Biomedical subjects

P Remy

Publications and source records attributed to P Remy.

At least 19 recordsLinked to original sources

PubMed2006

Dihydropteridine reductase deficiency: levodopa's long-term effectiveness without dyskinesia.

We report an adult patient lacking endogenous synthesis of monoamines (dopamine, serotonin, and catecholamines) due to a severe dihydropteridine reductase (DHPR) deficiency. With levodopa and 5-hydroxytryptophan (5HTP) supplementation, the patient exhibited moderate mental retardation, acute episodes of parkinsonism, and episodes of depression. Despite the use of levodopa from age 3 months, he exhibited no dyskinesia or dopaminergic cell loss as suggested by normal PET imaging of the dopamine transporter.

5-Hydroxytryptophan↗

PubMed2006

Distribution of grey matter atrophy in Huntington's disease patients: a combined ROI-based and voxel-based morphometric study.

The striatum, a subcortical structure, is the principal target of the neurodegenerative process in Huntington's disease (HD). The measurement of striatal atrophy using the bicaudate ratio on CT scanner images has therefore been used for years to assess disease progression, but this measure only takes into account unidimensional changes in the head of the caudate nucleus. Recently, voxel-based morphometry (VBM), which permits automated statistical comparisons of whole-brain MRI images, has been proposed to quantify striatal atrophy. However, VBM was not originally designed to study subcortical structures, and severe deep brain deformations that occur in HD may hamper the automatic processing of VBM. Here, we validate the use of the optimised protocol of VBM to quantify subcortical atrophy in HD by comparing results obtained with this method to those provided by manual segmentation of subcortical structures. We studied 20 patients with early HD and 12 controls matched for age, sex and handedness using an improved T1-weighted sequence that eased grey matter segmentation. Both manual and automated methods evidenced the dorso-ventral gradient of striatal atrophy, a loss of grey matter in the globus pallidus and the thalamus, and similar correlations between clinical scores and subcortical atrophy. Furthermore, we were able to detect with VBM grey matter loss in the substantia nigra, the hypothalamus, the amygdala, the insular cortex and the premotor and sensorimotor cortices. Finally, VBM provided results consistent with previous post mortem results and proved to be a sensitive biomarker capable of correctly managing subcortical distortions throughout HD patients' brains.

Adult↗

PubMed2006

Minimal change nephrotic syndrome and classical Hodgkin's lymphoma: report of 21 cases and review of the literature.

Minimal change nephrotic syndrome (MCNS) is described as a paraneoplastic manifestation of classical Hodgkin's lymphoma (cHL). We reassessed the pathophysiological and clinical significance of this association. A retrospective study was performed to evaluate a cohort of adult patients who developed MCNS and cHL. Twenty-one patients recruited in 15 French centers were analyzed. cHL was associated with inflammatory and general symptoms in most cases. The morphological subtype was predominantly nodular sclerosis (71.4%). MCNS appeared before the diagnosis of lymphoma in eight patients (38.1%) and in this case, it was characterized by a nephrotic syndrome (NS) frequently resistant (50%) or dependent (12.5%) to steroid treatment. Interestingly, diagnosis (3-120 months after MCNS) and effective treatment of the hemopathy were associated with the disappearance of the MCNS. cHL was diagnosed before MCNS in nine patients (42.9%), and in this case, glomerulopathy was associated with cHL relapse in 55.5% of cases. In four patients (19%), the two diseases occurred simultaneously. Extensive immunohistochemical study of lymph nodes was performed in eight patients and did not reveal particular features. In conclusion, MCNS associated with cHL is frequently dependent or resistant to steroid regimen, but remission of NS is obtained with the cure of lymphoma.

Adolescent↗

PubMed2006

Diffusion-weighted MR imaging characteristics of an acute strokelike form of multiple sclerosis.

The characteristics of multiple sclerosis (MS) lesions on diffusion-weighted sequences and apparent diffusion coefficient (ADC) mapping at the very early phase of symptoms have not been clearly described. We report the case of a young woman who presented with a sudden pseudostroke form of MS resulting in hemiplegia and sudden aphasia. MR imaging showed a lesion of the left internal capsule with reduced ADC, which suggests an ischemic stroke. This case shows that very acute MS lesions may have reduced ADC on MR imaging, reflecting cytotoxic and not vasogenic edema.

Acute Disease↗

PubMed2005

[Advantages and limitations in the assessment of neuroprotective treatment of Parkinson's disease by functional imaging].

INTRODUCTION: The development of neuroprotective strategies is a crucial issue for Parkinson's disease, since up to now only symptomatic therapies are available. The clinical evaluation of neuroprotective drugs is difficult considering the long-term effect of anti-Parkinsonian medication that nearly make impossible accurate measurement of the "true" clinical stage of the disease in the early years of progression. BACKGROUND: Two recent functional imaging studies (CALM-PD and REAL-PET) using positron emission tomography (PET) or single photon emission computed tomography (SPECT), suggest that dopamine agonist may have a neuroprotective effect compared to L-Dopa. CONCLUSION: These results are still controversial, notably because of the lack of clinical-imaging correlations, the absence of a placebo group and some important methodological considerations. Nevertheless, these studies are encouraging and give some arguments for the potential neuroprotective role of dopamine agonists. The aim of this work is first to present the pros and cons of these studies and second to propose guidelines in order to improve the design and methodology for future studies designed to assess the neuroprotective properties of new drugs in Parkinson's disease.

Antiparkinson Agents↗

PubMed2005

[Transient ischaemic attacks due to hypoplasia of the internal carotid artery in a patient with congenital Horner's syndrome].

INTRODUCTION: Hypoplasia of the internal carotid artery (ICA) is a rare developmental anomaly sometime revealed by transient ischaemic attaks (TIA). Association with a Horner's syndrome is very rare. CASE REPORT: We report the case of a 42-year-old woman who presented with a TIA and a cervical murmur. Horner's syndrome with iris hypopigmentation was present shortly after birth. Magnetic resonance imaging showed no dissection but hypoplasia of the ICA. Blood flow in the ICA was antegrade through several branches constituting a rete mirabile across the carotid canal, and via collateral arteries from ipsilateral external carotid artery. CONCLUSION: Horner's syndrome in the setting of TIA evokes a carotid dissection. A skull base CT scan demonstrating carotid canal hypoplasia can rule out an ICA dissection and allows diagnosis of a congenital arterial anomaly.

Adult↗

PubMed2005

Necrotizing fasciitis during de novo minimal change nephrotic syndrome in a kidney transplant recipient.

Skin infections and particularly necrotizing fasciitis (NF) represent a rare but serious complication after transplantation. Optimal management depends on prompt diagnosis with identification of the causative organisms to allow appropriate antibiotic therapy in association with surgical debridement. We report a case of a methicillin-resistant Staphylococcus aureus (MRSA) NF as the single pathogen in a renal transplant recipient, during the course of a de novo minimal-change nephrotic syndrome, treated with high-dose steroids. Antibiotic therapy together with surgical debridement and discontinuation of immunosuppressive treatment led to a complete recovery, despite persistence of the nephrotic syndrome. The development of de novo minimal-change nephrotic syndrome after renal allograft transplantation should alert physicians to the possibility of MRSA NF during an increase in the immunosuppressive regimen.

Fasciitis, Necrotizing↗

PubMed2004

Tolerance and short term efficacy of rituximab in 43 patients with systemic autoimmune diseases.

OBJECTIVE: To assess the tolerance and efficacy of rituximab in patients with various autoimmune diseases seen in daily rheumatological practice. METHODS: 866 rheumatology and internal medicine practitioners were contacted by e-mail to obtain the files of patients treated with rituximab for systemic autoimmune diseases. Patients with lymphoma were analysed if the evolution of the autoimmune disease could be evaluated. RESULTS: In all, 43 of 49 cases could be analysed, including 14 with rheumatoid arthritis (RA), 13 with systemic lupus erythematosus (SLE), six with primary Sjogren's syndrome (pSS), five with systemic vasculitis, and five with other autoimmune diseases. Rituximab was prescribed for lymphoma in two patients with RA and two with pSS. In the 39 other cases, rituximab was given because of the refractory character of the autoimmune disease. The mean follow up period was 8.3 months (range 2 to 26). There were 11 adverse events in 10 patients and treatment had to be discontinued in six. Efficacy was observed in 30 patients (70%): RA 11, SLE 9, pSS 5, vasculitis 2, antisynthetase syndromes 2, sarcoidosis 1. The mean decrease in corticosteroid intake was 9.5 mg/d (range 0 to 50) in responders. Seven patients experienced relapse after mean 8.1 months (5 to 15). Three patients died because of refractory autoimmune disease. CONCLUSIONS: Despite absence of marketing authorisation, rituximab is used to treat various refractory autoimmune diseases in daily rheumatological practice. This study showed good tolerance and short term clinical efficacy, with marked corticosteroid reduction in patients with SLE, pSS, vasculitis, and polymyositis.

Adult↗

PubMed2004

PET evidence for a role of the basal ganglia in patients with ring chromosome 20 epilepsy.

BACKGROUND: Studies in animal models and epileptic patients have suggested that circuits of the basal ganglia may control epileptic seizures and that striatal dopaminergic transmission plays a key role in seizure interruption. Ring chromosome 20 (r[20]) epilepsy is a very homogenous type of epilepsy and is clinically characterized by long-lasting seizures suggesting a dysfunction in the seizure control system. The hypothesis that these long-lasting seizures are associated with a reduction of striatal dopamine was addressed in the present study in drug-resistant patients with r(20) epilepsy using PET. METHOD: The authors performed [18F]fluoro-l-DOPA PET in 14 patients with r(20) epilepsy and compared uptake constants in the putamen and the caudate with those of 10 controls. In addition, the authors examined the correlation between these constants and the percentage of cells with r(20) mosaicism. RESULTS: [18F]fluoro-l-DOPA uptake was significantly decreased bilaterally in the putamen and in the caudate nucleus of patients. This reduction was equal for both nuclei and was not correlated to the percentage of cells with r(20). CONCLUSION: Striatal dopamine is modulated in r(20) epilepsy; dysfunction of this neurotransmission may impair the mechanisms that interrupt seizures.

Adolescent↗

PubMed2004

Totally laparoscopic aortobifemoral bypass: a case report.

Since a few years, vascular surgeons are becoming interested in laparoscopic vascular techniques. After initial experience with the hand-assisted laparoscopic technique, we now adopt the totally laparoscopic approach for aortoiliac surgery. Our first case with this second technique is presented.

Blood Vessel Prosthesis Implantation↗

PubMed2004

Neuroprotective gene therapy for Huntington's disease, using polymer-encapsulated cells engineered to secrete human ciliary neurotrophic factor: results of a phase I study.

Huntington's disease (HD) is a monogenic neurodegenerative disease that affects the efferent neurons of the striatum. The protracted evolution of the pathology over 15 to 20 years, after clinical onset in adulthood, underscores the potential of therapeutic tools that would aim at protecting striatal neurons. Proteins with neuroprotective effects in the adult brain have been identified, among them ciliary neurotrophic factor (CNTF), which protected striatal neurons in animal models of HD. Accordingly, we have carried out a phase I study evaluating the safety of intracerebral administration of this protein in subjects with HD, using a device formed by a semipermeable membrane encapsulating a BHK cell line engineered to synthesize CNTF. Six subjects with stage 1 or 2 HD had one capsule implanted into the right lateral ventricle; the capsule was retrieved and exchanged for a new one every 6 months, over a total period of 2 years. No sign of CNTF-induced toxicity was observed; however, depression occurred in three subjects after removal of the last capsule, which may have correlated with the lack of any future therapeutic option. All retrieved capsules were intact but contained variable numbers of surviving cells, and CNTF release was low in 13 of 24 cases. Improvements in electrophysiological results were observed, and were correlated with capsules releasing the largest amount of CNTF. This phase I study shows the safety, feasibility, and tolerability of this gene therapy procedure. Heterogeneous cell survival, however, stresses the need for improving the technique.

Animals↗

PubMed2003

Low levels of ventricular CSF orexin/hypocretin in advanced PD.

The origins of excessive daytime sleepiness in Parkinson disease (PD) are unclear. The authors hypothesize that orexin neurons, a recently identified wake promoting system, could contribute to its pathophysiology. They measured orexin-A/hypocretin-1 concentration in ventricular CSF in 19 parkinsonian patients and compared it with neurologic controls. Orexin levels were lower in patients and decreased with the severity of the disease. The authors suggest that orexin neurons contribute to daytime sleepiness in late stage PD.

Antiparkinson Agents↗

PubMed2001

Identification of interaction partners for two closely-related members of the ETS protein family, FLI and ERG.

Fli and erg are two members of the ETS gene family that encodes transcription factors related to the c-ets-1 proto-oncogene. The products of the ETS genes act as transcriptional effectors in cell proliferation, differentiation, and oncogenic transformation. FLI and ERG, two closely-related proteins, bind, as do all the ETS proteins characterized so far, to DNA sequences with an invariable central GGA core flanked by preferred nucleotides. Nevertheless, promoter-specific responses to FLI or ERG may be driven by mechanisms involving multicomponent complexes. Using a yeast two-hybrid screen, we have identified several proteins that physically interact with either FLI or ERG proteins used as bait. The Xenopus developmentally implicated Xvent-2 and Xvent-2B proteins, and the Xenopus splicing factor RNP-C/U1C physically interact with Xl-FLI and Xl-ERG, both in the yeast two-hybrid system and in vitro. We also report the potential interaction of FLI and ERG with Sox-D, a stabilizing protein that may modulate their transcriptional activity. Furthermore, the possible involvement of the transcriptional effectors FLI and ERG in mRNA processing, hematopoiesis or in the control of angiogenesis is suggested through possible interactions with, respectively, RNA binding proteins and hnRNPs, a repressor of the hematopoietic pathway (SAP18), and the HAF protein.

Animals↗

PubMed2001

Case report of pallido-pyramidal disease with supplementary motor area involvement.

An C-flumazenil positron emission tomography (PET) study in a patient with pallido-pyramidal disease revealed a marked decrease in benzodiazepine-receptor density in the precentral gyrus cortex and the mesial frontal cortex. We suggest that, in addition to dysfunction of basal ganglia-dependent systems, degeneration of the supplementary motor area could also be involved in the patient's bradykinesia.

Adult↗

PubMed2001

Renal transplantation in a patient with hypocomplementemic urticarial vasculitis syndrome.

We describe a 36-year-old man who presented with hypocomplementemic urticarial vasculitis syndrome (HUVS) with severe renal involvement. Despite steroid therapy, the patient developed end-stage renal disease (ESRD) leading to chronic hemodialysis therapy. Renal transplantation was performed after hemodialysis therapy (secondary), and the patient developed a typical HUVS relapse 9 months after transplantation despite conventional immunosuppressive therapy that was successfully treated with plasma exchange. This case shows for the first time that HUVS can induce severe renal involvement responsible for ESRD and that HUVS can relapse after renal transplantation. It also suggests that plasma exchange therapy may be of value for rapidly controlling the clinical symptoms.

Adult↗

PubMed2001

Lack of evidence of a specific role for C4A gene deficiency in determining disease susceptibility among C4-deficient patients with systemic lupus erythematosus (SLE).

The aim of the present study was to investigate the prevalence of C4 and C2 deficiencies and to characterize genomic alterations in C4 genes in a large cohort of 125 unselected patients with SLE. We determined the protein concentration and functional activity of C2 and C4, as well as the C4 phenotype. C4 genotyping included Taq 1 restricted fragment lengh polymorphism (RFLP) analysis and polymerase chain reaction using sequence-specific primers (SSP-PCR). Type I C2 deficiency was diagnosed by PCR. Overall, 79.2% of the patients exhibited abnormalities of the C4 genes including deletion, non-expression, gene conversion and duplication. Among C4-deficient patients (n = 66, 52.8% prevalence), 41.0% of the patients exhibited a C4A deficiency and 59.0% a C4B deficiency. Half of the C4 deficiencies were due to a gene deletion. There was a strong association between C4A and C4B gene deletion and the presence of the DRB1*03 allele. Among the silent C4A genes, only two cases were related to a 2-bp insertion in exon 29 of the C4A gene. A gene conversion was demonstrated in eight patients (6.4%). One patient had a homozygous C4A deficiency. Three (2.4%) patients presented with a heterozygous type I C2 deficiency and none with homozygous deficiency. Our results argue against a specific role for C4A gene deficiency in determining disease susceptibility among patients with SLE that are C4-deficient.

Adolescent↗

PubMed2000

The Ets-transcription factor family in embryonic development: lessons from the amphibian and bird.

This chapter reviews the expression and role of Ets-genes during embryogenesis of amphibians and birds. In addition to overlapping expression domains, some of them exhibit cell type-specific expression. Many of them are expressed in migratory cells: neural crest, endothelial, and pronephric duct cells for instance. They are also transcribed in embryonic areas affected by epithelio-mesenchymal transitions. Both processes involve modifications of cellular adhesion. Ets-family genes appear to coordinate changes in the expression of adhesion molecules and degradation of the extracellular matrix upon regulation of matrix metalloproteinases and their specific inhibitors. These functions are essential for physiological processes like tissue remodelling during embryogenesis or wound healing. Unfortunately they also play a harmful role in metastasis. Recent studies in the nervous system showed that Ets-genes contribute to the establishment of a cellular identity. This identity could rely on definite cell-surface determinants, among which cadherins could play an important role. In addition to cell-type specific expression, other factors contribute to the specificity of function of Ets-genes. These genes have a broad specificity of recognition of target sequences in gene promoters, insufficient for accurate control of gene expression. A fine tuning could arise from combinatorial interactions with other Ets- or accessory proteins.

Animals↗

PubMed2000

Heterotopic expression of the Xl-Fli transcription factor during Xenopus embryogenesis: modification of cell adhesion and engagement in the apoptotic pathway.

In the Xenopus laevis embryo, the overexpression of the Xl-FLI protein, a transcription factor of the ETS family, provokes severe developmental anomalies, which affect anteroposterior and dorsoventral polarities, optic cup formation, head cartilage morphogenesis, and erythrocyte differentiation. It has been proposed that these effects could be correlated to modifications of cell adhesion properties and/or to an increased engagement of cells in the apoptotic pathway during early development (Remy et al., Int. J. Dev. Biol. 40, 577-589, 1996). To address these questions, we have first analyzed the behavior of cells overexpressing the protein in both aggregation and adhesion assays. We observe perturbations of cell-cell interactions as well as perturbations of cell adhesion and spreading on fibronectin and extracellular matrix (ECM). Second, we have analyzed apoptosis of cells overexpressing the Xl-FLI protein, by testing DNA fragmentation, caspase-3 activity and by performing TUNEL assay. We show that Xl-Fli overexpression results in the appearance of hallmarks of apoptosis, including exclusion of cells from the interior of the embryo, internucleosomal fragmentation of DNA and dose-dependent induction of caspase-3, resulting in the hydrolysis of poly(ADP-ribose) polymerase. In addition, a dominant-negative mutation of BMPs receptors decreases the effects of Xl-Fli overexpression, suggesting that a modification of the BMP signalling could be responsible for increased apoptosis. The latter appears to affect predominantly ventral and ventrolateral regions of the embryo.

Animals↗