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Biomedical subjects

D Figarella-Branger

Publications and source records attributed to D Figarella-Branger.

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

Diagnostic evaluation of clinically normal subjects with chronic hyperCKemia.

The authors analyzed muscle biopsy specimens of 104 patients with creatine kinase activity greater than 500 UI/L (normal 10 to 170 UI/L) without signs of muscle weakness. They achieved a definite or probable diagnosis in 55% of cases. The most frequently identified diseases were glycogen storage diseases, muscular dystrophies, and inflammatory myopathies. The probability of making a diagnosis was higher in children and when creatine kinase level was greater than 2,000 UI/L.

Adolescent↗
PubMed2006

Identification of genes differentially expressed in glioblastoma versus pilocytic astrocytoma using Suppression Subtractive Hybridization.

Glioblastoma (GBM) is a highly malignant glioma, which has the propensity to infiltrate throughout the brain in contrast to pilocytic astrocytoma (PA) of the posterior fossa, which does not spread and can be cured by surgery. We have used Suppression Subtractive Hybridization to define markers that better delineate the molecular basis of brain invasion and distinguish these tumor groups. We have identified 106 genes expressed in PA versus GBM and 80 genes expressed in GBM versus PA. Subsequent analysis identified a subset of 20 transcripts showing a common differential expression pattern for the two groups. GBM differs from PA by the expression of five genes involved in invasion and angiogenesis: fibronectin, osteopontin, chitinase-3-like-1 (YKL-40), keratoepithelin and fibromodulin. PA differs from GBM by the expression of genes related to metabolism (apolipoprotein D), proteolysis (protease-serine-11), receptor and signal transduction (PLEKHB1 for Pleckstrin-Homology-domain-containing-protein-family-B-member-1), transcription/translation (eukaryotic-translation-elongation-factor-1-alpha1) processes and cell adhesion (SPOCK1 for SPARC/Osteonectin-CWCV-kazal-like-domains-proteoglycan). The expression of these genes was confirmed by real-time quantitative RT-PCR and immunohistochemistry. This study highlights the crucial role of brain invasion in GBM and identifies specific molecules involved in this process. In addition, it offers a restricted list of markers that accurately distinguish PA from GBM.

Aged↗
PubMed2006

[MR spectroscopy of brain tumors].

MR spectroscopy (MRS) can complement MRI in the evaluation of intracranial tumors. Before treatment, MRS can contribute to the differential diagnosis between tumor and non tumoral lesion (especially intracranial abscesses), to assess the aggressiveness of a glial tumor or to determine its extension to better delineate the surgical removal or the target volume of radiotherapy. During treatment follow-up, MRS helps differentiate recurrent tumor from radionecrosis or physiological post-surgical contrast enhancement. The current studies are trying to determine if the indications of MRS, alone or in association with other MR sequences can further be extended in the study of brain tumors, in particular the follow-up of lesions undergoing chemo or radiotherapy.

Brain Neoplasms↗
PubMed2006

In vitro identification and functional characterization of glial precursor cells in human gliomas.

Human gliomas including astrocytomas and oligodendrogliomas are defined as being composed of neoplastic astrocytes and oligodendrocytes respectively. Here, on the basis of in vitro functional assays, we show that gliomas contain a mixture of glial progenitor cells and their progeny. We have set up explant cultures from pilocytic astrocytomas, glioblastomas and oligodendrogliomas and studied antigens that characterize glial lineage, from the precursor cells (glial restricted precursors and oligodendrocyte-type2-astrocyte/oligodendrocyte precursor cells expressing the A2B5 ganglioside) to the differentiated cells (oligodendrocyte and type-1 and type-2 astrocytes). All tumoral explants contain A2B5+ cells and can generate migrating cells with distinctive functional properties according to glioma subtypes. In pilocytic astrocytomas, very few migrating cells are dividing and can differentiate in type-2 astrocytes or towards the oligodendrocyte lineage. In glioblastomas, most migrating cells are dividing, express A2B5 or glial fibrillary acid protein (GFAP) and can generate oligodendrocytes and type-1 and type-2 astrocytes in appropriate medium. Oligodendroglioma explants are made by actively dividing glial precursor cells expressing A2B5 or PSA-NCAM. Only few cells can migrate and differentiation towards oligodendrocyte lineage does not occur. Isolated A2B5+ cells from both glioblastomas and oligodendrogliomas showed similar genetic alterations as the whole tumour. Therefore, pilocytic astrocytomas contain slowly dividing oligodendrocyte-type2-astrocyte/oligodendrocyte precursor cells in keeping with their benign behaviour whereas both glioblastomas and oligodendrogliomas contain neoplastic glial restricted precursor cells. In oligodendrogliomas, these cells are trapped in undifferentiated and proliferating state. The precursor cells properties present in gliomas give new insight into their histogenesis and open up new avenues for research in the field of gliomagenesis.

Adult↗
PubMed2005

[NK cells: new insights on physiology and clinical implication in diseases].

INTRODUCTION: Natural killer cells are cytotoxic lymphocytes of innate immunity. These last ten years our knowledge about the mechanisms that regulates NK cell function has greatly improved. Our purpose is to present a review of these new acquisitions and their potential implications in human disease. CURRENT KNOWLEDGE AND KEY POINTS: NK cell function is regulated by a repertoire of NK cell receptors and is diversified by recognition of MHC class I by a multigenic and multi-allelic family of NK receptors. Analysis of NK cell repertoire has been used to investigate features that characterize NK cells in pathological situations. Apart from their direct cytotoxic potential to eliminate target cells, recently identification of mechanisms that control NK cell mediated cytokine production and cross talk with dendritic cells emphasize the role of NK cells in the regulation of acquired immune response. FUTURE PROSPECTS AND PROJECTS: These findings have lead to a better knowledge of the importance of the NK cells in several human diseases. It has been shown that NK cells are actors of the immunosurveillance of tumoral and infectious challenges. Allo or auto reactivity of the NK cell compartment have also been suggested in autoimmune diseases, infertility or foetal loss and transplantation. Ongoing research on NK cells in the fields of human diseases is increasing and will clarify the utility of the evaluation of the NK cell compartment and their receptors in clinical practice.

Animals↗
PubMed2005

Temozolomide in combination with BCNU before and after radiotherapy in patients with inoperable newly diagnosed glioblastoma multiforme.

BACKGROUND: The aim of this study was to evaluate the efficacy and safety of carmustine (BCNU) in combination with temozolomide as first-line chemotherapy before and after radiotherapy (RT) in patients with inoperable, newly diagnosed glioblastoma multiforme (GBM). PATIENTS AND METHODS: Forty patients were treated with BCNU (150 mg/m2) on day 1 and temozolomide (110 mg/m2/day) on days 1 through 5 of each 42-day cycle for up to four cycles prior to conventional RT (2 Gy fractions to a total of 60 Gy). After RT, BCNU + temozolomide was administered for four additional cycles or until progression. The primary end point was response rate; secondary end points included progression-free survival (PFS); overall survival (OS) and safety. RESULTS: Sixty per cent of patients completed four cycles of neo-adjuvant BCNU + temozolomide. Objective response rate (intention-to-treat) was 42.5% (95% confidence interval 27% to 58%), including two (5%) complete and 15 (37.5%) partial responses. In the eligible population (n=37) the objective response rate was 46%. Nine (24%) patients had stable disease and 14 (35%) had progressive disease. Median PFS and OS were 7.4 and 12.7 months, respectively. Age was the only significant prognostic factor and tumor location (lobar versus multifocal versus corpus callosum) showed a trend. Grade 3-4 toxicities included thrombocytopenia (n=11) and neutropenia (n=7) for both pre- and post-RT chemotherapy. Four patients required platelet transfusions. No patient discontinued treatment because of toxicity. CONCLUSIONS: The combination of BCNU plus temozolomide as neo-adjuvant therapy in inoperable GBM exhibited promising activity with a good safety profile and warrants further evaluation.

Adult↗
PubMed2005

[Dermatomyositis with cutaneous necrosis revealing a fallopian tube carcinoma].

INTRODUCTION: Adult dermatomyositis is a rare inflammatory myopathy associated with typical cutaneous lesions and an increased incidence of internal malignancies, notably cancers of the female genital tract. Nevertheless, fallopian tube carcinoma is exceptionally associated with dermatomyositis. EXEGESIS: We report an unusual case of dermatomyositis because of cutaneous necrosis revealing a cancer of the fallopian tube. CONCLUSION: Predictive factors of cancer can improve prognosis of dermatomyositis due to earlier diagnosis of associated cancer. In our observation as in literature review, cutaneous necrosis lesions are highly predictive of an associated neoplasia even as rare as a fallopian tube carcinoma.

Carcinoma↗
PubMed2005

LGMD2A: genotype-phenotype correlations based on a large mutational survey on the calpain 3 gene.

We present here the clinical, molecular and biochemical findings from 238 limb-girdle muscular dystrophy type 2A (LGMD2A) patients, representing approximately 50% (238 out of 484) of the suspected calpainopathy cases referred for the molecular study of the calpain 3 (CAPN3) gene. The mean age at onset of LGMD2A patients was approximately 14 years, and the first symptoms occurred between 6 and 18 years of age in 71% of patients. The mean age at which the patients became wheelchair bound was 32.2 years, with 84% requiring the use of a wheelchair between the age of 21 and 40 years. There was no correlation between the age at onset and the time at which the patient became wheelchair bound, nor between the sex of the patient and the risk of becoming wheelchair bound. Of the cases where the CAPN3 gene was not affected, approximately 20% were diagnosed as LGMD2I muscular dystrophy, while facioscapulohumeral muscular dystrophy (FSHD) was uncommon in this sample. We identified 105 different mutations in the CAPN3 gene of which 50 have not been described previously. These were distributed throughout the coding region of the gene, although some exons remained free of mutations. The most frequent mutation was 2362AG-->TCATCT (exon 22), which was present in 30.7% of the chromosomes analysed (146 chromosomes). Other recurrent mutations described were N50S, 550DeltaA, G222R, IVS6-1G-->A, A483D, IVS17+1G-->T, 2069-2070DeltaAC, R748Q and R748X, each of which was found in >5 chromosomes. The type of mutation in the CAPN3 gene does not appear to be a risk factor for becoming dependent on a wheelchair at a determined age. However, in the cases with two null mutations, there were significantly fewer patients that were able to walk than in the group of patients with at least one missense mutation. Despite the fact that the results of phenotyping and western blot might be biased due to multiple referral centres, producing a diagnosis on the basis of the classical phenotype is neither sufficiently sensitive (86.7%) nor specific (69.3%), although western blot proved to be even less sensitive (52.5%) yet more specific (87.8%). In this case LGMD2I was a relevant cause of false-positive diagnoses. Considering both the clinical phenotype and the biochemical information together, the probability of correctly diagnosing a calpainopathy is very high (90.8%). However, if one of the analyses is lacking, the probability varies from 78.3 to 73.7% depending on the information available. When both tests are negative, the probability that the sample comes from a patient with LGMD2A was 12.2%.

Adolescent↗
PubMed2005

[Pediatric supratentorial oligodendrogliomas: Marseilles and Lyons experiences].

BACKGROUND AND PURPOSE: The goal of this study was to analyze the main aspects of oligodendrogliomas observed in children. METHOD: The records of 35 children aged 15 years or younger (23 from Marseilles and 12 from Lyons) were reviewed. Clinical signs and symptoms, imaging findings (CT scan and pre- and post-operative MRI), extent of surgical resection, histology according to the WHO and Ste-Anne grading and survival were analysed. Considering all these factors, a statistical analyzis was undertaken in order to identify prognostic factors. DISCUSSION AND CONCLUSION: Oligodendrogliomas are rare tumors in children. The most important differential diagnosis to discuss is dysembryoplastic neuroepithelial tumor. Our study allowed us to distinguish several subgroups of patients with a different prognosis: thalamic tumors with a dismal prognosis versus hemispheric tumors. A group of cortical tumors we called "DNT-like" (hemispheric cortical tumor, isolated epilepsy, without neurological deficit and reased ICP, without edema and mass effect on MRI) with an excellent prognosis like the group with epilepsy. Histological grading (grade A/grade B and grade II/grade III) is also a prognostic factor.

Adolescent↗
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

Fetal brain injury.

Improvements in MRI techniques widen the indications for fetal brain imaging and fetal brain injury represents the third indication of fetal brain magnetic resonance imaging (MRI) after the evaluation of suspected central nervous system (CNS) malformations and ventricular dilatation. Optimal MR imaging technique is necessary in order to collect as much data as possible about the fetal brain. Diffusion images can be used routinely in addition to the standard protocol of fetal brain MRI that consists of T1 and T2 weighted images of the fetal brain. Monovoxel proton magnetic resonance spectroscopy can also be performed in utero, but this technique is still more part of research protocol than of routine clinical protocol. Fetal brain injury includes hypoxia-ischemia, congenital infections (especially toxoplasmosis and cytomegalovirus infections), brain damage due to malformation such as vascular brain malformation and heart malformation, pregnancies at risk of fetal brain damage, and even inherited metabolic diseases, especially mitochondrial diseases. MRI findings in fetal brain injury consist of acute or chronic lesions that can be seen alone or in combination. Acute response of the fetal brain is less commonly seen than the chronic response compared to the brain response encountered in the postnatal period.

Brain Injuries↗
PubMed2004

Tau aggregates are abnormally phosphorylated in inclusion body myositis and have an immunoelectrophoretic profile distinct from other tauopathies.

Sporadic inclusion body myositis (s-IBM) is the most frequent progressive acquired inflammatory myopathy in people older than 50 years. Abnormal aggregates of 'Alzheimer's proteins', including tau proteins, have been previously demonstrated in s-IBM. In the present study, we have investigated by immunohistochemistry and immunoblotting analysis the presence of tau proteins in muscle biopsy samples from patients with s-IBM and other myopathies with rimmed vacuoles, using newly developed antibodies raised against tau protein epitopes found in Alzheimer's disease brain. Tau immunoreactivity was shown in rimmed vacuoles or inclusions, preferentially with antibodies directed against phosphorylated carboxy-terminal epitopes of tau proteins. Cytoplasmic reactivity was also demonstrated in atrophic, nonvacuolated fibres, as well as in non-necrotic fibres invaded by inflammatory cells. Abnormally phosphorylated tau aggregates were also found in other compartments of the muscle fibre in s-IBM and other myopathies. Tau immunoblotting showed an electrophorectic profile of a doublet within the range of 60-62 kDa isovariants, which was different from tauopathies of the central nervous system. Finally, the unique pattern of immunoreactivity of s-IBM samples towards anti-tau antibodies is a new clue to a possible distinct subclass of peripheral tauopathy, different from the tauopathies of the central nervous system.

Adult↗
PubMed2004

Histopathological observations on vestibular schwannomas after Gamma Knife radiosurgery: the Marseille experience.

BACKGROUND AND PURPOSE: Radiosurgery has become a successful treatment modality in the management of vestibular schwannomas (VS) during the past four decades. Although the number of treated cases has been increasing continuously we know relatively little about the pathological effect of high dose irradiation on VS following radiosurgery. The purpose of this study was to analyze histopathological changes in VS after Leksell Gamma Knife (LGK) radiosurgery. METHODS: Out of a series of 1350 VS cases treated with LGK surgery 22 patients underwent craniotomy for tumor removal in 6-92 Months interval after radiosurgery. Surgical pathology material was available in 17 cases. Routine histological and immunohistochemical investigations were performed on the tIssue samples. Histopathological findings were compared with clinical and radiological follow-up data. RESULTS: Coagulation necrosis in the central part of the schwannomas surrounded with a transitional zone containing loosened tIssue structure of shrunken tumor cells covered with an outer capsule of vigorous neoplastic cells was the basic histopathological lesion. Granulation tIssue proliferation with inflammatory cell infiltration, different extent of hemorrhages and scar tIssue development was usually present. Endothelial destruction or wall damage of vascular channels was a common finding. Analyzing the follow-up data it turned out that 7 patients out of the 22 were operated on because of radiological progression only without clinical deterioration and 4 of them was removed during the latency period after radiosurgery. CONCLUSION: Results of the present histopathological study suggest that radiosurgery works with double effect on VS: it seems to destroy directly tumor cells (with necrosis or inducing apoptosis), and causes vascular damages as well. The loss of central contrast enhancement on CT and MR images following radiosurgery might be consequence of necrosis and vascular impairment. From clinical-pathological point of view we think that patients should not undergo craniotomy just because of radiological progression of the tumor without clinical deterioration, mainly in the latency period. This requires consultation and common decision-making between the radiosurgical and the microsurgical team.

Adult↗
PubMed2003

Mixed meningeal and brain plasma-cell granuloma: an example of an unusual evolution.

We report a study of a 22-year-old woman with a plasma-cell granuloma (PCG), a rare intracranial lesion characterized by a non-neoplastic polyclonal proliferation of plasma cells and other mononuclear cells. She presented after a generalized seizure and CT-scan and magnetic resonance images demonstrated a left temporo-basal tumour mass involving both the meningeal layers and the brain parenchyma. Histopathological examination of a biopsy led to the diagnosis of a typical PCG. After a short course of steroid administration, the clinical and radiological features improved and complete regression of the lesion was shown after one year and persisted at four-year follow-up. This dramatic regression of an intracranial PCG shows that neither surgical removal nor radiation therapy is required to treat a broad skull base PCG.

Adult↗
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↗