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Biomedical subjects

D Duboc

Publications and source records attributed to D Duboc.

At least 73 records · Page 4Linked to original sources
PubMed1991

Exercise-induced muscle modifications: study of healthy subjects and patients with metabolic myopathies with MR imaging and P-31 spectroscopy.

Exercise-induced variations in proton signal intensity at magnetic resonance (MR) imaging and in intracellular pH were studied in the forearm muscles of healthy subjects and patients with muscular glycogenoses. The relative increase in T2 was measured from MR images obtained at 0.5 T, and end-exercise pH was measured with surface coil phosphorus-31 spectroscopy at 2 T. Eight healthy subjects showed a relative increase in T2 ranging from 20% to 44% in the flexor digitorum superficialis muscle and a drop in pH ranging from 0.35 to 1.1. Seven patients with muscular glycogenosis (six with McArdle disease and one with phosphofructokinase deficiency) showed only a slight variation in T2 (0%-17%) and no decrease in pH. Variations in T2 and in end-exercise pH were found to be correlated, perhaps reflecting the stimulation of muscular perfusion caused by acidosis.

Adult↗
PubMed1991

[Effect of sinorphan, an endopeptidase inhibitor on severe congestive cardiac insufficiency].

Sinorphan is a powerful inhibitor of enkephalinases or endopeptidases 24-11, enzymes implicated in the degradation of the atrial natriuretic factor (ANF). In healthy volunteers, it increases plasma concentrations of endogenic ANF and increases diuresis and natriuresis. In order to study the tolerance and biological effects of pharmacological increase of plasma concentrations of endogenic ANF in severe congestive cardiac failure, 12 patients (in functional Classes III or IV of the NYHA classification) were given a single oral dose of 10, 20 or 40 mg of Sinorphan. Sinorphan was clinically well tolerated. The diastolic blood pressure decreased slightly (- 10 +/- 9 mmHg) but significantly (p less than 0.05). Systolic blood pressure and heart rate were unchanged. Despite spontaneously high plasma ANF concentrations (on average 15 times higher than normal subjects), Sinorphan induced an additional increase of 80 to 100% of plasma ANF concentration compared to the initial values (p less than 0.01) with no dose-dependent response for the dosages used. The inhibition of plasma endopeptidase activity attained 47% at the 30th minute. Urinary cyclic GMP excretion increased by 30% at the second hour (p less than 0.05). In addition, a statistically non significant tendency to increase diuresis and natriuresis was observed. These results show that Sinorphan increases plasma ANF concentrations by inhibition of its degradation in severe congestive cardiac failure and that this increase seems to be associated with potentially beneficial biological changes. The concept of endopeptidase inhibition should constitute a new therapeutic approach in cardiac failure, a situation in which the ANF seems to exert a favourable effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

[Demonstration of abnormalities of myocardial mitochondrial oxygenation in cardiac graft rejection].

Abnormalities of myocardial metabolism during acute rejection may be due to ischemia to primary metabolic changes related to rejection. An experimental study of heterotopic cardiac transplantation in the rat was undertaken to study myocardial mitochondrial oxidation during acute rejection. The receivers were Lewis rats and the donors Fischer (FL: allograft) or Lewis (LL: isograft) rats. The oxygen consumption of the mitochondria (VO2m) isolated from the transplanted and native hearts was measured by oxygraphy six days after transplantation. Using maleate and glutamate substrates, the VO2m of transplanted hearts was significantly lower than that of native hearts in the two groups of rats (FL, p less than 0.01; LL, p less than 0.01). In addition, the VO2m of FL allograft transplanted hearts was significantly lower than in the LL rats (30 +/- 9 vs 100 +/- 15 nanoatoms of oxygen/min.mg/prot, p less than 0.01) as was the VO2m of the native hearts (FL: 106 +/- 23 vs LL: 164 +/- 26, p less than 0.02). The respiratory control ratio (RCR) was significantly lower in the transplanted than in the native hearts in both the FL and LL groups (p less than 0.05 and p less than 0.01 respectively). The comparison of the RCR in the two groups (FL vs LL) showed no significant difference for transplanted or native hearts. Electron microscopy of transplanted (rejected or not) and native hearts showed no morphological abnormality of the mitochondria. The lower VO2m of the allograft group indicates a disturbance in the mitochondrial respiratory pathway during acute rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

[Abnormalities of the skeletal muscle in hypertrophic cardiomyopathy. Spectroscopy using phosphorus-31 nuclear magnetic resonance].

There have been several reports of electromyographic and histological changes of striated skeletal muscle, especially of the type I oxidative fibres, in hypertrophic cardiomyopathy. In order to determine whether these anomalies also cause metabolic changes, a P-31 magnetic resonance spectroscopic study was undertaken at rest and on exercise in 5 pauci-symptomatic patients and 10 control subjects. The 5 patients had primary hypertrophic cardiomyopathy without alteration of systolic function or signs of congestive cardiac failure (Stages I or II). There were no clinical signs of myopathy. None of the patients were receiving betablocker therapy at the time of investigation. No significant difference was observed at rest. Intracellular acidosis was particularly pronounced in 2 of the 5 patients at the peak of exercise. In addition, the phosphocreatine recovery time (T1/2) was longer in the patient group (3.4 +/- 1.7 vs 1.6 +/- 0.9 mn; p less than 0.01) suggesting a mitochondrial metabolic oxidation abnormality. These results suggest that some patients with primary hypertrophic cardiomyopathy have abnormalities of mitochondrial oxidation in their striated skeletal muscle which can be demonstrated by P-31 magnetic resonance spectroscopy. This would suggest a global abnormality of striated muscle which, at a more advanced stage of the disease, could account for decreased effort tolerance in these patients.

Adult↗
PubMed1991

[Myocardial involvement in 2 women, carriers of Duchenne de Boulogne muscular dystrophy].

Duchenne muscular dystrophy is the commonest genetic muscular disease. The prognosis, which depends on cardiac involvement, is poor. In boys, this takes the form of a hypokinetic cardiomyopathy particularly affecting the postero-lateral wall of the left ventricle which then dilates. The recent identification of the gene which transmits the disease on the X chromosome and of the coded protein, dystrophin, has improved our understanding of the disease. We report two cases of isolated cardiac involvement in two female carriers of the disease, classically thought to be unaffected. They presented with apparently idiopathic dilated cardiomyopathies. These cases show that Duchenne muscular dystrophy is an original example of a genetically determined diffuse muscular disease with cardiac involvement.

Adult↗
PubMed1990

Discriminant factor analysis of 31P NMR spectroscopic data in myopathies.

Discriminant factor analysis (DFA) enables one to distinguish among diagnostic groups using diagnostic variables. It provides discriminant functions that are linear combinations of the diagnostic variables and that optimally separate diagnostic groups. It was used to enhance the accuracy of 31P NMR data in the diagnosis of myopathies. DFA allowed a good separation of normal subjects, congenital neuromuscular disorders with type I fiber predominance, and McArdle's diseases. It elicited an unexpected homogeneity of idiopathic rhabdomyolyses, the metabolic origin of which is unknown, and suggested that the abnormality could involve the mitochondrial oxidative metabolism in some of them. In mitochondrial myopathies, an expected heterogeneity is shown by DFA. It may allow an automatic diagnosis of some myopathies from 31P NMR data or guide biochemists by comparing biochemical features of a new patient to those of previously established groups.

Adult↗
PubMed1990

Spectroscopic MRI: a tool for the evaluation of systemic lipid storage disease.

Spectroscopic MR imaging allows to measure the lipid content of a region inside the human body. This technique has been applied to the case of a woman with a severe multisystemic triglyceride storage disease. Lipid contents of liver, pancreas, kidneys, left ventricle, skeletal muscles (calves, thighs, arms) were measured by using the Dixon spectroscopic imaging sequence. In some heterogeneous muscles, localized proton spectra were recorded. Results agreed with clinical findings (muscle weakness, normal renal and cardiac function, diabetes). These techniques could help to quantify the severity of the disease and to follow up its evolution under therapy.

Adult↗
PubMed1990

[Constrictive pericarditis and Whipple's disease].

The authors report the case of a 61 year-old patient treated by tetracycline for very probable Whipple's disease who developed constrictive pericarditis requiring pericardectomy. Although intestinal biopsy was negative, histological examination of the resected pericardium was very suggestive of a cardiac localisation of Whipple's disease, showing a fibrous pericarditis with a mononuclear infiltration including PAS-positive histiocytes. In addition, the same histological changes were found in a small fragment of myocardial biopsy. This case illustrates the prevalence and consequences of cardiac involvement in Whipple's disease.

Cineradiography↗
PubMed1990

[Peripheral circulatory and metabolic changes in cardiac insufficiency. Therapeutic implications].

Many peripheral changes are observed in heart failure concerning regional blood flow, vasomotor tone and oxygen uptake by skeletal muscle. They contribute to the alteration of exercise capacity and have to be taken into consideration in adapting therapy. A regression of these peripheral abnormalities is often observed after prolonged treatment which implies evaluation of efficacy on effort tolerance after a sufficiently long period of administration.

Blood Circulation↗
PubMed1990

[Dilated cardiomyopathy with deep, completely reversible dysfunction of the left heart in alcoholic patients. Report of 2 cases].

Two cases of dilated, hypokinetic cardiomyopathy complicated by cardiac failure, are reported in a 29 year old woman and a 55 year old man, with no etiological factors other than chronic major alcoholism (consumption of over 100 ml of alcohol per day for over 5 years). This was completely reversed 10 and 14 months after cessation of alcohol consumption. The isotopic left ventricular ejection fraction increased from 22 to 70 p. 100 and from 12 to 73% respectively. These cases are are and are evidence in favour of an alcoholic cardiomyopathy rather than alcohol being an aggravating factor in patients with cardiomyopathy.

Adult↗
PubMed1990

Evidence of mitochondrial impairment during cardiac allograft rejection.

NADH laser fluorimetry and mitochondrial oxigraphy were used to study myocardial oxidative energy metabolism during cardiac allograft rejection. Heterotopic cardiac transplantation was performed on Lewis rats; allografts (with Fischer rat donors) were compared with isografts (with Lewis rat donors). In vivo and in vitro assays were performed six days after transplantation. Myocardial NADH fluorescence was recorded in vivo from grafted hearts, at baseline; during brief, complete ischemia; and during reperfusion. Oxygen consumption of mitochondria isolated from both native and grafted hearts was determined. Neither baseline levels nor maximum ischemic levels of NADH fluorescence (F0 = k[NADH]) were found to be significantly different between allografts (0.45 +/- 0.05 to 0.87 +/- 0.10) and isografts (0.45 +/- 0.04 to 1.11 +/- 0.05). During recovery, the rate of fluorescence decrease was significantly lower in allografts than in isografts (0.024 +/- 0.001 vs. 0.038 +/- 0.002 delta F0.s-1, P less than 10(-3], indicating a lower rate of NADH reoxidation. In the presence of malate and glutamate substrates, mitochondrial O2 consumption was significantly lower in allografts than in isografts (30 +/- 9 vs. 100 +/- 15 nanoatoms O2. min-1.mg prot-1, P less than 10(-2]. These results indicate that mitochondrial oxidative metabolism was impaired during the rejection process. Such energy production disturbances may contribute to the dysfunction of rejecting hearts.

Animals↗
PubMed1988

Congenital valvular aortic stenosis in adults.

Based on a study of 20 patients operated on between the ages of 21 and 38 for congenital valvular aortic stenosis, the distinguishing features of congenital aortic valvular stenosis in adults are reviewed: valvular calcification (75%), valvular dome rarely present (10%), usually moderate cardiac disability (70%), diminished or inaudible second heart sound (50%), associated diastolic murmur (75%), electrocardiographic left ventricular hypertrophy (70%), and an infrequent protosystolic click (30%). Surgery is necessary for symptomatic patients. If patients are asymptomatic, surgery is decided after measuring the left ventricle-aortic pressure gradient by continuous Doppler wave study, or by cardiac catheterization. If surgery is not performed, a regular follow-up is necessary because stenosis can evolve. Valvular replacement by a mechanical valve is preferable. Even if the aortic valve is not calcified and a simple commissurotomy is technically possible, it is only a palliative method with unsatisfactory results and an annual mortality rate after surgery of 1%.

Adult↗
PubMed1988

Change in human cardiac rhythm induced by a 2-T static magnetic field.

The influence of a 2-T static magnetic field on the cardiac rhythm was studied with 24-hour electrocardiographic monitoring in 12 healthy volunteers for 1 hour before exposure, 1 hour during exposure, and 22 hours after exposure. Four other subjects were exposed to 1 T, and nine control subjects were exposed to 0 T. In the 2-T group, the mean cardiac cycle length (CCL) was 912 msec +/- 83 before exposure. A significant 17% increase in CCL was observed after 10 minutes of exposure. No further significant variation was observed during exposure, and the CCL was back to preexposure values 10 minutes after exposure. No other arrhythmogenic effect was noted during the 24-hour monitoring. No statistically significant change was observed at either 0 or 1 T. The magnetically induced blood-flow potentials superimposed on the T wave were observed. The CCL increase during exposure could reflect a direct or indirect effect of magnetic fields on the sinus node, which is probably harmless in healthy subjects. However, its safety in dysrhythmic patients remains to be determined.

Adult↗
PubMed1988

In situ NADH laser fluorimetry of rat fast- and slow-twitch muscles during tetanus.

To investigate the variations of oxidation-reduction status of fast- and slow-twitch muscles during intense contractions, we performed in situ NADH laser fluorimetry during 25-s tetanus in extensor digitorum longus (EDL) and in soleus (SOL) muscles of eight Sprague-Dawley rats anesthetized with pentobarbital sodium. At base line the compensated NADH fluorescence (F0) was not significantly different between EDL and SOL. In EDL, tetanic stimulation induced an increase of F0, which rapidly reached a plateau that was 124% over the base-line value and stable until the end of the stimulation. In SOL, after an initial shouldering there was a continuous increase of F0 until the end of tetanus, reaching 275% of the base-line value. After the stimulation the initial rate of recovery was significantly faster in SOL than in EDL. We conclude that during and after intense contraction the variation of NADH content vs. time can be evaluated by in situ NADH laser fluorimetry in different muscle types. This nondestructive method can be helpful to differentiate in situ the various physiological or pathological oxidative capabilities of skeletal muscles.

Animals↗
PubMed1988

[Primary cardiomyopathies and disorders of myocardial energy metabolism: causes or consequences?].

In this review paper, the authors summarize the studies which support the theory that a defect in production of energy by the myocardial cells is a determinant factor in the genesis and/or aggravation of dilated cardiomyopathy. Points that are common to this metabolic theory and to the other pathogenetic mechanisms usually described (notably viral or toxic mechanisms) are presented.

Animals↗
PubMed1988

[Laser fluorimetry of NADH].

Laser fluorimetry of reduced nicotinamide adenine-dinucleotide (NADH) in situ is a new technique used for real-time studies of the degree of reduction of the first link in the mitochondrial respiration chain. We present here the first results obtained in animal experiments and in clinical exploration: In rats, coronary occlusion produces a substantial rise in mitochondrial NADH, followed by a fall below basal level during reperfusion. Tetanic contraction of slow-twitch muscles in rats results in a rise in NADH level higher than that produced by contraction of fast-twitch muscles. During coronary angiography, injection of the contrast medium induces a rise in NADH in patients with a significant degree of coronary stenosis. Intravenous nitroglycerin reduces both left ventricular end-diastolic pressure and NADH fluorescence concomitantly, due to preferential distribution of the coronary blood flow to sub-endocardial layers. Exercise-induced ischaemia results in a decrease of muscular NADH concentration in Mc Ardle syndrome, due to phosphorylase deficiency.

Animals↗