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C Desnuelle

Publications and source records attributed to C Desnuelle.

At least 55 records · Page 3Linked to original sources
PubMed1992

Polymyalgia rheumatica and mitochondrial myopathy: clinicopathologic and biochemical studies in five cases.

PURPOSE: The coexistence of mitochondrial myopathy and polymyalgia rheumatica without giant cell arteritis is an interesting association. The frequency of this association was assessed in a prospective study. PATIENTS AND METHODS: Muscle biopsy specimens were obtained from 15 patients with polymyalgia rheumatica. When ragged red fibers (RRF) were observed, histochemical, ultrastructural, and biochemical studies were performed. RESULTS: In five cases, we found the typical appearance of mitochondrial myopathy, with the presence of numerous RRF. Histochemical and biochemical results confirmed these mitochondrial myopathies, showing miscellaneous deficiencies of mitochondrial respiratory chain enzymes. CONCLUSION: Persistence of histologic and biochemical abnormalities after steroid treatment in two patients seems to indicate that a subclinical mitochondrial myopathy preceded polymyalgia rheumatica. How a mitochondrial myopathy could induce or facilitate the emergence of a polymyalgia rheumatica remains unknown.

Aged↗
PubMed1992

Uneven distribution of mitochondrial DNA mutation in MERRF dizygotic twins.

A new family of myoclonic epilepsy with ragged-red fibers (MERRF) was studied at clinical, histological, biochemical and molecular genetic levels. There was a remarkable variation in the age of onset, the clinical presentation and the severity of symptoms. Multiple defects affecting respiratory chain complexes I, III and IV were detected in 2 patients. The point mutation at 8344 of the mitochondrial genome was found in all the maternal lineage with a relatively narrow range of variation in the percentage of mutant mitochondrial genomes. The one exception was represented by a set of dizygotic twins, one clinically affected and showing high proportions of mutant mitochondrial DNAs (mtDNAs) in blood cells, while the other was asymptomatic and showed very small amounts of mutant mt-DNAs in blood and skin. This could suggest an early segregation of the mitochondrial genome during ovogenesis.

Adult↗
PubMed1992

Defects of the mitochondrial respiratory chain complexes in three pediatric cases with hypotonia and cardiac involvement.

Three children displaying hypotonia, cardiac involvement and defects of the mitochondrial respiratory chain complexes are reported. The first case showed severe neonatal hypotonia, failure to thrive, hepatomegaly, dilation of the right cardiac cavities, profound lactic acidosis and amino aciduria. The boy died at the age of 7 weeks. In the second case hypotonia, severe cardiomyopathy, cyclic neutropenia, lactic acidosis and 3-methylglutaconic aciduria occurred. The boy died at the age of 27 months. The third case presented at the age of 16 months as an acute hypokinetic hypertrophic cardiomyopathy with transient hypotonia and mild lactic acidosis. Spontaneous clinical remission occurred. In all cases muscle biopsy was performed. Morphological studies failed to show ragged-red fibers but there was lipid storage myopathy and decreased cytochrome c oxidase activity. Biochemical studies confirmed the cytochrome c oxidase deficiency in muscle in all cases. It was associated with complex I III deficiency in case 1 and with severe deficits of all respiratory chain complexes in case 2. Post-mortem studies in case 1 indicated that complex IV was reduced in the liver but not in the heart and quantitative analysis of mtDNA revealed a depletion in muscle. Cases 1 and 2 shared some clinical features with fatal infantile myopathy associated with cytochrome c oxidase deficiency, while case 3 displayed a very unusual clinical presentation. The histochemical enzyme reaction of cytochrome c oxidase is useful for the diagnosis of mitochondrial myopathy because ragged-red fibers may be lacking. Finally, biochemical measurement of the different mitochondrial respiratory chain complexes is required because multiple defects are frequent and occasionally related to mtDNA depletion.

Abnormalities, Multiple↗
PubMed1992

31P NMR spectroscopy and ergometer exercise test as evidence for muscle oxidative performance improvement with coenzyme Q in mitochondrial myopathies.

Two patients with mitochondrial encephalomyopathy due to complexes I and IV deficiencies received 150 mg/d of coenzyme Q10 (CoQ). We studied them with a bicycle ergometer exercise test and 31P NMR spectroscopy before and after 10 months of treatment. Before treatment, we observed a low phosphocreatine/inorganic phosphate (PCr/P(i)) resting value along with abnormally high resting lactate concentration. During exercise, there was a pronounced acidosis with delayed kinetics of postexercise recovery for blood lactate, pH, PCr, and PCr/P(i) ratio. Oxygen uptake during exercise was reduced while the lowering of the ventilatory threshold indicated an early activation of glycolysis. After treatment, the bicycle ergometer exercise test indicated a significant improvement with a decrease in resting blood lactate level, an increase in oxygen consumption during exercise, and an increase in the kinetics of lactate disappearance during the recovery period. A shift of the ventilatory threshold to higher workload was present. 31P NMR spectroscopy confirmed the improvement, showing a significant increase in the PCr/P(i) ratio at rest and in the kinetics of recovery for pH, PCr, and PCr/P(i) ratio following exercise in patient 1. For patient 2, we observed a less pronounced acidosis correlated with a lesser amount of Pi produced during exercise. These observations indicate an improvement of mitochondrial function and a shift from high to low glycolytic activity in both patients consequent to CoQ treatment.

Adolescent↗
PubMed1992

[Cholesterol emboli with neurologic manifestation in the spinal cord].

A 71-year old man presented with a progressive chronic paraparesis combined with inflammatory biological features including hypereosinophilia and an aneurysm of the abdominal aorta. Disseminated cholesterol embolization of arterioles was evidenced by the identification of cholesterol crystals in biopsies of the quadriceps muscle and of an iliac lymph node. Despite the lack of post mortem study of the spinal cord, the presentation was highly suggestive of cholesterol emboli in the spinal arteries. Only ten documented cases have been reported.

Aged↗
PubMed1992

[Segmental dystonia and mitochondrial encephalomyopathy].

A 55 year-old male experienced a dystonia of the right upper limb followed by a ptosis with complete ophthalmoplegia and cataract. He developed a sensory neuropathy and personality changes. Ragged-red fibers were found on muscle biopsy. There was a major defect in complex III and IV activity.

Blepharoptosis↗
PubMed1992

[Inclusion body myositis and neuromuscular diseases with rimmed vacuoles].

A retrospective study of 40 patients with various neuromuscular disorders and more than 3 muscle fibers with rimmed vacuoles has been performed. Two subgroups of patients were distinguished according to the presence or absence of inflammatory exudates. In the first group (14 patients), inflammatory exudates were observed and numerous fibers showed partial invasion. Abnormal filamentous inclusions (16-18 nm in diameter) were found by electron microscopy in muscle fibers cytoplasm and/or nuclei. The diagnosis of inclusion body myositis (IBM) was made in these cases. They presented with insidious proximal muscle weakness and were not improved by immunosuppressive therapy. Immunohistological studies demonstrated T lymphocytes predominance, only few natural killer and B lymphocytes. The number of T8 lymphocytes was high in endomysial sites while T4 were more numerous in perivascular exudates. Abnormal membranous expression of class I MHC antigens was observed on muscle fibers lying near the inflammatory exudates. In the second group of cases (26 patients), no inflammatory exudate was observed. This group of neuromuscular diseases with rimmed vacuoles was heterogeneous. In 10 cases, abnormal filamentous inclusions (16-18 nm in diameter) were observed in rimmed vacuoles. However, this ultrastructural feature did not help in distinguishing subgroups. Various neuromuscular disorders were observed in this group: oculopharyngeal muscular dystrophy (12 cases with IBM like filaments in 4 cases), chronic spinal atrophy (5 cases with IBM like filaments in 3 cases), post poliomyelitis syndrome (2 cases with IBM-like filaments in one), muscle glycogenosis with IBM like filaments (2 cases), hereditary limb girdle myopathy or distal myopathy (3 cases) and 1 patient clinically presenting with polymyositis and another with cramps and myalgias. No abnormal sarcolemmal expression of class I MHC was found in this group. The pathogenesis of IBM is discussed. Besides T cell mediated cytotoxicity, denervation may be involved. The nature of the abnormal 16-18 nm filamentous inclusions remains unknown. These filaments are not IBM specific.

Adult↗
PubMed1992

[Inflammatory myalgic syndrome and muscular mitochondrial abnormalities: 4 cases].

Histologic and biochemical anomalies of muscle mitochondria were identified in four patients with predominantly rhizomelic myalgia clinically suggestive of an inflammatory disease but inconsistent biologic evidence of inflammation. This clinical pattern was initially suggestive of atypical polymyalgia rheumatica and could not be ascribed to any other disease. To explain this combination of anomalies, several hypotheses can be put forward, including coincidence, aging, and nonspecific mitochondrial anomalies resulting from immunologic or inflammatory disease. The speculation that these patients have an autonomous syndrome cannot be outruled but should be considered with caution. A therapeutic trial with coenzyme Q is under way.

Aged↗
PubMed1991

Multiple defects of the mitochondrial respiratory chain in a mitochondrial encephalopathy (MERRF): a clinical, biochemical and molecular study.

We describe a young man with a progressive neurological disorder including myoclonus, mental retardation, muscle weakness and a mitochondrial myopathy (myoclonus epilepsy and ragged red fibres--MERRF). Multiple abnormalities of the mitochondrial respiratory chain in skeletal muscle are shown by direct measurement of the flux through the individual complexes, low-temperature redox spectroscopy and decreased immunodetectable subunits of complexes I and IV by immunoblotting. No abnormality of mitochondrial DNA was found. This is the first report of combined defects of complexes I, III and IV as a cause of this clinical syndrome. However, we propose that the occurrence of multiple respiratory chain defects may be more common than previously recognised and that this particular combination of defects, involving complexes I, III and IV, may be the predominant biochemical abnormality in MERRF.

Adult↗
PubMed1991

[Anomaly in the neurotransmitter amino acids in amyotrophic lateral sclerosis: a therapeutic application].

Although the cause of amyotrophic lateral sclerosis remains unknown, the excitatory amino acids may be involved in its pathogenesis. Glutamate level analysis shows a differential distribution of the amino acids. One of the therapeutic methods consists of reinforcing the inhibitory amino acid activity using L-threonine which has been shown to improve some symptoms and signs of ALS.

Adult↗
PubMed1991

[Mitochondrial and ocular myopathies (62 cases)].

The authors report the clinical signs and histological findings in 62 patients with ocular myopathies divided into two groups: (a) ocular myopathies with mitochondrial abnormalities, themselves divided into pure (19 cases) or progressive (15 cases) ophthalmoplegia, and multisystemic myopathies (14 cases); (2) oculopharyngeal myopathies (15 cases) in elderly subjects, with constant intranuclear tubulofilamentous inclusions. Among myopathies with mitochondrial abnormalities, ocular forms with a favourable prognosis coexisted with earlier and more severe multisystemic lesions.

Adolescent↗
PubMed1991

[Slowly progressive myopathy with accumulation of tubular aggregates].

Slowly progressive myopathy with tubular aggregates is rare and dominantly or recessively inherited. Three sporadic cases are reported in the present study occurring in 2 men and 1 young woman. All patients had proximal limb weakness without severe atrophy. They also complained of exercise-induced stiffening and cramps of their leg muscles. In 1 case severe cardiomyopathy caused unfavorable clinical course and death. Serum creatine kinase activity was normal and electromyogram showed only slight myopathic changes. Tubular aggregates were found to be the sale morphological abnormality. They were present in type II fibres in 1 case and in type I and type II fibres in the others. An immunocytological study with a polyclonal antibody against Ca2+ SR-ATPase showed positivity of the tubular aggregates with this antibody. A quantitative analysis (SAMBA 2000 alcatel TITN) was carried out on frozen sections stained for calcium. It showed a lower calcium content in tubular aggregates than in other part of the fibre. Slowly progressive myopathy with tubular aggregates may be distinguished from other diseases where tubular aggregates are the sale structural change, such as myopathies with myasthenic features and some neuromuscular diseases with exercise intolerance without progressive course. Usually, tubular aggregates are not a specific finding; they have been described in various disorders in association with other structural changes.

Adolescent↗
PubMed1990

A simple device for the optimized isolation of fat cells.

We describe a simple cell isolation device that allows the separation and sequential collection of fat cells as they are released from adipose tissue fragments exposed to a collagenase preparation. This is done without interrupting the digestion process. Use of the device allows for appreciable lowering of the degree of cell damage and the extent to which larger cells are ruptured during the isolation process. Fat cells isolated by this technique elicit a higher level of metabolic activity as reflected by their improved response to the lipolytic action of epinephrine.

Adipose Tissue↗
PubMed1990

[Intolerance to exercise caused by carnitine palmitoyltransferase deficiency].

Exercise intolerance with slight myalgia worsened by a cold environment resulted in the diagnosis of CPT deficiency in a young boy with no family history. Recurrent myoglobinuria is not the hallmark of such a deficit. Biochemical examination of muscle biopsy in suggestive situations is the way to diagnosis. Concomitant myoadenylate deficiency in this patient could represent a precipitating factor. Partial CPT deficiency in all the patients reported was first explained through the mechanism of intra mitochondrial fatty acid transport but raises questions about the regulation of CPT synthesis.

Acyltransferases↗