in which multivariate stepwise regression discriminant analysis showed that cardiac MIBG uptake was more potent to predict survival than other indices: H/M (p less than 0.0001), x-ray cardiothoracic ratio (p = 0.0017), echographic end-diastolic diameter (p = 0.0264) and radionuclide left ventricular ejection fraction (p = 0.0301). Moreover, multivariate life table analysis showed that cardiac MIBG uptake was also the best predictor for life duration: H/M (p = 0.0001), radionuclide left ventricular ejection fraction (p = 0.0098) and x-ray cardiothoracic ratio (p = 0.0139); echographic data were not useful. Thus, cardiac MIBG imaging may be helpful for heart transplantation decision making in patients with heart failure.

3-Iodobenzylguanidine↗
PubMed1991

The effect of nifedipine on myocardial perfusion and metabolism in systemic sclerosis. A positron emission tomographic study.

We assessed the effect of nifedipine on myocardial perfusion and metabolism in 9 patients with systemic sclerosis, using positron emission tomography with a perfusion tracer (potassium-38) and a metabolic tracer (18F-fluorodeoxyglucose [18FDG]). Nifedipine, 20 mg 3 times daily for 1 week, induced a significant increase in 38K myocardial uptake, a significant decrease in 18FDG myocardial uptake, and a significant increase in the myocardial 38K: 18FDG ratio. These results indicate that the increase in myocardial perfusion is associated with modifications in myocardial energy metabolism, which probably result from a beneficial anti-ischemic effect of nifedipine in patients with systemic sclerosis.

Animals↗
PubMed1991

Intracranial arachnoid cysts in myotonic dystrophy.

Clinically apparent brain dysfunction is common in myotonic dystrophy. In a sample of fourteen adult patients with the definite form of this disease, brain magnetic resonance imaging detected frequent white matter abnormalities and ventriculomegaly. In addition, two patients exhibited an intracranial arachnoid cyst, a condition of neurosurgical interest that could be related to the generalized dysmaturational process present in this disease. Patients with myotonic dystrophy deserve a careful screening for brain involvement. Further MRI studies should ascertain the actual prevalence of brain anomalies in myotonic dystrophy and define the role of this procedure in the workup of this disease.

Adult↗
PubMed1991

Deletions of mitochondrial DNA in Kearns-Sayre syndrome and ocular myopathies: genetic, biochemical and morphological studies.

Genetic, biochemical and morphological investigations were conducted on skeletal muscle mitochondria from 6 cases of ocular myopathy: 4 cases with Kearns-Sayre syndrome (KSS) and 2 with chronic progressive external ophthalmoplegia. All of these 6 cases showed mitochondrial DNA (mtDNA) deletions in addition to normal sized DNA in the quadriceps muscle. The deletions ranging from 3 to 8 kbp were also mapped between nucleotides 5500 and 16000 by Southern blot. The deleted genes encoded for some subunits of complexes I, IV, V and 5-10 tRNAS. The boundaries of the deletions have been sequenced in three patients. Five patients had mitochondrial respiratory chain deficiency in complex I as shown by the low oxygen consumption in isolated mitochondria using three NAD(+)-linked substrates. Mitochondria with an abnormal ultrastructure were also observed in 2 cases. A good relationship between the cytochrome c oxidase deficiency and the amount of deleted mtDNA was shown in our present investigations.

Adult↗
PubMed1991

Diagnosis of muscular glycogenosis by in vivo natural abundance 13C NMR spectroscopy.

Natural abundance 13C NMR (nuclear magnetic resonance) spectroscopy was used to distinguish patients suffering from muscle glycogenosis type V (McArdle's disease) from normal subjects by measuring their muscle glycogen content at rest. Proton-decoupled 13C spectra were obtained in 10-15 min from calf muscles at rest. The ratio of the glycogen/creatine signal areas was 12.9 +/- 1.7 in four McArdle's disease patients and 2.0 +/- 0.7 in seven normal subjects. This technique thus allows the non-invasive diagnosis of muscle glycogenosis.

Adult↗