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J F Pellissier

Publications and source records attributed to J F Pellissier.

At least 19 recordsLinked to original sources
PubMed2006

In vivo and in vitro characterization of skeletal muscle metabolism in patients with statin-induced adverse effects.

OBJECTIVE: Statins (3-hydroxymethylglutaryl-coenzyme A reductase inhibitor) are widely used to treat hypercholesterolemia. They are generally well tolerated, but myotoxic effects have been reported and the corresponding mechanisms are still a matter of debate. The aim of the present study was to determine whether impairment of calcium homeostasis and/or mitochondrial impairment could account for the adverse effects of statins in skeletal muscle. METHODS: Eleven patients with increased creatine kinase levels and myalgias after statin treatment were evaluated using in vitro contracture tests (IVCTs), histology, and 31P magnetic resonance spectroscopy (31P-MRS). RESULTS: IVCT results were abnormal in 7 of the 9 patients, indicating an impaired calcium homeostasis. The 31P-MRS investigation disclosed no anomaly at rest, and the aerobic function assessed during the postexercise recovery period was normal. On the contrary, the pH recovery kinetics was significantly slowed down as indicated by a reduced proton efflux, which could be ultimately linked to a failure of calcium homeostasis. Overall, our observations indicate a normal mitochondrial function and raise the possibility that statins may unmask a latent pathology involving an impairment of calcium homeostasis such as malignant hyperthermia (MH). CONCLUSION: In case of susceptibility to MH, statins treatment must be administered with caution, and signs of adverse effects should be checked.

Aged↗
PubMed2006

'Cap myopathy': case report of a family.

We report the observation of an 18-year-old girl, whose clinical presentation was very suggestive of a congenital myopathy with neonatal onset. A congenital myopathy had been already diagnosed in her brother and in addition her half-cousin died diagnosed with a severe nemaline myopathy at age 4 years. A muscle biopsy performed on both siblings revealed histological and ultrastructural features of 'cap myopathy'. This case report suggests that 'cap myopathy' and some cases of nemaline myopathy with neonatal onset might be two phenotypic expressions of the same genetic disorder. These two entities could therefore, perhaps, be regarded as 'Z-line disorders' possibly caused by defective myofibrillogenesis.

Actins↗
PubMed2005

[Cytochrome c oxydase-deficient Leigh syndrome with homozygous mutation in SURF1 gene].

Leigh syndrome is a heterogeneous disorder, usually due to a defect in oxidative metabolism. Mutations in SURF1 gene have been identified in patients with cytochrome c oxidase deficiency. We report a homozygous splice site deletion [516-2_516-1delAG] in a young girl presenting with cytochrome c oxidase-deficient Leigh syndrome. Identification of molecular defect is indispensable for genetic counselling and prenatal diagnosis.

Cytochrome-c Oxidase Deficiency↗
PubMed2005

Expression of the beta chemokines CCL3, CCL4, CCL5 and their receptors in idiopathic inflammatory myopathies.

The idiopathic inflammatory myopathies (IIM) are a group of autoimmune diseases characterized by chronic lymphocytic and macrophagic infiltration in muscle. Because the mechanism for recruitment of these cells probably involves chemokines, we focused on the study of the expression pattern of some beta chemokines and receptors because it may provide a basis for selective immunotherapy. The expression of CCL3 (MIP-1alpha), CCL4 (MIP-1beta), CCL5 (RANTES) and their main receptors (CCR1 and CCR5) was studied by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry in a series of 16 IIM and five controls (four normal muscles and one tonsil). Except for CCL5, strong expression was observed by RT-PCR with all molecules in all IIM subtypes in comparison to control muscle. Immunohistochemistry revealed diffuse CCL4 expression in all vessels in dermatomyositis. In both polymyositis and sporadic inclusion body myositis (s-IBM) it was restricted to vessels in the vicinity of inflammatory exudates. CCL5 expression was low, restricted to a few inflammatory cells in all IIM; CCR1 expression was mainly restricted to macrophages and s-IBM endothelial cells, whereas CCR5 was localized in inflammatory cells invading non-necrotic muscle fibres. Expressions of both receptors were also recorded in few muscle fibres. In conclusion, the upregulation of beta chemokines and receptors in IIM and their differential expression by various cells may contribute to chronic inflammation and to the peculiar distribution of inflammatory exudates in these diseases.

Adolescent↗
PubMed2004

Value of fetal autopsy after medical termination of pregnancy.

We carried out a retrospective study of 352 medical terminations of pregnancy (MTP) carried out in a large French administrative region over two consecutive years. We analysed the indications for MTP and then compared the prenatal ultrasound diagnosis with fetal autopsy findings in order to demonstrate the value of pathological examination of the fetus in prenatal diagnosis and genetic counselling as well as the need to check by autopsy the quality of ultrasound screening. Preliminary analysis of the indication for these MTP showed that in 69.9% ultrasound screening had been carried out, revealing mainly brain abnormalities (22.2%) and heart defects generally associated with chromosomal abnormalities (32.1%). Prenatal findings were in agreement with autopsy results, showing no false-positive prenatal diagnoses. However, in 7.9% of cases in which brain abnormalities were detected, confirmation was not possible at autopsy because of tissue autolysis, showing the need for optimal conditions of expulsion. In 35.8% of cases, confirmation of the diagnosis by autopsy was not useful for management but still added to medical knowledge and demonstrated to the mother the reality of the defects. In 50.9%, the autopsy findings were decisive for genetic counselling.

Aborted Fetus↗
PubMed2004

[Andersen syndrome: a particular form of paralysis with cardiac dysrhythmia].

Andersen syndrome includes a clinical triad with periodic paralysis, cardiac arrhythmia and dysmorphic features most often mild but relevant. It is a potassium channelopathy due to mutation of KCJN2 gene coding for Kir 2.1 protein. We report a familial case with mutation R218W of Kir 2.1 and discuss the main phenotypic and genetic aspects of Andersen syndrome. Muscle manifestations are essentially a periodic paralysis most often of hypokaliemic type. Muscle biopsy reveals tubular aggregates but can be normal as it is shown in the same patient in our kindred. Our proband complained of paralytic attacks since childhood and at adult age she demonstrated a mild permanent deficit of pelvic girdle muscles as it has been described in other types of periodic paralysis after a long duration course. Cardiac manifestations may include in a variable manner a long QT syndrome, premature ventricular contractions, complex ventricular ectopy, polymorphic or bidirectional ventricular tachycardia. Imipramine had a positive effect on arrhythmia in our case. Dysmorphic features are often mild and have to be cautiously looked for as a clue to the diagnosis of Andersen syndrome. They can be easily overlooked if not systematically looked for. Clinical expressivity is variable including in the same family. In our observation, the daughter showed a complete triad, early expressed, which allowed the diagnosis. Her father was late diagnosed on ventricular dysrhytmia but without muscle manifestations and dysmorphic features. Since KCJN2 gene mutation identification, locus heterogeneity of Andersen syndrome was shown. Andersen syndrome kindreds without mutations in KCNJ2 were clinically indistinguishable from KCNJ2-associated subjects. KCNJ2 gene encodes the inward rectifier K+ channel Kir2.1 which plays an important role in maintaining membrane potential and during the terminal phase of cardiac action potential repolarization. Several studies showed a dominant negative effect of the mutation on Kir 2.1 channel function.

Adolescent↗
PubMed2004

Gastrointestinal tract symptoms in Maternally Inherited Diabetes and Deafness (MIDD).

OBJECTIVE: To evaluate the prevalence and clinical consequences of gastro-intestinal manifestations in Maternally Inherited Diabetes and Deafness syndrome (MIDD). METHODS: We report the case of fatal intestinal pseudo-obstruction in a patient with severe MIDD. Using a standardized questionnaire, we evaluate the frequency of gastrointestinal tract (GIT) symptoms in 10 patients with MIDD (8 A3243G and 2 T14709C mutations of mitochondrial DNA). The reference population consisted of 50 patients with type 1 diabetes matched for disease duration. In 4 patients with digestive manifestations endoscopic examination of upper and lower GIT was performed allowing multiple biopsies for ultrastructural and molecular analysis. RESULTS: GIT symptoms were frequently reported in MIDD specially in patients bearing the mt 3243 mutation. The manifestations i.e. constipation, diarrhea or both, were more frequent in this subgroup than in type 1 diabetic population (88% vs 28%, p<0.05). Ileus is a rare and severe complication with a frequent fatal Issue. Ultrastructural analysis of the mucosa from oesophagus, stomach, duodenum, colon and rectum showed mild modifications such as accumulation of normal mitochondria and lipId droplets. Heteroplasmy levels were determined in 4 patients harboring the 3243 mutation. In three patients the percentage of mutated DNA increased from upper to lower GIT. CONCLUSIONS: Gastrointestinal symptoms are frequent in MIDD secondary to 3243 mutation. They might explain the lower body weight observed in these patients in comparison to reference diabetic populations. They can also lead to a severe complication namely the intestinal pseudo-obstruction.

Constipation↗
PubMed2003

Limb-girdle muscular dystrophy in a 71-year-old woman with an R27Q mutation in the CAV3 gene.

The authors report a 71-year-old woman with limb-girdle muscular dystrophy (LGMD) associated with an R27Q mutation in the CAV3 gene. Immunohistochemistry showed a >90% reduction of caveolin-3 on the sarcolemma by western blot, and anti-dysferlin immunoreactivity was reduced. This case emphasizes that an R27Q missense mutation in the CAV3 gene can lead to various clinical phenotypes including hyperCKemia, rippling muscle disease, distal myopathy, and LGMD1C.

Aged↗
PubMed2003

Histopathological differences of myotonic dystrophy type 1 (DM1) and PROMM/DM2.

Muscle biopsy findings in DM2 have been reported to be similar to those in DM1. The authors used myosin heavy chain immunohistochemistry and enzyme histochemistry for fiber type differentiation on muscle biopsies. Their results show that DM2 patients display a subpopulation of type 2 nuclear clump and other very small fibers and, hence, preferential type 2 fiber atrophy in contrast to type 1 fiber atrophy in DM1 patients.

Adult↗
PubMed2003

[Restrictive cardiomyopathy due to myofibrillar myopathy].

UNLABELLED: Early and severe cardiomyopathy may be related to myofibrillar myopathy. CASE REPORT: We report a one-year-old child with early and severe restrictive cardiomyopathy. The diagnosis of myofibrillar myopathy was obtained on skeletal muscle and endomyocardial biopsies. The patient died despite inotropic support and mechanical ventilation. CONCLUSION: Myofibrillar myopathy must be considered when exploring the etiology of a restrictive cardiomyopathy in children. The diagnosis relies on examination of endomyocardial or skeletal muscle biopsy samples.

Biopsy↗
PubMed2003

[Case history of mitochondrial cytopathy with cardiac expression].

Childhood dilated cardiomyopathies comprise a wide aetiological spectrum for which the prognosis and treatment sometimes vary considerably. We report the case of a patient affected by a rare form of mitochondrial cardiomyopathy in whom the diagnosis of acute myocarditis had initially been made. The progression was fatal even though the patient was awaiting a cardiac transplant. Beyond the difficulties of diagnosis and treatment of this pathology, this clinical case underlines the significance of an early aetiological diagnosis based on the results of an endo-myocardial biopsy. Cardiac transplantation should be envisaged for this type of patient based not only on the clinical status but equally by taking account of the prognosis of this disease for which deterioration can sometimes be very rapid.

Adolescent↗
PubMed2002

Pituicytomas, a mis-diagnosed benign tumor of the neurohypophysis: report of three cases.

Pituicytoma is a rare benign primary tumor of the neurohypophysis, occurring in the sellar and suprasellar spaces. We report here three new cases with immunohistochemical and electron microscopic study. Particular attention was paid to the expression of some cell adhesion molecules. These tumors were characterized by bundles of elongated cells strongly immunoreactive to anti-vimentin, S-100 protein, neural cell adhesion molecule and neuron-specific enolase antibodies. Glial fibrillary acidic protein (GFAP) was not recorded. It expressed the very late antigen alpha2 (VLAalpha2), but not VLAalpha5, and lacked epithelial markers expression (epithelial membrane antigen, E-cadherin), and specific neuronal markers (synaptophysin, chromogranin, neurofilament). Staining for pituitary hormones was negative. At the ultrastructural level, tumor/blood vessel basal lamina and cytoplasmic intermediate filaments were observed but desmosome or pericellular basal lamina were lacking. In one case few secretory granules were recorded. Differential diagnoses include granular cell tumors, pilocytic astrocytomas and spindle cell tumors such as solitary fibrous tumors, fibroblastic meningiomas and schwannomas. However, the unique pattern of antigenic expression and ultrastructural features of pituicytomas distinguish this rare tumor. As a subpopulation of pituicytes (which are distinctive glial cells of the neurophypophysis), some pituicytomas do not expressed GFAP. This suggests that pituicytomas presumably arise from pituicytes at various stages of their differentiation.

Astrocytoma↗
PubMed2002

Myopathy with lobulated muscle fibers: evidence for heterogeneous etiology and clinical presentation.

The clinico-pathological features of 17 patients displaying a myopathy with lobulated (trabeculated) fibers are reported. All these patients had a limb girdle phenotype and at least 20% of lobulated fibers in their muscle biopsies. There were ten females and seven males. The onset of symptoms ranged from 2 to 55 years (mean 24). The average age at the time of muscle biopsy was 39 (range 3-63). Interestingly, in six patients, high prevalence of lobulated fibers was observed at the second biopsy only, performed on average 11 years after the first or in another muscle. Six patients had a suggestively positive family history. Facial weakness was noted in two patients (genetic study confirmed FSH dystrophy). The course and the severity of weakness varied from one patient to another. Immunohistochemistry and Western blot analyses revealed one Duchenne carrier, one alpha-sarcoglycanopathy, no dysferlinopathy and four calpain deficiencies (including one patient with FSH dystrophy), but SSCP revealed mutation in the calpain gene in only one of the patients. These results show that (1) myopathies with lobulated fibers are clinically and genetically heterogeneous, (2) lack of calpain expression by Western blot analysis is not always associated with null mutation, (3) a molecular diagnosis is made in less than 40% of myopathy with lobulated fibers, (4) when observed, lobulated fibers are most prominent in proximal muscles and require time to appear.

Adolescent↗
PubMed2002

[Dermatomyositis and polymyositis].

Dermatomyositis (DM) and polymyositis (PM) are the two main forms of idiopathic inflammatory myopathies. They have in common a proximal muscle weakness, but skin manifestations, juvenile forms and increased incidence of malignancies are clinical characteristics of DM. The follow up of creatine-kinases is the best biological test in spite of their possible normality. The significance of antibodies titers is uncertain, except the association Jo-1 interstitial and lung disease indicating a poor prognosis. The association with HLA haplotypes expresses a genetic predisposition of a dysimmunity to develop DM or PM. Pathological changes are well known with a humoral immune effector mechanism in DM, and a muscle fibre aggression by CD8 + T cells in PM. Non inflammatory forms of DM and PM and rhabdomyolytic forms of PM are not very rare, they are recognized by the HLA class 1 immunoreactivity. Pathophysiological processes involve muscle fibers, inflammatory cells and endothelial cells of capillaries, with a complex intervention of cytokines, adhesion molecules, MHC classe 1, membrane attack complex, anti endothelial cells antibodies, perforin secretion and sometimes apoptotic Fas-mediated mechanisms. Despite these recent advances, causal antigens and activator processes of endothelial cell lysis and autoinvasive cytotoxicity of muscle fibers remain to be identified.

Biomarkers↗
PubMed2001

Neurocutaneous melanosis: radiological-pathological correlation.

We report the case of a young patient with neurocutaneous melanosis (NCM) who presented with temporary aphasia and right hemiparesis followed by progressive coma and death. To our knowledge, this is the first case of this disease examined by CT, MRI, angiography and in which an autopsy was performed to assert the diagnosis with histology. Besides, we discuss differential diagnoses and interest of MRI for early diagnosis.

Adult↗
PubMed2001

CCR2A and CCR2B, the two isoforms of the monocyte chemoattractant protein-1 receptor are up-regulated and expressed by different cell subsets in idiopathic inflammatory myopathies.

The idiopathic inflammatory myopathies (IIM), including dermatomyositis (DM), polymyosititis (PM) and inclusion body myositis (IBM), are a group of autoimmune diseases characterized by chronic lymphocytic and macrophagic infiltration in muscle. The mechanism for recruitment of these cells probably involves chemokines. We have previously reported that monocyte chemoattractant protein-1 (MCP-1), a beta chemokine, seems to play a major role in mononuclear cell recruitment especially in DM. Here we have investigated the distribution of the main MCP-1 receptors CCR2A and CCR2B in IIM by polymerase chain reaction (PCR), immunohistochemistry and in situ hybridization. We have shown by reverse transcription-PCR that both CCR2A and CCR2B were expressed at low level in normal muscle and that CCR2A was up-regulated in IIM (P=0.02) and was higher in PM and IBM than in DM (P=0.04). By immunohistochemistry and in situ hybridization we have observed that CCR2 isoforms were expressed by different cell subsets in both normal and IIM muscle. CCR2A was expressed in vessel walls and by some mononuclear cells, especially in cells involved in partial invasion in PM and IBM. CCR2B expression was observed in all satellite cells, in the muscular domain of neuromuscular junctions and in some regenerative fibers of IIM, but not in inflammatory exudates. In conclusion, the present study highlights the major role played by MCP-1 and its counter-receptor CCR2 in the pathophysiology of IIM, and shows that the CCR2 receptors are cell specific. The variation of the total amount of CCR2A and its local distribution according to the type of IIM might be a new path towards the understanding of the constitution of mononuclear infiltrates in IIM.

Adolescent↗